Digitized by tine Internet Arciiive in 2010 witii funding from Open Knowledge Commons (for the Medical Heritage Library project) http://www.archive.org/details/textbookofhumanp1904land TEXT-BOOK HUMAN PHYSIOLOGY TEXT-BOOK HUMAN PHYSIOLOGY INCLUDING HISTOLOGY AND MICROSCOPICAL ANATOMY WITH ESPECIAL REFERENCE PRACTICE OF MEDICINE DR. L. LANDOIS PROFESSOR OF PHYSIOLOGY AND DIRECTOR OF THE PHYSIOLOGICAL INSTITUTE IN THE UNIVERSITY OF GKEIFSWALD TENTH REVISED AND ENLARGED EDITION EDITED BY ALBERT P. BRUBAKER, M.D. PROFESSOR OF PHYSIOLOGY AND HYGIENE IN THE JEFFERSON MEDICAL COLLEGE ; PROFESSOR OF PHYSIOLOGY IN THE PENNSYLVANIA COLLEGE OF DENTAL SURGERY ; LECTURER ON PHY-SIOLOGY AND HYGIENE IN THE DREXEL INSTITUTE OF ART, SCIENCE AND INDUSTRY, PHILADELPHIA TRANSLATED BY AUGUSTUS A. ESHNER, M.D. PROFESSOR OF CLINICAL MEDICINE IN THE PHILADELPHIA POLYCLINIC ; PHYSICIAN TO THE PHILADELPHIA HOSPITAL : ASSISTANT PHYSICIAN TO THE PHILADELPHIA ORTHOPEDIC HOSPITAL AND INFIRMARY FOR NERVOUS DISEASES mkitb 394 IFllustratione PHILADELPHIA P. BLAKISTON'S SON & CO IOI2 Walnut Street 1904 L232 1404 Copyright, 1904, by P. Blakiston's Son & Co PRESS or WM. r. rr-LL company PHrl.ADKI.PHlA PUBLISHERS' PREFACE. The fourth EngHsh edition of Professor Stirhng's translation of Landois' "Physiology," published in 1891, has been out of print for some years. Since the date of publication of this English edition, the work has passed through three more large editions in Germany. On each occasion Professor Landois still further enhanced its merits by incorporating all those results of physiological investigation which in his judgment would have a permanent value not only for advanced students but for practitioners of medicine as well; and hence there is probably no work which so thoroughly and satisfactorily represents the existing state of physiological science and its relations to patholog}' and clinical medicine, as that of Professor Landois. For the reason that pathological processes are but variations of physiological processes in one direction or another, there is appended to almost every section those variations which are regarded by the clinician as pathological. In this way the student is made to realize not only the close interdependence of physiology and pathology, but the necessity for a thorough and accurate knowledge of the former for an intelligent comprehension of the latter. The work of Landois thus becomes a guide which conducts the student from the physiological laboratory to the work of the clinician. That it has been successful in this respect, and that it meets the needs of students and practitioners of medicine, is the only explanation that can be offered for the ex- traordinary fact that it has passed through ten large editions in Ger- many in twent}^ years, and, in addition, has been translated into French, Russian, English, Italian, and Spanish. The continued success of each successive edition in Germany and the frequent requests for an English edition have convinced the pub- lishers that a new translation would be acceptable to students and practitioners of the present day and decided them to issue the work in its present form. The translation was intrusted to Dr. A. A. Eshner, Professor of Clinical Medicine in the Philadelphia Polyclinic. In this he was ably assisted by Drs. Bernard Kohn, E. A. Shumway, Maurice Ostheimer, R. Max Goepp, Brooke M. Anspach, C. A. Fife, D. J. McCarthy, and W. B. Stanton. The text has been revised and edited by Dr. Albert P. Brubaker, Professor of Physiology in the Jefiferson Medical College. The proof has been largely read and the index pre- pared by Dr. Colin C. Stewart, Assistant Professor of Physiology in Dartmouth College. The publishers wish to express their appreciation of the conscientious care which has been given by each and all to the preparation of this edition. PREFACE TO THE TENTH EDITION. In spite of the short interval that has elapsed between the appear- ance of the ninth and that of this new edition all sections of the book have been subjected to extensive revision, with the inclusion of the results of the most recent investigations. The number of illustrations has been increased and some have been replaced by better ones. Since the book has been placed in the hands of students and phy- sicians in ten large editions, as well as in several English editions, a Russian translation in a second edition, an Italian, a French, and a Spanish translation, I have become more firmly established in the conviction that the plan according to which I have labored, both as author of this book and as teacher, is the correct one. Physiology is the foundation of internal medicine, and it should, therefore, be so taught that the physician can continue to build upon it and find sup- port in it. This has been my endeavor; in this sense the book has been revised uniformly throughout in this edition. L. Laxdois. Greifswald. FOREWORD. TENDENCY AND PURPOSE OF THE WORK. In the preparation of the forelying concise Textbook of Physiology the author has been governed by an endeavor to provide for physicians and students a book that should supply the needs of the practising physician in larger measure than is done by the majority of similar works. With this end in view a brief outline of pathological variations is appended in every section to the description of the normal processes. This is done for the purpose of directing the attention of the student from the outset to the field of his future professional activity and of pointing out the extent to which the morbid process represents a de- rangement of the normal- On the other hand, opportunity is by this means afforded the practising physician to renew acquaintance readily with the theoretical doctrines that as a rule slip away from him all too soon in the pursuit of his vocation. Here he can without effort look back from the morbid phenomena under treatment to the normal pro- cesses and in the recognition of these obtain new suggestions for correct interpretation and treatment. From this standpoint the author has described fully all those methods of investigation that may Jje employed by the practitioner with great advantage and that as a rule are but briefl}' treated in books on physiology. Reference may be made here to the following sections: Blood-examination; graphic study of the normal and abnormal heart -beat; heart-sounds and heart -murmurs ; the pulse; the venous pulse; transfusion; normal and abnormal re- spiratory murmurs ; ventilation ; examination of the air in dwellings ; the sputum ; deviations from the normal digestive processes ; diabetes ; cholemia; the digestion in febrile patients; thermometry and calor- imetry in the febrile state; examination of drinking-water; meat and meat-preparations; excessive deposition of fat and muscle, and the means for its relief ; examination of the normal urine and the determina- tion of all pathological constituents, as well as of urinary concretions; uremia, ammoniemia, uric-acid diathesis; morbid disturbances in retention and evacuation of urine ; pathological alterations in the sudorif- erous and sebaceous secretions; galvanic conductivity through the skin; gymnastics and therapeutic gymnastics; pathological alterations in the motor functions; laryngoscopy and rhinoscopy; pathology of phonation and articulation ; physiological principles underlying the therapeutic application of electricity; constant currents and electrical apparatus. In the consideration of every individual nerve and the differ- ent nerve-centers a sketch of the pathological manifestations is added. With relation to the nerve-centers the derangements of the reflexes, those of conduction to the central organs, those of the respira- VIU FOREWORD. tory center, together with the means for resuscitating asphyxiated persons, and the group of angioneuroses, have received especial con- sideration. Particular importance has been attached to the physio- logical topography of the surface of the cerebrum in man with reference to modern investigation into the localization of the functions of the brain. The same principle has been followed also with relation to the physiology of the organs of special sense. Evidence of this will be found in the discussions of abnormalities of ocular refraction, the use of spectacles, ophthalmoscopy, the orthoscope, color-blindness and its practical significance, further investigations into the functions of the other special senses and their principal disorders. The embryological section has given especial consideration to the subject of developmental defects, and to malformations as the most important of these; and also to the means for determining the period of development reached by human embr3'os. In description it was the aim of the author to be as concise and comprehensive as possible. Elaborate discussions have been scrupu- lously avoided. At the same time the typography has been so arranged that the more important and purely physiological matters are presented in conspicuous type. Also, the beginner can without disadvantage pass over the pathologic-physiological sections; , the student during the period of clinical instruction will, however, with advantage review the field of normal physiology from the latter. The author has, further, considered it advisable to add to each physiological section a brief outline of the historical development of the subject in hand, and likewise a summary of the comiparative physi- ology of the animal kingdom. Finally, the histology and microscopic anatomy have been more fully considered in each section than is the case with most textbooks of physiology. On the basis of the plan thus outlined the appearance of the fore- lying work is I believe justified. That this plan has not been fallacious is indicated by the numerous discussions in the medical journals of North and South Germany, Austria, Switzerland, Hungary, Russia, France, England, Italy, Scandinavia, America, which have received the book with favor, and recognition. The author, however, is par- ticularly gratified that the book has been received with approval by physiologists. In order to dispel any anxiety on the part of those who perhaps may fear that the scientific eminence of our science, of funda- mental importance in the entire domain of medicine, may suffer from the attempted association of ph3'siology with the practical department of medicine, I shall quote a few words from a letter written by one of our most illustrious and most versatile phvsiologists : "Should anyone publish a handbook like that of yours, of which the first half is before me, he will be entitled to the thanks not only of the students, but also of the teacher and investigator. And as it is my ambition to combine in myself the three qualities indicated, my thanks are tendered you with all my heart. Your pathological descrip- tions are in their condensed brevity so masterfully clear that I promise myself from your book a most beneficial action and reaction upon the field of clinical medicine." .... If these words have been realized I should find m this fact a perfect reward for my endeavors. It has always appeared to me in my academic activity as a teacher that my principal aim must lie in the thorough FOREWORD. IX preparation of physicians for physiological thought. And if to this, mv aim, there l)e apposed the statement of prouder sound, "we make physiologists," this would not deflect me from my course as a teacher, of which 1 believe, in the words of the master lieroj^hilus: 'ttw ravrw ehui L. Landois. TABLE OF CONTENTS. INTRODUCTION. PAGE The Scope and Aim of Physiology and its Relation to Allied Branches of Physical Science, 17 Matter 18 Forces, 19 Law of the Constancy of Energy, 23 Animals and Plants, 25 Kinetic Energy and Life, 28 PHYSIOLOGY OF THE BLOOD. Physical Properties of the Blood 29 Microscopic Examination of the Blood, 31 The Red Blood-corpuscles (Erythrocytes) , 34 Preservation of Red Blood-corpuscles, 36 Permeability of Erythrocytes. — Isotonia (Hyperisotonia and Hypisotonia) . — Demonstration of the Stroma. — Lake coloration of the Blood 37 Form, Size, and Number of Erythrocytes in Different Animals 40 Development of Red Blood-corpuscles 41 Destruction of Red Blood-corpuscles 43 The White Blood-corpuscles (Leukocytes) , the Blood-plates and Elementary Granules 45 Abnormal Changes in the Red and White Blood-corpuscles, 50 Chemical Constituents of the Red Blood-corpuscles, 51 Preparation of Hemoglobin-crystals, 52 Quantitative Estimation of the Hemoglobin, 52 Employment of the Spectroscope for Hemoglobin Examination; Oxygen- combinations of Hemoglobin: Oxyhemoglobin and Methemoglobin, ... 55 Carbon-monoxid Hemoglobin and Carbon-monoxid Poisoning, 58 Other Hemoglobin-combinations 59 Decomposition of Hemoglobin 60 Hemin (Hematin Chlorid) ; Identification of Blood by Means of the Hemin- test, 61 Hematoidin, 63 The Colorless Proteid of Hemoglobin, 63 Proteid Bodies in the Stroma, 63 Remaining Constituents of the Red Blood-corpuscles, 64 Chemical Constituents of the Leukocytes 64 The Blood-plasma and Its Relation to the Serum, 65 Fibrin; Its General Properties; Coagulation 65 General Phenomena Attending Coagulation, 67 Nature of Coagulation, 68 Source of the Fibrinogenous Substances, 7° Relations of the Red Blood-corpuscles to Fibrin-formation : 71 Chemical Constitution of the Blood-plasma and the Serum, 72 THE GASES OF THE BLOOD. Absorption of Gases by Solid Bodies and by Fluids, 74 Diffusion of Gases: Absorption of Gaseous Mixtures 75 Separation of the Gases of the Blood 76 Quantitative Estimation of the Gases of the Blood, 77 Special Facts Concerning the Gases of the Blood 78 xi Xll TABLE OF CONTEXTS. PAGE As to the Presence of Ozone in the Blood, 79 Carbon Dioxid and Nitrogen in the Blood, 80 Estimation of the Individual Constituents of the Blood, 81 Arterial and Vcnovis Blood 82 The Amount of Blood, 8^ Abnormal Increase in the Amount of Blood or of Its Individual Parts, .... 84 Abnormal Diminution in the Amount of Blood or of Its Individual Con- stitvients, 86 PHYSIOLOGY OF THE CIRCULATION. Cause, Purpose, Division, 88 The Heart, 89 Arrangement of the Muscle-fibers of the Heart and Their Physiological Sig- nificance, 89 Arrangement of the Mtisculature of the Ventricles, 90 Pericardium; Endocardium; Valves, 91 The Coronary Vessels; Automatic Regulation, Nutrition, and Isolation of the Heart, 93 The Movements of the Heart. Variations in Tone 96 Pathological Disturbance of the Function of the Heart, 99 The Apex-beat. The Cardiogram, 100 The Time-relations of the Movements of the Heart, 104 Pathological Variations in the Heart-beat, • 107 The Heart-sounds, no Abnormalities in the Heart-beat, 112 Duration of the Movement of the Heart, 113 The Cardiac Nerves, 114 Irritability of the Automatic Motor Centers in the Heart and of the Heart- Muscle, 115 The Cardiopneumatic Movement, 121 Influence of the Respiratory- Pressure on the Dilatation and Contraction of the Heart, 122 THE MOVEMENT OF THE BLOOD IN THE CIRCULATION. Toricelli's Theorem on the Velocity of Escape of Fluids, 125 Propelling Force, Velocity and Lateral Pressure, 126 Movement through Capillary Tubes, 128 Continuous and Undulatory Movement in Elastic Tubes 128 Structure and Properties of the Blood-vessels, 129 Pulse-movement. — Technic of Pulse-examination 133 The Pulse-tracing, the Recoil-elevation and the Elasticity-elevations, 138 The Dicrotic Pulse, 142 Difterences in the Time-relations of the Pulse 143 Variations in the Strength, the Tension, and the Volume of the Pulse 145 Sphygmographic Tracings from Different Arteries, 146 Phenomena of Anacrotism 147 Influence of the Respirator^' Movements on Sphygmographic Tracings 149 The Influences of Pressure on the Shape of Sphj'-gmographic Tracings 152 Velocity of Propagation of Pulse-waves, 153 Propagation of Pulse-waves in Rubber Tubes 153 Propagation-velocity of the Pulse-waves in Man 154 Other Pulsatory Phenomena, 156 Vibration of the Body Due to the Action of the Heart and the Course of the Blood-waves 157 The Movement of the Blood 1 158 Schematic Reproduction of the Circulation 160 Capacity of the Ventricles 161 Methods for Measuring the Blood-pressure 162 The Blood-pressure in the Arteries, 165 The Blood-pressure in the Capillaries, 168 The Blood-pressure in the Veins 169 The Blood-pressure in the Pulmonarv Arterv 169 Measurement of the Velocity of the Blood-current, 171 TABLE OF CONTENTS, Xlll I'ACE ^75 The Velocity of the Current in the Arteries, Capillaries, and Veins.. . Estimation of the Capacity of the \"entricles from the Current-velocity by the Method of Carl V'ierordt, ^ 176 The Duration of the Circulation, 177 The Work of the Heart 178 The Movement of the Blood in the Smallest Vessels, . 178 The Migration of the Blood-corpuscles from the Vessels; Stasis; Diapedesis, 180 The Movement of the Blood in the Veins 182 Soimds and Murmurs in the Arteries, 183 Acoustic Phenomena within the Veins, 184 The Venous Pulse. The Phlebogram, 185 The Distribution of the Blood, 188 Plethysmography, 189 Transfusion of Blood 19° The Ductless Glands. Internal Secretions 193 Comparative, 198 Historical ^99 PHYSIOLOGY OF RESPIRATION. Objects and Subdivisions, 201 Strvicture of the Air-passages and the Lungs, 201 Mechanism of the Respiratory Movements. Abdominal Pressure, 204 Respiratory Volumes, 205 The Rate of Respiration, 207 The Time Relations of Respiratory Movements. Pneumatography, 207 Types of Respiratory Movements, 210 Pathological Variations in the Respiratory Movements, 210 Svimmary of the Muscular Mechanism Concerned in Inspiration and Ex- piration 212 Action of the Individual Respiratory Muscles, 213 Dimensions and Expansibility of the Thorax 217 Respiraton,' Excursion of the Lungs, 218 Variations 'from the Normal Percutory Conditions in the Thorax, 220 The Normal Respiratory Soimds '221 Pathological Respirator}'- Soimds, _. . 222 Pressure in the Air- Passages during Respiration . 223 Mouth-breathing and Nasal-breathing 224 Modified Respirators^ Acts, 225 Chemistrv of Respiration, 226 Quantitative Estimation of the Carbon Dioxid, the Oxygen, and the Aqueous Vapor in Gaseous Mixtures, 226 Methods of Investigation , 227 Composition and Properties of Atmospheric Air, 229 Composition of Expired Air 231 Extent of the Daily Interchange of Gases, 232 Factors Influencing the Extent of the Respiratory Exchange of Gases, 232 Diffusion of Gases within the Respiratory Organs, • 237 Interchange of Gases between the Blood in the Pulmonary Capillaries and the Air in the Alveoli 23S The Respiratory Gaseous Exchange as a Dissociation Process 240 Cutaneous Respiration 241 Internal Respiration or Tissue-respiration, 241 Respiration in a Closed Space, or with Artificial Changes m the Amounts of Oxygen and Carbon Dioxid in the Respired Air, 244 Respiration of Foreign Gases 245 Other Injurious Substances in the Inspired Air, • • • 245 Renewal of the Air in Living-rooms (Ventilation). Examination of the Air, 246 Normal Secretion of Mucus in the Air-passages. The Expectoration (Sputum) -49 Effects of Atmospheric Pressure, 251 Comparative. Historical 254 XIV TABLE OF CONTENTS. PHYSIOLOGY OF DIGESTION. PAGE The Motith and Its Glands, 256 The Salivary Glands, 257 The Secretory Activity of the Salivary Glands, 259 The Nerves of the Salivary Glands, 259 The Influence of the Nervous System on the Secretion of Saliva, 260 The Saliva from the Individual Glands, 262 The Mixed Saliva, the Secretion of the Mouth, 263 Physiological Actions of the Saliva 264 Tests for Sugar ■ 267 Quantitative Estimation of Sugar, 268 The Mechanics of the Digestive Apparatus, 270 The Prehension of Food 270 The Movements of Mastication, 270 Structure and Development of the Teeth 272 Movements of the Tongue, 276 The Act of Swallowing (Deglutition) , 277 The Movements of the Stomach. — Vomiting, 280 The Movements of the Intestines, 282 The Evacuation of Feces (Defecation) ,....■ 283 Nervous Influences Affecting the Intestinal Movements, 286 The Structure of the Gastric Mucous Membrane, 289 The Gastric Juice, 292 The Secretion of the Gastric Juice, 293 Methods of Obtaining the Gastric Juice. The Preparation of Artificial Digestive Fluids; Demonstration and Properties of Pepsin, 295 The Process and the Products of Gastric Digestion 297 The Gases of the Stomach, 301 Structure of the Pancreas, 302 The Pancreatic Juice, 303 The Digestive Activity of the Pancreatic Juice, 304 The Secretion of the Pancreatic Juice, 307 The Structure of the Liver, 308 Chemical Constituents of the Liver-cells, 311 Diabetes Mellitvis, 313 The Constituents of the Bile, 315 Secretion of Bile, 319 Excretion of Bile, 321 Resorption of Bile, 322 Action of the Bile, 324 Final Fate of the Bile in the Intestinal Canal 325 The Intestinal Juice, 326 Fermentative Processes in the Intestines Due to Microbes; Intestinal Gases, 329 Processes in the Large Intestine. Formation of the Feces 335 Morbid Alterations in Digestive Activity, 339 Comparative Physiology of Digestion, 343 Historical, 346 PHYSIOLOGY OF ABSORPTION. Structure of the Organs of Absorption, 348 Absorption of the Digested Food '. 351 Absorptive Activity of the Wall of the Alimentary Canal 354 Influence of the Nervoixs System, 359 Nourishment by Means of " Nutritive Enemata," 359 System of Lacteal and Lymphatic Vessels, 360 Origin of the Lymph-channels. Lymphatics, 361 The Lymph-glands, 363 Properties of the Chyle and the Lymph, 366 Quantitative Relations of Lymph and Chyle, 368 Origin of Lymph, 369 Circulation of Chyle and Lymph, 371 Absorption of Parenchymatous Effusions, 373 Lymph-stasis and Serous Effusions, 374 TABLE OF CONTEXTS. XV PACK Cc)mparativc 375 Historical 375 PHYSIOLOGY OF ANIMAL HEAT. Sources of Heat 377 Animals with Constant and with Variable Temperature, 381 Methods of Estimating the Temperature: Thermometry, 382 Temperature-topography 385 Influences Affecting the Temperature of Individual Organs, 387 Measurement of the Volume of Heat: Calorimetry, 389 Heat-conduction of Animal Tissues. Expansibility of Animal Tissues by Heat, 390 Variations in the Mean Bodily Temperature, 391 Regulation of the Temperature 394 Heat-balance, 399 Variations in Heat-production, 400 Relation of Heat-production to the Work Performed by the Body, 400 Accommodation to Variations in Temperature 402 Accumulation of Heat in the Body 403 Fever 404 Artificial Elevation of the Bodily Temperature, 406 Employment of Heat, 407 Post-mortem Elevation of Temperature, 407 The Influence of Cold upon the Body, 408 Artificial Reduction of the Bodily Temperature in Animals 409 Employment of Cold, 411 The Temperature of Inflamed Parts 411 Historical. Comparative 411 PHYSIOLOGY OF METABOLISM. Scope of Metabolism, 413 SYNOPSIS OF THE MOST IMPORTANT SUBSTANCES USED AS FOOD. Water. Examination of Drinking-water 413 Structure and Secretory Activity of the Mammary Glands, 417 Milk and Milk-preparations, 419 Eggs, 423 Meat and Meat-preparations, 423 Vegetable Foods, 426 Condiments: Coffee, Tea, Chocolate, Alcoholic Drinks and Spices 428 PHENOMENA AND LAWS OF METABOLISM. Metabolic Equilibrium, 430 Metabolism in the State of Starvation, 439 Metabolism with an Exclusive Diet of Meat, Albumin or Gelatin, 442 An Exclusive Diet of Fats or Carbohydrates, 443 Laws Governing Metabolism on a Mixed Diet of Meat and Fat or Carbohy- drates, 443 Origin of the Fat in the Body, 444 Deposition of Fat and Flesh in the Body (Hypemutrition) . Corpulence and the Means for its Correction, 445 The Metabolism of the Tissues, 448 Regeneration, 451 Transplantation and Adhesion 454 Increase in Size and in Weight in the Process of Gro-wth, 455 SUMMARY OF THE CHEMICAL CONSTITUENTS OF THE ORGANISM. Inorganic Constituents, 45^ Organic Constituents. The Proteid Bodies or Protein-Substances. The True Albuminous Bodies, 457 The Albuminoid Bodies, 460 Nitrogenous Glucosids, 462 XVI TABLE OF CONTENTS. PAGE Nitrogenous Pigments, 462 Organic Non-nitrogenous Acids, 462 The Fats 462 The Alcohols, 464 The Carbodyhrates, 464 Ammonia-derivatives and Their Combinations, 467 Aromatic Bodies, 468 Historical 468 THE SECRETION OF URINE. Structure of the Kidney 469 The Urine. The Physical Characters of the Urine, 472 THE ORGANIC CONSTITUENTS OF THE URINE. Urea 475 Qualitative and Quantitative Estimation of Urea, 478 Uric Acid, 479 Qualitative and Quantitative Estimation of Uric Acid, 482 Kreatinin, Xanthin-bases, Oxaluric, Oxalic, and Hippuric Acids, 482 Coloring-matters of the Urine 485 Substances Forming Indigo, Phenol, Kresol, Pyrocatechin , and Skatol. Other Substances 487 THE INORGANIC CONSTITUENTS OF THE URINE. Spontaneous Alterations in the Urine on Standing; Acid and Ammoniacal Urinary Fermentation, 493 Albumin in the Urine: Proteinuria, Albuminuria, 494 Blood and Hemoglobin in the Urine: Hematuria, Hemoglobinuria 497 Biliar}- Constituents in the Urine: Choluria, 500 Sugar in the Urine: Glycosuria 501 Cystin, 503 Leucin and Tj-rosin, 503 Sediments in the Urine, 503 Schematic Resurne for the Recognition of all of the Sediments in the Urine, 506 Urinary Concretions, 507 The Physiological Process of Urinary Secretion 509 The Preparation of the Urine, 513 The Passage of Various Substances into the Urine, 514 Influence of the Nerves upon the Secretion of the Kidneys, 514 Uremia; Ammoniemia; Uric-acid Dyscrasia, .' 516 Structure and Fimctions of the Ureters, 517 Structure of the Urinary Bladder and the Urethra, 519 Collection and Retention of the Urine in the Bladder. Evacuation of the Urine, 520 Morbid Derangement of Urinary Retention and of Micturition 523 Comparative. Historical, 524 FUNCTIONS OF THE EXTERNAL INTEGUMENT. Structure of the Skin, 525 The Nails and the Hair, 527 The Glands of the Skin, 531 The Skin as an External Covering, 532 Cutaneous Respiration. Cutaneous Secretion. Sebum. Sweat. Pigment- formation, 533 Influences Affecting the Secretion of Sweat ; Nervous Control Affecting the Secretion of Sweat, 536 Nervous Control Affecting the Secretion of Sweat 536 Physiological Care of the Skin. Pathological Abnormalities in the Secre- tion of Sweat and Sebum, 538 Absorption through the Skin. Galvanic Conductivity, 539 Comparative. Historical ' 540 TABLE OF CONTENTS. XVll PHYSIOLOGY OF THE MOTOR APPARATUS. PAGE Structure and Arrangement of the Muscles 542 Physical and Chemical Properties of Muscular Tissue 547 Metabolism in Muscle. The Source of Muscular Energy, 549 Muscular Rigidity (Cadaveric Rigidity, Rigor Mortis), 552 Irritability, Stimulation, and Death of the Muscle 555 Change of Shape in Active Muscle 558 The Time-relations of Muscular Contraction. Myography. Simple Con- traction. Tetanus. Isotony. Isometry, 560 Rapidity of Propagation of Muscular Contraction 568 Muscular Work, 569 The Elasticity of Passive and Active Muscle. Myotonometry 572 Heat-production in Active Muscle 576 The Muscle-murmur, 578 Fatigue of Muscle 579 Mechanism of the Bones and Their Attachments, 581 Arrangement and Function of the Muscles in the Body, 5S3 Gymnastic Exercises and Therapeutic Gymnastics. Pathological Varia- tions in the Motor Functions 587 SPECIAL MOVEMENTS. Standing, 589 Sitting, 592 Walking, Rvmning, Jumping, 592 Comparative Study of Motion, 596 VOICE AND SPEECH. Scope of the Voice. Preliminary Physical Considerations Concerning the Production of Sound in Reed-apparatus 599 Arrangement of the Lar}'nx 600 Examination of the Larj'nx 606 Conditions Influencing the Sounds of the Vocal Apparatus 609 Range of the Voice 610 Speech. The Vowels, 611 The Consonants 615 Pathological Variation in Voice and Speech, 617 Comparative. Historical, 618 GENERAL PHYSIOLOGY OF THE NERVOUS SYSTEM AND ELECTRO-PHYSIOLOGY. General Conception of the Nervous System. Structure and Arrangement of the Elements of the Nervous System, 621 Chemistn,- of Nervous Tissue. Mechanical Properties of Nerves, 626 Metabolism in Nerves, 628 Irritability of Nerves. Stimuli 629 Diminished Irritabilit}-; Death of the Nerve. Nerve-degeneration and Nerve-regeneration, 6^^ ELECTRO-PHYSIOLOGY. Preliminary Physical Considerations. The Galvanic Current. Electro- motors. Conduction-resistance. Ohm's Law. Conduction through Animal Tissues. The Rheocord, 63 8 The Action of the Galvanic Current upon the Magnetic Needle. The Multi- plicator, 641 Electrolysis. Transition-resistance. Galvanic Polarization. Constant Batteries and Unpolarizable Electrodes. Internal Polarization of Moist Conductors. Cataphoric Action of the Galvanic Current. Sec- ondar}' Resistance . 643 Induction. The Extra Current. Magnetization of Iron by the Galvanic Current. Voltaic Induction. Unipolar Induction-effects. Magneto- induction, 645 XVlll TABLE OF CONTENTS. PAGE Du Bois-Reymond's Sliding Induction-apparatus. Pixii-Saxton's Magneto- induction Machine, 646 Electrical Currents in Resting Muscle and Nerve. Cutaneous Currents. Glandular Curj-cnts 648 Currents of Stimulated Muscles and Nerves and of Secretory Organs, 652 Currents in Nerves and in Mtiscles in the Electrotonic State, 656 Theories and Currents in Muscles and Nerves, 657 Altered Irritability of Nerve and Muscle in Electrotonus 660 The Development and the Disappearance of Electrotonus. The Law of Contraction. The Law of Polar Stimulation 663 Rapidity of Conduction of the Stimulus in Nerves, 667 Double Conduction in Nerves, 669 Employment of Electricity for Therapeutic Purposes. Degenerative Reac- tions of Muscle and Nerve ' 669 Comparative. Historical 675 PHYSIOLOGY OF THE PERIPHERAL NERVES. Classification of Nerve-fibers According to Function 677 THE CEREBRAL NERVES. Olfactory Tract and Bulb, 678 Optic Nerve and Tract. 679 Oculomotor Nerve 680 Trochlear Nerve, 682 Trigeminal Nerve 683 Abducens Nerve, 693 Facial Nerve,. 694 Auditory Nerve, 699 Glossopharyngeal Nerve 703 Vagus Nerve 704 Accessory Nerve of Willis, 712 Hypoglossal Nerve, 71^ The Spinal Nerves, 713 Sympathetic Nervous System 718 Comparative. Historical ,... 721 PHYSIOLOGY OF THE NERVOUS CENTERS. General Considerations, 723 THE SPINAL CORD. The Structure of the Spinal Cord, 723 The Spinal Reflexes, 728 Inhibition of Reflexes, 731 Centers in the Spinal Cord, 734 Irritability of the Spinal Cord, 736 Conducting Paths in the Spinal Cord 7:;8 THE BRAIN. General Ovttline of the Structure of the Brain, 741 The Medulla Oblongata, 748 Reflex Centers in the Medulla Oblongata 748 The Respiratory Center and the Innervation of the Respiratory Apparatus, 750 The Center for the Inhilntory Nerves (Diminishing the Frequency and the Strength) of the Heart and the Fibers Passing to the Vagus 758 The Center for the Accelerator and Augmenting Cardiac Nerves and the Fibers to which it Gives Rise, 760 The Vasomotor Center and Nerves, '. 762 The Vasodilator Center and Nerves, 771 The Spasm-center. The Sweating Center, 773 Psychic Functions of the Cerebrum 774 The Motor Cortical Centers of the Cerebrum 780 The Sensorial Cortical Centers 785 TARLR OF CONTENTS. XIX PAGE The Cortical Thermic Center, 788 Physiological Topography of the Surface of the Cerebrum in Man 791 The Basal Ganglia of the Cerebrum, The Midbrain. Forced Movements. Other Cerebral Functions 802 Functions of the Cerebellum 807 Protective and Nutritive Apparatus of the Brain, 809 Comjiarative. Historical 811 PHYSIOLOGY OF THE ORGANS OF SPECIAL SENSE. Introductory Remarks 813 THE VISUAL APPARATUS. Preliminary Anatomical and Histological Observations. The Intraocular Pressure, 815 Preliminary Dioptric Considerations, 823 Application of Dioptric Laws to the Eye. Construction of the Retinal Image. The Ophthalmometer. Erect Images, 829 Accommodation of the Eye, 83 1 Refractive Power of the Normal Eye. Anomalies of Refraction, 835 Measure of the Power of Accommodation, 837 Spectacles, 839 Chromatic and Spherical Aberration. Defective Centering of the Refracting Surfaces. Astigmatism, 840 The Iris, 841 Entoptic Phenomena. Subjective Optical Manifestations 844 Illumination of the Eye, and the Ophthalmoscope, 847 The Function of the Retina in Vision, 850 Perception of Colors, 856 Color-blindness: Its Practical Importance, 860 Time-relations of Retinal Stimulation. Positive and Negative After- images. Irradiation. Contrast 862 Ocular Movements and Octtlar Muscles, 866 Binocular Vision, 870 Single Vision. Identical Retinal Points. Horopter. Suppression of Double Images, 871 Stereoscopic Vision. Judgment of Solidity 873 Estimation of Size and of Distance. False Estimates of Size and Direction. 877 Organs for the Protection of the Eye, 879 Comparative. Historical, 881 THE AUDITORY APPARATUS. Plan of the Structure of the Ear, 885 Preliminary Physical Considerations, 886 Auricle. External Auditory Canal 887 The Tympanic Membrane, 888 The Auditory Ossicles and Their Muscles, 890 Eustachian Tube. Tympanic Cavity, 894 Sound-conduction in the Labyrinth, 896 Structure of the Labyrinth and the Terminations of the Auditory Nerve,. . 897 Quality of Auditory Perceptions. Perception of the Pitch and Intensity of Tones, 899 Perception of Timbre. Analysis of Vowels 903 Function of the Labyrinth in the Act of Hearing, , 907 Simultaneous Action of Two Tones. Harmony. Beat. Discord. Differ- ential Tones and Summation-tones 90S Auditory Perception. Fatigue of the Ear. Objective and Subjective Hearing. Associated Sensations. Auditor}^ After-sensations 910 Comparative. Historical 912 THE OLFACTORY APPARATUS. Structttre of the Olfactory Apparatiis 913 Sensation of Smell Q14 XX TABLE OF COXTENTS. PAGE THE GUSTATORY APPARATUS. Situation and Structure of the Organs of Taste 916 Gustatory Sensations, 917 THE TACTILE APPARATUS. Terminations of the Sensory Nerves 920 Sensory and Tactile Sensations, 922 Sense of Space, 924 The Pressure-sense, 927 The Temperature-sense, 930 Common Sensation. Pain, 934 The Muscular Sense. Power-sense 936 PHYSIOLOGY OF REPRODUCTION AND DEVELOPMENT. Varieties of Generation 938 The Seminal Fluid, 942 The Ovum, 946 Puberty 951 Menstruation, 951 Erection, 9c;5 Ejaculation. Reception of the Seminal Fluid 957 Impregnation of the Ovum, 958 Cleavage, Morula, Blastula, Gastrula, Formation of the Germinal Layers. First Rudiments of the Embryo, 961 Formations from the Epiblast, 966 Formations from the Hypoblast and the Mesoblast, 969 Foldi'ng Off of the Embryo. Formation of the Heart and the First Circu- lation, 970 Further Development of the Body, 972 Formation of the Amnion and the Allantois, 974 Human Fetal Membranes. Placenta. Fetal Circulation 975 Chronology of Human Development. Fetal M^jvements 980 Development of the Osseous System, 983 Development of the Vascular Sj'stem, 990 Development of the Alimentary Canal, 993 Development of the Urinary and Sexual Organs, 995 Development of the Central Nervous System, 1000 Development of the Organs of Special Sense, looi Parturition 1002 Comparative. Historical, 1004 LIST OF ILLUSTRATIONS. 1. Human and Ami)hibian Colored Blood-corpuscles, 32 2. Apparatus of Abbe and Zeiss for Counting the Corpuscles, ^^ 3. The Mclangeur Pipct or Mixer, 33 4. Red Blood-corpuscles, 34 5. Formation of Red Blood-corpuscles within " Vaso-formative Cells," from the Omentum of a Rabbit Seven Days Old, 42 6. White Blood-corpuscles of Man and Frog, 45 7. Human Leukocytes, showing Ameboid Movements, 47 S. Various Forms of Leukocytes and Erythrocytes, 48 9. " Blood-plates" and their Derivatives 49 10. Hemoglobin-crN'stals, 52 1 1 . V. FleischTs Hemometer, 53 12. Diagrammatic Representation of the Spectroscope for Study of the Ab- sorption-spectra of the Blood, 55 13. 14. The Absorption-spectra of Oxyhemoglobin, and of Gas-free Hemo- globin with Increasing Concentration, 56 15. The Various Absorption-spectra of Hemoglobin, 57 16. The Absorption-spectra of Hematoporphyrin, 60 17. Hemin-cr\^stals, 62 18. Hemin-cni'stals Prepared from Blood-stains, 62 19. Hematoidin-cn-stals 63 20. Diagrammatic Representation of Pfluger's Pump for the Extraction of the Gases of the Blood, 77 21. Diagrammatic Representation of the Circulation 88 22. Course of the Muscle-libers in the Left Auricle ijoh. Reid). Distribu- tion of Transversely Striated Muscle-fibers on the Superior Vena Cava (Flischer) , .' 90 23. Course of the Muscle-fibers in the Ventricles (C. Ludwig) , 91 24. Semilunar Valves Closed and Opened, 93 2 5 . Diagrammatic Representation of the Auricular Systole with Ventricular Diastole, and of Auricular Diastole with Ventricular Systole, 96 26. Plaster Cast of the Ventricles of the Human Heart, Viewed from Behind and Above 98 27. The Closed Pulmonary Semilunar Valves of Man, Viewed From Below, . 99 28. Curves of the Apex-beat 10 r 29. Changes of the Heart during Systole, and Sections of the Thorax, 102 30. Contraction-curves from the Ventricle of a Rabbit Registered on a Plate Attached to a Vibrating Tuning-fork 105 3 1 . Curves Showing the Movements of the Separate Portions of the Heart {Chauveaii and Marey) 106 32. Simultaneous Record Showing Cardiogram, the Curve of the Ventric- ular Pressure and that of the Aortic Pressure from the Dog {K. Hiirthle),. 107 33. Various Forms of Pathological Apex-beat Curves, 109 34. Topography of the Thorax and of the Thoracic Viscera {v. Luschka and V. Diisch) iir 35. Landois' Cardiopneumograph, and Cardiopneumatic Curves Obtained with its Aid 122 36. Apparatus for the Demonstration of the Influence of Respiratory Ex- pansion and Contraction of the Thorax on the Heart and the Cir- culation 124 37. Pressure- vessel Filled with Water ' : 125 ^8. A Pressure- vessel, 126 XXn LIST OF ILLUSTRATIONS. FIG. ^ PAGE 39. Small Arterial Twig Showing the Individual Layers of the Arterial Wall, 130 40. Capillar}' Vessels, 131 41. Poiseuilie's Box-cabinet Sphygmometer, 134 42. The Tubular Sphygmometer of Herisson and Chelius, 134 43. Marey's Sphygmograph (Diagrammatic), 135 44. Brondgeest's Pansphygmograph Constructed on Upham's and Marey's Principle of the Propagation of Movement through Air-containing Drums Covered with Elastic Membranes, 135 45. Landois' Angiograph Represented Diagrammatically 136 46. Dudgeon's Sphygmograph, 137 47. Sphygmographic Tracing from the Radial Artery made with Landois' Angiograph Attached to a Vibrating Tuning-fork, 138 48. Landois' Gas-sphygmoscope, 138 49. Hemautographic Tracing from the Posterior Tibial Arter\- of a Large Dog ' 139 50. Sphygmographic Tracings from Arteries, 140 51. Normal Pulse-production of the Dicrotic Pvilse, 143 52. Alternating Pulse, 145 53. Tracing from the Posterior Tibial Arter}', Recorded on the Tablet At- tached to a Vibrating Tuning-fork by means of Landois' Angiograph. . 147 54. Anacrotic Tracings from the Radial Artery, 148 55. Anacrotic Pulse Cur\-es 149 56. Influence of Respiration on the Sphygmographic Tracing (Riegel) 150 57. The Effect of Marked Expiratory and Inspiraton,- Pressure on Sphyg- mographic Curves 151 58. Paradoxical Pulse (Kussmaul), 152 59. Variations in the Shape of Sphygmographic Curves Produced by In- creasing the Pressure 152 60. Method of Recording the Pulse-cur\-es Obtained from an Elastic Tube on a Tablet Attached to a Vibrating Tuning-fork, 154 61. Tracings from the Carotid and Posterior Tibial Arteries 155 62. Tracing from the Ulnar Artery on a Recording Surface Attached to a Vibrating Timing-fork, 156 63. Vibration Cur^-es and Apparatus for Registering Same 158 64. Model of the Circulation by Ernst Heinrich Weber, 161 65. Ludwig's and Pick's Kymographs (C Lududg and Einbrodt), 163 66. Adolph Pick's Flat-spring Kymograph, 164 67. Hurthle's Kymograph, 164 68. A. W. Volkmann's Hemodromometer and C. Ludwig's Rheometer, . . . . 172 69. Vierordt's Hemotachometer; Chauveau's and Lortet's Dromograph; Dromographic Cur\"e, 173 70. Diagrammatic Representation of Cybulski's Photohemotachometer. . . . 174 7 1 . Small Mesenteric Vessel from a Frog showing the Migration of Leuko- cytes, :••••. i^i 72. Various Forms of Venous Pvdse, chiefly after Friedreich 186 73. Mosso's Plethysmograph, 189 74. Diagrammatic Representation of the Circulation 198 75. Cross-section of Several Pulmonar}- Alveoli 202 76. Hutchinson's Spirometer 206 77. Brondgeest's Tambour and Curve 208 78. Air-volume Recorder (Pneumoplethysmograph) (Gad), 209 79. Pneumatograms Recorded by Means of Riegel's Stethograph 209 So. Frontal Section of the Thorax at the Extremity of the Twelfth Rib on Each Side to Demonstrate the Form of the Diaphragm During Expiration and Inspiration, 213 81. Diagrammatic Representation of the Mechanism of the Intercostal Muscles 216 82. Cvrtometer-curve from a Case of Left-sided Retraction of the Thorax in a Twelve-year-old Girl {Eichhorst) 217 83. Sibsons Thoracometer 218 84. Topography of the Boundaries of the Lungs and the Heart during In- spiration and Expiration {v. Dusch) 219 85. Apparatus for the Collection of Expired Air (Andral ajid Gavarret); Carl Vierordt's Anthracometer 226 86. Respiration Apparatus of Scharling 227 LIST OK 1 1, LUSTRATIONS. XXUl FIG. PACE 87. Diagrammatic Representation of Rcgnault and Rcisct's Resjiira- tion Ap])aratus 228 88. Diagram of v. Pettenkofer's Respiration Apparatus, 229 8c). Apparatus for Measuring the Temperature of the Expired Air, 231 90. Puhiionary Catheter, 239 91. Stratified CiHatcd Cylindrical Epithelium of the Larynx (Horse) {Toldt) 246 92. Objects Found in the Sputum, 250 93. Section through Lym])h-follicles of the Root of the Tongue (Scheiik) . . . . 256 94. Histology of the Salivary Glands 257 95. Diagrammatic Representation of a Salivary Gland, 258 96. Potato Starch, 265 97. Apparatus for the Quantitative Estimation of Sugar, 268 98. The Soleil-Ventzke Saccharimeter, 269 99. Longitudinal Section through an Incisor Tooth 272 [oo. Transverse Section through Dentine . 273 roi. Interglobular Spaces in the Dentine 273 [02. Dentine and Enamel 274 [03. Transverse Section of the Root 274 ro4. ) [05. y Development of a looth, 274, 275 [06. j [07. Transverse Section through the Esophagus, 279 [08. The Perineum and its Muscles 284 [09. The Levator Ani and External Sphincter Ani Muscles 285 10. Sectional View of the Gastric Mucous Membrane, showing the Crater- like Depressions of the Gastric Crypts, 289 11. Fundus-gland of the Stomach, 290 . Goblet-cells of the Stomach. Pyloric Gland of the Stomach, 290 13. Portion of a Gastric Gland, 290 14. Vertical Section through the Gastric Mucous Membrane, 291 15. Changes in the Cells of the Pancreas in the Different Stages of Ac- tivity, 302 16. Diagrammatic Representation of an Hepatic Lobule, 309 17. Various Appearances of the Liver-cell, 310 18. Blood-capillaries, Finest Biliary Ducts, and Liver-cells, in Their Mu- tual Relations in the Rabbit's Liver {E. Hering) 310 19. Interlobular Bile-duct from the Human Liver {Schenk) 310 :2o. Longitudinal Section through the Small Intestine of a Dog, 327 . Transverse Section throtigh Lieberkiihn's Glands, 328 [22. Bacterium Aceti and Bacillus butyricus, 330 [23. Hay-bacillus (Bacillus subtilis) 332 :24. Longitudinal Section through the Large Intestine, 336 [25. Feces, 337 :26. Bacteria of Feces, 339 '■I . Structure of the Absorption-apparatus of a Villus, 349 [28. Blood-vessels of an Intestinal Villus, 350 [29. Apparatus for Diosmosis, 352 [30. Origin of the Lymph-channels, 361 [31. Blood-vessels, Recticulum, and Sheath of a Lymph-follicle, 364 [32. Part of a Lymph-gland 365 ^?>?>- Water Calorimeter {Favre and Silbenuann) , 379 34. Walferdin's Metastatic Thermometer 383 [35. Diagrammatic Representation of Thermo-electric Apparatus for the Measurement of Temperature, 384 [36. Variations in the Bodily Temperature during Health within Twenty- four Hours, 393 [37. Milk-glands during Inaction and Secretion, 417 [38. Section through a Grain of Wheat, 427 [39. Section through a Potato, 428 [40. Yeast-cells Growing 429 [41. Composition of Animal and Vegetable Foods 436 [42. Structure of the Kidneys 470 [43. Graduated Cylinder and Flask for Measuring the Amount of Urine, .... 473 [44. Urinometer 473 XXIV LIST OF ILLUSTRATIONS. FIG. PACK 145. Graduated Buret, 475 146. Urea and Urea Nitrate, 476 147. Graduated Pipet, 479 148. Different Forms of Uric Acid, 481 149. Kreatinin-zinc Chlorid 484 150. Hippuric Acid, 485 151. Spectrum of Urobilin in Acid Urine, ' 486 152. Spectrum of Urobilin in Alkaline Urine, 486 153. Sediment due to Acid Urinary Fermentation, 493 154. Sediment due to Ammoniacal Urinary Fermentation 494 155. Micrococcus ureas, 494 156. Esbach's Albtmiinimctcr, 496 157. Thorn-apple shajjcd Blood-corpuscles in the Urine, 497 158. Peculiar Changes in the Shape of the Red Blood-corpuscles in Case of Renal Hematuria (Friedreich) 497 159. Red and White Blood-corpuscles of Varying Size, 498 160. Greatly Shrtmken Red Blood-corpuscles in the Urine from a Case of Catarrh of the Bladder, in the midst of numerous Leukocytes and Small Crystals of Triple Phosphates, 498 161. Spectroscope for Examination of the Urine as to the Presence of Hemo- globin 499 162. Cystin and Oxalate of Lime, 502 163. Leucin, Tyrosin and Ammonium Urate, 503 164. Fungi in Urine, 304 165. Epithelial Tube-casts, 504 i66. Blood-casts 505 167. Casts of Leukocytes (v. Jaksch), 505 168. Acid Sodium Urate in the Form of Tube-casts 505 169. Finely Granular Tube-casts, 50=5 170. Coarsely Granular Tube-casts {v. Jaksch) , 503 171. Hyaline Casts 505 172. Calcic Carbonate and Phosphate 506 173. Ammonio-magnesium Phosphate, 507 174. Imperfectly Developed Crystals of Ammonio-magnesium Phosphate,. . 507 175. Acid Ammonium Urate {v. Jaksch) , 507 176. Basic Magnesium Phosphate 507 177. Lower Portion of the Male Bladder, with the Commencement of the Ureter, Opened through a Median Incision in the Anterior Wall, and spread out (Henle) , 518 178. Histolog)' of the Skin and the Epidermoidal Structures 526 179. Cutaneous Papillae Deprived of their Epidermis and the Vessels In- jected, 1527 180. Transverse Section of One-half of a Nail, through the True Nail-bed (Biesiadecki) 528 181. Transverse Section of a Hair below the Neck of the Hair- follicle, 530 182. Longitudinal Section through a Hair- follicle, with the Hair in Pro- cess of Change (v. Elmer) , 530 183. Sebaceous Gland with a Lanugohair, 532 184. Histology of Muscular Tissue, 543 185. Muscle-fibers with Nerve-ending, from the Lizard (IF. Kiihne), 544 186. Cross-section through the Gastrocnemius Muscle of the Frog {Griiizner) , 545 187. Unstriated Muscle-hbers, isolated by means of Diluted Alcohol 546 188. Special Forms of Unstriated Muscle-fibers from the Muscular Coat of the Aorta {v. Ebncr) , 546 189. Muscle-cells from the Frog's Stomach with Distinct Fibrils {Engel- mann) ^46 190. Sensor}- Nerve in a Tendon, 547 191. The Microscopic Phenomena of Muscular Contraction in the Individual Elements of the Fibrils {Engehnann) 5:^9 102. Diagrammatic Representation of v. Helmholtz's Myograph 561 193. Myogram of an Isotonic Contraction, , 362 194. Muscle Curves 564 195. Muscle Curves, Tetanus 566 196. Curves of Vokmtary Impulses, .■ 567 197. Isometric Muscular Act, 56S LIST OF ILLUSTRATIONS. XXV FlO. PAOK 198. Blix's Elasticity Recorder 574 199. Diagrammatic Representation of the Action of Muscles on the Bones,. . 585 200. Phases of the Movement of Walking, 593 201. Slow Walking, Pliotographed in Instantaneous Pictures (Marey) 594 202. Instantaneous Photograj^hs of a Runner (^Marey) 594 203. Instantaneous Photographs of a High Jump (Marey), 595 204. Anterior View of the Larynx, with its Ligaments and Muscular In- sertions, 601 205. Posterior View of the Larynx, after Removal of the Muscles 601 206. Posterior View of the Larjmx, with the Muscles 602 207. Nerves of the Larynx 602 208. Diagrammatic Horizontal Section through the Larynx 603 209. Diagrammatic Horizontal Section through the Larynx, to Illustrate the Action of the Arytenoid Muscles, 603 210. Diagrammatic Horizontal Section through the Larynx, to Illustrate the Action of the Internal Thyroarytenoid Muscles in Narrowing the Glottis, 604 211. Vertical Section of the Head and Neck, 605 212. Method of Making a Laryngoscopic Examination ; 606 213. The Laryngoscopic Image During Respiration, ; . . . . 606 2 14. Image of the Larynx when a Sound is Begun, 607 215. View of the Trachea as far as the Bifurcation 607 216. Position of the Laryngeal Mirror in the Practice of Rhinoscopy 607 217. The Rhinoscopic Image 608 218. Parts Concerned in Phonation, 613 219. Tumors of the Vocal Cords, Causing Diphthongia, 617 220. Histology of Nervous Tissues, 623 221. MeduUated Nerve-fiber Stained Black by Osmic Acid 624 222. Transverse Section through a Portion of the Median Nerve 624 223. Degeneration and Regeneration of Nerves, 634 224. Diagrammatic Representation of the Rheocord of du Bois-Reymond, . . 641 225. Scheme of a Galvanometer, 642 226. Scheme of an Induction Machine, 647 227. Magneto-induction Apparatus with Stohrer's Commutator, 647 228. Scheme of the Muscle Current 649 229. Diagrammatic Representation of the Capillary Electrometer, 649 230. Diagrammatic Representation of Bernstein's Differential Rheotome,. . . 655 231. Nerve Current in Electrotonus, 656 232. Diagrammatic Representation of the Electrotonic Relations of Irri- tability 661 233. Testing the Irritability in Electrotonus, 662 234. Diagrammatic Representation of the Distribution of the Electric Current in the Arm on Galvanization of the Ulnar Nerve 662 235. v. Helmholtz's Method for Determining the Propagation- velocity of the Nerve-stimulus, 668 236. Motor Points of the Radial Nerve and of the Muscles supplied by it. Dorsal Aspect of the Upper Extremity {Eichhorst) , 670 237. Motor Points of the Median and Ulnar Nerves, as well as of the Muscles supplied by them. Palmar Aspect of the Upper Extremity (Eichhorst) , 670 238. Motor Points of the Sciatic Nerve and its Branches, the Peroneal and Tibial Nerves (Eicliliorst) , 671 239. Motor Points of the Peroneal and Tibial Nerves on the Anterior As- pect of the Leg and Thigh. Peroneal Nerve on the left, Tibial Nerve on the Right {Eiclihorst) , 672 240. Diagrammatic Representation of the Semidecussation of the Optic Nerves, 679 241. Medulla Oblongata and Quadrigeminate Bodies, Magnified, 681 242. MediiUa Oblongata and Quadrigeminate Bodies, Magnified, 683 243. Semidiagrammatic Representation of the Ocular Nerves, the Con- nections of the Trigeminus and Its Ganglia and Those of the Facial and Glossophar\-ngeal Nerves, 690 244. Distribution of the Sensory Nerves of the Head, together with the Situ- ation of the Motor Points on the Neck 691 245. Motor Points of the Facial Nerve and of the Muscles Supplied by It (Eicliliorst) , 696 XXVI LIST OF ILLUSTRATIONS. FIG. PAGE 246. Scheme of the Branches of Vagus and Accessorius, 702 247. Distribution of the Cutaneous Nerves of the Upper Extremity (Henle), . 714 248. DistriVjution of the Cutaneous Xerves of the Lower E.xtremity (Henle). . 715 249. Diagrammatic Representation of the Course of a Thoracic Branch of the Sympathetic, 718 250. Transverse Section of the Spinal Cord at the Level of the Eighth Dor- sal Xerve (Scltu'albe) 724 251. Scheme of the X'erve Distribution of the Spinal Cord 725 252. System of Conducting Tracts in the Spinal Cord, at the Level of the Third Dorsal Vertebra (Flechsig), 726 253. Diagrammatic Representation of the Principal Tracts of the Spinal Cord 727 254. Diagrammatic Representation of the Structure of the Brain 743 255. Course of the Paths for Voluntar)^ Movement, 745 256. Course of the Motor and Sensory Paths through a Transverse Section of the Spinal Cord, 746 257. Course of the Sensory- Fibers from the Posterior Roots through the Spinal Cord upward to the Cerebrum 747 258. Cerebrum of Dog. Rabbit, Pigeon, Frog, and Carp 782 259. The Psycho-optic and Psycho-auditory Centers and the Sensors- Sphere of the Dog's Brain (H. Munk), ' .' 786 260. The Cerebrum with the Principal Convolutions and Sulci (A. Ecker) in its Longitudinal Relation to the Skull 793 261. Secondary' Degeneration of the Motor Tracts in the Cerebral Peduncle, the Pons and the Pyramid (Charcot) , ... 795 262. View of the Median Surface of the Human Brain ... 796 263. Cerebrum of Man 803 264. Frontal Section through the Cerebrum, 805 265. Lymphatic Structure of the Cornea, 815 266. Meridional Section through the Corneoscleral Junction, 816 267. Diagrammatic Representation of the Blood-vessels of the Eye (Th. Leber), 818 268. Laj-ers of the Retina, 820 269. Transverse Section of a Mammalian Retina (Ramon y Cajal), 820 270. Fibers of the Lens, 821 271. Horizontal Section through the Optic Nerve, at its Entrance into the Eyeball through the Coats of the Eye 822 272. Action of Lenses on Light, 824 273. Refraction of Light 825 274. Construction of the Refracted Ray, 825 275. Optical Cardinal Points, 826 276. Construction of the Direction of the Refracted Ray 827 277. Construction of the Image 827 278. Refracted Ray in Several Media, 828 279. Visual Angle and Retinal Image 829 280. Ophthalmometer (v. Hehnholtz) , 830 281. Anterior Quadrant of a Horizontal Section of the Eyeball 832 282. Diagrammatic Representation of Accommodation for Xear and Far Objects 833 283. The Images of Purkinje-Sanson, 834 284. Scheiner's Experiment 835 285 and 286. Refractive Condition of the Xormal Eye, at Rest and in Ac- commodation 836 287 and 288. Refractive Condition of the Short-sighted and the Far-sighted Eye, 836 289. Power of Accommodation 838 290. Cylindrical Glasses for Astigmatism 841 291. The Entoptic Shadows, S45 292. Apparatus for Illuminating the Back of the Eye 847 293. Scheme of the Indirect Method, .' 848 294. Action of a Divergent Lens, 848 295. Action of a Divergent Lens 848 296. The Optic-nerve Entrance, with the Surrounding Structures, of a X'ormal Eyeground (Ed. Jaeger) , 849 297. Mechanism of the Orthoscope 850 LIST OK ILLUSTRATIONS. XXVU FIO. PACE 298. Horizontal Section of the Right Eye, 852 299. Perimetric Chart of a Healthy and of a Diseased Eye 854 300. Geometric Color-chart, 858 301. Diagrammatic Representation of the Young-Helmholtz Color Theory, . . 859 302. Lines of Traction and Axes of Rotation of the Ocular Muscles 869 303. Diagrammatic Representation of Identical and Nonidentical Retinal Points, 872 304. Horopter for the Secondary Position, with Convergence of the Visual Axes 872 305. I, Diagramniatic Representation of Brewster's stereoscope; II, that of Wheatstone: III, two stereoscopic drawings; IV, v. Helmholtz's telestereoscope 874 306. Wheatstonc's Prism-pseudoscope, 875 307. Ewald's Mirror Pseudoscopc 875 308. Rollett's Glass Plate Apparatus 878 309. Vertical Section through the Upper Lid {Waldcycr) , 880 310. Eye of the Cross-sjjider, 882 311. Individual Eye of a Libellula Larva (Dragon-fly) 882 312. Eye of a Sea-snail (Patella cccrulea) 883 313. Eye of a Sea-snail (Haliotis tuberculata) 883 314. Diagrammatic Representation of the Auditory Apparatus 886 315. The External Auditory Canal, and the Tympanum, 888 316. Tj'mpanic Membrane and Auditory Ossicles (left) viewed from Within (from the tympanic cavity) , 889 317. Tympanic Membrane of a Newborn Infant, view^ed from the Outside, with the Handle of the Malleus shining throttgh, 889 318. Tympanic Membrane and Ossicles (left) viewed from Within, 889 319. The Auditory Ossicles (right) 891 320. Tj-mpanic Membrane and Atiditory Ossicles (left), enlarged 892 321. Tensor Tympani Muscle; the Eustachian Tube (left) 893 322. Stapedius Muscle (right), 894 323. Section through Eustachian Tube (diagrammatic), 895 324. External Conformation of the Labyrinth, 896 325. Scheme of the Cochlea, 897 326. Organ of Corti, 898 327. Curve of a Muscle Note and Its Overtones 904 328. Flame Pictures and Phonautographic Tracings of the Vowels 906 329. Olfactory Cells 914 330. Nasal Cavity and Nasopharynx, 914 331. Circumvallate Papilla and Taste-buds, 917 332. Vertical Section of Skin, 920 333. Vater-Pacinian Corpuscle, 921 334. Spherical End-bulb in the Human Conjunctiva (Longworth) 921 335. Longitudinal End-bulb, . 921 336. Grandry-Merkel Corpuscles, 922 337. Tactile Discs with Nerves from the Epidermis (snout of the pig) 922 338. Nerve-endings in the Corneal Epithelium 923 339. Compasses for Testing Sensation, 926 340. Sieveking's Esthesiometer, 926 341. Pressure Points 927 342. Landois' Mercurial Pressure-balance, 929 343. Cold-points and Heat-points 931 344. Topography of the Cold-sense and the Heat-sense on the Same Part of the Anterior Surface of the Thigh 933 345. Ovum from the Uterus of a Sexually Mature Proglottis of the Taenia solium 938 346. Encapsulated Cysticerci (from Taenia solium) in the Flesh of the Sar- torius Muscle in Man, 938 347. Cysticerci from Tfenia solium, with their Connective-tissue Capsule Removed, 938 348. Cysticercus from Taenia solium with Everted Hollow Bud (Cephalic Segment) _ 939 349. Portion of an Echinococcus-cyst with Brood-capsule, 939 350. Taenia mediocanellata 939 351. Sexually Active (Middle) the Proglottis of Taenia mediocanellata (Soiii- mer) , 940 XXVIU LIST OF ILLUSTRATIONS. FIG. PAGE 352. Heads of Ttenia solium and Taenia mediocanellata and Mature Pro- glottids of Each 941 353. Seminal Crystals 942 354. Spermatozoa, 943 355. Spermatogenesis (semidiagrammatic) 945 356. A Fresh Ovum from the Ovary of a Woman Thirty Years Old 947 357. Mature Rabbit Ovum {Waldcyer) , 948 358. Ovary and Polar Globules 949 359. Diagrammatic Representation of a Mesoblastic Ovum (Waldeyer) , 950 360. White and Yellow Yolk-globules 950 361. Diagrammatic Longitudinal Section of a Hen's Egg, 950 362. The Ovary and the Fallopian Tube {Hcnle), 952 363. Sagittal Section through the Normal Endometrium, Together with a Portion of the Contiguous Muscular Layer, 953 364. Horizontal Section of the Normal Endometrium {Orihmann) , 953 365. Fresh Corpus luteum {Balbiani) 953 366. Lutein-cells from the Corpus luteum of the Cow {His), 954 367. Corpus luteum of the Cow, enlarged one and one-half times {His) , 954 368. Anterior Pelvic Wall with the Urogenital Diaphragm {Henle), 956 369. Ovum of Scorpaena scrofa 959 370. Ovum of a Starfish (asteracanthion) , 959 371. Four Stages of Division of an Impregnated Ovum of Echinus saxatilis, 960 372. Development of the Hypoblast {Kupffer) , 962 373. Ovum of the Rabbit {van Bencden) , 963 374. Germinal Plate of Bird's Egg, 964 375. Stages of Nuclear Division {Rabl) , 965 376. Schemata of Development, 967 377. Lateral View of the Brain of a Human Embryo {His) , 968 378. Scheme of the Formation of the Chorda and the Coelom through Eva- gination of the Hypoblast 970 379. Isolated Portion of Villi from a Human Placenta, 977 380. Section through the Uterus and the Attached Placenta at the Thirtieth Week {Ecker) , . 978 381. Left-sided Hare-lip, 985 382. Formation of the Face and Developmental Defects of the Face, 986 383. Ossification of the Innominate, 988 384. Development of the Heart (in part diagrammatic), 990 385. Development from the Aortic Arches, 991 386. Veins of the Embryo, 992 387. Development of the Veins of the First and the Second Circulation, and of the Portal System, 993 388. Development of the Intestine 994 389. Development of the Lungs, 994 3go. Development of the Great Omentum 994 391. Transverse Section through the Primitive Kidney, the Rudimentary Duct of Muller, and the Sexual Gland in a Chick at the Fourth Day (Waldeyer), 996 392. Development of the Internal Organs of Generation, 997 393. Development of the External Genitalia 998 394- Development of the Eye looi NTRODUCTION. THE SCOPE AND AIM OF PHYSIOLOGY AND ITS RELATION TO ALLIED BRANCHES OF PHYSICAL SCIENCE. Physiology is the science of the vital phenomena of organs, or, briefly, the study of life. In accordance with the classification of organisms the following divisions are made, namely, Animal Physiology, Vegetable Physiology, and the Physiology of the Lowest Forms of Life, which occupy the boundary between animals and plants, the protists, micro- organisms or microbes, and the elementar}^ organisms or cells occupying the same plane. It is the aim of physiology to establish these phe- nomena, to determine their regularity and their causes, and to correlate these with the general fundamental laws of natural science, especially those of physics and chemistry. The relation of physiology' to allied branches of natural science is shown in the following scheme: BIOLOGY, The science of organized beings or organisms (animals, plants, protists, and ele- mentar>- organisms). Morphology. The stud}^ of the form of organisms. General Morphology. Special Morphology. The study of the formed elementary The study of the parts and organs constituents of organisms (Histology) : of organisms (Organology, Anatom)-) : (a) Histology of plants. (a) Phytotoniy. {b) HistologA^ of animals. (6) Zootomy. Physiology. The study of the vital phenomena of organisms. General Physiology. Special Physiology. The study of vital phenomena in The study of the functions of indi- general: vidual organs: (a) Of plants. (a) Of plants. {b) Of animals. (6) Of animals. Embryology. The study of the generation and development of organisms. Morphologic division i. Developmental his- Physiologic S? division of the study of develop- tory of the individual of the study of develop being (for instance, man) from its germ, germinal history {Ontogeny) : (a) In plants. (6) In animals. 2. Developmental his- tory of entire species of organisms, from the low- est forms of creation up- ward, familj' history {Phytogeny') : (a) In plants, (fc) In animals. 17 ment, that is, the study of the conformation at dif- ferent stages of develop- ment: (o) General. {b) Special. inent, that is, the study of functional activity during development : (a) General. (6) Special. 15 MATTER. If it be desired to give a special position in the system of organisms to those beings that occupy the lowest ]:)lane of development and that, representing to a cer- tain degree the prototype in the family history, ha\"e as yet not been differentiated into animal and vegetable, the so-called protists (Haeckel), these likewise wovild occupy a distinct place in the foregoing arrangement by the side of animals and plants. Morphology and physiology are coordinate branches of biology. A knowledge of morphology is a prerequisite for the comprehension of physiology, inasmuch as the functions of an organ can be correctly understood only if its external form and its internal structure are pre- viously known. The developmental history occupies an intermediate position between morphology and physiolog^^ It is a department of morphology in so far as it has to do with a description of the parts of the developing organism ; it is a physiologic study in so far as it investi- gates the functions and vital phenomena during the period of develop- ment of the organism. In all the branches of biologic science it is neces- sary to enter upon a consideration of physical and chemical principles. MATTER. The entire visible world, including all organisms, consists of matter, that is, of the material or substance that occupies space. A distinction is made between ponderable matter (in ordinary language often desig- nated simply matter), w^hicli can be weighed upon the scales; and im- ponderable matter, which cannot be weighed upon the scales. The latter is designated ether (also luminiferous ether or light-ether). Ponderable matter or bodies possess jorui (or shape), that is, the outline of their limit- ing surfaces; also volnnie, that is, the amount of space they occupy; and finally an aggregate condition, which takes a solid, liquid, or gaseous form. The ether fills the space of the universe, at any rate, with certainty to the most remote visible stars. This light-ether, notwithstanding it's imponderability, possesses quite definite mechanical properties. It is infinitely more attenuated than any other knowm form of gas, and never- theless its behavior corresponds rather with that of a solid body than with that of a gas. It more nearly resembles a gelatinous mass than air. It takes part in the vibrations of the atoms of the most distant stars associated with the luminous phenomena of the latter, and it is thus the carrier of light, which through its vibrations it conducts to the visual apparatus with inconceivable rapidity (300,000 kilometers in the second). Imponderable matter (ether) and ponderable matter (substance) are not sharply delimited from each other; on the contrary, the ether pene- trates the interstices present in the smallest particles of ponderable matter. If ponderable matter be conceived to be divided into gradually smaller and sinaller parts, in the process of progressive subdivision parts would eventually be reached whose aggregate condition would still be recognizable. These are designated particles. Particles of iron would still be recognized as solid, those of water as fluid, and those of oxygen as gaseous. If it be conceived that the process of division of the parti- cles be carried to a further degree, a point will finally be reached beyond which further division cannot be effected either by mechanical or by physical means. In this way the molecule is obtained. A molecule, MATTER. 19 accordingly, is the smallest portion of a Ijody that is capable of existence in a free state, and that, further, as a unit no longer exhibits the aggre- gate condition. The molecule is, however, not the ultimate unit of the body. On the contrary, every molecule consists of a collection of the smallest units, which are known as atoms. An atom is incapable of occurring alone in a free state, but atoms unite with other atoms of the same or of different character to form atom-complexes, desig- nated molecules. Atoms are unconditionally insusceptible of division; whence the name. Atoms, further, are conceived to be of constant size and solid in themselves. From the chemical standpoint the atom of an elementary body (element) is the smallest amount of an element that is capable of entering into chemical combination. Just as ponderable matter consists in its ultimate parts of ponderable atoms, so also does the ether, imponderable matter, consist of analogous particles of smallest size, namely, ether-atoms. Within ponderable matter the ponderable atoms are arranged in quite a definite order with relation to the ether-atoms. The ponderable atoms are drawn mutually toward one another (attraction) ; the pon- derable atoms likewise attract the imponderable atoms; but the ether- atoms mutually repel one another. It thus comes about that in the ponderable mass ether-atoms are collected about every ponderable atom. These collections, designated "dynamids" by Redtenbacher, tend, in accordance with the powers of attraction of the ponderable atoms, to approach one another, but only so far as permitted thus to do by the repellent power of the surrounding ether-atoms. Therefore the pon- derable atoms can never cohere without interstices, but the entire mass of matter must be considered as loose in texture in consequence of the interposed ether-atoms, which prevent immediate contact between pon- derable atoms. The aggregate condition of the body depends therefore upon the mutual arrangement of the molecules (namely, those sinall particles of matter that may still occur isolated in a free state). Within solid bodies, which are characterized by constancy of volume, as well as independence of form, the molecules are arranged in a fixed and unchangeable relation with one another. In fluid bodies, which are characterized by constancy of volume, though by variability of form, the molecules are in constant movement, just as in a mass of moving worms or insects the individual animals are incessantly changing their place with relation to one another. If this movement of the molecules attains such proportions that the individual molecules scatter in all directions (just as the moving collection of insects separates into its constituent parts), the body becomes gaseous, and is characterized in this form both by its inconstancy of form and its variability in volume. The study of molecules and their motor phenomena is the part of physics. FORCES. Gravitation; Work of a Force. — All phenomena appertain to matter. They are the appreciable expression of the forces inherent in matter. The forces themselves are not appreciable ; they are the causes of the phenomena. The first of the forces to be considered is gravita- tion. According to the law of gravitation every particle of ponderable matter in the universe attracts every other particle with a certain degree 20 FORCES. of force. This force diminishes inversely as tlie square of the distance between the two bodies. The power of attraction is further directly proportional to the quantity of the attracting matter, though without any relation to the quality of the body. The intensity of the force of gravitation can be measured by the extent of the movement that it communicates to a freely falling body previously supported in a vacuum but deprived of its support. This figure is 9.809, because the force of gravity operating for one second upon the freely falling body imparts to this a velocity of 9.809 meters. The final velocity of the freely falUng body at the end of the first second (deter- mined experimentally) is designated thus, g ^ 9.809 meters. The velocity, v, of the freely falling bod\' is in general proportional to the time, t, occupied in falling. Therefore v = gt (i), that is, at the end of the first second v = g, i = g = 9.809 meters. The distance through which the body falls, s := - 1- (2) ; that is, the 2 distance through which a body falls is as the square of the time occupied in falling. From (i) and (2) there follows (by eliminating t) v = y'^gs (3). The velocity is as the square root of the distance traversed in falling, thus —- = s (4) A freely falling body, and also in general every mass in movement, possesses kinetic energy (actual energy) ; it is to a certain degree a reposi- tory of force. The kinetic energy of a body in movement is always equal to the product of its weight (determinable by scales) and the height to which it would rise from earth if it were raised from the earth with the velocity peculiar to it. If the kinetic energy of the moving body be designated W and its weight P. then W = P, s; then, from (4), W = P— (5). The kinetic energy of a body is therefore proportional to the square of its velocity. If an accelerating force operating on a body (pressure, traction, or tension) drives it for some distance in the direction of its activity, the force thus expends work. This is equal to the product that is obtained if the amount of pressure or traction that propels the body is multiplied by the length of the path traversed. If K represents the pressure or the traction with which the force operates upon the body and S the path, then the work A = KS. In the same way the attraction between the earth and a body raised above it (as, for instance, a ram) is a source of work. It is customary to express the value of K in kilograms, but, on the other hand, that of S in meters. Accordingly the unit of work is the kilogrammeter (according to some the grammeter), that is, the force that is capable of raising i kilo (according to some i gram) to the height of I meter. Potential Energy. — Transformation of Potential Energy into Kinetic Energy, and the Reverse. — In addition to the kinetic energy referred to, bodies may possess also mechanical potential energy. By this designation is understood an aggregation of forces that are still inhibited in their free evolution, and that, further, are causes of movement, without FORCES. 21 themselves being movement. The wound clock-spring prevented from unwinding by a catcli, the stone resting upon the cornice of a tower, are illustrations of bodies possessing potential energy. Only an impulse is required to evolve actual from potential energy or to convert the poten- tial into kinetic energy. The stone resting upon the cornice of the tower was raised to that place by means of work (A). A = p, s, p representing the weight and s the height, p = m, g, thus the equivalent of the product of the mass (m) and the force of gravity (g) ; therefore A = m, g, s. This is at the same time the expression for the potential energy residing within the stone. This elastic energy may readily be converted into kinetic energy by causing the stone to fall from the edge of the tower by means of a slight push. The actual energy of the stone is equal to the terminal velocity with which it reaches the ground. V = -^i^gs (see 3). V^ = 2gS mV^ = 21TlgS m , -' -V- = m2;s 2 m, g, s represents the potential energy residing within the stone at rest in its elevated position; — v^ is thus the kinetic energy correspond- ing to this potential energy. Actual energy and mechanical potential energy can be transformed into each other under most varied conditions; they can also be con- veyed from one body to another. Of the first statement the movement of a pendulum furnishes a striking illustration. The pendulum-bob. located at the highest point of the excursion, and which must be considered to be in a state of absolute rest at this point for a moment, is, exactly as the resting stone in the previous illustration, provided with potential energ^^ In the free movement that now takes place this potential energy is. converted into kinetic energy, which is greatest when the bob with greatest movement is in the vertical plane. Rising again from this point, the kinetic energ)', with diminution in the free movement, is transformed into poten- tial energy', which again attains its maximum at the resting-point at the height of the excursion. In the absence of constantly operating resistances (resistance of the air, friction) this play of the alternate transformation of kinetic energy into potential energy and the reverse taking place in the pendulum would continue uninterruptedly (as in a mathematical pendulum). If it be conceived that the swinging pendulum-bob encounters exactly in the vertical plane a movable body resting at this point, such as a sphere, then (assuming perfect elasticity on the part of the pendulum-bob and the sphere) the kinetic energy of the pendulum-bob would be transmitted directly to the sphere: The pendulum would come to rest, while the sphere would continue in movement with equal kinetic energy (again providing there is no resistance). This is an instance of the transmission of kinetic energy from one body to another. Finally it may be conceived that a coiled clock-spring in unwinding causes another to become coiled. This would be an instance of the transmission of potential energy from one body to another. From the illustrations given the general proposition may be deduced : If in a system the individual moving masses approach a final condition of equilibrium, the sum of the kinetic energies in the system will be increased; and if the particles are removed from the final condition of equilibrium, then the sum of the potential energies is increased at the expense of the kinetic energies; that is, the kinetic energies diminish. 22 HEAT. The pendulum approaching the vertical plane (the position of equilibrium for a -resting pendulum) from the highest point of its excursion possesses in this position the greatest amount of kinetic energy: and ascending to the highest point of its excursion on the other side it attains, at the expense of the progressively diminishing movement and thereby also the kinetic energy, again gradually the maximum of potential energy.-. Heat : Its Relation to Kinetic Energy and to Potential Energy. — If a leaden weight be thrown from the summit of a tower to the earth and there encounter an unyielding surface, its movement in mass will come to rest, but the kinetic energy, which to the eye appears dissipated, is transformed into an actively vibratory movement of the atoms. On striking the ground heat is generated, the amount of which is proportionate to the kinetic energy that is transformed by the impact. At the moment of contact on the part of the falling weight the atoms are set into vibration by the concussion. They impinge upon one another and then rebound in consequence of the potential energy that tends to prevent their immediate apposition; they separate to a maxi- mum degree in so far as the power of attraction of the ponderable atoms permits and they oscillate to and fro in this manner. All atoms oscillate like a pendulum until their movement is transmitted to all the surrounding ether-atoms, that is, until the heat of the heated mass is radiated. Heat is a vibratory movement of the atoms. As the amount of heat generated is proportionate to the kinetic energy that is transformed by the impact, it must be possible to find an adequate measure for both forms of force. The heat-unit (calory), that is, the energy that raises the tempera- ture of I gram of water i° C, serves as the measure of the amount of heat. This heat-unit corresponds to 425.5 grammeters; that is, the same amount of energy that raises the temperature of i gram of water 1° C. is capable of raising a weight of 425.5 grams to a height of i meter; or, a weight of 425.5 grams falling from the height of i meter would in its impact generate so much heat as would raise the temperature of I gram of water 1° C. The mechanical equivalent of the heat-unit is therefore 425.5 grammeters. It is evident that from the impact of masses in motion an amount of heat of immeasurable degree may be generated. If this statement be applied to the planets, their impact would result in the production of an amount of heat greater than could be generated by any form of earthh' combustion. If the earth were suddenly checked in its course and if through the force of gravitation it plunged into the sun [in the course of which it would eventually have acquired a terminal velocity of 630.7 kilometers in a second] an amount of heat would be generated in consequence of the collision equivalent to that produced by the combustion of more than 5000 equally heav}- masses of pure carbon. In this manner the dem- onstration can be made scientificall3^ that even the sun's heat niay have been produced by the impact of cold matter. If the cold matter of the universe were thrown into space, and there left to the attraction of its particles, the impact of these masses would eventually extinguish the light of the stars. In the same way numerous cosmic bodies still collide in space, and innumerable meteors constantly plunge into the sun (from 9400 to 1 88, 000 billions of kilos in each minute). Thus, the action of the force of gravitation is in fact perhaps the exclusive origin of all heat. The following is an instance of the transformation of kinetic energy into heat: The smith makes a piece of iron hot by hammering. The fol- lowing is an instance of the transformation of heat into kinetic energ\": The hot steam of the steam-engine causes the piston to rise. The following is an illustra- tion of the transformation of potential energy- into heat: The unwinding of a coiled metallic spring, rubbing upon a rough surface, produces heat by friction. Exam- CHEMICAL Al-KIXITY OF ATOMS. 23 pies of like character, as well as of other transformations, could be readily given in any number. Chemical Affinity of Atoms : Relation to Heat. — While the force of gravitation acts upon the particles of matter without reference to the character of the body, still another form of force is found in the realm of atoms, which is effective between the atoms of chemically different bodies, namely, chemical affinity. This is the force by means of which the atoms of chemically different bodies unite in chemical combination. The energy itself is extremely variable between the atoms of different chemical bodies. A distinction is made between strong chemical affinities (or rela- tions) and weak affinities. Just as it is possible to determine the kinetic energy of a body in motion from the amount of heat that it generates in its impact upon an unyielding surface, so the degree of chemical affinity can be determined from the amount of heat that is produced, as the atoms of chemically different bodies unite in chemical combina- tion; for if a complex body is formed from individual, chemically different atoms heat is, as a rule, generated. If as a result of the force of affinity the atoms of i kilo of hydrogen and 8 kilos of oxygen unite to form the chemical combination water, an amount of heat is generated that is equal to that developed by the impact of a weight of 47,000 kilos in falling from a height of 300 meters above the surface of the earth. One gram of hydrogen converted into water by addition of oxygen yields 34,460 heat-units (calories). One gram of carbon con- verted into carbon dioxid yields 8080 calories. Whenever in the course of chemical processes considerable affinities are satisfied heat is set free, that is, generated from the force of affinity. The force of affinity is a form of potential energy acting between the various atoms that in the course of the chemical process is transformed into heat. It is thus likewise explicable that in the course of those chemical processes through which strong affinities are dissolved, in which the chemically united atoms are again separated, cooling takes place, or, as is commonly stated, heat becomes latent. That is, the energy of the heat rendered latent is transformed into chemical poten- tial energy, and this in turn, after disintegration of the complex chemical body, appears between its isolated, individual atoms as chemical affinity. LAW OF THE CONSTANCY OF ENERGY. Julius Robert v. Mayer (1842) and Hermann Helmholtz (1847) have established the important law that in a system that receives no influ- ence or impression from without the sum of all the contained kinetic energies is always equal. The energies may be transformed one into another, so that the potential energy may be converted into kinetic energy, and the reverse, but never is even the slightest amount of the energy lost. The transformation that takes place in the energies occurs in a definite manner, so that from a definite measure of a given force an equally definite measure of the new-appearing force always results. The forces occurring in the animal organism appear in the following modifications : I. .45 movement in mass (generally designated simply movement). 24 LAW OF THE CONSTANCY OF ENERGY. such as the movement of the entire body, of the extremities and many of the viscera; also appreciable even microscopically in cells. 2. As movement of the atom: in the form of heat. As is well known, the vibration of atoms results in the production of heat or of light or in chemically active waves in accordance with the number of vibrations in the unit of time. The smallest number of vibrations are those of heat, the highest those that are chemically active, and between the two are the vibrations of light. In the human body only heat-waves have of these three been observed, but some lower forms of life are capable of causing also luminous phenomena. In the human organism movements in mass are constantly trans- formed in certain organs into heat, as, for instance, the kinetic energy in the circulatory organs, and which is transformed into heat by the resistance within the vascular apparatus. The measure of these trans- formations also is the unit of energy = i grammeter, and the unit of heat = 425.5 grammeters. 3. In the form of potential energy (latent energy) the organism con- tains many chemical combinations characterized especially by great complexity of constitution and imperfect saturation of the contained affinities, and, therefore, by their great tendency to break down into simpler bodies. The body is capable of generating both heat and kinetic energy from potential energies; kinetic energy, however, is always in combination with heat, while heat may be produced alone. The simplest measure of the potential energies is the amount of heat that can be obtained by the combustion of the chemical bodies in question representing the potential energy. As a secondary matter the number of equivalent units of energy can be determined in turn from the amount of heat generated. 4. It is known that the phenomena of electricity, magnetism and diam^agnetism, may make themselves manifest in two directions, namely, in the form of movement of minutest particles, which may be recog- nized in the incandescence of a thin wire (the seat of great resistance) traversed by a strong current; and also in the form of movement in mass, as exhibited in the attraction or repulsion of the magnetic needle. In the body electric phenomena appear in the muscles, nerves, and glands ; but as compared with other forms of energy they are of subordinate importance. It is not improbable that the electric energy of the body is transformed almost wholly into heat. The endeavor to obtain a measure for electric energy, the unit of electricity, as a means of direct comparison with the heat-unit and the unit of energy, has likewise been attended with definite success. Luminous phenomena do not occur in the bodies of the most highly developed animals. The significant investigations of Hertz have shown that the phenomena of light exhibit the greatest analogy with those of electricity in the most important connections, so that the relations be- tween the two forms of energy must accordingly be admitted. It is certain that in the body also the different forms of energy can be transformed one into another in a definite and constantly invariable degree, and that new energy never develops spontaneously in the body, while that present is never destroyed; and thus also the organisms are a theater in which the law of the constancy of energy is in unceasing operation. ANIMALS AND PLANTS. 25 The original statement of Julius Robert v. Mayer may be appropriately quoted at this point: "There is but one energy, which operates with unceasing change in dead and in living things, and nowhere in either does any change take place without alteration in the form of energy. Physics has but to investigate the metamorphoses of energy, as chemistry has to investigate the transformations of matter. The generation as well as the destruction of energy is beyond the range of human thought and action: Nothing comes from nothing, nothing can give rise to nothing. If chemistry teaches the immutability of matter, then it is the obliga- tion of phj-sics to demonstrate the qviantitative immutability of energy notwith- standing all variability in form. Gravitation, motion, heat, magnetism, electricity, chemical diti'erence, are all but varying modes of manifestation of one and the same natural force ,that reigns throughout the universe, for any one can under special conditions be converted into another." (Lucretius Carus, born 95 B. C, had already said: " NuUam rem a nihilo gigni, .... neque ad nihilum interimat res.") ANIMALS AND PLANTS. Locked up in the constituent elements of the animal body is an aggregation of chemical potential energies (Lavoisier, 1789). The total amount of these in the human body could be measured if the entire cadaver were completely burned in a calorimeter and the number of heat-units generated were noted as a result of its combustion. The chemical combinations in which are bound up the potential energy are characterized by complexity in the arrangement of their atoms, by imperfect saturation of the affinities of the atoms, by a relatively small oxygen-content, and by a great tendency to and readiness of disintegra- tion. It may be conceived that food is withheld from an individual. The fasting person loses hourly 50 grams of body- weight; the tissues in which his potential energy is bound up are thus consumed. Through the taking up of oxygen combustion continually takes place, and as a result of this process the complex elements of the body are converted into simpler ones, whereby the potential energy forming the connecting link between them is transformed into kinetic energy. It is a matter of indifference whether the process of combustion takes place rapidly or slowly; the same amount of chemical matter always yields the same amount of kinetic energy, as, for instance, heat. After the lapse of a certain time the fasting person becomes conscious of the state of threatened exhaustion of his stored potential energy, and the condi- tion of hunger sets in. The hungry person takes food; all food for the animal kindgom is derived either directly or indirectly from the vege- table world. Even carnivorous animals, which eat the flesh of other animals, consume in the final analysis organized material formed from vegetable food. Thus, the existence of the animal kingdom necessarily implies unconditionally the previous existence of the vegetable king- dom. Vegetable structures thus contain all of the nutritive materials necessary for the animal body. In addition to water and inorganic matters, vegetables contain, among other organic combinS-tions, espe- cially also the three principal representatives of nutrient bodies, namely, fats, carbohydrates, and proteids. All of these are the seat of abundant potential energy in accordance with the complexity of their chemical constitution. 26 ANIMALS AND PLAXTS. Fats contain • '' ^" ^— ^^ ^^^^ ^ ^^"^ ^"^' I rats contain. ^ _ ^^jj_ (0H)3=- glycerin | f C76.5 Animal fats contain : - H 12.0 (On. 5 Carbohydrates contain: CgHioOj *-^ 50-55 -•^e. 6-7-3 Proteids contain in percentages: Xij-ig 0,9-2, Man, who partakes of a certain amount of these nutrient materials, adds to them through the respiratory process the oxygen of the air, whence there results a process of combustion, in the course of which chemical potential energy is converted into heat. It is evident that the products of this combustion must be bodies of simple constitution, bodies with uniform arrangement of their atoms, with most complete saturation of the affinities of their atoms, of great constancy, partly rich in oxygen and possessing slight or no chemical potential energy. These bodies are carbon dioxid (CO2), water (H2O), and, as the most important representative of the nitrogen-containing derivatives, urea (COCXH,),), which, while endowed with a small measure of potential energv is, outside of the bodv, readily transformed into CO, and ammonia (NH,). Thus, the animal body is an organism in which, through the inter- mediation of oxidation-phenomena, the coinplex nutritive matters of the vegetable world, representing high potential energy, are trans- formed into simple chemical bodies, in the course of which the potential energy is transformed into an equivalent amount of kinetic energy (heat, work, electric phenomena). The question naturally arises, How do plants, which, as the first products of creation, found for their nourishment no preexisting mate- rials endowed with potential energy, and still suffer from no lack thereof — how do plants form the complicated nutrient matters mentioned, rich in stored-up potential energy? This potential energy of vegetable life must obviously have been derived from some other form of energy, for it cannot be created out of nothing. This kinetic energy is furnished plants through the light of the sun, whose chemical rays they absorb. Without sunlight there can be no vegetable life. From the air and the earth the vegetable organism obtains COj, HjO, NH3, and N, of which carbon dioxid, water, and ammonia (from urea) constitute also the excrementitious matters of the animal body. The plant obtains from the rays of the sun the kinetic energy of its light and converts it into potential energy, which, as in all vegetable matter, so also in the nutrient material produced, accumulates in the process of the growth of the plant. This formation of complex chejnical combinations takes place in asso- ciation with elimination of oxygen. The Papillonacea^, as, for instance, peas, beans, lupines, acacias, are capable of assimilating the free nitrogen of the air in the tissues of their root-bulbs, through the agency of sj^mbiotic micro-organisms lodged upon these, Rhizobium legumino- sarum. Thus, these plants are capable of building up their nitrogen-containing tissues even in soil entirely free from nitrogen. In this way they play an im- portant fertilizing role in agriculture (lupine) and forestry (acacia). Also lower ANIMALS AND PLANTS. 27 forms of vcsctablo life, as, for instance, the anaerobic bacterium, Clostridium pasteurianum, is capal>le of assimilating^ free nitrogen. At times plants also exhibit free kinetic energy such as it is customary to encounter in the case of animals. Certain plants, as, for instance, the aroids and others, develop considerable amounts of heat during the llowering-period. It is also to be borne in mind that, in the development of the solid parts of plants, the transformation of formative lluids into solid matter causes heat to be set free. Absorption of oxygen and elimination of carbon dioxid have also been observed in plants. These processes are, however, so insignificant as compared with those described as typical in the vegetable kingdom, that they may be considered as of little or no importance. Thus, plants are, on the whole, organisms that through the agency of reduction-processes convert simple stable combinations into complex ones, with the transformation of kinetic solar energy into the chemical potential energy of vegetable matter. Animals are living organisms in which through the agency of processes of oxidation the atom-groups of complex construction furnished by plants are split up, the potential energy being transformed into kinetic energy, which makes itself mani- fest in the animal. Thus a circulation of materials and a constant interchange of energ}'' take place between animals and vegetables. All of the energy of animals is derived from plants and all of the energy of plants is derived from the sun. Therefore, the latter is the cause, the ultimate source of all of the energy of organism, that is, of life as a whole. As the generation of the sun's heat and light can be explained by the gravitation of masses, so it is possible that the force of gravita- tion is the sole ultimate form of energy for all living things. "The sun is the constantly bent spring that brings about the activity in the atmosphere, that raises the waters to the clouds, that causes the tides. Light, the most mobile of all forms of force, intercepted by the earth in flight, is transformed by plants into a rigid state, for plants produce upon it a continuous sum of chem- ical difference, constitute a reservoir in which the fugitive rays of the sun are faxed and, adapted for useful purposes, are deposited. Plants take one form of energ}^ light, and reproduce another, chemical difference. In the course of the processes of life, but one transformation, both of matter, as well as of energy, takes place, but never is the one or the other produced " (Julius Robert v. Mayer, 1845). ("Omnia mutantur, nihil interit." — Ovid.) The generation of kinetic energy in the animal body from the poten- tial energy of the plant can be made readily comprehensible by means of a comparison. The atoms of the matter generated in organisms may be conceived to be simple small bodies, spherules or blocks. So long as these lie in a single layer or at least arranged in a few layers upon the ground, a condition of rest and constanc}'' will prevail in consequence of this simple and stable arrangement. If, however, an artificially arranged formation of unstable construction is built up from the small bodies, there will be required (i) the motor force of the constructing agency, which raises and combines the units. As soon, however, as '(2) an impulse from without acts upon the completed unstable structure, the atoms collapse and the impact of their fall generates heat (eventually also kinetic energy in the course of other complicated transformations), that is, the energy applied by the constructing agency is transformed into the form of energy last named. In plants the complicated unstable construction of the atom-groups takes place, the sun being the con- structing agency. In the animal body, wherein the plant is consumed, the atomic structure is disintegrated into simpler elements, with the generation of kinetic energy. 28 KINETIC ENERGY AND LIFE. KINETIC ENERGY AND LIFE. The forms of kinetic energy that are active in organisms, namely, plants and animals, are precisely the same as those that are recognizable in inanimate matter. A so-called, "vital energy," which is supposed to act as a special form of force of peculiar character and cause and control the vital phenomena of living organisms, does not exist. The forces of all matter, both organic and inorganic, are bound up in their smallest particles, the atoms. As, however, the smallest particles of organ- ized matter are generally united in a most complex manner, in con- trast to the ordinarily much simpler constitution of inorganic bodies, the forces inherent to the smallest particles of organism will appear in much more complicated phenomena and combinations, and as a result the explanation of the vital phenomena in the organism by the simple principles of physics and chemistry is rendered extremely difficult and in many respects appears impossible. Metabolism as an Index of Life. — A special form of interchange in matter and energy appears peculiar to the living organisms of the earth. This consists in the ability to adapt themselves to the materials of their environment, and to assimilate them, so that for a time they represent integral parts of the living being, later again to be given off. The complete chain of these phenomena is designated "metabolism," which consists accordingly in ingestion, assimilation, reduction and excretion. It has already been suggested that metabolism differs in character in animals and in plants. As a matter of fact, this is, as has been shown, actually the case in animals and plants typically and characteristically developed. There is, however, a large group of organisms that in their complete organization exhibit such atypical development that they must be considered as undift'erentiated fundamental forms of organisms. They cannot be recognized as either plants or animals, but represent the simplest form of animate matter. These organisms, as the earliest and most primitive forms, h.ave been designated protists. It must be assumed absolutely that these also have a simple metabolism as a condi- tion of life, but with respect to this adequate observations are wanting. PHYSIOLOGY OF THE BLOOD. PHYSICAL PROPERTIES OF THE BLOOD. The color of the blood varies from bright scarlet-red in the arteries to the deepest dark bluish-red in the veins. Oxygen, therefore also the air, makes it bright red, while deficiency in oxygen renders it dark. The oxygen-free venous blood is dichroic, that is, it appears dark red in reflected light and green in transmitted light. In thin layers the blood is opaque, as one can readily convince himself, if blood be poured upon a glass plate and be permitted to flow off, by attempting to read printed matter through it. The blood thus behaves as a covering pigment, as its coloring matter is suspended in the plasma in the form of small granules, namely, the red blood-corpuscles. For this reason the granular coloring matter of the blood can be separated from the blood-plasma by tiltration. This, however, is possible only after admix- ture of the blood with fluids that render the blood-corpuscles rough or viscid. If mammalian blood is mixed with one-seventh of its volume of concentrated sodium sulphate, or if frog's blood is mixed with two per cent, solution of cane sugar, and then filtered, the blood-corpuscles will remain upon the filter. The reaction of blood is alkaline from the presence of disodium phosphate (Na^HPO^). The alkalinity rapidly diminishes in intensity after escape from the vessel, and the more rapidly the greater the pre- vious alkalinity. The change depends upon the development of an acid, in which the red blood-corpuscles take part in consequence of a decomposition of as yet undetermined origin. This generation of acid is increased by high temperature and the addition of alkali. The alkalinity of the blood is diminished (A) by active muscular exercise, in consequence of the development of acid in the muscular tissue. (B) By coagulation. Fresh clot has a more intensely alkaline reaction than blood-serum. (C) After the persistent use of soda the alkalinity of the blood is increased, and after the use of acid it is diminished. (D) Old blood or blood dissolved with water from dry places generally has an acid reaction. The blood of children and women exhibits a lesser degree of alkalinity than that of men, and that of nursing women a lesser degree of alkalinity than that of pregnant women. The alkalinity is less also dur- ing digestion than during fasting. Method of Examination. — As in consequence of the normal color of the blood red litmus-paper cannot be employed directly in testing the reaction, the following plan is pursued: Blood is mixed with an equal volume of concentrated solution of sodium sulphate, and the mixture is placed upon highly porous and sensitive lilac- tinted litmus blotting-paper. The blood-corpuscles remain upon the surface while fluid is taken up by the paper and gives rise to the reaction. For the quantitative estimation of the alkalinity dilute tartaric acid is added to a volume of blood (7.5 grams of crystalline tartaric acid to i liter of water, 1 cu. cm. of which saturates 3.1 mg. of soda) until the blue paper is reddened. One hundred cu. cm. of human blood contains the alkaline equivalent of from 260 to 300 mg. of soda (in guinea-pigs 150 mg. , in camivora 180 mg. of soda). Landois' method for the quantitative determination of the alkalinity of the blood with only a few drops of blood: Tartaric acid in the concentration already stated is emploj-ed to neutralize the alkalinity of the blood. Of this the following mix- tures are made by addition of concentrated solution of neutral sodium sulphate: (i) 10 parts of tartaric-acid solution and 100 parts of concentrated sodium- 29 30 PATHOLOGICAL. sulphate solution; (2) 20 parts of tartaric-acid solution and 90 parts of sodium- sulphate solution; (3) 30 parts of tartaric-acid solution and So parts of sodium- sulphate solution; (4) 40 parts of tartaric-acid solution and 70 parts of sodium- sulphate solution; (5) 50 parts of tartaric-acid solution and 60 parts of sodium- sulphate solution; (6) 60 parts of tartaric-acid solution and 50 of sodium-sulphate solution; (7) 70 parts of tartaric-acid solution and 40 parts of sodium-sulphate solution; (8) 80 parts of tartaric-acid solution and 30 parts of sodium-sulphate solution; (9) 90 parts of tartaric-acid solution and 20 parts of sodium-sulphate solution; (10) 100 parts of tartaric-acid solution and 10 parts of sodium-sulphate solution. To each glass an excess of crystallized sodium sulphate is added to the point of insolubility. Of the blood to be examined i drop is mixed in a graduated tube prepared for the purpose with an equal-sized drop of the acid-sulphate mixture. Into a glass tube with a diameter of i mm. and drawn out at one extremity mercury is sucked to a height of about 8 mm. so that the tube is filled to the tip. The upper extremity of the thread of mercury is marked by the scratch of a file. The mer- cury is now drawn into the tube until its lower border reaches the file-mark. The upper border of the mercury is now marked with another file-scratch. In this way the small measuring apparatus is improvised. In order now to test the blood, one drop of the tartaric-acid sodium-sulphate mixture is sucked up to the lower mark, and then, after scrupulously drying the tip, the blood is drawn up until the fluid reaches the upper mark. After again cleansing the tip of the tube its contents are blown into a watch-glass, are well stirred and then tested with reagent-paper. Successively the mixtures 2, 3, 4, etc., are treated in the same way. The reagent-paper is cut into strips 3 mm. wide, and these are partially dipped in the blood-specimens in the respective watch-glasses. The blood-corpuscles collect about the immersed extremity of paper, while the fluid is sucked up beyond and indicates the reaction. If the test has been made successively in this manner with the mixtures from i to 10 it will be readil}^ seen when the blue tint of the alkaline reaction ceases and the red tint of the acid reaction begins. In human beings the blood can always be obtained directly from a small needle-pvxncture. Exact suction into the tube can be effected with certainty and convenience if the upper extremity of the measuring glass is connected b}- means of a short rubber tube with a hypodermic syringe, the movement of whose piston through a twisting motion facilitates an exact degree of suction. All of the tests must be completed with equal rapidity and at the same temperature. The degree of alkalinity in the adult will in general be satisfied by mixture 5 or 6, and m the child by mixture 4. If all parts of the blood are uniformly dis- solved previously by addition of water this solution, which obviously can no longer be designated blood, exhibits a somewhat higher degree of alkalinity. If blood is tested slowly by the method described the alkalinity will be that of stich a solution. Pathological. — Persistent vomiting and chlorosis are attended with increased alkalinity, while diabetes, as well as cachectic states, rheumatism, uremia, leuke- mia, profound anemia, high fever, cholera, carbon-monoxid poisoning, and degen- eration of the liver are attended with diminished alkalinity. Poisons that cause destruction of red blood-corpuscles likewise bring about reduction in the alkalinity. Blood has a peculiar odi>r. This "halitus sanguinis" differs in human beings and in animals, and depends upon the presence of volatile fatty acids. If sulphuric acid be added to blood, and these acids are in consequence set free from their combination with the alkali of the bloo'd, the characteristic odor appears more distinctly. The blood possesses a salty taste, derived from the salts dissolved in the blood-plasma. The specific gravity of the blood is 1058 (from 1046 to 1067) in men, and from 1051 to 1055 in women, while the blood of children has a lower specific gravity. The specific gravity of the red blood-corpuscles is 1 105, that of the plasma from 1027 to 1028.3. This fact explains the tendency of the former to sink to the bottom. Method of Determination. — For clinical investigation the following method (a modification of that described by Roy) can be recommended. In a glass tube, MICROSCOPIC EXAMINATION OF THE BLOOD. 31 narrow at the bottom and covered with a rubber cap, a fresh drop of blood ob- tained by puncture with a needle is permitted to enter from below. The tube is at once immersed in a glass vessel lilled with a solution of olive-oil in chloroform, and by pressure upon the rubber cap the drop of blood is expelled into the fluid. Various concentrations of the latter with a specific gravity between 1050 and 1070 are prepared, and that solution in which the drop remains suspended indicates the specific gravity of the blood. The specific gravity is dependent principally upon the hemoglobin-content of the blood, much less upon the number of erythrocytes. It is high in the newborn, namely, 1066. The drinking of water and hunger will reduce the specific gravity temporarily, and it falls also after loss of blood and is lower in the presence of aneinia, chlorosis, marasmus, and nephritis (down to 1025). It is increased by thirst, the digestion of solid food, by sweating, acute loss of water through the intestines and the kidneys, as well as cyanotic stasis (down to 1068). The entrance of an increased amount of salts into the blood is shortly followed by dilution, while the salts of the biliary acids, on the other hand, exert a concentrating infiuence. The specific gravity is increased by vasomotor contraction of the vessels and, con- versely, it is diininished by vascular dilatation. The blood-serum of women is heavier than that of men. If blood is made artificially to pass repeatedly through an organ its specific gravity increases in consequence of the taking up of dis- solved substances and the giving off of water. For the determination of the specific gravity of the red blood-corpuscles, these must be isolated by sedimentation. This takes place rapidly in the case of horses' blood. The erythrocytes are said to be somewhat heavier in women and to con- tain more hemoglobin than those of men. The freezing-point of the blood is about — 0.56° C. It increases as the oxygen-content diminishes. MICROSCOPIC EXAMINATION OF THE BLOOD. The red blood-corpuscles or erythrocytes (Fig. i) were discovered in man by Leeuwenhoeck in 1673 and in the frog by Swammerdam in 1658. Physical Properties. — Human erythrocytes are coin-shaped discs with biconcave surfaces and rounded margins. The diameter is 7.5 /j., the thickness of the edge 2.5 ,a, and the central thickness from 1.8 to 2 ,« (Fig. 1). In health the diameter varies from 6 to 9 // ; the average being from 7.2 to 7.8 It. The corpuscles are diminished in size by inanition, elevation of the bodily temperature, carbon dioxid and morphin, and increased in size by oxygen, a watery state of the blood, cold, ingestion of alcohol, quinin, hydrocyanic acid. [Pathological conditions are discussed on p. 50.] The volume of an erythrocyte equals 0.000000077217 cu. mm., the superficies 0.000128 sq. mm. If the total volume of the blood in man be assumed to be 4400 cu.cm., all of the contained blood-corpuscles have a superficies of 2816 square meters, that is, the equivalent of a square with sides of 80 paces. In a second 176 cu.cm. of blood are driven into the lungs and whose blood-corpuscles exhibit a superficies of 81 square meters, that is, a square with sides 13 paces. The volume of all of the erythrocytes can be approximately determined by introduc- ing the blood into a narrow graduated glass tube ("hemokrit" of Hedin), either unmixed or defibrinated or mixed with an equal amount of a preservative fluid capable of preventing coagulation, as, for instance, 2.5 percent, potassium-bichrom- ate solution or 0.S6 percent, sodium-chlorid solution with some ammonium oxalate, and subjecting it to centrifugation. Treated in this manner healthy human blood is found to contain from 42 to 48 per cent, of corpuscles (anemic blood 30 per cent, and less). The erythrocytes, however, undergo changes in vol- ume, at least after escape of the blood, by the taking up or giving off of fluid material, as exhibited beyond doubt by shrunken and distended forms. Venous blood contains a greater volume of erythrocytes than arterial blood. The iveight of an erythrocyte can be determined by multiplying its volume by its specific gravity (1105) ^ 0.000000085325 mg. 32 MICROSCOPIC EXAMINATION OF THE BLOOD. Alexander Schmidt determined the weight of the red blood-corpuscles in loo parts of blood in the following manner: He ascertained (i) the percentage of dry- residue of the blood = T; (2) the percentage of dry residue of the corresponding blood-serum = t; (3) the dry residue of the erythrocytes contained in 100 grams of blood = r: the dry residue of the serum obtained from 100 grams of blood is then T — r, the corresponding amount of serum of the erythrocytes in 100 parts of blood =100- looX (T- 100 X (T — r). — ; further, the weight the latter equals 48 grams in 100 grams of blood from a man and 35 grams in the same amount of blood from a woman. Number. — In men the number of red blood-corpuscles is more than 5,000,000, while in women it is about 4,000,000 in i cubic millimeter, making 25 billions in 5 kilos of blood. The number is in inverse pro- portion to the amount of the plasma, and from this fact it will be seen Fig. I. — -A, human colored blood-corpuscles: i, on the flat; 2, on edge; 3, rouleau of colored corpuscles. B, amphibian colored blood-corpuscles: x, on the flat; 2, on edge. C, ideal transverse section of a human colored blood-corpusde magnified 5000 times linear: ab, diameter; cd, thickness. that the number must vary in accordance with the state of contrac- tion of the vessels, conditions of pressure and diffusion - currents and the like. The number of red blood-corpuscles is increased in venous blood (at times in small cutaneous veins and in the presence of stasis) , after the ingestion of solid food, after rest at night, after marked loss of water through the skin, the intestine or the kidneys, during inanition (in consequence of the consumption of blood- plasma), in the blood of the newborn, at times after late ligation of the umbilical cord (from the fourth day the number again becomes reduced) , in persons of vigorous constitution and in residents of the country. The number is dimin- ished during pregnancy and after copious libations. The capillaries contain relatively few blood-corpuscles. Apparent increase or diminution must also ac- company variations in the amount of plasma, and to this fact special attention should be given in investigating the effect of certain influences upon the number of erythrocytes. Thus, for instance, the increased number observed in those re- siding at a high altitude may depend, wholly or in part, upon a greater or lesser reduction in the plasma. In the earlier stages of fetal life the number is from ^ to I million in i cu. mm. Method of Counting Blood-corpuscles. — An exact mixing apparatus for the dilution of the blood is the first requirement. For this purpose the mixer of Potain will answer (Fig. 3). This is a carefully calibrated, pipet-like glass instru- METHOD OF COUXTIXG BLOOD-CORPUSCLES. 33 ment. whose tip is dipped into the l^lood, which hv suction throu£?h a rubber tube IS drawn into the i)i].et either to the mark i or to the mark i. 'The tip carefully dried IS then immersed in 3 per cent, sodium-chlorid solution, which is sucked up until It reaches the mark 10 1. By shaking the mixer a spherule (a) in the bulbous enlargement of the apparatus is moved about so as to effect a homogeneous mix- ture If the blood be sucked up to the mark ^ the mixture will be as i to 200 and if up to the mark i as i to 100. For the enumeration of the cells a small amount of the blood-mixture is intro- duced into the Abbe-Zeiss counting-chamber (Fig. 2), the hrst few drops being thrown away. L pon a slide is cemented a glass cell, o.i mm. deep, upon whose floor are etched a series of squares and which is surrounded by a groove or depres- sion and IS provided with a cover-glass to be placed over it. The space overlving each square has a capacity of ^oVrr cu. mm. The number of cells in each square IS estimated and this multiplied by 4000 gives the number of corpuscles in each Fig. 2.— .\pparatus of Abbe and Zeiss for Counting the Cor- puscles: A, in section; C, surface \ie\v without cover- glass; B, microscopic appearance with the blood-cor- puscles. Fig. 3. — The Melangeur, pipet or mixer. CU. mni^ The result thus obtained must be multiplied by 100 or 200, according as the blood has been diluted 100 or 200 times. To ensure greater accuracy the contents of a large number of squares should be counted and the average taken. Vierordt, Malassez, Gowers, and others have devised similar forms of apparatus tor the same purpose. To count the white blood-corpuscles alone in the chamber the blood is mixed with 10 parts of a ^ per cent, solution of acetic acid, which dissolves out the red corpuscles. It is advisable to stain the leukocytes in the blood-mixer and this can be done with some such solution as the following: 50 cu. cm. of a f per cent, of solution of sodium chlorid with 5 drops of a 5 per cent, alcoholic solution of gentian- violet or hexamethyl-violet. 3 34 THE RED BLOOD-CORPUSCLES. The red blood-corpuscles are characterized by their great elasticity, flexibility, and softness. THE RED BLOOD-CORPUSCLES (ERYTHROCYTES). Individually the red corpuscles are of a yellowish color with a greenish tint. They are unprovided with either capsule or nucleus, but consist throughout of a homogeneous mass. This consists (i) of a framework of exceedingly pale, soft protoplasm, the stroma or cytoplasm, and (2) of the red blood coloring-matter, the hemoglobin, which impregnates the stroma (like paraplasm), in the same way as a sponge takes up fluid. INFLUENCES AFFECTING THE VITAL PHENOMENA OF RED BLOOD- CORPUSCLES. Blood-corpuscles retain in unimpaired degree their vital and func- tional activities in shed blood and even in defibrinated blood subse- quently returned to the circulation. Heat has an influence upon their vitality. If blood be heated to a temperature in the neighbor- hood of 52° C. the vital activity of the erythrocytes is destroyed. This fact is evident from the circumstance that the corpuscles in such blood are soon dissolved when returned to the circulation. Kept in Fig. 4. — Red Blood-corpuscles: a, b, normal human red corpuscles, the central depression more or less in focus; c, d, e, mulberry, and g, h, crenated forms; k, pale corpuscles decolorized by water; 1, stroma; f, frog's blood- corpuscle acted on by a strong saline solution. the cold — in a flask exposed to the influence of ice-water — mammalian blood may retain its functional activity for 4 or 5 days. Removed from the body for a longer period of time and theii returned to the cir- culation the red corpuscles rapidly undergo destruction — an evidence that they have lost their vital activities within this time. The erythrocj'tes in blood recently removed from a vessel frequently exhibit changes in form that result in their assuming a mulberry-like appearance. These have been attributed to active contraction on the part of the stroma. Nevertheless, it must as yet be considered doubtful whether this is to be looked upon as an obvious vital phenomenon. It is true, however, that Max Schultze has observed active contractilit}' and motility in the red blood-corpuscles of quite young embryo chickens. In support of the vital activity of the red corpuscles the fact may be cited that certain substances dissolved in the plasma are INFLUENCES AFFECTING PHYSICAL RED BLOOD-CORPUSCLES. 35 not capable of diffusing into the red blood-corpuscles, as, for instance, solutions of potassium, of iron, and of manganese, although other sub- stances do enter, as, for instance, sugar and chloroform. Nucleated erythrocytes are undoubtedly cells, while the non-nucleated ery- throcytes cannot properly be so considered. The latter have, therefore, been designated blood-plastids. INFLUENCES AFFECTING THE PHYSICAL PHENOMENA OF RED BLOOD- CORPUSCLES. The color of the red corpuscles is changed characteristically by a number of gases. Thus, oxygen, therefore also the air, renders the blood scarlet red, deficiency of oxygen renders it dark bluish red, carbon monoxid renders it cherry red, nitrogen monoxid renders it violet red. All agents that cause marked contraction of the erythrocytes induce a bright scarlet-red color; as, for instance, concentrated solution of sodium sulphate, from the action of which the corpuscles become mulberrv- shaped or distorted into the shape of a key, and in a measure attenu- ated. The color thus produced is brighter than is ever observed in the arteries. Those agents that make the corpuscles globular, as particu- larly water, cause the color of the blood to become darker. If a dry preparation of blood be treated with concentrated solution of methyl- ene-blue diluted half with water some of the erythrocytes, particularly degenerated ones, become stained. It is the larger ones that are especially numerous in the presence of anemia and leukemia. Change in Position and Form. — A phenomenon frequently observed in recently shed blood ,is the arrangement of the corpuscles like rolls of coin (Fig. i, A, 3). The conditions that increase the coagulability of the blood favor this phenome- non, which is to be attributed, in addition to the attraction of the discs, to the formation of a viscid substance. The condition is favored by warming moderately the slide upon which the fresh drop of blood is received. If under such circum- stances agents are added to the blood capable of causing the corpuscles to swell, the rolls separate as the individual corpuscles are transformed into globules. The adhesive substance uniting the erv'throc^'tes, and which not rarely is drawn out into hlamentous threads, is derived from the peripheral layer of the corpuscles. It consists of the stroma-fibrin, formed on the surface of the corpuscles in conse- quence of the inception of an injury at the periphery, and which has become viscid. The changes in shape that the erythrocytes may gradually undergo after leaving the body, up to the point of dissolution, are of especial interest. Some agents bring this series of changes about in rapid suc- cession. If, for instance, blood is exposed to the action of the spark of a Leyden jar, all of the corpuscles become at first mulberry-shaped, that is, the surface becomes rough and soon covered with at times small, at other times large, round nodules (Fig. 4, c d e). If the action be more pronounced the blood-corpuscles become almost globular, with many projecting points, thorn-apple-like (gh); this is probably an indication of the death of the corpuscle. At a further stage the action causes the corpuscles to assume a perfectly globular shape (i i). In this form they appear smaller than normal, as their disc-shaped mass is contracted into a sphere with a lesser diameter. The globules thus formed are viscid, and adjacent corpuscles readily adhere to one another and like fat-globules they may unite to form larger spheres. If the 36 PRESERVATION OF RED BLOOD-CORPUSCLES. action be continued for a still longer time, the blood coloring matter eventually separates from the stroma (k), and the blood-plasma con- sequently becomes reddened, while the stroma is recognizable only as a faint shadow (i). The changes in shape described represent the effects also of a number of other injurious agents causing dissolution of the red blood-corpuscles. Thus, for instance, all of the changes in shape can be observed also in putrid fluid. Influence of Heat. — If a blood-preparation be heated upon a warm stage the corpuscles will be seen to undergo remarkable changes in shape" when the temperature reaches 52° C. They become in part globular, in part draM^n out into the shape of a biscuit, at times per- forated, or larger or smaller drops of the substance of the body are com- pletely constricted off and float about in the surrounding fluid. This is an evidence that considerable degrees of heat destroy the histological individuality of the corpuscles. If the temperature be high and its influence long continued, the erythrocytes are finally entirely dissolved. In the case of burns the blood-corpuscles may undergo the same changes within the vessels. The addition to blood of a concentrated solution of urea acts in the same way as heat. Blood-corpuscles can be broken into fragments in microscopic preparations by strong pressure. The disintegration of blood-corpuscles into frag- ments may be designated erythrocytotrypsy, in contradistinction from their dis- solution, which is known as erythrocytolysis. If a finger moistened with blood be passed over a hot glass plate so that the thin layer of fluid is rapidly dried, the most remarkable forms of long drawn-out distorted blood-corpuscles can be seen. This ex- periment demonstrates in a striking manner their marked softness and elasticity. If blood be mixed with a concentrated solution of mucilage and if, while being examined under the microscope, concentrated solution of sodium chlorid is added, the corpuscles becoine drawn out into longitudinal masses (dragon-shaped) . The same change is observed if blood be admixed with an eqvial amount of liquid gela- tin at a temperature of 36° C, and sections are made after the gelatinous mass has hardened. PRESERVATION OF RED BLOOD-CORPUSCLES. The following are admirable preservative fluids for red blood-cor- puscles : Pacini's Mixture. Hayetn's Fluid. Mercuric chlorid, 2. Mercuric chlorid, 0.5. Sodium chlorid, 4. Sodium sulphate, 5. Glycerin, 26. Sodium chlorid, i. Distilled water, 226. Distilled water, 200. To be diluted with two parts of dis- tilled water before being used. In order to avoid all influence of the air in the examination of fresh blood the following procedure is recommended: A drop of Pacini's fluid is placed upon a portion of the skin, which is then punctured with a fine needle through the fluid. In this way the blood rises into the preserva- tive fluid without having at any time come in contact with the air and the form of the corpuscles is at once fixed. In examining blood for medico-legal purposes the microscope is naturally always employed. Dried spots are carefully softened by PERMEABILITY OF ERYTHROCYTES. 37 means of concentrated or 30 per cent, solution of potassic hydrate, or with some preservative fluid, without friction. By softening them with the aid of concentrated tartaric-acid solution the leukocytes appear with especial distinctness. Often, however, search for the presence of blood-corpuscles will be fruitless. Red, suspicious fluids are examined directly. If the blood-corpuscles in the fluid have possibly already become pale, or if they are present only as stroma, the addition of a wine-yellow aqueous solution of iodin-potassium-iodid to the micro- scopic preparation will at times render them much more distinct. Saturated solution of picric acid, 20 per cent, solution of pyrogallic acid and 30 per cent, solution of silver nitrate have also been recom- mended for this purpose. PERMEABILITY OF ERYTHROCYTES.— ISOTONIA (HYPERISO- TONIA AND HYPISOTONIA).— DEMONSTRATION OF THE STROMA-LAKE COLORATION OF THE BLOOD. All substances soluble in water attract water with a certain intensity. The energy by means of which this attraction takes place is known as hygroscopic energy or osmotic tension. The manner in which this behaves with regard to living cells was discovered by de Vries (1884). A vegetable cell consists of a membrane, which is permeable to salts and to water. This membrane is in contact by its inner surface with the adjacent cell-protoplasm, which likewise is permeable to water, but not to salts. If fresh vegetable cells are placed in distilled water, this passes through the cell-membrane and through the cell-protoplasm, and causes the cells to swell. If, however, the cells are placed in a strong saline solution, the cell-contents shrink, because water is abstracted from them. The shrinking of the cellular protoplasm is shown by the fact that the protoplasm contracts upon all sides and becomes detached from the cell-membrane. This detachment of the shrunken cell-body from the cell-wall in consequence of loss of water is designated plasmolysis by de Vries. Plasmolysis is the more pronounced the more concentrated the saline solution surrounding the vegetable cell. The saline concentra- tion that brings about the first signs of plasmolysis can be determined experimentally for every variety of cell. The different salts must be employed in various concentrations, in order to bring about the same degree of plasmolysis. Solutions of difterent salts that exert the same effects in the process of plasmolysis are designated isotonic solutions. The necessary concentrations are to e^ch other as the molecular weights of the different salts. For instance, a 0.58 per cent, solution of sodium chlorid causes the beginning of plasmolysis in the same way as a i.oi per cent, solution of potassium nitrate, or as a 1.5 per cent, solution of sodium iodid. The molecular weights of the three substances are 58, loi, and 150 respectively. Isotonic solutions have the same freezing- point, which always becomes lower with increasing concentration; and also the same boiling-point, which becomes higher with the degree of concentration. There is thus for the red blood-corpuscles a given concentration for certain but not all substances in which they neither shrink nor swell. For mammalian erythrocytes this is a 0.9 per cent, solution of sodium chlorid — for the frog 0.6 per cent. If the equally effective degree of 38 PERMEABILITY OF ERYTHROCYTES. centration is determined for other salts, the isotonic solutions will be established. Obviously the blood-plasma likewise is such an isotonic solution, as the erythrocytes retain their form perfectly within it. Those solutions are hypcrisotonic, that is, of greater concentration, that abstract water from the erythrocytes and therefore cause them to shrink; while those solutions are designated hypisotonic, that is, of feebler concentration, that yield up water to the erythrocytes and there- fore cause them to swell. Although the erythrocytes preserve their form in isotonic solutions, nevertheless an interchange may take place between the soluble sub- stances in their interior and those of the surrounding fluid. Thus, chlorids, phosphates, and proteids, for instance, pass from one to the other. Under such circumstances, however, the isotonia is preserved. If, therefore, substances pass from the erythrocytes into the surrounding blood-plasma, other substances must, conversely, pass into them in order to preserve the isotonia. The red corpuscles thus possess the property of maintaining a constant degree of osmotic tension with refer- ence to certain substances. If, for instance, small amounts of an acid, and also carbon dioxid, be added to blood, albumin and phosphates pass from the corpuscles into the plasma, while, conversely, chlorids pass from the latter into the erythrocytes to maintain the isotonia. In consequence, the corpuscles become somewhat globular and their diam- eter diminishes in size. The blood-corpuscles exhibit the reverse inter- change and effect in shape after addition of small amounts of alkali. Van 't Hoff discovered in 1887 the law that the interchange of sub- stances in solution takes place according to the same laws as those applicable to gases, namely, the osmotic pressure corresponds entirely to the tension of a gas. The laws of gases laid down by Boyle- Mariotte are, therefore, applicable also to substances in solution. Ac- cordingly, and by reason of the diversity of the soluble substances con- tained within the cells and in the surrounding fluids currents must arise between the two in consequence of the osmotic pressure. If, therefore, erythrocytes, which behave like 'sacs filled with saline solutions, are placed in another saline solution, phenomena appear entirely analogous to those that occur when a sac filled with gas is introduced into another gas. The er^^throcytes floating in a solution retain their volume only if the fluid is isotonic; that is, if it exerts the same osmotic pressure and if the substances dissolved in the surrounding solution cannot enter the corpuscles. If the osmotic pressure in the surrounding fluid is dimin- ished the corpuscle swells until it becomes completely dissolved in water, whose osmotic pressure is zero. The blood then becomes lake- colored. Exactly the same effect as is produced by distilled water must be produced also by the solution of a substance, quite independ- ently of the degree of its osmotic pressure, if the substance in solution readily penetrates the blood-corpuscles, and therefore can exert no pressure upon its wall. Under such circumstances also the corpuscle will undergo dissolution and the blood become lake-colored. The phenomenon of the blood becoming lake- colored, which is easily recognizable, indicates, therefore, that the blood-corpuscles are either in a solution of low osmotic pressure or in a solution whose osmotic pressure is not manifest because the wall of the corpuscles is impervious PKRMIiABILITY OV E RVTIl ROC VTES. 39 to the substance in sokition. Among those solutions in wliich the blood- corpuscles are dissolved, independently of the degree of osmotic pres- sure of the solution, urea occupies the first place. The ammonium salts, with the exception of the sulphate, behave in the same manner. Certain exceptions to which the laws of osmotic pressure for the Ijlood- corpuscles do not appear to apply H. Koeppe has been able to explain according to the theory of solutions of van 't Hoff. The circumstance must be taken into consideration, as Ostwald was the first to point out, whether, in accordance with the concentration of their solution, the dissolved substance has or has not completely dissociated itself into its ions. Many agents separate the coloring-matter from the stroma. In consequence the hemoglobin is dissolved in the blood-plasma, and the blood becomes transparent, as it contains the coloring-matter in the form of a transparent pigment. It is, therefore, designated lake- colored. Lake-colored blood is dark red. In the dissolution of the erythrocytes the change does not affect the aggregate condition, but it consists only in a transposition of the hemoglobin, which leaves the stroma and passes over into the blood-plasma. Therefore, no reduction in temperature takes place. Method. — For the microscopic demonstration of the stroma it is recommended that a one per cent, solution of tartaric acid blood mixed with an equal volume of concentrated sodium sulphate be carefully added. In order to obtain an abundance of stroma for chemical examination, dehbrinated blood is mixed with 10 volumes of a solution of sodium chlorid containing i volume of the concentrated solution and from 15 to 20 volumes of water. In this the stromata are precipitated as a whitish sediment. The following agents effect separation of stroma and hemoglobin : (a) Physical agents: (i) Heating of the blood to a temperature of 60° C. The degree of heat differs, however, in different animals. (2) Repeated freez- ing and thawing. (3) The static spark, although not after salts have been added to the blood, and the constant and induced currents. (b) Chemically active substances generated within the body : (4) Bile or bile-salts. (5) Serum from other species of animals. Thus, for instance, the serum of dogs' blood and of frogs' blood dissolves the blood-corpuscles of the rabbit in a few minutes. According to Rvimmo, Maragliano, and Castellino the blood-serum in cases of acute infectious disease and chronic dyscrasias is said to be destructive to the erythrocytes of healthy individuals. (6) Lake-colored blood from a number of other species of animals. (c) Other chemical reagents: (7) Water. (8) Exposure to the vapors of chloroform, ether, amylene; small amounts of alcohol, paraldehyd, thymol, nitrobenzol, ethylic ether, acetone, petroleum ether, and others. (9) Antimony hydrid, hydrogen arsenid, carbon disulphid. (10) Solutions of certain salts may be mixed with blood in a definite concentration without causing change in the red blood-corpuscles. If the saline solution is made either more dilute or more concentrated, dissolution of the corpuscles takes place. This is the case, for instance, with sodium chlorid. Traces of alkali render the erj^throcytes more resistant to such solutions, Avhile traces of acid exert an injurious effect. Accord- ing to Bernstein and Becker salts cause an increase in the resistance to physical solvents, but a reduction to chemical solvents. (11) Addition of boric acid, i per cent., to amphibian blood causes the red mass, which at the same time sur- rounds the nucleus when present and is designated zooid, to escape from the stroma, which is designated ecoid, to withdraw from the periphery to the inte- rior of the corpuscles, and often entirelj^ to pass out. Brucker, therefore, consid- ers the stroma to a certain degree a repository within which is lodged the remain- ing substance of the blood-corpuscles especially endowed with vital phenomena. (12) Strong acid solutions dissolve the blood-corpuscles, while weaker solutions cause precipitates in the hemoglobin. This can be distinctly observed in the case of carbolic acid. (13) Alkalies in moderate concentration cause sudden dis- solution. Addition of potassic-hydrate solution of about 10 per cent, to the blood 40 FORM, SIZE, AND NUMBER OF ERYTHROCYTES IN ANIMALS. from the margin of a cover-glass permits the process of dissolution to be readily observed microscopicall}'. At lirst the corpuscles abruptly become globular in jerks and thus apparently smaller; later they swell up like soap-bubbles. The influence of the gaseous content of the red blood-corpu.scles upon their solubility is remarkable. The corpuscles in blood containing much carbon dioxid are dissolved most readily; those in blood containing much oxygen are much less readily dissolved; while between the two are the corpuscles containing much carbon monoxid. Total removal of the gases of the blood causes of itself the devel- opment of a lake-color. The erythrocytes possess a certain degree of resistance to the action of solvents. The following method may be employed to determine this degree readily. A drop of blood is mixed with an equal amount of a 3 per cent, solution of sodium chlorid, and then as much distilled water is added as is required to dissolve all of the red blood-corpuscles. The method is carried out as follows with human blood: With the aid of the blood-mixer of the blood-corpuscle counting-apparatus (Fig. 3) blood is collected from a puncture of the skin up to the mark i, and is expelled for microscopic examination into a concave glass cell, in which previously an equal amount of a 3 per cent, solution of sodium chlorid had been placed. Well admixed, all of the erythrocytes will be preserved. Now, by means of the same apparatus, distilled water is added, and the changes observed under the microscope until all of the red corpuscles are dissolved. The glass cell is covered after each addition in order to prevent evaporation. The erythrocytes of some persons are more readily dissolved than is normal, being soft and plastic and under- going striking changes. In addition, reference may be made to the following states: All blood-mixttires that jeopardize the normal condition of the erythro- cytes, such as cholemia, intoxications with substances that cause dissolution of the blood-corpuscles and high grades of venosity. Interesting observations may be made further in the presence of blood-diatheses and infectious processes, hemo- globinuria, and burns. The resistance appears diminished in case of anemia and of fever. FORM, SIZE, AND NUMBER OF ERYTHROCYTES IN DIFFERENT ANIMALS. All mammals, with the exception of the camel, the llama, the alpaca, and related animals, as well as the cyclostomata among fish, for instance the lamprey, have coin-shaped circular erythrocytes. The mammalia excepted have oval erythrocytes without nuclei, while birds, reptiles, amphibia (i, B) and fish, with the exception of the cyclostomata, have similarly shaped erythrocytes with nuclei. Coin-shaped Oval Blood-corpuscles. Blood-corpuscles. Short Diameter. Long Diameter. Elephant, 9-4 /' Llama, 4.2 // 7-5 /' Man, 7-5 " Pigeon, 6.5 " 14.7 " Dog, 7.2 " Frog, 16.3 " 23.0 " Rabbit, 7.16 " Triton, 19.5 " 29-3 " Cat, 6.2 " Proteus, 35.6 " .^8.2 " Sheep, 5-0 " The corpuscles of the amphiuma are about a Goat, 4-25 " third larger than those of proteus. Musk-deer 2-5 " Among vertebrates, the blood of the amphioxus is colorless. The large blood- corpuscles of many amphibia can be seen with the naked eye. In those of the frog a nucleohis is demonstrable. It is readily explicable that the larger the blood-corpuscles the smaller must be their number and their total superficies in a given voluine of blood. Only in birds is the number relatively larger than in other classes of vertebrates, notwithstanding the greater size of the corpuscles. This probably depends tipon the fact that in them metabolism exhibits the greatest energy. Among mammals carnivc ra have a larger number of blood- nEVELOPMEXT Ol- RED R LOOD-CORPUSCLES. 41 corpuscles than lurlnvdra. In goats the blood contains 19,000.000 blood-corpus- cles in the cubic millimeter; in the llama, 13,186,000; in the bull finch, 3,600,000; in the lizard, i. 292, 000; in the frog, 408,900; in the proteus, 33,600. During the sleep of winter Vierordt observed the ntnnber of blood-corpuscles in the mar- mot diminish from 7,000,000 to 2,000,000 in a cu. mm. In invertebrates the blood is generally colorless, with colorless cells. In some invertebrates, for instance the earth-worm, the larva of the large gnat, and others, the plasma is red and contains hemoglobin, l)ut the blood-corpuscles arc colorless. Red, violet, brownish, greenish, opalescent blood, with colorless corpuscles (ame- boid cells), is found in some mussels. In the cephalopods and in certain snails and crabs a bluish, globulin-like coloring-matter is present in the blood, containing copper and combining with oxygen, hemocyanin, which is decolorized by a defi- ciency of oxygen. Certain round-worms have a green respiratory pigment, chloro- cruorin, while other animals have a 3-ellow, red, or brown pigment of similar function. DEVELOPMENT OF RED BLOOD-CORPUSCLES. A. The ciubryoiial development of the blood-corpuscles begins in the chicken as early as the first day. The corpuscles develop in groups within large globules of protoplasm that detach themselves from the walls of the vascular spaces resulting from the apposition of the forma- tive cells. At first they are globular, rough, nucleated, larger than the permanent cells and unpigmented. At a later period they take up the coloring-matter and attain their definite form, with reten- tion of the nucleus. Only when the vessels enter into communication with the heart, are the corpuscles swept away or isolated in groups, and then become set free in the circulation. Remak demonstrated all stages of their multiplication by division. Cells dividing by mitosis are observed most abundantly between the third and the fifth day of incubation, but no longer after their escape. Multiplication takes place by division also in the larvae of amphibia, as well as during fetal life in mammals in the spleen, the bone-marrow and the liver, and in the circulating blood. Neumann, further, found in the liver of the embryo, protoplasmic cells— descendants of the vas- cular endothelium or of the liver-cells — enclosing red blood-corpuscles. Besides, there were found in the liver cells with large nuclei, in part con- taining hemoglobin, in part free from hemoglobin, which divided by mitosis and then, with shrinking of the nucleus, became transformed into definitive blood-corpuscles. Foa and Salvioli observed endogenous formation in the lymphatic glands, in addition to the liver and spleen, also within large protoplasmic cells. The spleen also is considered a seat for the formation of the red blood-corpuscles, though only during embryonal life. Here the red corpuscles are believed to be formed of yellow, round, nucleated cells, representing transitional forms. From the embryonal bodies (erythroblasts), always at first nucleated, there result, in the later stages of embryonal life, the characteristically shaped and at the same time non-nucleated corpuscles; the nucleus, together with a portion of the protoplasm, disappearing. In the human embryo only nucleated corpuscles are present in the fourth week. In the third month they constitute only from one-eighth to one-quarter of all the erythrocytes, while at the end of fetal life nucleated corpuscles are found only with great rarity (Fig. 8). According to some observers, mammalian erythrocytes contain a nucleus-like central body, which Lavdow-sky considers as the remains of nuclear substance. According to J. Arnold, the central body sometimes observed consists of a gran- 42 DEVELOPMEXT OF RED BLOOD-CORPUSCLES. ular-filamentous transformation of the previous nucleus. This body, designated nucleoid, is surrounded by a zone of paraplasm, enclosing hemoglobin and gran- ular and h3-aline matter in a filamentous framework. Nucleoid and paraplasm may under certain conditions be extruded from the erj'throcytes. Perhaps these contribute to the formation of blood-plates. B. Development of Vessels and Blood-corpuscles in the Earliest Post- embryonal Period. — Following J. Arnold, Golubew believes that the blood - capillaries present in the tail of frog -larvae form in various situations at first solid buds that grow more and more deeply into the tissues, enter into anastomotic union with adjacent buds and finally become hollow, with disappearance of their protoplasmic contents. The capillaries would thus like an intricate branched network make their way into the tissues and spread like a foreign intruder. Ranvier observed the same process of growth in the omentum of newborn cats. The development of the capillaries and at the same time of the blood- corpuscles in their interior has been observed in an especially instruc- tive manner in the large omentum of the young rabbit. When a week old, the omentum in these animals exhibits dull- white spots in whose in- terior lie so-called vessel- forming or vaso-formative cells (Fig. 5), that is, strongly refracting cellular elements varying widely in shape, and provided with protoplasmic processes (a). The protoplasm of these cells resembles that of the lymph-cells, particularly with respect to its mark- edly refracting character. In the interior of these cellular structures can be seen rod-shaped nuclei ar- ranged longitudinally (K K) and red blood-corpuscles (r r), both sur- rounded by protoplasm. From the vessel-forming cells protoplasmic shoots and processes arise, which in part terminate free and in part unite to form a delicate network. In some places nucleated connec- tive-tissue corpuscles arranged longitudinally lie upon the structures. These constitute the beginning of the connective-tissue perivascular sheath. The vessel - forming cells appear in various shapes, either longi- tudinally cylindrical, with pointed extremities, or round or oval, rather resembling large lymph -cells or connective-tissue cells. These cells are always the seat of origin of non-nucleated erythrocytes, which thus arise in the protoplasm of the vessel-forming cells, as the chlorophyl- grains or starch-granules arise in the protoplasm of vegetable cells. Only after the blood-corpuscles have thus formed within their interior do these cells unite through their processes with the vascular system. Their tubular arrangement becomes connected with adjacent vessels and the blood-corpuscles are washed away. In rabbits from four to six weeks old these areas contain fewer and fewer corpuscles. If it be Fig. 5. — Formation of Red Blood-corpuscles within "Vaso-forma- tive Cells." from the Omentum of a Rabbit Seven Days Old; r, r, the formed corpuscles; K. K, nuclei of the vaso-forma- tive cell; a, a, processes which ultimately unite to torm capQlaries. DESTRUCTION' OF RED BL(JOD-CORPUSCLES. 43 borne in mind that Schafer observed similar formative processes in the subcutaneous connective tissue of young rats, the question must arise whether such blood-forming stations do not exist in many parts of the body and constitute seats for tlie regeneration of the blood. For purposes of demonstration it is only necessary to observe omentum of suitable agje in a fresh state in peritoneal fluid, evaporation being prevented by applying ]iaraffin to the edges of the cover-glass. Landois saw preparations of this highly interesting developmental process in the laboratory of Ranvier at Paris with such a degree of distinctness as to leave in his mind no doubt as to the accuracy of the observation. Neumann saw analogous formations in the einbrj-onal liver, Wissotzky in the amnion of the rabbit, Nicolaides in the mesen- tery of the guinea-pig, Klein in the amniotic sac of the chicken's egg, Bayerl in the cartilaginous capsules of ossifying cartilage, Leboucq and Hayem in other situations, all indicative of the fact that the blood-cells develop endogenously in certain cellular structures of considerable size whose protoplasm serves at the same time for the formation of the vessel-wall. C. -4/ a later period of life the red blood-corpuscles develop from special nucleated cells, the erythroblasts. It is believed that the latter gradually assume the form and color of perfect erythrocytes. Accord- ing to Neumann they possess blood coloring-matter from the outset. In caudate amphibia and fish the spleen, and in all other vertebrates, the bone-marrow constitutes the seat for the formation of those juve- nile forms that multiply by division. Particularly in the latter all stages of the transformation may be seen, especially pale, contractile cells resembling white blood-corpuscles, and later on red nucleated corpuscles that must be considered as the progenitors of the red corpuscles and that are capable of undergoing multiplication by mitosis. After copious loss of blood the process of transformation and the entrance into the blood-stream is said to be observed in especially marked degree. J. Arnold found in the protoplasm of the nucleated erythrocytes of bone-marrow granules resembling those of hemo- globin-free cells. In the process of transformation into red blood- corpuscles these granules become invisible through transformation. The products of the mitotic division of the pale cells especially are to be considered as the progenitors of the nucleated erythrocytes. In the red bone-marrow, perhaps also in the spleen, the small veins and most of the c&pillaries have no definite wall. The formed erythrocytes accord- ingly can at any time be swept into the circulation from these parts. The bones of the skull and most of those of the trunk contain red (blood- forming) marrow, while the extremities contain only fatty marrow, or only the upper portions of the femur and the humerus contain red inarrow. When active regenerative processes are taking place in the blood the fatty marrow may be transformed into red marrow, and indeed from the upper portion of the bones named downward, even through all the bones of the extremities. Red, blood- corpuscle-forming marrow may develop even in the ossified lar\-ngeal cartilages and in pathological bony tumors. DESTRUCTION OF RED BLOOD-CORPUSCLES. As erythrocytes are being constantly formed, it must be assumed that they are being constantly destroyed. Further, the situations are known in which this occurs especially. Among these is first the liver, as the elements of the bile are formed from blood coloring-matter and the blood of the hepatic veins contains a smaller number of red blood-corpuscles. The splenic pulp also contains cells indicative of 44 DESTRUCTION OF RED BLOOD-CORPUSCLES. disintegration of erythrocytes. These are the blood-corpuscle-con- taining cells described in connection with the spleen. The investigations of Quincke have rendered it probable that the red blood-corpuscles — whose span of life may cover more than three or four weeks — if they are to be eliminated are taken up by the white blood-corpuscles of the liver-capillaries and by perhaps identical cells of the splenic pulp and of the bone-marrow, and preferably deposited in the liver-capillaries, the spleen, and the bone-marrow. The erythrocytes taken up are, without having previously been dissolved, converted in part into yellow and in part into colorless iron-albuminates, hematosiderin, which can be demonstrated microchemically in part in granular, in part in soluble form, giving rise to a greenish discoloration on addition of ammonium sulphid. In the spleen and in the bone-marrow, in part perhaps also in the liver, these are again employed for the regeneration of red blood-cor- puscles, while another portion of the iron is eliminated through the liver. Latschenberger has found pigmented and colorless plates in the blood, the latter at times in flakes of fibrin, and these he considers as the terminal prod- ucts of the disintegration of all morphological blood-elements. The pigmented plates are derived from the erythrocytes and exhibit in part the iron-reaction of hematosiderin, and in part that of biliary coloring-matter. These plates are retained and ftirther transformed in the spleen and in the bone-marrow. As a sign of the degeneration of the er\^throcytes that may precede their death Ehrhch mentions their property of staining violet with eosin-hematoxylin or blue ^vith methylene-blue. The rarity with which cells containing blood-cor- puscles are found in the general circulation justifies the conclusion that corpuscles are taken up within the spleen, the liver, and the bone-marrow, being favored by the slowness of the circulation in these parts. Pathological. — Among pathological conditions there may be quantitative dis- turbances in the processes of blood-destruction and blood-formation. Accumula- tion of iron-containing materials from red blood-corpuscles maj- take place in the spleen, the bone-marrow, and the liver-capillaries: (i) if the destruction of red blood-corpuscles is increased, as, for instance, in cases of anemia; (2) if the for- mation of new red elements from old material is retarded. If elimination through the liver-cells is interfered with, the iron accumulates in them, and it is then present in the blood-plasma also in increased amount, and it may be eliminated by other glands, although a deposit of iron may take place in these (cortex of the kidney, pancreas) within the glandular cells and in the tissue-elements of other organs. After abundant regeneration of blood in dogs the leukocytes of the liver- capillaries are in the course of four weeks enormously rich in iron-containing granules; likewise the cells of the spleen, of the bone-marrow, of the lymphatic glands, further the liver-cells and the epithelium of the cortex of the kidney. The iron-reaction in the two situations last named takes place also after intro- duction of hemoglobin or of iron-salts into the blood. Within thrombi and also in extravasations of blood that diffuse into the sur- rounding living tissue hematosiderin hkewise develops, in addition to hematoidin. which forms when not in contact with the tissues. The stage of iron-reaction of the products of the disintegration of the erythrocytes is, however, not of con- sequence, as in the progress of time the residuum no longer exhibits this reaction. V. Recklinghausen designates as hemochromatosis a brownish discoloration of the tissues dependent upon abnormal dissolution of er\-throcytes or local extrava- sations of blood, and which is caused by the iron-containing hematosiderin and the iron-free hemofuscin derived from it. Landois observed these conditions after extensive transfusion. If it be remembered that after repeated copious loss of blood and after every menstruation the blood is regenerated within a relatively short period of time, it is evident that an active process of regeneration must take place. As to the amount of corpuscles destroyed daily the amount of biliary and urinary pigment formed from the blood coloring- matter affords some idea. THE WHITE BLOOD-CORPUSCLES. 45 THE WHITE BLOOD-CORPUSCLES (LEUKOCYTES), THE BLOOD- PLATES AND ELEMENTARY GRANULES. Through the lymph-stream colorless cells, designated white blood- corpuscles or leukocytes, are swept into the blood. In addition to the blood they are found in the lymph, in adenoid tissue, in bone-marrow and as wandering cells in the connective tissues of various parts, as well as betw^een glandular and epithelial cells. They consist of globular masses of viscid, bright or granular, highly refracting, soft, motile, unencapsulated protoplasm (Fig. 6). In the fresh state (A) they exhibit no nucleus, which appears only after addition of water or acetic acid (B), and in consequence of which also the definition becomes more distinct. Water, besides, renders the contents more granular and more turbid, while acetic acid causes them to clear up. The nucleus contains one or more nucleoli. The diameter of the cells varies from 4 to 13 //. The leukocytes are dissolved by peptone. In accordance with their form and size leukocytes are differentiated as follow's: (i) Small lymphocytes, approximating erythrocytes in size, with a large, round, deeply staining nucleus and a thin margin of proto- plasm. (2) Large cells, with an extensive oval, feebly staining nucleus and a heavy cortical layer of protoplasm. (3) Cells resembling those last described except that the nucleus is constricted. (4) Somewhat smaller cells, con- stituting about three-quar- ters of the total number, with polymorphous, lobulated or variously convoluted nu- clei, or nuclei separated into from one to four parts. forms of cells have a genetic connection. The leukocytes increase by division, in part by mitosis, in part by amitosis especially in their germ-centers, that is, the lymphatic glands and adenoid tissues. Division has not as yet been observed in the small lymphocytes found in the lymphatic glands (Fig. 8, o 0). Perhaps these represent juvenile forms. Also sessile cells in the connective tissue may undergo multiplication by division and send their offspring into the blood through the lymph-stream. The number of leukocytes in a given division of the vascular system may differ widely. At times they may be found increased in one place or another, as, for instance, as a result of chemotaxis, while at other timcb a large number may be sent into the blood-stream from the lymphatic apparatus. The increase is designated leukocytosis. The number of leukocytes is considerably less in shed blood than in circulating blood. Immediately after removal from the vessels nine- tenths of all of the leukocytes are destroyed (fibrin-formation). Local heat diminishes, and cold increases, the number of leuko- cytes in the vessels of the part of the body treated, as they are re- strained in the blood-vessels contracted bv cold. Fig. 6. — A, human white blood-corpuscles, without any re- agent; B, after the action of water; C, after acetic acid; D, frog's corpuscles, changes of shape due to ameboid movement. The last three 46 THE WHITE BLOOD-CORPUSCLES. NUMBER OF LEUKOCYTES IX PROPORTION' TO THE RED BLOOD- CORPUSCLES IN SHED BLOOD. Under Normal Conditions. I : 335. Welcker, I : 357, Moleschott, I : 500-800, V. Jaksch. (Ill children the number is said to be somewhat greater than in adults.) In Various Situations. Splenic vein, i : 60, Splenic arterj-, i : 2260, Hepatic vein, i : 170, Portal vein, i : 740, The number is in general greater in the veins than in the arteries. Under Various Conditions. The number is increased b}' digestion, blood-let- ting, long-continued suppuration, menstru- ation, the puerperium, the death-agony, tonic medicaments (quinin, bitters) , ingestion of nuclein. gout. The number is dimin- ished by hunger and impaired nutrition. The movement of the leukocytes — observ^ed b}'- Wharton Jones in 1846 in the ray, and by Davaine in 1850 in man — which has been desig- nated ameboid, because it corresponds entirely with that of the ameba, is due to alternate contraction and relaxation of the protoplasm surrounding the nucleus. It can be recognized especially from the fact that processes are sent out from the surface and withdrawn (Fig. 7) like the pseudopods of the ameba. At the same time the protoplasm has an internal current, which can be seen particularly in the polymor- phonuclear cells. Movement has been seen also in the nucleus itself. The movement is attended with two sets of phenomena: (i) The migra- tion of the cells, inasmuch as they draw themselves along by means of protrusion and retraction of their viscid processes. In this way they may migrate even through the interstices of intact vessels. Arnold considers the capability of certain wandering cells to develop into epithelioid or giant cells as demonstrated. (2) The taking up of small granules, such as fat, pigment, foreign bodies, which at first adhere to the surface and through the internal current are drawn into the interior of the leukocytes and which finally may be again extruded, in the same way as ameb'se take up food. Thus they take up fat-globules, peptones and albuminous bodies that have gained entrance into the blood-stream and which they may later deposit elsewhere. Metschnikoff dwells upon the activity of the leukoc\-tes in retrogressive pro- cesses, the parts to be broken down being taken up in the forms of particles and therefore in a measure devoured. He designates the cells with these activities as devouring cells— phagocytes. Thus they act as cliondroc lasts and osteoL-lasis in the absorption of cartilage and bone respectively. Cells of similar activity are found in the tails of batrachia, and which take up portions of the tissue, as, for instance, fragments of fibrils, in the disappearance of the tails during the process of metamorphosis. (See also absorption of the deciduous teeth.) Thus, schizomycetes or particles of other substances that have gained entrance into the blood have been fotmd taken up in part by leukocytes. Later, the leu- koc^-tes yield up these substances to the endothelial cells of the capillaries of the liver and the lungs, less commonly of the spleen. The motility of the leuko- c\-tes is destroyed by quinin. The leukocytes exhibit still another interesting peculiarity, namely that of chemotaxis (chemotropism) , which consists in the attraction of freely motile cells — Hke some lower organisms — by certain substances, and their repulsion by certain others. Especially the metabolic products of pathogenic and non-path- ogenic microorganisms exert a strong attractive influence upon the leukocytes. HUMAN" LEUKOCYTES, SHOWING AMEBOID MOVEMENTS. 47 If, therefore, colonies of staphylococcus (bacteria of suppuration) collect at a given part of the body their metabolic products attract the leukocytes from the neighbor- mg vessels, and in this way inflammatory reaction and suppuration result. The poison is either eliminated with the pus or is destroyed by the phagocytic activity of the leukocytes. The leukocytes also secrete special chemical substances that destroy the injurious microorganisms. These substances are known as alexins. In warm-blooded animals the leukocytes exhibit movement for a long time upon a warm stage — at a temperature of 40° C. for about two or three hours; a temperature of 47° C. induces rigidity: heat-rigidity and death. The lowest degree of temperature at which ameboid move- ment is possible is 14° C. In cold-blooded animals, such as the frog the leukocytes can be seen to make their way out of a small coagulated blood-clot in a moist chamber and move about in the express- ed serum. v. Reck- linghausen observed motile phenomena on the part of leukocytes in a moist chamber for as long as three weeks. Oxygen is necessary for the movement. Induc- tion-currents cause the leukocytes sud- denly to become round, like irritated amebae through re- traction of all of their processes. If the electric current be not too strong, the leuko- cytes resume their movements in the course of a short time. Strong and long-continued currents destroy them, causing them further to swell and undergo complete disintegration. The dissolution of w^hite blood- corpuscles is known as Icukocytolysis . It occurs as a norrnal phenom- enon in the circulating lymph and in the blood in limited degree. With regard to the source and the functional significance of the different varieties of leukocytes complete knowledge is as A-et wanting. An attempt has been made to obtain a sharper differentiation of the leukocytes through the property of the smallest granules within the protoplasm of the cells to stain only with acid or with basic or with neutral pigments. Method. — Recently shed blood is spread in a thin layer upon a cover-slip, dried in the air, then placed in an air-bath at a temperature of i2 5°C. for two hours. Next it is stained, washed with water, dried in the air and enclosed in Canada balsam. The granules of the oxyphile or eosinophile cells (Fig. S. a.b. with un.stained nucleus: "in c the nucleus is stained violet with hematoxylon) are stained only by acid pigments, such as a saturated solution of eosin in 5 per cent, carbolglycerin. The source of these cells is the bone-marrow. In normal human blood they con- stitute only about 10 per cent, of all of the leukocytes, but in cases of leukemia they pass in large number from the bone-marrow into the blood-stream — myel- ogenous leukemia. The tine granules of the large mononuclear cells of normal blood are stained only by basic pigments, such as a concentrated watery solution of methylene-blue (f. g), as well as those of the majority in lymphemic blood. The cells known as mast-cells contain basophile granules of other size (d, e). These cells are rare in normal blood, but they often occur in large number in leukemic blood. Mast- FlG. 7. — Human Leukocytes, Showing Ameboid Movements. 48 VARIOUS FORMS OF LEUKOCYTES AXD ERYTHROCYTES. cells may be found also in the connective tissue of other organs in the vicinity of the epithelial layer, as, for instance, in cutaneous areas the seat of chronic inflarnmation, and from which they then find their way into the blood. Fine neutrophile granules are rendered visible by neutral stains, as, for instance, acid fuchsin neutralized with methylene-blue. These cells exhibit peculiarly sharp, polymorphous nuclear figures (h) or apparently several small nuclei. They are encountered in abundance in normal blood and in the presence of leukocytosis (i is such a cell in the fresh state, while in k and 1 the nucleus alone is stained). The smaller number of neutrophile cells contain a large nucleus, .surrounded by a thin layer of protoplasm (m n) . They are derived from the spleen and the bone- marrow. Between these two forms (h and m n) there are transitional varieties. The leukocytes h i migrate in the presence of inflammation. In cachectic states the mononuclear cells (m n) preponderate, while both forms are increased in num- ber in association with acute leukocytosis. The h'mphocytes o o, with a large reticulated nucleus, are derived from the l^'mphatic glands. Neusser found numeroiis granules of nucleoalbumin in the leukocytes in cases of gout as the forerunners of uric-acid formation. The leukocytes exhibit the reac- tion for glycogen in the presence of progressive suppuration. '^ i=i;^. Fig. 8. — Various Forms of Leukocytes and Erythrocytes. X looo. [.\11 figures are dr;i\va after the same scale: I, a normal erythrocyte drawn into the scale; i = i /a.] The blood- plates of Bizzozero (Fig. 9) deserve especial consideration as a third morphological constituent of the blood. These are pale, color- less, viscid, biconcave discs of varying size, averaging 3 /j. in diameter. One cu. mm. contains 245,000 plates. Bizzozero has observed them in the circulating blood — in the mesentery of the guinea-pig and the wing of the bat. They collect in large numbers upon a thread immersed in fresh blood. They can be obtained from escaping blood after ad- mixture with one per cent, solution of osmic acid or with Hayem's fluid (Fig. 9, 3). In shed blood they rapidly undergo transformation into varied shrunken forms (5), disintegrating into small particles and THE BLOOD-PLATES. 49 being finally dissolved. Where they are collected together they readily cohere into masses (7), and pass over into aggregations resembling stroma-fibrin, which in coagulated blood mav be united with shreds of fibrin (6, 8). Bizzozero believes that they furnish the material for the fibrin in the process of coagulation, and he, as well as Eberth and Schimmelbusch, attribute the initial formation of white thrombi to them. According to Lowit they are formed from disintegrated leukocytes, and according to Lilienfeld from the nuclein and albumin of the nuclei of these cells. According to Wooldridge they are globulin-precipi- tates from the plasma. J. Arnold followed their extrusion and detachment from erythrocytes; in smaller measure they are derived from leukocytes. Halla found them increased in pregnant women, Mosen after hemorrhage, Afanassiew in the Sresence of regenerative states of the blood, Cadet in association with hunger, [aj^em after the crisis of certain infectious diseases, and Fusari in cases of afebrile anemia. They are diminished in the presence of fever, as well as of severe infec- tions and blood-stasis, and also after injection of leech-extract. The blood of cold-blooded animals and of birds contains also small spindle-shaped, nu- cleated cells. © -2\--'' s f 1l # Fig. 9. — "Blood-plates" and Their Derivatives: i, a red blood-corpuscle on the flat; 2, on the side; 3, unchanged blood-plates; 4, lymph corpuscle, surrounded by blood-plates; s, altered blood-plates; 6, lymph corpuscle with two heads of fused blood-plates and threads of fibrin; 7, group of fused blood-plates; 8, small group of partially dissolved blood-plates with fibrils of fibrin. Demonstration in Mass.^If 10 parts of blood are mixed with i part of a 0.2 per cent, solution of ammonium oxalate in 0.7 per cent, solution of sodium chlorid, and the mixture is centrifugated, a grayish-red layer principally of leukocytes will form above the erythrocytes, and over this a white layer consisting almost solely of blood-plates, while above all is the clear plasma. In addition, a few small granules, so-called elementary granules, occur in the blood. These are irregular masses of protoplasm derived from disintegrated leukocytes or blood-plates. According to H. F. Mialler there are constantly present also, especially after the ingestion of food, minute, globular, highly refracting granules, which are not fat, and which he designates blood-dust, or hemokonien. Coagulated blood contains delicate threads of fibrin (Fig. 9, 6, 8), strung like a spider's web between the corpuscles. They become iso- lated after dissolution of the corpuscles. Where many such threads occur together a nodular accumulation takes place. 4 5© ABNORMAL CHANGES IN RED AND WHITE BLOOD-CORPUSCLES. ABNORMAL CHANGES IN THE RED AND WHITE BLOOD- CORPUSCLES. Loss of blood is always followed by diminution in the mtmber of erythrocytes in proportion to the extent of the hemorrhage, and the number may fall to even less than 400,000 in the cu. mm. The loss is soon made good by the absorp- tion of lymph from the tissues. Menstruation furnishes an indication that moderate loss of red blood-corpuscles may be replaced in twenty-eight days. In case of considerable loss of blood, causing a reduction in all of the formative processes, this period may be prolonged to five weeks. In cases of acute febrile disease the elevation of temperature is generally attended with a reduction in the number of red blood-corpuscles, though with an increase in the number of white corpuscles. Chronic diseases diminish the number and often the hemoglobin-con- tent of the erythrocytes in still greater degree. In some individuals, in whom the red blood-corpuscles are deficient in resistance, these undergo dissolution in consequence of the action of profound cold upon peripheral portions of the body, as, for instance, from the application of ice-water, while the blood-plasma becomes reddened and hemoglobinuria may even develop. Diminished regenerative activity on the part of new erythrocytes will also cause reduction in their number, as blood-corpuscles are constantly tmdergoing destruction. If with this there be associated direct loss of blood, as, for instance, menstruation, the reduction may become considerable. In the case of chlorosis a congenital deficiency in the development of the blood-forming and blood-pro- pelling apparatus, that is the vascular system, appears to constitute the cause. The heart and the vessels are scnall, and the absolute number of blood-corpuscles may be reduced even one-half. In the blood-corpuscles themselves, whose relative number may be either maintained or even reduced as much as one-third, the hemo- globin is reduced about one-third. The total volume of erythrocytes has been found diminished. The iron-content of the blood has been reduced, even to one- half. Courses of treatment with iron again increase the amount of hemoglobin and iron in the blood. So-called progressive pernicious anemia, which is char- acterized by the fact that the progressive impoverishment of the blood may even finally terminate fatally, is probably dependent upon some profound derange- ment of the blood-forming organs. In the presence of this disease the erythro- cytes are reduced in number, while their hemoglobin-content is increased. Invo- lution-forms, disintegrating-products (microcytes and poikilocytes) and earlier developmental stages of erythrocytes (nucleated erythrocytes of normal and of excessive size: normoblasts and megaloblasts) are also present. Numerous chronic intoxications, as with lead, swamp-miasm or syphilis, are likewise attended with reduction in the number of blood-corpuscles. The size of the corpuscles varies in disease between 2.9 and 12.9 ", with an average size of from 6 to 8 ". Dwarf blood-corpuscles (6 " and below, microcytes) have been considered as juvenile forms and are found in abundance in almost all forms of anemia (Fig. 8, 6). Giant corpuscles (megalocytes, 10 " and above) are found constantly in cases of pernicious anemia, occasionally in cases of leuke- mia, chlorosis, and cirrhosis of the liver (Fig. 8, 4, 5, represents a nucleated megalocyte as the forerunner of a non-nucleated megalocyte) . If the erj-throcvtes exhibit marked variation in form and size, they are designated poikilocytes (Fig. 8, 6). Abnormalities in the form of the red blood-corpuscles have been observed after severe bums. The corpuscles appear much reduced in size and the thought sug- gests itself that under the influence of the heat accompanying the bum droplets of the corpuscles have become detached, in the same way as this can be ob- served in microscopic preparations on application of heat. Disintegration of blood-corpuscles in many such droplets (erj-throcytotrypsy) has been observed in connection with various disorders, as, for instance, severe malarial fevers. These particles represent fragments of blood-corpuscles and not independent, intact, small, individtial corpuscles. From these fragments there result dark pigment-particles closely related to hematin and which at first float about in the blood (melanemia) . This condition can be developed artificially in rabbits by introducing carbon disulphid (7 parts to 90 parts of oil) subcutane- ously. The leukocytes take up a number of these particles, which later on are fotmd deposited in various tissues, particularly the spleen, the liver, the brain, and the bone-marrow. In some cases the red blood-corpuscles exhibit abnormal softness, so that they CHEMICAL CONSTITUENTS OF THE RED BLOOD-CORPUSCLES. 51 undoij^o marked changes in form as the result even of slight extraneous influences. With regard to lessened resistance on the part of the erythrocytes, reference may be made to p. 35. The nitrogen-content of the erythrocytes is diminished in cases of secondary- anemia, and it is increased in cases of pernicious anemia. In the interior of the erythrocytes of birds, frogs, turtles, etc., low forms of animals develop at times in the form of round pseudovacuoles, and out of which free blood-worms subsequently develop. Also in cases of malarial infection in human beings microbes of varying form (hemameba, Lavtran) have been observed within the erythrocytes, and which probably are conveyed by stinging insects (mos- quitos) — in the same way as Texas fever is conveyed by ticks. They destroy the red blood-corpuscles and in turn are destroyed by quinin. The li'liile blood-corpuscles are generally increased in all acute diseases in which exudation takes place. They exhibit excessive increase in association with so-called leukemia. In this disease the proportion of red to white blood- corpuscles may be as 2 to i. In consequence, the blood acquires an appear- ance as if it were mixed with milk. At the same time the number of erythrocytes is diminished. Leukemia depends upon hyperplasia of the lymphoid tissue or the bone-marrow. These causes are responsible for lymphatic and myelogenous leukemia respectively. Lymphocytes and myelocytes are to be carefully differentiated. The enlargement of the spleen is only secondary; there- fore a pure variety of lienal leukemia is not accepted. Myelogenous leukemia belongs probably among the active forms of leukocytosis. An active leukocytosis is one that results through movement or migration of leukocytes into the blood- current. This may involve the polynuclear — neutrophile or eosinophile — or the mixed cells — the latter with involvement of mononuclear elements containing granules: myelemia. The passive form of leukocytosis comprises the various forms of lymphemia. CHEMICAL CONSTITUENTS OF THE RED BLOOD-CORPUSCLES. The blood coloring-matter hemoglobin — abbreviated Hb — causes the red color of the blood. It is found besides in muscular tissue and in traces, probably only as a contamination through dissolved cells, in the blood-plasma. In the spectroscope it exhibits an absorp- tion-band in the green (Fig. 15, 4). Its percentage-composition ac- cording to Hufner is for the blood of swine, as compared with that for the ox, in parentheses, C, 54.71 (54.66); H, 7.38 (7.25); N 17.43 (17.70); S, 0.479 (0-447); Fe, 0.399 (0.336); O, 19.602 (19.543). For one atom of iron there are two atoms of sulphur in the horse, and three in the dog. According to Hiifner, the formula is C636Hio25Ni64FeS30i,i); the molecular weight is 14,129. Hemoglobin is soluble in water; when heated it coagulates only with decomposition, retaining the sulphur in firm union. Although it is a colloidal substance, it nevertheless undergoes crystallization in all classes of vertebrates from which it has thus far been obtained, in figures belonging to the rhombic system, principally in rhombic plates or prisms, and from the guinea-pig in rhombic tetrahedra. The squirrel, however, forms an exception, in- asmuch as its crystals appear as hexagonal plates. The crystals simply separate in all classes of vertebrate after slow evaporation of blood rendered lake-colored, though with varying degrees of readiness. It is to be inferred that the variations in the form of the crystals in different animals are dependent upon slight changes in chemical constitution. The hemo- globin is readily crystallized from the blood of man, the dog, the mouse, the guinea- pig, the rat, the marmot, the cat, the leech, the horse, the rabbit, birds, and lish; and with difficulty from^ the blood of sheep, oxen, and swine; and not at all from the blood of the frog. Rarely the hemoglobin oif a single blood-corpuscle can be seen to form a small cr\^stal with inclusion of the stroma, as Landois also ob- served in the case of rabbits' blood that had stood for a long time. Within the large blood-corpuscles of fish the small crystal lies at times within the stroma by the side of the nucleus. In this class of vertebrates colorless crystals also have at times been observed. 52 PREPARATION OF HEMOGLOBIN-CRYSTALS. The crystals of hemoglobin are doubly refracting and pleochromatic, that is, they appear bluish red in transmitted light and scarlet red in reflected light. The crystals, which contain from 3 per cent, to 9 per cent, of water of crystallization and therefore become disintegrated from es- cape of this water on exposure to the air, are always soluble in water, though dififerent varieties dissolve with varying degrees of facility. They are more readily soluble in dilute alkali. The solutions are dichroic, that is, they ap- pear red in reflected light and greenish in transmitted light. They are insolu- ble in alcohol, ether, chloroform and fats. As a result of the process of crystalliza- tion the hemoglobin itself appears to under- go an internal change. Previous to crystal- lization it does not diffuse as a true colloidal body, but it actively decomposes hydrogen dioxid. Dissolved in the form of crystals, however, it is slightly diffusible, and does not decompose hydrogen dioxid, through the action of which it is decolorized. The crys- tals of hemoglobin collect like an acid at the positive pole of an electric current. As the hemoglobin thus exhibits alterations after its separation from the erythrocytes, Hoppe- Seyler believed that the oxyhemoglobin was united with lecithin within the erythrocytes, and also the hemoglobin. The former combination he designated artertJi and the latter pJilebiri. Fig. 10. — Hemoglobin-crystals: a b, from hu- man blood; c, from the cat; d, from the guinea-pig; e, from the marmot; and f, from the squirrel. PREPARATION OF HEMOGLOBIN-CRYSTALS. Method of Rollcit. — Defibrinated blood, made lake-colored by freezing and thawing, is poured into a shallow vessel, whose bottom is covered therewith to a height of only ih mm. Evaporation is permitted to take place slowly in a cool place and as a result the crystals separate. Method of Hoppe-Scylcr. — Defibrinated blood is inixed with 10 volumes of a solution of sodium chlorid or of sodium sulphate (i volume of a concentrated solution to 9 volumes of water) and permitted to stand. After the lapse of two days the clear supernatant layer is removed with a pipet, while the thick sediment of blood-corpuscles is washed with water into a glass flask, and shaken with an equal volume of ether until the blood-corpuscles are dissolved. After standing for a short time the supernatant ether is removed, and the lake-colored fluid filtered in the cold; then one-fourth volume of cold (0°) alcohol is added. This mixture is permitted to stand for several days at a temperature of — 5° C. The crystals that will thus have formed in abundance can be collected upon a filter and dried by pressure between blotting-paper. Through the gradual action of the alcohol upon the hemoglobin-solution, by introduction into a dialyzer, it is possible to obtain crystals several millimeters long. Mctliod of Gschcidlen. — Cscheidlen obtained the largest crystals, several centi- meters in length, by melting in small glass tubes defibrinated blood that had been exposed to the air for 24 hours, and preserving for several days at a tem- perature of 37° C. Spread upon a glass plate the crystals readily appear. QUANTITATIVE ESTIMATION OF THE HEMOGLOBIN. (a) From Its Iron-content. — As in the dry state (100° C.) hemoglobin contains 0.42 per cent, of iron by weight, the amount of hemoglobin can be estimated from the amount of iron in the blood. If m represents in percentage the weight QUANT1TATI\ K 1£STI M ATK )X OF THli II li MOGLOU I X . 53 of metallic iron found, the juTccntagc of hcmoRl(jl)in in the blood will be as loo in : 0.42. The mode of procedure is as follows: A measured amount of blood is reduced to ash and this is exhausted with hydrochloric acid for the jjreparation of ferric chlorid. Next the ferric chlorid is converted into ferrous chlorid, and this is titrated with a solution of potassium permanganate. (/>) Colon'iitciric Method. — A dilute watery solution of crystallized hemoglobin is prepared, the exact strength of which is thus known. With this are compared watery dilutions of the blood to be examined, water being added to the latter until the color is the same as that of the hemogloljin-solution. The specimens to Fig. 1 1 . — V. Fleischl's Hemometer. To wash out the graduated pipct the larger tube held over it is employed. be compared are contained in similar vessels of exactly the same thickness (hema- tinometer). Hoppe-Seyler has recently devised a colorimetric double pipet for this purpose. The blood-specimens are saturated with carbon monoxid. For clinical purposes v. Fleischl's hemometer is recommended (Fig. 11). This consists of a cylinder moimted upon a metallic plate and divided into two equal parts, which are closed at one extremity by a disc of glass. Each half is filled with water, and then a measured amount of blood, obtained with a pipet of deter- mined capacity from a punctured wound, is introduced into the one half and dissolved. The color of the red solution thus produced is compared with that of a ruby-red glass wedge viewed through the clear water in the other half of the cylinder and capable of being moved forw"ard and backward by a screwy until 54 EMPLOYMENT OF THE SPECTROSCOPE. the color appears the same in both. The illumination of the blood-solution and the red wedge takes place fr^.m below by means of the light of a lamp. The glass wedge is provided with a scale, and when the colors in the two halves of the cylinder are alike the number on the wedge indicates the amount of hemo- globin in terms of percentage of the normal blood; thus, for instance, the figure 80 indicates that the examined blood contains So per cent, of the hemoglobin in normal blood. (c) With the aid of the spectroscope Preyer found that a solution of 0.8 per cent, of oxyhemoglobin in water — i cm. thick — yielded in addition to red and yellow the first band of green in the spectroscope (Fig. 15. i). Of the blood to be examined about 0.5 cu. cm. is taken and is diluted with water until the identical of effect in the spectroscope is obtained. In addition to having the layers of fluid equal thickness — nameh- 1 cm. — the width of the slit in the spectroscope and the dis- tance between this and the vessel, as well as the intensity of the source of light (stearin candle), must be the same. If k represents the amount of hemoglobin in percentage that permits the passage of the green color (0.8 per cent.), and b the volume of blood to be examined (about 0.5 cu. cm.), and w the amount of water necessary for dilution, then x equals the amount of hemoglobin in the blood to be examined expressed in percentage, that is x =k (w— b) : b. It is advantageous to add a trace of potassic hydrate to the blood and to saturate it with carbon monoxid. The amount of hemoglobin is in men 13.77 per cent, of the total volume of blood, in women 12.59 per cent., in pregnant women — with progressive diminution — from 12 to 9 per cent. According to Lichten- stem and Wintemitz the hemoglobin is most abundant in the blood of the newborn, but this is no longer the case after the age of ten weeks. Between six months and five years of age it is smallest in amount and reaches its second maximum between twenty-one and forty-five years, after which it falls again. The hemoglobin in female blood grows less after the tenth year. The ingestion of food is followed by transitor}^ diminution in the amount of hemoglobin in consequence of the dilution of the blood. The amount of hemoglobin in different animals is as follows: 9.7 per cent, in the dog; 9.9 per cent, in cattle; 10.3 per cent, in sheep; 12.7 per cent, in swine; 13. 1 per cent, in the horse, and from 16 to 17 per cent, in birds. In moist er\^throcytes Hoppe-Seyler found the hemoglobin to con- stitute 40.4 per cent, of all the organic elements, while in the dry cor- puscles the amount was 95.5 per cent., the amount being smaller in the nucleated corpuscles of animals. Pathological.— A reduction in the amount of hemoglobin in the blood takes place during convalescence from febrile diseases, as well as in the presence of pulmonar\- tuberculosis, carcinoma, ulcer of the stomach, diseases of the heart, chronic disease, chlorosis, lettkemia, pernicious anemia, and in conjunction with vigorous mercurial treatment for syphilis. In the presence of hunger the hemo- globin is more resistaht than the remaining solid elements of the blood. EMPLOYMENT OF THE SPECTROSCOPE FOR HEMOGLOBIN EXAMINATION. The spectroscope (Fig. 12 and Fig. 161) consists (i) of a tube A, having at its peripheral extremity a slit S. which can be made larger and smaller. At the other extremity is a double convex lens C, known as a collimator, so adjusted that the slit is placed exactly at the focus of this lens. Light, from the sun or a lamp, illuminating the slit, passes therefore in parallel lines through C. (2) The prism P, by means of which parallel rays are refracted and broken up into the spectral colors, r-v. An astronomic telescope, inverting the image, is directed toward the spectrum r-v, which appears magnified from 6 to 8 times to the view of the observer B with the aid of the telescope. (3) The tube O contains a delicate scale M etched upon glass, and the image of which when illuminated is thrown upon the surface of the prism, whence it is in turn reflected to the eye of the OXYGEN-COMBINATIONS OF HEMOGLOBIN. 55 observer. In this way the observer can sec the spectrum and in or over it the scale. To exclude extraneous, disturbing light, the prism and the inner extremities of these tubes are enclosed within a metallic capsule whose interior is colored black. Absorption-spectra. — If a colored medium, as, for instance, a solution of blood, be placed between tlie slit of the spectroscope and a source of light, the interposed solution does not permit the passage of all of the rays of white light, but some of these are absorlied. Therefore, that portion of the spectrum whose rays are not permitted to pass appears dark to the observer. Fig. 12. — Diagrammatic Representation of the Spectroscope for Study of the .\bsorption-spectra of the Blood. Flame-spectra. — If combustible substances are permitted to bum before the slit in a non-luminous (gas) flame at the extremity of a platinum wire the elements of the ash yield bands of a special color occupying a definite position. Thus, sodium gives rise to a yellow, potassium to a red and a violet line, which are found on combustion of the ash of almost all organs. If sunlight alone is permitted to pass through the slit the spectrum exhibits a large number of lines (Fraun- hofer's lines) occupying definite positions within the colors and according to which different parts of the spectrum can be localized. These are designated A, B, C,|D, etc., a, b, c, etc. (Fig. 15). OXYGEN -COMBINATIONS OF HEMOGLOBIN METHEMOGLOBIN. OXYHEMOGLOBIN AND Oxygen-hemoglobin or Oxyhemoglobin — abbreviated to 0-Hb — is read- ily developed when hemoglobin comes in contact with oxygen or with air (details on p. 78). Oxyhemoglobin is somewhat less readily soluble than hemoglobin. On spectroscopic analysis it exhibits two dark absorption-bands in the yellow and the green, whose position and v/idth in an 0.18 per cent, solution are shown in Fig. 15 (2). Oxyhemoglobin is contained within the er^'throcytes in the circu- lating blood of the arteries and capillaries, as may be demonstrated by spectroscopic examination of the ear of the rabbit and of the thin layers of skin between two fingers placed in apposition. It is an exceedingly unstable chemical combination, yielding its oxygen even through the influence of such agents as release absorbed gases, as, for instance, setting free of gas through the action of an air-pump or the passage of other 56 OXVGEN-COMBINATIONS OF HEMOGLOBIN. gases, particularly carbon monoxid, and heating to the boiling-point. Also in the circulating blood the oxygen is readily given up to the tissues of the body, so that in animals dead from suffocation only gas-free — reduced — hemoglobin is found in the veins. Also con- stituents of the serum and sugar remove the oxygen. By addition of reducing substances to a solution of oxyhemoglobin, as, for instance, ammonium sulphid, the two bands of oxyhemoglobin disappear and reduced gas-free hemoglobin results (Fig. 15, 4). This is recognizable from its wide ill-defined absorption-band. Agitation with air, how- ever, at once restores both bands through the formation of oxyhemo- globin. Solutions of oxyhemoglobin are readily distinguished by their scarlet color from the wine-violet-red tint of reduced hemoglobin. The yellowish-green color of the solar spectrum thrown isolated upon the closed upper eyelid causes a sensation of dark. If the base of two fingers be ligated to the point of interrupting the circulation it will be seen on spectro- scopic examination of the intervening red cutaneous seam that the oxyhemo- FiGS. 13 and 14.— The Absorption-spectra of Oxyhemoglobin (Fig. 13) and of Gas-free Hemoglobin (Fig. 14 ) with Increasing Concentration. The letters of the lower line indicate the Fraunhofer lines. The figures at the side indicate the percentage-strength of the solutions (after Rollett). globin is soon transformed into reduced hemoglobin. This reaction is delaj-ed under the influence of cold; it is accelerated in youth, during muscular activity or with suppression of breathing and generally also in the presence of fever. A beating heart also exerts a reducing influence upon oxyhemoglobin. The absorp- tion-spectra naturally vary with the concentration of the solution ; in the presence of a greater amount of hemoglobin the bands are wider and may become confluent, and tinally the largest part of the spectrum may thus become dark. Figs. 13 and 14 show how the absorption-bands appear in solutions of varj-ing strengths: from a I per cent, solution (above) the concentration progressivelv diminishes down- ward by gradations of o.i per cent., until at O (J the fluid is without hemo- globin. The thickness of the laj^ers of fluid is placed at i cm. Spectroscopic examination of small blood-spots, possibly for medico-legal purposes, may be of the greatest importance. Often a minute spot is sufficient. Dissolved with one or two drops of distilled water it may be introduced longitu- dinally in a thin glass tube before the narrow slit of the spectroscope, and the two bands of oxyhemoglobin appear. Preserved in alcohol, oxyhemoglobin is transformed into a modification in- soluble in water but otherwise identical, namely parahemoglobin. OXYGEN-COMBINATION'S OF HEMOGLOBIN. 57 A second oxvgen-containing isomerif, but chemically more stable crystallizable coml)ination is methcmoglobiu, whose molecule contains the same amount of oxygen as oxyhemoglobin, but in different ar- rangement. Its spectrum closely reseml:)les that of hematin in acid solution (Fig. 15, 5). The band toward the red is the heaviest, while the others are narrow and are in part designated as not characteristic. Demonstration. — i. By oxidizing substances, such as ozone, potassium iodid, chk>ratcs, nitrates. 2. By reducing substances, such as nascent hydrogen and pvrogallol. 3. By indifferent influences, such as prolonged heating or slow desic- cation of the blood. Potassium ]5crmanganate, potassium ferrocyanid and ferri- cvanid exert an intense effect, wiiile nitrites transform the oxyhemoglobin into Cviini'l Blue. O.xyhcmoglobin 0.18 per cent. O.xyhemogloliin 0.18 per cent. Carbon-mono.xid hemoglobin. Gas-free or reduced hemoglobin. Methemoglobin; also hematin in acid solution. Hematin in alkaline solution. Hemochromogen in alkaline solution; also reducedhematin. 'iiMj I n I 1 1 iiiiii III 1 1 11 iLi iiiLi.im Liii 1 1 ! 11 i 1.11 1 1 1 1 iin iiii I 111 I '. r\Ti\ 1 1 40 5o 60 70 80 qo 100 110 A a B C D Eb F Fig 15 -The Various .\bsorption-spectra of Hemoglobin. In all of the spectra the various Fraunhofer hnes and a scale in millimeters are drawn. a mixture of methemoglobin and nitrogen-monoxid hemoglobin. Not alone lake-colored blood, but also the hemoglobin of intact erythrocytes may be transformed into methemoglobin, as, for instance, by potassium chlorate, antifebrin and other substances, and also by mtoxication Avith these sub- stances. Often both conditions are present in combmation. The occurrence of methemoglobin in solutions in the blood-plasma of a poisoned mdividual is designated methcmo plasm ia, and the occurrence of the methemoglobin m the pre- 58 CARBOX-MOXOXID HEMOGLOBIN'. served blood-corpuscles meiliemacytosis. Lesser degrees of the latter may recede spontaneously in the body without destruction of the er^-throcytes. Profound influences resulting in the production of methemoglobin destroy the blood- corpuscles and require transfusion. Preparation of Crystals. — To the solution of isolated er\-throcytes described on p. 37 is added double its volume of a concentrated solution of ammonium sul- phate, and evaporation is permitted to take place in the cold. There form brown- ish-red needles, prisms or plates with marked pleochroism. Methemoglobin develops in part spontaneously in the body, as, for instance, in bloody urine, in the sanguinolent contents of cysts, in old extravasates and in dried blood- crusts. The addition of a trace of ammonia to a solution of methemoglobin pro- duces an alkaline solution of methemoglobin, which exhibits two bands similar to those of oxyhemoglobin, but of which the first is the wider and extends the more toward the red. If a reducing solution of ammonium sulphid be added to solu- tions of methemoglobin, reduced hemoglobin develops. CARBON-MONOXID HEMOGLOBIN AND CARBON-MONOXID POISONING. Carhon-monoxid liemoglohin is a more stable combination than the preceding and is produced when carbon monoxid is brought into con- tact with hemoglobin or oxyhemoglobin. It is cherr^^-red in color, not dichroic, and it exhibits in the spectrum two absorption-bands that closely resemble those of oxyhemoglobin, but are somewhat closer together and more toward the violet (Fig. 15, 3). It can be readily recognized, however, from the fact that reducing substances, which influence the oxyhemoglobin, do not dissolve these bands, that is, do not transform the carbon-monoxid hemoglobin into reduced hemoglobin. A further means of recognition consists in the sodium- test: a 10 per cent, solution of sodium hydroxid added to carbon-mon- oxid hemoglobin and heated gives rise to a cinnabar-red color. The same solution added to oxyhemoglobin produces a black-brown- greenish mass. The spectrum-analytical examination and the sodium- test permit the recognition of three-tenths carbon-monoxid hemoglobin mixed with seven-tenths oxyhemoglobin. Carbon-monoxid hemoglobin reactions : Modified sodium-test : The blood is diluted 20 times and an equal amount of sodium hydroxid of a specific gravity of 1.34 is added in a test tube. Carbon-monoxid blood assiimes a beauti- ful red color after addition of ammonium sulphid — 2 grams of sulphur being added to 100 grams of yeUow ammonium sulphid — and 30 per cent, acetic acid, while normal blood assumed a greenish-gray coloration. Both kinds of blood exhibit also difi"erences in color when treated as follows; Dilute potassic hydrate is added, and then a few drops of a watery- solution of pyrogallic acid; the mixture is shaken at once and permitted to stand protected from the air. For the purpose of the test, blood made lake-colored with water mav be used, as well as blood in which the erythrocytes are preser\-ed bv addition of concentrated solution of sodium sulphate. Three cu. cm. of blood are diluted with 100 cu. cm. of water; 10 cu. cm. of this are mixed with 2 cu. cm. of 2 per cent, solution of grape-sugar and 2 cu. cm. of saturated solution of barium carbonate or Ume-water. and the whole is heated almost to the boihng-point. From 4 to 5 volumes of lead acetate added to the blood cause a distinct differ- ence accordingly as oxygen or carbon-monoxid blood is present. Oxidizing substances, as, for instance, solutions of potassium permanganate — 0.025 per cent., potassium chlorate — 5 per cent., and dilute chlorin-water. render solutions of carbon-monoxid hemoglobin cherr>'-red, while they render solutions of oxyhemoglobin pale yellow. Both varieties of hemoglobin thus treated acquire the bands of methemoglobin, the carbon-monoxid hemoglobin considerably later. Subsequent addition of ammonium stdphid transforms the forms of hemoglobin thus altered back again into oxyhemoglobin and carbon-monoxid hemoglobin. By reason of its greater constancy carbon-monoxid hemoglobin resists putre- faction for a long time, as well as the action of hydrogen sulphid. POISOXIKG WITH CARIiOX MOXOXID. 59 If carbon monoxid be inspired it gradually displaces, volume for volume, the oxygen of the hemoglobin, and death finally results; looo cu. cm. of carbon monoxid will kill human beings if breathed at once. Small amounts of carbon monoxid in the air (tt/ttt)— nrTiTf). how- ever, suffice to generate comparatively large amounts of carbon-monoxid hemoglobin within a short time. As by means of long-continued treatment of carbon-monoxid hemoglobin with other gases, particularly oxygen, — passing them through — the carbon monoxid may be grad- ually again separated from the hemoglobin, with the re-formation of oxyhemoglobin, so in the body also the carbon monoxid is eliminated through the respiratory process in the course of a few hours, a por- tion of the carbon monoxid apparently being oxidized into carbon dioxid. Poisoning with Carbon Monoxid. — Carbon monoxid results from incomplete combustion of carbon, as, for instance, tlirough premature closure of stove- valves and badly smoking lamps. It occurs in illuminating gas in a proportion of from 12 to 28 per cent. As carbon monoxid has 200 times as great an affinity for hemoglobin as oxygen, more and more of the latter is displaced from the blood by the breathing of air containing carbon monoxid, and life naturally can continue only so long as sufficient oxygen is conveyed by the blood as is necessary to main- tain the processes of oxidization essential to life. Death occurs amid peculiar phenomena, even before all of the oxygen is expelled froni the blood; under the most unfavorable circumstances one-fifth of the oxygen will be retained in the blood. Applied directly to nerve and muscle the gas has no influence whatever. Acting through the blood, however, phenomena appear that are indicative primarily of stimulation, but secondarily of paralysis of the nervous system. Thus, there occur at first severe headache, great restlessness, excitement, increased cardiac and respiratory activity, salivation, tremor, twitching, and spasm. Later, mental confusion, exhaustion, drowsiness, and paralysis set in, and even loss of consciousness, labored stertorous breathing, finally complete loss of sensibility, cessation of breathing and of the heart-beat and death. The tem- perature at the beginning exhibits an elevation of perhaps a few tenths of a degree C; then there follows a decline of about 1° C. and more. The pulse-beat at first exhibits increased energy, while later the pulse becomes small and frequent. Garland-like constrictions of the vessels, followed later by marked dilatation, with hyperemia of the viscera, accompanied by a fall in the blood-pressure, indicate primary stimulation and secondary paralysis of the vasomotor center. The change in temperature mentioned is to be referred to the same cause. This would also explain the appearance of sugar in the urine sometimes observed — in dogs only after abundant feeding of proteid. After the intoxication has ter- minated the excretion of urea is said to be increased, because the albuminates exhibit a greater tendency to disintegration. In cases of poisoning the great hyperemia of the viscera with fluid cherry-red blood and the dilatation of the vessels are conspicuous. Further, there are friability and softening of the brain, marked catarrh of the respiratory organs and granular degeneration of the muscles. Liver, kidneys, and spleen appear hyperemic, large, flabby, in a state partly of granular and partly of fatty degeneration. All of the muscles and viscera exhibit an exquisite cherry-red color. The spots of postmortem lividity are bright red. Poisoned persons if still living should be at once brought into the fresh air. High degrees of intoxication demand transfusion. After recovery from the poisoning, sometimes paralysis, rarely anesthesia, trophic disorders and derange- ment of cerebral activity persist. If mixed with pure oxygen carbon monoxid acts less rapidly. OTHER HEMOGLOBIN-COMBINATIONS. Nitric-oxid hemoglobin is formed when nitric oxid enters into com- bination with hemoglobin. As this gas in contact with oxygen is at once transformed into nitrous acid. 6o DECOMPOSITION OF HEMOGLOBIN. all of the oxygen must first be removed from the blood and the apparatus, possibly- through the passage of hydrogen, in the preparation of nitric-oxid hemoglobin. For this reason it cannot be formed within the body. Nitric-oxid hemoglobin is a still more active chemical combination than carbon-monoxid hemoglobin. It is of a bluish-violet color and in the spectrum it exhibits two absorption-bands, pretty much like those of the two other gas-combinations, biit less intense, and not dissolved by reducing substances. The three combinations of hemoglobin with ox3^gen, carbon monoxid and nitric oxid just considered crystalHze like gas-free hemoglobin. They are isomorphous and their solutions are not dichroic. All three gases unite in equal amounts with hemoglobin and they can be ex- pelled in a vacuum. Hydrocyanic acid also forms readily decomposed combinations with hemo- globin. These develop in cases of hydrocyanic-acid poisoning, and they exhibit two bands that are situated somewhat nearer the violet than those of oxyhemo- globin and are slowly obliterated by reducing substances. This hj'drocyanic-acid hemoglobin appears to consist of hydrocyanic acid plus oxyhemoglobin. There is, besides, a further combination of hydrocyanic acid with oxygen-free hemo- globin. DECOMPOSITION OF HEMOGLOBIN. Hemoglobin can be decomposed into: (i) iron-containing, pig- mented hematin and (2) albuminoid, colorless globin, containing sul- phur: (a) by addition of all acids, even feeble carbon dioxid in the presence of much water; (b) by strong alkalies; (c) by all agents that coagulate albumin, as well as bv heat at a temperature of from 70° to 80° C. ; ((i) by ozone. Hematin. — C32H32N4Fe04 represents about 4 per cent, of the hemo- globin in the dog. It is of blackish-blue color in reflected light, brown in transmitted light, insoluble in water, alcohol and ether, but soluble in dilute alkalies and acids, as well as in alcohol containing sulphuric acid or ammonia. It does not occur within the body. Hematin thus developed appears in an amorphous form, although it has also been possible to produce it crystallized in needles and rhombic plates. Hemato- porphyrin in acid solution Hemato- ! orphyrin in alkaline solution. i"! |i I, : i ■ '• 1 II 1 1 1 1 1 V 1 1 M 1 1 ' 1 ' 1 1 1 1 1 "^ 700 650 BO 600 D 560 600 Eb F 450 G Fig. 16. — The Absorption-spectra of Hematoporphyrin, with the Fraunhofer Lines and a Scale Whose Figures Indicate the Wave-lines of Light in Millionths of a Millimeter. In the decomposition of hemoglobin containing oxygen hematin at once results, oxygen being bound. On the other hand, oxygen-free hemoglobin yields in a similar process of decomposition, at first a forerunner of hematin deficient in oxygen, namely purple-red hemochromogen (C34H38NFe405) . This, however, is transformed into hematin in the presence of oxygen by taking up the latter. Hematin therefore represents an oxidization-stage of hemochromogen. The latter IDENTIFICATION' OF BLOOD. 6l substance is soKiblc.with exclusion of oxygen, in dilute alkalies, with the formation of a cherry-red color, and exhibits two al>sor])tion-bands, namely, one between D and E, and another and narrower between E and b (Fig. 15, 7). Hemochromogen can be prepared in crystalline form by mixing upon a glass slide one drop of defibrinated blood with one drop of pyridin and covering the whole. The preparation exhibits the absorption-bands and at times also small crystals arranged in the form of stars or sheaves. In the bloody extract of spirit-preparations no longer fresh putrefaction often produces the beautiful red hemochromogen in alkaline solution. Dilute acids in alcoholic solution withdraw the iron from the hemochromogen and there thus results hematoporphyrin — CkjHisNiOs, which is isomeric with bilirubin, and is permanent in the air. This can also be prepared from hematin by means of strong sulphuric acid. It exhibits in acid solution a small absorption- band in the orange and a wider band in the yellowish-green (Fig. 16, i). The spectrum of the same substance in alkaline solutions is shown in Fig. 16, 2. Hematin occurs in solution as — (A) Hematin in acid solution. If acetic acid be added to a solution of hemo- globin the latter becomes mahogany-brown in color, as hematin in acid solution develops and is recognized by four absorption-bands in the yellow and the green (Fig. 15, 5)- . . (B) If this solution be over-saturated with ammonia hematin in alkaline solution develops, exhibiting an absorption-band at the junction between the red and the yellow (Fig. 15, 6). (C) Addition of reducing agents causes disappearance of this band and pro- duces two wide bands in the yellow, due to the reduced liernatin thus formed (Fig. 15, 7), and which, according to Hoppe-Seyler, is identical with the hemo- chromogen in alkaline sokition. Hematin is prepared in substance by precipitation from a solution of hemin in a weak alkali by addition of a dilute acid. Hemoglobin is transformed into green sulphur-methemoglobin by hydrogen sulphid. This substance also causes the green coloration of putrid portions of the cadaver. Hematin when reduced in alkaline solution with tin and hydrochloric acid yields urobilin. The latter results likewise through the action of hydrogen dioxid on acid hematin. Urobilin is occasionally found in cysts, exudates, and transudates. It forms likewise in sterile blood kept at the temperature of the body. HEMIN (HEMATIN CHLORID); IDENTIFICATION OF BLOOD BY MEANS OF THE HEMIN-TEST. Teichmann prepared in 1853 from the anhydrid of hematin crystals that Hoppe-Seyler recognized as hematin chlorid — CgjHjoN^OgFeHCl. As these may be obtained in characteristic form even from traces of blood they play an important role in forensic medicine. The demonstra- tion of their presence depends upon the fact that the hemoglobin dried and heated with an excess of water-free acetic acid — so-called glacial acetic acid, which must bum on a glass rod held in the flame — and addition of sodium chlorid yields hemin-crystals (Figs. 17 and 18). These appear in the form of small rhombic plates, columns, or rods, although they probably belong to the monoclinic system. Not rarely they take the form of hemp-seeds or shuttles or paragraph- signs. At times some lie crossed or in tufts. In crystalline form the hemin-crystals of all varieties of blood examined are identical. They are doubly refracting, appearing yellow and glistening under the polarization-microscope, in contrast with their dark surroundings, with marked absorption of the light parallel with the longitudinal axis of the cr^'stal. They are pleochromatic, that is, bluish-black and glisten- 62 IDEXTIFICATIOX OF BLOOD. ing like polished steel in reflected light and mahogany-brown in transmitted light. (i) Preparation from Dry Blood-stains. — Several particles of the dry mass are placed upon a glass slide, two or three drops of glacial acetic acid and a minute crystal of sodium chlorid are added, and after the cover-slip has been placed in position heat is carefull}'' axjplied some distance above a spirit-lamp until a number of small bubbles form. On cooling the crystals will be visible in the preparation (Fig. iS). (2) Preparation from stains upon porous bodies, from which the hemoglobin cannot be scraped. The stained object — fabric, wood — is extracted with a dilute solution of potassic hydrate and then with water. To both filtered solutions a solution of tannic acid is added, and finally acetic acid until an acid reaction is pro- duced. The resulting precipitate is washed upon a filter, then to a portion thereof upon a glass slide a cr>'stal of sodium chlorid is added, and the whole is dried. Finally, the dried object is treated according to the method just described. (3) Preparation from Liquid Blood. — The blood should always have been pre- viously dried slowly and carefully. Then the process is contintied as in the first method. V \' \ < ^ ^ V ^^ • \ ^ ^ /^rv.v ^ ^ 4 ^^^ ^ t ^ ^ "^ V ^ f ^> ^ ' ^K • / N^- '^ \ - ' S - ^ Fig. 17. — Hemin-crystals: i, from a human being; 2, from a Fig. 18. — Hemin-crystals Pre- seal; 3, from a calf; 4, from a pig; 5, from a lamb; 6, pared from Blood-stains, from a pike; 7, from a rabbit. (4) Preparation from Dilute Solutions Containing Hemoglobin. — To the fluid is added ammonia, next tannic acid and then acetic acid until the reaction is acid. A blackish precipitate of hematin tannate forms rapidly. This is washed upon a filter with distilled water, then dried and heated in the same way as accord- ing to the first method, except that instead of sodium chlorid a crystal of ammo- nium chlorid is added. Not rarely at least small hemin-crystals can be obtained from putrid and lake- colored blood, but under such circumstances the test often fails. Dried with iron- rust, as upon weapons, blood usually no longer yields the reaction. Under such cir- cumstances the matter is, according to Heinrich Rose, scraped away and boiled with dilute potassitim-hydrate solution. If blood be present the dissolved hematin forms a fluid that in thin layers presents a bile-green color, but in thick layers a red color. Hemin-crystals have been demonstrated in all classes of vertebrates, as well as in the blood of the earth-worm. From some kinds of blood, as, for instance, that of cattle and of swine, only irregular masses, scarcely recognizable as having crystalline form, at times develop. Hemochromogen, hematoporphyrin, blood rubbed with sand or animal charcoal, addition of certain salts of iron, lead, mercur3^ and silver and lime prevent the development of the reaction. The crystals of hemin are insoluble in water, alcohol, ether, and chlorofomi. They are dissolved by concentrated svilphuric acid, with expulsion of hydrochloric acid and the development of a violet-red color. They are dissolved by dilute alkalies. If a solution of hemin-crystals in ammonia is evaporated, then heated to 130° C, next treated with boiling water, which removes the ammonium chlorid formed. IIEMATOIDIX. 63 hematoporphyrin results. This is a bluish-black, amorphous powder, becoming brown when rubbed. Its solutions in caustic alkalies are dichroic: that is brownish- red in retlected light, garnet-red in a thick layer with transmitted light and olive- green in a thin layer. The acid solutions are monochromatic — brown. For the preparation of hemin-crystals in large amount, it is advisable to heat dry horses' blood with 10 parts of formic acid until bubbles form. If the hemin- crystals are suspended in methyl-alcohol, they dissolve after addition of iodin and application of heat, with the development of a purple color, which becomes brown after addition of bromin and green after the passage of chlorin-gas. All of these exhibit a characteristic appearance in the spectroscope. The glacial acetic acid may be replaced by an alcoholic solution of oxalic or tartaric acid, and the sodium chlorid by salts of iodin or bromin. In the latter event bromin-hematin or iodin-hematin is formed. HEMATOIDIN. An important derivative of hemoglobin is sorrel-colored hematoidin — CaoHjgNjOg (Fig. 19), which forms in the body from hematin through loss of iron and taking up of water when- ever blood stagnates [outside of the circula- tion and undergoes decomposition, as, for instance, in apoplectic extravasations of blood, in coagulated plugs in blood-vessels (thrombi). It develops regularly in every Graafian follicle from the drop of blood poured out at the menstrual rupture of the follicle. It is free from iron, crystallizes in clinorhombic prisms, and is soluble in fig. 19.— Hematoi.im-crysiais. chloroform and in warm alkalies. Probably it is identical with the biliary coloring-matter, bilirubin. Pathological. — After extensive dissolution of blood in the vessels, as, for instance, after transfusion with foreign blood, hematoidin-crystals have been ob- served in the urine. THE COLORLESS PROTEID OF HEMOGLOBIN. This is designated globin and is closely related to histon. Demonstration.— A solution of hemoglobin is made feebly acid with hydro- chloric acid, then one-tifth volume of alcohol is added and the mixture is shaken with ether. The coloring-matter is taken up by the ether and the globin is precipitated by the ammonia. Hydrochloric or nitric acid likewise precipitates the globin, which, however, is redissolved on boiling. Hematin and globin are probably not the sole products of the decomposition of hemoglobin. As hemoglobin-crystals can be decolorized under special conditions, it is most probable that they owe their form to the proteid body. On introducing hemoglobin-crystals with alcohol in a dialyzer surrounded by ether acidulated with sulphuric acid Landois svicceeded in decolorizing the crystals. PROTEID BODIES IN THE STROMA. These constitute from 5.10 to 12.24 per cent, of the dry red blood-corpuscles of man, including a globulin participating in fibrin- formation and possible traces of a sugar-forming ferment. Under special conditions it has been observed that the stromata, coherent in masses, form a substance — stroma-fibrin — resembling fibrin. L. Brunton has found in the nuclei of nucleated red blood-corpuscles a iimcin- containing body, Miescher nuclein and Kossel histon united wdth the latter. 64 REMAINING CONSTITUENTS OF THE RED BLOOD-CORPUSCLES. THE REMAINING CONSTITUENTS OF THE RED BLOOD- CORPUSCLES. The red corpuscles contain further: Lecithin, 1.867 P^r cent, in dry erythrocytes; urea, equally divided between erythrocytes and serum; cholestcriu, 0.151 per cent.; no fats; lactic acid, in the dog. Lecithin and cholesterin can be obtained by agitating considerable amounts of stroma or isolated blood-corpuscles with ether. If the ether is permitted to evaporate the characteristic globular myelin-forms of lecithin and the crystals of cholesterin will be recognized. Water, 631.63 in the thousand. After abstraction of considerable quantities of blood the amount of water diminishes and the amount of dry substance, as well as the nitrogen of the ery- throcytes, increases. The opposite effect is brought about by infusion of physio- logic salt-solution. Inorganic matters, 7.28 in the thousand, particularly combinations of potassium and phosphoric acid. The phosphoric acid is derived only from consumed lecithin, the sulphuric acid in large part from the hemoglobin consumed in the analysis. Some manganese also is present. Blood-analysis. — One thousand parts by weight of horses' blood are made up as follows : 344.18 parts blood-corpuscles, with 128 of solids — 383 in the dog, 655.82 parts plasma, with 10 per cent, of solids — 617 in the dog. One thousand parts by weight of moist blood-corpuscles are made up as follows : Solids, 367.9 (swine), 400.1 (cattle), 435 (horse), Water, 632.1 (swine), 599.9 (cattle), 565 (horse). The solids include: Hemoglobin, 261 (swine) 280.5 (cattle) Albumin, 86.1 Lecithin, cholesterin and other organic matters, . . 12.0 Inorganic matters 8.9 Including potassium 5-543 magnesium 0.158 chlorin 1.504 phosphoric acid, 2.067 sodiuni, o CHEMICAL CONSTITUENTS OF THE LEUKOCYTES. Leukocytes from the plasma of lymphatic glands, as well as pus- corpuscles contain proteids as follows: little albumin, alkali-albuminate and an albuminate resembling myosin and coagulating at 48°, two globulins coagulable at 48.5° and 75° C. respectively, together with serum-globulin, peptone and a coagulating ferment, further consider- able nucleins from the nuclei, nucleo-histon, little glycogen, lecithin, cerebrin, cholesterin, fats, protagon, inosite, amido valerianic acid. Lymphocytes contain 11.5 per cent, of dry matter. In 100 parts by weight of dry pus there are 0.416 earthy phosphates. 0.143 sodium chlorid, 0.606 sodium phosphate, 0.202 potassium, in part in the form of monopotassium phosphate. 'ine) 2 So 5 107 / 5 4 S 0 747 0 017 I 635 0 703 2 093 THE BLOOD-PLASMA AND ITS RKLATlOX TO THE SERUM. 65 THE BLOOD-PLASMA AND ITS RELATION TO THE SERUM. The unnioditied lluid of the blood is known as plasma. In tliis, how- ever, there separates, generally soon after escape of the blood from the vessels, a fibrillated substance, namely fibrin. After this separation, the remaining clear fluid, which no longer undergoes coagulation spon- taneously, is known as serum. The plasma is a clear, transparent, somewhat consistent fluid, which in most animals is almost colorless, but in human beings is yellowish and in the horse of citron-yellow color. DEMONSTRATION OF PLASMA. (A) Without admixture. As plasma cooled to a temperature of 0° C. does not undergo coagulation, the blood flowing from a vein — particularly of the horse, which is peculiarl)^ suitable on account of the slowness of coagulation and the rapidity with which sedimentation of the blood-corpuscles takes place — is received into a narrow, graduated cylinder standing in a cold inixture. In the blood, which remains fluid, the erythrocytes sink to the bottom within a few hours, and the plasma forms above a clear fluid, which can be removed with a cooled pipet. If this is further passed through a filter upon an ice-cold funnel the plasma will also be freed from leukocytes. The amount can be read fi'om the graduated cylinder, but only approximately, because of the presence of plasma between the sedimented corpuscles. If heated, the plasma, in so far as it contains leukocytes, is transformed, through the forma- tion of fibrin, into a tremulous jelly. If, however, it be whipped with a rod the fibrin will be obtained as a stringy mass. Plasma free from leukocytes is not capable of coagulation. If the ainount of fibrin in a volume of plasma isolated by whipping (varyin<^ between 0.7 and i.o per cent.) and in the same manner the amount in a volume of blood be determined the two resvilts afford a basis for estimating the amount of plasma in the blood. (B) With saline admixture. If the blood flowing from a vein into a graduated cylinder be mixed with agitation with \ volume of concentrated solution of sodium sulphate or with a 25 per cent, solution of magnesium sulphate (i volume to 4 volumes of blood), the cells sink to the bottom in a cool place, while the clear supernatant saline plasma, which can be measured, is pipetted off. If the salt be removed from the plasma by means of the dialj^zer coagulation takes place. The same result is brought about by dilution with water. FIBRIN: ITS GENERAL PROPERTIES; COAGULATION. Fibrin is the substance that brings about coagulation in shed blood as well as in plasma and likewise in lymph, and in the chyle, by solidification. If the fluids mentioned are placed at rest and left to themselves the fibrin forms innumerable microscopically delicate (Fig. 9) doubly refracting filaments, which hold the blood-cells together like a spider's web, and with the cells form a mass of gelatinous consistencv that is known as blood-clot (placenta sanguinis). At first this is quite diffluent and it is only in the course of from two to fifteen minutes that a number of filaments appear upon the surface that can be removed with a needle, while the interior of the blood-mass is still liquid. In a short time the filaments extend throughout the entire mass. The blood in this stage of coagulation has been designated cruor. Later, in the course of from twelve to fifteen hours, the threads of fibrin contract more and more firmly about the corpuscles, and there then results the more solid, gelatinous, tremulous substance, which can be cut with a knife, and which has expressed a clear fluid, know^n as blood-scrum {serum sanguinis). The blood-clot takes the shape of the vessel in which 66 FIBRIN. the blood has been received. By solution with water of the blood- corpuscles in the broken-up blood-clot the fibrin can be isolated. If the blood-corpuscles sink rapidly in the blood, and if the advent of coagulation be delayed, the upper layer of the blood-clot is only ■stained yellow on account of the absence of enclosed erythrocytes. "This is the rule with horses' blood, but it has been observed in the case ■of human blood, particularly when inflammation was present in some part of the body. Therefore, this layer has also been designated crusta plilogistica. Such blood is richer in fibrin and therefore coagulates more slowly. The crusta forms also under other conditions, but the cause of its formation is not always clear. Thus it occurs when the specific gravity of the blood-cor- puscles is increased or that of the plasma is diminished, as in cases of hydremia and chlorosis, in consequence of which the corpuscles sink more rapidly, and during pregnanc5^ The taller and narrower the vessel, the higher is the crusta. It can be readily understood why the blood-clot undergoes greater contraction and appears more contracted in the neighborhood of the unpigmented layer free from corpuscles. If freshly shed blood is whipped with a rod the filaments of fibrin that form collect about the rod, and in this way the fibrin is obtained as a fibrous, grayish-yellow mass from the blood now become defi- brinated. The plasma exhibits analogous phenomena, but it forms only a soft, tremulous jelly, by reason of absence of the resistant blood-corpuscles. The plasma undergoes coagulation only when it contains leukocytes. If these be removed by filtration the plasma is no longer coagulable. Although the fibrin appears voluminous, it constitutes only from O.I to 0.3 per cent, of the mass of the blood. In this connection, it is noteworthy that in two different specimens of the same blood the amount of fibrin may vary considerably. Fibrin is insoluble in water or ether. Alcohol causes it to shrink by dehydration, while hydrochloric acid causes it to swell and assume a vitreous appearance, with transformation into syntonin. In the fresh state fibrin is tough and elastic. If dried, it becomes horn-like, trans- lucent, brittle, and pulverizable. Fresh fibrin is capable of actively decomposing hydrogen dioxid into water and oxygen, just as other fresh animal or vegetable tissue is likewise capable of doing. " Boiled or preserved in alcohol it loses this power. In the fresh state it is soluble in from 6 to S per cent, solutions of sodium nitrate or sodium sulphate, with the formation of globulin; and in dilute alkalies and ammonia, with the formation of alkali-albuminate. These solutions are not coagu- lated by heat. Also weak solutions of haloid salts (sodium chlorid, ammonium chlorid, potassium iodid, sodium iodid, sodium fluorid, ammonium fluorid) dis- solve fibrin at a temperature of 40°, as, for instance, sodiuin-chlorid solution, from 7 to 20 parts in the thousand, with the production of globulin-bodies and pro- peptone. Fibrin from swine is dissolved by 0.5 per cent. h}-drochloric acid and also "by malic, oxalic, butyric, acetic, citric, and lactic acids; fibrin from cattle, with greater difficulty. Fibrin exposed to air for a considerable time is not soluble in nitric acid, although it is soluble in neurin. As a result of putrefaction it likewise undergoes solution, with the formation of albuinin. Fibrin contains lime, iron, and magnesium. According to Schmiedeberg the fibrin obtained from plasma has the elementary formula Cin8Hi8,N3nS034, while blood-fibrin has the following composition: CiizHies^soSOgs + ^HjO. GENERAL PHENOMENA ATTENDING COAGULATION. 67 GENERAL PHENOMENA ATTENDING COAGULATION. Blood does not undergo coagulation in immediate contact with the living and unaltered vessel-wall. Therefore, Briicke was able to preserve unco- agulated for eight days blood cooled to o° in the still beating heart of dead turtles. The blood coagulates rapidly within the dead heart or vessels (but not in the capillaries) or within other channels, as, for instance, the urethra. If blood stagnates in a living vessel, coagulation takes place in the central axis, because it is here not in contact with the living vessel- wall. Coagulation is of the greatest importance in the control of hem- orrhage from injured vessels, which otherwise might terminate fatally. The injured and necrotic tissues of the wound and the vessel-wall lead to the formation of the occluding thrombus by coagulation. If the vessel-wall is altered by pathological processes, as, for instance, rough or inflamed in consequence of a lesion of the intima, coagulation may take place in such a situation even though the circulation be maintained. Coagulation of the blood is prevented or retarded: (a) By addition of alkalies or of ammonia, even in small amounts; further, of concentrated solutions of neutral salts of alkalies and earths — alkaline chlorids, also sulphates, phosphates, nitrates, carbonates ; disodium phosphate in 3 per cent, solution, soluble salts of calcium, strontium and barium dissolved in the Vjlood to the extent of 0.5 per cent. Simultaneous addition of sodium chlorid inhibits coagulation in still further degree. Magnesium sulphate — i volume of a 28 per cent, solution to 3^ volumes of horses' blood — acts most effectively in inhibit- ing coagulation. (b) By precipitation of the calcium by means of oxalic acid. Feeble acids also exert an inhibiting effect. Thus, coagulation ceases after addition of acetic acid to the point of producing an acid reaction. The presence of a large amount of carbon dioxid likewise retards coagulation; therefore, venous blood — and also the blood after asphyxiation^coagulates more slowly than arte- rial blood. (c) By addition of egg-albumin, sugar-solution, glycerin, soaps or much water. If uncoagulated blood be brought in contact with a layer of already separated fibrin coagulation is retarded. (d) Cold (0° C.) retards coagulation for as long as an hour. If blood be permitted to freeze at once, it will still be liquid on thawing, when it undergoes coagulation. Coagulation is retarded also when the shed blood is exposed to high pressure; likewise when it is brought in con- tact with foreign substances to which it does not adhere, as, for instance, anointed substances. (e) The blood of embryo birds does not coagulate at all before the twelfth or fourteenth day on account of the absence of fibrin-forming cells, and that of the hepatic veins but slightly. Blood from the dog passed only through the heart and the lungs does not coagulate for a long time. Blood from the renal vein, also blood cut off from circulation through the liver and intestines, does not coagulate at all. Fetal blood at the moment of birth coagulates early, but slowly, as the amount of fibrin it contains is small. Menstrual blood exhibits a slighter tendency to undergo coagulation if admixed with a considerable amount of alkaline mucus from the genital canal. 68 COAGULATION IS ACCELERATED. (/) In cases of bleeders' disease — hemophilia — coagulation appears to be want- ing on account of deficiency in the fibrin-generators, in consequence of which wounds of the vessels are not occluded by fibrinous thrombi. The peptic ferment of the pancreas dissolved in glycerin and injected into the blood inhibits its coagu- lation, as does also the diastatic ferment. Schmidt-Mulheim noted the same result after injection of pure peptone into the blood of dogs — 0.5 gram to i kilo of dog, and 1.5 of rabbit. This is eft'ective, however, only in the presence of the liver. The buccal secretion of the leech, the poison of vipers and the highly toxic substance in the serum of eels' blood likewise inhibit coagulation. Coagulation is accelerated: (a) By contact with foreign substances to which the blood adheres, as, for instance, threads and needles introduced into the veins. Also the entrance of air-bubbles into the vessels or the passage of other indifferent gases, as, for instance, nitrogen and hydrogen, exerts an accelerating effect. Removed from the vein, the blood coagulates quickly on the walls of the container, on its surface exposed to the air, on the rod with which it is whipped, etc. (h) Man}"- products of the retrogressive metamorphosis of albuminates , including uric acid, glj^cin, taurin, leucin, tyrosin, guanin, xanthin, hypoxanthin (not urea), as well as the biliary acids, further lecithin, cholin hydrochlorate, protagon, accelerate coagulation through in- creased ferment-formation. Added in excess, however, they exert an inhibiting effect. Solutions of gelatin injected into the veins cause the blood to coagulate almost instantly after escape from the vessels. (c) If hemorrhage takes place rapidly the last amounts of blood coagulate earliest. Fresh fibrin, if permitted to remain for a consider- able time in blood, is again dissolved in part. {d) Heating to a temperature of from 39° to 55° C. accelerates coagulation. In the shed blood of inan coagulation begins in the course of three minutes and forty-five seconds; in that of woman after two minutes and thirty seconds. Hunger exerts an accelerating effect. Among vertebrates the blood of birds coagulates almost instantly, that of cold-blooded animals distinctly more slowl^^ while the blood of mammals occupies an intermediate position. The blood of invertebrates, which mostly is colorless, forms a soft, white fibrinous coagulum. As the process of coagulation involves a change in the aggregate state, heat demonstrable with the thermometer must be set free. In blood removed from a vein the degree of alkalinity diminishes up to the point of completed coagulation, probably from the formation of acid in the blood as a result of decomposition-processes. In the process of coagulation a diininution in the amount of oxvgen in the blood has been observed, although this takes place also in blood that has not vet undergone coagulation. There is, likewise, elimination of traces of ammonia. Both processes, however, appear not to stand in causal relation with the formation of fibrin. NATURE OF COAGULATION. Alexander Schmidt discovered in 1861 that coagulation is a fermen- tative process that consists in the transformation of the soluble albumin of the plasma into the solid substances of the fibrin through the activity of an enzyme that is designated fibrin-ferment or thrombin. This pro- teid is nothing but fibrinogen. NATURE OF Ct)AGULATIO\. 69 The enzymes or hydrulytic ferments behave in common in the organism in such a manner that they break up the bodies upon which they act into two other substances by taking up water. It, therefore, appears probable that as a result of the action of thrombin decomposition of the fiVjrinogen 'into fibrin and a lesser amount of a globulin-body that remains liquid and that Hammarsten has designated fihrin-globiilin , takes place, with the taking up of water. Demonstration of Fibrinogen — CnzHjojiNjoSOas. — Pulverized sodium chlorid is added to lymphatic transudate to the point of saturation. The fluid poured out into the serous sac surrounding the testicle (hydrocele) is especially useful for this purpose. The precipitated fibrinogen is collected upon a filter. This substance is found also in the lymph and in the chyle. Saline plasma also is capable of precipitating fibrinogen by admixture of equal volumes of plasma and a concentrated solution of sodium chlorid. For purposes of purification it may then be dissolved rapidly and repeatedly in a dilute — 8 per cent. — solution of sodium chlorid and again precipitated by a concentrated solution of sodium chlorid. The fibrinogen contained in the sodium-chlorid solu- tion is precipitated by addition of water and is rapidly changed so that it resembles fibrin. Fibrinogen in saline solution coagulates at a temperature of from 52° to 55° C. Solutions free from salt do not coagulate if quickly brought to the boiling-point. Fibrinogen behaves like globulin. It is soluble in dilute alkalies and it is precipitated from such solutions by the passage of carbon dioxid. It is further soluble in dilute solution of sodium chlorid, while addition of large amounts of sodium chlorid causes its precipitation as a soft, viscous, tough mass. It is dissolved also by dilute hydrochloric acid, although it is soon transformed into a body resembling syntonin (acid albuminate). In the fresh state it actively decomposes hydrogen dioxid. Its specific rotatory power is 52.2°. Demonstration of Fibrin-fennent — Thrombin. — Blood-serum from cat- tle,which contains a larger amount of ferment than the serum of camivora, is admixed with twenty times its volume of strong alcohol. The result- ing precipitate is collected upon a filter after the lapse of from two to four weeks. It contains the coagulated albumin and the ferment. It is dried over sulphuric acid and reduced to powder. One dram of this powder is stirred for ten minutes in 65 cu. cm. of water. If the mixture is not filtered, the ferment, dissolved in water, alone passes through the filter. Thrombin is formed from a forerunner, a zj^mogen, which is present within the leukocytes and is designated prothrombin. Both are soluble with greater difficulty in an excess of acetic acid than globulins. Even small amounts of the ferment may cause coagulation of fluids containing fibrinogen and most readily at a temperature of 40° C. Prothrombin is destroyed at a temperature of 65°, thrombin at a temperature between 70° and 75°. The amount of ferment formed in the blood is the 'greater the longer the time that has elapsed between the escape and the coagulation of the blood. Blood flowing directly from the vein in alcohol 3'ields no ferment. Coagulation. — If the separate solutions (1) of the fibrinogenous sub- stance and (2) of the ferment are admixed fibrin-formation takes place at once. The most favorable temperature for this is that of the body. A temperature of 0° C. prevents coagulation, while the boiling tem- perature destroys the ferment. The amount of ferment is a matter of indifference. Larger amounts cause more rapid, but not increased, separation of fibrin. For the formation of fibrin the presence of a certain amount of salt in the fluid is requisite — one per cent, sodium chlorid. Otherwise the process takes place but slowly and is only partial. The presence of a calcium-salt favors coagulation. If the 70 SOURCE OF THE FIBRIN'OGENOUS SUBSTANCES. calcium is precipitated by alkali-oxalate this prevents coagulation, although it is true that the presence of a large amount of ferment in the blood is capable of neutralizing the influence of the calcium. Fibrin- ogen and fibrin contain equal amounts of calcium. Probably the action of the calcium bears some relation to the formation of the fibrin- ferment, for the plasma contains a substance that exerts a marked coagulative effect after addition of calcium-salts. According to Kossel and Lilienfeld the leukonuclein contained in the nuclei of the leukocytes, and the nucleinic acid restdting from its decomposition, accelerate coagulation. If coagulation has taken place in the plasma of the blood, all of the fibrinogenous material in the serum is utilized for the formation of fibrin. On the other hand, fibrin-ferment will still be present in the serum in sufficient amount. Therefore, if blood-serum be added to a fluid containing fibrinogen, as, for instance, hydrocele-fluid, coagulation will at once take place anew. SOURCE OF THE FIBRINOGENOUS SUBSTANCES. Alexander Schmidt has found that both fibrin-factors are formed from the destruction of leukocytes. In the circulating blood of man and of mammals, the fibrinogenous substance is already dissolved in the plasma as a soluble product of the physiologic involution-processes of the white cells. The circulating blood, however, contains a much larger number of leukocytes than was previously believed. As soon as the blood is shed, large numbers of white blood-corpuscles are dissolved — according to Alex. Schmidt 71.7 per cent, in the horse. The decom- position-products dissolve in the blood-plasma, and as a result the fibrin- ferment develops, to a certain extent as a cadaveric product, causing the separation of fibrin. Accordingly the fibrin-ferment does not preexist within the uninjured corpuscles. Also the so-called transitional forms between colorless cells and er}'throcytes in mammalian blood furnish the fibrin-factors as a result of their destruction, which takes place immediately after escape of the blood ; likewise perhaps also the blood- plates. The ferment develops with the escape of the blood, and its formation reaches the maximum during the process of coagulation itself. The influence of adhesion in favoring coagulation depends upon the fact that as a result the blood-corpuscles are caused to give up a portion of their contents — phosphoric acid and alkaline phosphates — to the plasma, to combine with salts of calcium and magnesium present principally in the plasma. If the calcium be precipitated from the blood by means of oxalic acid — i gram of potassium oxalate to i liter of blood — coagulation no longer takes place. If, how- ever, calcium chlorid be again added to this mixture coagulation will result. In the blood of amphibia and birds it is the red blood-corpuscles that after escape undergo destruction in large numbers and furnish the fibrin-forming mate- rials. In the blood of these animals Alex. Schmidt convinced^ himself at the same time that also the fibrinogenous substance was originally a constituent of the blood- corpuscles. It is thus clear that as soon as the fibrin-factors pass into solution in consequence of dissolution of the blood-corpuscles the separation of fibrin must take place through the combination of the two substances. If considerable amounts of leukocytes are introduced into the circulation of an animal they are quickly dissolved in large numbers in the blood, so that even RELATION'S OF THE RED BLOOD-CORPUSCLES. 7 1 death may take place in consequence of widespread coagulation. If the animal survive immediate death by reason of the moderate extent of coagulation, the blood subsequently will be wholly incoagulable in consequence of the absence of leukocj^es. All protoplasmic structures may in combination with plasma set the fibrin-ferment free. The nitrogenous metabolic products of proteids are likewise capable of producing fibrin-ferment in plasma free from cells. These latter active substances can be extracted from the tissues — cells of the liver, the spleen, the lymph-glands, red and white blood-corpuscles, frog-muscle — by means of alcohol. If after alcoholic extraction the residue of such tissues is extracted with water, this watery extract absolutely inhibits coagulation. The substance thus extracted by water is designated by Alex. Schmidt cytoglobin, which is the forerunner of fibrinogen and also of serum-globulin. In accordance with the preponderance in the plasma of either of the substances capable of extraction with alcohol or cytoglobin, coagu- lation is induced or inhibited respectively. Within the living body the inhibitory action of the cells preponderates, while outside the body the coagulating effect is operative. Those substances, such as the cytoglobin, that inhibit coagulation within the circulation furnish out- side of the body the material for the formation of fibrin. As Alex. Schmidt, after addition of cytoglobin to filtered plasma, induced coagu- lation by addition of extractives in large amount, the amount of fibrin was more than doubled. The blood retains its fluidity in the circulation as long as the amount of cytoglobin exceeds that of the proteid metabolic products of the tissues. The blood may, however, remain fluid also because both of these do not pass over into the plasma. Pathological. — From the investigations of Alex. Schmidt in collaboration with his pupils Jakowicki and Birk, it has been shown that even healthy functionating blood contains some fibrin-ferment from the destruction of white blood-corpuscles normally undergoing dissolution, and in greater amount in venous than in arterial blood. Nevertheless, it is always more abundant in shed blood. The fact, how- ever, is particularly noteworthy that the amount of fibrin-ferment in the blood in cases of septic fever may increase to such a degree that spontaneous coagulation- thrombosis takes place and even terminates fatally. After injection of putrid matters leukocytes are dissolved in large number, but the ferment is present rather abundantly also in the blood of febrile patients generally. Also injection of pep- tone, of hemoglobin and in lesser degree of distilled water is followed by dissolution of numerous leukocytes. There are thus true blood-diseases in which the products of the dissolution of the leukocytes accumulate in the blood-plasma. In conse- quence, spontaneous coagulation naturally occurs within the circulator}" organs, and as a result death may even be brought about. At least febrile elevation of tempera- ttire usually takes place. At the termination of such conditions the coagulability of the blood is naturally diminished. Wooldridge showed that a fibrinogen — tissue-fibrinogen — occurs in the chyle and in the lymph as a product of the lymphatic glands. In human beings in whom blood-stasis exists in any part of the body, coagulation may take place, with the formation of thrombi, throvigh admixture of lymph, as a certain amount of ferment is already present in the blood. The intestinal mucosa, the skin, and the lungs also appear to produce small amounts of fibrinogen constantly, while the liver and the kidneys constantly destroy it. RELATIONS OF THE RED BLOOD-CORPUSCLES TO FIBRIN- FORMATION. After it had been determined by a number of investigators that also the erythrocytes of birds, of the horse, of the frog, may contribute to the 72 CHEMICAL CONSTITUTION OF BLOOD-PLASMA AND SERUM. production of fibrin, Landois was able in 1874 to follow directly under the microscope the transformation of the stromata of the red blood-cor- puscles of mammals into fibrin-fibers. If a drop of defibrinated rabbit's blood be introduced into frog's serum, without agitation, it will be observed that the erythrocytes attach themselves to one another. They become viscous upon the surface, and on pressure on the cover-slip it will be seen the adhesion can be broken up only with a certain amount of force, the adjoining surfaces of the swollen, globular corpuscles often being drawn out into threads. Even after the process has been in operation for a short time, all of the corpuscles are transformed into globules of lesser diameter and those lying nearest the periphery permit their hemoglobin to escape. The decolorization progresses from the periphery of the drop to the center, and finally only a coherent mass of stroma remains. The substance of the stroma exhibits great tenacity. At first the round contours of the individual blood-corpuscles can still be recognized, but as soon as a current is set up in the surrounding fluid by pressure upon or movement of the cover-glass, the stroma-mass becomes agitated to and fro and the stromata lying close together and adherent to one another become drawn out into delicate filaments and bands, with simultaneous disappearance of the previous contour of the cells. In this way the formation of fibrin-filaments from the stro- mata of the red blood-corpuscles can be followed step by step. Erythro- cytes from human beings and from animals undergoing dissolution in the serum of different animals often exhibit the same phenomena. Stroma-fibrin can be prepared also in the following simple manner: A one per cent, solution of sodium chlorid is shaken in a reagent-glass with ether and a few drops of defibrinated blood. The mixture soon becomes lake-colored. Put aside, the ether, which rises to the top, carries with it the filamentous stroma- fibrin to the surface of the fluid. Stroma-fibrin and Plasma-fibrin. — Landois has designated stroma- fibrin that which arises directly from the stroma of the erythrocytes. On the other hand, the fibrin that is produced through the combination of the fibrin-factors dissolved in the coagulating fluid — plasma — is plasma- fibrin, or ordinary fibrin. Both designations are fully justified, if only to indicate the mode of origin of the fibrinous mass. Substances that cause rapid dissolution of the erythrocytes bring about extensive coagulation, as, for instance, injection of bile or salts of the biliary acids, or of lake-colored blood into the veins. The effective agent under these circumstances is the stroma, through the development of the ferment, and in lesser degree the hemoglobin. As foreign blood after injection often undergoes rapid disintegration in the blood-stream of the recipient, extensive coagulation is often observed under such circumstances, while at the same time the individual smaller vessels are often occluded by plugs of stroma-fibrin. CHEMICAL CONSTITUTION OF THE BLOOD-PLASMA AND THE SERUM. The proieids constitute about 8 or 10 per cent, of the plasma. Of these only about 0.2 per cent, are bodies producing fibrin. If these be eliminated through the process of coagulation, the plasma is trans- formed into serum. The specific gravity of human serum is between 1027 and 1029. The blood-plasma contains, besides, the following proteids: SERUM-ALBUMIX, SERUM-GLOBULIN. 73 (a) Scrnni-albuniiii — C7jiHi2i,X2oS024 — from 3 to 4 Per Cent. — Its per- centage-composition is C 53.1, H 7.1, N 15.9, S 1.9, O 22, Ash 0.22. Its coagulation-temperature is from 51° to 53° C.; its specific rotatory power — 61°. In the horse and the rabbit it crystallizes in hexagonal prisms, with a pyramid upon one side. The crystals are doubly refracting, up to I cm. in length, and are coagulable by heat. It is a remarkable fact that serum-albumin is absent from the blood of starving snakes and it makes its appearance only after feeding. (6) Scriim-glohnlin — also known as fihrin aplastic substance or para- globulin and also as scriim-cascin — from 2 to 4 per cent. If magne- sium sulphate in substance is added to serum to the point of saturation, serum-globulin is precipitated at a temperature of 35° C. It is washed upon a filter with concentrated solution of magnesium sulphate. It is soluble in a 10 per cent, solution of sodium chlorid, and coagulates at a temperature of from 69° to 75° C. Its specific rotatory power is — 47.8°, and its formula is CiiyHiT^NaoSOag. After precipitation of the serum-globulin from the serum by means of mag- nesium sulphate the scnim-albiimin is precipitated by further saturation with so- dium sulphate. Neutral ammonium sulphate, added to the point of saturation, precipitates all of the proteids of the blood-serum, and also those of egg- albumin and of milk : further, propeptone. but not peptones. Globulin can be precipitated also by dialysis of the serum, as it is insoluble in solutions free from salt. During hunger the amoimt of globulin increases, while that of albumin dimin- ishes. After abstraction of blood the amount of globulin in the blood increases. Paraglobulin occurs also in erythrocytes, as well as in the fluids of the connective tissue and the cornea. According to von Jaksch, 100 cu. cm. of blood contain 22.62 grams of albumin, while an equal amount of serum contains more than 8 grams. The latter figure varies under pathological conditions. Fats — from o.i to 0.2 Per Cent. — Xeiitral fats — stearin, palmitin, olein — occur in the form of minute microscopic droplets, whose presence often renders the serum of a milky turbidity after abundant ingestion of fat and also of milk. They are more abundant during hunger and in drunkards. There occur, besides, soaps, lecithin, and its decompo- sition-product, glycerin-phosphoric acid, and cholesterin. Hiirthle found cholesterin oleate and palmitate — 0.17 per cent. According to Hanriot a ferment, known as lipase, occurs in blood and which breaks up neutral fat into glycerin and fatty acids. Lipase is found also in the pancreas and in the liver, and traces also in some other parts of the body. A certain amount of grape-sugar — from o.i to 0.15 per cent., some- what more in the blood of the hepatic veins, derived from the liver and the muscles and increased after loss of blood ; some glycogen — increased in cases of diabetes; a trace of animal gum, a reducing substance, insusceptible of fermentation and soluble in ether, jecorin, which is a combination of dextrose and lecithin ; a dextrose-forming diastatic fer- ment, inactive at a temperature of 65° C. For a discussion of the sugar- destroying power of the blood reference may be made to the section on the liver. The amount of sugar in the blood is increased by absorption of sugar from the intestinal tract, and in greatest degree in the blood of the portal and hepatic veins. It is increased also in arterial blood, although here it is rapidly changed. For purposes of demonstration blood is coagulated by boiling after addition of sodiixm sulphate, and the amount of sugar in the expressed fluid is determined with the aid of Fehling's solution. Pavy digested the blood thrice successively 74 ABSORPTION OF GASES BY SOLID BODIES AND FLUIDS. with six times its volume of alcohol, then boiled and expressed the product. The extract, which is evaporated, contains all of the sugar. Kreatin, urea — during hunger 0.035 P^^ cent., in the stage of maxi- mum formation o. 153 per cent. ; at times succinic acid, hippuric acid, and uric acid (i : 6000 in gouty individuals); gtianin (? carbamic acid); in the blood after death also sarcolactic acid. All of these are present in exceedingly small amount. Inorganic matters — 0.85 per cent.; principally sodium-combina- tions. The amount of salts is increased by a meat-diet, while it is dimin- ished by a vegetable diet. Ammonium is present in the proportion of I mg. to 100 cu. cm., and three or four times as abundantly in the blood of the portal vein. Human blood-serum contains the following salts : Sodium chlorid, 4.92 in 1000. Sodium sulphate, 0.44 Sodium carbonate, 0.21 Sodium phosphate, 0.15 Calcium phosphate, ^ ., Magnesium phosphate, J '^ The alkaline reaction of the serum depends principally upon the sodium car- bonate present. It is only half that of the blood. The serum of blood containing carbon dioxid in large amount exhibits a more pronounced alkaline reaction and the amount of chlorin contained is diminished. This is dependent upon the fact that hydrochloric acid and water enter the blood- corpuscles, while the alkali remains behind. If salts in considerable amount are introduced into the blood, the larger amount disappears in the course of a few minutes, diffusing principally into the tissues. Gradually they are eliminated from the body through the kidneys. The same statement is applicable to sugar and peptone. Water — about 90 per cent. Yellowish pigments. One pigment can be separated by agitation with methyl-alcohol. It exhibits two absorption-bands of lipochrome, like lutein. Hydrobilirubin was found by Maly, and choletelin by MacMunn. Blood, and also blood-serum free from cells, as well as lymph, possess bacter- icidal properties, which are augmented by increase in the alkalinity, but, on the other hand, disappear on addition of water, on heating to a temperature oJE 55° C, on exposure to diffuse daylight, and likewise if mineral matters are removed by dialysis. Egg-albumin and fresh milk exhibit the same properties. The corpuscle- destroying — globulicidal — action of fresh serum is peculiar to the latter, in con- junction with its bactericidal effect after bacterial invasion. Both properties are due to certain proteid bodies known as alexins. The serum of an individual rendered immune by inoculation to any infectious disease exerts an antitoxic effect against the poison of the corresponding infectious agent, and it can there- fore be employed against the latter for curative purposes. Large numbers of microbes may gain entrance into the blood-stream during the death-agony. The serum of individuals suffering from typhoid fever contains a substance of diagnostic importance, designated agglutinin, which causes agglutination of typhoid bacilli in cultures. THE GASES OF THE BLOOD. ABSORPTION OF GASES BY SOLID BODIES AND BY FLUIDS. Between the particles of solid, porous bodies and gaseous substances there exists a marked attraction of such a character that the gases are attracted by the solid bodies and condensed within their pores; that is, the gases are absorbed by the solid bodies. Thus, for instance, one volume of boxwood charcoal, at a tem- DIFFUSION OF GASES. 7 5 perature of 12° C. and a pressure of 760 mm. of mercury, absorbs 35 volumes of carbon dioxid, 9.4 volumes of oxygen, 7.5 volumes of nitrogen, 1.5 volumes of hydrogen. The absorption of the gases is invarialjly attended with the generation of heat, which is in proportion to the energy with which absorption takes place. Non-porous bodies are in an analogous manner surrounded intimately upon their surface by a layer of condensed gas. Fluids are in like manner capable of taking up or absorbing gases. In this connection it has been learned that a given amount of fluid at different pressures nevertheless always absorbs an equal vohime of gas. Whether the pressure be great or small, the volume of gas absorbed is always the same. It is, however, known, according to the law of Boyle-Mariotte, governing the compression of gases, that with twice, thrice or greater ainounts of pressure, twice, thrice or greater amounts of gas by weight arc contained within an equal volume of gas. From this there is formulated the law that while at varying pressures the volume of gas absorbed remains the same, the amount of gas by weight contained within the same volume is directly proportional to the amount of pressure. If, therefore, the pressure is zero the amount of the absorbed gas must likewise be zero; whence it follows that Ihiids under the air-pump in a vacuum may be deprived of their absorbed gases. The coefficient of absorption represents that volurne of gas that is absorbed by I volume-unit of a fluid at a given pressure and temperature. From what has been said with regard to the volume of absorbed gases the coefficient of ab- sorption must be wholly independent of the pressure. The temperature has an important influence upon the coefficient of absorption. When the temperature is low the coefficient is highest, declining at a higher tem- perature and becoming zero when the fluid boils. From this it follows that ab- sorbed gases can also be expelled from fluids by heating the latter to the boiling- point. The coefficient of absorption increases, however, for various fluids and gases with increasing temperature in a peculiar, and by no means uniform, manner, which must be determined empirically for each. At the temperature of the body the coefficient of absorption of carbon dioxid is 0.5283, of nitrogen 0.0 119, of oxy- gen, at a pressure of 699 mm., 0.0231. DIFFUSION OF GASES; ABSORPTION OF GASEOUS MIXTURES. Gases that do not enter into chemical combination with one another are capable of forming a uniform mixture. If, for instance, the necks of two flasks are connected of which the lower contains carbon dioxid and the upper, placed vertically and inverted above the other, contains hydrogen, both gases combine, independently of dift'erences in specific gravity, within each flask so as to form identical mixtures. This phenomenon is known as the diffusion of gases. If a porous membrane be previotisl}^ interposed between the two gases the interchange of gases takes place just the same. Nevertheless different gases pass through the interstices of the membrane with unequal rapidity in the same way as in the case of fluids in the process of endosmosis, so that at first a larger amount of gas will be present upon the one side than upon the other. According to Graham the rapidity with which gases pass through the interstices is inversely as the square root of their specific gravity, but according to Bunsen, not exactly so. Gases mutually exert no pressure upon one another. Therefore a gas escapes from a space containing another gas as from a vacuum. If, accordingly, the sur- face of a fluid in which a gas is absorbed be placed in communication w'ith a large amount of another gas, the absorbed gas passes over into the other gas. Therefore, absorbed gases can be removed if the fluids containing them are treated with other gases by agitation or by passing them through. If two or more gases in mixture lie over a fluid within a closed space the separate gases will be absorbed, and according to weight in proportion to the pressure to which each gas would be exposed if it were alone present in the space. This pressure is known as partial pressure. The amount of gas absorbed from mixtures is therefore proportionate to the partial pressure. The partial pressure of a gas in a space partially filled by a fluid is at the same time an expression of the ten- sion of the absorbed gas in this fluid. The air contains 0.2096 volume of oxygen and 0.7904 volume of nitrogen. If, therefore, one volume of air is present at a pressure P over water, the partial pressure under which oxygen is absorbed is 0.2096 x P, and that for nitrogen equals 0.7904 X P. At a temperature of 0° C. and at 760 mrn. pressure i volume 76 SEPARATION OF THE GASES OF THE BLOOD. of water absorbs 0.02477 volume of air, consisting of 0.00862 volume of oxygen and 0.01615 volume of the nitrogen. It accordingly contains 34 per cent, of oxyg;en and 66 per cent, of nitrogen. Water, therefore, absorbs from the atmos- pheric air an amount of gas that is by percentage richer in oxvgen than the air itself. SEPARATION OF THE GASES OF THE BLOOD. The expulsion of the gases of the blood and their collection for cheinical analysis are effected by means of the mercurial air-pump. The Pfliiger pump for the extraction of gases is illustrated diagrammaticallv in Fig. 20. It consists of a blood-receptacle (A), a glass flask with a capacity of from 250 to 300 cu. cm., drawn out above and below into tubes, each of which can be closed by means of a stop-cock (a b). The cock b is an ordinary stop-cock, while the cock a has a channel passing through its longitudinal axis and opening at x in such a manner that in accordance with its adjustment it leads either into the receptacle (position x a) or downward through the lower tube (position x' a')- This receptacle is first completely deprived of air by application to a mercurial air-pump and is then weighed. Next, the extremity x' is tied in an arterv or a vein of an animal and by placing the lower cock in the position x a the blood is permitted to flow into the receptacle. When the desired amount has been col- lected the lower cock is again placed in the position x' a', the exterior is carefully cleaned and the receptacle is weighed in order to determine the weight of the blood collected. The second portion of the apparatus is the froth-vessel chamber (B) , likewise drawn out above and below into tubes, which can be closed by means of the cocks c and d. The purpose of the froth-chamber is to take up the froth formed in consequence of the active escape of the gases from the blood. Below, the froth- chamber is connected with the receptacle by means of a ground-glass tube and above likewise through a well-fitting tube with the drying apparatus (G). This consists of a U-shaped tube expanded below into a glass bulb. The latter is half filled with sulphuric acid, while each arm contains bits of pumice-stone saturated with sulphuric acid. In passing through this apparatus, which likewise may be closed by means of the two stop-cocks e and f, the gases of the blood yield up their watery vapor to the sulphuric acid, so that they may be conveyed through the cock f in a perfectly dry state. The short tube D is similarly connected with the prolongation from f by means of a properly ground surface, and it is provided with a small manometer from which the degree of vacuum can be read. The tube D communicates with the pump-apparatus proper. This consists of two large glass flasks, E and F, terminating above and below in open tubes, the lower of which, Z and w, are connected by means of a rubber tube G. Both flasks and the tube are filled with mercury to about half the height of the flasks. The flask E is secured, while the flask F can be raised and lowered by means of a pulley-apparatus attached to a stand. W^hen F is raised E becomes filled, and when F is lowered E is emptied. The upper extremity of E divides into two tubes, g and H, of which g is connected with D. The tube h, passing tipward, becomes greath^ narrowed and further on is so curved that its free extremity, i, dips into a basin containing mercury, v, with its opening below the tube for the reception of the gases, J (eudiometer- tube) completely filled with mercury. At the junction of g and H there is a cock with a double channel, which in the position H connects the flask E with A B G D, and in the position K closes A B G D and connects the flask E with the tube J. In the first place, B G D is completely exhausted of air by the following steps: The stop-cock is placed in the position K; and F is raised until globules of mercury pass from the free tube i, which is as yet not placed below J, into the basin. Then the stop-cock is placed in the position H, when F is depressed. Next, the cock is placed again in the position K, and so on, until the manometer y indicates that evacuation has taken place. Now, J is placed over i. If the cocks c and b are opened, so that the receptacle A cominunicates with the remainder of the apparatus, the gases of the blood pass actively into B, with the generation of foam, and through G, dried, to E. The depression of F brings them principally into E. Finally, the cock is placed in the position K, while F is raised, and the gases are conveyed to J above the mercury. Repeated depression and elevation of G with appropriate adjustment of the cock will finally bring all of the gases into J. The removal of the gases from the blood is materially facilitated by placing the recipient A in a vessel containing water at a temperature of 60° C. It is QUANTITATIVE ESTIMATION OF GASES OF THE BLOOD. 77 advisable in the analysis of the gases of the blood to evacuate at once the blood discharged from the vein into the receptacle, Vjecause on standing outside ot the body tlTc> amount of oxvgen undergoes a diminution. , ^, , . 'Mavow in 1670, was the first to observe gases arise from the blood in a vacuum, and Priestley demonstrated the presence of oxygen and Davy that of carbon Fig. 20— Diagrammatic Representation of Pfluger's Pump for the Extraction of the Gases of the Blood. dioxid Magnus, in 1857, investigated the percentage-composition of the gases of the blood The important recent investigations have been made principally by Loth. Meyer, in 1837, and by C. Ludwig and Pfliiger and their pupils. QUANTITATIVE ESTIMATION OF THE GASES OF THE BLOOD. The evacuated gases consist of oxygen, carbon dioxid, and nitrogen. The erases of the blood obtained %vith the aid of the pump \vill be found in the eudiSmeter-tube (Fig. 20, J), an accurately graduated glass tube m ^vhose 78 THE GASES OF THE BLOOD. closed upper portion two platinum wires, p n, are soldered. The eudiometer is closed below by mercuiy. Estimalion of the Carbon Dioxid. — A globule of potassic hydrate fused to a platinum wire and moistened on its surface is brought from below through the mercury into the gaseous mixture. The carbon dioxid unites with the potassium hydrate to form potassium carbonate. After remaining in place for a considerable period of time, the globule is removed in the same way. The diminution in the volume of the gases indicates the volume of the carbon dioxid removed. Estimation oj the Oxygen. — In the same way as in estimating the carbon dioxid a globule of phosphorus is introduced into the eudiometer-tube by means of a platinum wire and which takes up the oxygen for the formation of phosphoric acid; or a dry globule of coke or papier mach6 saturated with a solution of pyro- gallic acid in potassic hydrate, which eagerly takes up oxygen. After removal of the globule the diminution in volume of the gases indicates the amount of oxygen. The oxygen can be determined most accurately and most rapidly, according to Volta and Bunsen, by explosion in the eudiometer. An abundance of hydro- gen, whose volume is carefully determined, is introduced into the eudiometer-tube. Then an electric spark is made to pass through the tube between the wires p and n. The oxygen and the hydrogen combine to form water. In consequence a reduction in the volume takes place in the eudiometer, of which a third represents the oxygen required for the formation of the water. Estimation of ilie Xitrogeti. — If the carbon dioxid and the oxygen are removed from the gas-container according to the methods described the remainder consists of nitrogen. SPECIAL FACTS CONCERNING THE GASES OF THE BLOOD. Oxygen is present in arterial blood from the dog on an average to the amount of 18.3 volumes per cent., at a temperature of 0° C. and i meter of mercurial pressure. Arterial blood is saturated, according to Pfluger, to f'o. according to Hufner that of the dog to |i, with oxygen. By means of thorough artificial respiration in animals in the state of apnea or by active agitation of the blood with air the amount of oxygen can be brought up to 23 volumes per cent. Venous blood con- tains on the average 8.15 volumes per cent, less of oxygen than arterial blood, although the amount of oxygen varies widely in accordance with the tissues and the circulatory conditions. Sczelkow found 6 volumes per cent, in the blood of resting muscles. Only traces are present in the blood after asphyxiation. In the more highly colored blood of active glands, such as the salivary glands and the kidneys, oxygen is undoubtedly present in larger amount than in ordinary, darker venous blood. The oxygen occurs in the blood as follows: (a) From o.i to 0.2 volume per cent, are in a state of simple absorp- tion in the plasma — thus only a minimal portion, not exceeding that which distilled water at the temperature of the blood and at the partial pressure of oxygen in the air of the lungs would take up. ' (6) Almost all of the oxygen of the blood is combined chemically, and with the hemoglobin of the erythrocytes, with which it forms oxy- hemoglobin ; it is therefore not subject to the laws of absorption. The total amount of blood acts with regard to the chemical absorption of oxygen like a gas-free solution of hemoglobin, except that the absorp- tion of oxygen by the blood takes place more rapidly than by a solution of hemoglobin. At a temperature of 0° and at moderate atmospheric pressure — 760 mm. of mercury — i gram of hemoglobin takes up from 1.6 to 1.8 cu. cm. of oxygen — according to Hufner 1.592 cu. cm. OZOXE IX THE BLOOD. 79 The absorption of oxygen on the part of the blood is thus independent of the pressure. This is seen also in shed blood, which, on the one hand, permits more abundant escape of the chemically combined oxygen only when the pressure becomes reduced to about 30 mm. of mercury (at a temperature of 12° C. with increasing temperature at a lower jjressure), while, on the other hand, it takes up only little more oxygen even if the air-pressure be enormously high, up to six atmospheres. The same phenomenon is exhibited by the blood in the living body, for both on the highest mountains as well as in the deepest valleys it takes up oxygen in accordance with its requirements. Also, animals breathing in a closed space are capalile of abstracting the oxygen from the surrounding air down to the minutest trace. In spite of the chemical combination existing between the hemo- globin and the oxygen, the total amount of oxygen in the blood can be driven out by those agents that set free absorbed gases: (a) by evacuation ; (b) by boiling ; (c) by the passage of the gases ; because the chemical union of oxyhemoglobin is so feeble that it is broken up by the physical procedures named. Among chemical agents, reducing substances, such as ammonium sulphid, hydrogen sulphid, solutions of alkaline subsalts, iron filings, etc., extract oxygen from the blood. The amount of iron present in the blood — 0.55 in 1000 parts — is in direct proportion to the amount of hemoglobin, this to the number of erj'throcytes and the latter in turn approximately to the specific gravity of the blood. The amount of oxygen taken up by the blood has been shown to be almost proportional to the specific gravity of the blood. It is, therefore, also proportional to the amount of iron in the blood. According to Hoppe-Seyler i atom of iron may combine with 2 atoms of oxygen in the blood. According to Bohr the combination is said to be an unstable one. The latter investigator even differentiates several varieties of com- bination between oxygen and hemoglobin, in accordance with the amount of bound oxygen — namely, 0.4 or 0.75 or 3 cu. cm. of oxygen, at a temperature of 15° C. and an oxygen-pressure of 150 mm. — to i gram of hemoglobin. Also carbon monoxid is believed by Bohr to be taken up in varying amounts in an analogous manner. Immediately after escape of the blood a slight loss of oxygen takes place as a physiological manifestation of tissue-respiration within the living blood. After having been outside the circulation for some time the amount of oxygen is found to undergo progressive diminution, and after a long time and at a high temperature the oxygen may have wholly disappeared from the blood. This latter loss of oxygen is due to decomposition within the shed blood, in consequence of which reducing substances form and these take up the oxygen. Not all varieties of blood act in this connection with equal energy in tHe destruction of oxygen. The venous blood of active muscles acts most energetically, while the blood of the hepatic veins is scarcely at all active. In place of the oxygen that has dis- appeared carbon dioxid makes its appearance in the blood, whose color becomes dark. At times the amount of carbon dioxid is even larger than that of the oxygen destroyed. AS TO THE PRESENCE OF OZONE IN THE BLOOD. On account of the varied and in part active oxidation-processes that take place through the intermediation of the blood, the question has been raised whether the oxygen in the blood may not be present in the form of ozone (O3). However, neither in the blood itself nor yet in the gases evacuated from the blood can ozone be found. Nevertheless, the red blood-corpuscles, as well as the hemoglobin, have a definite relation to ozone. The hemoglobin acts as a conveyer of ozone, that is, it is capable of taking away the ozone from other bodies, and conveying it to other oxi lizable substances. So CARBON DIOXID AND NITROGEN IN THE BLOOD. Oil of turpentine that has been exposed to the air for a consideraVjle time always contains ozone. Among reagents for ozone are potassium-iodid paste, which becomes blue, as the ozone releases the combination of iodin and potassium, and the iodin causes the starch-paste to become blue; further, freshly prepared solution of guaiac-resin in alcohol, which also is made blue by ozone, A solution of guaiac is dropped in water, the resin forming a milky precipitate, and oil of turpentine is added. At tirst no reaction occurs, but if blood or hemoglobin be added, with agitation, a bluish discoloration appears, that is, the blood takes the ozone from the oil of turpentine and conveys it to the guaiac-resin. It has been stated that hemoglobin acts as an ozone-producer; that is, it is capable of generating ozone from the inactive oxygen of the air with which it comes in contact. For this reason, red blood-corpuscles alone also cause guaiac to become blue. The reaction is most successful if the solution of guaiac is per- mitted to dry upon blotting-paper and then several drops of blood diluted from 5 to 10 times are added. That under these circumstances the condition is one of stimulation of the surrotmding oxygen through the hemoglobin, is shown by the observation that even red blood-corpuscles containing carbon monoxid bring about the blue coloration, naturally not when the extraneous oxygen of the air is excluded. According to Pfluger these reactions take place only with decompo- sition of the hemoglobin, and for this reason it is believed that the blood-corpus- cles as such do not act as producers of ozone. Also hydrogen sulphid is decomposed by the blood, as by ozone itself, into sulphur and water. Hydrogen dioxid likewise is decomposed by the blood into oxygen and water. This can be prevented by the addition of a small amount of hydrocyanic acid. Crystallized hemoglobin does not bring this result about, and hydrogen dioxid can be cautiously injected into the veins of animals. From this it would appear that unaltered hemoglobin has no ozone-producing effect. There are three varieties of oxygen: (i) Ordinary or inactive oxygen (O,), as, for instance, that of atmospheric air. (2) Active or nascent oxygen (O), which can never occur in the free state, but which on its development at once enters into chemical combination as a most powerful oxidizing agent. This is capable of oxidizing water into hydrogen dioxid, the nitrogen of the air into nitrous and nitric acids, and also carbon monoxid into carbon dioxid — which ozone is not capable of doing. This gas certainly plays an important role in the organism. (3) Ozone (O3) forms through the breaking up of certain molecules of ordinarv oxygen (Oj) into two atoms each (O), and union of each of these atoms with an undecomposed molecule of oxygen. Ozone is a form of oxygen compressed to two-thirds of its volume. CARBON DIOXID AND NITROGEN IN THE BLOOD. Carbon dioxid is present in arterial blood in from 34 to 38 volumes per cent., at a temperature of 0° C. and a pressure of i meter; in venous blood on the average in 9.2 volumes per cent, more than in arterial blood, varying greatly in accordance with the situation and the circulatory conditions. The total amount of carbon dioxid in the blood does not equal even one-half of that which the blood would actually be capable of taking up. Thus, the blood after asphvxi- ation may contain as much as 52.6 volumes per cent. The amount of carbon dioxid in the lymph after asphyxiation is less than that in the blood. The carbon dioxid can be completely pumped out of the total volume of blood without the formation of acids in the process of evac- uation— in consequence of decomposition of the constituents of the blood — which might take part in driving out the carbon dioxid. The Carbon Dioxid of the Plasma or the Serum. (a) This is absorbed in smallest part simply by the blood-plasma. (6) The largest part of the carbon dioxid is combined chemically with the blood-plasma, independently of the pressure. This combi- nation may take place in the following manner: I. A portion of the carbon dioxid is loosely combined with sodium carbonate, forming sodium bicarbonate, one equivalent of carbon dioxid being taken up by INDIVIDUAL CIJNSTITUENTS OP THE BLOOD. 8l the simple carboiiiitc: COsXaj -f COj -|- HjO =2C03NaII. In this way considerable amounts of carbon dioxid may be bound. As the sodium bicarbonate releases the carbon dioxid but slowly in a vacuum, while blood releases it with violence, it must be borne in mind that perhaps sodium combined with a jjroteid (serum- globulin alkali) contains the carbon dioxid in a ccnnplex combination, frtjm which it readily separates in a vacuum. 2. A minimal portion of the carbon dioxid of the jjlasma mip;ht be combined chemically with neutral sodium phosphate: One efjuivalent of this salt may combine with one equivalent of carbon dioxid, so that acid sodium phosphate and acid sodium carbonate result: PO^NajH -f- C0j4- HjO = POiNalij + COgNaH. In the process of evacuation the carl:)on dioxid escapes, with the formation of neutral sodium phosphate. As, however, the sodium phosphate formed in blood- ash has resulted almost wholly from the combustion of lecithin and nuclein, only the small amount of this salt already present in the plasma can be taken into consideration. The Carbon Dioxid in the ]:>lood-corpuscles. The erythrocytes also contain carbon dioxid in loose chemical com- bination. In defibrinated human blood 31.2 volumes per cent, of carbon dioxid have been found in the serum, and only 4.5 in the blood- corpuscles. The combination of the carbon dioxid is effected in part through the hemoglobin, therefore through the formation of carbohem- oglobin, in part from the globulin-alkali combinations of the erythro- cytes. The leukocytes also combine with carbon dioxid in accordance with the character of the constituents of the serum, and in about the proportion of from j^ to \ of the absorptive power of the serum. Accoi"ding to Bohr there are three varieties* of carbon-dioxid combination with hemoglobin, which, while closely resembling one another, take up different amounts of carbon dioxid — namely 1.5, 3 and 6 cu. cm. of carbon dioxid respec- tively to I gram of hemoglobin, at the same partial pressure for the carbon dioxid and at the same temperature. Spectroscopically, carbon-dioxid hemoglobin re- sembles reduced hemoglobin, except that its absorption-band lies somewhat nearer the violet, and it absorbs more light in the green. Hemoglobin can take up oxy- gen and carbon dioxid at the same time, and each independently of the other. Therefore it is probable that oxygen and carbon dioxid unite with different con- stituents of the hemoglobin. The amount of carbon dioxid in the blood is diminished by alcoholic intoxica- tion, while it is increased by inhalation of ether, which reduces the amount of oxygen. Subcutaneous injection of morphin or chloral diminishes the amount of oxygen. After administration of iodin, mercury, sodium oxalate and nitrate there is a reduction in the amount of carbon dioxid in arterial blood. The same result is brought about in the blood of animals by injection of peptone into the veins, and also in the febrile state on account of the lessened alkalinity of the blood. Nitrogen is present in the blood in the proportion of from 1.4 to 1.6 volumes per cent, in a state of simple absorption. For every 100 parts of nitrogen there are 2.1 parts of argon, which, however, is present only in the plasma. The blood contains more nitrogen when the number of erythrocytes is larger than when the number is smaller and when the blood is lake-colored. Jolyet and Sigalas believe, therefore, that the erythrocytes, like solid bodies, absorb nitrogen at their surface. On standing outside the body, the blood yields small amounts of ammonia, particularly with access of oxygen and application of heat, perhaps in consequence of decomposition of an as yet unknown ammonium-salt. ESTIMATION OF THE INDIVIDUAL CONSTITUENTS OF THE BLOOD. Estimation of the Water and of All of the Solid Constituents of the Total Blood or of the Sentni. — About 5 grams of serum or defibrinated blood are evaporated in a crucible of known weight over a water-bath and dried in a drying chamber 6 82 ARTERIAL A\D VEXOUS BLOOD. at a temperature of iio° C. The loss of weight represents the amount of water that was present. The dry residue is determined by subtracting the weight of the crucible. For clinical purposes Stintzing weighs a few drops of blood in a light, covered glass dish. This he dries for six hours at a temperature of 65° C. ^nd weighs the residue. The amount of water was found to be in men 78.3, in women 79.8. The dry residue corresponds approximately with the amount of proteids contained in the blood and it declines in the presence of anemia. Estimation 0} the Fibriji. — A measured volume of blood is whipped with a rod. -After complete separation, all of the librin is collected upon a satin filter and ■washed with water; then placed in a dish and again washed with water, alcohol and ether; next dried in a drying chamber at a temperature of 110° C, and finally weighed. Kossler and Pfeiffer estimate the amount of nitrogen in the serum and in the plasma according to the method of Kjeldahl; the difference represents the amotmt of nitrogen in the fibrin. The fibrin in 100 cu. cm. of plasma contains 39 mg. of nitrogen (from 30. S to 45). The fibrin is increased in cases of pneumonia, acute articular rheumatism, erysipelas, scarlet fever, peritonitis (to between 80 and 152 mg.). Estimation of the Fats (Ethereal Extract) in the Serum or the Total Blood. — About 15 grams of defibrinated blood or serum are dried in a dish at first over a water-bath, then in a drying chamber at a temperature of 120° C, rubbed up, and placed in a flask with ether, which is repeatedly renewed. The method just described is followed in preparing an alcoholic extract from the total blood or the serum. Estimation of the Inorganic Salts in the Total Blood or Serum. — About 25 grams are dried in a weighed platinum crticible and then reduced to ash over a free flame at red heat. The amount of ash is determined by weighing. If this ash be repeatedly extracted with hot water, and the latter be entirely evaporated in a weighed dish, the weight of the salts soluble in water will be obtained. Estimation of the Total Pr^^icids in Blood or Serum. — E. Salkowski precipitates all albuminates by means of sodium chlorid and acetic acid. For this purpose he places 20 grams of pulverized sodium chlorid and 50 cu. cm. of blood in a dry flask and adds 100 cu. cm. of a mixture of 7 volumes of concentrated solution of sodium chlorid and i volume of acetic acid, agitating for 20 minutes and filtering. The filter is dried and weighed. V. Jaksch takes i gram of blood from a cupping glass, estimates the amount of nitrogen contained by the method of Kjeldahl, and multiplies the result obtained by 6.25. Estimation of the Proteids of the Blood-corpuscles. — If the proteids contained in one part by weight of the total blood and also of the serum have been deter- mined, and if the amount obtained for the serum be deducted from that obtained for the total blood in the proportion in which red blood-corpuscles and serum are present in the total blood, the result will represent the proteids of the blood -corpus- cles, although only approximately. Estimation of the Red Blood-corpuscles by Weight. — Defibrinated blood is mixed with thrice its volume of a concentrated solution of sodium sulphate and filtered. The blood-corpuscles remaining upon the filter are coagulated by immersing the filter in boiling concentrated sokition of sodium sulphate. Then the filter can be w^ashed out with distilled water, after which it is dried and weighed. The increase in the weight of the previously weighed filter is due to the presence of the blood- corpuscles. ARTERIAL AND VENOUS BLOOD. Arterial blood contains in solution all those materials that are neces- sary for the nutrition of the tissues, many that are to be emplo^-ed in secretion and in addition the larger amount of oxygen. Venous blood need contain less of these matters, while the waste materials of the tissues, the products of retrogressive metamorphosis, will be present in greater amount, including a larger quantity of carbon dioxid. As, however, the interchange through the blood takes place rapidly, no great difference in many of these substances can be looked for at a given moment. In many respects analysis fails to furnish conclusive evidence. A little consideration, further, will show that the blood from THE AMOUNT OF BLOOD. 83 some veins must be characterized l)y special peculiarities, such as the blood from the portal vein and the hepatic veins. The essential differ- ences between the two kinds of blood may be summarized as follows: ARTERIAL BLOOD CONTAINS More Less Oxygen, water, fibrin, extractives, Carbon dioxid, blood-corpuscles, pro- salts, at times chlorids, sugar, fat; teids, alkali, urea, and the temperature is on an average 1° C. higher. The bright red color of arterial blood is due to oxyhemoglobin, to which it is peculiar; while the dark color of venous blood is due to a deficiency in oxyhemoglobin and an abundance of reduced hemoglobin. The larger amount of carbon dioxid in venous blood is not responsible for the dark color, for if equal amounts of oxygen be added to two portions of blood and to the one also carbon dioxid, the latter effects no change in color. THE AMOUNT OF BLOOD. The amount of blood in the adult equals y^ of the body-weight, in the newborn yy . According to A. Schiicking the amount of blood in the infant when the umbilical vein is ligated immediately after birth is y^- while that in the infant when ligation is practised later is as much as ^ of the body- weight. Immediate ligation, therefore, causes a reduction of the amount of blood in the newborn child of about 100 grams. Further, the number of red corpuscles is less in the blood of the newborn child after immediate ligation than in that of infants in which ligation is practised later. For the estimation of the amount of blood, first practised by Valen- tine in 1838 and by Ed. Weber in 1850 by unreliable methods, the fol- lowing may be employed: Welcker's Mctliod. — Blood from the incised carotid of a previously weighed animal, with a cannula tied in the vessel, is received into a weighed flask, in which it is defibrinated by agitation with pebbles. It is then measured. A portion of the defibrinated blood is made cherry-red by the passage of carbon monoxid, because ordinary blood possesses varying coloring power in accordance with the amount of oxygen present. Now a I — shaped cannula is tied in both extremities of the divided carotid and a 0.9 per cent, solution of sodium chlorid is permitted to flow steadily from a pressure- vessel, while the resulting wash-water that escapes from the divided jugular veins and the inferior vena cava is collected until it becomes as clear as water. Then the entire body is minced, and with the exception of the weighed contents of the stomach and intestines, whose weight is deducted from that of the body, the mass is extracted with water and expressed after the lapse of 24 hours. This water and the sodium-chlorid wash-water are mixed and weighed. A portion of this mixture is likewise saturated with carbon monoxid. Of this a specimen is placed in a glass chamber with parallel walls, i cm. apart — a so-called hema- tinometer, while in a second chamber water is added to the undiluted blood from a buret until both fluids exhibit the same shade of color. From the amount of water that is necessary to make the dilution of the blood of the same tint as the wash-water the amount of blood present in the latter can be estimated. In mincing the muscles alone the coloring-matter yielded by them can be considered as muscle-pigment and need not be taken into account. By multiplying the volume of blood by its speciflc gravity the absolute weight of the blood can be determined. As the differences in the color of the specimens can be esti- mated most accuratelv this method is to be commended. 84 ABNORMAL IXCRKASK I X THE AMOUXT OF BLOOD. The weight of tlie blood of mice has been found to be from -,'.. to -jV of the body-\Yeight, exclusive of gastric and intestinal contents; of guinea-pigs ^. (from ^^ to _'.) ; of rabbits J^ (from ^\ to y. ); of dogs ,\ (from ' to ^); of cats'-' ; of birds from - to ' ; of frogs ' to -; 13 1^^ II 21-5 1.5 10' o 20 IS of fish from ' to ' . 19 14 Vierordt's method, which is based upon the determination of the amount of blood by indirect means, is discussed under circulation time. The specific gravity also should be determined in a study of the blood. In states of inanition the amount of blood has been observed to be reduced. Obese individuals have relatively less blood. After hemorrhage the blood lost is readily replaced by water, while the blood- corpuscles are only gradually regenerated. After extensive, deple- thoric transfusion with defibrinated blood Landois, as well as Panum, observed the amount of blood and its specific gravity to be maintained. In the living animal Grehant and Quinquatid permitted a measured amount of carbon dioxid to be inspired, then withdrew a quantity of blood and estimated the amount of carbon monoxid present. From this the amount of blood can be readily determined. A quantity of carbon-monoxid blood could also be transfused and shortly thereafter the proportion of shed blood containing carbon monoxid, and that free from carbon monoxid, be estimated. The estiination of the amount of blood in individual organs is made after sudden ligation of their veins during life. The organs are cut up into small pieces and the amount of blood contained in the wash-water is determined by comparison with a specimen of blood to be diluted. The estimation after death in a state of freezing is to be rejected. ABNORMAL INCREASE IN THE AMOUNT OF BLOOD OR ITS INDIVIDUAL PARTS. An increase in the total mass of blood uniformly in all its parts is known as polycmia or pletJwra. It may occur as a inorbid manifestation in individuals with excessive nutritive and assimilative activity. A marked bluish-red color of the external integument, with swollen veins and large arteries and a hard and full pulse, injection particularly of the capillaries and smaller vessels of the visible mucous membranes are the readily explicable signs, accompanied by cerebral hyperemia, which may give rise to attacks of vertigo, and hyperemia of the lungs, which may give rise to dyspnea. Also after ampiitation of large portions of the extremities, with avoidance of loss of blood, a relative increase in the amount of blood has been described (plethora apocoptica). Polyemia can be induced artificially by injection of blood from the same species. If the normal amount of blood be increased up to 83 per cent, no ab- normal condition develops; in particular, the blood-pressure does not becoine permanently raised. The blood finds its way especially into the greatly distended capillaries, which as a result become stretched beyond their normal elasticity. An increase in the amount of blood, how'ever, up to 150 per cent, jeopardizes life directly, with considerable variations in blood-pressure, and which Landois has observed to terminate fatally in consequence of direct rupture of vessels. Following upon the injection of blood the formation of lymph rapidly in- creases. Then the serum is disposed of in the course of one or two days, the water being eliminated principally through the urine, and the proteids in part converted into urea. Therefore, the blood at this time appears to be richer in red blood-corpuscles. The red blood-corpuscles undergo destriiction much more slowly and the materials furnished by them are converted in part into urea and in part into the biliary pigment, though not constantl^^ Nevertheless an excess of red blood-corpuscles may be observed for as long as a month. That as a matter of fact the blood-corpuscles are slowly destroyed in the process of metabolism is shown from the circumstance that the formation of urea is greater w^hen the animal ingests the same amount of blood than if it receives an equal amount by transfusion. In the latter event a moderate increase in ABNORMAL INCREASE IN THE AMOUNT OF BLOOD. 85 the amount of urea persists often for a number of days as a sign of slow destruc- tion of the red corpuscles. Marked plethora is attended, further, with loss of appetite as well as a tendency' to hemorrhages from the mucf)us membranes. Serous polycmia is the name given to that condition of the blood in which the amount of serum or plasma is increased. Thp condition can he produced artificially by injecting into the veins of animals serum from the same species. Under such circumstances the water is soon excreted with the urine, while the allnimin is decomposed into urea, without passing over into the urine. An animal forms more urea from a given amount of injected serum than from an equal amount of blood — an indication that the blood-corpuscles are capable of Ijeing preserved for a longer time than the serum. If, however, an animal be injected with the serum from another species, in which the blood-corpuscles of the recip- ient undergo solution, as, for instance, if dogs' serum be injected into a rabbit, the blood-cells of the recipient are dissolved and hemoglobinuria develops, and even death may take place if the dissolution be extensive. Simple increase in the amount of water in the blood, aqueous polyemia. occurs as a transitory phenomenon after copious ingestion of fluid, but increased diuresis soon restores the normal conditions. Disease of the kidneys attended with de- struction of the secreting parenchyma of the glands induces, together with aqueous polyemia, often general anasarca through the leakage of water into all of the tissues. Ligation of the ureter likewise gives rise to an increase in the watery elements of the blood. Stintzing and Gumprecht found the dry residue of small amounts of blood after evaporation of the water to be from 19.8 per cent, in women to 21.6 per cent, in men, while in cases of anemia it falls to 8.5 per cent. An increase of the red blood-corpuscles beyond the normal mean — polycy- themic plethora or hyperglobulia — has been thought to be present in robust individ- uals when hemorrhages that have regularly taken place cease and in general all of the symptoms of polyemia are present. The cessation of menstrual, hemorrhoidal, and nasal hemorrhages is considered as a cause, as well as the omission of venesection previously employed systematically. Nevertheless, the poly- cythemia under such circumstances is only inferred and not established by enu- meration. On the other hand, a condition of polycythemia has been positively observed. Thus, after transfusion of blood from the same species a portion of the blood-plasma is soon consumed, while the blood-corpuscles are preserved for a longer time. An increase in the number of red blood-corpuscles up to 8,820,000 in a I cu. cm. in case of severe heart-disease, with marked stasis, in which more water escapes from the vessels by transudation, is a remarkable fact. The num- ber is for the same reason greater also in cases of hemiparesis upon the paralyzed side presenting phenomena of stasis. After attacks of diarrhea that cause a reduction in the amount of water in the blood there is likewise an increase in the number of red corpuscles, and it is probable that the same result is brought about by profuse sweating and by polyuria. Agents that influence the caliber of the vessels, such as alcohol, chloral hydrate, amyl nitrite, give rise to an increase in number when they cause con- traction of the vessels and to a diminution when they cause relaxation. A transitory increase in the ancestors of the red blood-corpuscles is encountered as a reparative process after profuse hemorrhage or after acute disease. In cachectic states the increase is permanent on account of interference with the transformation into red corpuscles. In the last stages of cachectic states the number progressively diminishes, as at this time the production of the ancestral forms also ceases. The designation hyperalbuminous plethora has been applied to an increase of the albuminates in the plasma such as it may be inferred occurs after abundant absorption from the digestive tract. The same condition may be induced experi- mentally by injection of serum from the same species of animal, the elimination of urea increasing at the same time. Injection of egg-albumin induces albu- minuria. Melitemia or an excess of sugar in the blood. The sugar of the blood is eliminated in part with the urine, in marked degree up to i kilo daily, and the amotint of urine may be increased to 25 kilos. To replace this loss an abundance of nourishment and much fluid are necessary, and in this way the amount of urea may at the same time be increased threefold. The marked pro- duction of sugar also induces destruction of proteid tissue, so that the amount of urea is increased, even if the supply of albumin be insufficient. The patients emaciate, all of the glands, particularly the testicles, undergo atrophy or degenera- 86 ABNORMAL DIMIXUTIOX IX THE AMOUNT OF BLOOD. tion, the skin and the bones become thin, while the nervous system resists the longest. The crystalline lens becomes turbid in consequence of the presence of sugar in the fluids of the eye, which abstract water from the lens. Wounds heal badly on account of the abnormal constitution of the blood. If a drop of blood be spread upon a glass slide, then treated with a solution of Bieberich's scarlet or alkaline mcthylcne-blue and heated for ten minutes at a temperature of 35°.. it will not take the stain if derived from a case of diabetes, while normal blood is stained. Instead of grape-sugar excessive accumulation of inosite or of milk-sugar has also been found in the blood and in the urine. Lipemia. — Increase in the amount of fat in the blood occurs normally after the ingestion of food rich in fat, as, for instance, in nursing kittens, so that the serum itself may acquire a milky turbidity. Pathologically, this is observed in still more marked degree in drunkards and in obese individuals. In conjunction with marked destruction of proteids in the body, therefore, in a large number of wasting diseases, the amount of fat in the blood' is increased; likewise after abundant administration of easily digestible carbohydrates, together with much fat, in the food. V. Jaksch found traces of fatty acids in the blood of febrile and leukemic patients. After injuries to bones involving the marrow large numbers of fat-globules often pass from the vessels of the marrow, in part unprovided with walls, into the blood-stream, so that fat may even find its way into the urine, and may give rise to dangerous fat-emboli iii the lungs. The salts are usually preserved with great tenacit}-. If sodium chlorid be withheld, albuminuria results; and if salts in general, paralytic phenomena. Excessive administration of salty food, as in the form of pickled meat, has not rarely been followed by death through fatty degeneration of the tissues, par- ticularly of the glands. Withdrawal of calcium and phosphoric acid brings about softening or atrophy of the bones. In the presence of infectious diseases and of anasarca the amount of salts in the blood has often been found increased, while in the presence of inflammation (sodium chlorid is wanting in the urine in cases of pneumonia) and of cholera the amount is diminished. The amount of fibrin in the blood is increased in the presence of inflamma- tion, particularly of the kmgs or the pleura. Therefore venesection under such circumstances is followed by the formation of the so-called buffy coat. The hbrin maj' be increased also in other diseases attended with blood-destruction. Sigrn. Mayer observed an increase likewise after repeated venesection. Blood rich in fibrin usually coagulates more slowly than blood deficient in fibrin, although exceptions to this statement are not wanting. ABNORMAL DIMINUTION IN THE AMOUNT OF BLOOD OR OF ITS INDIVIDUAL CONSTITUENTS. Reduction in the mass of the blood as a whole — true oligemia — occurs after every direct loss of blood. In the newborn a hemorrhage of even a few cu. cm., in children a year old a hemorrhage of 250 cu. cm., and in advilts a loss of one- half of their blood may prove dangerous. Women withstand better than men even considerable loss of the blood. In them the regeneration of the blood appears to take place more readily and more quickly in consequence of the periodic restoration of the blood lost at each menstrual period. Obese persons, as well as the aged and the debilitated, are less tolerant to loss of blood. The hemorrhage is the more dangerous the more rapidly it takes place. General pallor and coldness of the skin, a sense of fear and oppression, relaxation, the appearance of spots before the eyes, roaring in the ears and vertigo, loss of voice and svncopal attacks usually accompany profuse hemorrhage. Dyspnea ("and breathing rapidlv he exhales life in a purple stream:" Sophocles' Antigone), cessation of glandular secretion, profound loss of consciousness, then dilatation of the ptipils, involuntary discharge of urine and feces, and linall}' general convulsions are the positive premonitions of rapid death from hemorrhage. In the state of greatest danger life can be saved only by transfusion. As much as one-quarter of the normal amount of blood can be withdrawn from animals without permanently lowering the blood-pressure in the arteries, because the latter by contraction adapt themselves to the smaller volume of blood in consequence of the anemic irritation of the vasomotor center in the medulla oblongata. Loss of blood up to one-third of the volume of blood causes marked reduction in the blood-pressure. Dogs recover after loss of one-half of the volume ABNORMAL DIMINUTIOX IN THE AMOUNT OF BLOOD. 87 of blood. If two-lhinls be removed one-half of the animals die, while the remaining half recover spontaneously. If the hemi>rrhage does not terminate fatally, the water of the blood, with the dissolved salts, is first replaced through absorption from the tissues, with gradual increase in the blood-pressure; and later the proteids. Considerable time is required for the regeneration of the blood-corpuscles. The blood, there- fore, contains for a time an al)normal amount of water — hydremia; a.nd finally it exhibits an abnormal deticiency in cells — oligocyilicmia, hypoglobulia. With the increased lymph-stream toward the blood the leukocytes are soon considerably increased above their normal number. Also fewer red blood-corpuscles appear to be consumed during the period of restitution, as, for instance, in the formation of bile. After moderate venesection in animals Bvmtzen observed the volume of blood restored in a few hours, and after severe hemorrhage in the course from 24 to 48 hours. The red blood-corpuscles, however, were, after venesection of from i.i to 4.4 per cent, of the body-weight, fully restored to the normal only after the lapse of from 7 to 34 days. The commencement of the regenerative process could be recognized in the course of 48 hours. During this period of reorganization the nximber of the embryonal forms of the blood-corpuscles was increased. The newly formed blood-corpuscles appear at first to contain less hemoglobin than normal. Also in human beings the duration of the period. of regeneration ap- pears to be dependent upon the amount of hemorrhage. The reduction in the amount of the hemoglobin of the blood after venesection is approximately pro- portional to the amount of the blood removed. Of especial significance is the state of metabolism in the body of an anemic patient. The decomposition of proteids is increased, and as a result the elimina- tion of urea is increased. The combustion of fats in the body is, however, correspondingly diminished, and the amount of carbon dioxid given of? is cor- respondingly reduced. Anemic as well as chlorotic patients therefore readily put on fat. The same significance is to be attached to the lipomatosis of anemic convalescents after acute diseases interfering with blood-formation. The fattening of animals is, accordingly, favored by occasional venesection. The same statement is applicable to intercurrent hunger. Aristotle had already pointed out that swine and birds readily take on considerable fat after days of intercurrent hunger. Anemia results also from faiKire on the part of the blood-forming organs. The alarming anemia from the presence of the bothriocephalus, which may pursue a course similar to pernicious anemia is remarkable. It is probably dependent upon a toxic effect induced by the parasite, which impairs the vitality of the blood-corpuscles. Excessive concentration of the blood through loss of water is designated dry oligemia. This condition has been observed in human beings after copious, watery diarrhea, particularly in cases of cholera, and the thick, tarry blood stag- nates in the veins. Probably copious loss of water through the skin as a result of diaphoretic treatment, particularly in association with restriction of fluids, may give rise to drv oligemia, even though only in moderate degree. If the proteids of the blood are diminished in abnormal degree a condition of hypallniminoiis oligemia is present. The proteids may be diminished more than half. In their place an excessive amount of water usually finds its way into the blood, so that the salts of the plasma are likewise diminished. Loss of proteids from the blood is due directly to albuminuria, which may furnish even 25 grams of proteid daily; to long-continued suppuration, extensive weeping cutaneous sur- faces, excessive loss of milk, albuminous diarrhea (dysentery). Frequent and copious hemorrhage, also, induces at first hypalbuminous oligemia, as the loss primarilv is principallv made good by the taking up of water into the vessels. V. Jaksch found that the amount of proteids failed to decline in correspondence with the reduction in the number of blood-corpuscles. PHYSIOLOGY OF THE CIRCULATION. CAUSE, PURPOSE, DIVISION. The blood maintains itself within the vascular system in an unin- terrupted circulating movement that, proceeding from the cardiac ven- tricles through the largest arterial trunks arising therefrom (the aorta and the pul- monary artery) to the furthermost branches of these vessels, then through a system of capillary vessels, from which it is collected into the venous channels, which progressively increase in size by coalescence, terminates finally in the auricles. The cause of this circulatory movement resides in the difference in pressure to which the blood is exposed in the aorta and the pulmonary artery, on the one hand, and the two venag cavae and the four pulmonary veins on the other. The blood naturally flows continuously toward that portion of the closed system of tubes where the pres- sure is lowest. The greater this difference in pressure the more active will be the move- ment of the stream. Abolition of this differ- ence in pressure, as after death, will natur- ally cause a cessation of the flow. The purpose of the circulation is, on the one hand, to carry nourishment through the blood to all the tissues of the body, while on the other, the blood carries away from the tissues to the organs of excretion the waste products of their metabolism. The circulation of the blood is divided into: 1. The greater circtilatiou , comprising the pathway from the left auricle and the left ventricle through the aorta and its branches, the capillaries and the veins of the body, to the termination of the two venae cavae in the right auricle. 2. The lesser circulation, comprising the pathway of the right auricle and the right ventricle, the pulmonary artery, the pulmonary capillaries and the four pulmonar}^ veins arising therefrom up to their point of entrance into the left auricle. 3. The portal circulation is occasionally considered as a separate circulatory system, although it is only a second capillary ramification Fig. 21. — Diagrammatic Representa- tion of the Circulation: a, riglit auricle; \, right ventricle; b, left auricle; B, left ventricle; i, pulmonary artery; 2, aorta, with semilunar valves; 1, lesser cir- culation; k, greater circulation, including superior vena cava, o; G, greater circulation, including inferior vena cava, u; d d, intesti- nal tract; m, mesenteric arteries; q, portal vein; L, liver; h, hepa- tic veins. THE IIKART. 89 inserted into a venous pathway. It is composed of the portal vein, which represents the union of the veins of the abdominal viscera — the superior gastric, the superior and inferior mesenteric, and the splenic veins — and which breaks up in the liver into capillaries that again unite to form the hepatic veins, which empty into the inferior vena cava. Strictly speaking, this dilTcrcntiation of the portal systcin into a seijarate circulation is not justitialilo. In many animals similar conditions are found in still other organs, as, for exaniple, the suprarenal of the snake and the kidney of the frog. When an artery breaks up into numerous small branches that shortly reunite, without the intervention of capillaries, to again form an artery, the cluster of branches thus formed is called a "wonderful network," rete miral)ile. such as is seen in apes and edentates. Microscopical networks of this character are found in the mesentery of man. The glomerulus of Bowman's capsule in the kidney also is an example of this peculiar arterial division. Analogous formations in the veins are called venous "wonderful networks." THE HEART. The mammalian heart-muscle (Fig. 184, 8) is composed of short, closely and finely striated, unicellular elements which are devoid of sarcolemma and, in man, from 50 to 70 /' long and from 15 to 23 // wide. The ends are rather blunt and generally split, and by these split ends the fibers are joined together anastomotically to form a network. The individual muscle-cells are imited by a cement-substance, which is soluble in 33 per cent, potassium-hydrate solution and is stained black by silver nitrate. Each cell at its center contains a nucleus, rarely two smaller nuclei, 14 u long bv 7 n wide, in its central axis. The transversely striated sub- stance frequently contains molecular granules arranged in rows. The fibrils are placed side by side and are divided by the perimysium into bundles, which, after solution of the connective tissue by boiling, may be isolated. The shape of the bundles on transverse section is rather circular in the auricles, while in the ventricles it is rather flat and laminated; here also several of the smaller bundles may unite to form a thicker band. The interstices between the bundles serve to carry the lymph- vessels. ARRANGEMENT OF THE MUSCLE-FIBERS OF THE HEART AND THEIR PHYSIOLOGICAL SIGNIFICANCE. Musculature of the Auricle. — The study of the embryonal heart furnishes the key to the understanding of the complicated arrangement of the muscle-fibers. The simple heart-tube of the embryo exhibits an outer circular and an inner longitudinal layer of muscle-fibers. The septum is formed later, so that it is obvious that both in the ventricles as well as in the auricles the fibers belong, in part at least, to both halves, as they originall}^ enclose only a single cavity. On the other hand, the fibers of the auricles are generally separated from those of the ventricles by the fibrous ring; nevertheless certain of the muscle-bundles pass from the auricles to the ventricles. In the auricles the embryonal arrange- ment of the fibers remains fundamentally unchanged. In the ventricles the arrangement is obliterated because during the process of development the fibers here undergo a peculiar bending and looping, as in the stomach, together with a spiral rotation. The musculature of the auricles is in general arranged in tw-o la^^ers: an outer transverse, which is continuous over the two auricles, and an inner longitudinal. The outer fibers can be traced from the entering veins upon the anterior and posterior walls. The inner fibers are especially prominent where they are attached vertically to the fibrous rings, but in certain parts of the anterior wall in particular thev are not arranged continuously. On the septum of the auricles the ring-like muscular laver surrounding the oval fossa, the opening of the oval foramen in the embryo,' is especially prominent. Around the openings of the veins emptying into the auricles are found circular muscle-bundles; these are least well marked around the inferior cava, while around the superior cava they are well developed and extend upward around the vessels for 2.5 cm. (Fig. 22, II). At the entrance of the four pulmonary veins in man and in some mammals, transversely striated muscle-fibers, arranged in an inner circular and an outer longitudinal layer, ex- 90 MUSCULATURE OF THE VENTRICLES. tend upon the pulmonary veins as far as the hikis of the lung; in other animals (apes, rats) they extend even into the lung itself; indeed, in some mammals (mouse, bat) this muscular layer penetrates the lung so tar that m the small veins the entire wall is composed almost wholly of striated muscle-fibers. Muscle- fibers, chiefly circular, are also found at the termination of the great cardiac vein and in the coronary valv'e of Thebesius. Many elastic fibers are present in the perim\-sium of the auricles. From the physiological standpoint the foregoing anatomical data explain the following facts with relation to the contractions of the auricles. The auricles are able to contract independently of the ventricles; this is particularly manifest in the cessation of the heart's activity, as under such circumstances two or more contractions of the auricle alone are often seen to take place, followed now and then by a single con- traction of the ventricle. However, when the action of the heart is Fig. 22. — I, Course of the Muscle-fibers in the Left Auricle: the outer transverse and the inner longitudinal fibrous layer are \-isible and in addition the circular fibers of the pulmonary veins, v. p. V, left ventricle (Joh. Raid). II, Distribution of Transversely Striated Muscle-fibers on the Superior Vena Cava (Elischer): a, entrance of the azygos vein; v, auricle. unimpaired the auricles in their contraction transmit the motor impulse to the ventricles. Whether this stimulation is brought about through nerve-fibers or, as is more probable, through connecting muscle-bundles, has not yet been decided with certainty. The two chief layers of fibers (transverse and longitudinal), which cross each other, serve to effect uniform contraction of the auricular cavitv from all sides, as is the case likewise with most hollow^ muscular organs. The circular fibers surrounding the entering venous trunks, through their contraction, which occurs in unison with that of the auricles, cause in part an emptying of blood into the auricle and in part a hin- drance to a return of the blood in anv considerable measure. ARRANGEMENT OF THE MUSCULATURE OF THE VENTRICLES. The Muscle-fibfrs oj the \'ciitriclcs. — Beneath the pericardium there is first met an outer longitudinal layer (Fig. 23, A), consisting of only occasional bundles on the right ventricle, while on the left it comprises a compact layer of about one-eighth of the entire thickness of the wall. A second layer of longitu- dinal fibers lies on the inner surface of the ventricles, being especially well marked at the orifices, as well as inside the perpendicularly placed papillary mtiscles. pericardium; endocardium; valves. 91 while m other situations it is replaced bv the irregularly running fiVjers of the muscular trabccula>. Between the two longitudinal layers lies the most powerful transverse layer, the libers of which are separable into individual, leaf-like ring-shaped bundles. The three layers, however, are not wholly indejiendent and separated from each other, but rather there is a gradual transition between the transverse and the outer and inner longitudinal layers bv means of oblique fibers The common assumption is that the entire outer 'longitudinal layer passes gradually nito the transverse and this in turn wholly into the inner longitudinal as is shown diagrammatically in Fig. 23, C. This is not justifiable, and is ne-'-atived by the great preponderance in the thickness of the middle layer. In general the outer longitudinal fibers pursue such a course as to intersect the course of the libers of the inner longitudinal layer at an acute angle. The intervening trans- verse layer constitutes the medium for a gradual transition between these courses - \\ "A 't ' « Fig. 23. — Course of tlie Muscle-libers in the Ventricles: A. course upon the anterior surface; B, view of the apex with the "whirl" (Hcnie); C, diagrammatic representation of the course of a muscle-fiber within the wall of the ventricle; D, course of such a fiber into the papillary muscle (C. Ludwig). At the apex of the left ventricle external longitudinal fibers, uniting in the so-called "whirl" (B), pass in a curved direction inward and upward within the muscle-substance and extend into the papillary muscles (D). Nevertheless it is an error to consider that all of the ascending libers in the papillary muscles are derived from these vertical muscle-bundles of the outer surface, as many arise independently from the wall of the ventricle. Neither can the origin of these longitudinal fibers on the outer surface of the heart be traced solely to the fibrous rings or to the roots of the arteries. Finally, mention should be made of the special circular layer of fibers that surrounds the left orifice like a sphincter. Numerous lymph-vessels are present in all the interstices between the muscle-fibers and the blood-vessels. These eventually empty into the lymph-vessels and nodes of the mediastinum. PERICARDIUM; ENDOCARDIUM; VALVES. The pencardimn. which includes between its two layers a lymph-space^the pericardial cavity — containing a small amount of lymph, exhibits the structure of a serous membrane; that is, it is composed of connective tissue containing delicate ^2 pericardium; exdocardium; valves. ■elastic fibers, and is covered on its free surface with a single layer of irregular polygonal, flat, endothelial cells. A rich network of lymph-vessels lies within the pericardium itself, as well as more deeply toward the muscle-mass of the heart. Stomata are wanting in both layers of the pericardium. In the subserous tissue of the pericardium, especially in the sulci for the coronary vessels, are deposits of fat, and lymphatics. The endocardium presents all of the characteristics of a vessel-wall. Facing the cavity of the heart, there is first a single layer of flat, polygonal, nucleated endothelial cells. Then there comes, as the true groundwork of the whole mem- brane, a layer of delicate elastic fibers (more marked in the auricles, and even forming a fenestrated membrane) , in the inidst of which but little connective tissue occurs. The latter, much more loosely arranged and intermixed with elas- tic fibers, is present in larger amount toward the heart-muscle. Scattered bundles of unstriated muscular fibers, usually arranged longitudinally, are found between the elastic elements (in smaller amount in the auricles) . These obviously have the task of combating the pressure and the tension exerted on the endocar- dium during the cardiac contraction; for wherever throughout the body a wall composed of soft parts is exposed to repeated high pressure muscular elements are found, and never elastic tissue alone. The endocardium is non-vascular. The valves — both the arterial (semilunar) and the venous (mitral and tricuspid) — also are a part of the endocardium. The venous and arterial orifices on the right side are separated from each other in the wall of the ventricle, while the two orifices on the left are united into a single large opening. The valves are attached to their basal margins by means of resistant fibrous rings composed of connective-tissue and elastic fibers. They consist of two layers: (i) The fibrous, which is a direct continuation of the fibrous ring, and (2) a layer of elastic elements. The elastic layer of the auriculo-ventricular valves is a direct prolongation of the endocardium of the auricle, and is therefore directed toward that cavity. At their bases the valves are united by their adjacent margins. The tendinous cords are inserted on the free margin and on the under surface of the valves. The semihmar valves possess a thin, elastic layer, thickened at their base and turned toward the arteries. The auriculo-ventricular valves contain also striated muscle-fibers. Radiating fibers, arising from the auricles, extend into the valves, and it is their function in part to retract the valves toward their bases dviring the time of auricular svstole, and thus to enlarge the passage-way for the flow of blood into the ventricles. Paladino describes still other longitudinal fibers derived from the ventricles. Besides these, there is directed rather ! toward the ventricular aspect, a con- centric muscular layer, following the basal attachment of the valves, which appears to have a sphincter-like action — drawing the bases of the valves together during the period of ventricvilar contraction when the valves are under tension, and thus preventing excessive distention. The larger of the tendinous cords also contain striated muscle-fibers; and the Thebesian and Eustachian valves like- wise contain a delicate muscular network. The name "Purkinje's fibers" has been applied to a grayish network of muscular elements found in mammals and in birds chiefiy beneath the endocar- dium of the ventricle, but occurring also in the muscular mass itself. These appear to represent a stage of embryonal development (on account of the partial striation) . They are absent in man and in the lower vertebrates. Blood-vessels occtir in the auriculo-ventricular valves in considerable number only where there are muscle-fibers. In children delicate vessels extend to the free margin of the valve. The semilunar valves are devoid of blood-vessels except under pathological conditions. A network of lymphatics extends from the endo- cardium to the middle of the valves. Weiglii and Size of the Heart. — According to W. Miiller, the weight of the heart in children and in older persons having a body- weight tip to 40 kilos, is 5 grams for every kilo of body-weight; in individuals having a body-weight of from 50 to 90 kilos, the proportion is 4 grams of heart for each kilo; in individuals having a body-weight of 100 kilos, 3.5 grams of heart for each kilo of body-weight. The auricles become stronger with increasing age. The right ventricle weighs half as much as the left. In man the heart weighs 30Q grams; in woman, 274 grams. Blosfeld and Dieberg found the heart in man to weigh 346 grams; in woman, from 310 to 340 grams. The thickness of the left ventricle in man aver- ages II. 4 mm.; in woman, 10.15 I'nm.; the thickness of the right ventricle, 4.1 and 3.6 mm. respectively. THE CORONARY VESSELS. 93 THE CORONARY VESSELS; AUTOMATIC REGULATION, NUTRI- TION, AND ISOLATION OF THE HEART. With reference to the origin of the coronary arteries the question at once arises whetlier the orifices of these vessels are closed by the eleva- tion of the semilunar valves during systole as a result of the application of the valve-leaflets to the walls of the vessels or whether such occlusion does not take place. Anatomical. — The two coronary arteries arise from the region of the sinus of Valsalva. The point of origin varies: (i) It is either within the concavity of the sinus; or (2) the mouths of the vessels are not completely within the range of the margin of the valve, and this is frequently the case with the left coronary of man and the ox; or (3) the orifices project beyond the margins of the val\-e (this is rare). These findings alone make it improbable that closure of the mouths of the coronary arteries by the semilunar valves during ventricular systole is a constant physiological phenomenon. AUTOMATIC REGULATION OF THE HEART. According to Brticke the openings of the coronary arteries are covered by the semilunar valves during systole, so that they can be filled only during diastole. The advantage of this arrangement resides in the fact that (a) the diastolic distention of the ventricular vessels stretches the muscular fibers of the ventricular wall and thus corre- spondingly dilates the ventricle for the reception of the blood that pours in from the auricle during diastole. (6) On the other hand, the systolic distention of the coronary arteries would be useless because the dilatation of the ventricular wall (due to the distention of the arteries already mentioned) would resist the systolic contraction, and because the systolic distention of the coronary arteries and the expulsion of the blood from them would tmnecessarily diminish the power of the ventricle. Accordingly, the diastolic distention of the coronary arteries would be most consistent with the mechanical conditions present. This mechanism Brticke has designated the "auto- matic regulation of the heart." Fig. 24. — Semilunar Valves, Closed. Semilunar Valves, Opened. This theory and its underlying principles are untenable, for — 1. The filling tinder high pressure of the coronary arteries of a dead heart not only is followed by no dilatation, but actually causes a contraction of the cavity of the ventricle. 2. The chief branches of the coronary arteries lie in the sulci of the heart embedded in the loose subpericardial fatty tissue, where their dilatation and con- traction could scarcelv have any effect upon the size of the cavities of the heart. 3 . Brown-Sequard found in animals and v. Ziemssen in a woman with a large deficiency in the wall of the left thorax that the coronary pulse was synchronous with that in the pulmonary artery. Newell-Martin and Sedgwick, by introducing manometers into the coronarv and carotid arteries of a large dog, obtained simul- 94 AUTOMATIC REGULATIOX OF THE HEART. taneous pulsatory elevations. In accordance with these observations is the fact that an incised coronary artery spurts continuously, with sj'stolic exacerbations, as do all other arteries. 4. If a strong stream of water is passed intermittently through a sufficiently large tube introduced into the left auricle of a fresh pig's-heart, and it is forced through the auriculo-ventricular orifice on into the aorta ; and if the aorta beyond its arch is connected with a large tube directed upward (in order to establish pressure in the aorta), the water will be seen to spurt continuously from the divided coronarj^ artery, with systolic exacerbations. 5. There is constantly present in the sinuses of Valsalva an amount of blood sufficient to fill the arteries in question during systole. 6. The valves when elevated are not applied closely against the wall of the aorta, even with the greatest amount of pressure that can be exerted by the ventricle. On the contrary, there remains between each valve-leaflet and the aortic wall a semilunar space filled with blood, as is shown in Fig. 24. 7. Undoubted cases of extensive destruction of the semilunar valves that with certainty render closure of the mouths of the coronary arteries impossible are directly opposed to this theory. 8. Observations on muscle have shown that during contraction its small vessels vmdergo dilatation and the blood-stream through it is accelerated. It is. therefore, difficult to believe that in the contracted heart-muscle the movement of the blood should cease. As, during the systole, the small arterial branches lying close to the ventricular cavity are exposed to a pressure greater than that of the aorta a systolic compression of their lumen occurs, with a forcing out of their contents in the direction of the veins. The ventricular con- traction thus aids the flow of the blood in the coronary vessels ; marked dilatation of the heart diminishes it. The capillary vessels of the myocardium are numerous in correspond- ence with the energetic activity of the heart; they, like the small vessels generally, lie within the muscle-bundles in contact with the muscle- cells. With their transition into veins several of them coalesce almost at once to form a large vein, from which the extremely easy passage of the blood into the veins is readily understood. The veins are provided with valves. As a result it happens that (i) with the s3'stole of the right auricle (therefore during the ventricular diastole) the venous stream is interrupted; (2) with contraction of the ventricle the flow of blood in the cardiac veins is accelerated in the same way as it is in the veins of the muscles. This systolic acceleration of the venous flow permits of the conclusion that the arterial circulation is not interrupted at this time. The coronary arteries, between which no anastomoses occur, are characterized by the great thickness of their elastic and connective-tissue intima, and this per- haps explains the frequency of calcification in these vessels. Man}' of the lower vertebrates have no vessels in the heart-substance (anangiotic hearts) — for example, the frog; but this statement is disputed. The motor disturbances and even the complete cessation of action that have been observed in the heart after partial or complete occlu- sion of the coronary vessels are of importance, particularh' as analogous conditions are observed in man in consequence of occlusion or narrowing of the coronary arteries (for example, as a result of calcification). Meihod. — In rabbits, under the influence of curare and with artificial respira- tion, or after previous section of the vagi (in order to exclude the inhibitory influence of this nerve), it is possible to clamp oft" the coronary arteries close to their origin froin the aorta with a spring clamp. Ligation is less satisfactory, as it cannot be accomplished without wounding the heart. In dogs it is possible to push a glass rod provided with a button-like extremity from the subclavian AUTOMATIC REGULATION OF THE HEART. 95 artery into the mouth of a coronfiry artery. Injections of various substances capable of causing occlusion have also been tried. In 1867, V. Bezold noted in rabbits after clamping off the coronary artery that the heart-beat grew rapidly smaller and smaller; then the contractions occurred in groups, periodically; later on the regular movement of the ventricle ceased entirely, and in its place the muscle- wall exhibited a peculiar fibrillary contraction; finally the heart stood still. As the circulation was reestablished after removal of the clamp, the phenomena appeared in reverse order until the heart regained its normal beat. If in a dog the right descending coronary artery and the circumflex artery, together with the artery of the septum, are occluded, the heart soon ceases to beat. The closure of only two of the three arteries caused a cessation of contraction in 9 out of 14 animals; while closure of the septal artery or of the right coronary artery alone had no effect. In almost all instances the auricles likewise cease beating. The heart of a dog that has once ceased to beat recovers only with great difficulty. It appears that the fibrillary contractions are due to irritative injury in- flicted during the operation, and not alone to the stasis of the blood. If in rabbits only the left coronary artery is occluded the beat of the left heart is slowed and weakened, while the right heart pulsates without change. As a result it occurs that the left half of the heart can no longer empty itself completely, so that particularly the left auricle becomes filled to distention with blood, while at the same time the unaffected right heart continues to drive blood into the lungs. In consequence edema of the lungs develops as a result of the high pressure in the lesser circulation which is transmitted from the right heart through the pulmonary vessels into the left auricle. According to Sig. Mayer persistent dyspnea has a similar effect, with earlier weakening of the left than of the right ventricle; the pulmonar}^ edema preceding death can be explained in this manner. The heart in the higher animals can maintain its activity only when the circulation of blood through its walls is maintained. The heart from which the blood is completely removed rapidly ceases to con- tract. The coronary circulation must convey the necessary oxygen and nutritive materials to the myocardium, as well as remove the metabolic products from it. The excised "isolated" mammalian heart, which is fed at body-heat through the coronary vessels with bright-red blood, remains active. Langendorft" maintains the circulation in the isolated heart by allowing the coronary arteries to be filled from the aorta. Other fluids, for example, lake- colored blood or serum, are incapable of maintaining the heart's activity. At most, such sokitions (as, for example, alkaline salt-solution mixed with egg-albu- min— 1000 albumin diluted with water, o.i sodium chlorid, o.i calcium chlorid, 0.075 potassium chlorid), in so far as they exert a slightly irritating effect, are capable of stimulating the heart for a time. If the heart is placed in pure oxygen the pulsation may be maintained for a considerable time by passing serum through the cardiac vessels. Also the isolated frog's heart can be included in a circulation by means of suitable tubes. To maintain its contractions oxygen and nutritive fluid are necessary to distend its cavities. This object is best fulfilled by arterial blood; indifferent fluids (0.6 per cent, sodium chlorid) quickly bring about a condition of "apparent death," from which, however, the organ can be revived by nutritive fluids. 96 THE MOVEMENTS OF THE HEART. The frost's heart is less readily exhausted than that of the higher vertebrates.. Serum-albumin, alkaline salt-solutions of blood, or of milk, made slightly viscid with allnnnin or gum aralaic and saturate.d with oxygen, arc capaljlc of main- taining the activity of the heart for a long time. Pathological. — In the presence of so-called sclerosis of the coronary arteries in old age there occur acute or chronic attacks of cardiac disability. Weakness of the heart, alterations in rhythm and freqviency (to 8 in a minute), constitute, together with dyspnea, syncope, stasis, attacks of pulmonary edema, the most characteristic phenomena; and they may terminate in death from so-called heart- faikire. In a case of occlusion of the left coronary artery in a man Hammer saw the pulse fall from So to 8, the beats being interrupted by spasmodic vibra- tion. THE MOVEMENTS OF THE HEART. VARIATIONS IN TONE. MctJiod. — In addition to direct observation, the kinematograph may be used to great advantage for recording and projecting the movements of the heart, par-- ticularly at a slow rate. D.a.-S.v. Fig. 25. — Diagrammatic Representation of the Auricular Systole with Ventricular Diastole, and of Auricular ■ Diastole with Ventricular Systole. The movement of the heart is appreciable as alternate contraction and relaxation of the heart-walls. The entire motor phenomenon designated the cardiac cycle consists of three parts: contraction of the auricles {auricular systole) ; contraction of the ventricles {ven- tricular systole), and the pause, during which the auricles and the ven- tricles are relaxed {diastole). During the contraction of the auricles the ventricles are at rest, during the contraction of the ventricles the auricles are relaxed. The following phenomena can be noted successively during a cycle of the heart : (A) The blood streams into the auricles, which in consequence are distended. The cause for this resides in: THE MOVEMENTS OF THE HEART. 97 1. The pressure of the blood in the venae cavae (on the right) and the pulmonary veins (on the left), which is greater than the pressure within the auricles. 2. The elastic traction of the lungs, which after the completed con- traction tends to separate the relaxed yielding walls of the auricles lying in contact with each other. The auricular appendages are distended coincidently with the auricles. The appendages serve in a measure as reservoirs for the auricles, to accommodate the large amount of blood flowing in from the veins. (B) The Attricles Contract. — There occur in rapid sequence: 1. The contraction and evacuation of the auricular appendages in the direction of the auricle. Simultaneously, the entering veins are con- stricted by the contraction of their circular muscular layers, especially the superior vena cava and the site of entrance for the pulmonary veins. 2. The walls of the auricles contract rapidly in a wave-like manner from above downward, particularly toward the auriculo- ventricular orifices, in consequence of which — 3. The blood is forced downward into the relaxed ventricles, which now become considerably dilated. As a result of the auricular con- traction there occur: (a) A slight stasis of the blood in the large venous trunks, such as can be readily observed particularly in rabbits on exposure of the point of junction of the jugular and subclavian veins after division of the muscles of the chest. There is no actual reflux of the blood, but only a slight stasis due to partial interruption of the flow into the auricle, because, as has been stated, the sites of entrance for the veins are nar- rowed; because, further, the pressure in the superior vena cava and in the pulmonary veins soon counteracts the tendency to regurgitation;, and, finally, because in the further ramifications of the inferior and to some extent also of the superior cava and of the cardiac veins, valves prevent the refiux. In the blood thus stagnated in the vense cavae the movement of the heart causes a regular pulsating phenome- non that, when abnormally increased, may give rise to the appearance of a venous pulse. (6) The principal motor effect of the auricular contraction is the distention of the relaxed ventricles, which in small measure are dilated by the elastic traction of the lungs. Earlier and later investigators have attributed the distention of the ven- tricles in part to the elasticity of the muscular walls. It has been thought that the strongly contracted ventricular walls, like a compressed rubber bulb, in re- turning to their resting normal shape, through their own elasticity, aspirate the blood with negative pressure. Such suction-power on the part of the ventricle is, however, effective only in slight degree, if at all. (c) With the distention of the ventricles the auriculo-ventricular valves at once float upward (Fig. 26), being in part forced up by the counter-stroke of the blood from the wall of the ventricle; in part they are capable, by reason of their lower specific gravity, to spread out and float horizontally; in part, finally, they are drawn upward by the longi- tudinal muscular fibers passing from the auricles upon the valves. (C) The ventricles now contract and the auricles relax. In this phase — I. The muscular walls contract on all sides and reduce the size of the ventricular cavity. 7 98 THE MOVEMENTS OF THE HEART. ■2. At the same time the blood presses against the under surface 'of the auriculo-ventricular valves, the inverted margins of which interdigitate and become hermetically applied to one another (Fig. 26). The valve-leaflets are prevented from being forced back into the auricular cavity, because the tendinous cords hold their under surface and margins firmly like an inflated sail. The approximation of the edges of adjacent valves is favored further by the circumstance that the tendinous fibers always pass from one papillary muscle to the edges of two opposed valves. To the extent that the lower ven- FlG. 26. — Plaster Cast of the Ventricles of the Human Heart, Viewed from Behind and Above. The walls are removed, only the fibrous rings and the auriculo-ventricular valves being retained: L, left; R, right ventricle; ■S, situation of the septum; F, left fibrous ring, with closed mitral valve; D, right fibrous ring, with closed tri- cuspid valve; A, aorta, with the left (ci) and the right (c) coronary artery; 5, sinus of Valsalva; F, pul- monary arterj-. tricular wall approaches the valves during contraction and thus might render possible a bulging backward of the valves into the auricle, com- pensation is provided by the shortening of the papillary muscles and of the large muscle-containing tendinous cords themselves. The valves when closed present an approximately horizontal surface. There re- mains, therefore, in the ventricles, even at the height of contraction, always a remnant of blood, the so-called residual blood. 3. When the pressure in the ventricle exceeds that in the arterial PATHOLOGICAL DISTURBANCE OF FUNCTION OF HEART. 99 vessels, the semilunar valves are opened, become stretched like tendon above their concave sinuses (Fig. 24), without becoming applied to the arterial wall, and allow the blood to enter. Goltz and Gaule found, by meims of maximal and minimal manometers, a negative pressure in the ventricles during a certain phase of the heart's con- traction amounting in the dog to — 23.5 mm. of mercury in the left ventricle. They suspected that this phase coincided with the diastolic dilatation and for which they thus assumed a considerable power of aspiration. Moens is of the opinion that this negative prcssvire prevails in the ventricle shortly before the systole has reached its maximum. He explains the aspiration as being produced by the formation of a vacuum in the ventricle, which must develop as a result of the active movement of the blood, through the aorta and the pulmonary arterv, behind the circulating mass of blood, therefore in the ventricle. Gaule and Mink believe that the systolic enlargement of the aorta must at the same time cause a dilatation of the conus arteriosus of the left ventricle. (D) After the ventricular contraction has attained its height and relaxation has commenced, the semilunar valves close with an audible sound (Fig. 27). The diastole of the ventricle is followed by the pause. Under normal conditions the two halves of the heart contract and relax simultaneously and uniformly. The heart-muscle exhibits in its activity certain variations in tone, that is, it does not with every systole contract from the same degree of relaxation to the same degree of contraction, but, rather, there follow in rhythmical periods series of contractions that arise from a considerable degree of relaxation of the heart-muscle, alternating with series of contractions that begin in a less com- plete degree of relaxation. With the latter the degree of contraction is greater than with the former. These variations in tone have been found especially in the auricle of the tortoise-heart. When the arterial blood- pressure is moderately increased, the heart expels a larger amount of blood; if, however, the arterial pressure is greatly increased, the amount of blood expelled at each systole becomes less. Extracts of testicle, suprarenal gland, pituitary gland and spleen in 0.7 per cent, sodium-chlorid solution added to blood exert a tonic effect upon the heart; the extent of the contractions increases and the beats become more regular. Under the influence of alcohol the heart Fig. 27.— The Closed Pulmonary exhibits a marked degree of relaxation and a low Semilunar Valves of Man, degree of contraction. The influence of various poi- ^'^"^^"^ ^■""'^ ^^'°^- sons is variable. Heat increases the variations in tone. Whether the relaxation of the heart-muscle is an active dilatation or not has been decided in the affirmative by some investigators. Stimulation of the vagus (likewise digitalis and strychnin) is said to increase the active dilatation; while section of the vagus (likewise atropin) is said to diminish it. PATHOLOGICAL DISTURBANCE OF THE FUNCTION OF THE HEART. All obstructions to the blood-flow through the different portions of the heart or of the vessels connecting them give rise to a permanent increase in the work of that portion of the heart especially concerned with relation to the affected section of the circulation, and in consequence to an increase in the thickness of the muscular walls, with dilatation of the cavity. Should the resistance affect not alone one section of the heart, but consecutively other parts further on in the course of the blood-stream, these also will undergo secondary hypertrophy. If, in addition to increasing the muscle-substance of the aft'ected portion of the heart, its cavity is at the same time dilated, as is often the case, the condition is designated excentric hj^pertroph}'', or hypertrophy with dilatation. The obstructions under consideration in the domain of the vascular channels are : constriction (stenosis) of the arterial or venous orifices and likewise defective lOO THE APEX-BEAT. THE CARDIOGRAM. closure (insuiriciency) of the valves. The latter causes resistance to the blood- flow by permitting regurgitation of a portion of the blood already propelled onward. In this way there results: 1. Hypertrophy of the left ventricle from hindrances to the blood-flow in the territory of the greater circulation, chiefly in the arteries and capillaries, not in the veins. In this category belongs stenosis of the aortic orifice and of the aorta further on; also calcification and loss of elasticity in the large arteries, irregular dilatations of the arterial walls (aneurysm) ; insufficiency of the aortic valves, as a result of which the left ventricle is continually subject to the aortic pressure; finally, afl^ections of the kidney, in consequence of which a greater arterial pressure is required in order that the urine may be excreted. In the presence of mitral regurgitation also, hypertrophy of the left ventricle is necessary for compensation, and a similar enlargement occurs in the left auricle in conse- quence of the heightened pressure in the lesser circulation. 2. Hypertrophy of the left auricle results from mitral stenosis and from mitral regurgitation, and also consecutively to aortic regurgitation because the auricle must overcome the uninterrupted aortic pressure that is present in the left ventricle. 3. Hypertrophy of the right ventricle results from (a) hindrances to the blood-flow in the territory of the lesser circulation. These are: (a) atrophy of vascu- lar areas of considerable size in the lungs in consequence of destrtiction, contrac- tion or compression of the lungs and from loss of numerous capillaries in emphysematous lungs. (/?) Ovcrdistention of the lesser circulation with blood in conseqvience of stenosis of the mitral orifice or of insufficiency of the mitral valve; also consecutively to hypertrophy of the left auricle resulting from aortic regur- gitation, (b) Hypertrophy of the right ventricle must occur also in conjunction with instifficiency of the pulmonary valves, which permits the blood to regurgi- tate into the ventricle, so that the pressure of the pvilmonary artery prevails continually in the cavity. This condition is exceedingly rare. 4. Hypertrophy of the right auricle develops consecutively to the condition last mentioned, likewise in association with stenosis of the right auriculo-ventricu- lar orifice, or from insufficiency of the tricuspid valve. This condition is un- common. When several obstructions in the circulation occur together there is a combination of the resulting phenomena. O. Rosenbach has investigated the manner and method by which the heart maintains its activity after the occur- rence of valvular lesions. If the aortic valves were perforated, with or without simultaneous injury to the mitral and tricuspid valves, the heart performed first an increase of work, which counteracted the physical defects, so that the blood- pressure did not fall. The heart, therefore, possesses reserve powers, which are brought into play only when they are required. In consequence of the valvular insufficiency dilatation first develops as a result of the regurgitation of blood into the affected chamber of the heart. Then follows hypertrophy, but until this is completed the compensation must be effected by the reserve power. Under the conditions that especially render diastole difficult there should yet be mentioned: large effusions into the pericardial sac or pressure on the heart from tumors. The systole is greatly interfered with by adhesions between the heart and the connective tissue of the mediastinum. Under such circumstances the surrounding tissues, even the thoracic wall, must be drawn upon with each con- traction of the heart, so that systolic retraction and diastolic projection occur in the situation of the apex-beat. THE APEX-BEAT. THE CARDIOGRAM. By the term apex-beat (ictus s. impulsus cordis) is understood the visible and palpable elevation of a circumscribed area of the fifth (less commonly the fourth) left intercostal space, caused by the action of the heart. At times the apex-beat is less distinct, especially when the heart strikes against the fifth rib itself. Changes in the position of the body alter somewhat the situation and the force of the apex-beat. A graphic representation of this movement can be obtained by means of a registering apparatus — the apex-beat tracing or the cardiogram. Method. — To obtain a tracing of the apex-beat the cardiograph of Marey may be employed. The instrument has been modified by various investigators. The THE APEX-BEAT. THE CARDIOGRAM. lOI pansphy.e;mograph of Brondgcest is essentially the same as Marey's apparatus, with unimi)i)rtant changes. Marey's sphygmograj^h can also be used. In animals the cardiogram can be "registered by ligating the tube of the pansphygmograph in the pericardium. In the normal tracing of the apex-beat of man (A) or of the dog (B) the following details are distinguishable: ab corresponds to the period of the pause and of the contraction of the auricles. As the auricles con- tract in the direction of the heart's axis from the right and above to the left and downward it is not surprising that the apex of the heart advances toward the intercostal space. In this portion of the tracing there can be seen generally two or even three slight elevations which may be due to the rapidly successive contractions of the venous endings, the auricular appendages, and the auricles themselves. Fig. 28. — ^A, Normal apex-beat tracing from man. B, from a dog; C, tracing of an accelerated apex-beat from a dog; D and E, normal apex-beat tracings from man recorded upon a \-ibrating tuning-fork plate. Each serration represents 0.01613 second of time. In all of the tracings a b indicates the auricular contraction, b c, the ventricular contraction; d, the closure of the aortic valves; e, the closure of the pulmonary valves; e f, relaxation of the ventricles. Naturally the last, occasionally distinct, elevation, occurring shortly before b (corresponding to B v and C v in Fig. 31), will be looked upon as th6 true auricular contraction; v. Ziemssen and Ter Gregorianz were able to register the elevation of the auricular appendix preceding the auricular contraction in a woman with an exposed heart. The line b c is caused by the ventricular contraction. It is this alone that is appreciable to the palpating finger as the apex-beat. The first sound of the heart commences with the beginning of the ventricular contraction. I02 THE APEX-BEAT. THE CARDIOGRAM. The cause of the ventricular impulse resides in the following factors: 1. The base of the heart (the junction of auricles and ventricles), which in diastole presents the form of a transverse ellipse (Fig. 29, I, F G), is contracted to a rather circular figure (a b). In this way, the large diameter of the ellipse (F G) is naturally diminished and the small diameter {d c) is increased, and in consequence the base is brought nearer to the chest-wall {e). This alone, however, does not produce the apex- beat, but the base of the heart, thus brought somewhat nearer the chest- wall, and hardened during systole, affords the apex the possibility of making the movement that constitutes the apex-beat. 2. The ventricles, which during the period of relaxation have their apex (Fig. 29, II, i) directed obliquely downward in the line of their long Fig. 29. — I. Horizontal Section through the Heart and the Lungs, Together with the Chest-walls, for the Demon- stration of the Change in the Shape of the Base of the Heart during the Contraction of the Ventricles: P G, transverse diameter of the ventricles during diastole; c, position of the anterior ventricular wall; a b, transverse diameter of the ventricles during systole with e, the position of the anterior ventricular wall during systole. II. Lateral View of the Position of the Heart: », the apex-beat during diastole; p, during systole (in part after C. Ludwig and Henke). diameter, so that the angles {b ci and a c i) formed by the junction of the ventricular axis with the diameter of the base are unequal, represent a symmetrical cone, with its axis perpendicular to its base. Accordingly, the apex (z) must be elevated from below and behind for- ward and upward (p) (W. Harvey: "Cor sese erigere"), and it thus thrusts itself, hardened during systole, into the intercostal space (Fig. 29, II). 3. During the systolic contraction the ventricles of the heart undergo a slight spiral rotation about their long axes ("lateraleminclinationem," W. Harvey), so that the apex is carried from behind slightly forward, THE APEX-BEAT. THE CARDIOGRAM. IO3 while at the same time a considerable area of the left ventricle is turned forward. This rotation is due to the fact that many of the fibers of the ventricular muscles that arise from the portion of the fibrous ring that is turned toward the chest-wall at the junction of the right auricle and ventricle pass obliquely from above and to the right downward and to the left, in part to the posterior aspect of the left ventricle. Thus, they draw the apex of the heart upward in the direction of their course, and its posterior aspect slightly toward the anterior wall of the thorax. This rotatory movement is favored by the circumstance that the aorta and the pulmonary artery, which are applied to each other in a slightly spiral manner, effect a rotation of the heart in the same direction at the time of systolic tension. According to an earlier opinion the cardiac impulse was held to be produced or at least increased by : 4. The recoil that the ventricles arc supposed to experience (like a dis- charged firearm) at the instant when the column of blood empties itself into the aorta and the pulmonary artery. The apex would, of course, be driven in the opposite direction by this recoil, that is, downward and a little outward. Landois, however, has pointed out that the blood-column is discharged into the vessels 0.08 second after the beginning of the ventricular contraction, while, on the other hand, the apex-beat begins simultaneously with the first sound. As, however, the apex-beat is observed in bloodless hearts taken from animals after death, and as the apex of the heart is not, as it would be on the theory of the recoil, displaced downward and to the left during systole, but upward and to the right (as has been confirmed by v. Ziemssen in a woman whose heart was exposed), the recoil cannot be regarded as a factor in the problem. After the ventricles by their systolic movement have traced the greatest part of the apex-beat curve, as far as its apex (c), the curve rapidly descends and the ventricles pass from a state of extreme con- traction to one of relaxation. Soon, however, two small elevations appear in the descending limb of the curve at d and e. These are due to the abrupt closure of the semilunar valves, which, being effected with a certain degree of force, is transmitted along the axis of the ventricles as far as the apex, and through the latter even causes concussion of the intercostal space; d corresponds to the closure of the aortic valves, e to that of the pulmonary valves. The valves, therefore, do not close at the same time, there being an interval of about from 0.05 to 0.09 second on the average. Owing to the greater pressure of the blood in the aorta the aortic valves close earlier than those of the pulmonary artery. While investigators are agreed that the first sound of the heart begins at the point b of the cardiogram, various statements have been made with regard to the point at which the registration of the second sound of the heart takes place. Martius designates the depression between c and d (Fig. 28, E) as the point that corresponds to the second heart-sound; Landois the apices d and e, when the tension of the semilunar valves is increased; Hurthle, Einthoven and Geluk 0.02 second after e; Marey and Fredericq about midway between e and f ; and, finally,. Edgren at a point immediately in front of f . Method. — In order to determine the time when the heart-sounds are heard, their vibrations are trans:nitted to a microphone attached to the thorax. The instrument, which is thrown into vibration by each sound of the heart, opens and closes an electric circuit with each vibration and thus attracts an electromagnet, or sets a capillary electrometer (Fig. 229) in motion. If by means of another contrivance the cardiogram is made to register at the same time, the points on the latter at which the heart-sounds are heard can be seen. From the point e to the foot of the curve (at f) comprises the time during which complete diastolic relaxation of the ventricles takes place. I04 TIME-RELATION'S OF THE MOVEMENTS OF THE HEART. THE TIME-RELATIONS OF THE MOVEMENTS OF THE HEART. Method. — The time-relations of the individual phases of the movements of the heart can be most rehably discerned in the curves of the apex-beat: When the distance traversed at a uniform rate in a unit of time is known for the registering surface, the time corresponding to each portion of the curve can be ascertained by direct measurement (as in the case of pulse-curves) . Landois determined the time by having the curves traced on a tablet vibrating on the arm of a large tuning-fork (Fig. 60) . The curve then contains in all of its segments small undulations due to the vibrations of the tuning-fork. In Fig. 28, D and E represent apex-beat curves of healthy students registered in this way (in D the elevation d is not distinct) . A complete vibration of the tuning-fork (from the apex of one vmdulation to that of the next) corresponds to 0.01613 second: by counting the number of undulations and multiplying by the factor the time is obtained. Although there is a certain regularity in the time of the individual phases of the movement, the readings nevertheless vary between Avide limits even in healthy individixals. The value of a b, which is equivalent to the pause plus the auricular •contraction, is subject to the widest variations and depends chiefly on the frequency of the pulse; for, the more rapidly the heart-beats follow one another, the shorter, naturally, will be the pause, until it finally disappears altogether. Even when the rate of the heart is slow, it is often impossible to distinguish in the curve the portion corresponding to the pause, which, owing to the gradual filling of the heart and the resulting slight bulging of the intercostal space, has a gently ascending form, from that due to the auricular contraction and appearing as a hillock. In one case in which the heart-beats were 55 in a minute, Landois found the pause to be 0.4 second and the auricular contrac- tion 0.177 second. In Fig. 28, A, the pause plus the auricular con- traction, when the heart beats 74 times in a minute, is found on measurement to be 0.5 second. In D the corresponding period a b is equivalent to from 19 to 20 vibrations, or 0.32 second; in E the period is equivalent to 26 vibrations, corresponding to 0.42 second. The ventricular systole is estimated from b, the beginning of the contraction, to e, the completed closure of the semilunar valves of the pulmonary artery. It, therefore, extends from the first to the second heart-sound. This period is also variable, though considerably more constant. When the action of the heart is accelerated, the period becomes less, when the action is slower the period increases; in E it is 0.32 second, in D 0.29 second; when the heart-beats were only 55 Lan- dois found it to be 0.34 second; but when the frequency is exceedingly great it declines to 0.199 second. Landois was able to ascertain the interesting fact that when the left ventricle is enormously hypertrophicd and dilated, the duration of the ventricular contrac- tion does not materially exceed the normal. That the ventricle contracts more slowly when the action of the heart is weakened is shown when the registering instrument is placed on the ventricle of an animal that has been killed, and the heart-beat is recorded. In Fig. 30, from the ventricle of a rabbit the slow heart-beats (B) are at the same time of longer ■duration. This affords an opportunity to determine accurately the length of the period to be allowed for the ventricular systole. Landois thought it wise, in order to avoid misunderstanding, to distinguish the following three separate factors: 1. The interval between the two heart-sounds, that is, from the beginning of the first to the end of the second sound (Fig. 28, b— e). 2. The time occupied by the blood in entering the aorta: This evidently ter- minates at the depression between c and d (Fig. 28, E) ; its beginning, however. TIMK-KF. l.ATIOXS OF THE MOVEMENTS OF THE HEART. IO5 does not coincide with 1), as from 0.085 to 0.073 '-'^ 0.06 second elajjscs between the bejjinning of the ventricular contraction and the opening of the semilunar valves of the aorta. According to this calculation the entrance of the blood into the aorta (aortic inflow) would occupy from 0.08 to o.oq second. Landois arrived at this result by the following calculation: The interval between the first sound of the heart and the ])ulse at the a.xillary artery is 0.137 second. The propagation of the pulse-wave along the distance from the root of the aorta to the axillary artery, which is equivalent to 30 centimeters, cannot occupy more than 0.052 second of this time (corresponding to the analogous velocity in the distance — 50 cm. — from the axillary to the radial artery = 0.087). Hence, the pulse-wave in the aorta cannot take place earlier than 0.137 niinus 0.052 = 0.085 second after the beginning of the first sound of the heart. Landois found in agreement with Hiirthle that in some cardiograms the point that inarks the beginning of the flow of blood into the arteries, or, what is the same thing, the time of the opening of the semilunar valves, is indicated in the ascending limb by a small interval between b and c. The current in the pulmonary artery is not interrupted until the point € is reached. 3. Finally, the tirne occupied by the muscular contraction of the ventricle may be considered. The contraction begins at b, reaches its greatest degree at c, and is not followed by complete relaxation until f is reached. The apex of the curve c may, however, be higher or lower, according as the intercostal space yields more or less; the position of c is, therefore, variable. The time that elapses between d and e, that is, between complete closure of the semilunar valves and of the pulmonary artery, is greater in proportion as the pressure within the aorta exceeds that within the Fig. 30. — Contraction-curves from the Ventricle of a Rabbit Registered on a Plate .Attached to a Vibrating Tuning- fork (one \-ibration = 0.01613 second): A, soon after death; B, taken while the ventricle was in process of dying. pulmonary artery, as the closure of the valves is effected by the pres- sure from above. This interval may vary from 0.05 second to more than twice that length of time ; in the latter event the second sound of the heart is also duplicated. If, however, the tension in the aortic system diminishes and the pressure in the pulmonary artery rises, the interval between d and e may be diminished to such a degree that the two coincide at one point in the curve. The time occupied by the ventricles in relaxing (e f ) after closure of the pulmonary valves is also subject to a certain degree of variation; in healthy adults the average may be given as o.i second. When the action of the heart is greatly accelerated, the time occupied by the pause is the first to become shortened, as Bonders and Landois have found; then the time occupied by the auricular and ventricular systole also is shortened, in lesser degree, though quite distinctly. With the highest degree of pulse-frequency the beginning of the auricular systole coincides with the closure of the arterial valves of the preceding heart-beat, a phenomenon that is strikingly illustrated in the tracing from a dog (Fig. 28, C). As during the registration of apex-beat curves the heart is separated from the registering instrument by the soft parts of the intercostal space, which vary in thickness and in resistance and cannot in every case follow the movements of the • heart with entire ease, it cannot be expected that the various portions of the curve shall coincide with mathematical accuracy with the corresponding phases of the heart's movements. io6 TIME-RELATIOXS OF THE MOVEMENTS OF THE HEART. Gibson had the opportunity of taking cardiograms from a case of fissure of the sternum in a man, and obtained the following time-values: Auricular contrac- tion (a b) =0.115, ventricular contraction (b d) = 0.28, interval between the closure of the valves (d e) = 0.09, ventricular diastole (e f) = o.ii, pause = 0.45 second. In large mammals (horses) Marey and Chauveau, in 186 1, by a most thorough method obtained records of the phases of the movements of the heart in the following manner: Long catheter-like tubes, provided at their lower ex- tremity with a closed and compressible rubber bulb, were connected by means of a flexible piece of tubing attached to the other end with the registering drum of the cardiograph (Fig. 44, KS). It is evident that with ever\' compression of the Aorta. Apex of the Heart. Fig. 31. — Curves Showing the Movements of the Separate Portions of the Heart (Chauveau and Marey). rubber bulb the stylus connected with the registering drum of the instrument will be elevated. Fig. 31 shows a number of curves: In making A the rubber bulb was in the right auricle, having been introduced through the jugtilar vein and the superior vena cava; in making B the bulb was introduced into the right ventricle through the tricuspid orifice; in making D it was introduced through the carotid as far as the root of the aorta; in making C, through the semilunar valves of the aorta into the left ventricle; and, finally, in making E the bulb was applied extemallv to the apex of the heart between this and the inner aspect of the chest-wall. In all of the curves v indicates the auricular contraction, V the ventricular contrac- tion, s the closure of the semilunar valves (which occurred earlier in B than in C) , and P the pause. As the recording surface moves at a uniform rate and the PATHOLOGICAL VARIATION'S IN THE HEART-BEAT. 107 scale for the distance covered in each second is given, the individual periods of time can be incasured. It seems probable, however, that the introduction of the tubes into the heart is not without influence on the regular, undisturbed course of its activity. In order to determine the conditions present coincidently with the pressure in the ventricle and in the aorta in the dog, Hurthle employed his blood-pressure recorders (Fig. 67), which were connected by means of tubes with the interior of the ventricle and of the aorta. A cardiogram was taken at the same time. The vertical lines o, i, 2, 3 indicate conditions identical in time in the three curves. The point o corresponds with the beginning of the ventricular contraction and the first sound of the heart; while the entrance of the blood into the aorta occurs after an interval, namely at the point i. The points 2 and 3, according to Hurthle, indicate the closure of the semilunar valves (second sound of the heart). Fred- ericq obtained similar results by means of other experiments. One point remains to be cleared up, namely, whether the auricle and the ventricle work in exact alternation, in such a way that the auricle relaxes at the instant when the ventricle begins to contract, or whether the ventricle begins to Cardiogram. Aorta. Time-Recorder. Ventricle. Fig. 32. — ^Simultaneous Record Showing Cardiogram, the Curve of the Ventricular Pressure and that of the Aortic Pressure, from the Dog. Each division of the time-curve = o.oi second (K. Hurthle). contract while the auricle still remains contracted for a short time, so that for a short period of time at least the entire heart is contracted. Heart-beat curves taken from human subjects appear to show that the ventricular contraction begins as the auricular contraction ends; v. Ziemssen and Ter Gregorianz, who made curves directly from the auricle of the exposed heart of a woman, are likewise in accord with the view that the auricular contraction continues for a time while the ventricles are beginning to contract; and also Heigl, on the strength of a similar observation. A. Fick, who believes that the contractions alternate, considers this alternation as a means for maintaining the pressure in the large venous trunks approximately constant. As the auricle relaxes at the instant when the ventricular systole begins, there is no impediment to the flow of venous blood into the auricle; whereas if the auricular contraction were to persist, the blood would be dammed back. As, fiirther, the auricle contracts at the instant of ventricular relaxation, there will be no abnormal pressure in the veins. In this way the pressure within the auricle may remain more uniform and the blood-stream in the ends of the veins more constant. PATHOLOGICAL VARIATIONS IN THE HEART-BEAT. The position of the heart-beat is altered: (i) By the accumulation of fluid (serum, pus or blood) or of gases in one pletxral cavity. Copious effusions into the pleural cavity, which at the same time compress the lung and force it upward, may displace the heart as far as the right nipple. Effusions into the right pleura cause displacement of the heart to the left. As the right heart is forced Io8 PATHOLOGICAL VARL\TIOXS IX THE HEART-BEAT. to greater exertion in order to propel the blood through the compressed lung, the apex-beat under such circumstances is usually accentuated. Marked disten- tion of the lungs (emphysema), which depresses the diaphragm, also causes down- ward and inward displacement of the apex-beat. Conversely, elevation of the diaphragm, as a result of contraction of the lungs or of pressure by the abdominal organs, has the effect of displacing the apex-beat upward — sometimes as far as the third intercostal space — and a little to the left. Thickening of the muscular wall of the heart with dilatation of the cavities (hypertrophy and dilatation) , when it affects the left ventricle, causes an increase in the length and breadth of the chamber, and the accentuated apex-beat becomes palpable to the left of the nipple-line, sometimes in the axillar\' line in the sixth, seventh, or even eighth intercostal space. Hypertrophy and dilatation of the right ventricle cause an increase in the width of the heart: the apex-beat is felt further to the right, sometimes even to the right of the sternum, but at the same time also a certain distance beyond the left nipple-line. In the rare cases of transposition of the viscera, in which the heart is situated in the right half of the thorax . the apex-beat is of course found in exactly the corresponding situation on the right side of the thorax. Landois was the first to take an apex-beat curve from a heart of this kind and found that it presented all of the normal features. When the heart-beat extends to the left beyond the nipple-line or to the right beyond the parasternal line, the area of cardiac impulse is enlarged transversely, a condition that always indicates hypertrophy of the heart. When this transverse enlargement is unusu- ally great, the apex-beat may extend over several intercostal spaces or over both sides of the thorax. The apex-beat appears abnormally weak in association with atrophy and degeneration of the heart-muscle, or when the innervation of the controlling nerves is impaired. The cardiac impulse may be weakened or even completely obliterated also when the heart is forced away from the chest-wall by an accumulation of fluid or of gas in the pericardium, by a greatlv distended left lung, or by an effusion into the left pleural cavity. The same condition results either when the left ventricle is imperfectly filled during contraction (in consequence of marked stenosis of the mitral orifice) or when, owing to extreme narrowing of the aortic orifice, it can empty itself but gradually and slowly. An increase of the apex-beat is observed in the presence of hypertrophy of the walls of the heart, as well as in association with the most diverse irritative conditions (psychic, inflammatory, febrile, toxic) affecting the heart and its con- trolling nerves. Extreme hypertrophy of the left ventricle causes a heaving apex- beat, so that a portion of the chest-wall is elevated, with systolic concussion. In some cases the apex-beat is quite distinct or even abnormally distinct, while the pulse is quite small. This phenomenon is due to insufficient emptying of the ventricles (spurious contraction of the heart) . Systolic retraction is not infrequently observed on the anterior chest-wall in the third and fourth intercostal spaces on the left side under normal conditions, especially when the action of the heart is accentuated and when there is excentric hypertrophy of the ventricles. As the apex is somewhat displaced with each ventricular contraction and the ventricles at the same time diminish in size, the yielding soft parts of the intercostal space are drawn in to fill the vacuum thus formed. When the heart is adherent to the pericardium and the surrounding connective tissue, movement of the heart during systole becomes impossible and the apex-beat is replaced bv systolic retraction of the apical area. Under such circumstances the chest -wall bulges during diastole, in a measure representing a kind of diastolic apex-beat. The changes in the apex-beat that occur in as.sociation with functional dis- orders of the heart are best studied by tracing apex-beat curves, as has been done b}'^ a number of clinicians since Landois first published his method in 1876. In the curve shown in Fig. 33, P, in reduced size and obtained from a case of marked hypertrophy and dilatation of the left ventricle, the ventricular contrac- tion as a rule is exceedingly large (b c) . although the time occupied in contraction by the greatly increased muscular mass of the ventricular wall is not materially longer than tinder normal conditions. The curves P and Q were obtained frorn a man with a high grade of excentric hypertrophy of the left ventricle, resulting from instifficiency of the semilunar valves of the aorta. The curve O was taken purposely at a point near the epis;astrium where systolic retraction was present. Although the position of the individual portions of the curve is changed, the individital phases of the heart's action are nevertheless well shown. PATHOLOGICAL VARIATIONS IN THE HEART-BKAT. lOQ' Fig. E represents the apex-beat in a case of stenosis of the aortic orifice. The auricular contraction (a b) is quite brief, the ventricular contraction is visibly prolonged and after a short rise (b c) exhibits a series of indentations (c e) caused by the mass of blood forcing its way through the stenotic and roughened entrance to the aorta. Fig. F represents the aj)ex-beat in a case of insufficiency of the mitral valve; a b is well marked in consequence of the increased activity of the left ventricle; the shock (d) caused by the closure of the aortic valves is slight on account of the diminished tension in the arterial system. On the other hand, the shock of the accentuated pulmonic second sound (e) stands like a huge accent high upon the summit of the curve. In conserjuence of the tension in the pulmonary artery Fig. 33- — Various Forms of Pathological Apex-beat Curves. In all of these curves a b indicates the auricular contraction; b c, the ventricular contraction; d, the close of the aortic semilunar valves; e, that of the pul- monary valves; e f, the time occupied by the rela.xation of the ventricles. the pulmonary second sound may be so accentuated and it may follow so quickly- after the second aortic sound (d) that the two almost or quite coincide (H and K). The curve in a case of stenosis of the left auriculo-ventricular orifice (G) presents first of all a long, irregular, indented auricular contraction (a b), due to the fact that the blood is forced through the narrow orifice \yith considerable agitation and friction. The ventricular contraction (b c) is feeble on account of the imperfect filling of the left chamber. The closures of the two valves d and e are separated by a comparatively long interval and the ear distinctly hears a duplicated second heart-sound. The aortic valves close rapidly because the aorta receives only a small amount of blood, while the more abundant flow of blood into the pulmonary artery causes retarded closure of the pulmonary valves. When the heart-beats are rapid and weak and the tension in the aorta and the pulmonary artery is low, the signs of closure of the valves in the latter no THE HEART-SOUNDS. may be entirely obliterated, as in curve L taken from a girl with exophthalmic goiter who suflfered from nervous palpitation of the heart. In rare cases of mitral insufliciency — a condition in which the right ventricle is greatly overfilled with blood, while the left contains but little, so that the right has to work harder to empty itself than does the left — a peculiar action of the heart has been observed, both ventricles appearing at times to contract together and then again the right ventricle alone (Fig. M after Malbranc). Curve I, which appears in every respect like a normal apex-beat curve, was taken when the entire heart was active; there was present an arterial pulse corresponding to this apex- beat. Curve II. on the other hand, appears to have been recorded by the right heart alone, and it accordingly lacks the closure of the aortic valves (d) ; nor was there an arterial pulse corresponding to this contraction. With respect to the cases just considered Landois expressed the opinion as early as 1S79 that the phenomenon could not be explained on the mere supposition that the right ventricle alone is active during the phases in question, without any parallel action on the part of the left. He regarded such a condition as impossible, if for no other reason because of the common arrangement of the muscles in the two ventricles and their equally common innervation. The period of apparent rest of the left ventricle is probably no more than a period of exceedingly feeble action, not strong enough to record itself in the apex-beat curve by the closure of the aortic valves and by a pulse in the arteries. This supposition has in fact been confirmed by Riegel and Lachmann, Eger, Eichhorst, Stem, H. E. Hering. and others. THE HEART-SOUNDS. On listening over the region of the heart, either directly with the ear applied to the thorax, or with the aid of the stethoscope, or in ani- mals to the exposed heart, two sounds are audible that really do not deserve the name of tones, but which in contradistinction from pathologi- cal heart-murmurs are designated heart-sounds. As they possess a cer- tain tonal color, it has been possible to determine their musical pitch. The first sound of the heart is somewhat duller, longer, and lower in pitch by a third or fourth, fluctuating between d sharp and g, not clearly defined, especially at the beginning, and synchronous with the ventricular systole. The second sound of the heart is clearer, more valvular, shorter, and therefore more distinctly marked, varying between f sharp and b fiat, clearly defined, and synchronous with the closure of the semilunar valves. The first sound is separated from the second by a short interval, and the second sound from the succeeding first sound by a longer interval. In musical parlance the first sound appears as a rising beat to the second, which is then followed b}' the pause. The vibration-values and the rhythm may accordingly be expressed as follows : V V Bu - tup (lub-dup) Bu - tup (lub-dup) The first sound is caused by two factors. As it is heard, though faintly, in excised hearts in which the auriculo-ventricular valves are prevented from being stretched and relaxed, and as it is heard also when the movement and closure of the valves are prevented by means of a finger introduced into the auriculo-ventricular orifice, the principal cause of the sound is to be sought in the muscular murmur, produced by the contracting muscular fibers of the ventricles. THE HEART-SOUN'DS. Ill The sound is augmented and reinforced by the tension and vibra- tions of the auriculo-ventricular valves and their tendinous bands at the instant of ventricular contraction. Wintrich, in 1873, succeeded by the use of suitable resonators in dis- tinguishing one sound from the other; the clearer and shorter valvular sound from the deeper and more protracted muscular tone. Fig. 34. — Topography of the Thorax and of the Thoracic \'iscera: a. d., right auricle; o. s., left auricle; v. d., right ventricle; I, left ventricle \vith Ii apex of the heart; A, aorta; II, pulmonary artery; C, superior vena cava; L L, boundaries of the lungs; P P, boundaries of the parietal pleura (v. Luschka and v. Dusch). Under pathological conditions, such as typhoid fever and fatty heart, in which the heart-muscle is greatly enfeebled, the first sound of the heart may be inaudible. In the presence of insufficiency of the aortic valves, when, owing to the regurgita- tion of the blood from the aorta into the ventricle, the mitral valve is made tense gradually and before the ventricular systole begins, the first sound of the heart is also not infrequently absent. Both of these pathological instances prove that the cooperation of muscle-tone and valve-tone is required for the production of the first sound of the heart and that when one of these elements is lost the heart- sound may become inaudible. It should further be mentioned that the vibra- tions of the semilunar valves before or during their closure and the vibrations of the fluid elements of the blood itself have been adduced as contributory factors in the explanation of the first sound of the heart. 112 ABNORMALITIES OF THE HEART-BEAT. The cause of the second sound of the heart, according to the gener- ally accepted view, is the abrupt closure of the semilunar valves. It is, therefore, said to be chiefly a valvular sound. It is, however, in part due also to a sudden concussion of the fluid particles in the large arterial vessels. Landois has shown from apex-beat curves taken from healthy in- dividuals that the semilunar valves of the aorta and those of the pul- monary artery do not close at the same time. As a rule, however, the difference in time is so slight that the two sets of valves generate only one sound. On the other hand, if, owing to increase of the difference in pressure in the aorta and in the pulmonary artery, this interval be- comes greater, a duplication or splitting of the second sound may become quite perceptible. This may occur in perfectly healthy individuals, especially at the end of inspiration or at the beginning of expiration. It is important to remember, however, that although the second sound corresponds with the closure of the semilunar valves, it appears proved that the closure itself gives rise to no sound ; it is only an instant later,, when the tension of the valves becomes greater, that the second sound becomes audible. It is generally believed that the points on the chest-wall at which the heart - sounds are heard inost distinctly on auscultation correspond to the points in the neighborhood of which they are produced. The first valvular sound produced at the right auriculo-ventricular orifice is heard most distinctly at the junction of the fifth rib with the sternum on the right side, and is transinitted from that point somewhat inward and obliquely upward along the sternum (Fig. 34, i). As the left auriculo-ventricular orifice is directed more posteriorly, toward the interior of the thorax, and is covered in front by the arterial orifices, the first mitral valvular sound is heard best at the apex or immediately above it, where a strip of the left auricle is in immediate contact with the chest-wall (Ij, I). As the orifices of the aorta and pulmonary artery are so close together, it is advisable to listen for the aortic second heart- sound in the prolongation of the axis of the aorta, that is, at the right border of the sternum, at the inner extremity of the right costal cartilage (at 2). The pulmonic second heart-sound is heard most distinctly in the second left intercostal space a little to the left and beyond the edge of the sternum (at II). The aortic second sound is clearer, sharper, and shorter, and is heard over a larger area than the pulmonic second sound. To determine the intensity of the heart-sounds quantitatively H. Vierordt inserts between the chest-wall and the ear a series of solid rubber plugs, which are poor conductors of sound, placed one upon the other in the form of a column. ABNORMALITIES IN THE HEART-BEAT. Accentuation of the first sound of the heart in both ventricles indicates a more powerful contraction of the ventricular muscle and a consequent, sudden, and increased tension of the auriculo-ventricular valves. Accentuation of the second sound is a sign of increased tension in the interior of the corresponding large vessels. Hence accentuation of the pulmonic second sound, which is svxch an important diagnostic sign, always indicates hyperemia and excessive tension in the lesser circulation. Feeble heart-sounds are caused by sluggish, weakened heart-action or abnormal ischemia; they are observed particularly^ in cases of morbid degeneration of the heart-muscle. The cause of weakness of individual heart-sounds can be deduced from the foregoing explanation. The term emhryocardia is used when the two sounds of the heart are exactly alike with respect to strength and the intervals between heart-beats, resembling the ticking of a clock; the phenomenon indicates weakening of the heart-muscle. Irregularities in the structure of individual valves may render the heart- sounds impure by causing irregular vibrations. When pathological cavities filled with air are present in the immediate neighborhood of the heart, they may act as. DURATION OF THE MOVEMENT OF THE HEART. 113 resonators and reinforce the heart-sounds, so that the latter often assume a metalHc, ringing character. Both the first and the second heart-sound may be dupUcated or split. Duplication of the first sound of the heart is explained by failure of the tricuspid and mitral valves to contract at the same time. Some- times a sound may be heard that is caused by the contraction of a well-developed auricle and precedes the first sound like a presystolic murmur. As the closure of the aortic valves does not coincide exactly with that of the pulmonary valves, duplication or splitting of the second sound merely represents an exaggeration of physiological conditions. All factors that cause acceleration in the closure of the aortic valves — such as ischemia of the left ventricle — and retardation in the closure of the pulmonary valves — such as the presence of an excessive quantity of blood in the right ventricle, and both factors together when there is stenosis of the left auriculo- ventricular orifice — favor duplication of the second sound. When the valves of the heart are the seat of irregularities in association with either stenosis or insufficiency, throwing the blood-stream into eddies or oscilla- tions or producing friction, the heart-sounds are replaced by murmurs, that is, sounds produced by the fluids and always associated with circulatory disturb- ances and the valvular changes referred to. It is rare for deposits and new-growths projecting into the ventricle to give rise to murmurs in the absence of valvular lesions or circulatory disturbances. Heart-murmurs are always associated with the systole or diastole. As a rule, systolic murmurs are louder and more accentu- ated than diastolic. Sometimes they are so loud that even the thorax is thrown into vibration — purring tremor. Diastolic murmurs always depend on structural changes in the mechanism of the heart, such as insutFiciency of the arterial valves or stenosis of the venous orifices (usually on the left side only). Systolic murmurs are not always due to disturbances of the cardiac mechanism. In the left heart systolic murmurs may be caused by insufficiency of the mitral valve, stenosis at the aortic orifice and by calcification or abnormal dilatation affecting the ascending aorta. Systolic murmurs in the right heart, which are much more rare, are due to insufficiency of the tricuspid valve or stenosis at the pulmonary' orifice. Systolic murmurs are often present, although never so loud, in cases without any valvular lesion, being caused by abnormal vibration of the valves or of the walls of the arteries. They are heard most frequently at the pulmonary orifice, next at the mitral, and more rarely at the aortic and tricuspid orifices. Anemia and acute febrile affections are the causes of these murmurs. Heart-murmurs are sometimes produced by the friction of opposed roughened surfaces of the inflamed pericardium (friction-mtirmurs) . The friction-sound may be both audible and palpable. DURATION OF THE MOVEMENT OF THE HEART. The excised heart continues to beat independently for a time: in cold-blooded animals for a long period, even for days, in warm- blooded animals for a much shorter time. The last vestige of cardiac action has, however, been observed in the rabbit after 15^ hours, in the mouse after 46^ hours, in the dog after 96^ hours, and in a three-m^onths- old human embryo after 4 hours. The contraction of the excised heart may be reinforced and accelerated by irritation. The contraction of the ventricle first becomes enfeebled, and it is further observed that the contraction of the auricle is not always followed by a ventricular systole, two or more auricular contractions being succeeded by only one feebler ventricular movement. The contractions of the ventricles, in addition to being more infrequent, require a longer time for their completion, and give the impression of being labored and sluggish (Fig. 30). Later, the ventricles cease to contract altogether and only the auricles continue to beat feebly. Direct irritation of the ventricles, however, as by a prick, is followed by a single contraction. Still later the left auricle ceases while the right auricle continues to beat, and it is the right auricular appendage that continues to beat the longest, being accord- ingly known to the ancients as "ultimum moriens." The same obser- 114 THE CARDIAC NERVES. vation has been made in executed criminals. In the opened heart the papillary muscles fail to contract synchronously with the auricular wall after from two to three minutes. Engelmann made the interesting observation that the muscles of the auricle may lose their power of contracting, in response to irritation of the vagus or as a result of immer- sion and swelling in- water, without losing the power of conducting stimuli. An analogous phenomenon has been observed with respect to the nerves. After the heart has ceased beating altogether, it can be temporarily roused by direct stimulation, especially by heat; and again the auricles and auricular appendages are the last to react. As a rule, when the heart has been temporarily stimulated to greater activity it ceases to beat the earlier; before the orderly succession of beats ceases altogether tremu- lous, "undulating" movement of the muscle-bundles usually takes place. In mammals, when the irritability of the heart has ceased, it can be temporarily restored by injecting arterial blood into the coronary vessels. In the frog the heart, which at first becomes rigid, may be revived by filling its cavities with fresh blood. As the heart uses up oxygen and eliminates carbon dioxid, it is quite conceivable that it should beat longer in oxygen than in nitrogen, hydrogen, carbon dioxid, hydrogen sulphid or in a vacuum, even when, to avoid desiccation, aqueous vapor is generated in the vacuum. When the heart, after it has ceased to beat, is returned to a medium containing oxygen, it begins to beat again. THE CARDIAC NERVES. The cardiac plexus is formed by : i . The cardiac branches of the trunk of the vagus nerve ; these include cardiac branches from the external branch of the supe- rior laryngeal nerve, the inferior laryngeal nerve, and sometimes the pulmonary branches of the vagus, in larger number on the right than on the left side. 2. The superior, middle, inferior, and lowest cardiac branches from the three cervical ganglia and the first thoracic ganglion of the sympathetic nerve, which frequently vary in number and in size (sometimes one of the branches ' accompanies the descending branch of the hypoglossus for a part of its course). The branches of the plexus are the deep and the superficial nerves; the latter usually contain a ganglion at the bifurcation of the pulmonary artery beneath the arch of the aorta. The following structvires are regarded as belonging to the cardiac plexus: (a) The right and left coronary plexuses, which convejr the vasomotor nerves of the coronary vessels through the vagus portion and the dilators through the sympathetic; and in addition contain sensoiy fibers derived from the vagus and passing principally to the pericardium. In patients suffering from disease of the heart the presence of sensory nerves is indicated by the occurrence of constant or paroxysmal pain. In the frog, reflex phenomena may be induced from the ventricle in the various portions of the heart, and they probably have their reflex center in the medulla oblongata. (b) The nerves embedded in the heart-muscle and in the furrows, which are richl}^ supplied with ganglia and which have been designated the automatic motor centers of the heart. The heart contains a circle of nerves richly supplied with ganglia at the edge of the interauricular septum and another at the junction of the auricles and the ventricles. Wherever the two meet they exchange fibers. The ganglia are for the most part found near the pericardium. In mammals the two larger ganglia are situated close to the orifice of the superior vena cava; in birds the largest node of nerve-tissue, containing thousands of ganglia, occupies the posterior point of decussation of the longitudinal and transverse sulci. These nodes of nerve-tissue send smaller branches into the muscular walls of the auricles and ventricles, and these branches in turn are the seat of smaller ganglia. In the frog a large collection of ganglia, Remak's ganglion, is situated, together with the vagus fibers, within the wall of the sinus of the vena cava (the dilated orifice of the venae cavag in the right auricle whose independent movement pre- IRRITABILITY OF THE AUTOMATIC MOTOR CEXTERS. II 5 cedes that of the auricles). From this gangHon the vagus fibers pass as the anterior and posterior septal nerves, each of which is provided with a ganghon at the auriculo-ventricular junction, the ventricular ganglion, or Bidder's ganglion. The nerve-libers, which are for the most part non-medullated, can be traced further in connection with the ganglia. The motor libers terminate with slightly clubbed extremities in each muscle- cell; the sensory, which are derived from meduUated libers, in flat, expanded terminal plexuses, which are quite abundant in the endocardium and the peri- cardium. All ganglion-cells are bipolar or multipolar. In the frog most of them are surrounded by a network of fibers; in Bidder's ganglion spindle-shaped cells with two processes, one at each extremity, predominate. In the rabbit and in the frog the ganglion-cells belonging to the sympathetic system have two nuclei, while the vagus ganglia have only one. After division of the vagus branches (in the frog) the spiral process and the pericellular network from which it originates undergo degeneration. The straight process gives off the muscle-nerves. The bulb of the aorta contains numerous nerves for its muscle-fibers; but whether it contains ganglia also is doubtful. IRRITABILITY OF THE AUTOMATIC MOTOR CENTERS IN THE HEART AND IN THE HEART-MUSCLE. There are at the present time only two theories with regard to the irritability of the heart and its spontaneous rhythmic action. 1. The older theory teaches that the "automatic centers" that excite the movements and maintain an orderly rhythm are situated within the heart and that this function resides in the ganglia. 2. It is assumed that not one but several such centers are present in the heart and are connected with one another by conducting paths. So long as the heart is intact the various centers are stimulated to rhythmic activity in a definite order from the principal center, the impulse being conveyed through the conducting paths from that center. The forces that excite these regular continuous movements are not known. If, however, diffuse stimuli, of -which the simplest is a strong electrical current, are applied to the heart, all of the centers are thrown into action and a spasmodic contraction of the heart takes place without any rhythm of movement. The dominating center is situated in the auri- cles (in the frog), whence, therefore, the regular progressive movements usually proceed. When its irritability is reduced, as by applying opium to the septum with a cotton pledget, a different set of centers appears to gain control, and the movement may then be propagated from the ventricles to the auricles. 3. The nerve-centers of the auricles are more irritable than those of the ventricles; hence they continue to beat independently for a longer time when the heart is left to itself. 4. All stimuli of moderate strength acting directly on the heart cause primarily an increase in the rhythmic heart-beats; stronger stimuli cause, in a short while, diminution progressing to paralysis, often pre- ceded by spasmodic tremulous "undulation or flickering." Increased activity on the part of the heart exhausts its strength the more rapidly. 5. Individual weak stimuli, such as are insufficient to exert any effect on the heart, may be rendered efficient by repetition, as the heart is capable of summation of the individual stimuli. 6. Even the feeblest stimuli that are at all capable of exciting a contraction always excite an active contraction, that is, "the minimal stimulus has a maximal effect." Il6 IRRITABILITY OF THE AUTOMATIC MOTOR CENTERS. 7. Each contraction of the heart is followed by a short period during which the heart is less susceptible to subsequent stimuli (Marey's re- fractory period) and the conducting-power of the muscle-substance is reduced. 8. Stimulation of the heart-centers, apparently reflex, takes place on the inner surface of the heart. Feeble stimuli from this surface are more effective in accelerating and exciting the action of the heart than stimuli from the external surface of the heart. Stronger stimuli, which cause arrest of the heart, also act more readily from the internal than from the external surface of the heart; under such conditions also the ventricular portion is always first to be paralyzed. 9. Portions of the heart that are devoid of ganglia are incapable of independent movement unless a stimulus be applied ; they contract only once to a single direct stimulus, or they may beat rhythmically if the stimuli are applied continuousl3\ Such a stimulus may be provided by the continuous pressure of fluid within the cavities of the heart or by means of chemical agents brought in contact with the heart. ID. The pulsations of stimulated portions of the heart devoid of ganglia indicate that the ganglia are not absolutely necessary for the production of rhythmic contractions; but the ganglia are more irritable than the muscle itself. They control also the regular alternating action of the various portions of the heart, so that normal cardiac action must be regarded as under the control of the ganglia. II. If the heart be cut in such a way that the individual pieces remain in communication, the regular contractions beginning in the auricles and propagated in peristaltic or undulating movements to the ventricles persist for some time. When, however, the heart is completely divided into two pieces, auricle and ventricle, the movements of both continue separately — naturally, no longer in orderly succession, but quite independently. The principal experiments on which the foregoing propositions are based are as follows: Experimental Division and Ligation of the Heart. — These experiments have been performed chiefly on frogs' hearts. Ligation differs from division in the fact that the physiological connection is destroyed by drawing a hgature tightly around the parts and loosening it again, while the anatomical continuity of the heart-wall and the integrity of the cavities of the heart are maintained. I. Stanniiis' Experiment. — After separation in a frog's heart of the sinus of the vense cavse from the auricle, either by incision or by constriction, the heart is arrested in diastole, while the sinus continues to beat independently. If the heart be again divided at the atiriculo-ventricular junction, the ventricle, as a rule, begins at once to beat again, while the auricles continue in diastolic arrest. In accordance with the position of the second line of division the auricles may continue to beat in association with the ventricles, or the auricles alone may contract, while the ventricles remain at rest. The experiment has been interpreted in the following manner: The sinus of the venas cavae contains Remak's ganglion, which is remarkable for its extreme irritability, while Bidder's ganglion, which is situated at the auriculo- ventricular junction, possesses a lesser degree of irritability. In the normal heart the latter receives its motor impulses from the former. When the sinus of the vense cavEe is severed, the stimulating Remak's ganglion is without any influence on the heart. The latter becomes arrested for two reasons: because Bidder's gangUon by itself does not possess sufficient power to set the heart in motion, and because the division stimulates the inhibitory nerves of the heart (vagus) , which are situated at this point. Pulsation can, however, be induced in a heart that has been ar- rested in this way by irritation of Bidder's ganglion, as by gently pricking the auriculo- ventricular junction, or by the passage of a moderately strong constant IRRITABILITY OF THE AUTOMATIC MOTOR CEXTERS. II7 current. In the latter event the ventricular heat sometimes pr.ecedes that of the auricles. If, now, the auriculo-ventricular junction be divicled, the ventricle begins to pulsate, partly because the ]:)r( >cetlurc stimulates Bidder's ganglion, and partly because the heart is no longer under the influence of the vagus, which had been stimulated by the first division. If the division at the auriculo-ventricular junction is made in such a way as to leave Bidder's ganglion in the auricle, the latter would pulsate and the ventricle remain at rest; if the ganglion is divided into two halves, both the auricles and the ventricles pulsate, because each is stimulated by its own half of the ganglion. 2. When the ventricle alone is divided in the frog's heart by ligature or in- cision at the auriculo-ventricular furrow, the sinus and the auricles continue to beat undisturbed, while the ventricle is arrested in diastole; the ventricle responds to a local irritant with a single contraction. If the incision is made in such a way as to leave the lower edge of the interauricular septum attached to the ventricle, the latter also continues to pulsate. In the case of the rabbit's heart, also, the ventricles continue to pulsate if a small strip of the auricles is preserved, separated from the auricular nerves. 3. Experiments performed by A. Fick in 1874 first showed that the irritative process in the contractile tissue of the frog's heart is propagated in all directions and that the entire frog's heart acts in a measure like a single continuous muscle- fiber. Thus, for example, a transverse incision, involving the ventricle of the frog's heart, does not prevent the appended flap from taking part in the systolic contraction. This is shown also by the following experiments of Engelmann. If the heart is cut into strips, as by zigzag incisions, in such a manner that the individual pieces remain in connection with one another by means of muscle- substance, the strips pulsate in regular succession, in whatever way they may be connected with one another, as a result of the direction of the incisions. The velocity of propagation, under such circumstances, is from ten to thirty millimeters in the second. These experiments also confirm the observation that the continuous stimulus that propagates the contraction is not conducted by nerve-paths but by the substance of the contractile mass. 4. When the apex of the heart has been separated from the rest of the organ by a ligature it ceases to take part in the contraction of the heart, which continues to pulsate; a direct stimulus, such as a stab of the apex, is followed by only a single contraction. If the heart is filled with saline solution under pressure (both of which act as stimuli), the apex will continue to pulsate. The same thing is observed after poisoning with delphinin or quinin. If a cannula is tied in the ventricle from a point above the auriculo-ventricular junction to the apex, the latter is likewise arrested; if, however, the apical portion is filled through this cannula with oxygenated blood under steady pressure, the apex will pulsate. The excised apex of the heart resting spontaneously, when stimulated by induction-currents, responds to the weakest efficient stimulation by a maximal contraction; but the application of tetanizing currents is not followed by true tetanus. Closing and opening the constant current applied to the severed apex give rise only to the ordinary closing and opening contractions. 5. When the point of ligation is within the auricles, the pulsations of the heart occur in successive periods (group-formation) , and the contractions often increase in strength by regular gradations (stair-case ascent) . 6. When the bulb of the aorta, which is devoid of ganglia, is isolated by con- striction (frog), it continues to pulsate when the internal pressure is moderate; after it has ceased beating, a single stimulus will give rise to a series of renewed contractions. The number of contractions is increased by raising the temperature to 35° C. and by increasing the internal pressure. 7. The isolated venae cavse and their sinuses exhibit normal contractions. If they are still connected with the heart the}- will control the movements of the heart, that is, contraction of the entire heart may be induced from the position of each of the large veins and the rhythm of the heart may be thus influenced. Conduction takes place only through the muscle-substance and not through the nerves. Porter maintains with regard to the hearts of the dog and the cat that any part of the heart that is excised may continue to pulsate if only it be suffi- cienth' nourished. , In opposition to the doctrine that has just been expounded, namely that the stimulating influence is sent out by the cardiac ganglia, it may be observed that this theory has recently begun to wayer. In view of the Il8 DIRECT STIMULATION OF THE HEART. fact that the embryonal heart, in which it has been impossible to dem- onstrate the presence of ganglia, pulsates like the heart of certain inverte- brates, some recent investigators assert that the automatism of the cardiac action resides in the muscle itself. Similarly, His, Jr., and Romberg, on developmental grounds, teach that the ganglia belong really to the sensory nerves of the heart, and that, therefore, there are no automatic nerve-centers at all. When Krehl and Romberg isolated portions of the rabbit's heart devoid of ganglia by crushing, but in such a way that, so long as the circulation was maintained, they represented anatomical portions of the heart, they found that these pieces continued to pulsate for hours. It is said that even excision of the entire septum of the frog's heart, including Remak's ganglion, has no disturbing effect on the heart-beat. The propagation of the contraction from the auricles to the ventricles is said to take place through the muscle-fibers that pass from the former to the latter. That the conduction of the stimuli from auricle to ven- tricle, which does not take place continuously, but periodically in the same rhythm as the heart-beats, is not transmitted through the nerve- paths is' proved by the slow rate at which it is effected, the conduction being 300 times slower than in motor nerves. Engelmann expresses his views upon these questions as follows: The muscle-cells of the heart itself and not a system of nerve-ganglia constitute the excito-motor central organ; as such they generate the motor stimuli that cause the heart to beat. As those muscle-cells that surround the large veins emptying into the heart are most susceptible to the irritating influence of automatic move- ment, the systolic contraction occurs first at this point, to spread then in a peris- taltic manner successively to the auricles, the ventricles, and the bulb of the aorta. The motor stimulus is propagated directly from muscle-cell to muscle-cell. All of the muscle-cells of the entire heart form together a single physiologically conducting contractile mass. Within each individual portion of the heart — venous trunks, venous sinuses, auricles, ventricles, bulb of the aorta— the motor stiraulus is propagated rapidly, in a manner comparable to the contraction of a striated muscle. Those muscle-cells, on the other hand, that form the connecting bridges between the individual portions of the heart conduct slowly, in a manner comparable to tinstriated or embrv-onal muscles. Consequently every individual portion of the heart contracts practically at the same time as a whole; while, on the other hand, the svstole of each portion of the heart situated farther on in the course of the blood-stream can take place only after an actual interval, long enough for the blood to be carried from one part of the heart into the next. As the fibers of the heart-muscle, in the act of contraction, temporarily lose their contractility and conducting power, as a sort of fatigue-phenomenon, they contain within themselves the periodicity of contraction and relaxation — systole and dias- tole. A cvcle of the entire heart may be induced from any point in the large veins. When the cardiac stimuli succeed one another slowly, each individual car- diac cycle becomes shorter, but more powerful. The blood is then propelled in larger quantities and with greater force; while if the succession is more rapid, less blood is propelled with a lesser degree of force. Direct Stimulation of the Heart. — All direct cardiac stimuli act much more vigorously from the internal than from the external surface of the heart. When the stimulation is severe or protracted, the ventricular portion is always paralyzed first. (a) Thermic Stimuli. — Descartes had already observed m 1644 that the eel's heart could be made to pulsate more rapidly by the application of heat. Alex. v. Humboldt explained the acceleration of the pulse that takes place in man in a hot medium in the same way. As the temperature continues to rise, the heart- beats at first often reach a considerable frequency. They then becom.e more infrequent again, and finally cease altogether, and the muscle is found to be con- tracted. As a rule, the ventricular portion is arrested before the aviricles, some- times after a period of tetanic undulatory spasm. At a temperature of 25° C. and above, the ligated frog's heart immersed in a 0.6 per cent, saline solution, MECIIAXICAL STIMULI. ELECTRICAL STIMULI. II9 soon becomes arrested, and continues at rest if kept at this temperature. Up to 38° C. Landois has seen it recover if removed quickly. The inner surface of the heart reacts much more readily to all degrees of temperature than the external surface. If the heart, after having been arrested, is removed from the warm bath, it begins to beat rapidly after a pause, which may be interrupted by one or two beats, the frequency gradually diminishing until the normal rate is attained. If the ventricle alone is heated, the frequency of pulsation is not increased. The volume and the extent of the cardiac contractions increase up to a tem- perature of about 20° C. and beyond that point they begin to diminish again. The functional power increases between 8° and ;i^° C; but the frequency increases more than the eflicicncy of the pulsations. The duration of the contraction at 20° C. is only about one-tenth of what it is at 5° C. The heated heart reacts to rapidly intermittent stimuli, the cold heart only when the intervals are of consid- erable length. The mammalian heart ceases to beat at from 44.5° to 45° C. As the heat of the blood diminishes, the heart pulsates more slowly. When a frog's heart is placed on ice between two watch-glasses, its rate diminishes considerably; between 4° C. and 0° C. the pulsations of the frog's heart cease. When a frog's heart is suddenly removed froin warm water and placed on ice, the beat is accelerated; conversely, when it is transferred from ice to warm water, the beat is at first slowed and only after a time accelerated. (6) Mcchantcnl Stimuli. — Pressure applied to the outside of the heart causes an acceleration of the cardiac action. In man also light pressure applied to the auriculo-ventricular junction of an exposed heart gave rise to a secondary shorter contraction of both ventricles following each heart-beat. Heavy pressure causes an irregular, undulatory contraction of the muscle, such as may be produced by compressing the excised heart of a warm-blooded animal between the fingers. Increase of the blood-pressure in the interior of the heart effects a similar accelera- tion, and decrease of the pressure a corresponding diminution in the number of heart-beats. When the intracardiac pressure is excessive, the overstimulation results in irregularity or even slowing of the heart-beat. A resting heart that is still irritable will react by a single contraction to a mechanical impulse (prick). (c) Electrical Stimuli. — A moderately strong constant current passing continu- ously through the heart produces an increase in its rate. Ziemssen succeeded in accelerating the beat of an exposed heart two-fold or three-fold by passing a strong galvanic current uninterruptedly through the ventricles. Exceedingly strong constant currents, as well as tetanizing faradic currents, produce tetanic undulatory contractions of the heart-muscle, with lowering of the blood-pressure. If the ventricle of the frog's heart has been permanently relaxed by being clamped at the auriculo-ventricular junction, and one electrode of a constant current is applied to the ventricular wall, and the other to any portion of the trunk, systolic contraction of the ventricle takes place when the current is closed only if the kathode is .placed in contact with the ventricle; conversely when the current is opened only if the anode is in contact with the heart-wall. The feeblest faradic currents accelerate the heart-beat; stronger currents produce irregularities, which may go on to fibrillation. A single induction-impulse applied to the ventricle in systolic contraction has no effect either in the frog or in the mammal. W'hen. however, it is applied to the ventricle in diastolic relaxation, the succeeding systole takes place earlier. The auricles and the apex of the heart, which is devoid of ganglia, but may be excited to activitv by suitable stimulation, react in the same way. During their systole an induction-impulse is ineffective, but in diastolic rest the impulse gives rise to a contraction, which is followed by a ventricular contraction. Even strong tetan- izing induction-currents applied to the heart are unable to produce tetanus of the entire musculature. There develop between the electrodes localized, white, cylin- drical elevations, as in the muscles of the intestines, which may persist for several minutes. After severe and continued tetanization the undulaton^ contractions outlast the stimulus. Also the isolated apex of warm-blooded animals may exhibit this undulatorv contraction only so long as the stimulus lasts. The heart of a previously Avarmed frog, as well as the isolated apex, reacts to electric stimuli by flickering' The fibrillating or flickering rabbit's heart often returns spontaneously to its normal contractions, the dog's heart with greater difficulty. After the contractions of the frog's heart have become weak and irregular, they can be made regular and isochronous with the rhythm of the stimulus by means of elec- tric stirnuli applied in rhythmical succession. The feeblest stimuli that are at all efficient act as well in this connection as the strongest; even with the weakest I20 CHEMICAL STIMULI. Stimulus the contraction of the heart is the most vigorous possible. Hence, this minimal electrical heart -stimulus is as effective as a maximal stimulus. V. Ziemssen was unable even with strong induction-currents to cause a variation in the rate of the beat of the exposed human heart. The ventricular diastole alone appeared to be no longer complete, and in addition certain minor irregularities were observed in the contractions. By opening and closing or by reversing a strong constant current applied to the heart of a woman, it was possible to increase the number of heart-beats, and the increased number of pulsations cor- responded with the number of the electrical impulses. For example, from a normal of So the number of heart -beats was raised to from 120 to 140 to 180 by the application of from 120 to 140 to iSo electrical impulses. Conversely, it was possible also to reduce the normal nvunber of pulsations from 80 to 60 or 50 by applying an equal number of powerfvil stimuli. In the healthy subject also v. Ziemssen found that he covdd influence the rh\thm and the strength of the heart by applying an electrical current through the chest-wall. (d) Chemical Sthmili.—'Many chemical agents, particularly when applied in a state of dilution to the inner surface of the heart, increase the number of pvdsa- tions, but when applied in concentrated form or when allowed to act for some time diminish the nvmiber or paralyze the heart. Bile and bilian.- salts diminish the number of heart -beats, as does also absorption of the bile into the blood. In dilute solution, however, both accelerate the action of the heart. The same effect is produced by acetic, tartaric, citric and phosphoric acids. Chloroform and ether when applied to the inner surface of the heart have a distinctly retarding or even paralyzing effect; in small amoimts ether accelerates the heart-beats. Opium, strychnin, alcohol, and chloral hydrate have an analogous action. Klug caused blood impregnated with various gases to pass through the frog's heart and found that sulphurous acid, chlorin-gas. nitrous-oxid gas. hydrogen sulphid and carbon monoxid acted as heart-poisons. In the same way. blood saturated with carbon dioxid exhausts the heart, which, however, may recover if the carbon dioxid escapes. A deficiency of oxygen produces a grouped rhx-thm, in the same way as the phenomena of asph\-xiation manifest themselves in the respiratory apparatus in grouped movements. Rossbach foiind that local irritation of a circumscribed area of the frog's ventricle by means of mechanical, chemical, or electrical stimuli dviring contraction causes immediate relaxation in partial diastole of the part to which the stimulus is applied. The immediate after-effect of this form of irritation is a permanent shrinking of the irritated portion of the heart-fibers, and this is Ukewise strictlv confined to the area of irritation. The shrunken portion ceases to functionate and remains permanently robbed of its vital properties. If the same stimuH are applied during diastole, the irritated pori:ion relaxes earlier than the portion that has not been irritated, and the diastole of the irritated portion lasts longer than that of the non-irritated portion. If the weakest stimtdi are allowed to act for a considerable length of time on any part of the frog's ventricle, the irritated portion always relaxes earlier than the non-irritated, and the diastole of the irritated portion lasts longer than that of the non-irritated. Heart-poisons comprise such substances as have a special effect in diminishing or abolishing the movements of the heart. In this respect the neutral salts of potassium are most remarkable. In small doses they accelerate the heart-beat. YeUow potassium ferrocyanid. when injected into a frog's heart, will cause systolic arrest of the ventricles, even when greatly diluted. If blood subsequentlv enters the ventricle as the result of the contraction of the auricle, the ventricle maj'^ again take part in the contraction. Under such conditions, the ventricular muscles sometimes relax in areas after first undergoing reddening. The contraction of the ventricle, which is exceedingly sluggish, later travels from the auriculo-ventricular junction in a peristaltic wave to the apex. The Javanese arrow-poison, antiar, causes systolic arrest of the ventricles, with diastolic arrest of the auricles; mus- carin causes diastolic arrest of the heart, which can be overcome by means of atropin. Some of the heart -poisons in small doses cause slowing and in larger doses not infrequently acceleration of the heart -beat: digitahs Cand the toxic substances of oleander and the ma\^ower, which are similar to it 1 . morphin. and nicotin. Others in small doses cause acceleration and in large doses slowing: veratrin. aconitin. camphor. THE CARDIOPXEUMATIC MOVEMEXT. 121 THE CARDIOPNEUMATIC MOVEMENT. As the heart during systole occupies a smaller space in the interior of the thorax than during diastole, air must enter the thorax as the heart contracts if the glottis is open. When, however, the heart relaxes in diastole, air must escape through the open glottis as the heart enlarges. A similar influence must be due to differences in the degree of fulness of the intrathoracic vascular trunks. This cardiopneumatic movement is, in animals in which during hibernation the respiratory movements are suspended, of the greatest importance for the maintenance of metabolism, which continues in moderate degree. The interchange of carbon and oxygen in the lungs is greatly facilitated by agitation of the pulmonary gases, and this interchange suffices to aerate the blood passing slowly through the lungs. Method. — The movement may be demonstrated by means of; 1. The manometric flame, the trachea of a curarized animal being opened and connected with a bifurcated tube, one branch of which leads to the gas-tubing and the other to a small gas-flame. As in this manner a free communication is established between the organ of respiration and the gas-supply, the mov^ements of the heart will be transmitted to the gas-flame. In inan it is possible, after a little practice, to transmit the movement in an analogous manner to the gas- flame through one nostril after closure of the other nostril and the mouth, or through the mouth after closure of the two nostrils. 2. By acoustic means, namely by introducing an exceedingly sensitive whistle constructed from a hollow sphere, in animals into the trachea divided transversely, in man — especially when the heart's action is stimulated — into the mouth, after closure of the nose, it is possible to demonstrate the cardiopneumatic movement, particularly if the whistle is blown continuously and with extreme softness. 3. By means of the cardiopneumograph (Fig. 35). This consists of a tube, which is "held between the lips (D), while respiration is suspended, the glottis is opened and the nostrils are closed. The extremity of the tube, which is bent upward, perforates a small plate (T) , over which a delicate membrane consisting of a mixture of collodion and castor-oil is stretched with moderate force. From the center of the membrane a glass thread (H) passes over the free edge of the plate and is provided at its extremity with a delicate hair, which registers the movements of the membrane on a tablet (S) moved by clocWork. Every ex- piratorv movement of air causes depression and every inspiratory movement elevation of the recording point. Attached to the side of the tube is a valve with a sufficiently large opening (K) and which may be opened to allow the indi- vidual to breathe'freelv during a pause. The periodic movements of the respiratory gases propelled b}^ the heart-beat cause associated movements in the delicate collodion membrane, and these are in turn transmitted to the recording lever. The graphic curve (Fig. 35, A and B) exhibits the following details: 1. The respiratory gases undergo a sudden expiratory movement coincidently with the first sound of the heart because at the instant of the ventricular systole the blood from the ventricles has not yet left the thorax, while venous blood is pouring into the right auricle through the vense cavae, and because in the same instant of svstole the dilating branches of the pulmonan,^ artery must cause approximately the same quantity of air to escape from the nearest air-passages in the lungs. ' In fact, the blood contained in the right auricle does not leave the thorax at all; it is onlv transferred to the lesser circulation. This expiratory movement would often be greater if it were not limited by two factors, namely: (a) because the muscular mass of the ventricle occupies a somewhat srnaller vol- ume during contraction, and (6) because the thoracic cavity in the region of the fifth intercostal space is somewhat enlarged outwardly by the apex-beat. 2. There follows immediatelv a marked inspiratory movement of the respira- torv gases, in consequence of which the large ascending limb of the curve is re- corded. As soon as the blood-wave has advanced from the root of the aorta to those portions of the large arteries that He at the boundaries of the thoracic cavitv, a much larger quantity of arterial blood begins to leave this cavity, because venous blood is at the same" time being poured into it through the venae cavae. 122 IXFLUEXCE OF RESPIRATORY PRESSURE OX THE HEART. This inspirator^' movement would also be larger were it not for a slight diminution in the volume of the oral and nasal cavities, attended with an expiratory rnove- ment that takes place at the same time on account of the filling of its arteries — oral pulse, nasal pulse. 3. After the second sound of the heart (at 2), which at times causes a slight depression at the apex of the curve, the blood is dammed back in the thorax, in correspondence with the retrograde wave. As a result a second expiratory- movement manifests itself in the descending portion of the curve. 4. The subsequent secondary wave-movement of the blood from the heart immediately again causes an inspiratory movement of gases, which produces the recoil elevation in the arteries of the body. 5. More blood no%v begins to flow into the thorax through the veins with slight fluctuations, and the next heart -beat takes place. Fig. 35. — Landois' Cardiopneumograph, and Cardiopneumatic Curves Obtained with its Aid. A and B, from man; i and 2 correspond to the period of the first and sec»nd heart- sounds; C, cur\-es from the dog; D, showing the instrument in use- Pathological, — In the healthy human subject a crepitating sound is not rarely heard close to the heart, resulting from the movement of the air in the Ivmgs, brought about by the movement of the heart. If there are near the heart abnor- mally narrow places in the bronchi, through which the respirator^' gases are forced, so that they generate a sound or murmur, a fairly loud, sibilant or whistling murmur, known as the pathological cardio pneumatic murmur, is heard in rare cases. In the presence of cardiac lesions characterized by considerable fluctuations in the quantity of blood in the vessels of the lesser circulation, the cardiopneumatic movement mu.st be quite marked, as, for example, in cases of insufficiency of the pulmonary and mitral valves. INFLUENCE OF THE RESPIRATORY PRESSURE ON THE DILA- TATION AND CONTRACTION OF THE HEART. The variations in pressure to which all the parts within the thorax are subjected by its inspirator}' expansion and expiratory contraction exert a visible influence on the diastole and systole of the heart. The conditions in various positions of the resting thorax with the glottis open will be considered first. The diastolic dilatation of the cavity of the heart is brought about Vjy the elastic traction of the lungs, as well as by the inflow of venous blood and the elastic stretching of the relaxing muscular walls. This traction is greater in proportion as the INFLUENCE OF RESPIRATORY PRESSURE ON THE HEART. 1 23 lungs are more fully expanded (inspiration), and become less effective in proportion as the lungs have already been contracted (expiration). From this it follows: 1. That in the most extreme expiratory position of the thorax, with the greatest possible contraction of the pulmonary tissue, when, there- fore, what is left of the effective elastic traction of the lungs is exceedingly slight, but little blood enters the cavities of the heart; the heart during diastole is small and contains but little blood. Accordingly, the systolic contractions will be small, that is, a small pulse results. 2. In the most extreme inspiratory position, when the elastic lungs are distended to their utmost, the force of the elastic traction of the limgs is, naturally, greatest, being in fact equivalent to 30 millimeters of mercury. The effect of this traction may be great enough to counter- act the contractions of the thin-walled auricles and auricular appendages and prevent these structures from emptying their contents completely into the ventricles. In cases of cardiac weakness it would even appear as if the ventricular activity were impaired by the strong elastic pulmo- nary traction, as the diminution in the strength of the heart-sounds that is sometimes observed attests. The heart, therefore, is greatly distended in diastole and filled with blood; nevertheless the resulting pulse-waves may be small in consequence of the limitation of auricular activity. Thus, Bonders often found the pulse smaller and slower. 3. When the thorax is in the position of moderate rest, a condition in which the elastic traction of the lungs is of moderate strength only, namely, 7.5 millimeters of mercury, the conditions for the action of the heart are most favorable. On the one hand, diastolic distention of the cavities of the heart is adequate, and, on the other hand, their complete evacuation during systole is not impeded. A much greater influence on the action of the heart is exerted by the increase or diminution in the intrathoracic pressure produced voluntarily by muscular action. 1. If the thorax is first brought into the position of deepest inspira- tion, then the glottis is closed, and now the space within the chest is greatly reduced with the aid of the expiratory muscles; the cavities of the heart may be so greatly compressed as to cause momentary sus- pension of the movement of the blood within them. In this position the elastic traction is greatly diminished, and in addition the pulmonary air, which is under high tension, exerts pressure on the heart and the intrathoracic vessels. As no venous blood can enter the thoracic cavity from without, the visible veins become enlarged, the blood is driven more rapidly into the left heart, and the latter empties itself into the circulation as quickly as possible. The lungs are, as a result, anemic and the cavities of the heart empty. Therefore, there is plethora in the greater circulation, associated with anemia in the lesser and in the heart. The heart-sounds cease, the pulse disappears. 2. If, conversely, the glottis is closed, while the thorax is in the position of most extreme expiration, and the thoracic cavity is now for- cibly dilated in inspiration, the heart is strongly dilated; for the cavities of the heart are distended not only by the elastic traction of the lungs, but also on account of the extreme rarefaction of the pulmonary air. The contents of the veins are poured copiously into the right heart, and in proportion as the right auricle and the ventricle are capable of 124 INFLUENCE OF RESPIRATORY PRESSURE ON THE HEART. overcoming the outward traction, the blood-vessels of the lungs will be distended with blood. Much less blood will be driven out of the left heart, so that the pulse may even be temporarily arrested. The result is an overdistended, enlarged heart and the presence of an increased amount of blood in the lesser circulation, as compared with the greater. As, when the breathing is normal, the tension of the pulmonary air is diminished during inspiration and increased during expiration, this normal alternation of pressure tends to assist the circulation: inspira- tion hastens the venous and lymphatic flow through the venae cavae (if the axillary or the jugular vein is opened during an operation, air may be sucked in and cause death) and thus favors complete diastole; Fig. 36. — Apparatus for the Demonstration of the Influence of Respiratory Expansion (II) and Contraction (I) of the Thorax on the Heart and the Circulation. expiration hastens the movement of blood into the arterial system and favors systolic emptying of the heart. At the same time the val- vular arrangement of the heart secures a constant direction to the accelerated blood-current. The elastic traction of the lungs also exerts a favorable influence on the lesser circulation, which is contained entirely within the thorax; for the blood within the pulmonary capillaries is under the same pres- sure as the pulmonary air, while that of the pulmonary veins is under lower pressure, as the elastic traction of the lungs by distending the left auricle necessarily hastens the flow of blood from the pulmonary veins into the left auricle. On the other hand, the elastic traction of MOVEMENT OK THE lU.ooD IN THE CIRCULATION. '25 the lungs is prevented from interfering to any marked degree with the action of the right ventricle and, therefore, with the movement of blood through the pulmonary artery, because of the sufficient resistance of the blood, right ventricle and the pulmonary artery against the elastic pulmonary traction. The apparatus illustrated in Fig. 36 shows clearly the influence of inspiratory and expiratory movements on the expansion of the heart and on the current of blood in the large vascular channels leading to and from the heart. The large glass bottle represents the thorax, and its l)Ottom has been replaced at D by an elastic rubber membrane, which represents the diaphragm. P P are the lungs; L the trachea, the entrance to which (glottis) may be closed by means of a stop- cock; H is the heart; E represents the course of the venie cavae; and A the aorta. When the tracheal stop-cock is closed and the expiratory position, as shown at I, is established by elevating the membrane D, with diminution in the size of the thoracic cavity, the air in P P is condensed, while at the same time the heart H is compressed; the venous valve closes, while the arterial valve is opened and the fluid is driven out through A. The manometer M, inserted into the flask, shows the increased intrathoracic pressure. Again, when the stop-cock 1 is closed (in II), and the membrane is strongly depressed, the lungs pp expand, and Avith them the heart h. The venous valve opens, while the arterial valve closes, and the venous blood enters the heart through e. Thus, inspiration always hastens the venous and inhibits the arterial flow, while expiration inhibits the venous and hastens the arterial flow. If the glottis (L and 1) remains open, the air in P P and p p naturally is changed as the thorax passes from the inspiratory to the expiratory position (D and d). Accordingly, the effect on the heart (H and h) and on the blood-vessels is smaller, btit even under such conditions it must persist in small measure. THE MOVEMENT OF THE BLOOD IN THE CIRCULATION. TORICELLI'S THEOREM ON THE VELOCITY OF ESCAPE OF FLUIDS. According to Toricelli's law, the velocity (v) with which a fluid escapes, for example, through an opening in the floor of a hollow cylindrical vessel, is equal to the velocity that a freely falling body would attain in falling from the level of the fluid to the level of the open- ing (the height of the propelling force h). Hence v = 1/2 g h; in which g = 9.8 meters. The velocity of outflow increases, as has been shown experimentally, as the height of the propelling force (h) increases, and it preserves the ratio_ of i, 2, 3 as the propelling force increases in the ratio of i, 4, 9; that is, the velocity of outflow is proportionate to the square root of the height of the propelling force. It thtis follows that the velocity of outflow depends solely on the distance between the level of the fluid and the opening, and not on the nature of the escaping fluid. Whenever a fluid is fo.und escaping with a definite velocity, the force that causes the flow may be expressed by the height of a column of fluid (h) in a vessel the height of the pro- pelling force. Toricelli's law, however, is applicable only when all possible resistance that may be offered to the escape of the fluid is left out of account. As a matter of fact, certain resisting forces are present in anj^ physical ex- periment of this kind. Hence, the force that is ex- pressed by the height of the propelling force (h) not only causes the escape of the fluid, but also overcomes the sum of all the resist- ances. These two forces mav be expressed by the heights of two columns of water superposed the one upon the other ; namely, by the height of the velocity Fig. 37. — Pressure-vessel Filled with Water: h, height of the column of fluid; F, height of the velocity; D, height of the resistance. 126 PROPELLING FORCE, VELOCITY AND LATERAL PRESSURE. F (which effects the velocity of escape) and the height of the resistance D (which overcomes any resistance that may be present) : hence h = F -;- D. PROPELLING FORCE, VELOCITY AND LATERAL PRESSURE. If a fluid passes through a tube (which it completely fills), the first thing to determine is the propelling force h with which the current flows at different points in the tube. The degree of the propelling force depends on two factors: 1. The velocity of the current, v; 2. The pressure (resistance-height) to which the fluid is subjected at different points in the tube, D. 1. The velocity of the current v is determined: (a) from the lumen of the tube 1, and (b) from the quantity of fluid q, that passes through the tube in a given unit of time. Then v = q : 1. Both values, q as well as 1, can be deter- mined directly by measurement. The circumference of a circular tube, the diameter of which is d, is 3.14 X d. The cross-section (the lumen of the tube) is 1 = ^^ X d^- 4 After the value of v has been determined in this way, the so-called velocity- height F (of hydraulic engineers) can be estimated from v; that is, the height from which a body would have to fall in a vacuum in order to acquire the velocity of V. This is F = — (in which g indicates the distance through which the body falls in one second, or 4.9 meters). 2. The pressure D (resistance-height) is measured directly at various points in the tube by inserting manometer-tubes (Fig. 38). The propelling force at any selected point in the tube will thus be : h = F + D or h = - -f D 4g For experimental investigation the large cylindrical pressure-vessel (Fig. 38, A) may be used, within which by a suitable arrangement water can be maintained at a constant level h. The rigid tube a b, passing oft' from the bottom of the vessel, and of uniform size, is provided with a number of vertical tubes (i, 2, 3) consti- tuting a piezometer, for the measurement of the pressure; at the extremit}' b the tube is provided with an opening di- rected upward. From the lat- ter the water, providing the level at h remains the same, will be thrown to a constant height, and this distance is equivalent to F, the velocity- height. As the pressure Di, Dj, D3 in the manometric tubes I, 2, 3 can be read oft" directlv, it follows that the propelling force of the water at the posi- tion of the tubes I, II, III is respectively h = F -|- D,; F -[- D,; F-f D3. At the extremity of the tube (at b) where Dj = o, h = F + o, hence h = F. Within the pressure-vessel itself, it is the constant force h that influences the movement of the fluid. It is, therefore, at once apparent that the propelling force of the water has become progressively smaller from the point where the fluid enters the tube from the pressure-vessel to the end of the tube b. The water in the pressure-vessel falling from h rises at b only to the height F. This diminution in the propelling force is due to the resistances encountered by the current in the tube, which neutralize a part of the kinetic energ\' (that is, convert it into heat). As, when the water has reached b. the motor power h in the vessel has been re- duced to F, the dift'erence having been netitralized by the resistances, the sum of these resistances must be D = h - F, from which it follows that h = F + D. h ■ ^^s D \^<4 ^ I IT K Fig. 38. — A Pressure-vessel, A, with Outflow Tube, a b, and Manom eters, D^Di D3, Inserted at Different Points. METHOD OF ESTIMATING THE RESISTANCES. I27 METHOD OF ESTIMATING THE RESISTANCES. When a fluid passes tlirough a tube of \iniform caliber throughout its entire length, the propelling force h diminishes progressivel)' in consequence of the resistances that operate uniformly at every point. The sum of all the resistances in the tube is, therefore, directly proportional to its length. In a tube of uniform caliber the fluid passes through each transverse section at a constant velocity; hence v (and, therefore, F) is the same at any point in the tube. The diminution that takes place in the propelling force h can, therefore, be due only to a diminution of the pressure D, as F remains the same everywhere (and h = F + D). The experiment with the pressure- vessel shows, in fact, that the pressure progressively diminishes toward the discharging extremity of the tube. In a tube of uniform width the pressure-height found to prevail in the manometer-tube is the expression of the sum of the resistances that must be overcome by the current in its course from the point examined to the free discharge-opening of the tube. Forms of Resistance. — The resistances encountered by a stream of fluid reside first of all in the cohesion of the fluid-particles. The outermost parietal layer of the fluid, which is in contact with the tube, remains absolutely quiescent during the passage of the current. All the other layers of the fluid, which may be concerned as a series of concentric c\dinders one within the other, move with a progressively increasing velocity from the periphery to the axis of the tube, while "the axial thread itself finally represents the most rapidly moving portion of the fluid. In the displacement of these cylindrical layers of fluid at their surfaces of contact, the particles of fluid in juxtaposition must naturally be pulled apart and a portion of the active propelling force will be lost. The degree of resistance depends essentially on the degree of cohesion between the particles of fluid; the more intimate the cohesion between the fluid-particles, the greater will be the resistance; and conversely. It is thus evident that the resistances encountered by the viscous blood in its passage must be greater than those that would be encountered, for example, by water or ether. Four and one-half times as much pressure would be required to drive the same quantity of blood as of water through a tube. Heat diminishes the cohesion of the particles and it is, therefore, a means for diminishing the resistance encountered by the current. It is also evident that the resistances are only the result of movement, as the forcible separation of the fluid-particles does not begin until the column is set in motion. It is, further, obvious that the greater the velocity of the current — the greater the number of fluid-particles that are torn apart in a unit of time — the greater will be the sum of the resistances. The parietal layer of fluid in contact with the surface of the tube remains, as has been said, in absolute quiescence; it follows, therefore, that the material composing the walls of the tube has no influence on the resistances. INFLUENCE OF INEQUALITIES IN THE SIZE OF THE TUBE. When the velocity of the current remains the same, the intensity of the resistances depends on the diameter of the tube ; the smaller the diameter the greater the resistance, and the larger the diameter the less the resistance. The resistances, however, increase more rapidly in narrower tubes than the diameter of the tubes increases. This has been proved by experimental investigation. In tubes that exhibit inequality in size in their course, the velocity of the current varies, being naturally slower in the wide portions and more rapid m the narrower portions. In general the velocity of the current in tubes of unequal caliber is inversely proportional to the transverse section of the dift'erent portions of the tube, that is, if the tubes are cylindrical inversely proportional to the square of the diameter of the circular transverse section. While in tubes of uniform size the propelling force of the moving fluid dimin- ishes uniformly section by section, the diminution is not uniform in tubes of unequal width; for since, as has just been shown, the resistance is greater in a narrow than in a wide tube, the diminution in the propelling force must naturally be greater in the narrow places than in the wide places. At the same time, it has been shown that the pressure in the wider places is greater than the sum of the resistances still to be overcome: while, on the other hand, at the narrower places it is smaller than the sum of these resistances. Curvature and tortuosity of the vessels give rise to new resistances. In con- sequence of centrifugal force the fluid-particles cling more closely to the convex 128 MOVEMENT THROUGH CAPILLARY TUBES. side of the arch and thus encounter a greater resistance to their progress than on the concave side. When the tube divides into two or more branches, the propelhng force is also diminished on account of the creation of additional resisting forces. When a current is divided into two smaller currents, some fluid-particles will be retarded, while others will be accelerated on account of the unequal velocity of the various layers of the fluid. Many particles that in the main current, as a part of the axial stream, had the greatest velocity will in the secondary currents when situated in the parietal layers move more slowly; while, conversely, many parietal layers in the main current become more centrally situated in the secondary current with increased velocity. As a result of the resistance thus produced a part of the propelling force is naturally lost. The separation of the fiuid-particles as the current divides has a similar effect. If, on the other hand, two tubes join to form a single tube, additional resistance acting in a manner opposite to that described must lessen the propelling force. The sum total of the mean velocity in both branches of the current is independent of the angle formed at the point of division. The opening of a lateral branch that forms part of a tube accelerates the main current to the same degree, irrespective of the size of the angle formed by the lateral branch with the main tube. MOVEMENT THROUGH CAPILLARY TUBES. The movement of fluids through capillary tubes is, in accordance with the capillary- attraction prevailing in capillary vessels, and in contravention of the laws that have just been developed, governed by certain rules, for the formulation of which credit is due Poiseuille. These rules are as follows: 1. The quantity of fitiid that escapes from a capillary tube is proportional to the pressure. 2. The time necessary for the escape of a like quantity of fluid (the pressure, the diameter of the tube, and the temperature remaining the same) is propor- tional to the length of the tube. 3. The products of the outflow (all other conditions remaining the same) vary with the fourth power of the transverse diameter. 4. The velocity of the current is proportional to the pressure-height and to the square of the diameter, and inversely proportional to the length of the tube. 5. The resistances in the capillar}- tubes are proportional to the velocities of the current. CONTINUOUS AND UNDULATORY MOVEMENT IN ELASTIC TUBES. If an uninterrupted, uniform streain of fluid is permitted to flow through an elastic tube, the movement of this current is subject to the same laws that govern its passage through rigid tubes. If the propelling force increases or diminishes, the elastic tubes are either dilated or constricted, and their relation to the column of fluid is, therefore, simply like that of wider or narrower rigid tubes. If, however, successive amounts of fluid are introduced at intervals into an elastic tube entirely filled with fluid, the initial portion of the tube will be suddenly distended in accordance with the amount of fluid introduced. The impact imparts to the fluid-particles an oscillator^' movement, which rapidly communicates itself to all the fluid-particles from the beginning to the end of the tube; there results a positive wave, which rapidly propagates itself through the entire tube. If the elastic tube be closed at its peripheral extremity, the positive wave will rebound at the point of closure; it becomes a positive recurrent wave and it may even pass backward and forward repeatedly, becoming gradually smaller and smaller, until it finally subsides. Hence, in a closed tube of such character, the sudden periodic impulsion of a mass of fluid produces only a wave-like movement, that is, mereh' an oscillatory movement or the movement of a form. 3. If, however, additional amounts of fluid are at intervals pumped into the initial portion of an elastic tube entirely filled with fluid already in continu- ous movement, the continuous movement is combined with the undulatory movement. In such a case the continuous movement of the fluid, that is, the displacement or movement of the fluid in mass through the tube, must be rigidly distinguished from the undulatory or oscillating movement, the movement of the change in form of the column of fluid. The former is a translator^•, the latter an oscillatory movement. The continuous movement is slower in elastic tubes, while the undulatory movement is more rapid. STRUCTURE AND PROPERTIES OF THE B I.OOD-VESSELS. I 29 The conditions in the arterial system are the same as those just described. The blood in the arteries is already engaged in continuous motion from the root of the aorta to the capillaries (continuous movement) ; and the injection at inter- vals of a mass of blood into the root of the aorta with each systole of the left ventricle produces a positive wave (pulse), which propagates itself with great rapidity to the end of the arterial system, while the constant movement progresses much more slowly. It is of great importance to compare the movements of fluids in rigid tubes with the movements of fluids in elastic tubes. When a certain quantity of fluid is forced into a rigid tube under a certain pressure, an equal quantity of fluid will at once escape from the end of the tube, unless such a result is prevented by the development of special resistances. The conditions are, however, different in the case of an elastic tube. Immediately after the injection of a definite quantity only a relatively small quantity of fluid escapes at first, the escape of the re- mainder taking place only after the injecting force has subsided. If equal quantities of fluid are injected at intervals into a rigid tube, a corre- sponding amount escapes with each impulse and the discharge continues as long as the impulse, and the pause between each two periods of escape is always equal to the period between two impulses. In the case of elastic tubes the conditions are different. As the escape of the fluid continues for some time after the cessation of the impulse, it will always be possible to establish a continuous outflow through elastic tubes by making the interval between two injections shorter than the duration of the outflow that takes place after the impulse has been completed. Thus, the periodic injection of fluid into a rigid tube produces an isochronous, sharply limited ovitflow of fluid, which can become permanent only when fluid enters the tube in a continuous stream. In the case of elastic tubes, on the other hand, intermittent introduction of fluid produces under the same conditions a continuous outflow with systolic reinforcement. Hamel's investigations have shown that elastic tubes permit the passage of more fluid when they are supplied in a rhythmical pulsatory manner than when the fluid enters in an uninterrupted stream under constant pressure. The advan- tage of the rhythmical impulse for the propulsion of the circulating fluid, as com- pared v/ith a uniform pressure, appears to reside in the fact that the alternating movement preserves the elasticity of the arterial w^alls. STRUCTURE AND PROPERTIES OF THE BLOOD-VESSELS. The large blood-vessels in the body are designed solely for the purpose of acting as conducting canals for the mass of blood, while the thin-walled capillary vessels eft'ect the interchange of substances between the blood and the tissues and in the opposite direction. The Arteries differ from the veins in the possession of thicker walls in con- sequence of the considerable development of muscular and elastic elements, as well of a greatly developed middle tunic, with a relatively thin adventitial coat. The walls of the arteries consist of three coats (Fig. 39) : The -intima is lined on its inner surface by a nucleated endothelium (a) consisting of flat, irregular, oblong cells. External to the endothelium is a thin, finelv granular layer containing more or less distinct fibers and numerous spindle-shaped or stellate protoplasmic cells embedded in a corresponding system of plasma-canals. To the outer side of this is the inner elastic layer (b), which in the smallest arteries is represented by a structureless or fibrous, elastic mem- brane and in the medium-sized arteries by a fenestrated membrane; while in the largest it assumes the appearance of a stratified, fibrous or fenestrated, elastic membrane consisting of two or three layers and united by connective tissue. All of the larger and medium-sized arteries contain longittidinal fibers situated between tv.ro elastic plates. Acting together with the circular fibers they are capable of narrowing the caliber of the vessel; but they possess also the faculty of widening the lumen and maintaining it at a uniform width. On the other hand, it is im- probable that they are capable of independent action or that such independent action is capable of dilating the vessel. The middle coat has for its most characteristic constituent unstriated muscle- fibers (c). In the smallest arteries this appears to be composed of scattered, transverse, smooth muscle-fibers occupving an intermediate position between the intima and the adventitia. The connecting material consists of a finely granular tissue traversed by a few delicate elastic fibers. Passing from the smallest to the 9 130 STRUCTURE AXD PROPERTIES OF THE BLOOD-VESSELS. smaller arteries, the number of unstriated muscle-fibers increases progressively until they form a strong layer of circular muscle-fibers with almost complete dis- appearance of the connecting substance. The outer elastic layer forms the bound- ar\' between the media and the advent itia. In the large arteries the connecting substance greatly predominates over all other tissues; Separated by layers of delicate fibrous tissue there are numerous (as many as 50) thick, elastic, fibrillated or fenestrated membranes arranged in concentric layers and chiefly in the trans- verse direction. Scattered here and there between these membranes are occa- sional smooth muscle-cells arranged transversely, less commonly obliquely, or longitudinally. The initial portions of the aorta and pulmonary artery, the arteries in bones and the retinal arteries are devoid of muscle-tissue. The descending aorta and the common iliac and popliteal arteries possess oblique and longitudinal muscle- fibers lying among the transverse fibers. The renal, splenic and internal sper- matic arteries contain longitudinal bundles at the inner surface of the media; the umbilical arteries, which are exceedingly rich in muscle- tissue, contain longitudinal bvmdles both on the inner and on the outer surface. The external or adventitious coat in the smaller arteries is a delicate, structureless membrane containing a few protoplasmic cells. In somewhat larger vessels there is an additional layer of elastic 'tissue of delicate fibers containing strands of fibrillated con- nective tissue (d) . In the medium-sized and largest arteries the greater part of the ad- ventitia consists of bundles of fibrillated connective tissue containing connective-tissue cells, and not infrequenth' an admixture of fat -cells, running obliquely and crossing each other at numerous points. Among them and chiefly toward the media are found fibrous or fenestrated elastic laj-ers. At the boundary between the adventitia and the media the elastic elements in the smaller and medium- sized arteries fuse to form a more indepen- dent elastic membrane (Henle's outer elastic membrane). Longitudinal unstriated mus- cle-fibers in scattered bundles are found in the adventitia of the arteries of the penis, of the descending aorta, the renal, splenic, in- ternal spermatic, iliac, hypogastric, and superior mesenteric arteries. Bonnett suggests the following natural division of the layers of the arterial wall: I. The intima embraces the endothelial tube and the tissues as far as the inner elastic layer. 2. The media contains all those parts that are situated between the inner and the outer elastic layer. 3. The adventitia includes the layers found to the outer side of the elastic membrane. The Capillaries, which undergo frequent division without suffering diminu- tion in caliber, and in their subsequent course unite again, have diameters varying from 5 to 6 ," (retina, muscles) to from 10 to 20 u (bone-marrow, liver, choroid) . The tubes are formed of a single layer of nucleated endothelial cells, with protoplasmic cell-bodies, which in the smaller tubes are spindle-shaped and in the larger vessels are more polygonal (as is the case with the cells of serous cavities) ; they are connected by numerous intercellular bridges in the depths of the cell-substance (like epithelial cells). The boundaries of the cells are demonstrable as black lines by injection of a solution of silver nitrate. The stained cement-substance exhibits in some places intercalated areas of larger size. Whether these are to be regarded as true openings or stomata, through which it is possible for red and white cells to escape, or merely as denser aggre- gations of the stained cement-substance is still an undecided question. Delicate Fig. 30- — Small Anerial Twig Showing the In- di\idual Layers of the .Arterial Wall: a, endothelium; b, elastic inner coat: c, layer of circular muscle-fibers; d, con- nective-tissue adventitia. STRUCTURE AND PROPERTIES OF THE BLOOD-VESSELS. 131 anastomosing fibrils derived from non-medullated nerves terminate by small end-plates in the capillary walls. Ganglia in communication with the nerves of capillary vessels are found only in the distribution of the sympathetic nerves. The minute blood-vessels that communicate directly with the capillaries possess, in addition to cndnthelium, an entirely structureless investing membrane. The Veins dilTer from the arteries in the main in the fact that they have a larger calilx-r than the corresponding arteries and thinner walls on account of the much feebler development of the elastic and muscular elements. Among the latter longitudinal fibers are much more commonly found than transverse. Veins are also distinctly more distensible with the same degree of traction. The adven- titia is as a rule relatively the thickest coat. The presence of valves is limited to certain areas of the body. The intima or internal coat is provided with short endothelial cells, beneath which, in the smallest veins, is a structvireless layer, which in the somewhat larger vessels is composed principally of longitudinal elastic Hbers (always thinner than in the arteries). In the large veins this layer may assume the character of a fenestrated membrane, which here and there in the femoral and iliac veins is even duplicated. It is held together by a delicate connective tissue containing spindle-cells. The intima in the femoral and popliteal veins contains a few scattered muscle- fibers. The media or middle coat in the larger veins is 'constituted of alternate layers of elastic and muscular elements, with a fairly abundant fibrillar connective tissue. The media is always thinner, however, than in the corresponding arteries. The number of these alternating layers becomes progressively smaller in the following veins, in the order of their enumera- tion: popliteal vein, veins of the lower extremity, veins of the upper extremity, superior mesenteric, the remaining veins of the abdominal cavity, the hepatic, pulmonary, and coro- nary veins. The following veins are altogether devoid of mus- cle-tissue; the veins of bones, muscles, the central nervous system and its membranes, the retinal veins, the superior cava with the large trunks that empty into it, and the upper portion of the inferior cava. In these vessels the media is much more feebly developed. In the smallest veins the media consists merely of a delicate fibrillar connective tissue in which a few scattered longitudinal and transverse unstriated muscle-cells make their ap- pearance as the center of the circulation is approached. The adventitia or external coat of the veins is, generally speaking, thicker than that of the corresponding arteries. It always contains more abundant connective tissue, usually consisting of longitudinal fibers, and on the otherhand fewer large- meshed networks of elastic elements. Some veins, however, contain also longi- tudinal muscle fibers: the renal vein, the portal vein, the inferior cava in the hepatic region, the veins of the lower extremity. The valves consist of finely fibrillated connective tissue in w^hich stellate cells are embedded; the convex surface of the valves is covered with a network of elastic fibers, and both surfaces are invested with endothelium. The valves contain many muscle-fibers. The sinuses of the dura mater are spaces lined with endothelium between duplicatures, or cleft -like invaginations of this membrane. Cavernous spaces may be regarded as having been produced by numerous divisions and anastomoses of fairly large veins of unequal size, closely following one another. The vessel-wall frequently appears cribriform or like a sponge — the Fig. 40. — Capillary Vessels, — the Boundaries of the Cells (Cement- substance between the Endothelial Cells) have been Stained Black with Silver Nitrate and the Nuclei of the EndotheUal Cells Made Prominent by Staining. 132 STRUCTURE AND PROPERTIES OF THE BLOOD-VESSELS. interior traversed by trabeculse or threads. The surface directed toward the blood is covered with endothehum. The investing wall consists of connective tissue, which is often quite firm and tendinous, as in erectile tissue. It not infre- quently contains unstriated muscle-fibers. An example of an analogous cavernous formation in arteries is found in the coccygeal gland of man. This mysterious structure, which is richly supplied with sympathetic nerve-libers, consists of nucleated connective tissue and represents a convolution of ampulliform or spindle-shaped dilatations of the median sacral artery, traversed and surrounded by unstriated muscle-fibers. The vasa vasorum do not differ in structure from other vessels of similar caliber. Intercellular blood-channels devoid of walls are present in the granulation-tissue of wounds. At first nothing but blood-plasma is found between the constituent cells, and it is not until later that blood-cells are driven through the channels by the blood-current. In the incubated egg the primary basis of the blood-vessels is formed in a manner similar to that of the formative cells of the germinal layer. The blood-vessels without walls in the bone-marrow and in the spleen are con- sidered on p. 43. __, Among the properties of blood-vessels their contractility should be mentioned first, that is, the ability to contract by virtue of the unstriated muscle-fibers contained in their walls. The intensity and force with which this contraction takes place are proportional to the degree of development of the muscle-tissue. Heat causes contraction of the blood-vessels (in the mesentery of the frog). Excised arteries contract when filled with dilute alkaline solutions, digitalin, atropin, and antiarin. The isolated apex of the heart also beats more freely in alkaline solutions. When the vessels are filled with a dilute solution of lactic acid they dilate, and the apex of the heart when immersed in such a solution also beats more rapidly. According to Roy, blood-vessels undergo shortening under the influence of heat, if precautions are taken to prevent evaporation and the load remains the same. If blood containing an admixture of certain substances— -such as amyl nitrite, chloral hydrate, morphin, quinin, and atropin — is allowed to flow through the vessels of a recently excised, living organ, dilatation takes place ; urea and sodium chlorid have the same efi^ect on the renal vessels; while digitalin and veratrin cause contraction. The capillaries also possess the power of dilating and contracting, derived from the protoplasmic granules of the cells of which they are composed. The capillaries have been designated "protoplasm in tubular form," and motor phenomena have been observed in them, especially after irritation in the living animal. Strieker observed this chiefly in the capillaries of young frog- spawn. At a later period of the animal's life the reaction of the capillaries to stimuli is much less distinct. Rouget observed the same phenomena also in new- born mammals. Similar observations have been made by Golubew and Tarchanoff. Accordingly, the shape of individual cells varies with the quantity of blood con- tained in the vessels. In greatly distended vessels the cells are flat; but when the vessel is collapsed, the cells are more cylindrical and project into the lumen. Among the physical properties of blood-vessels their elasticity should next be mentioned. The elasticity is slight, that is, the vessels offer little resistance to the distending forces, such as pressure or trac- tion; but it is, at the same time, complete, that is, after the distending force has ceased to act, the vessels regain their previous form. According to Ed. Weber, Wertheim and A. W. Volkmann, the length of blood- vessels (like that of moist portions of the animal body generally) does not increase in proportion to the weight employed to extend it, but the elongation is considera- bly less with progressive increase in the weight. Hence the extensibility of the dead artery is greatest when it has been slightly distended by intravascular pres- PULSE-MOVEMENT. 133 sure. After repeated experiments, however, Wundt was led, as a result of ex- perimental observations, to the conclusion that blood-vessels also are subject to the general law of elasticity mentioned. He maintains that it is necessary to take into consideration not only the first distention that occurs after the application of the load, but also the "elastic after-effect" that follows gradually. This terminal distention, which often proceeds slowly, is so gradual during the last moments that observation with a magnifying lens is necessary to determine when the condition of definitive distention is completed. Deviations from the general law occur; for when a certain load is exceeded, lesser degrees of distention and at the same time permanent changes not infrequently result. A normal vein may be stretched at least 50 per cent, without exceeding the limit of elasticity. Pathological. — Nutritive disturbances modify the elasticity of the arteries. When death has been preceded by marasmus, the arteries are found relatively more dilated than under normal conditions. Beginning connective-tissue forma- tion in the intima, combined with fatty degeneration, at first increases the dis- tensibility and diminishes the strength of the wall. As the development of the connective tissue progresses in cases of arteriosclerosis, the elasticity and firmness of the arteries are again augmented. Diminished distensibility is found also in connection with atheroma, in cases of nephritis and in the arteries of drunkards. A property peculiar to the walls of the blood-vessels is their power of cohesion, which enables them to resist rupture, even when the in- ternal tension is considerable. It has been found that the carotid artery does not rupture until the internal pressure has been raised artificially to fourteen times the normal. The resistance of veins to rupture is relatively greater than that of arteries with the same thick- ness of wall. According to Grehant and Quinquaud the carotid and iliac arteries in man resist a pressure up to eight atmospheres and the veins more than half of this amount. Pathological, — Diminished power of cohesion of the blood-vessels, especially the arteries, is not uncommon in old age. PULSE-MOVEMENT.— TECHNIC OF PULSE-EXAMINATION. The physicians of antiquity devoted more attention to abnormal excitation of the pulse than to the normal pulse. Thus, Hippocrates (460-377 B. C.) speaks only of the former condition and applies to it the term acpvy/joc. Later, Herophilus (300 B. C.) in particular compared the normal pulse (-a/f/6r) with the abnormally excited pulse. He laid especial stress on the time-relations existing between dilatation and contraction of the arterial tube and defined more accurately the properties, volume, fulness {a(pv}/wg raxi'c) and frequency (^advy/xo^ TzvKvog) . His Alexandrian colleague Erasistratus (who died 280 B. C.) was the first to make correct statements in regard to the propagation of the pulse-waves; for he stated distinctly that the pulse appears earlier in the arteries nearer the heart than in the more distant vessels. Erasistratus also felt the pulse below a cannula introduced in the continuity of an artery. Archigenes claims especial interest, particularly with respect to the pathology of the pulse, because he was the first to designate the dicrotic pulse, which he had the oppor- tunity of observing in febrile diseases. Galen (131-202 A. D.) determined more accurately than his predecessors the principles governing expansion and contraction of the arteries during the movement of the pulse. His explanation of the slow pulse was that the time of expansion was prolonged. Galen made also note- worthy observations with regard to the rhythm of the pulse and the effect of temperament, sex, age, season of the year, climate, sleep and waking, emotional influences, and cold and warm baths. Cusanus (1565) was the first to count the pulse-beats with a time-piece. INSTRUMENTS EMPLOYED IN THE EXAMINATION OF THE PULSE. It is possible by means of instrumental examination to obtain trustworthy information with regard to the nature of the movement of the pulse. Apart from those instruments by means of which the undulatory movement in the arterial tube can be demonstrated only after this has been opened, the following are "Worthy of mention: 134 INSTRUMENTS FOR INVESTIGATING THE PULSE. Poiseuille's Box-sphygmometer. — The exposed artery (Fig. 41, a a) is en- closed for a distance in its continuity in an oblong box (K K), filled with some indifferent fluid. There communicates with the interior of the box a graduated vertical tube (b), filled to a certain point, in which the fluid rises and falls, in accordance with the quantity of blood contained in the artery. The box is constructed like an ordinary box, one half representing the body and the other half the lid. A circular opening is made in each end of the box, one half being contributed by the body and the other half by the lid, in which the artery is hermetically sealed by means of soft fat. Poi'seuille found the distention of the carotid during diastole in the horse to be equal to .h, and in the dog to 5V of the entire volume of the arterial segment. The instrument does not record any more minute details in regard to the movement of the artery during the phases of the pulse. Herisson's Tubular Sphygmometer (Fig. 42) consists of a glass tube closed at its lower extremity by an elastic membrane and filled to a certain level with mercury. The apparatus is placed vertically on the skin over a pulsating artery, the beats of which set the column of mercurv in motion. A similar instrument Fig. 41.— Poiseuille's Box-cabinet Sphygmometer: a a, the exposed artery; K K, the surrounding box with the vertical tube and scale b. Fig. 42.— The Tubular Sphygmometer of Hi^risson and Chelius. was used in 1850 by Chelius, who succeeded with its aid in discovering the double beat of the normal pulse. "After it (the mercury) has been raised by the impact of the blood-wave, it falls again as suddenly to its lowest level, after first makino- another short pause at some intermediate point." '^ Marey's Sphygmograph is based on a combination of the lever (which was first employed by Vierordt in 1855 in the construction of his "sphygmograph") with an elastic spring (Fig. 43, A). The latter, which is screwed fast at one extremity (z) , while the other extremity is free and provided with a round pad (y) , presses against the radial artery with a force equal to that of the spring. To the upper part of the pad is fixed a short vertical ratchet (k^l , which, when acted upon by a weak spring (e) , turns a small cogwheel (t) , from the axis of which a light wooden lever (v) extends almost horizontally. This writing lever is provided at its outer extremity with a delicate point (s) , which records the movements of the pulse on the smoked surface of a plate (P) made by clockwork (u) to pass in front of the point of the writing lever at a uniform rate. Marey's instrument is trustworthy and is quite extensively used. Marey's sphygmograph is adapted solely for the radial pulse. It is placed INSTRUMENTS FOR INVESTIGATING THE PULSE. 135 lengthwise on the forearm, where it is steadied by means of two short metallic supports (S) and fastened with a tape, which must not Vjc drawn too tight. The apparatus is also provided with a secondary screw (H), which can be made to act on the spring (A). If the screw is tightened the spring is compressed and rendered shorter, less yielding and movaltle with greater dilticulty; when the pres- sure is entirely released, the spring (A) has free play, is more yielding and the position of the pad (y) is higher. Fig. 43.— Marey's Sphygmograph (Diagrammatic). yiareys SplivgmograpJi ivith Transmission oj Air — of which many modifications have been made, for example bv Knoll; Fig. 44 illustrates the modification de- signed by Brondgeest and designated " pansphygmograph " — is constructed on the principle of the pneumatic telegraph. Two pairs of shallow metallic cups — (S S and S' S') so-called Upham's capsules— are each pierced from below at their center by a small tube. The ends of these tubes are connected with rubber tubes (K and K') . Over the mouth of each of the four cups a delicate rubber membrane is Fig. 44.— Brondgeest's Pansphvgmograph Constructed on Uphatn's and Marey's Principle of the Propagation of Movement through Air containing Drums Covered with Elastic Membranes. The figure represents also diagrammatically Marey's cardiograph. Stretched and from the middle of each of the two rubber membranes S and S' there projects a button-shaped process (p and p'). ^vhich is applied to the pulsating arterv and held in place bv metallic arches B B', the extremities of which rest on the surrounding skin. From the center of each of the other two rubber mem- branes which are directed horizontallv upward, there projects a knife-edge, which is apphed close to the balancing center (h and h') of the delicate wnting levers Z and Z' It is evident that anv pressure applied to the buttons wall cause a 136 INSTRUMENTS FOR INVESTIGATING THE PULSE. bulging upward of the membrane of each of the upper cups, the movements of which are propagated to the writing levers. The instrument sketched in Fig. 44 shows the entire registering apparatus in duplicate. An instrument of this kind may, therefore, be placed with the two pads on two different arteries; for example, when it is desired to demonstrate that the pulse occurs earlier in the arteries near the heart than in more distant vessels. Although the instruments described are convenient to handle, it has been found by experience that sudden variations in pressure are not accurately recorded in consequence of vibration of the instrument itself; while when the variations in pressure are less sudden, the records may under certain circumstances be fairly accurate. Another disadvantage is that the movement of the writing lever Z is not entirely sjmchronous with that of the button p. For this reason instruments constructed on this principle are not well adapted for accurate time work. The entire apparatus may also be filled with water, in which event leaden pipes are used instead of the connecting rubber tubes. Thus adapted, the apparatus is more accurate for slower movements, while a pneumatic instrument is better adapted for rapidly varying phases, such as are presented by the movements of the pulse. Landois' Augiograph. — From one extremity of a plate (Fig. 45, G G) serving as a base, arises a pair of arms, between the upper parts of which the lever (d r) moves freely between two points. The long arm of this lever is provided with a pad (e), directed downward, which is to be applied to the pulse. The short arm of the lever on the other side carries a counter- weight (d) , heavy enough to maintain Fig. 45. — Landois' Angiograph Represented Diagrammatically. In order to shorten the figure a piece has been cut out of the writing lever. the entire lever in equilibrium. The extremity (r) carries a spring- ratchet, which presses against a cogwheel. The latter is immovably fixed to the axis of the light writing lever c f, which is also suspended between points and is supported by the two uprights q and attached to the opposite end of the base G G. The writing lever also is maintained in perfect equilibrium by means of a small counter- weight. The needle k is suspended from the extremity of the writing lever 1, where it is secured by a hinge and is readily movable; it is carried by its own weight toward the tablet (shown in the figure in profile) , and as it moves up and down it records the curve with a slight scratching movement on the delicately smoked surface of the tablet. The lever d r at a point approximately opposite the juncture with the pad e supports on the end of a vertical rod the flat plate q for the reception of weights to increase the load on the pulse. The advantages of the instrument are : (i) The load can be varied at will and can be accurately determined (while in Marey's sphygmograph the pressure of the spring increases as the lever is raised) ; (2) although the needle is constantly in contact with the smoked surface, it never- theless records with a minimum degree of friction; (3) the movement of the writing lever is a vertical up-and-down movement and not a curved movement as in Marey's apparatus, thus considerably facilitating an accurate stvidy and measurement of the curves. In the construction of his sphygmograph Sommer- brodt adopted the improvements embodied in Landois' angiograph. In the choice of a sphygmograph the guiding principle should be that the INSTRUMENTS FOR INVESTIGATING THE PULSE. 137 Fig. 46. — Dudgeon's Sphygmograph. most complete instrument and the one whose curves most closely correspond with the pressure-variations actually taking place in the artery is that in which the resistance within the apparatus itself is reduced to a minimum, in which those parts that execute the largest movements are as light as possible, but in which the bulk of that portion of the instrument that is directly set in motion by the movement of the blood in the artery, is strong enough and heavy enough for its equilibrium to be but slightly disturbed by even considerable force. Useful sphygmographs have been described by other investigators, as Nau- mann, Frey, and others. For practical purposes Dudgeon's instrument, which is easily manipulated, may be recommended; the load is applied by the pressure of a spring, ^^ or, better, by a weight and beam, and the tablet moves horizontally. A system of lines is recorded together with the curve, making it possible to determine by measurement the size and chronological development of the pulse- beats. Nomenclature of Pulse-tracings. — In every pulse-tracing (sphygmogram or arterio- gram) there are distinguishable the as- cending limb, the apex, and the descend- ing limb. Irregular elevations in the course of the descending limb are called catacrotic elevations, while those in the ascending limb are known as anacrotic elevations. The de- scending limb almost always contains sec- ondary elevations, while the ascending limb almost always appears as a simple rising line. When a recoil-elevation, which will be described more fully later on, occurs once or twice in the descending limb, the sphygmo- graphic curve is called dicrotic or tricrotic. When, as happens if the pulse- beats follow one another in rapid succession, the succeeding beat cuts off the recoil-elevation of the preceding curve, the curve is called monocrotic. Method of Making Sphygmographic Tracings. — The tracings are recorded on smooth glazed paper like that used for visiting cards, which has been covered with a delicate translucent layer of soot by exposure over burning camphor or a smoking lamp. The tracing is fixed by immersing the paper in a solution of shellac and alcohol, after which it is allowed to dr^^ Mensuration of Sphygmographic Tracings. — When a tablet is made to move at a uniform rate by means of clockwork, the vertical height and horizontal length of individual portions of the tracing can be measured with a fine rule. The distance traversed by the tablet in a second being known, it is possible by actual measurement to compute the duration of the individual portions of the pulse-movement. Accurate measurements of this kind must be made under the microscope with the aid of an ocular micrometer, a low magnification and direct illumination being employed. The sections to be measured are placed be- tween two lines that, in the ca.se of sphygmographs like Marey's, which make a curved tracing, must be arcs of a circle (of which the writing lever is the radius), and in the case of the angiograph must be vertical. An especially convenient method consists in recording the curve on a tablet attached to one end of a vibrating tuning-fork (Fig. 60). Another less accurate method consists in recording the vibrations of a tuning-fork on the tablet of the sphygmograph at the same time that a sphygmographic tracing is being recorded, the latter being above the tuning-fork record. The Gas-sphygmoscope. — To meet the objection that has frequently been urged against instruments for registering the pulse, namely that the secondary elevations observed in the sphygmogram are due to the after-vibrations of the apparatus from inertia, Landois constructed a gas-sphygmoscope, in which the movement of solid bodies is excluded and any after-vibration of inert masses that have been set in motion is, therefore, impossible. The superficial arteries, whose movement is communicated to the overlying skin, will, naturally, through the movement imparted to this layer of the skin, cause also a movement in the contiguous layers of air. The thin layer of air above the pulsating cutaneous area (Fig. 48) a is excluded by means of a shallow 138 INSTRUMENTS FOR INVESTIGATING THE PULSE. metallic gutter b, which is placed on the skin so that its concavity covers the artery like a small tunnel. The narrow space between the wall of the tunnel and the skin is filled with illuminating gas. To this end one extremity of the metallic tunnel is connected with the gas-tube g, while the other extremity com- municates by ineans of a short ru]:)ber connecting piece x q with a small tube t, bent upward at an angle and the point of which is drawn out to a minute opening for the escape of the gas. The gas is allowed to pass through the metallic tunnel, under low pressure, the inflow being regulated so that the flame v is not more than a few millimeters long. It is readily seen that the fiame increases in height synchronously with each pulse-beat and that the descent is interrupted by a distinct after-beat, von Kries photographed the image of the flame. The measurements of the accoinpany- ing curve are as follows : 1—2 = 7.5 = 0.121 sec. 1—3 = 16 = 0.258 1-4 = 22.5 = 0.363 ^_^^_^^_^ 1-5 = 39-5 = 0.638 Fig. 47. — Sphygmographic Tracing from the Radial .-Vrtery Made with Landois' Angiograph Attached |to a Vibrating Tuning-fork. Each indentation corresponds to 0.01613 sec. Hemauiograpliy. — If a freely exposed artery be divided in an animal so that the blood-stream spurts forth and is allowed to impinge on a glass plate or a sheet of paper moved vertically at some distance, the resulting tracing will coincide almost perfectly with the normal curve of the artery as recorded by the sphygmo- graph. In addition to the primary elevation (Fig. 49, P), the recoil-elevation (R) and the elasticity-elevations (e e) are appreciable. This self-registration of the Fig. 48. — Landois' Gas-sphygmoscope. blood-wave furnishes a convincing proof that the movement is produced in the blood itself and is commvmicated as an undulatory movement to the arterial wall. Bv determining the quantity of blood contained in the several portions of the hemautographic tracing it is found that the quantity of blood that escapes from the divided artery during systole is to the quantity that escapes during diastole (that is during contraction and dilatation of the vessel) approximate! v as 7 : 10. The quantity of blood that escapes during a unit of time while the artery is di- lating is equal to a little more than twice the quantity that escapes during' a unit of time while the vessel is contracting. THE PULSE-TRACING, THE RECOIL-ELEVATION AND ELASTICITY-ELEVATIONS. THE The sphygmogram presents an ascending limb, recorded during the distention (diastole) of the artery; the apex (Fig. 50, P) ; and the de- scending limb, which corresponds to the contraction (systole) of the ORIGIN AXD PROPERTIES OF THE DICROTIC ELEVATION. ^39 artery. The most conspicuous features of the sphygmographic tracing are the two entirely distinct elevations in the descending limb of the curve. The more prominent of the two occupies approximately the center of the descending limb, where it appears as a distinct elevation (R); it is known as the dicrotic after-beat or, with reference to its origin, as the recoil-elevation. The sphygmographic tracing reproduces the chronological course of the pressure exerted by the undulatory mov'ement of the blood on the arterial wall, the pad of the sphygmograph, which is supported on a spring, rising and falling with the variations in pressure; the instrument therefore records "pressure- pulse." ORIGIN AND PROPERTIES OF THE DICROTIC ELEVATION. The recoil-elevation (also designated secondary or dicrotic) is pro- duced in the following manner: After the column of blood propelled into the arterial system by the ventricular systole has generated a positive wave, which, beginning at the aorta, extends rapidly to all of the arteries, even to the minutest arterial branches, in which it disappears, the arteries contract as soon as closure of the semilunar valves prevents the further entrance of blood. The elasti- city and the active contraction of the blood-vessels thus exerts a counter pressure on the blood-column. The blood is forced to seek an outlet. In its progress toward the periphery it finds no obstacle in its path, but the portion that escapes toward the center of the circulation recoils from the already closed semilunar valves. The impact of the blood sets up another posi- tive wave, which is again propagated into the arteries and disappears as before in the remotest minute branches. If, how- ever, there is sufficient time for the com- plete development of the sphygmographic tracing, a second reflected wave is pro- duced in the proximal arteries (especially in the short course of the carotids, but also in the arteries of the upper ex- tremities, but not in those of the lower extremities because of their great length) in the same way as the first. Just as the pulse appears somewhat later in the more peripheral arteries than in those nearer the heart, so the secondary wave, produced by the recoil of the blood from the aortic valves, also appears later in the more distant arteries. Both kinds of waves, the primary and the secondary pulse-wave, and possibly also the tertiary recoil -wave, originate at the same point and are propa- gated in the same way. The longer the distance to be traveled before they reach a given point in the artery, the later will be their arrival at that point. The following laws with regard to the recoil-elevation have been determined experimentally: Fig. 49. — Hemautographic Tracing from the Posterior Tibial Artery of a Large Dog: P, primary pulse-wave; R, re- coil-elevation; e e, elasticity-eleva- tions. I40 ORIGIN AND PROPERTIES OF THE DICROTIC ELEVATION. I. The dicrotic elevation appears later in the descending limb of the curve the longer the artery, measured from the heart to the peripheral termination of the artery. (The curves in Figs. 47, 53 and 57 may be measured to confirm this point.) ■ XI XII XIII XIV XV Fic ro— I II III Sphygmographictracingsfromthecarotidartery; IV, from the axillary, V, IX, from the radial; X 'big'eminate pulse from the radial; XI, XII, sphygmographic tracings from the femoral; XIII, from the posterior tibial; XIV, XV, from the dorsalis pedis. In all of the tracings P indicates the apex of the curve; R, the dicrotic elevation; e e, the elasticity-elevations; k, the elevation caused by the closure of the aortic semilunar valves. The shortest accessible arterial course is that of the carotids, where the dicrotic elevation attains its greatest height about 0.35 or 0.37 second after the beginning of the pulse. The next shortest accessible arterial course is that of the upper extremity, where the apex of the dicrotic elevation is traced about o 36 or I0.38 or 0.40 second after the beginning of the pulse. ^^" ■■ -^ The longest ORIGIN AND PROPERTIES OF THE ELASTICITY-ELEVATION. I4I course is that of the arteries of the lower extremity, in which the apex of the recoil-elevation is formed about 0.45 or 0.52 or 0.59 second after the beginning of the curve, in accordance with the size of the individual. In children and in small individuals the recoil-elevation occurs accordingly earlier in all of the arteries. If a rubber tube be connected with the carotid or the femoral artery of a dog, the sphygmographic tracing may be recorded also from this tube. Under such circumstances the interval between the beginning of the .curve and the dicrotic elevation will naturally be directly proportional to the length of the tube. 2. The dicrotic elevation in the descending limb of the curve will be the lower and the more indistinct the greater the distance of the artery from the heart. It is not surprising that the secondary wave becomes smaller and more indistinct the further it must travel in the arterial tube. 3. The dicrotic elevation in the pulse will be more distinct the shorter and the more vigorous the primary pulse-wave. It is, there- fore, relatively largest with a short, powerful systole of the heart. 4. The dicrotic elevation is greater the greater the tension in the arterial tube. In Fig. 50 IX and X are recorded with low, V and VI with moderate, and VII with high tension of the arterial wall. Influences Affecting Vascular Tension. — A number of influences are known that afifect the tension in the arterial tube. The tension is diminished by beginning inspiration, vasomotor paralysis, venesection, intermission of the heart's action, heat, and elevation of a part of the body. The tension is increased by beginning expiration, accelerated heart-action, stimulation of the vasomotor nerves, inter- ference with the flow of blood to the periphery (as by conditions of inflammatory stasis), certain poisons (such as lead), compression of other large arterial trunks, the eftect of cold and of electricity on the small vessels of the skin, and inter- ference with the venous flow. Likewise, exposure of the arterial trunks is followed by increased vascular tension on account of the stimulation caused by the atmos- pheric air coming in contact with the arterial wall. Increased arterial tension is observed also in association with a variety of morbid conditions. When the ten- sion is high, the entire sphygmographic tracing is, as a rvile, lower. In conformity with the conditions named, increased tension will be indicated by a lower, more indistinct dicrotic elevation; and diminished tension in the arterial tube, on the other hand, by an enlarged and more distinct dicrotic eleva- tion. A consideration of the laws governing the dicrotic elevation is of great practical significance in the study of the pulse. Moens asserts that the interval elapsing between the primary elevation and the dicrotic wave increases directly as the diameter of the vessel, and that the thickness of the wall diminishes as the coefficient of elasticity becomes smaller. ORIGIN AND PROPERTIES OF THE ELASTICITY-ELEVATION. In addition to the dicrotic elevation a series of more numerous, though much less distinct, often almost imperceptible, movements are appreciable in the sphygmographic tracing. These (marked e e in Fig. 50) are produced by the vibrations of the elastic vessel, which behaves like a tense elastic membrane when it is rapidly and vigorously stretched by the pulse-wave, just as a relaxed elastic sheet of rubber undergoes a series of oscillations when it is suddenly and vigorously stretched and made tense. Similarly, the elastic tube will exhibit oscillatory movements when it passes suddenly from a condition of tension to one of relaxation. These minor elevations produced in the sphygmographic tracing by the elastic vibrations of the arterial wall are known as elas- ticity-elevations. As the elasticitv-elevations are due to the vibrations of the stretched coat of the blood-vessel, the following facts will be readily understood: 142 THE DICROTIC PULSE. 1. In the same artery the variations in elasticity increase in num- ber as the tension of the arterial wall increases. Especially high tension has been encountered chiefly during the cold stage of malarial fever (intermittent fever), and precisely in this connection has the most obvious increase in the elevations also been observed. 2. If the tension of the arterial wall is greatly diminished, the elas- ticity-elevations may disappear. As diminution in the tension favors the development of a dicrotic elevation, the two kinds of elevations have, with respect to their magnitude, an inverse relation to each other. 3. In the presence of diseases of the vessel-wall that diminish or even destroy its elasticity, the elasticity-elevations are either greatly diminished in size or altogether abolished. 4. The greater the distance of the artery from the heart, the greater will be the elasticity-elevations in the descending limb of the curve. 5. When the mean pressure in an artery is heightened on account of interference with the flow of blood in the arteries, the elasticity-eleva- tions are nearer the apex of the curve. 6. The elasticity-elevations vary in number and position in the sphygmographic tracings from the different arteries in the human body. When the arm is held in the vertical position, relaxation and diminution in the elastic tension appear in the course of five minutes in the arteries of the upper extremity, which at the same time contain less blood. The elevations that are designated elasticity-elevations are believed by Moens to owe their origin to numerous small waves that appear to be superadded to the dicrotic elevation. Grashey thinks them only in part due to elastic vibrations. The laws governing the movement of the pulse may be most readily demon- strated by means of investigations in regard to the undulator>' movements in elastic rubber tubes, as has been done by Marey, Landois, Moens. Grashey, G. v. Liebig, and others. THE DICROTIC PULSE. Under the influence of excessive elevation of temperature the pulse in man is sometimes observed to be composed of two beats (Fig. 50), the first being large and the second small and apparently secondai^- to the first. A couple of these beats always correspond to a single systole of the heart. By the sense of touch it is quite possible to feel the two unequal beats separately. The study of the pulse with the sphygmograph has taught that the dicrotic pulse is only an exaggeration of the normal pulse. The palpable secondary beat is only a greatly magnified dicrotic elevation, which under normal conditions cannot be recognized by the palpating finger, but which, when increased by some morbid condition, becomes recognizable by the sense of touch. As regards the causes that are responsible for this increase in the size of the dicrotic elevation, Landois' investiga- tions have yielded the following results: 1. The production of a dicrotic pulse is favored by a short primary pulse- wave, such as occurs usually in the presence of fever, a condition in which the corutractions of the heart are comparatively rapid and unproductive. 2. The dicrotic pulse is favored by reduction of the tension in the arterial system. A short systole combined with diminished arterial tension offers the most favorable condition for the production of the dicrotic pulse. Sometimes the dicrotic pulse is felt only in a certain arterial distribution, while in all the others the pulse-beat is single. This happens especially in the brachial artery on one or other side of the body. Under such circumstances the conditions' for the production of dicrotism in the corresponding arterial area must be especially favorable. These conditions will be found in the local diminution of vascular tension in this area in consequence of paralysis of the vasomotor nerv^es con- trolling it. If the tension be increased, as can readily be done by compressing adjacent or other arterial trunks of considerable size or the corresponding veins, the dicrotic pulse is converted into a single pulse. In the presence of fever, dicro- tism appears to be due to the elevation of temperature (from 39° to 40° C), which causes greater distention of the artery and shorter and quicker heart-beats. DIFFERENCES IN THE TIME-RELATIONS OF THE PULSE. 143 3. It is absolutely indispcnsaljle for the production of the dicrotic pulse that the arterial wall possess its normal elasticity. In old persons with calcified arterial walls dicrotism does not ajijiear. In Fig. 51. .4, B. C illustrate the gradual transition from the normal radial curve (.4) to the dicrotic pulse {B , C) , in which the recoil-elevation (r) appears as an independent elevation. Fig. 51. — Normal Pulse-production of the Dicrotic Pulse. P. caprizans — P. monocrotus. If in the presence of dicrotism of febrile origin the pulse becomes more and more frequent, the next succeeding pulse-beat may begin before the descending portion of the recoil-elevation is completed (Fig. 51, I>, E, F) , or it may even begin at the apex {G) — P. caprizans. Finally, if the next succeeding beat begins in the depression (/) between the primary elevation {p) and the recoil-elevation (r), the latter disappears altogether, and the curve {H) assumes the monocrotic form. DIFFERENCES IN THE TIME-RELATIONS OF THE PULSE. FREQUENT AND INFREQUENT PULSE. In accordance with the number of pulse-beats in one minute, the pulse is designated either frequent or infrequent. Under the influence of fever or other agencies the number of pulse-beats may be considerably increased until they reach 120 or more. Reduction of the pulse-beats to about 40 is observed under certain normal conditions (during the puerperium, in states of hunger, and as an idiosyncrasy in some individuals) . In rare cases these limits may be exceeded in either direction. In periodic attacks as many as 250 pulse-beats have been counted. Such attacks must be designated pyknocardia (the term tachycardia is incorrect because rnx'vr is equivalent to quick) . Abnormal infrequency or spanicardia (the term bradycardia is incorrect because iSpmU^g is equivalent to slow) also occurs; 15, 10, and even 8 beats in the minute have been counted. Under such conditions, disease of the cardiac nerves or of the muscle from over- exertion or disorders in the coronary circulation should be thought of. Deepening of the respiration without acceleration usually causes sorne increase in the frequency of the pulse. Accelerated but superficial breathing is w-ithout effect, while deep, rapid respirations increase the number of pulse-beats. QUICK AND SLOW PULSE. When the development of the pulse-wave is such that the distention of the arterial tube goes on slowly to its maximum and collapse of the distended artery likewise occurs gradually,' the slow pulse is produced: while under opposite conditions the quick pulse results. Among the factors that increase the quickness of the pulse are: slowness of cardiac action; greatly diminished resistance of the arterial coats: dilatation of the smallest arteries, diminishing the resistance to the flow of blood; greater proximitv to the heart. The curve in a sphygmo- graphic tracing from a quick pulse is high and the apex pointed ; a slow pulse yields a low sphygmographic curve, the ascending portion being particularly short, while the apex is broad. 144 COXDITIOXS IXFLUENCING THE FREQUENCY OF THE PULSE. CONDITIONS INFLUENCING THE FREQUENCY OF THE PULSE. In the normal adult male the number of pulse-beats is 71 or 72 in the minute, in the female about 80. Other factors that influence the frequency are : (a) Age: Beats in the Beats in the Minute. Minute. New-bom 130-140 ioth-i5th year 78 1 year 120-130 i5th-2oth " 70 2 years 105 2oth-2 5th " 70 3 " 100 25th-5oth " 70 4 " 97 60th year 74 5 " 94- 90 80th year 70 10 years about 90 Soth-goth year over 80 (b) The length of the body stands in a definite relation to the frequency of the pulse. Volkmann gives the formula p ""l^, in which P and Pj represent the pulse-frequency and L and Lj the body-length. Rameaux suggests the following formula: Ni = N^ 'jy in which N and Xj represent the ptilse-fre- quency and D and Dj the body -length. By means of this formula the pulse- frequency has been calculated from the body-length in a number of healthy individuals with the following results: Length of the Body Pulse: in Units of 10 Cm. Estimated Observed. So-90 90 103 90—100 86 91 loo-iio 81 87 no— 120 78 84 120-130 75 78 130—140 72 76 140-150 69 74 150-160 67 68 160-170 65 65 170-180 63 64 Over 180 60 60 As it is possible to determine the pulse-frequency from the body-length, it must also be possible to calculate the body-length from the pulse-frequency. For this purpose the following is deduced from the foregoing formula: These calculations, naturally, have only a theoretical interest, and it is obvious that for purposes of comparison none but perfectly healthy individuals of the same age and sex and living under absolutely identical conditions must be selected. (c) Of other factors that influence the frequency of the ptilse, it has been observed that muscular activity, heightening of the arterial blood-pressure, in- gestion of food, elevation of teiTiperature , pain, unpleasant sensations in the alimentary tract, nausea, and psychic or sexual excitement accelerate the pulse. Further, the pulse is somewhat more frequent in the standing position (also when the body is raised passively) than in the recumbent posture. Music accel- erates the heart-beat in man and in animals and at the same time raises the blood-pressure. Exposure to increased atmospheric pressure diminishes the pulse-frequency. In the latter condition the first elasticity-elevation more nearly approaches the summit. (d) The diurnal periodicity of the pulse-frequency is of especial interest. The variations rarely exceed a few beats and in a general way XYvey correspond with the course of the temp era ture-ciirve. According to Haim the pulse is most fre- quent with the advent of winter and is least frequent with that of summer. (e) Frequency of the pulse in various animals: Elephant 28, high-bred stallion about 30 (in mares and work-horses it is a little higher), neat cattle about 50, sheep and swine 75, dog 95, cat 130, rabbit from 120 to 150 in one minute.' VARIATIONS IX TIIK RHYTHM Ol- TIIK PULSE. I45 VARIATIONS IN THE RHYTHM OF THE PULSE (ALLORRHYTHMIA;. When the linger is applied to the normal arterv no special rhythm is observed, the beats apparently succeeding one another at regular intervals, although small dirterences may be observed in the intervals between the ])ulse-beats; any more complicated rhythm must be considered an abnormal pulse-movement. Some- times a beat is suddenly dropped from the normal succession — omission of th: pulse. When this is due simply to weakness of the systole, the pulse is designated intcrmiitcnl; when due to the absence of systole, the pulse is designated deficient. The latter occasionally occurs in the obese and has no pathological significance. More rarely a series of pulse-beats is characterized by the successive diminution of individual beats, followed after an interval by a return to the original strength P. myurus. Sometimes a supernumerary pul'se-beat appears to be interpolated in the normal series — intercurrent pulse. These forms of pulse are not infre- quently produced reflexly through the gastro-intestinal tract, or they are observed in cases of neurasthenia after psychical disturbances, often after i'ntoxi- FiG. 52. — .Alternating Pulse. cation with alcohol or tobacco, in the absence of any changes in the heart. Occasionally an intercurrent systole of the auricles takes place in conjunction with the deficient or the intermittent pulse. The regular alternation from a high to a low pulse is known as alternating pulse. The peculiarity of the bigeminate pulse consists, according to Traube, in the circumstance that the pulse-beats always occur in pairs, so that the second beat always begins close to the descending limb of the curve of the first. In the same w^ay a trigeminate or a quadri- geminatc pulse may be produced. Knoll found in experiments on animals that these varieties of the pulse occur whenever greater resistances develop in the circulation, increasing the demands on the heart. In man also their occur- rence points to a disproportion between the strength of the heart-muscle and the work to be performed. Absolute irregularity of the heart is designated arrhythmia or delirium cordis. VARIATIONS IN THE STRENGTH, THE TENSION, AND THE VOLUME OF THE PULSE. The relative strength of the pulse-beat (strong and feeble pulse) may be deter- mined by observing the weight the pulse is capable of raising. For this purpose a weighted sphygmograph may be used, the pad of which is applied to a section of the artery that must be constant in extent. The writing lever naturally ceases to act as soon as the pressure on the artery exceeds the strength of the pulse- beat. The load directly indicates the strength of the pulse. According to G. v. Liebig the pulse in a man with a tendency to pulmonary tuberculosis is readily compressed (feeble) and it has at the same time a tendency to dicrotism. The pulse appears hard or soft when the artery, in conformity with the mean blood-pressure but independently of the strength of the individual beat, offers a greater or lesser resistance to the palpating finger — hard and soft pulse. The pulse is said to be full when the artery is greatly distended and over- filled, irrespective of the size of the pulse itself, and empty w^hen the artery is thin and poorly filled. In determining the tension of an arter}^ and of the pulse, that is, whether the latter is hard or 50//, it should always be noted whether the artery exhibits that qualitv only during the pulse-wave or also \vh'\\e the vessel is at rest. All arteries are harder 'during the pulse-beat than in their resting state, but an artery-- that during the pulse-beat is quite hard may during the pause between the beats appear hard, or under other circumstances soft, as, for example, in cases of aortic in- 146 SPHYGMOGRAPHIC TRACINGS FROM DIFFERENT ARTERIES. sufficiency, in which, after the contraction of the left ventricle, a large quantity of blood flows back into the ventricle through the leaky semilunar valves of the aorta, and the arteries consequently become relatively bloodless. The pulse-ten- sion is lowest in the standing, higher in the sitting, and highest in the recumbent position. Other things being equal, the volume of the pulse-waves may be directly determined from the size of the sphvgmographic tracings. Thus, the foUowmg types of pulse are distinguished: the targe and the small pulse; the imequal pulse; the extremely weak pufse, which is felt only as a succession of faint tremors {ircmtilous pulse); and the indistinct, scarcely appreciable pulse {filiform and insensible pulse). A large soft pulse is designated a dilated pulse; a small hard pulse a contracted pulse; a small pulse of great frequency a vermicular pulse; a large, hard, frequent pulse a serrate ■p^As&■, a large, extremely hard pulse a t'^ferani pulse; and a pulse that is different in two corresponding arteries on o^osite sides of the body (due to stenosis, compression or kinking on one side) a different pulse. SPHYGMOGRAPHIC TRACINGS FROM DIFFERENT ARTERIES. SPHYGMOGRAPHIC CURVE FROM THE CAROTID ARTERY. (Fig. 50, I, II, III; Fig. 57, C and Q.) The ascending limb is exceedingly steep, the apex of the curve (Fig. 50, I, P) , traced with a minimum degree of friction, being pointed and prominent. The first elevation below the apex is a small one, the valve-closure elevation (Fig. I, K); this is due to the positive wave, which is produced during the abrupt closure of the semilunar valves at the root of the aorta and is propagated with but little loss of force into the carotid artery. Close to this elevation and visible only in curves traced with a minimum of friction is the highest elasticity- elevation, which is small (Fig. 50, II, e). Further down, but still above the middle of the descending limb, is the dicrotic elevation (R), which is usually larger and is produced by the recoil of the positive wave from the already closed semilunar valves. Relatively, that is, in comparison with the remaining portions of the curve, the dicrotic elevation is slight, in consequence of the high tension prevailing in the carotid artery. After the dicrotic elevation has been formed, the descending limb falls at first abruptly to about the upper third and from this point, in well-traced curves, the writing lever in its downward movement usually traces two more small elevations, the upper of which is an elasticity- elevation, while the lower, which under favorable conditions appears much larger (Fig. 50, III, Rj), represents the second dicrotic elevation. We have here a true tricrotism, Avhich is the more readih' recorded in the carotid, because that artery is shorter than the arteries of the extremities. SPHYGMOGRAPHIC TRACING FROM THE AXILLARY ARTERY. (Fig. 50, IV.) The ascending limb of the curve is exceedingly steep. Not far from the apex there is a small valve-closure elevation (K), not unlike that seen in the carotid tracing. Below the middle is found the dicrotic elevation (R), which is fairly high, higher than in the carotid tracing, because in the axillary artery the reduc- tion in arterial tension permits of a greater development of the dicrotic wave. Further down, between the apex of the recoil-elevation and the foot of the curve, two or three smaller elasticity-elevations (e e) are seen. SPHYGMOGRAPHIC TRACING FROM THE RADIAL ARTERY. (Fig. 47; Fig. 50. V-X; Fig. 57, R and R'.) The ascending limb (Fig. 50, V) is of medium height; the ascent is moderately abrupt and suggests the shape of the letter f . The apex (P) is usually well marked. Below the apex there appear, when the tension is considerable, two (V, e e), w^hen the tension is slight, only one elasticity-elevation (VI, IX, e). There then follows at about the m'iddle of the descending limb the recoil-elevation (R), which is usually well marked. This is the more distinct and the better pronounced the larger the number of factors present that favor the development of the secondary wave. It is smallest when the pulse is small and hard, and the artery is greatly distended (Fig. 50, VII, R) ; larger when the tension is moderate; greatest" in the SPHYGMOGRAPIIIC TRACINGS FROM DIFFERENT ARTERIES. M7 dicrotic pulse. In the remaining portion of the descending Hmb, down to the base of the curve, two or three lesser elevations are encountered, the first two being elasticity-elevations (e e) and the lowest apj^reciable only in rare cases and probably indicating a second recoil-wave. The sphygmographic curve of the brachial artery at the bend of the elbow is somewhat larger, but does not differ materially from the radial curve. SPHYGMOGRAPHIC TRACING FROM THE FEMORAL ARTERY. (Fig. 50, XI, XII.) The ascending limb is steep and high; on the apex of the curve, which is quite frequently somewhat flat and broad, there is recorded the closure of the semilunar valves (K) . From that point the curve falls in an abrupt manner to about the lower third. The recoil-elevation (R) appears late after the beginning of the curve, and beyond that point the curve is interrupted in both its ascending and its descending portion by small elasticity-elevations (e e) . SPHYGMOGRAPHIC TRACINGS FROM THE DORSALIS PEDIS ARTERY AND FROM THE POSTERIOR TIBIAL ARTERY. (Fig. 50, XIV, XV.) (Fig. 50, XIII, and Fig. 53.) In the sphygmographic tracing from the dorsalis pedis artery the signs indi- cating the great distance from the wave-producing apparatus (the heart) arc obvious. Thus, the ascending limb of the curve exhibits a gradual ascent and is low, while the re- coil-elevation takes place late. In the descending limb two elasticity-elevations are found so near the apex (Fig. 50, e Cj) that the upper one usually occupies a point close to the latter. The elasticity- elevations in the lower portion of the descending limb are, as a rule, poorly developed. The tracing from the posterior tibial artery in many respects resembles the preceding, especially with regard to the time-relations. The tracing shown in Fig. 53 was taken from a medical student, wiiose height was 180 cm., with the aid of the angiograph, a moderate weight being used and the tracing being recorded on a tablet attached to a vibrating tuning-fork. Fig. 5,5. — Tracing from the Pos- terior Tibial .\rtery, Recorded on the Tablet Attached to a Vi- brating Tuning-fork by means of Landois' Angiograph. By measurement it is found that 1-2 9.5 I1-3 20 1 1-4 .30-5 1-6 61 One vibration is equivalent to 0.01613 .second (-0.: = 0.153 second 323 ,492 .984 PHENOMENA OF ANACROTISM. As a rule, the ascending limb in the sphygmographic tracing presents the shape of the letter f, with a rather abrupt rise. The pulse-beat throws the arterial w^all into elastic vibration, as has been explained, the number of vibrations de- pending largely upon the degree of arterial tension. In general the distention of the artery, or the tracing of the ascending limb of the curve, which is the same thing, is completed so rapidly that the time is equivalent to a single elastic vibration. The long-draAvn-out f-shaped figure is practically nothing but a long-drawn-out elastic vibration. When, however, the number of elastic vibrations is small, and the evolution of the ascending limb of the curve is relatively prolonged, two long-drawn-out hump-like curves are some- times seen in the ascending limb of the tracing. A condition of this kind, however, is still to be regarded as normal. (See the elevations in Fig. 50, VIII, at i and 2 ; and at X I and 2.) If, however, a number of closely set elastic vibrations are produced toward the upper portion of the ascending limb of the sphygmographic tracing, so that the apex appears cut off obliquely from the ascending limb and indented, there results the phenomena of anacrotism (Fig. 54, a a), which, like the dicrotic pulse, belong in the domain of pathology. Anacrotism is observed: i. When the time occupied by the inflow of blood 148 PHENOMEXA OF ANACROTISM. is longer than the duration of the elastic vibration, for example in cases of dilatation and hypertrophy of the left ventricle. This is illustrated in Fig. 54,^ A, which represents the radial curve from a patient with contracted kidney. Under such conditions the great mass of blood propelled with each systole requires an ab- normally long time to effect distention of the already greatly distended artery. 2. \Vhen the distensibility of the arterial tuVje is diminished, a quantity of blood, which in itself is not increased, will require a longer time to effect distention of the walls. Such a condition is observed in old persons whose arterial walls have acquired great rigidity. As cold tends to contract the arteries, so that they are reduced to a condition of diminished distensibility, it is not difficult to under- stand that the pulse is likely to assume the characters of anacrotism within an hour ^ter a cool bath (Fig. 54, D). The carotid jjulse in the rabbit becomes anacrotic after irritation of the vasomotor nerves. 3. When, owing to blood-stasis as a result of extreme retardation of the blood- current, such as occurs in paralyzed limbs, the quantit}- of blood injected into the arterial system with each systole is incapable of effecting normal distention of the arterial wall, anacrotic elevations are seen in the sphygmographic tracing (Fig. 54. B). 4. When, after ligation of an artery, the blood can enter the peripheral segment through the relatively small collateral circulation only within a comparatively long time, the distention of the arterial coat will be marked by several elastic vibrations. Wolff succeeded in producing these in tracings from the radial artery not yet possessing distinct anacrotic characters by applying compression above the brachial artery and thus retarding the flow of blood into the radial artery. Also in cases of aortic stenosis, a condition in which the blood can enter the arteries but slowly through the aorta, anacrotism has frequently been observed (Fig. 54, C). Fig. 54. — Anacrotic Tracings from the Radial .\rtery : a a, anacrotic notches. In the same category belongs also the phenomenon of the so-called recurrent pulse. When the radial arten' is compressed at the wrist, the pulse at once reappears at a point situated peripherally from the site of compression, being transmitted by the arterial palmar arches. The tracing from such a pulse ex- hibits anacrotism and in addition (as is readily understood) a diminished recoil-elevation, as well as more numerous and more distinct elasticity- elevations. 5. A peculiar form of anacrotism is observed in connection with high grades of aortic insufficiency. The most characteristic sign of this lesion is the permanent patency of the aorta. Hence, not only will waves be propagated in the root of the aorta by the movements of the ventricle, but also the contraction of the hypertrophied left auricle will cause a wave-movement in the ventricular blood that is at once propagated through the patulous orifice of the relatively flaccid aorta and its branches. This is followed by the true pulse-wave, which is pro- duced by the contraction of the ventricle. It is obvious that not only is the wave produced by the contraction of the auricle smaller, but it also precedes the principal wave. The peculiarity of the anacrotism in sphygmographic tracings from large vascular trunks, taken from cases of insufficiency of the aortic valves, is that the auricular wave occurs before the ventricular wave in the ascending limb. This anacrotism manifests itself in curves taken from the larger vascular trunks because the wave, in itself but small, gradually disappears as it advances peripherally toward the smaller vessels. Fig. 55, I, represents a sphygmographic tracing from the carotid of a man. It exhibits an abrupt ascending limb, caused by the force of the hypertrophied heart. At the apex of the curve there appear quite constantly two sharp inden- tations, the more anterior of which, having a narrower base, requires less time for IXFLUEXCE OF THE RESPIRATORY MOVEMENTS. '49 its development than the second. The anterior (A) is the anacrotic auricular wave, the second (V) the ventricular wave. Fig- 5.V II- represents a sphygmographic tracing from the subclavian artery of the .same individual. It is recognized at once l)y the peculiarity that the anacrotic notch (a) occupies approximately the junction of the lower and middle thirds of the ascending limb. The recoil-elevation (R) in this curve also is rela- tively small, for the same reason as in the carotid curve. Below the recoil-eleva- tion are seen feebly developed elasticity-elevations. Tracings from the femoral artery made with a minimum of friction on the part of the writing stylus exhibit an indentation (Fig. 55, III, a) immediately preceding the ascending limb of the curve, which is blurred in coarse curves. A comparison of this indentation with the anacrotic notch at the lower portion of the ascending limb of the curve from the subclavian artery (Fig. II) will convince the observer that the anacrotic auricular notch must be sought in this well-marked elevation. It should be mentioned at this point that sphygmographic tracings from cases of aortic insufficiency are characterized further by the following peculiarities: Fig. 53. -I, II, III, Curves E.xhibiting Anacrotic Elevation, a, in .\.ssociation with^Insufficiency of the Aortic Valves. I, the great height of the curve; 2, the rapid fall of the writing lever from the apex. Both of these peculiarities are due to the fact that a large quantity of blood is thrown into the arteries by the enlarged and hypertrophied ventricle, a considerable portion of which flows back into the ventricle after the completion of the systole. In accordance with observations i and 2 the pulse is therefore a quick one. 3, A distinct notch is not rarely found at the apex representing an elastic vibration of the greatly distended arterial wall. 4, In tracings taken from cases of aortic insufficiency, as, for example, in that shown in Fig. 55, I, the recoil-elevation (R) is moderate as compared with the size of the curve, because, owing to the lesion of the aortic valves, the pulse-wave in its recoil does not impinge upon a suffi- ciently large surface. When the destruction of the semilunar valves is considerable, the recoil-elevation must be produced by the impact of the recurrent wave against the opposite ventricular wall. Below the recoil-elevation the curve presents two or three faintly marked elasticity-oscillations (i, 2, 3). The enormous height of the entire curve is sufficiently explained by the massive column of blood injected into the arterial system by the greatly hypertrophied and dilated ventricle. INFLUENCE OF THE RESPIRATORY MOVEMENTS ON SPHYG- MOGRAPHIC TRACINGS. The respiratory movements exert a distinct influence on the move- ments of the pulse by virtue of two different factors: (i) the purely physical diminution of arterial pressure that accompanies each inspira- tion, and the increase attendant upon each expiration; (2) the variations in blood-pressure, due to excitation of the vasomotor nerve centers, which attend the respiratory movements. 150 INFLUENCE OF THE RESPIRATORY MOVEMENTS. When it is remembered that during inspiration, owing to the dila- tation of the thorax, the arterial blood is retained in larger quantities within the chest-cavity, while the venous blood is more actively drawn into the right auricle by aspiration, it is evident that the tension within the arteries must at first diminish during inspiration. The expiratory diminution in the size of the thorax, on the other hand, favors the flow of arterial blood into the vascular trunks and dams the venous blood back toward the venae cavag, — two factors that tend to heighten the tension in the arterial system. Furthermore, the expiration that immediately precedes an inspiration allows less blood to enter the heart, so that systolic contractions at the beginning of inspiration throw a somewhat smaller quantity of blood into the aorta; the opposite result attends the inspiration that immediately precedes an expiration. These variations in tension explain the differences in the size of sphygmographic tracings taken during inspiration and during expira- tion, as seen in Fig. 56, and in Fig. 50, I, III, IV, in which / indicates the inspiratory, and E the expiratory curve. The differences are as follows: (i) the greater tension in the arteries during expiration causes a general heightening of the level of all curves coinciding with expira- tion; (2) during expiration the ascending limb is prolonged because the expiratory movement of the thorax tends to increase the force of the wave produced during expiration; (3) the magnitude of the recoil-ele- vation must be less on account of the increase in pressure during ex- FiG. 56. — Influence of Respiration on the Sphygmographic Tracing (after Riegelj. piration; (4) for the same reason the elasticity-elevations are more distinct and approach more nearly the level of the apex of the curve. During the stage of expiration the pulse is somewhat more frequent than during the stage of inspiration. This purely mechanical effect of the respiratory movements is modi- fied by the stimulation of the vasomotor center that takes place at the same time. Owing to this nervous influence the arterial pressure — which, it is true, is lowest during inspiration — begins to rise during inspiration and continues to increase until the end of that phase, reaching its maximum at the beginning of expiration. During the remainder of expiration the blood-pressure falls, and again reaches its lowest level at the beginning of inspiration. These influences leave their im.print upon the sphygmographic curves, which, accordingly, present the signs of increasing or diminishing arterial tension, in accordance with the phases of respiration. There is thus to a certain extent a displace- ment of the pressure-curve to correspond with the respiratory curve. The statements of different observers vary with regard to the effect of strong expiratory pressure and of forced inspiration on the shape of the pulse-waves. The simplest way of producing strong expiratory pressure is by means of Valsalva's experiment. During this procedure there is at first an increase in the blood-pressure, with the formation of pulse-waves resembling those produced during ordinary expiration — IN'FLUliXCE OF THE RESPIRATORY MOVEMENTS. 151 the recoil-elevation particularly being distinctly less pronounced. If, however, the forced pressure is maintained, the sphygmographic curves begin to exhibit signs of diminished tension. This is due to the influ- ence of the vasomotor center, acting refiexly through the pulmonar\' nerves. It must be assumed that forced pressure — such as is produced in Valsalva's experiment — when continued, exerts a depressing effect on the vasomotor center. Coughing, singing, and reciting act in a manner similar to Valsalva's experiment; the pulse-frequency being at the same time increased. On the conclusion of Valsalva's experi- ment the blood-pressure rises until it exceeds the normal by almost as much as it had before been diminished, to return again to the normal after a few minutes. Conversely, when the circulation is more completely emptied by means of J. Miilier's experiment, the sphygmographic curve at first exhibits the characteristic signs of diminished pulse-tension, particularly a higher and more distinct recoil-elevation. After a time, however. C: Fig. 57. — The Effect of Marked Expiratory and Insniratory Pressure on Sphygmographic Curves: C and R, tracings made from the carotid (C) and the radial (R) during Mailer's experiment; Ci and Ri , similar traangs made during Valsalva's experiment. The curves were recorded on a tablet attached to a \ibrating tuning- fork. likewise owing to nervous influences, increased tension may manifest itself. In Fig. 57, C and R represent carotid and radial curves recorded during Miiller's experiment, in which the great recoil-elevation clearly shows the diminished tension in the vessels; d and Rj represent curves taken from the same individual during Valsalva's experiment and clearly show the opposite condition. Expiration into a vessel like a spirometer (Waldenburg's respiratory apparatus, for example) filled with compressed air has the same effect as Valsalva's experi- ment, causing after a time a slight lowering of the blood-pressure and a simulta- neous increase in the frequency of the pulse. Conversely, inspiration of rarefied air from the same apparatus acts like Muller's experiment, heightemng the effect of inspiration, and it may after a time increase the blood-pressure, which, as the experiment is continued, may remain high or fall again. Inspiration of compressed air lowers the mean blood-pressure, and the after- effect is maintained. The pulse during and after the experiment is increased in frequency. Expiration into rarefied air increases the blood-pressure. These last-mentioned alterations emanate from the nervous system; they are not produced as readily and are not equally marked in all individuals. Exposure to compressed air (in the pneumatic chamber) lowers the pulse- curve: the elasticitv-oscillations become correspondingly more distinct, as the recoil-elevation diminishes and finally disappears. At the same time the heart s 152 INFLUENCES OF PRESSURE ON SPHYGMOGRAPHIC TRACINGS. action becomes slower and the blood-pressure is raised. Exposure to rarefied air has the opposite effect as the sign of diminished tension in the arterial system; but only when as a result the breathing is enfeebled and the pulse is accelerated. Pathological, — In the presence of adhesions between the heart and the large blood-vessels, on the one hand, and the stirrounding structures on the other, the Fig. 5S. — Paradoxical Pulse (after Kussmaul), pulse may be much diminished in size and otherwise altered during inspiration, or it may even disappear altogether. This phenomenon has been called the paradoxical pulse. It is due to flattening of the subclavian artery in consequence of elevation of the first rib. Varieties of this pulse can be produced also in healthy individuals by voluntary alteration of the breathing during inspiration. THE INFLUENCES OF PRESSURE ON THE SHAPE OF SPHYG- MOGRAPHIC TRACINGS. The changes induced in the movement of the pulse by increasing the pressure upon it aft'ect both the shape of the sphygmographic curves and their time-rela- tions. Fig. 59 shows at a, b, c, d and e a series of radial curves; a was taken with a minimal pressure and the remainder with a pressure of 100, 200, 250 and 450 grams respectively. The curves A and B, on the other hand, show^ the time-relations of curves taken when the pressure was progressively increased. A sttidy of these curves yields the following results: IIIIP T^ 200 250 ^50 Fig. 5q. — Variations in the Shape of Sphygmographic Curves Produced by Increasing the Pressure. 1. With a small load the recoil-elevation is relatively indistinct; the entire curve appears high. 2. With a moderate load, about from 100 to 200 grams, the recoil-elevation is most distinct ; the entire curve appears somewhat smaller. 3. As the load is increased, the height of the recoil-elevation diminishes. 4. The smaller elasticity-oscillation immediately preceding the recoil-elevation manifests itself only Avhen the load becomes considerable (from 200 to 300 grams). 5. The quickness of the pulse varies as the load is increased, the time required for the development of the ascending limb being shortened, and that required for the descending limb prolonged. 6. The height of the entire curve diminishes as the load increases. These points sufficiently emphasize the importance of taking the load of the registering instrument into consideration and the necessity of indicating the actual VELOCITY OF PROPAGATION OF PULSE-WAVES. I 53 weight employed, in order to form a correct interpretation of the shape of the pulse-waves. It appears from an examination of the radial curves A and B, the former of which was taken with a weight of 100 grams, and the latter with a weight of 220 grams, from the same individual and at the same time (i vibration 0.016 13 second), that changes in the load may produce differences also in the chronological develop- ment of the sphj'gmogram. When the pressure on an artery is continued for a considerable period of time, the force of the pulse gradually increases. If the greater load is then removed and a smaller one substituted, the sphygmographic curve not infrequently assumes the form of a dicrotic pulse-wave and the recoil-elevation Vjecomes distinctly marked. During the high pressure the blood is forced to make a passage for itself by dilating the collateral vessels. If, then, the main channel is again thrown open, the entire bed of the .stream, of course, suddenly becomes much wider. In consequence, there results a greater development of the recoil-elevation. Tracing X in Fig. 50 represents such a dicrotic series, taken after the application of a heavy weight. VELOCITY OF PROPAGATION OF PULSE-WAVES. As the pulse-wave passes from the root of the aorta into all the arteries toward the periphery, the pulse is felt earlier in the arteries nearer the heart than in those at a greater distance. This phenomenon was variously confirmed and variously disputed until E. H. Weber determined the movement of rapidity of the pulse- wave from the difference in time of the pulse in the external maxillary artery and in the dorsalis pedis artery and found it to be 9.240 meters in a second. With such great velocity of the pulse-wave, says this investigator, it cannot be regarded as a short wave traveling along the arteries, but so long that a single pulse-wave cannot find room in the entire distance from the beginning of the aorta to the artery of the big toe. PROPAGATION OF PULSE-WAVES IN RUBBER TUBES. As it is possible by the intermittent injection of water into rubber tubes to produce waves similar to those produced by the pulse, it is important to learn the results that have been obtained from a study of this undulatory movement. According to E. H. Weber, the propagation- velocity of these waves is 11.259 meters in one second. Positive and negative waves are propagated with equal velocity and the velocity of the waves is the same whether they have been pro- duced slowly or rapidly. 2. According to Bonders, the velocity of the waves is directly proportional to the coefficient of elasticity of the walls of the tubes. It is proportional to the square root of the coefficient of elasticity of the walls of the tubes, with the same lateral pressure. 3. The velocity of the waves increases with the thickness of the walls; it is proportional to the square root of the thickness of the walls, with the same lateral pressure. 4. The velocity is inversely proportional to the square root of the diameter of the tubes, the pressure remaining constant. 5. According to Marey, the velocity diminishes as the specific gravity of the fluid increases. It is inversely proportional to the square root of the specific gravity. Experiments with Rubber Tubes. — In determining the time-relations Landois employed the following method. He recorded the waves by means of the angio- graph on a recording surface attached to a vibrating tuning-fork (Fig. 60) . After measuring a certain distance on a long rubber tube, the extremities a and b are placed under the pad of the sphygmograph. B is a compressible bulb, by com- pression of which a positive wave is thrown into the tube, Q is a portable mercu- rial manometer, which indicates the pressure in the apparatus. As the pulse- wave first passes through at a and then at b, two elevations, i and 2, are recorded. Each small indentation is equivalent to 0.0 16 13 second. The time-relations can be determined by simply counting these indentations. P ro pagation-velocity of Water-waves and M ercury-waves within Elastic Tubes. — Landois' experiments, published in 1879, yielded a propagation-velocity of 11.809 meters in i second, with an internal pressure of 75 millimeters of mercury. 154 PROPAGATION-VELOCITY OF THE PULSE-WAVES IN MAN. Landois was unable to find any difference in the propagation-velocity whether the waves were produced rapidly or slowly, or whether they were large or small. In order to determine whether the material of which the elastic tube is made has any influence on the propagation-velocity of pulse-waves, Landois employed a rather rigid, slightly distensible tube made of gray vulcanized rubber. It was found that the propagation-velocity of the waves in this tube is greater than in a softer and more distensible elastic tube. This observation is in accord with the fact that the intravascular pressure Fig. 6o. — Method of Recording the Pulse-curves Obtained from an Elastic Tube on a Tablet Attached to a Vibrat- ing Tuning-fork. Each indentation is equivalent to 0.01613 second. exerts a demonstrable influence on the propagation-velocity of the pulse-waves; for when the pressure was raised, the waves were propagated with a somewhat diminished velocity. This phenomenon is due to the fact that the distensibility of rubber tubes increases with the pressure, whereas in the arteries the distensibility of the walls diminishes under the same conditions. The influence exerted by the specific gravity of the fluid was determined by Landois for mercury, the waves of which move with about one-fourth the velocity of waves produced in water. PROPAGATION- VELOCITY OF THE PULSE-WAVES IN MAN. Method of Examination. — Landois attached to two different arteries long levers consisting of reeds and so arranged that they both recorded their pulse- curves simultaneously on the same recording surface attached to a vibrating tuning- fork. A quick tap on the fork noted the identical moment on both curves, and by counting the indentations from this point to the beginning of each cxirve the difference in time was obtained. In this way Landois developed the following values from a student 174 cm. PROPAGATION-VELOCITY OF THE PULSE-WAVES IN MAN. 155 in height: The dilYcrence between the carotid and the radial was 0.074 second (the distance being estimated as 62 cm.); between the carotid and the femoral, 0.068 second; between the femoral (at the fold of the groin) and the posterior tibial, o.oc)7 second (the estimated distance being 91 cm.). Results. ^The foregoing observations yield a propagation-velocity for the pulse-waves in the distrilnition of the arteries of the upper extremities of 8.43 meters in i second, and for the arteries of the lower extremities 9.40 meters in i second. It appears that in the less distensible arteries of the lower extremities the propagation-velocity is greater for the same distance than in the arteries of the upper extremities. For the same reason it is less in the peripheral arteries and in the more yielding arteries of the child. Modifying Influences. — -Increase in blood-pressure accelerates, reduction in blood-pressure diminishes, the propagation-velocity of the pulse-wave. Hence, in animals, hemorrhage, slowing of the heart-beat through stimulation of the vagus, division of the spinal cord, dilatation of the vessels (by heat, profound morphin- narcosis or amyl nitrite) cause retardation; while, on the other hand, irritation of the spinal cord causes an acceleration in the movetncnt of the pulse-wave. The length of the pulse-waves is found by multiplying the time occupied by the entrance of the blood into the aorta, which is from 0.08 to 0.09 second, by the propagation- velocity of the pulse-waves. A more convenient method is to apply the two tambours of Brondgeest's pan- sphygmograph (Fig. 44) to the two points on the artery to be examined and have one writing-lever record its tracing above that of the other on a plate at- tached to a tuning-fork. The method may be made quite trustworthy by con- structing both apparatus with leaden pipes and filling these with water, in which the propagation of the pulse-wave is quite uniform. A short tap on the tuning- fork (at points indicated by the arrows in Fig. 61) marks the identical instant Tib. fost. I Carot. Fig. 61^ — Tracings from the Carotid and Posterior Tibial Arteries, Made Simultaneously with Brondgeest's Pan- sphygmograph on a Tablet Attached to a Vibrating Tuning-fork. The arrows indicate identical moments. in the two curves. The difference in time is determined by simply counting the vibrations. Fig. 61 shows the curves from the carotid and the posterior tibial taken at the same time from a tall healthy student. The time-difference is 0.137 second. If the arteries are widely separated or if the observation is made on the heart and on an artery, it is possible to connect the two pads by means of a forked tube with a single writing-lever, and the two pulse-curves, when traced one into the other, can be recognized in the sphygmogram. In Fig. 62, A is the curve of the ulnar artery, B the same, together with the curve produced by the contraction of the ventricle v H p running through it, and obtained by means of a forked tube. In the curve B, H indicates the apex of the ventricular contraction, P the primary pulse-apex of the ulnar curve; v indicates the beginning of the ventricular contraction, p that of the ulnar pulse. It appears from these curves that the interval between the beginning of the ventricular con- traction and the beginning of the pulse in the ulnar artery, in the individual examined, was equivalent to 9 vibrations = 0.15 second. Grashey applied two sphygmographs to two different arteries and caused the writing-levers to strike sparks into their respective curves from a spark-inductor, so that the sparks marked the identical instant of time in each curve. In this way he determined the propagation-velocity (from the diflference between the rad'ial pulse and that of the dorsalis pedis) to be 8.5 meters in i second. Pathological. — In cases presenting diminished elasticity of the arteries, as, for 156 OTHER PULSATORY PHENOMENA. instance, due to calcification, the propagation of the pulse-wave must be more rapid. Local dilatation of the arteries, such, for example, as has long been known in the form of aneurysms, cause a retardation of the pulse-wave; local steno- sis has a similar effect. Relaxation of the vessel-walls during high fever retards the movement of the pulse-wave. In accordance with what has been said concerning the course of the recoil- wave, its time of appearance must also be affected by the differences mentioned. Fig. 62. — Tracing from the Ulnar Artery on a recording surface Attacfied to a Vibrating Tuning-fork (1 = 0.01613 sec): P, the ape.\ of the curve; e e, elasticity-Wbrations; R, recoil-elevation; B, curves from the same ulnar artery, taken at the same time with v H P = the ventricular contraction of the same individual. It must appear earlier when the blood-pressure is raised, and also in atheromatous than in healthy arteries; but relatively late in the elastic arteries of the child. The latter point was determined by Landois by mensuration. While in a man, 30 years of age and 172 cm. in height, the apex of the recoil-elevation was reached 0.387 second after the beginning of the radial curve, Landois found that the apex in a girl, 8 years old and 103 cm. in height, occurred at the end of 0.387 second, evidently indicating a relative delay. OTHER PULSATORY PHENOMENA. Oral and Nasal Pulse; Tympaiu'c Pulse. — In consequence of the pulsatory movement in the arteries of the soft tissues, the air contained within the oral and nasal cavities is also set into pulsating movement when the glottis is closed, and which can be registered with the aid of the cardiopneumograph. The tracings obtained in this way, and which must closely resemble the sphygmographic tracings from the carotid artery, are of course relatively small, but they can be made larger by increasing the force of the heart. This pulse may be considerably intensified in the presence of pathological enlargement of the heart, dilatation of the left ventricle and thickening of its walls. If a ring containing a 'soap- bubble be inserted hermetically between the lips, the light-reflex in the bubble (seen in a mirror) reproduces almost perfectly the oscillations of the oral pulse. As a result of the systolic swelling of the vascular soft parts in the tympanic cavity analogous pulsation may be observed in the intact drumhead, or possibly in small bubbles of froth accidentally adherent to openings in a perforated membrane. If the visual field be darkened, each pulse-beat during violent exertion is often accompanied by a pulsatory illumination. Conversely, if the visual field be brightly illuminated, a corresponding obscuration of the field may take place. Pulsation is sometimes observed in the retinal arteries with the ophthalmoscope, especially in cases of aortic insufficiency. The orbicularis palpebrarum muscle under similar conditions contracts syn- chronously with the pulse. This contraction appears to be due to the fact that the beat of the ptxlse excites the sensory nerves and reflexly causes a contraction. In this connection attention should be called to an observation made by the brothers Edward and William Weber, which seems to be in accord with this point. They found that, in walking, the pulse and the step not infrequently coincide. Landois believed that this phenomenon may be explained by assuming that the pulse-beat stimulates the muscular mass of the thigh into contraction, to which gradtially all the mitscles of the thigh accommodate themselves at each step. As the blood-vessels dilate while the muscles are contracting and the movement of the venous blood is accelerated, the coincidence of pulse and step has the addi- tional advantage that the mass of blood to be moved, which is greater during the pulse-beat, is thereby better enabled to pass through the masses of muscle-tissue. VIBRATION' OF THE BODY DUE TO ACTION OF THE HEART. I 57 When the legs are crossed, the pulse-beat and the rucoil-elevation arc dis- tinctly recognized in the supported limb. If with the body at rest in the recumbent position the lower and upper incisors are brought gently in contact and kept so, a double beat of the teeth against each other will become audible, as the pulse-wave in the facial arteries elevates the lower jaw. The rapidly succeeding second impact is not due to the recoil- elevation, however, but to the concvission produced 1)y the closure of the semilunar valves. A pulsator}^ movement is communicated to the brahi by the large arteries at its base and in which all the individual features of sphygmographic tracings made from the cerebral arteries are recognized. Among the pathological phenomena of the arterial pulse must be mentioned the systolic pulsations in the epigastrium, which are produced in part by the heart in cases of hypertrophy of the right or left ventricle when the diaphragm is depressed, and in part by the forcible pulsation of the abdominal aorta or of the celiac axis, which is usually dilated under such conditions. Abnormal dilata- tions (aneurysms) of the arteries also occasion abnormally strong pulsations in other situations, as, for example, in the trachea in cases of aneurysm of the ascend- ing or transverse position of the aorta. Hypertrophy and dilatation of the left ventricle may cause marked pulsation in the arteries lying nearest the heart. In the presence of similar conditions in- volving the right ventricle the pulsation of the pulmonary artery in the second left intercostal space is intensified and becomes both visible and palpable (Fig. 34). In cases of aortic insufficiency with good compensation in vigorous individuals when the spleen is swollen and palpable (acute infection), this organ also pulsates. Pulsation is visible also in the penis. In cases of exophthalmic goiter the spleen may pulsate for months. VIBRATION OF THE BODY DUE TO THE ACTION OF THE HEART AND THE COURSE OF THE BLOOD-WAVES. The movement of the heart and of the pulse communicates a vibration to the body as a whole. When a person stands erect on the platform of a spring- scales, the pointer instead of assuming a position of rest plays up and down in accordance with the phases of the heart's action. In his observations (Fig. 63, I) Landois employed a low box open at the top (K), with a number of rubber bands, close together, stretched across, not far from one of the narrow sides at a b. A quadrangular board (B) was then placed with one extremity resting on the rubber bands and the other on the narrow edge of the box. The subject to be experimented with (A) takes his position on this board and stands erect and steady. In order to determine the cause of the individual indentations in the curve, the vibration-curve and the curve of the apex-beat were recorded at the same time for the same individual. For this purpose one box (p) of Brondgeest's pan- sphygmograph (Fig. 44) is applied to the vibrating board, and the pad of the other box to the situation of the apex-beat in the person to be examined. Both writing-levers record their curves on the plate attached to the vibrating tuning- fork: the upper is the vibration-curve, the lower the curve of the apex-beat. As it is impossible to exclude the marked vibrations in the apparatus itself, the information obtained with regard to the mode of production of the vibrations is only approximately accurate. At the instant of ventricular systole there occurs a short depression, corresponding to the greater pressure of the body on the elastic support ; then the body rises suddenly in response to the upward impulse of the blood-wave in the carotid and subclavian arteries. After the closure of the semilunar valves, which is registered by a slight elevation, the blood- wave, as it courses down the body again, causes increased pressure on the platform. The upward movement that now follows may be due to the centripetal wave that precedes the dicrotic wave. The number of inertia-oscillations of the vibrating base that take place until the next heart-beat will depend on the duration of the individual heart-beats. Pathological. — In cases of insufficiency of the aortic valves the vibration com- municated to the body by the action of the heart is marked (Fig. 63. III). The highest apex of the curve, as well as the characteristic drop immediately preceding the ascending limb, corresponds to the ventricular sy.stole. Below the apex of the 158 THE MOVEMENT OF THE BLOOD. highest elevation is a small notch, which is produced by a slight vibration com- municated to the blood by the partly destroyed semilunar valves in their ineffective effort at closure. The enormous wave of blood that passes through the descending aorta to the iliac arterv after the closure of the semilunar valves is the cause of II Fig. 63. — I. Elastic Platform for Registering Vibration- curves. II. Vibration-curves Taken from the Body of a Healthy Indindual. III. Vibration-curves Taken from a Man Suffering from Aortic Insufficiency and a High Degree of Cardiac Hypertrophy. the lowest drop of the elastic platform. This is followed by a rise caused by the centripetal movement of the wave. The third rise, which then follows and M'hich is relatively low, appears to correspond with the development of the dicrotic wave in the portion of the arterial systom that is directed downward. THE MOVEMENT OF THE BLOOD. The closed system of blood-vessels with its many branches, endowed as its walls are with elasticity and contractility, is not only completely filled with blood, but it is in fact overfilled. The volume of the entire mass of blood slightly exceeds the available space within the entire vascular system. It follows, therefore, that the mass of blood everywhere exerts a pressure on the vessel-walls that causes a corresponding distention of the elastic coats. This is true, however, only during life. After death the muscles of the blood-vessels relax and blood-plasma escapes into the tissues, so that the vessels after death are found partially empty. If the volume of blood be conceived as equally distributed in the entire vascular s^^stem, and as everywhere subject to the same pressure, it would be in a condition of passive equilibrium, as is the case shortly before death. If, however, the pressure to which the blood is subjected be heightened at one point of the system of tubes, the blood will escape from this point of increased pressure to some point where the pressure is less; the movement (displacement of the blood-column) is, therefore, the result of the existing difference in pressure. If the venae cavae or the aorta in a living animal be suddenly occluded, the blood will continue to flow at a gradually diminishing rate until the differences in pressure in the entire circulation have been equalized. The velocity of the blood-stream is directly proportional to the THE MOVEMENT OF THE BLOOD. X59 difference in pressure and inversely proportional to the resistance en- countered by the blood-current. The difference in pressure that produces the movement of the blood is created by the heart. In the greater as well as in the lesser circulation the point of highest pressure is at the root of the arterial system, and the point of lowest pressure at the terminal portions of the veins. Hence, the blood constantly fiows from the arteries through the capillaries and into the large venous trunks. The heart maintains the difference in pressure necessary for the circulation of the blood by throwing a certain quantity of blood into the root of the aorta at each systole, after first withdrawing a like quan- tity of blood from the terminations of the venous trunks by means of the diastole of the auricles. To these laws relating to the causes of the movement of the blood- mass, and which were formulated chiefly by E. H. Weber, must be added an important one by Bonders. That investigator demonstrated that the heart, by the work it performs, not only produces the difference in pressure necessary for the movement of the blood, but it also increases the mean pressure existing in the circulatory system. The terminal portions of the large veins that empty into the heart are larger and more elastic than the initial portions of the arteries ; and if the heart transfers the same mass of fluid from the veins into the beginnings of the arteries, the arterial pressure must be increased in greater degree than the venous pressure is diminished, and the pressure as a whole must be raised. The movement of the blood-mass would be jerky or intermittent (i) if the walls of the tube were rigid; for pressure exerted on the fluid contained in rigid tubes is propagated at once throughout the entire length of the tubes, and the movement of the fluid ceases simultaneously with the impact that causes the increase in the pressure. (2) The move- ment would be intermittent also within elastic tubes if the interval between two successive systoles were longer than the duration of the movement of the column necessary to equalize the difference in pressure produced by the systole. If, however, this interval is shorter than is necessary for equalizing the pressure, the current becomes continuous. The more rapidly systole follows upon systole, the greater will be the difference in pressure, the elastic walls of the arterial tubes at the same time undergoing greater distention. In the continuous current thus produced the sudden increase in pressure caused by the systolic injec- tion of a mass of blood corresponding to the size of the ventricular cavity can always be recognized as an intermittent, jerky acceleration of the current (pulse). This intermittent acceleration of the current is propagated along the arterial pathway with the velocity of the pulse-wave, as both are due to the same cause. Each pulse-beat is therefore attended with a tem- porary, rapidly advancing acceleration of the fluid-particles. Just as the form of the pulse-movement, however, is not simple, so also is this pulsatory acceleration of the current not simple. The latter appears in the complicated form of the current pulse-curve, which likewise exhibits the primary elevation and the recoil-elevation like a (pressure-)sphygmo- graphic curve. Every up-stroke in the limb of the curve corresponds to an acceleration and every down-stroke to a retardation of the moving particles of fluid. l6o SCHEMATIC REPRODUCTION' OF THE CIRCULATION'. Physical Explanation. — The conditions detailed may be illustrated by means of simple physical experiments. If a rigid tube be connected with the nozzle of a syringe, every movement of the piston will be followed by an intermittent expulsion of water, which will correspond in time exactly to the movement of the piston. The effect of the intermittent injection of fluid into an elastic system of tubes is best exemplified in a fire-hose. Here the air contained in the air- chamber — which is under elastic tension — takes the place of the elasticity of the tubes themselves in the circulator}- apparatus. With slow intermittent strokes of the pump, the stream of water is interrupted; but if the movements of the pump are more frequent, the compressed air in the air-chamber effects a continuous outflow, although a distinct acceleration of the stream is seen in correspondence with each stroke of the pump. Landois was able without difficulty to demonstrate that the particles of water in an elastic tube are set in motion during the passage of the current by every pulsatile wave, in correspondence with the picture presented by the sphygmo- graphic tracing, by introducing in the course of a long elastic tube, in which both a continuous and an undulator}- movement could be produced by intermittent pumping, a short glass tube containing a thread passing through an opening in the side and floating to and fro in the stream. Immediately in front of the thread a sphygmograph was connected with the tube. Each pulse-beat caused a synchronous movement of the sphygmograph and of the thread, each upward stroke of the writing lever corresponding to a more marked oscillation of the thread toward the periphery (acceleration) , while each downward stroke was marked by a slight diminution in the oscillatory movement (retardation). In the capillary vessels the pulsatory acceleration of the current ceases with the disappearance of the pulse-wave. The two movements are gradually extinguished by the marked resistance encountered by the blood in the capillary system. It is only when the capillarv' vessels are greatly dilated and the pressure in the arterial system increases that both pulse and pulsaton,- acceleration of the current are sometimes communicated to the initial portions of the veins through the capillaries. Such conditions are observed in the vessels of the salivary glands after stimulation of the facial nerve, which dilates the vascular channels. After constriction of the finger with an elastic band, which impedes the return flow of venous blood, and causes an increase in the arterial pres- sure, with dilatation of the capillaries of the finger, the swollen skin is seen to become intermittently more deeply red isochronously with the well-known throbbing sensation. This is the capillary pulse. Pathological. — The capillar}- pulse is found sometimes when the action of the left ventricle is greatly increased, for example in cases of aortic insufficiency and of exophthalmic goiter, and often in cases of jaundice. SCHEMATIC REPRODUCTION OF THE CIRCULATION. The arrangement of the circulation as described permits a reproduction by physical means, of the most essential conditions, in the so-called model of the circu- lation. Weber's model wiU be briefly described here. The arterial system and the somewhat larger venous system are represented by portions of animal intestine (Fig. 64). The system of capillaries between the two is formed by a glass tube of sufficient size, the lumen of which, however, is occupied by a piece of sponge. A short section of intestine into each extremity of which a piece of glass tube is tied represents the heart. The glass tube directed toward the arterial trvmk is provided with the necessary- valves, w-hich are reproduced by having a piece of small intestine project beyond the edges of the glass tube and securing its free margins with three threads. Through this piece of intestine water can enter only in the direction from the glass tube toward the free intestine, but not in the opposite direction, as the free edges w-ould then come together and close the lumen. From the venous side a similar valve, mounted on the extremity of a separate piece of tube, is inserted into the glass tube directed toward CAPACITY OF THE VENTRICLES. I6l the heart. The two valves open in the same direction. The entire apjjaratus is moderately distended with water by means of a funnel. By compressing the heart-piece the contents are made to flow through the arterial valve into the arterial portion. When the compression ceases, the contents return from the venous portion through the venous valve into the heart. By means of this apparatus the blood-current becomes continuous when the heart is com- pressed in rapid succession, and the movement of the pulse can be demon- Artcrial Valve. Fig. 64. — Model of the Circulation by Ernst Heinrich Weber. strated. The latter does not extend beyond the capillar}^ region because the great resistance offered by the many pores of the sponge destroys the force of the pulse- waves. More complicated models of the circulation, which, however, do not essentially illustrate more than this primitive model by E. H. Weber, have been designed by numerous investigators. CAPACITY OF THE VENTRICLES. As the heart creates the difference in pressure necessarv for the circulation of the blood by throwing a definite quantity of blood into the roots of the two large arteries every time the ventricles are emptied by systolic contraction, it is desirable to determine this quantity of blood. As the right and left ventricles must contract simultaneously, and as, in addition, the same quantity of blood must pass through the lesser circulation as through the greater, it follows that the capacity of the right ventricle must be equal to that of the left. It must be remembered, however, that a moderate quantity of blood always remains in the ventricle, as this does not empty itself completely, even at the height of its contraction. Methods. — i. The capacity of the ventricles is determined directly by filling the chambers of the flaccid heart after death with a coagulable material and measuring the coagulated mass. This is an uncertain method, because the pressure in the living ventricles during their diastole, following the contraction of the auricles, is not known. 2. Indirect Estimation. — A. W. Volkmann, in 1850, estimated the capacity of the left ventricle in the following manner. The cross-section of the aorta and the velocity of the blood-current in the vessel are determined. From these data the quantity of blood that passes through the aorta in a unit of time is cal- culated. As the total quantity of blood in the body (y^^ of the body-weight) is known, the time required for the passage of this quantity through the aorta can easily be calculated. Finally, if the number of S3'Stoles that occur during the time of circulation be known, the quantity of blood for each systole will correspond to the capacity of the ventricle. On the basis of numerous animal experiments Volkmann estimated the ventricular capacity to be eqtial to ^^g of the bod}''- weight: or 187.5 grams for a man weighing 75 kilograms. The accuracy of this method also leaves much to be desired, becatise the velocity of the current in the aorta, which according to C. Ludwig and Dogiel is subject to considerable l62 METHODS FOR MEASURING THE BLOOD-PRESSURE. fluctuations, can only be determined approximately. Tigerstedt considers Volk- mann's figure much too high. He determined the quantity of blood expelled by the left ventricle with each systolic contraction in the rabbit by introducmg m the continuity of the aorta an instrument resembling a current-meter. From animal experiments he estimates that in man only 69 cubic centimeters are ex- pelled at each ventricular contraction. Place calculated as follows: A man uses about 500 liters of oxygen in 24 hours. In order that the venous blood, which contains on the average 7 volumes per cent, less of oxygen than arterial blood, may take up this quantity of oxygen, about 7000 liters of blood must be driven through the lungs in 24 hours. Allowing 100,000 heart-beats for the 24 hours, only 70 cubic centimeters are propelled with each systole. Other more recent investigators also have calculated that the quantity of blood expelled with each systole is equal only to i of the capacity of the dead ventricle, or 60 cubic centimeters. METHODS FOR MEASURING THE BLOOD-PRESSURE. A. In Animals. — i. Hales' Tube. — Stephen Hales, in 1727, first fastened a long glass tube in the lateral wall of a vessel and determined fhe blood-pressure by measuring the height of the vertical column of blood in the tube. Hales' tube was fitted at its lower extremity with a short copper tube, bent at a right angle and directed toward the heart; it therefore really represented a so-called Pitot's tube. Pitot, in 1731, used a similar tube to determine the velocity of the current in rivers. The water entering the horizontal portion of the tube, which is directed up-stream, rises in the vertical portion, which projects above the water, to a level proportional to the velocity of the current. This level represents the "velocity-altitude" and it indicates that the water flows Avith a velocity equivalent to that attained by a body falling freely from a height equal to the velocity-altitude. If a Pitot tube (Fig. 70, II, o p x) be introduced into a closed tube through which flows a fluid under pressure, and an ordinary manom- eter (x y) be introduced at the same time, the latter will register only the tension of the wall; but in a Pitot tube the fluid will rise to a higher level, for this column of fluid indicates not only the tension of the blood, but also its velocity-altitude. In arteries, however, the latter is extremely small as compared with the former. 2. Poiscuille's Hematodynamonieter. — Poiseuille, in 182S, used a U-shaped man- ometer-tube filled with mercury, which he inserted laterally b}- means of a rigid connecting piece into the wall of the vessel. A I- -shaped tube may also be used to connect the blood-vessel with the manometer, the short continuous extremities being inserted into the open vessel (Fig. 65, I, a a) and the vertical limb being connected with the manometer (M) by means of a leaden tube. 3. Ludwigs Kymograph. — Carl Ludwig. in 1847, placed afloat (Fig. 65, I, d s) on a column of mercury (as James Watt had already done for the manometer of the steam-engine). To"^ the float was attached a vertical wire carrj-ing a writing- contrivance, which records not only the height of the blood-pressure, but also the variations in the pulse-waves on the drum (C) , which is made to rotate by clock- work. A. W. Volkmann gave the name of kymograph (wave-tracer) to this instrument. The difference between the levels of the mercurial columns (c d) in the two parts of the tvibe indicates the pressure within the vessel (the height of the column of mercury multiplied by 13.5 gives the pressure-altitude of the corresponding blood-column) . Setschenow added a stopcock at the center of the lower bend of the tube (at b) . When this stopcock is turned so as to leave only a narrow orifice of communication, the pulse-waves cease to manifest themselves and the instrument records only the mean pressure. In this form the instrument is the most reliable for this purpose. The pulsatory variations in pressure are recorded by the kymograph as simple elevations (Fig. 65, III) and, therefore, they do not in the least correspond to the curves obtained with the sphygmograph. After the mercury has once been set in motion by the pulse-beats,' it simply undergoes movements up and down by virtue of its own oscillations and all the finer shades of the pulse are completely obliterated. For this reason the kymograph can be used only for recording the blood-pressvire, and never for pulse-tracings. In order to determine the mean pressure from a long blood-pressure tracing presenting numerous elevations and depressions, the planimeter is employed. This instrument is carried over the entire outline of the surface occupied by the curve — METHODS FOR MKASURIXG THE BLOOD-PRESSURE. i6- namely the curved line, the abscissa (base) and the initial and terminal ordinates— when the number of square millimeters contained in the entire area can he directlv read oft on the instrument. If the paper on which the curve is traced be divided into squares, the size of the area embraced by the curve can be approximatelv obtained by counting the squares. A. W. Volkmann cut out the curve-area and weighed It, and then compared with it the rectangle made from the same paper and having the same base-line, so that its altitude naturally represented the mean height of the curve. 4. A. Pick's Hollow-spring /Cyma^rap/z, which was designed in 1864 is con- structed on the principle of Bourdon's hollow-spring manometer (Fie 6^ ID which is frequently attached to steam-engines. v &• 0. ;■ A hollow spring bent in the shape of the letter C (F) and lilled with alcohol SP ^ Fig. 65. — I, Carl Ludwig's Kymograph; II, Adolph Fick's hollow-spring kymograph; III, blood-pressure curves (above) and respiratory curves (below), traced at the same time (after C. Ludwig and Einbrodt). is brought into connection at its lower extremity (a) with the lateral wall of the artery (x x) by means of a suitable cannula, while the other extremity of the spring is closed. As soon as the internal pressure is increased, the bent spring is straightened out. The closed extremity (b) is connected with an upright rod (g), which acts on a system of writing-levers (hike) composed of delicate pieces of reed, which records the variations in pressure on a moving recording surface. Both the blood-pressure and the variations in the pulse are recorded; the latter, however, without their characteristic peculiarities. Hiirthle reduced the apparatus to one-fourth of its original size, in which forrti the results recorded are quite accurate because of the slight displacement of fluid. 5. A. Fick's Flat-spring Kymograph (Fig. 66) has been used in preference to any other by its inventor since 1885. A tube, i mm. thick and filled with air (Fig. 66, a a), communicates with the blood-vessel by means of a cannula (c) , and ends in an excavated expansion covered with a rubber membrane, from which a point (5) projects downward. The latter presses upon a tightly stretched hori- 164 METHODS FOR MEASURING THE BLOOD-PRESSURE. zontal steel spring {F), which articulates by means of a connecting piece (6) through two joints {d i) with a writing-lever (ff). The parts of the instrument are held in a metallic frame (R R). In order to determine the absolute values of variations in pressure the apparatus must first be graduated empirically by com- paring it with a mercurial manometer. 6. Hurihle's Mancnneter (Fig. 67) is a similar instrument. A small metallic drum (Fig. 67, d) is intercalated in the course of an artery (c c) by means of tubes. The drum is covered with a thin rubber membrane, from the center of ■which a process (e) projects. The latter is supported by a spring (F), to which. Fig. 66. — Adolph Fick's Flat-spring Kjmiograph. at some convenient point that can be varied at will (v), the writing-lever is at- tached. The whole contrivance is attached to a stationary rod (i i) by means of a carrier (T). This apparatus also, Uke the preceding one, must first be gradu- ated empirically in order to determine in advance the height to which the point (s) of the writing-lever gradually rises with increasing pressure (from o to 100 mm. of mercury). Hurthle also constructed a torsion-manometer according to the plan of Roy, the pressure being measured by the torsion of a steel spring. B. In man the blood-pressure within an artery can be measured in the sim- plest manner by means of a graduated sphygmograph. The weight that just Fig. 67. — Hiirthle's Kymograph. suffices to arrest the movement of the writing-lever corresponds to the tension of the vessel. The radial artery of healthy students examined in this way tmder Landois' direction and loaded for a distance of i cm. exhibited an average blood- pressure of 550 grams. Manotnetric Method. — v. Basch determined the blood-pressure by a mano- metric method, applying his sphygmomanometer to the pulsating vessel. The hollow, air-containing cushion applied to the artery' communicates with an aneroid barometer, the pointer of which indicates the pressiire. As soon as the pressure indicated by the latter slightly exceeds the pressure in the artery, the latter is THE BLOOD-PRESSURE IN THE ARTERIES. 165 compressed and pulsation beyond the point of compression is abolished. In the temporal artery the pressure is from So to no mm. of mercury. Both of the foregoing methods not only demonstrate the blood-pressure within the arteries, but the pressure exerted by the cushion must exceed the arterial pressure to a degree sufficient to compress the empty artery (which in itself repre- sents a gaping tube). As compared with the blood-pressure, however, the resist- ance of the artery is extremely slight, being only 4 mm. of mercury, although naturally greater in cases of arteriosclerosis. In the same way the resistance offered by the soft parts superposed upon the artery must also be overcome and in individuals of firm fiber with an abundance of fat this resistance is not incon- siderable. In this way v. Basch found in adults a pressure of from 135 to 165 mm. of mercury in the radial artery; from 80 to no mm. in the superficial tem- poral. Federn thinks it is lower, namely from 80 to 100 131m. of mercury. In children the blood-pressure increases with age, size, and weight. In the superficial temporal it was found to be 97 mm. between 2 and 3 years of age, and 113 mm. of mercury between 12 and 13 years of age. The blood-pressure rises immediately after exercise; it is higher in the recumbent than in the sitting posture, and in the latter than in the erect posture. After a cold, as well as after a hot, bath the blood-pressure is at first raised and the flow of urine is increased. Hurthle employs the plethysmograph (Fig. 73) in the following manner for measuring blood-pressure. The glass cylinder communicates with a mercurial manometer. The forearm, first rendered bloodless by firmly bandaging it, is introduced into a cylinder containing water and closed in hermetically. When the blood is allowed to flow freely into the arm, the fluid in the cylinder is dis- placed and enters the manometer. The blood continues to flow into the arm until the manometric pressure is equivalent to the blood-pressure. The mean pressure in the arm is said to be about 100 mm. of mercury. Sphygmomanometers have been constructed by Marey and Mosso on similar principles. THE BLOOD-PRESSURE IN THE ARTERIES. The blood-pressure in the arteries is quite considerable, varying "within fairly wide limits. In the larger arteries of large mammals and probably also of man it is between 140 and 160 mm. of mercury. Examples : Carotidof thehorse, 161 mm. (Poiseuille) . Aorta of the frog, 22-29 mm. (Volkmann). 212-214 rnm. (Volk- Brachial artery of the pike, 35-84 mm. mann) . (Volkmann) . dog, i5imm.(Poiseuille). Brachial artery in man (after operation) " 130-190 mm. (Lud- 1 10-120 mm. (Faivre) ; perhaps a wig). little too low on account of the " goat, ii8-i35mm. (Volk- traumatism and the disease. mann) . " rabbit, 90 mm. (Volkmann). " chicken, 88-171 mm. (Volk- mann) . In patients about to be subjected to amputation of the thigh E. Albert, with the aid of a manometer, found the blood-pressure in the anterior tibial artery above the ankle to be between 100 and 160 mm. of mercury. The ptilsatory elevation of the column of mercury was from 17 to 20 mm. Coughing caused an increase of between 20 and 30 mm.; firm bandaging of the healthy leg an increase of 15 mm.; passive elevation of the body, in consequence of which the length of the hydrostatic column of blood was augmented, an increase of 40 mm. of mercury. The pressure in the aorta of large mammals is estimated to be between 200 and 250 mm. of mercury. In general, the blood-pressure is lower in large than in small animals because, on account of the greater length of the blood-channels, a greater resistance is to be overcome. In exceedingly young and exceedingly old animals the pressure is lower than in individuals at the height _of their vital activity. in embryos the arterial pressure is scarcely one-half as great as in the new- bom, but the venous pressure is greater. The difference between the arterial and the venous pressure in embn,^os was found to be scarcely one-half as great as in full-grown animals. l66 THE BLOOD-PRESSURE IN THE ARTERIES. "Within the large arteries the blood-pressure undergoes relatively slight diminution toward the peripher3% because the differences in the resistance in various sections of the large tubes are inconsiderable. As soon, however, as the arteries undergo frequent division and their caliber accordingly becomes greatly diminished, the blood-pressure rapidly diminishes, because the propulsive power of the blood is weakened by the effort to overcome the increased resistances produced in this way. The arterial pressure increases directly with the quantity of blood present in the arteries, and conversely. The pressure, therefore, Increases Diminishes 1. Asthe heart's action becomes stronger i. As the heart '.«; action becomes feebler and more rapid. and sloAver. 2. Jn plethoric individuals. 2. In anemic individuals. 3. After considerable increase in the 3. After profuse hemorrhage or loss from quantity of blood by the direct in- the blood in some other way, as iection of blood, and also after cop- for example, by profuse sweating ious ingestion of food. or copious diarrhea. The increase and decrease in blood-pressvu-e is not directty proportional to the increase and decrease in the quantity of blood. By virtue of their muscvdar libers the blood-vessels possess the facility of adapting themselves within fairly wide limits to the variable volume of blood. The blood -presstire, therefore, does not rise at once when the quantity of blood is moderately increased. The cir- ctmistance that fluid rapidly transudes from the blood into the tissues also assists in maintaining a constant blood-pressure. Moderate venesection, in the dog up to 28 per cent, of the body-weight, is not followed by any noteworthy diminution in the blood-pressure. After slight hemorrhages the pressure may even rise, but the removal of a large quantity of blood is followed by a considerable fall in the blood-presstire, and the loss of from 4 to 6 per cent, of the body-weight reduces it to zero. Increased pressiore within the vessels produced by engorgement tends to dilate the cutaneous and muscular vessels, especially those of the extremities, and affects the arteries in the viscera but little. After the pressure has fallen, the visceral blood-vessels return to their original caliber much more promptly than do the cutaneous and muscular blood-vessels. The arterial pressure rises as the capacity of the arteries is diminished, and conversely. This is accomplished by contraction or relaxation of the unstriated muscle-fibers of the arterial wall. The pressure within a certain area of the arterial system rises or falls accordingly as the blood-vessels in neighboring areas tmdergo contraction — or even become impermeable from compression or ligation — or dilatation. The application of heat or cold to a circumscribed portion of the body, also of pressure or diminution of pressure (the latter by introducing an extremity into a closed space containing rarefied air, as, for example, Junod's cupping boot), and the effect of stimulation or paralysis of certain vasomotor areas, furnish striking proofs of the cor- rectness of this statement. The respiratory movements produce regular variations in the arterial pressure, known as respirators" pressure-variations — the pressure falling with each deep inspiration and rising with each expira- tion. These variations are readily explained by the fact that at each expiration the blood in the aorta is subjected to the increased pressure of the compressed air in the thorax, while with each inspiration the blood undergoes a diminution in pressure, in consequence of the influence of the rarefaction of the air in the lungs, on the aorta. In addition, the in- spirator>" expansion of the thorax tends to draw the blood from the venae cavae into the heart, while during expiration the blood stagnates, and THE BLOOD-PRESSURE IN THE ARTERIES. 167 in this way influences the blood-pressure. Tlie changes are greatest in the arteries nearest the thorax. The respiratory variations in blood-pressure are in part dependent upon changes in the nervous impulses sent out by the vasomotor center, which coincide with the respiratory movements, and by virtue of which the arteries contract and thus increase the arterial pressure (Traube- Hering's pressure-variations). Fig. 65 III shows a respiratory curve (heavy line) and a blood-pressure curve traced at the same time. This figure shows that at the instant when expiration begins (at ex), the blood-pressure curve rises along with the expiratory pressure, and, con- versely, that both curves fall from the instant that inspiration begins (at in) ; yet the blood-pressure curve begins to rise a little earlier (at c) than expiration itself has begun, that is, during the last part of inspira- tion. This is due to the contraction of the arteries, which begins a little earlier in obedience to impulses sent out by the vasomotor center. The effect of the arterial contraction is reinforced by the circumstance that during the inspiratory stage the heart is more completely emptied on account of the increased venous flow. The respiratory variations in blood-pressure are observed also during artificial respiration; if this be suddenly interrupted (in curarized animals), the resulting irritation of the medulla oblongata due to the dyspnea causes a considerable rise in the blood-pressure. In accordance with the depth of the respirations and the corresponding pres- sure-variations of the air within the thorax, great inequalities are observed in the respirator}^ fluctuations. This is evident froin the fact that in man during quiet inspiration the diminution of pressure in the trachea is equivalent to only i mm. of mercury, while during the deepest possible inspiration (with the respiratory canal tightly closed) the diminution is 57 mm. Conversely, quiet expiration in man is attended with an increase in the pressure in the trachea of only 2 or 3 mm., while vigorous contraction of the abdominal muscles causes an increase of 87 mm. of mercury. Kronecker and Heinricius attribute the variations to mechanical causes, namely to the compression of the heart that accompanies respiration (because, according to them, rhythmical injections of air into the pericardium, which com- press the heart, also give rise to analogous variations in blood-pressure). Any interference with the diastole of the heart lowers the blood-pressure; as soon, therefore, as the lung has been distended during inspiration sufficiently to displace the heart, diastole is interfered with and the tension in the aortic system is in consequence lowered. As soon as the air can escape from the lungs and these organs contract, a greater quantity of blood enters the heart, and the arterial pressure rises. The movements of the pulse cause intermittent variations in the mean arterial pressure, the so-called pulsatory pressure-variations. The column of blood injected into the aortic system by the ventricle at each systole, acting in conjunction with the positive wave, produces an in- crease of pressure in the arterial system corresponding to this positive wave. The increase in pressure finds corresponding expression in the various elevations of the sphygmogram ; it also travels along the arteries with the same velocity as the pulse-waves. In the larger arteries of the horse Volkmann found the pulsatory increase of pressure to be j\, and in the dog jV of the total pressure. Hiirthle, with the aid of his hemodvnamometer, found that the pulsator>^ increase of pressure in the rabbit was equal to almost one-third of the pressure during the interval between pulse-beats. None of the pressure-recording instruments described shows the form of these pressure-variations with sufficient accuracy; most of them merely record elevations l68 THE BLOOD-PRESSURE IN THE CAPILLARIES. and depressions. Hiirthle's kymograph, however, furnishes sufficiently accurate pictures of the pressure-variations in the arteries: these resemble sphygmographic tracings. Hence, the sphygmographic pulse-tracing is at the same time a faithful expression of the pulsatory variations in blood-pressure. Muscular exertion increases the blood-pressure. At the beginning of a muscular contraction the pressure sometimes undergoes a tempo- rary fall. When the heart's action is interrupted by continuous stimulation of the vagus or a high positive respiratory pressure, the blood-pressure diminishes enormously in the arteries; while, on the other hand, it increases in the venous trunks because the blood flows from the arteries into the veins in order to equalize the difference in pressure. This experi- ment shows that when the difference in pressure is (almost) abolished, the resting blood continues to exert some pressure on the blood-vessel walls; that is, in consequence of distention with blood, even in the resting state, a lower pressure is exerted on the walls. Pathological. — In man it has been found that the blood-pressure, as determined by V. Basch's method, is increased in association with chronic inflammation of the kidneys, arteriosclerosis, lead-colic, after injections of ergotin, and in cases of cardiac hypertrophy with dilatation. It is diminished in the presence of cardiac insufficiency. Digitalis often raises the blood-pressure in cases of cardiac disease; after the injection of morphin the pressure falls. During fever the blood-pressure usually falls, as the shape of the pulse-curves also indicates; in cases of cardiac insufficiency, chlorosis and pulmonary tuberculosis the blood-pressure is also low. If the pressure falls to about 75 mm. in cases of diphtheria (children) , the prognosis is grave. THE BLOOD-PRESSURE IN THE CAPILLARIES. Method. — Owing to the minute diameter of the capillaries the pressure within these vessels cannot be determined directly. By applying a small glass disc of known dimensions to the vascular substratum and weighting it in a suitable manner until the capillaries become pale, the degree of pressure that just over- comes the pressure within the capillary region is determined approximately. The calculation is made as follows: The pressure (expressed in centimeters of a column of water) is obtained by dividing the number that represents the compressing weight (weight -f the weight of the glass disc) by the number of square centi- meters contained in the surface pressed upon. In the capillaries of the finger, when the hand is held up, this pressure is 24 mm. of mercury, and with the hand dependent, 62 mm. ; in the ear it is 20 mm. ; in the gums of the rabbit 32 mm. Roy and Graham Brown press the vascular area to be examined from below against a rigid glass disc by means of an elastic bladder provided with a manom- eter; the microscope can then be focused on the glass disc. The tension of the blood in the capillaries of a circumscribed area is increased by: (i) Dilatation of the small arteries supplying the area. If the latter are dilated, the blood-pressure can be propagated from the large trunks with less loss. (2) Increase of pressure in the small arteries supplying the area. (3) Constriction of the veins draining the capil- lary area. Occlusion of the veins causes a fourfold increase in the pressure. (4) Increased pressure in the veins, as, for example, by change of position (hydrostatic pressure). Diminution of the blood- pressure in the capillaries is brought about by the opposite conditions. Also, changes in the diameter of the capillaries must have some influence on the internal pressure. The inherent power of movement (movement of the proto- plasm) of the capillary cells, as well as the pressure, swelling, and consistency of the surrounding body-tissues must be considered in this connection. As the THE BLOOD-PRESSURE IN THE VEINS. 169 resistance to the blood-current is greatest in the small arteries and in the capillary system, the blood — especially in long capillaries — must be subject to different degrees of pressure at the beginning and at the end of such capillaries. In the middle of the capillary system the pressure may not be much less than one-half the pressure prevailing in the main arterial trunks. The capillary pressure exhibits many variations in different parts of the body. Thus, in the erect position, the pressure in the capillaries both of the intestine and of the glomeruli of the kidneys, as well as in those of the lower extremities, will be greater than in those of other regions of the body; in the former case on account of the two-fold resistance offered by the duplicate arrangement of the capillaries; in the latter case, from purely hydrostatic inflviences. THE BLOOD-PRESSURE IN THE VEINS. In the large venous trunks near the heart (innominate, subclavian, and common jugular veins) the blood is under a negative pressure, which is on the average equivalent approximately to o.i mm. of mercury. This enables the lymph-stream to empty itself freely into the large venous trunks. As the distance from the heart increases, the lateral pressure in the venous trunks gradually increases. In the external facial vein of the sheep it is +0.3 mm., in the brachial 4.1 mm., in branches of the brachial 9 mm.; in the femoral 11.4 mm. The following conditions influence the pressure in the veins : 1. All factors that tend to diminish the difference in pressure exist- ing between the arterial and the venous system, which maintains the circulation of the blood, necessarily increases the pressure in the veins, and conversely. 2. General plethora increases the pressure in the veins, while anemia diminishes it. 3. A special influence on the tension in the large trunks situated near the heart is exerted by the respiration; for during each inspiration the pressure diminishes and the blood rushes toward the thoracic cavity; while with each expiration the pressure increases and the blood stag- nates. This effect is intensified in proportion to the depth of the res- pirations, and when the respiratory passages are closed it must be par- ticularly great. 4. The slight stagnation of the blood in the venae cavae that accom- panies every contraction of the right auricle has already been discussed in the section devoted to the movements of the heart The respiratory, as well also as the cardiac, fluctuations can sometimes be detected in the common jugular vein of healthy individuals. 5. Changes in the position of the limbs or of the body through hydrostatic influences modify the pressure in the veins in various ways. The highest pressure is found in the veins of the lower extremities, and they are accordingly most abundantly supplied with muscle-tissue. When the muscles and valves in these veins become insufficient, dila- tation is likely to develop (varices). THE BLOOD-PRESSURE IN THE PULMONARY ARTERY. Method.— Direct estimation of the pressure in the p-ulmonary artery was made in 1850 by C. Ludwig and Beutner, who opened the left pleural cavity and con- nected the tube of a manometer directly with the left pulmonary artery, artificial respiration being resorted to. In this way the lesser circulation of the left lung was interrupted completely in cats and rabbits and almost completely in dogs. In addition to this disturbance, the normal flow of the venous blood into the right lyo THE BLOOD-PRESSURE IN THE PULMONARY ARTERY. heart ceases as soon as the thoracic cavity is opened, because the elastic traction of the lungs is abolished and the right heart itself is exposed to the full x^ressure of the air. The pressure was found to be in the dog 29.6, in the cat 17.6, and in the rabbit 12 mm. of mercury (in the dog 3 times, rabbit 4 times, and in the cat 5 times less than the pressure in the carotid) . Faivre and Chauveau, in 1856, introduced a catheter into the right ventricle through the jugular vein and connected it with a manometer. Knoll reached the pulmonary artery through the anterior mediastinum, with- out opening the pleural cavities, and introduced a cannula laterally into the trunk of the vessel. By this method he was able to observe the pressure in the artery during spontaneous breathing without restricting the lesser circulation and with- out displacing the heart. He thus found a mean pressure of 12.2 mm. of mercury in the rabbit. Indirect estimation can be made by comparing either the muscular walls of the right with those of the left ventricle, or the thickness of the walls of the pul- monary artery and of the aorta, for it must be assumed that there is a definite relation between the thickness of the walls and the pressure within the vessels. Beutner and Marey estimate the relation of the pulmonary pressure to the aortic pressure as i : 3 ; Goltz and Gaule, as 2 : 5. Fick and Badoud, in the dog, found the pressure in the pulmonary artery to be 60 mm., and in the carotid 11 1 mm. of mercury. According to Knoll the pul- monary pressure in the rabbit is 6.8 times less than the pressure in the carotid. In a child the pressure in the pulmonary artery is relatively greater than in the adult. The ptilmonary pressure exhibits certain rhythmical variations due to varia- tions in the tone of the heart's action. When the air-pressure in the lung falls, the pressure in the lesser circulation also falls, and conversely. The expansion of the lungs in the thoracic cavity is maintained by the nega- tive pressure on their outer pleural surface. When the glottis is open, the inner surface of the lungs and the walls of the alveolar capillaries traversing the lungs are exposed to the full pressure of the air. The heart and the large vascular trunks of the thorax, however, are subject not to the full pressure of the air, but to the pressure of the air minus the pressure corresponding to the elastic traction of the lungs. The trunks of the pulmonary artery and veins are accordingly subject to the same pressure-conditions. The elastic traction of the lungs is proportional to the degree of expansion of the lungs. The blood in the pul- monary capillaries will thus have a tendency to flow from these capillaries into the large vascular trunks. As the elastic traction of the lungs affects chiefly the more delicate pulmonary veins, and as regurgitation of the blood is prevented by the semilunar valves of the pulmonary artery, as well as by the contraction of the right ventricle, it follows from these pressure-conditions that the capillary blood in the lesser circulation is drained into the ptilmonary veins. Thin-walled tubes embedded within the stibstance of the walls of an elastic, distensible sac suffer a modification of their lumen, in accordance with the manner in which the sac is distended; for, if the sac is directly inflated so that the air- pressure in its interior increases, the lumen of the tubes is diminished; if, however, the sac is distended by rarefying the air in the closed space stirrounding it, the tubes embedded in the wall dilate. When the distention is brought about in the latter way, namely by the negative pressure of aspiration, the two pulmonary sacs within the thoracic cavity are maintained in a state of distention; therefore the vessels of air-containing lung are more dilated than the vessels of collapsed lung. Consequently, more blood flows through the lungs when they are distended within the thorax than when they are collapsed. Inspiratory distention has a similar effect and increases the flow of blood. The negative pressure prevailing in the lungs during inspiration causes a considerable dilatation particularly of the pulmonary veins, into which vessels, therefore, the pulmonary blood readily flows; whereas the blood of the pulmonary artery, flowing throvigh thick- walled trunks under high pressure, undergoes scarcely any alteration. The velocity of the blood in the pulmonary vessels is, therefore, increased during inspiration. The blood-pressure in the lesser circulation is higher also when the lungs are in a state of distention. Contraction of the vessels, which causes an increase of MEASUREMENT OF THE VELOCITY OP THE BLOOD-CURRENT. 171 pressure in the greater circulation, has the same effect in the lesser circulation because more blood Hows into the right heart. The vessels of the lesser circulation are exceedingly elastic and their tonicity is slight; hence impermeability even of large pulmonary branches is readily compensated for. Forcible contraction of the abdominal muscles (straining) causes at first a marked increase in the flow of blood from the pulmonary veins, which, however, gradually ceases, because the blood finds difficulty in entering the pulmonarj' vessels. When the abdomen is relaxed, the blood again enters the pulmonary vessels in large quantities. Noteworthy in this connection are the experiments of Severini, who found that the flow of blood through the pulmonary vessels is freer and more rapid when the lungs are filled with air rich in carbon dioxid, than with air containing a larger percentage of oxygen. He believes that these gases affect the vascular ganglia in the lesser circulation that control the size of the vessels. According to Morel, electrical and mechanical stimulation of the abdominal organs causes a considerable increase of the blood-pressure in the pulmonary artery (dog). According to v. Basch, increase of blood-pressure in the capillaries of the lungs produces greater rigidity and, therefore, diminished elasticity of the alveolar walls. Pathological. — The pressure in the pulmonary area is increased in man in connection with many morbid disturbances of the circulation and always produces accentuation of the second pulmonic sound, which is such an important pathogno- monic sign. It also causes an increase in size and an earlier appearance of the corresponding elevation in the apex-beat curve. But little has been determined with regard to the effect of physiological conditions; temporary suspension of breathing is said always to be followed by an increase in pressure. The influ- ence of the vasomotor nerves on the vessels of the lesser circulation is not so great as that upon those of the greater circulation. Influences that cause a rise or a fall in the blood-pressure in the greater circulation through the agency of the vasomotor or vasodilator nerves have no effect whatever on the pressure in the lesser circulation. Plethora of the pulmonary capillaries is followed by enlargement of the lungs, with more complete distention of the alveoli. The causes may be a diminished flow from the pulmonary veins or disturbances in the left heart. The development of pulmonary edema is discussed on p. 224. MEASUREMENT OF THE VELOCITY OF THE BLOOD-CURRENT. The following instruments are used for determining the velocity of the blood- current in the vessels; I. Alfred WiLhebn Volkmann's hemodromofneter measures directly the progress of the blood-column through a glass tube in a blood-vessel. A glass tube shaped like a hairpin, 130 cm. long and 2 or 3 mm. wide and mounted on a scale (Fig^ 68, A), is fastened to a metallic basal piece (B) in such a manner that each limb passes to a stopcock perforated all the way through in one direction and halfway through in the other. The basal piece is perforated lengthwise and the two extremities are provided with short cannulae (c c), which are tied into the two ends of the divided blood-vessel. The entire apparatus is next filled with a 0.6 per cent, sodium-chlorid solution. The stop- cocks, which are provided with an arrangement of cogs so that they always turn together, are first placed as shown in Fig. I: the blood then simply flows length- wise through the basal piece; that is, in the same straight direction as the artery. If at a given moment the stopcocks are turned as shown in Fig. 68, II, the blood is forced to flow through the longer channel represented by the glass tube. The blood will be seen pushing the paler column of water before it and the instant should be noted at which it reaches the extremity of the limb of the tube. The length of the tube being known and the time occupied by the blood in passing through it being determined, the velocity for the unit of time and the unit of length of the course is readily obtained. Volkmann found the velocity of the current in the carotid of the dog to be between 205 and 357 mm.; in the carotid of the horse, 306; in the facial of the horse, 232 ; and in the metatarsal artery, 56 mm. The observation occupies only a few seconds. The tube is narrower than the 172 MEASUREMENT OF THE VELOCITY OF THE BLOOD-CURRENT. blood-vessel; nevertheless the blood is said not to flow more rapidly through it than through the larger, iminjured blood-vessel. The intercalation of the tube ofters additional resistance to the blood-current, in consequence of which increased retardation must be produced. The apparatus is evidently imperfect; for the larger respiratory and pulsatory variations of pressure in the arterial system do not produce any perceptible changes in pressure. Fig. 68. — A. A. W. Volkmann's Hemodromometer. B. C. Ludwig's Rheometer. 2. CarL Ludwig's rheometer measures the velocity of the blood-stream from the amount of blood that passes from the artery into a communicating graduated glass bulb. Two communicating glass bulbs (Fig. 68, B, A and B), of the same capacity and accurately graduated, are attached by their lower extremities to metallic discs e Ci by means of tubes c and d. Each disc can be ttuned about the axis x y in such a way that after it has been turned the tube c communicates with f and the tube d with g; f and g are, in addition, provided with horizontal cannulas h and k, which are tied into the extremities of the divided arterv. When the instrument MEASUREMENT OF THE VELOCITY OF THE BLOOD-CURRENT. 173 is in the position shown in the figure, h is tied in the central, and k in the peripheral extremity of the vessel (for example, the carotid). The bulb A is filled with oil and the bulb B with delibrinated blood. At a given moment the blood-current is permitted to enter through h; the oil is displaced by the blood and passes over into B, while the delibrinated blood flows out from B through k into the peripheral portion of the vessel. As soon as the oil reaches m, the time is again noted, and the entire apparatus A B is turned about the axis x y, so that B occupies the place of A. The phenomenon is thus repeated, and the observation may often be con- tinued for some time. By observing the time required by the inpouring blood to fill one of the bulbs the quantity for each unit of time (second) can be cal- culated. 3. Carl Vierordt's hemotacliometcr measures the velocity of the blood-cur- rent by means of a device modeled after Eitelwein's velocity-quadrant, which is constructed on the principle that a pendulum suspended in a moving fluid is deflected by the current in proportion to the velocity. The apparatus consists of a small metallic box (Fig. 69, I, A) with parallel glass sides and provided at the narrow extremities wnth two cannula? (e, a) for the iG. 69. — Vierordt's Hemotachometer: II, Chauveau's and Lortet's dromograph; III, the dromographic curve according to Chauveau. entrance and exit of the blood. Within the box, opposite the entering blood- current, hangs a small pendulum (p), the oscillations of which are read off on a curvilinear scale and which increase with the velocity of the current. Before making an observation, water is allowed to flow through the instrument for the purpose of determining the velocity of the fluid that corresponds to each degree of deviation of the pendulum. 4. Chauveau's and Lortet's dromograph is constructed on the same principle, and is in addition provided with a recording contrivance. A sufficiently wide tube (Fig. 69, II, A B), provided with a lateral tube C, which can be connected with a manometer, is introduced into the divided artery (carotid of the horse). At a there is a small linear opening closed with a rubber plate through which a light pendulum a b projects into the tube. The pendulum is prolonged upward as a thin indicator (b) , w^hich makes excursions proportional to the velocity of the current, and w^hich can be read off on the scale S S. G repre- sents a handle for fixing the instrument. The apparatus is first tested with water to determine the excursions corresponding to the various velocities. As the indicating pendulum is exceedingly light it records the slightest changes in velocity. 174 MEASUREMENT OF THE VELOCITY OF THE BLOOD-CURRENT. The velocily-citrve (Fig. 69, III) is recorded by permitting smoked paper to pass slowly before the tip of the indicator in the'direction of its long axis. The apparatus is of value because it registers the characteristic variations m the veloc- ity of the blood-current that accompany each beat of the pulse. The dromographic curve resembles a pulse-curve, and, like the latter, it possesses a primary (P), as well as a secondary, recoil-elevation (R) . 5. CybiiLski's photohemotachometer is constructed on the principle of Pitot's tube. When fluid flows through a tube d e (Fig. 70, //) in the'direction indicated by the arrows, the column of fluid stands at a higher level in the manometer p than in the manometer ;;/. While m r I. indicates onlj^ the lateral pressure, p X indicates the lateral pressure and in addition the velocity-height of the fluid. The velocity of the current in the tube may then be de- termined from the difference in the two levels. Fluid may be per- mitted empirically to pass through the tube tide with varj'ing ve- locity and the dift'erence in level between the two tubes p m that corresponds to the dift'erent de- grees of velocity at the current be determined. The form of Pitot's tube em- ployed by Cybulski is somewhat different, being bent at a right angle (/, c p). The extremity c is tied into the central, and the ex- tremity p into the peripheral, por- tion of the divided artery. When the blood is allowed to flow freely, the fluid rises to a higher level m the manometer a, which lies in the direction of the current, than in b. In order to avoid excessive length in the manometers a and b and thus to render the apparatus practically useful, Cybulski con- nects the manometers a and b by a tube shaped like a hairpin, which is flUed with air and can be closed b}^ means of a stopcock (/) applied above the bend. The fluid is allowed to rise to the points i and 2. If the stopcock (/) is then closed, the tubes represent an air-manometer in which the dift'erence between the levels I and 2 is sharply defined. As the surfaces of the columns of fluid I and 2 continually alter their position with respiration and pulse-beat, that is, as the manometers record the respiratory and pulsatorv variations in the velocity of the fluid passing through the tube c p, the fluctuations of the two levels may be advantageously photographed with a camera provided with a rapidly moving background, K. Fig. C is a reproduction of the curves obtained from the carotid artery of the dog. During the time represented by the interval between ij and i the velocity was 238 mm. ; in the phase between 2^ and 2,225 "^^n. ; and, finally, between 31 and 3,177 mrn. The velocity is greatest at the end of inspiration and at the beginning of expiration. Asphyxia at first increases the velocity. It is increased by paralv^ sis of the sympathetic and becomes smaller when the nerve is stimulated. Divi- sion of the vagus increases the velocity, while stimulation of the nerve naturally diminishes it. Fig. 70. — I. Diagrammatic Representation of Cybulski's Photohemotachometer: II, Pitot's tube. VELOCITY OF THE CURRENT. 1 75 THE VELOCITY OF THE CURRENT IN THE ARTERIES, CAPILLARIES, AND VEINS. In analyzing the results of observation on the velocity of the blood it must be constantly borne in mind that the sectional area of the arterial system beginning with the trunk of the aorta increases pro- gressively by subdivision of the branches, so that in the capillary system the sectional area of the blood-channel is increased 700-fold and more. From this point, owning to the reunion of the venous trunks, the sectional area again diminishes, but it is still greater than at the beginning of the arterial system. Exceptions are found in the common iliac arteries, which, taken together, are narrower than the trunk of the aorta. The cross-section of the four ijulmo- nary veins, taken together, is also somewhat smaller than that of the pulmonary artery. An equal quantity of blood must pass through each successive trans- verse section of both the greater and the lesser circulation. Therefore, the same quantity of blood must flow through the aorta and the pul- monary artery in spite of the great difference between the pressure in the two vessels. The velocity of the blood-current in the individual transverse sections of the blood-channel must, thus, be inversely proportional to the lumen or their sectional area. Hence, there is a marked progressive diminution in the velocity from the root of the aorta and pulmonary artery to the capillaries; so that in mammals it is only 0.8 mm. a second (in the frog 0.53 mm.), and in man from 0.6 to 0.9 mm. According to A. W. Volkmann the velocity of the blood in mammals is 500 times less in the capillaries than in the aorta. Therefore, the total cross-section of all the capil- laries must be 500 times greater than that of the aorta. In the small afferent arteries Bonders found that the velocit}" was still 10 times greater than in the capillary vessels. In the venous trunks the velocity again becomes accelerated, being, in the large trunks, from 0.5 to 0.75 times less than in the correspond- ing arteries. The velocity of the blood-current does not depend on the height of the mean blood-pressure, and it may accordingly remain the same both in anemic and in plethoric vessels. On the other hand, the velocity in a given section of the circulation is determined by the difference between the pressure in the cross-section at the beginning and that at the end of the section. It will, therefore, depend on, 1, the vis a tergo (heart's action) and, 2, the amount of resistance at the periphery (dilatation or narrowing of the smaller vessels) to the arterial current. In accordance with the slight difference in pressure in the arterial and venous systems in the fetus the velocity here is low. In the arteries every pulse-beat causes an acceleration in the move- ment of the current (as well as an increase in the blood-pressure) corre- sponding to the form of the pulse-curve. In large vascular trunks C. Vierordt found the pulsatory increase of velocity to be from ^ to ^ of the velocity during the diastole. These pulsatory variations in the veloc- ity of the current have been recorded by Chauveau by means of his 176 ESTIMATION OF THE CAPACITY OF THE VENTRICLES. dromograph. Fig. 69 III shows the velocity-curve taken from the carotid of a horse and which corresponds with the pulse-curve in indicating the primary elevation (P), as well as the dicrotic elevation (R). Examination of an extremity with the plethysmograph also discloses this velocity-pulsation or volume-pulsation. In the small arteries an additional pulsatory acceleration is observed, which occurs more rapidly in the first phase than in the later ones. The small trunks themselves are not visilDly distended under such circumstances. As the capillary region is approached this phenomenon, like the pulse- movement in general, disappears. In the arteries the velocity must be retarded by each inspiration and increased by each expiration; but the differences here are exceed- ingly small. If what has been said in the foregoing concerning the influence of the respira- tory pressure on the dilatation and contraction of the heart, and, therefore, on the movement of the blood, be compared, it will be evident that the respiration must also have an accelerating influence on the blood-current. Likewise, artificial respiration has the same eft'ect: When artificial respiration is suspended in a curarized animal, the blood-current at once becomes slower. If, however, the suspension is continued for some time, the current becomes again accelerated in consequence of the resulting dyspneic irritation of the vasomotor center. In the veins many derangements in the uniform flow of the blood occur : i . Regular fluctuations caused by respiration and the movements of the heart at the points where the large trunks empty into the heart. 2. Irregular effects due to pressure, friction in the direction of the current or in the opposite direction, changes in the position either of the body or of the limbs, a pump-like action in the iliac vein due to walking, etc. During extension and outward rotation of the thigh the crural vein relaxes and collapses in the iliac fossa and the internal pressure becomes negative; while when the thigh is flexed and elevated, the vein becomes filled to distention and the pressure rises. By means of this pump-like action the blood (with the aid of the valves) is forced upward. A somewhat similar phenomenon takes place during walking. ESTIMATION OF THE CAPACITY OF THE VENTRICLES FROM THE CURRENT-VELOCITY BY THE METHOD OF CARL VIERORDT. There may be considered at this point Vierordt's attempt to estimate the capacity of the ventricles, which is based on the velocity of the blood-current in the innominate arter\% in the aorta immediately before the origin of this trunk, as well as in the coronary arteries; although his premises are exceedingly- uncertain. (a) The velocity of the current in the right carotid is 26.1 cm. in a second; the cross-section of the vessel is 0.63 square cm.; hence, the quantity of blood that flows through it is 26.1 X 0.63 = 16.4 cu. cm. (i). (b) The velocity of the current in the right subclavian artery is 26.1 cm. a second; the cross-section of the vessel is 0.99 square cm.; hence, the quantity of blood that flows through it is 26.1 cm. X 0.99 = 25.8 cu. cm, (2) By adding i and 2 the quantity of blood that flows through the innominate artery is obtained: 16.4 4- 25.8 = 42.2 cu. cm. The cross-section of this artery is 1.44 square cm. (c) The cross-section of the aorta immediately before the origin of the in- nominate artery is 4.39 square cm.; the velocity of the current in the aorta is estimated to be about one-fourth greater than in the innominate, that is, 36.6 cm.; hence, the quantity of blood that flows through it is 161 cu. cm. (3). {d) The quantity of blood that flows through the two coronary arteries may be assumed to be 4 cu. cm. (4). Hence, the entire quantity of blood that flow's THE DURATION OF THE CIRCULATION. I77 throu<;h the cross-section of these vessels is (1 + 2 + 3 "i 4) 207.2 cu. cm. As the left ventricle must furnish this quantity of blood in a second, and as, in addition, one and one-fifth of the systole corresponds to i second, the quantity of blood throw-n into the aorta at each systole must be 172 cu. cm., or 180 grams of blood — which is the capacity' of the left ventricle. THE DURATION OF THE CIRCULATION. The question as to the time required by the blood to make the entire circuit of the circulation was first investigated by Edward Hering, in 1829, in horses by injecting a solution of potassium ferrocyanid into the external jugular vein and noting the time when this substance first appeared in blood withdrawn from the corresponding vein on the opposite side of the neck. Carl Vierordt, in 1858, per- fected the technic of these experiments by having a number of cups on a rotating disc pass at uniform intervals beneath the opened vein on the opposite side of the body. The first appearance of the 2 per cent, solution of potassium ferro- cyanid is recognized by adding ferric chlorid to the serum separated from the specimen of blood and the development of a Prussian-blue reaction. The duration of the circulation was found to be as follows: In the horse 31.5 sec. In the goose 10.89 sec. dog 16.7 " " duck 10.64 " rabbit 7.79 " " buzzard 6.73 " hedge-hog 7.61 " " cock 5.17 " cat 6.69 " A comparison of these values with the normal pulse-frequency of the same animals yields the following laws: 1. The average duration of the circulation corresponds with 27 con- tractions of the heart. Applying this figure to man, the duration of the circulation is 22.5 seconds, with 72 pulse-beats in the minute. If, therefore, the entire quantity of blood passes through the heart in 22.5 seconds, j— of the entire quantity must pass through in i second. This quantity is designated the second-volume of the circulation. The latter multiplied by 60 gives the minute-volume, and as there are 72 heart-beats in the minute, the minute- volume divided by 72 represents the amount of blood propelled at each beat of the heart, that is, the pulse-volume of the ventricles. The last calculations, how- ever, are exposed to serious sources of error. 2. In general the mean duration of the circulation in two species of warm-blooded animals is inversely proportional to the pulse-fre- quency. Of the influences that affect the dtiration of the circulation there may be mentioned: 1. A greater length of the vascular channel (for example, from the metatarsal vein of one foot to that of the other) requires a longer time than a shorter channel. This excess in time may be equivalent to about 10 per cent, of the diameter of the circulation. 2. Young animals, with shorter vascular channels and greater pulse-frequency, have a shorter circulation-time than old animals. 3. Rapid and effective contractions of the heart, as during muscular exertion, shorten the time. On the other hand, rapid but ineffective contractions (as after division of both vagi), and slow but correspondingly larger contractions (as with slight irritation of the vagus) , appear to have scarcely any effect. Carl Vierordt has, further, attempted to determine the quantity of blood in man from his investigations in the following manner: In all warm-blooded animals the circulation is completed by 27 contractions of the heart; hence, the entire quantity of blood must be equal to 27 times the ventricular capacity; therefore, in man, 27 times 187.5 grams, or 5062.5 grams. This quantity of blood, estimated as J 3 of the body-weight, would correspond to a body-weight of 65.8 kilos. In 1879 Landois called attention to the fact that potassium ferrocyanid, being a neutral potassium-salt, is a heart-poison, which, in small doses, accelerates, and in large doses paralyzes, the heart. These experiments, in the course of which 178 THE WORK OF THE HEART. numerous animals die, thus, of themselves, cause disturbances in the circulation. It was therefore suggested that the experiments be repeated with a substance that truly is chemically indilferent, or perhaps with the microscopic demonstra- tion of particles introduced into the circulation (such as heterogeneous blood- corpuscles, milk-globules or pigment-granules) . Accordingly, L. Hermann, in 1884, selected the innocuous sodium ferrocyanid. Wolff thus found the duration of the circulation in the rabbit to be 5.5 seconds, and it is therefore probable that in other animals also the time is shorter than that given by Vierordt. Landois injected mammalian blood-corpuscles into the lateral abdominal vein of frogs and searched for them microscopically on the opposite side. In this way he found the time from 7 to 1 1 seconds, v. Kries has recently expressed some doubt as to the general applicability of the method even from a physical standpoint. The substances first encountered are carried along only in the axial stream of the blood-vessels, and no conclusion, therefore, can be drawn from their appearance as to the circulation of the entire mass of the blood. Stewart employed a different method. If the electrical resistance offered by an unopened artery is first determined with a galvanometer, and at a given moment some saline solution is injected into the circulation, the galvanic resistance will be diminished when the saline blood passes through the section in communication with the galvanometer. The instant when this takes place is also noted. In this way Stewart found for the lesser circulation about one-fifth of the entire duration of the circulation ( = 10.4 seconds, in the rabbit and in the dog). The duration of the circulation in the kidney was 8 seconds, in the liver 3.8 seconds. A venous state of the blood increases the duration of the circulation. Pathological. — In the presence of fever the duration of the circulation appears to be increased. THE WORK OF THE HEART. Following the method of Johann Alfons Borelli and Daniel Passavant, Julius Robert v. Mayer estimated the work of the heart according to physical principles. The work performed by a motor is expressed in kilogrammeters, that is, the num- ber of kilos that the motor is capable of raising to the height of i meter in the iinit of time. Robert v. Mayer calculated that the left ventricle propels with each systole 0.1 88 kilo of blood, and, in order to raise it into the aorta, has to overcome the pressure existing in that vessel, corresponding to a column of blood 3.21 meters in length. The work of the ventricle at each systole is, therefore, equivalent to 0.188 X 3-21 = 0.604 kilogrammeter. Allowing 75 systoles for each minute, the work of the left ventricle in 24 hours is equal to 0.604 X75X60X24 =65,230 kilogrammeters. The work of the right ventricle is only about J of that of the left, or, in other words, about 21,740 kilogrammeters. The work of the two ventricles taken together is, therefore, 86,970 kilogrammeters. The work per- formed by a laborer during 8 working-hours equals 300,000 kilogrammeters, thus not quite four times as much as that of the heart. As all of the kinetic energy of the heart is converted by the resistance encountered within the circula- tion into heat, the work of the heart must result in supplying the body with heat: 425.5 grammeters correspond to i unit of heat, that is, the same force that is capable of raising 425.5 grams to a height of i meter is also capable of raising the temperature of i cu. cm. of water 1° C. The body, therefore, acquires by the conversion of the kinetic energy of the heart about 204,000 units of heat. As I gram of coal yields 8080 units of heat when consumed, the working heart accomplishes as much for the body as if more than 25 grams of coal were burned in it for the production of heat. The values given would be much smaller if the capacity of the ventricles were assumed to be smaller; for example, 60 cubic centi- meters; on that basis the work of the heart woufd be equivalent onh?- to 20,000 kilogrammeters, or yV of the entire muscular work of the body. THE MOVEMENT OF THE BLOOD IN THE SMALLEST VESSELS. ^ In the study of the movement of the blood in the smallest vessels microscopic observation of transparent portions of living animals is the THE MOVEMENT OF THE BLOOD IN THE SMALLEST VESSELS. 179 most ■important method, and it has been repeatedly employed by various investigators since the time of Malpighi, v^ho was the first to observe the circulation of the blood in the pulmonary vessels of the frog. Method. — Suitable objects for study with transmitted light are the tails of tadpoles and young lishcs; the web, the tongue, as well as the mesentery stretched and secured by means of pins on a strip of wax pasted to the object- carrier, or the lung of a curarized frog; in mammals the wing of the bat and the nictitating membrane, drawn out froin the orbit and spread out by means of threads over a vertical glass slide; and inuch less advantageously the mesentery. The following objects can be examined with a low power by reflected light: the blood-vessels of the frog's liver, of the pia mater in the rabbit, of the frog's skin, and of the mucous membrane on the inner aspect of the lip in human beings, as well as of the palpebral and bulbar conjunctivae. With respect to the form and arrangement of the capillaries in the various tissues, the following points are worthy of note: 1. The diameter of the smallest vessels, which permits the passage of the blood-corpuscles only in single file, may, however, vary from 2 to 5 //, and in the larger vessels naturally permits the passage of several corpuscles abreast. 2. The length is, on the average, about 0.5 millimeter; beyond this limit the vessels either originate by the division of small arteries, or unite to form veins. 3. The number of capillaries is extremely variable, being largest in tissues in which metabolism is most active, as the lungs, the liver, and the muscles; and smaller in others, like the sclera and the nerve-trunks. 4. The presence of numerous anastomoses is particularly striking, with the formation of plexuses, the shape of which depends principally on the form and structure of the basal tissue. Thus, the capillaries are arranged simply in loops in the papillae of the skin; as polygonal, retiform meshworks in the serous mem- branes and on the surface of many glandular acini; as longitudinal tubes running close together between the muscles and the nerve-fibers and between the straight uriniferous tubules; in a radiating manner, converging to a central point in the liver; and in the form of arcade-like loops at the free border of the iris and at the corneo-scleral junction. With regard to the transition of the smallest arteries into the capillaries, a distinction should be made as to whether the minute arterial twigs are end- arteries — that is, such as do not anastomose with other arterial twigs of the same order, but break up directly into capillaries, and communicate with neighboring arterial twigs only by means of capillaries; or whether before breaking up into capillaries the neighboring arteries communicate by liberal anastomoses, large enough to be called arterial. The presence or absence of arterial anastomoses is important with respect to the nutrition of the region supplied by the vessels. In observing the blood-current itself it will be seen at once that the red blood-cells progress only along the center of the vessel in the axial stream, while the parietal, transparent layer of plasma remains entirely free from them. The latter, designated Poiseitille's space, is recognizable especially in the smallest arteries and veins, in which the axial stream occupies three-fifths, and the light layer of plasma one-fifth, of the entire width of the vessel. It is less distinct in the capillaries. Accord- ing to Rud. Wagner, Poiseuille's space is wholly absent in the smallest vessels of the lungs and the gills. The red blood-cells pass through the smallest capillaries in single file. In larger vessels they move close to- gether, frequently turning and twisting in their course. On the whole, the rate of progress in the larger vessels is uniform; occasionally, how- ever, as when there is a sharp bend in a vessel, the movement is at times somewhat retarded, at times again accelerated. Wherever the stream divides, a blood-cell occasionally remains attached to the projecting ridge at the point of division, bending at its edges on each side into the bifurcation of the capillary, and appearing somewhat thinned at the center. Often it may adhere in this way for a long while, until, the cur- l8o MIGRATION OF THE BLOOD-CORPUSCLES FROM THE VESSELS. rent becoming accidentally stronger on one side, it is set free, whereupon it rapidly regains its former shape by virtue of its inherent elasticity. When two vessels join to form one, the elasticity of the red blood-cells is again put to proof. Cells at such points are not infrequently heaped up and pushed together in one direction or another. Occasionally, an accumulation of this kind causes a temporary stagnation first in one of the branches and then in the other; the obstruction is then removed, and for some time both capillaries continue to pour their contents into the collecting tube, during which process the corpuscles are shaken up, like dice in a box. The movement of the white blood-cells is entirely different. They roll along the walls of the blood-vessels, their peripheral zone bathed by the plasma of Poiseuille's space and their inner spherical surface pro- jecting into the procession of red blood-cells. The explanation of this peculiar property on the part of the leukocytes of keeping close to the vessel-wall has been furnished by Schklarewski, who dem- onstrated by certain physical experiments that in capillary tubes in general (as, for example, glass tubes), containing artificial mixtures of different kinds of granular bodies, those possessing the lowest specific gravity are forced to the wall when a current is set up in the tube, while those having a higher specific gravity move along in the middle of the streami. Thus, when once forced against the wall, the leukocytes must keep on rolling, partly on account of the viscosity of their surface, which causes them to adhere readily to the vessel-wall, and partly because the surface directed toward the axis of the vessel, where the current is swiftest, receives the most effective impulse, often by the direct impact of red corpuscles driven against it. The rolling movement is not rarely intermittent, probably because different parts of the leukocytes adhere with equal tenacity to the vessel-wall. The viscosity of the leukocytes is also in part responsible for their slower movement, which is from ten to twelve times slower than that of the red blood-cells; this is, however, in part also due to the fact that, owing to their parietal position, the larger portion of the body of the leukocyte projects into the peripheral layers of the cylindrical stream, where the current is least rapid. It is an interesting observation that in the vessels first formed in the incu- bated egg, as well as in young tadpoles, the movement of the blood from the heart is intermittent. The velocity of the stream is influenced also by the diameter of the vessels at a given point. The latter is subject to periodical variations, not only in vessels provided with muscular tissue, but also in the capillaries — -in the latter in conse- quence of spontaneous contraction of the protoplasmic cells that form their walls. In the pulmonary capillaries the blood-stream is more rapid than in those of the greater circulation, whence it may be concluded that the total sectional area of the pulmonary capillaries must be smaller than that of all of the capillaries of the body (of the greater circulation) . THE MIGRATION OF THE BLOOD-CORPUSCLES FROM THE VESSELS ; STASIS ; DIAPEDESIS. If the circulation be observed in the mesenteric vessels it is not rarely possible, especially if, after the application of a mild irritant to this vascular tissue (the contact of the air alone is sufficient), an inflammatory process begins to develop, to see the migration of leukocytes in varying numbers through the vessel- wall. Instead of rolling along in a jerky manner in the plasmatic zone, the cells gradually move more and more slowly, accumulate in increasing numbers and adhere firmly MIGRATION OF THE BLOOD-CORPUSCLES FROM THE VESSELS. to the wall; soon they begin to penetrate into the wall and ultimately they make their wiiy completely through it and wander for some distance further into the peri- vascular tissue. It is still a matter of doubt whether the corpuscles force their way through interendothelial stomata, supposed to be present, and then enter the lymphatic vascular system, or whether they simply pass through the cement- substance between the endothelial cells. Several successive steps can be distin- guished in this process of migration, which is known as diapcdcsis. — (a) adhesion of the leukocytes to the inner surface of the vessel (after gradual retardation in their progress along the wall up to that point) ; (b) extension of processes into and through the vessel-wall; (c) withdrawal of the cell-body, which appears con- stricted at the instant of its passage through the wall of the compression; (d) com- plete passage through the vessel-wall and the further progress of the leukocyte by virtue of its ameboid movement. Hering observed that, even under normal conditions, the leukocytes in larger vessels, which are surrounded by lymph-spaces, pass into the lymph-spaces. This observation explains why cells may be found even in such lymph as has not j'^et passed through any gland. The cause of the migration from the vessels resides, in part, in the independent power of movement on the part of the leukocytes; in part it is a physical phenomenon, namely filtration of the colloid mass of the cell- bodies through the force of the blood-pressure, and in the latter connection, there- fore, essentially dependent upon the intravascular pressure and the velocity of the blood-current. Hering regards the migration of leukocytes and even of a few red blood-cells from the small vessels into the lymphatics as a normal process, which he was able to observe in the mesentery of the frog. The red blood-cells escape from the vessel in the presence of obstruction to the venous flow, which causes, tirst, escape of blood-plasma through the vessel-wall, and with the plasma the erythrocytes are also forced through, undergoing a marked change of shape on account of the torsion to which they are subjected at the moment when they pass through the vessel-wall, but regaining their shape again after the passage is completed. The migration of blood-cells had alread}' been described in 1824 by Dutrochet and in 1S46 by Waller; the phenomenon was next more carefully studied by Cohnheim. According to the latter, the migration is a sign of inflammation, and the leukocytes, which accumulate in considerable numbers in the tissue, are to be regarded as true pus-cor- puscles, which may later multiply by division. It should, however, be distinctly stated that, in addition, the connective-tissue cells are also capable, by multiplication, of produc- ing pus-corpuscles, which differ by their greater size from the migrated leukocytes found in pxis. When a vascular part is sub- jected to severe irritation, hyper- emic reddening and swelling of the part are at once observed. It has been shown by microscopic examina- tion of transparent parts that both the capillaries and the smaller ves- sels become dilated and engorged with blood-cells; sometiines dilata- tion is preceded by a temporary contraction of brief duration. At the same time, a change in the ve- • locitv of the blood-stream is observed in the vessels. Rarely, and, as a rule, onlv'for a short time, the blood-stream is accelerated; but generally it is retarded. If the irritation be continued, the retardation soon becomes so great that the current onlv advances intermittently, and a to-and-fro movement of the blood- column is observed, — a sign that obstruction has already taken place in peripherally situated vascular areas. Finally, the current in the distended vessels comes to a complete standstill (stasis) . Bonders points out the greater number of leukocytes in stagnating blood, and believes correctly that this accumulation of leukocytes is a greater obstacle to their progress, as compared with the erythrocytes. AVhile Fig. 71. — Small Mesenteric Vessel from a Frog Show- ing the Migration of Leukocytes: w w, vessel-wall; a a, Poiseuille's space; r r, red blood-corpuscles; 1 1, leukocytes moving along the wall, at c c in various stages of migration; f f, migrated ceDs. l82 THE MOVEMENT OF THE BLOOD IN THE VEINS. these processes are going on, the migration of the leukocytes and rarely also of the red cells takes place. Under favorable conditions the stasis may be relieved, generally with a reversal in the order of the phenomena that have attended its development. The escape of blood-corpuscles through the intact wall of the vessel is designated diapedesis. The swelling of inflamed parts is due in part to the dilatation of the vessels, but chiefly to the escape of plasma into the tissues. THE MOVEMENT OF THE BLOOD IN THE VEINS. In the smallest veins, which are formed by the union of capillaries, the velocity of the blood-current is greater than in the capillaries, but slower than in the smallest arteries. At the same time, the current is everywhere uniform, and according to hydrodynamic laws the venous current would continue with absolute regularity to the heart, if it were not subject to other disturbances. Such disturbances, however, are operative in various directions. Among special peculiarities of the veins to which interference with the uniformity of the current is attrib- utable the following may be mentioned: I. The relative relaxation, the great distensibility and compress- ibility of even the larger trunks; 2, the incomplete distention, which does not increase to any considerable degree the elastic tension of the walls; 3, the numerous and at the same time free anastomoses among neighboring trunks, both in the same tissue-plane and from above down- ward. By this means it is possible for the blood, when the venous area is partly compressed, to escape through numerous readily distensible channels, and thus the occurrence of actual stasis is prevented; 4, the presence of numerous valves, which permit the blood-current to move only in a centripetal direction. These are wanting in the smallest veins, and they are most numerous in the medium-sized veins. The valves are of great hydrostatic significance, inasmuch as they divide long columns of blood, as, for example, in the crural vein when the body is in the erect position, into sections, thus preventing the entire column from exerting its hydrostatic pressure down to the lowest portions of the vein. As soon as pressure is exerted on a vein, the nearest valves below the point of pressure close and those next above open, thus leaving a free passage for the blood to the heart. The pressure on the veins may be of varied character: in the first place from without, by contact with various objects. Further, thickened and contracted muscles may com- press the veins, especially in the movements of the extremities. That the blood escapes in a stronger stream from an opened vein when the muscles are moved at the same time can be seen whenever venesection is practised. If the muscles are permanently contracted, the venous blood, escaping from the muscles, collects in the parts that are not moved, especially in the cutaneous veins. The pulsatory pressure in the arteries accompanying the veins also tends to accelerate the venous current. Direct observations have been made as to the velocity of the venous blood- ciurent with the hemodromometer and the rheometer. Thus, Volkmann found a velocity of 225 mm. in a second for the jugular vein; but in view of the low- pressure that prevails in the venous system, the employment of instruments for measuring the velocity is necessarily attended with marked deviations from the normal. Reil observed that the quantity of blood escaping from an opening in an artery was two and a half times as great as the quantity of blood escaping from a similar opening in a vein. SOUNDS AND MURMURS IN THE ARTERIES. 183 As the smaller venous branches unite to form larger ones, the lumen gradually diminishes toward the venae cavae: hence the velocity of the current must increase in the same proportion. The velocity in the venae cavae may be half as great as that in the aorta. Borelli estimated the capacity of the venous system as four times as large as that of the arteries. According to A. v. Haller the proportion is as 9 :4. As the pulmonary veins are narrower than the pulmonary arteries, the blood moves more rapidly through the former than through the latter. SOUNDS AND MURMURS IN THE ARTERIES. The acoustic phenomena observed in the arteries must, from a strictly physical standpoint, be designated as murmurs. Nevertheless it is customar}^ in medical nomenclatvire, following the example of Skoda, to apply the term sound to those acoustic phenomena that are of short duration and sharp definition, like the heart- sounds; while those that are of longer duration and are not distinctly delimited are designated murmurs in the narrower sense. In many cases a sharp distinction between the two is, therefore, impossible. In the carotid, and more rarely in the stibclavian, two distinct sounds are heard in approximately four-fifths of all healthy individuals. These sounds cor- respond in duration and pitch to the two sounds of the heart and must be inter- preted as due to propagation of the sound from the heart by means of the blood as far as the carotid, and they are, accordingly, designated transmitted heart- sounds. Sometimes the second sound of the heart alone is heard, as the site of its production is nearer the carotid. The second sound of the pulmonary artery, which is in close contact with the aorta, may also be transmitted to the point mentioned. Sounds and murmurs occur either spontaneously or only after the application of external pressure, by means of which the lumen of the vessel is narrowed. Accordingly a distinction is made between (i) spontaneous sounds and murmurs and (2) pressure-sounds and pressure-murmurs. Arterial murmurs are developed most easily by exerting pressure on a circum- scribed portion of a large arter\', for example, the femoral. The pressure must be so regulated that only a small portion of the lumen remains open for the passage of the blood {stenotic murmurs). As a result, a small stream of blood wall pass through the stenotic point with great rapidity and force, and enter the wider por- tion of the artery beyond the site of compression. This so-called pressure-stream throws the fluid-particles into active oscillatory and rotatory movement and thus produces the murmur in the wider, peripheral portion of the vessel. Analo- gous conditions prevail wherever there is a kink, a sharp bend or a tortuosity in the course of the artery. The phenomenon is, therefore, as a rule a pressure- murmur generated within the fluid. With regard to the question as to the origin of these murmurs, Geigel takes the stand that they are due to static transverse vibrations of the vessel-walls. Below the point of compression a thrill is felt in the walls of the large arteries synchronously with the pressure-murmur. In cases of aortic insufficiency, exophthalmic goiter, and circumscribed arteriosclerosis this thrill is much more marked than in normal cases, and it is also appreciable over smaller arteries. A murmur of like character is that at times heard over the subclavian artery synchronously with the pulse and designated subclavian, murmur. This is pro- duced by adhesions of the two layers of the pleura at the apices of the lungs, especially in association with tuberculosis and other diseases of the lungs, and in consequence of which the subclavian artery, as a result of. torsion and kinking, undergoes local stenosis, which sometimes manifests itself by diminution or absence of the pulse-wave in the radial arter\^ (paradoxical pulse) . Pathological.— It is evident that murmurs will develop in the human body likewise: (a) When, owing to morbid conditions, the arterial tube is dilated at some point where the blood-current is forcibly introduced from a normal portion of the artery. Such dilatations (aneurysms) quite generally give rise to murmurs (bruits) . (b) Pressure-murmurs will be generated whenever an organ exerts pres- sure on an artery, as. for example, by the greatly enlarged uterus during preg- nancy, and by a pathological tumor pressing upon a large artery. 184 ACOUSTIC PHENOMENA WITHIN THE VEINS. In all cases in wliich there is no external pressure, it is found that the pro- duction of spontaneous acoustic phenomena is greatly facilitated if, during the period of arterial diastole, the arterial wall is as relaxed as possible and, therefore, becomes suddenly and greatly distended at the time of the pulse-wave, that is, when the systolic minimum of tension of the arterial wall is rapidly displaced by the diastolic maximum of tension. This is particularly the case with aortic in- suificiency, a condition in which the arteries are often the seat of widespread murmurs. If even during arterial rest the minimum of tension of the arterial wall is relatively high, the acoustic phenomena are faint and may even disappear altogether. The following factors favor the development of arterial murmurs: (i) A suffi- cient degree of delicacy and elasticity of the vessel-walls; (2) a low peripheral resistance, that is, accelerated and unobstructed escape of the blood from the end of the vascular channel; (3) a material difference between the pressure ot the fluid in the stenotic portion and that of the fluid in the peripheral dilatation; (4) large size of the artery. Murmurs may be heard also in normal pulsating arteries, especially when the vessel is the seat of sharp bends or tortuosities. In almost all cases in which arterial murmurs are heard, one or several of the foregoing factors can be demon- strated. It is evident that murmurs of this kmd will be most marked when two or three large arteries are found in close apposition. Hence the rather loud murmur generated in the many tortuous and dilated arterial trunks of the gravid uterus {uterine or placental souffle) and the much less distinct funic souffle in the two umbilical arteries. In this category belongs also the so-called cerebral murmur heard in almost one-half of all infants with thin skulls, as well as the murmur heard over the morbidly enlarged spleen, and the thrill in the thyroid gland in cases of exophthalmic goiter. When auscultation is practised over the ulnar artery under the favorable conditions mentioned, especially in lean individuals, every pulse-beat is found to be accompanied by two acoustic phenomena, which coincide with the primary and the dicrotic elevation. In old persons especially, and in individuals with a bigeminate pulse, the two sounds are quite distinct. Friedreich believes the first sound to be produced by the vessel-wall, that is, the sudden tension of the artery distended during diastole. The second murmur naturally is feebler, in correspond- ence with the lesser degree of distention of the artery by the dicrotic elevation. Occasionally a third sound is heard between the other two, which corresponds to the elasticity-oscillations between the apex of the curve and the dicrotic elevation. In the radial artery and in the dorsalis pedis only a single murmur is, as a rule, heard synchronously with the pulse-beat. In cases of aortic insufficiency characteristic acoustic phenomena are present in the femoral artery. When the vessel is compressed, there is heard a double blowing (murmur) , the first element of which is due to the fact that a large mass of blood is driven to the periphery synchronously with the pulse, and the second to the fact that during the contraction of the artery a large quantity of blood flows back into the ventricle. On the other hand, if the artery is not compressed, two feebler sounds are heard, which are due to the fact that the auricle and the ven- tricle send a wave of blood into the arterial system in rapid succession (Fig. 55, III). Gerhardt similarly heard, in cases of insufficiency of the pulmonary valves, two dull sounds over every portion of the pulmonary surface. In other cases (when there is also tricuspid insufficiency) the second sound is produced by the sudden snapping closure of the valves in the femoral veins, caused by the rebound of the venous blood. Also, when the arteries are rigid (atheroma) a double sound is sometimes heard synchronously with the pulse-wave. This sound is attributed to the anacrotism of the pulse observed under such conditions. ACOUSTIC PHENOMENA WITHIN THE VEINS. The Venous Hum. — Aljovc the clavicle, in the fossa l)ctween the origin of the two heads of the sternocleidomastoid muscle, most commonly on the rTo-ht side there is heard in many individuals (40 per cent.) a sound that 'may be continuous i or synchronous with the diastole of the heart, or even with inspiration, and of a roaring or buzzing, sometimes hissing or singing, character. This sound is generated within the bulb of the common jugular vein and is called a venous hum. If present even when no pressure is exerted with the stethoscope, it is a patholoo-ical symptom. The phenomenon may be heard in almost any subject if pressure be THE VENOUS PULSE. THE PHLEBOGRAM. 185 exerted and the head is at the same time turned to the opposite side and sHglitly upward. The pathological venous hum occurs chietiy in yovmg anemic individuals in whom also a thrill is felt over the vessel; it is present also in cases of goiter, at times in youthful individuals, but it becomes less common with adx'ancing age The cause of the venous hum resides in the wliirling entrance of the blood from the relatively narrow ])ortion of the common jugular vein into the dilated bulb situated below. It appears to be generated chielly when the walls of the thinner portion of the vein are in fairly close apposition, so that the blood-stream is obliged to force its way through. This explains the fact that the occurrence of the phenomenon is favored by pressure and by turning the head to the side and slightly upward. The intensity of the sound depends upon the velocity of the blood as it passes through the narrow portion of the vein, and for this reason the act of inspiration and the diastole of the heart, both factors accelerating the venous flow, intensify the venous hum. The same is true with regard to the favorable influence of the erect posture. In rare cases a sound similar to the venous hum is heard in the subclavian, axillary, thyroid (in cases of goiter), facial and innominate veins, the stipcrior vena cava, the crural vein, and the inferior vena cava at the blunt margin of the liver. Regurgitant Miir)iiurs. — The expiratory murmur heard at times in the crural vein after sudden efforts at bearing-down is produced by a centrifugal current of blood passing through the vein at the bend of the knee, the valves being incompetent or entirely absent. When the valves in the bulb of the jugular vein are incompetent, a regurgitant murmur may be produced either during expiration (expiratorj- jugular-valve murmur) or during the sj'stole of the heart (systolic jugular- valve murmur) . In the presence of insufficiency of the tricuspid valve a systolic murmur has been heard in the crural vein when its valves were incompetent. Valvular Sounds in the Veins. — Forced expiration may give rise to valvular sounds in the crural vein, as the valves close with a snap under the pressure of the blood forced back. In the presence of insufficiency of the tricuspid valve a large quantity of blood is thrown back into the venae cavae at each ventricular systole. Under such circumstances also the venous valves may close suddenly with the production of a sound. The phenomenon occurs both in the bulb of the jugular vein and in the crural vein at the bend of the knee, but only when the respective valves are competent. THE VENOUS PULSE. THE PHLEBOGRAM. Method. — If the movements of a vein are recorded by means of a lightly weighted sphygmograph — a heavy load would compress the vein or at least obliterate the delicate details of the ctirve — -a characteristic form will be observed in a successful venous pulse-curve or phlebogram (Fig. 72). In the proper interpretation of the details of the phlebogram it is especially important to determine its chronological relations to the phases of the heart's action; hence, it is advisable to record a cardiogram and a phlebogram simulta- neously (on a recording surface attached to a vibrating tuning-fork) . The begin- ning of the carotid pulse coincides approximately w^ith the apex of the cardiogram, that is to say, w-ith the descending limb of the phlebogram. The venous pulse within the common jugular vein is a normal phenomenon. A pulsating movement synchronous with the inovements of the heart is frequently observed in the course of this vein. (Compare Fig. 34.) The movement may extend only to the lower portion of the vein, the so-called bulb, or higher up to the trunk of the vein itself. When the valves of the common jugular vein above the bulb are incompetent, a condition that is not at all rare, even in healthy per- sons, the phenomenon is particularly marked. The undulating movement ad- vances from below upward; as a rule, it is observed only when the subject lies quietly in the horizontal position ; it is more common on the right than on the left side, because the course of the right vein is straight and the vessel is nearer the heart than the left vein. The movement is propagated more slowly than the arterial pulse-wave. The venous pulse possesses the peculiarities of the moveinent of the heart. The tracing exhibits in a marked degree all of the details of the apex-beat curve, especially in connection with the pathological conditions to be discussed presently, and it there- fore closely resembles such a curve, as is shown bej-ond a doubt by a comparison of the venous pulse-curve (Fig. 72, i) with the apex-beat curve (Fig. 28, A). i86 THE VENOUS PULSE. THE PHLEBOGRAM. If it be considered that the distended jugular vein, in which the blood is subject only to slight pressure, communicates directly with the auricle, it will be readily understood that a contraction of the auricle will be propagated peripherally into the jugular vein as a positive wave. In Fig. 72, 9 and 10 represent the venous pulse from healthy individuals: the section a b corresponds to the auricular contraction. Landois has occasionally seen this composed of two slight elevations, corresponding to the contraction of the auricular appendage and the auricle. As the blood of the right auricle is subsequently thrown into agitation by the sudden tension of the tricuspid valve, the closure of the latter, which is synchronous with the systole of the right ventricle, sends a positive wave into the jugular vein, and this appears in 9 and 10 as the section b c. Finally, the sudden closure of the pulmonary valves may even be propagated through the blood in the ventricle as far as the auricle and still further up in the jugular vein, and be registered by the production of a small positive wave (e) . As the aorta is in immediate contact with the pulmonary' artery, a delicate wave may, on sudden closure of the aortic valves (in 9 at d), be generated at this point in a similar manner. During the Fig. 72. — Various Forms of Venous Pulse, Chiefly after Friedreich: 1-8, with tricuspid insufficiency; g and 10, venous pulse from the jugular vein of a healthy indi^•idual. In all of the cur\'es a b indicate contraction of the right auricle; b c, that of the right ventricle; d, closure of the aortic valves; e, closure of the pulmonary valves; e f, diastole of the right auricle. diastole of the auricle and of the ventricle blood flows freely toward the heart, and in consequence the vein collapses and the writing-lever makes a down-stroke. According to Knoll the normal jugular pulse is due partly to the positive wave caused by the contraction of the right auricle and partly to the negative wave caused by the dilatation of the ventricle; while the increase in the venous pressure that takes place between these two phases is brought about by interference with the flow of venous blood to the heart during the auricular pause. In the sinuses of the skull the blood likewise exhibits piolsatory movement, because blood flows freely into the heart during diastolic relaxation. Under favorable conditions this ptdsatorj' movement may be propagated as far as the veins of the retina and tht:s give rise to the retinal venous pulse, which was familiar to the earlier investigators. Pathological. — The venous pulse may be much larger and much more pro- nounced in all its characteristic parts in cases of tricuspid insufficiency. A mo- ment's reflection will show that under stich circumstances ever}- contraction of the right ventricle must cause regurgitation of a certain quantity of blood into THE VENOUS PULSE. THE PHLEBOGRAM. 187 the veins, by which a marked wave may be produced. As a rule, the common jugular vein pulsates quite strongly in cases of tricuspid insufficiency; but when the valves at the bulb of the jugular vein are still competent, the pulse is not propagated into the vein itself. The jugular pulse is, therefore, not a necessary sign of tricuspid insufficiency, but only a sign of insufficiency of the valves of the jugtilar vein. The ventricular systole, however, is always propagated into the inferior vena cava, which is without valves, and there it produces especially the so-called liver-pulse. Each ventricular contraction throws a large quantity of blood as far as the hepatic veins and thus the liver undergoes systolic swelling and distention due to injection. The figures from 2 to 8 represent tracings from the common jugular vein. In all the curves, a b indicates the auricular contraction; the contracting auricle throws a positive wave into the veins. This portion of the curve appears at times as a simple anacrotic basal elevation (3). Not infrequently (as particularly in i, representing a curve from one of the thyroid veins) two or three small notches make their appearance at this point, and these may be compared with the analo- gous elevations in the cardiogram. In accordance with the tension of the vein, as well as with the freedom of the How of blood from the vein to the heart, and also with the respiratory position of the thorax, the auricular notch may appear in the descending portion of the foregoing curve, as in 5 and 8; at times alternately as in 3 and 8 (see 7); at other times, a portion of the auricular wave may be in the descending portion of the foregoing curve, while the remainder is found in the ascending portion of the same curve, as in 6, 2 and 4. When the action of the auricle is exceedingly feeble, the auricular wave may even be entirely abortive as in 7 at f . The ventricular elevation is caused by the large blood-wave thrown back into the vein by the evacuation of the ventricle. The apex of this wave (c) is at times higher, at other times lower, in accordance with the tension in the vein and the pressure of the sphygmograph. It is usually followed by at least one notch (4, 5, 6 e), produced by the sudden closure of the semilunar valves of the pulmonary artery. It is not surprising that the closure of these valves produces an undulatory movement in the ventricle that is propagated through the constantly open tricuspid valve into the auricle and the veins. The adjacent aorta may even produce a small wave next to e by the closure of its valves (as in i and 2d). When the valve-closure becomes feebler in consequence of diminished tension in the large arteries, the aortic-valve wave d is the first to disappear (as in 4 and 5) ; later also the elevation due to closure of the pulmonary valves e disappears (as in 3 and 7). After the closure of the valves the curve falls, in correspondence with the diastole of the heart, as far as f. An especially distinct venous pulse may be produced also when the right auricle is greatly overdistended, as in cases of mitral insufficieiicy or stenosis. In rare instances other veins pulsate in addition to the common jugular, such as the external jugular, some of the facial veins, the anterior jugular vein, the thyroid, the external thoracic, and the veins of the upper and lower extremities. Landois on one occasion saw extensive venous pulsation in a moribund woman without any cardiac lesion, in whom the autopsy revealed an enormous, white, fibrinous clot extending from the right ventricle^ into the auricle and making closure of the tricuspid valves impossible ; even the cutaneous veins on the anterior surface of the thorax could be seen pulsating strongly. It is evident that pulsations similar to those produced in the veins of the greater circulation in cases of tricuspid insufficiency must also be produced in the pulmonan' veins in cases of mitral insufficiency. Such pulsations are, however, not directly visible ; although it may be possible to demonstrate their presence by observing the cardiopulmonary movement. In rare cases the veins on the backs of the hands and the feet are seen to pulsate, because the arterial pulse is propagated to the veins through the capillaries, or possibly through some direct communication between the arterial branches and the veins. This phenomenon may occur even under normal conditions, espe- ciallv when the peripheral extremities of the arteries are dilated and relaxed, or when the pressure within them becomes high and falls rapidly again, as in cases of aortic insufficiency. . . • , 1. Diastolic collapse of the veins of the neck is observed in association with heart- disease at the instant when the tricuspid valve opens. It is due to deficient con- traction of the right auricle. In cases in which the interior of an artery com- municates directly with the interior of a vein as a result of traumatism or rupture, the arterial pulse "is propagated into the venous channels. l88 THE DISTRIBUTION OF THE BLOOD. THE DISTRIBUTION OF THE BLOOD. The methods employed for determining the quantity of blood contained in individual organs and members must unfortunately as yet be regarded as inade- quate, (i) The quantity of blood contained in the part may be determined after death in frozen cadavers. This method is inaccurate, because after death, par- ticularly through the stimulation of the vasomotor center, the quantity of blood contained in any given part undergoes profound changes in consequence of the fact that different parts of the body die and freeze at different times. (2) A part may be forcibly ligated oft' from an animal during life, then be at once severed, and the quantity of blood in the tissues be determined while they are still warm. This method is, unfortunately, inapplicable to many internal organs. J. Ranke determined in this way the distribution of the blood in the living rabbit at rest. He found one-fourth of the entire quantity of blood in (a) the resting muscles, (b) the liver, (c) the circulatory organs (heart and large arterial trunks), (d) the remaining organs taken to- gether; of the last the lungs contained between 7 and 9 per cent. The amount of blood is influenced by: (i) The anatomical distribution of the vessels in general, that is, the number of vessels in individual parts of the body; (2) especially the size of the vessels, which is dependent upon physiological causes: (a) the blood-pressure within them; (6) the state of irritability of the vasocon- strictor or vasodilator nerves; (c) the condition of the tissues in which the vessels are situated, for example, the intestinal vessels during the absorption of alimentary juices; the muscular vessels during the contraction of the muscles (vessels in in- flamed parts) . The most important factor influencing the quantity of blood in an organ is the activity of the latter. In this connection the ancient dictum "ubi irritatio, ibi affluxus" is applicable. Examples are afforded by the salivary glands, the stomach, and the muscles during activity. As, however, under normal conditions of the body, the individual organs in many ways relieve one another, one organ may in the course of a day be found in a condition of greater plethora at one time and another organ at another time. The variations in the dis- tribution of the blood coincide with the alternations in the functional activity of the organs. Thus, while one organ is in a state of increased activity, the remainder often are resting: the process of digestion is attended with muscular lassitude and mental relaxation; severe mus- cular exertion delays digestion ; when the skin is reddened and secreting freely, the action of the kidneys is temporarily in abeyance. Some organs (the heart, the respiratory organs, and certain nerve-centers) appear to maintain a constant level of activity and contain the same quantity of blood at all times. While an organ is active, the amount of blood present may increase up to 30 per cent, or even to 47 per cent. The organs of locomotion in young and vigorous individuals are likewise relatively more plethoric than those of older individuals with a feebler muscular system. During mental activity the carotid is dilated, and the dicrotic elevation of the carotid curve is increased, while the radial exhibits reverse conditions, and the pulse is accelerated. In this condition of greater activity the increased amount of blood usually undergoes more rapid renewal at the same time; for example, after muscular exertion the duration of the circulation is diminished. This circumstance may be affected by a great variety of influences that govern the movement of the blood. PLETHYSMOGRAPHY. 189 The development of the heart and the large blood-vessels is responsible for certain dilterences in the distribution of the blood in children and in adults. From childhood to puberty the heart is relatively small and the vessels are relatively large. After puberty, on the contrary, the heart is large and the arteries are comparatively small. Accordingly, the arterial blood-pressure in the greater cir- culation must be lower in a child than in an adult. The pulmonary artery is relatively large in childhood, the aorta relatively small; after the onset of puberty both arteries are approximately of the same size. Hence, it follows that the blood-pressure in the pulmonary vessels of the child must be relatively higher than in the adult. PLETHYSMOGRAPHY. The plethysmograph is an instrument employed to determine and register the amount of blood in an extremity and its variations. It is a perfected apparatus, modeled after the "box-sphygmometer" described by Chelius in 1850 (Fig. 41). It consists of a long container (G), designed for the reception of an entire extremity. The opening around the introduced part is made air-tight by means of rubber, and the interior of the vessel is filled with water. In the lateral wall of the receptacle is a communicating tube, which also is filled with water to a certain level. As each pulse-beat causes an enlargement of the extremity as a result of the increased flow of arterial blood, the water in the tube will indicate the magnitude of this positive variation in the qviantity of blood, Avhich will be transmitted to the drum (T), covered with an elastic membrane, and with which is connected a writing lever moving in a horizontal direction. The cylinder G may also be filled with air. v. Kries connects the tube with a gas-burner instead of with the registering drum (T) , so that the variations in the size of the arm are reproduced in the flame, the flickerings of which may be photographed. iK^ Fig. 73. — Mosso's Plethysmograph: F, communicating flask, by elevation of the level of which the hydrostatic pressure may be increased; T, the inscribing apparatus. Individual organs (spleen, kidney) may be enclosed in a box-like apparatus in a similar manner for the purpose of observing fluctuations in their size: onco- graph. The fluctuations of the plethysmograph permit recognition of the following phenomena: I. Pulsatory fluctuations in voltime. — As the venous current in the resting extremity may be regarded as uniform, any rise in the volume-curve must indicate a greater velocity in the movement of the arterial blood-current toward the periph- ery, and the reverse. The curves registered by this apparatus represent volume- pulsations and resemble a dromographic curve (Fig. 69, III). A rise in the limb of the curve indicates a greater flow of arterial blood, while a fall indicates a diminution in the flow. If the level of the cvirve remains the same, it is to be inferred that the arterial inflow of blood is equal to the venous outflow. At first sight the plethysmographic tracing (volume-curve, current-pulse) presents a great similarity to the sphygmographic tracing (pressure-pulse), espe- ciall}' from the fact that both exhibit the dicrotic elevation. More careful ex- amination, however, reveals several differences: In the plethysmographic tracing (current-ptilse) the curve descends to a much lower level after the primary apex. igo TRANSFUSION OF BLOOD. This marked fall, which is not accompanied by a corresponding fall in the pressure, is attributed by v. Kries to a peripheral reflection, that is, one in which a positive wave is reflected as such. The dicrotic elevation (secondary wave) appears, further, somewhat earlier in the plethysmographic curve (current-pulse) than in the sphygmographic curve; although it also has a centrifugal course, as in the sphyg- mographic curve. 2. The respiratory fluctuations, which correspond to the respiratory fluctua- tions in blood-pressvire. Active breathing and cessation of breathing produce a diminution in volume. Further, the part has been observed to undergo enlarge- ment in consequence of effects at bearing down and coughing, and reduction in size during sobbing. 3. Certain periodic fluctuations, dependent upon periodic- regulatory movements of the vessels, particularly of the smaller arteries. 4. Vari- ous fluctuations due to accidental causes that bring about alterations in the blood-pressure, such as change of position producing hydrostatic effects; dilatation or contraction of other large vascular areas. 5. Muscular movements in the ex- tremity introduced into the plethysmograph cause a reduction in volume, because the venous pulse is accelerated, and in addition the musculature itself is somewhat reduced in size, in spite of the fact that the intramuscular vessels are dilated. 6. High (from 33° to 36° C.) and low (from 4° to 8° C.) temperature, when applied to the skin of the arm, increase the volume of the member in consequence of paresis of the muscular coat of the blood-vessels caused by the thermic stimuli. 7. Mental exertion diminishes the volume of the extremity; sleep has the same effect. 8. Compression of the afferent artery causes diminution, while constriction of the veins naturally causes an increase in the volume. 9. Irritation of the vaso- motor nerves is followed by a decrease, that of the vasodilators by an increase, in volume. TRANSFUSION OF BLOOD. Transfusion is the physiological introduction of blood into the vascu- lar system of a living being. The first mention of direct exchange of blood between two individuals from vessel to vessel takes us back to the time of Cardanus. After the discovery of the circxilation of the blood. Potter in England again called attention to the prac- ticability of transfusion. Numerous experiments were made on animals. Attempts were made by the introduction of fresh blood particularly to resuscitate animals that had bled to death. The physicist, Boyle, as well as the anatomist, Lower, took an especially active part in these experiments. The blood of the same or of another species was used. The first transfusion in man was practised by Jean Denis in Paris in 1667 with lamb's blood. (a) The erythrocytes are the most important constituents to which the re- suscitating power of the blood is due. They retain their functions even after the blood has been defibrinated. The changes in the red blood-cells produced by time and by prolonged exposure to high temperatures have been described on p. 36. (b) With respect to the gases contained in the blood, it is to be remembered that oxygenated blood under no circumstance is injurious. Venous blood can, however, be infused into the blood-vessels of a living being without injury, provided the respiration is sufficient to arterialize the infused blood in its passage through the pulmonary capillaries. Under such circumstances the carbon dioxid contained in the blood is replaced by oxygen in the process of respiration. If the respiration, however, is arrested or if it is not carried on with sufficient activity, the blood, still rich in carbon dioxid, will be conveyed to the left heart and on through the arteries of the medulla oblongata. In consequence there results violent irritation of the centers in that region, followed later by paralysis and even by death. (c) The fibrin or the substances forming it take no part in the resuscitating activity of the blood. Therefore, defibrinated blood is capable within the body of assuming with equal success all of the functions that belong to non-defibrinated blood, (d) Investigations, especially by Worm-Muller, have shown that the vascular system (dog) is capable of taking up an excess of foreign blood up to S;} per cent., TRANSFUSION OF BLOOD. I9I without injurious consequences. It follows that the vascular system possesses to a certain degree the power of accommodating itself to large quantities of Ijlood, just as it is known to possess the power of adapting itself to a diminished volume of blood, as, for example, after hemorrhage. Transfusion is practised: i. In cases of acute anemia, especially after a hemorrhage when it is sufficiently great to threaten the life of the patient. The object under such circumstances is to replace directly with new blood (from 150 to 500 cu. cm.) that which has been lost and is necessary to main- tain life. 2. In cases of poisoning in which the blood has been vitiated by the admix- ture of a toxic substance and has thus become untit to maintain the vital functions, a large quantity of this vitiated blood may be removed by copious venesection under suitable conditions and normal blood be introduced into the vessels in place of the blood withdrawn {depletory transfusion) . The chief form of intoxication amenable to this treatment is that with carbon monoxid. Also the admixture of other poisons with the blood, especially those that dis- solve the erythrocytes or that cause marked methemoglobinemia, as, for ex- ample, potassium chlorate, as well as other toxic substances (ether, chloroform, chloral hydrate, opium, morphin, strychnin, snake-venom), may likewise furnish an indication to replace the poisoned mass of blood with normal blood. 3. Under certain morbid conditions, abnormal states of the blood may develop in the body and threaten its integrity; these may affect both the mor- phological elements, and the composition of the blood. The morbid alterations in the constitution of the blood include poisoning with urinary constituents (uremia) , with biliary constituents (cholemia) and with carbon dioxid. If severe they may cause death. Therefore, in desperate cases of this kind, especially when the cause is a temporary one, the vitiated blood may be in part replaced by normal blood. Whether hydremia, oligocythemia and pernicious anemia are iridications for transfusion will depend on the correct interpretation of the under- lying disease. Between a quarter-hour and a half-hour after transfusion, in accordance with the amount of blood introduced, a more or less violent febrile reaction takes place. The operative procedure varies accordingly as defibrinated or non-defibrinated blood is employed. When a defibrination is to be practised, the blood obtained by venesection from a healthy human being is collected in a vessel and beaten with a small rod until the fibrin has been completely removed. The blood is then filtered through an atlas-filter, without pressure, is heated to the tem- perature of the body by placing the vessel in warm water, and it is conveyed into the opened vessel with the aid of the buret-infuser of Landois or a syringe. The vessel selected may be a vein, as, for example, the basilic at the bend of the elbow, or the long saphenous vein at the internal malleolus. Under such circumstances the blood is injected in the direction toward the heart. The blood may be injected also into an artery (the radial or the posterior tibial), either in the centrifugal or in the centripetal direction. In any event, care rnust be exercised, especially when the blood is injected into the veins, to guard against the entrance of air, as such an accident "might even cause death. Death occurs when the air that has entered the right heart is churned up into froth by the movements of the heart and in this form is pumped into the smaller branches of the lesser circulation, thus arresting the flow of blood through the lungs. After the injection of air into the arterial system a few small bubbles of air may possibly pass through the capillaries of the greater circulation and thus be found every- where in the vessels. They disappear at once, however, because the oxygen enters into chemical combination and the nitrogen is absorbed. If defibrinated blood is not to be infused the divided vein of the donor is connected by means of a tube with the vessel of the recipient, so that direct trans- fusion takes place. The blood may also be taken up with an oiled syringe, to which the blood does not adhere, and transfused at once without defibrination. The latter procedure, however, is attended with the great danger that coagula- tion may take place during the operation, in consequence of which blood-clots may readily be introduced into the circulation of the recipient. The resulting obstruc- tion and even more so the possible conveyance of coagula to the heart and into the lesser circulation, may even threaten life. Landois has transfused without injury into animals the non-coagulable blood that has been sticked bv leeches after removal from them by stripping. From 192 TRANSFUSION OF BLOOD. the cephalic extremity of the leech hardened m alcohol, dried and pulverized, a decoction can be prepared by admixture with o.g per cent, saline solution (one head is boiled for ten minutes with 6 cu. cm. of a saline solution, and then filtration is practised). This decoction, when mixed in the proportion of 6 cu. cm. to 15 cu. cm. of blood obtained by venesection, stiftices to maintain the latter in a fluid state. The mixture will not coagvilate for some time and can be used without fear of injury. By this means the dreaded effect of the fibrin-ferment may be avoided. In Man the Injection of Animal Blood is Unjustifiable under Any Circumstances. — Direct transfusion of blood froin the carotid of a lamb into the brachial vein of a man was formerly employed not infrequently for therapeutic purposes. It is to be remembered, however, that the erythrocytes of the sheep are rapidly dissolved in human blood, and in consequence the most efficient constituents of the transfused blood are destroyed. In a general way, it is found that the blood- serum of many mammals has a rapid hemolytic effect vipon the blood-cells of other species of mammals. Thus, the serum of dog's blood has a rapid and intense hemolytic action, while that of the horse and of the rabbit is relatively slow in action. The erythrocytes of mammals possess a variable power of resistance to the sera of other species of mammals. Thus, the erj'throcytes of the rabbit, when mixed with the blood of another species, are readily dissolved; while the cells of the cat and the dog exhibit much greater resistance. The rapidit}^ with Avhich erythrocytes are destroyed in the blood of another species is proportional to the rapidity with which the blood-cells of the blood of the other species are dissolved in the blood-serum of the recipient. Thus, for instance, rabbit's blood and lamb's blood disintegrate within a few minutes in the circulation of a dog. When there is a difference in the size of the blood-corpuscles of the two species, the hemolysis can readily be observed in small specimens of blood obtained by puncture. As the erythrocytes dissolve, the blood-plasma is stained red by the liberated hemo- globin. A portion of this liberated material may supply the demands of metabo- lism in the body of the recipient and be utilized for katabolism and anabolism, while part of it is used up in the formation of bile. When, however, the quantity of hemoglobin liberated by the erythrocytes is considerable, hembglobin is excreted in the urine, and to a less extent in the intestine, in the ramifications of the bron- chial tree and into the serous cavities. In the last the heinoglobin inay subse- quently tmdergo absorption. Thus, in man hemoglobinuria has been observed after the injection of more than 100 grams of lamb's blood. When blood from another species is transfused into an animal, the blood-cor- puscles of the latter may undergo partial disintegration. This is the case when the erythrocytes of the recipient are readily soluble in the serum of the trans- fused blood. Upon this fact depends the great danger of transfusing a consider- able quantity of heterogeneous blood into the rabbit, whose erythrocytes so readily undergo solution. The same thing would happen if a dog's blood were transfused into the veins of a man. In animals whose erythrocytes readil}'^ un- dergo solution, as, for example, the rabbit, the injection of many kinds of sera, as, for example, that of the dog, of man, of the pig, of sheep, and of the cat, is followed by alarming symptoms, in accordance with the quantity of blood in- troduced, namely: acceleration of respiratory frequency to the point of dj'spnea, convulsions, and even death from asphyxia. Under such circumstances all the stages of hemolysis can be seen in a specimen of blood obtained by puncture. Animals possessing more resistent erythrocytes, such as dogs, tolerate the injec- tion of heterogeneous sera, as, for example, from sheep, neat cattle, horses and pigs, without exhibiting such marked symptoms. The injected foreign serum, being of feeble potency, is disposed of in the circulation of the recipient, before it has time to attack, not to say dissolve, the blood-cells to any great extent. The process of hemolysis is accompanied by two other phenomena, which render the transfusion of heterogeneous blood especially dangerous : i . Before the erythrocytes are dissolved, they usually adhere together tenaciously and form small masses, consisting of from 10 to 20 or more blood-cells, which are obviously capable of obstructing large capillary areas. When these masses have been present in the blood for some time they yield up their hemoglobin, leaving ovAy the fused remains of stroma. This forms a viscid, tenacious, string]v' mass (stroma-fibrin) , which likewise may occlude the smaller vessels. 2. The sudden appearance of large quantities of dissolved hemoglobin in the blood of an animal may cause extensive coagulation, principally in the venous system, but also in the larger vessels throughout a considerable extent. The processes described may produce death either suddenly or after a protracted course. Dissolved hemoglobin causes THE DUCTLESS GLANDS. INTERNAL SECRETIONS. I93 in the circulation the dissolution of numerous leukocytes, from whose disintegration the tibrin-factors result. It is curious that hemoglobin exposed to the air gradually loses this property; also librm-ferment in contact with hemoglobin is gradually destroyed or rendered inactive. As numerous small vessels are occluded as a result of the processes described, the signs of nnpeded circulation and of stasis will be encountered in the different organs of the body. In man, the injection of lamb's blood is followed by a bluish-red dis- coloration of the skin. The obstacles encountered by the blood-current in the lungs cause dyspnea or even laceration of the small vessels in the air-passages and bloody expectoration. The dy.spnca may increase if interference with the free circulation of the blood develops at the i"espiratory center. The digestive organs, for the same reason, exhibit increased intestinal peristalsis, diarrhea, evacuation of the bowels, tenesmus, vomiting and abdominal ])ain. These phenomena are explained by the fact that any disttirbance of the circulation in the abdominal vessels is followed by increased peristaltic movements. In the kidneys secondary degeneration of the glandular substance takes i^lace in consequence of occlusion of the vessels. The uriniferous tubules are occluded by casts consisting of coagulated albuminous material. In the muscles the occlusion of numerous vessels may cause stiffness, or even rigidity from coagulation of myosin, just as in Stenson's experiment, together with increased heat-production. Also the nervous system, the organs of special sense and the heart may exhibit various disturbances, all of which can be attributed to the occlusion of vessels and the resulting interference with the circulation. It is interesting to note that the transfusion of foreign blood is followed as a rule within half an hour by the development of active fever. Finally, it should be mentioned that lacerations of the vessel-walls have also been observed. These explain the obstinate hemorrhages that may occur not only on the free surfaces of mucous and serous membranes, but also in the parenchyma of organs, as well as in surgical wounds. The blood itself coagulates slowly and imperfectly. By far most of the facts bearing on the transfusion of heterogeneous blood that have been mentioned were discovered through Landois' investigations. Attempts to inject other substances instead of blood are not to be commended: from 0.75 per cent, to 0.9 per cent, saline solution, while capable of improving the circulatory conditions in a purely mechanical w^ay, and thus exerting a favora- ble influence, is obviously incapable of supporting life in cases of severe anemia, in which the quantity of blood remaining in the body is insufficient to maintain the vital processes. THE DUCTLESS GLANDS. INTERNAL SECRETIONS. Within comparatively recent times there has been attributed to the ductless glands, whose activity is still, for the most part, shrouded in obscurity, a special and important function, namely, the production of substances that enter the circulation and there in some peculiar way excite certain activities, or render innocuous certain poisonous sub- stances generated in the process of metabolism, either by destroying these or by manufacturing an antidote. In a similar manner it has been asserted of a number of other organs in the body that, in addition to their special function, they exert an important influence on the economy by means of such internal secretion. Thus, Brown-Sequard and d'Ar- sonval asserted that the kidneys are in part concerned in rendering innocuous the. toxic substances that accumulate in the body after nephrectomy; Tigerstedt and Bergman, that the kidneys produce a substance — renin — that increases the blood-pressure and has a powerful influence on the peripheral nerve-centers. The substances under consideration can be obtained from • the corresponding organs in the form of extracts and their action can then be tested upon the animal body. The spleen is contained in a firm fibrous capsule, which at the hilus gives off an investment for the entering blood-vessels. From the inner surface of the cap- 13 194 THE DUCTLESS GLANDS. INTERNAL SECRETIONS. sulc and the surface of the vascular sheaths there pass off numerous intersecting and branching trabeculse (the trabecula; of the spleen) , which form a rich mesh- work in the interior of the viscus, comparable to the cavities of a sponge. Fibril- lated connective tissue, mixed with elastic and unstriped muscle-fibers, forms the foundation of this portion of the viscus. The interior of the meshes contains a delicate reticulum of adenoid tissue (Fig. 131), which, together with the cellular elements contained in the meshes, is designated the splenic pulp. The smaller arterial branches, which gradually lose their fibrous sheath, ulti- mately break up into brush-shaped terminal twigs without anastomoses (peni- cils) . The points of division of the small arterial branches serve for the lodgment of the whitish Malpighian vesicles, which may attain the size of a pinhead and the structure of which in every respect resembles that of solitary lymph-follicles. The Malpighian bodies are found on examination to be spherical, lymphatic masses that have partially separated from the vascular .sheath. In some animals, instead of exhibiting a spherical form, they appear as loose arterial sheaths, in a measure as perivascular lymphatic sheaths, so to speak, which may extend to the smallest arterial twigs. According to Tomsa, lymphatic vessels coming from the Malpigh- ian vesicles are found in the subsequent course of the arterial sheath as far as the hilus of the spleen. Other lymphatics form a network in the capsule. With regard to the connection between the ends of the arteries and the veins, it is supposed that there is no continuous channel between the smallest capillary ar- terial twigs and the sinallest venous branches and that the meshwork of the pulp- reticulum represents an intermediate vascular area devoid of walls. The blood, accordingly, passes through the meshwork of the spleen traversed by the reticu- lum, just as the lymph-stream passes through the spaces of the lymphatic glands. According to another view, there is really a closed vascular channel connecting the ultimate arterial and the corresponding venous capillaries, which, however, con- sists of dilated spaces (like the cavernous spaces in erectile tissues) . These inter- mediary spaces are, however, completely surrounded by spindle-shaped endothe- lium. Within the meshes of the reticulum are found cellular elements of various kinds: (i) White blood-corpuscles of various sizes, some swollen and filled with a granular material; (2) leukoblasts or embryonal forms of leukocytes, which multi- ply by division; (3) erythrocytes; (4) embryonal forms of the latter, also desig- nated erythroblasts, which multiply by mitosis; (5) so-called blood-corpuscle-con- taining cells. The numerous nerves of the spleen consist of so-called Remak's fibers; they are sensory, motor, and vasomotor. Of the chemical constituents there should be mentioned globulin and nucleo- albumin, nucleinic acid, leucin, ty rosin, xanthin, hypoxanthin, taurin; further lactic, butyric, acetic, formic, succinic, uric, and glycero-phosphoric (?) acids; as well as fats, cholesterin, a gluten-like body, glycogen, inosite, iron-containing pigments, and even free iron oxid. The pulp becomes black on addition of ammo- nium sulphid. The ash is rich in phosphoric acid and iron, but poor in chlorin- combinations. With respect to the function of the spleen, the following points are note- worthy: 1. The spleen may be removed without injury to the individual, as has been proved both in animals and in man (inore than go cases, with about 40 recoveries). After removal of the spleen the hematopoietic activity of the bone-marrow appears to be increased. In frogs, extirpation of the spleen has been observed to be fol- lowed by the appearance of brownish-red nodules in the intestine, which have been regarded as vicarious spleens. Tizzoni speaks of splenic neoplasms in the omentum (horse, dog) after obliteration of the parenchyma and blood-vessels of the spleen. In extremely rare cases total absence of the spleen has been observed in man. 2. By virtue of its vmstriped muscle-fibers the spleen is capable of undergoing change in volume. Irritation of the spleen or of its nerves (by heat or electricity, by quinin, eucalyptus, ergot, and other agents) causes diminution in the size of the viscus, with anemia and granular change. As the spleen is found to be en- larged a few hours after digestion, at a time when the digestive organs have per- formed their work and contain less blood, the spleen has been regarded as an apparatus for the regulation of the vascularity of the digestive organs. According to Roy the circulation in the spleen is dependent not alone upon the blood-pressure in the splenic artery, but in marked degree on the contraction THE DUCTLESS GLANDS. IXTEkXAL SECRETIONS. 195 of the unstripcd musclc-filicrsof the ca])sule and the trabeculae, and which manifests itself in rhythmical movements lastinjj one minute. Paralysis of the splenic nerves, as in connection with certain febrile intoxica- tions (malarial fever, typhoid fever), causes enlari^ement of the organ. Division of the nerves has the same elTect. After extirpation of the small nerve-trunks scattered in the hilus Landois has observed circumscribed enlargement of the organ, with bluish-red discoloration. 3. The spleen has been regarded as a hematopoietic organ. In favor of this view is the fact that after extirpation the erythrocytes are diminished; further, the fact that a splenic infusion (or decoction, also an infusion of bone-marrow), when injected under the skin or into the peritoneal cavity, causes an increase of the ervthrocytes. The spleen is also a breeding-place for leukocytes. The blood from the splenic vein always contains numerous leukocytes, many of which are subse- quently destroyed in the circulation. Bizzozero and Salvioli discovered that a few days after great loss of blood the spleen became swollen, and the parenchyma was found to be rich in nucleated embryonal erythrocytes. 4. Other investigators regard the spleen as an organ for the destruction of blood-corpuscles, the presence of so-called "blood-corpuscle-containing cells" par- ticularlv supporting such a view. These cells are large leukocytes that have taken up red blood-corpuscles after the manner of phagocytes (similar cells are found also in extravasations of blood) . The red blood-cells gradually undergo degenera- tion within the leukocytes and yield as derivatives of hemoglobin iron-containing pigments resembling hematin. The spleen, therefore, contains more iron than can be accounted for by the amount of unaltered blood it contains. If with this fact there be yet compared the occurrence in the spleen of disintegration-products and of higher oxidation-products of the albuminous bodies, the spleen may prop- erlv be regarded as an organ for the destruction of erythrocytes. Additional sup- port for this view is found in the appearance of the salts of the red blood-corpuscles in the splenic juice. According to Schiff. extirpation of the spleen has no effect on either the absolute or the relative quantity of the red and white blood-cor- puscles. Even in the normal state the spleen exhibits frequent changes in size in the course of the day, particularly in conformity with varying activity of the digestive organs. In this respect the spleen resembles the arteries. Its vasomotor nerves have their center in the medulla oblongata. Stimulation of that center, especially bv asphyxia, causes contraction of the spleen. From the center fibers pass through the spinal cord (which is said to contain between the first and fourth cervical verte- brae ganglionic cells that likewise influence the contraction of the spleen) , further through the left splenic nerve and the semilunar ganglion into the splenic plexus. Irritation of the nerves, as well as the direct application of cold to the spleen or even to the splenic region, catises contraction of the viscus. Parah^sis of the nerves, by curare or by protracted narcosis, causes enlargement of the spleen. Apparently only the peritoneal investment contains sensory nerves. Pressure on the splenic vein causes slight enlargement of the spleen. In har- mony with this fact is the observation that increased blood-pressure wathin the splenic vein (in the presence of portal congestion or after the cessation of hemor- rhoidal or menstrual bleeding) is frequently attended with splenic enlargement. The injection of splenic extract has an effect opposite to thaf of injection of suprarenal extract. The thymus gland is relativelv well developed during fetal life and continues to grow during the first two years of life: but about the tenth year it becomes stationarv' in size and later degenerates to form the so-called thymic fai-body, the tissues of which still contain the remains of the lymphoid thymus-parenchyma. As long as it persists, the thvmus appears to have the function of a lymph-gland; for in the embrvo. w^hich possesses no lymph-glands, it is functionally active, and in reptiles and amphibia, which also possess no lymph-glands, it is a permanently functionating organ. The thvmus consists of acini varying in size from 0.5 to 1.5 mm. and possessmg the structure of simple lymph-follicle's. The Ivmph-cells lying within the reticulum mav exhibit various stages of disintegration. In addition, there are found scattered through the organ peculiar and mvsterious concentric Iwdies. especially during the time of involution. Numerous srnall lymph- vessels in part traverse the interior of the organ and in part spread out upon its surface. Blood-vessels are relatively numerous. . Among the chemical constituents there should be mentioned — m addition to 196 THE DUCTLESS GLANDS. INTERNAL SECRETIONS. gelatin, albumin, sodium albuminate, sugar and fat — leucin, thymus-nucleinic acid, xanthin, hypoxanthin; formic, acetic, butyric, lactic, and succinic acids. In the ash, potassium and phosphoric acid preponderate over sodium, calcium, magnesium (ammonium ?), chlorin, and sulphuric acid. Extirpation of the thymus gland in the frog is fatal. According to Svehla the infusion of thymus juice causes a fall of blood-pressure and acceleration of pulse, while large doses are fatal. The thyroid gland is an organ provided with vasomotor and secretomotor nerves, and composed of a richly cellular connective-tissue framework, containing closed circular or oval acini (from 0.04 to o.i mm. in diameter), which in the embrj'o and the new-bom are lined with a single layer of nucleated, granular, cuboidal cells. In 50 per cent, of all subjects accessory thyroid glands, up to four, are associated with the main gland; a small detached gland is occasionally found in front of the descending aorta. In addition, accumulations of epithelial cells are found in the acini and. in embryos, also beneath the common capsule. From birth the cells secrete a colloid substance by a transformation of their proto- plasm, at the same time undergoing morphological changes. Some of the cells are destroyed in this process of colloid degeneration. The acini of the thyroid gland evacuate their contents in part by rupture, with destruction of the epithelium, in part, in the process of pure colloid-produc- tion, by secretion into the intercellular interstices; and in this way the secretion reaches the interfoUicular lymph-spaces and then the blood. Blood-vessels of considerable size and importance enter the organ. Lymph- vessels partly begin in the interior among the acini, and partly form a network in the capsule that surrounds the entire organ. The constituents of the thyroid gland are colloid, nucleoalbumin, iodothyrin, leucin, xanthin; lactic, succinic, and volatile fatty acids. According to Schiff, Zesas, J. Wagner and others, extirpation of the thyroid gland is followed by death, with the symptoms of chronic intoxication. Dysphagia, vomiting and digestive disturbances, acceleration of the breathing; later dyspnea, alteration of the action of the heart, somnolence, slow and hesitating movements with fibrillar twitchings, which may go on to intermittent tonic convulsions (tetany) , palsies, alterations in cutaneous sensibility, desquamation of the skin, lowering of the body-temperature and of the blood-pressure, are the symptoms that precede death. Albuminuria, reduction of the amount of oxygen in the arterial blood and degenerations in the central and peripheral nervous system were observed by Albertoni and Tizzoni, Langhans, Kopp and Capobianco. In man, also, total extirpation of the thyroid gland (cachexia strumipriva) is a serious matter and often terminates fatally from tetany. The morbid phenomena may be counteracted, at least temporarily, by the internal administration of fresh or dry thyroid-gland substance, or by the sub- cutaneous injection of thyroid-gland extract or iodothyrin. The symptoms may be prevented by grafting a thyroid gland successfully in some other portion of the bod}-, and permitting the organ to form adhesions. These facts prove that the thyroid gland produces a substance that is indispensable for normal metabo- lism. Stated more accurateh', the function of the thj-roid gland is to neutralize a substance produced in the body, the accumulation of which has a toxic influence on the nervous system. The accessory thyroid glands and the hypophysis appear to possess similar functions: they undergo compensator^^ hypertrophy after extirpation of the thy- roid gland. Other investigators attribute the condition known as myxedema, that is, mucoid infiltration of the subcutaneous tissues of the head and neck, with profound disturbances of the nervous system, to the point of idiocy, to loss of the function of the thyroid. Especially noteworthy is the enlargement of the thyroid gland, together with the palpitation of the heart and protrusion of the eyeballs, in the condition known as exophthalmic goiter, which appears to be due to simultaneous (toxic?) irritation of the accelerator nerve of the heart, the sympathetic fibers of the unstriated muscles in the orbit and in the eyelids, as well as of the dilator nerves of the vessels of the thyroid gland. Myxedema and exophthalmic goiter seem to stand in a certain antagonistic relation to each other, the former depending on diminished, the latter on augmented, activity of the thyroid gland (hence extirpation has been recommended in cases of exophthalmic goiter). Landois observed in dogs that had been fed on thyroid glands a marked increase in the number and force of the cardiac contractions. The ingestion of thvroid gland causes an increased con- THE DUCTLKSS GLANDS. INTERNAL SECRETIONS. 197 sumption of oxygen and therefore a more rapid breaking down of the tissues (for which reason it is a famihar therapeutic procedure for reducing weight) . According to SchondorlTthe body-fat is first transformed, the albumin not being attacked until the fat has been reduced to a certain minimum. The .substance (solely?) active in this connection is iodothyrin, a body prepared in i8g6 by Baumann, and con- taining nitrogen, phosphorus, and iodin. In some localities marked enlargement of the thyroid gland (goiter) is quite common, and is not infrequently associated with idiocy and cretinism. In those cases in which the goiter is designated a follicular hyperplasia of the thyroid gland, the condition can be made to disappear by the administration of preparations of the thyroid gland. Fr. Hofmeister found, after extirpation of the thyroid gland in rabbits, degeneration in the cartilages and disturbances in the growth of the bones. According to Gegenbaur the thyroid gland is an actively functionating organ in some of the remote orders of animals (for example, among the tunicates, in which it appears as a groove and secretes a digestive juice) , which in vertebrates has undergone involution. The suprarenal bodies consist of a medullary and a cortical layer, and contain compartments formed by connective tissue and bounded by blood-vessels. In the cortical layer the compartments are oblong and radiate, while in the medullary layer they are rather circular. The former contain (embedded in a reticulum) polyhedral, nucleated, protoplasmic cells without walls, the substance of which contains pigment and fat-granules, and is darker and more resistent than that of the medullary cells. The medullary layer contains also small and multipolar, large sympathetic nerve-cells. Both cortex and medulla are richly supplied with nerve-fibers. The blood-vessels are relatively abundant. The suprarenal bodies contain the constituents of connective and of nervous tissue, besides leucin, hypoxanthin, benzoic and taurocholic acids, taurin, inosite, fat and pigment-forming bodies. Of inorganic substances potassium and phos- phoric acid preponderate. The function of the suprarenal bodies is practically unknown. After extirpa- tion of one suprarenal body, the other undergoes hypertrophy to double its original size. Bilateral extirpation is followed by death, with the symptoms of poisoning and paralysis. These symptoms, however, do not develop if a small piece is allowed to remain. It appears, therefore, that the suprarenal bodies also are designed to destroy a poisonous substance in the body, which exhibits its injurious effects after extirpation of the glands. The injection of a watery extract of supra- renal body is said to arrest temporarily the toxic symptoms that make their appearance after extirpation. Injection of the extract obtained from the medullary substance of healthy animals (and which does not contain albtimin and is soluble in alcohol) gives rise to marked contraction of the arteries and increase in blood-pressure, slowing of the pulse by central stimulation of the vagus, or even arrest of the auricles. After section of the vagi the heart again becomes more rapid and stronger, owing to the action of the drug on the substance of the heart itself. The extract has the same constricting effect on small blood-vessels and hence raises the blood-pressure. The splanchnic nerve contains vasodilator and secretory fibers for the organ. The breathing is superficial and accelerated. Large doses injected intravenously cause death through enfeeblement of the central nervous system, dyspnea, and cardiac paralysis. In frogs muscular paralysis results. Brown-S6quard believed that one of the functions of the suprarenal bodies is to inhibit excessive pigment-formation. In agreement with this view, Tizzoni found, after extirpation of the organs (in rabbits), abnormal pigmentations, espe- cially on the lips, and Boinet in the blood and subcutaneous cellular tissues (of rats) . In conditions in which erythrocytes are dissolved and converted into pig- ment the suprarenal bodies are found to be especially rich in pigment. In the medullary layer a substance is formed that becomes brown when exposed to the air or brought in contact with alkaline tissues. In man the skin often presents a bronzed pigmentation (bronzed skin, Addison's disease) when the suprarenal bodies and their capsules have undergone (tuberculous) degeneration. In hemi- cephalous monsters the organs are atrophic, even when only the anterior halves of the hemispheres are absent. Hypophysis Cerebri. Coccygeal Gland. Carotid Gland. — But little is known concerning the function of the pituitary body. The posterior portion belongs to the infundibulum, and here the nervous elements are, to a large extent, displaced by connective tissue and blood-vessels; while the anterior portion represents a IQo COMPARATIVE. constricted off and modified part of the invaginated mucous membrane of the pharynx and contains glandular ducts with clear or dark cells. The extract ob- tained from the pituitary body contains iodin and causes an increase in the blood- pressure, which, however, is less than that cavised by an extract of suprarenal gland: the heart-beat becomes slower and more forcible. The function of the coccygeal gland, which is situated at the extremity of the coccyx, is unknown. The carotid gland, which occurs in man and mammals, and contains a con- voluted plexus consisting of intricately anastomosing capillaries within an epithe- lioid cellular mass, supported by a reticulum, has been compared by Stilling to the suprarenal bodies. Its function is unknown. COMPARATIVE. The heart in fishes (Fig. 74, /) and in the gill-bearing larvae of amphibia is a simple venous organ, consisting of auricle and ventricle. The latter sends the blood to the gills, where it is arterialized, and passing to the aorta it is dis- FlG. 74- — Diagrammatic Representation of the Circulation. /. In Fish: A, auricle with the sinus venosus (5); F, ventricle; /?, bulb of the aorta; f, branchial arteries; J /, branchial vessels; Z5, branchiales veins; £, circulus cephalicus aorts; F, common aorta; G, caudal artery; H, ductus of Cuvier; /, anterior cardinal vein; A", posterior cardinal vein; i, caudal vein; .1/ J/, kidneys. //. In the Frog: /. sinus venosus; //, right auricle; ///, left auricle; IV, ventricle; I', common trunk of the aorta and bulb, gi\ing off the following: i, pulmonary arteries; 2, arch of the aorta; 3, carotid arteries; 4, lingual arteries (5 carotid gland); 6, a.xillary arteries; • 7, common aorta; 8, celiac artery; 9, cutaneous arteries; v. pulmonary veins; /> p, lungs. ///. In Saurians: 7, right auricle with vena? cava:; //, right ventricle; ///, left auricle; IV, left ventricle; I', anterior common aorta; i, pulmonary artery; 2, arch of the aorta; 3, carotid arteries; 4, posterior common aorta; 5, celiac artery; 6, subcla\ian arteries; 7, pulmonary arteries; 8, lungs. IV. In Turtles: /, right auricle with venee cavas; //, right ventricle; ///, left auricle; IV, left ventricle, i, right aorta; 2, left aorta; 3, posterior common aorta; 4, celiac artery; 5, subcla\ian arteries; 6, carotid arteries; 7, pulmonary arteries; 8, pulmonary veins. tributed to all parts of the body, returning finally through the capillaries and the veins to the auricle. The amphibia (frog. //) have two auricles and one ven- tricle. From the latter there arises a single vessel, which, after giving off the HISTORICAL. 199 pulmonary arteries, becomes the aorta and supplies all the organs of the body. The veins of the greater circulation empty into the right, those of the lesser circu- lation into the loft, auricle. Fishes and amphibia possess a dilated bulbus arterio- sus at the beginning of the aorta; and this is partly covered with strong muscular tissue. Among rejjtiles the saurians (///) possess two separate auricles, but the two ventricles are only imperfectly divided. The aorta and pulmonary artery arise separately froni the latter. The venous blood of the greater and the lesser circulation, wiiich flows separately into the right and the left auricle, becomes mixed in the cavity of the ventricle. In some reptiles, however, the opening in the ventricular septum appears to be capable of (voluntary or reflex?) closure. The complete separation of the two halves of the heart in turtles is shown in Fig. IV. The lower vertebrates possess valves at the orifice of the vena cava, which arc rudimentary in birds and in some of the mammals. All birds and mammals, like man, possess two separate auricles and two .separate ventricles. In the halicore, a graminivorous marine animal resembling the whale, the ventricular portion of the heart is divided by a deep cleft into two halves. In bats the veins of the wings pulsate. The lowest of all vertebrates, the amphioxus, has no heart at all, but rhythmically contracting vessels. Of the ductless glands, the thymus and the spleen are found constantly in vertebrates. The latter is wanting only in the amphioxus and in a few fishes. Among invertebrates closed blood-channels with pulsating movements are only found occasionally, as, for example, in the echinoderms (sea-urchin, star-fish, holothurians) and in the higher worms. Insects possess in the dorsal region a central circulatory organ (the "dorsal vessel"), a contractile, longitudinal duct, capable, by virtue of its muscle-fibers, of dilating, and provided with valves — which propels the blood rhythmically into the interstices of all the organs. Insects have no closed circulation. Shell-fish and snails have a heart and lacunar blood- channels. Cephalopods (sepia, cuttle-fish) have three hearts: an arterial, simple body-heart, and two venous, simple branchial hearts, one at the base of each gill. The circulation in most of these animals is closed. The lo\vest animals have either (multiple) pulsating vacuoles, which propel the colorless (blood-) juice into the soft body-parenchyma, like the infusoria; or they are totally devoid of any kind of vascular apparatus, the circulation of the juices being effected by the movements of the body (gregarines) . In the group of celenterates (polyps, jelly- fish) there is a " water- vascular system," which conveys the nutritive juice directly from the digestive cavity, and, at the same time, acts as a respiratory organ, as the water (which contains oxygen) passes through the system of tubes. HISTORICAL. The ancients (Empedocles, born 473 B. C.) were familiar with the movement of the blood, but Avere ignorant of the "circulation." According to Aristotle (384 B. C.) the heart, the acropolis of the body (which is present in every blood- animal), prepares the blood within its cavities and sends it through the arteries as a nutrient fluid to all the different parts of the body, like a system of constantly dividing brooks, irrigating the land and moistening and fertilizing it. The blood however, never flows back to the heart. Praxagoras (341 B. C.) named the "arteries" (as w^ell as the trachea) ; he was the first to distinguish arteries from veins. Together with Herophilus and Erasis- tratus (300 B.C.), the famous physicians of the Alexandrian school, he is responsible for the erroneous view, based on the fact that arteries are empty after death, that the arteries contain air conveyed to them through the respiration (hence the name "artery"). Galen (131-203 A. D.) refuted this error by vivisection. "When- ever," he says, "I injured an artery I saw blood escape. And when I tied a portion of an artery by means of tw^o' ligatures at either extremity, I showed that the included portion was full of blood." Even then the theory of the exclusively centrifugal movement of the blood was maintained; it was erroneously supposed that communicating orifices existed in the septum between the right and the left heart. Miguel Serveto (a Spanish monk, who was burned as a heretic in Geneva in 1553 at Calvin's instigation) was the first to show that the septum of the heart has no openings. He, therefore, searched for a communication between the right and the left heart and thus succeeded, in 1546, in discovering the lesser circulation: "fit autem communicatio haec non per parietem cordis medium (septum), ut vulgo 200 HISTORICAL. creditur, sed magno artificio a cordis dextro vcntriculo, longo per pulmones ductu, agitatur sanguis subtilis; a ])ulmonibus pracparattir, flavus efficitur et a vena arteriosa (Arteria pulmonalis) in arteriam venosam (Ven£e puimonales) trans- funditur." Almost a quarter of a century later, in 1589, Caesalpinus traced the course of the greater circulation. He was the first to use the word "circulation." Later, Fabricius ab Aquapendente (Padua, 1574) also recognized and confirmed the centripetal movement of the blood in the veins (which until that time was almost universally believed to be centrifugal, although Vesalius was familiar with the centripetal «urrent in the main trunks) from the position of the valves in the veins, of which he made an accurate study, although they had been men- tioned in the middle of the fifth century after Christ by Theodoretus, Bishop, of Syria, also by Sylvius, by Vesalius (1534) and by Canani (1546). William Harvey, a pupil of Fabricius (until 1604), finally constructed, between the years 1616 and 1 6 19, partly from his own investigations and partly from the results of former observers, the picture of the circulation of the blood, the greatest physiological achievement, which was published in 1628 and marks a new epoch in physiology. With respect to individual features of the vascular system, the following is yet worthy of mention: According to Hippocrates the heart is a fleshy organ and the root of all the vessels; he was familiar with the large vessels originating from the heart, the valves, the chordae tendinese, the auricles, and the closure of the semilunar valves. Aristotle first named the aorta and the vense cavae, the school of Erasistratus the carotid; the latter also explained the function of the venous valves. In Cicero mention is made of the distinction between arteries and veins. Celsus, in the fifth century after Christ, pointed out that the veins, when opened below a compressing bandage, bleed. Aretaeus (50 A. D.) knew that arterial blood is bright red and venous blood dark. Pliny (died 79 A. D.) described the pulsating fontanel in man. The presence of a bone in the septum of large mam- mals (ox, stag, elephant) was known to Galen (131-203 A. D.). In his opinion the veins ultimately communicate with the arteries by means of the finest tubes, and this view was later confirmed by de Marchettis (1652) and Blancard (1676) with the aid of injections, and by Malpighi, who made microscopic observations of the circulation of the blood in cold-blooded animals, as well as by William Cowper (1697) , who made similar observations on warm-blooded animals. Stenson, who was born in 1638, first demonstrated the muscular nature of the heart, al- though a statement to like eftect had already been made by the Hippocratic and Alexandrian schools. Cole demonstrated the progressive increase in the width of the arterial area as the capillary region is approached. Joh. Alfons Borelli (1608- 1679) was the first to estimate the power of the heart according to the laws of hydraulics. Craanen, in 1685, described systolic contractions in the pulmonary veins; Leeuwenhoeck (1694) the anatomical arrangement of the heart-muscle fibers among themselves. Chirac, in 1698. ligated a coronary artery of the heart in a dog, without, it is true, producing any result. According to Aristotle, turtles can live for a short time after the heart has been removed. Many of the ancients (the Israelites, Empedocles, Kritias, Lucretius) believed that the vital principle of the body, and even the soul (Aristotle and Galen) , had its seat in the blood. Aristotle was familiar with the poisonous effects of the vapor of burning charcoal; Porcia voluntarily chose to die by inhaling it. Vene- section was practised by Greek physicians soon after the Trojan war. The iron in the red blood-corpuscles was discovered by Menghini in 1746. PHYSIOLOGY OF RESPIRATION. OBJECTS AND SUBDIVISIONS. The purpose of respiration is to convey to the body the oxygen necessary for its oxidation-processes, as well as to remove the carbon dioxid resulting from the combustion processes. The activity required for this purpose is most effectively rendered by the lungs. A distinction is made between external and internal respiration. The first embraces the exchange of gases between the outer air and the gases of the blood contained in the respiratory organs (lungs and skin) ; the second in- cludes the exchange of gases between the capillary blood of the systemic circulation and the body tissues. STRUCTURE OF THE AIR-PASSAGES AND THE LUNGS. The lungs are compound tubular (grape-like?) glands that secrete carbon dioxid, and each of which sends its excretory duct (bronchus) to the common air- passage, the trachea. The trachea has for its foundation a number of C-shaped, superposed, hya- line, cartilaginous arches, held together by a rigid fibrous membrane of closely woven elastic network, intermixed with connective tissue, arranged principally in a longitudinal direction. The cartilages serve the ftmction of keeping the lumen of the tube patulous under the varying pressure-relations. They subserve a similar purpose in the bronchi and their branches. They do not occur in air- passages having a diameter of i mm. or less; and even in bronchioles of greater size they are less numerous and more irregular, occurring especially at the bifurca- tions in the form of irregular platelets. An outer layer of connective and elastic tissue covers the air-passages and branches of the bronchial tree. On the side toward the esophagus this layer is reinforced by additional elastic elements and a few bundles of longitudinal un- striated muscle-fibers. The trachea contains unstriated muscle-fibers, especially arranged transversely, connecting the ends of the cartilaginous arches posteriorly and being inserted into the cartilages by means of elastic tendons. This transverse layer is again covered by longitudinal bundles. The mucous membrane, besides containing connective tissue and leukocytes, is especially rich in longitudinal elastic fibers, which attain their greatest size immediately beneath the epithelial basement membrane. The otiter, narrow, scarcely separable submucosa is com- posed principally of connective tissue, and attaches the mucous membrane to the cartilages with their connecting fibrous membrane. The epithelium of the trachea is a stratified, ciliated epithelium, with the cilia waving toward the glottis, and with many interspersed goblet-cells. Numerous branched, tubular, mucous glands, with larger, brighter cells and smaller, darker ones (Gianuzzi's crescents) are found beneath the muscular layer of the trachea and bronchi. These glands are of a mixed type and have secretory ducts connected with their serous alveoli, but not with the mucous tubules. They secrete the viscid mucus that catches the dust-particles of the inspired air and is then removed from the bronchial tree and larynx by means of the ciliated epithelium. The air-passages are richly supplied with lymph-vessels and lymph-follicles, but are rather poor in nerves and blood- vessels. Ganglia are found on the nerve-trunks. The direction in which the branches of the bronchi penetrate into their respec- tive lobes corresponds with the inspiratory movement of the chest-wall covering ■each lobe; for example, the direction of the bronchi in the upper lobe is upward, forward, and outward. The small bronchi are distinguished from the larger ones bv a diminution in 202 STRUCTURE OF THE AIR-PASSAGES AND THE LUXGS. the amount of cartilage, and by the presence of a complete layer of circular muscle- fibers; mucous glands are wanting, and the epithelium is less developed. Goblet- cells secreting mucus are found as far as the smaller air-passages. After the small bronchi have by repeated branching become diminished in diameter to from 0.5 to 0.4 mm., they are succeeded by the smallest bronchi, which already bear a few alveoli on their walls. The smallest bronchi still possess ciliated epithelium and unstriated muscle-fibers. The respiratory bronchioles are the direct continuation of the smallest bronchi. In the bronchioles the cylindrical epithelium is gradually replaced, at first on one side only, by small, squamous cells, and later by a mixed epithelium of large plates and small, squamous cells. At the same time the mural alveoli become more numerous. Fig. 75- — Cross-section of Several Pulmonary Alveoli: A, alveolus with the blood-capiUaries (c) that arise from larger vessels (g g) bounding the alveoU. B, the epithelium of an alveolus: i. nucleated cells; 2, non-nu- cleated platelets; 3, large, fused, non-nucleated plates. C, section of an alveolus with its epithelium and subjacent capillaries. D, alveolus, n-ith its border covered by pulmonary epithelium and plates. E, alveolus whose boundary is indicated only by elastic fibers (f f). From these respiratory bronchioles there anse, finally, the blind, alveolar ducts, which are completely lined with mixed epithelium, containing the small, squamous cells only in small nests. The alveolar ducts subdivide further, and still contain a few isolated muscle-fibers in their walls. These subdivisions are entirely surrounded by numerous closely packed, hemispherical or spheroidal air-sacs (alveoli) . Concerning the structure of the alveoli, the following is to be noted (Fig. 75): (i) The supporting membrane of the sac is structureless, elastic, with enclosed nuclei. Fine pores in the walls of the septa connect neighboring alveoli. (2) Networks of numerous, fine, elastic fibers surround the air-sacs, and give to the pulmonary tissue its great elasticity. As the elastic fibers are characterized by STRUCTURE OF THE AIR-PASSAGES AND THE LUNGS. 203 considerable power of resistance, they are often found retaining their characteristic arrangement in the exjieetoration t)f patients suffering from j)ulmonary diseases. This is an infallible sign that the ptilmonary tissue is undergoing destruction. (3) The branches of the rich capillary network pass rather toward the lumen of the alveoli. The respiratory epithelium of the alveoli is a single layer of squamous epithelium. In it may be found scattered nucleated, protoplasmic cells (i), which are transformed later into small (from 7 to 15 //), non-nucleated, bright (2) or dark platelets. Finally, several of the latter unite to form larger (from 22 to 45 //;, non-nucleated plates. (3) Here and there incomplete fissures may be seen in these plates, which indicate previous interspaces between the platelets. The plates have been transformed from original cuboidal cells by the stretching of the lungs during respiration. See estimates the number of alveoli at 809 J millions, and their respiratory area at 81 square meters (54 times as great as the surface of the body). The alveoli are grouped together by connective tissue into distinct pulmonary lobules. The blood-vessels oj the lungs belong to two distinct systems: A. The system of the pulmonary vessels (the lesser circulation) . The branches of the pulmonary artery follow those of the air-passages, and are so closely applied to the latter that their pulsations may be communicated to the contained air. The capillaries arising from these branches form a rich network of moderately fine tubules. The pulmonary veins, whose branches likewise accompany the air- passages, are collectively narrower than the pulmonary artery, as a result of the loss of water that the blood undergoes in the hmgs. B. The system of the bronchial vessels conveys the nutrient material for the respiratory organs. The bronchial arteries, following the bronchi, give to them branches, as well as to the lymphatic glands at the hilus of the lungs, the large trunks of the pulmonary vessels (vasa vasorum), and the pulmonary pleura. Numerous anastomoses occur between the branches of the bronchial and pul- monary arteries. Part of the vessels arising from the capillaries communicate with the beginnings of the pulmonary veins; and for this reason any considerable stagnation of blood in the lesser circulation causes a like stagnation in the circula- tion in the bronchial mucous membrane, with resulting bronchial catarrh. An- other part of the bronchial capillaries forms special veins, which, as bronchial veins, traverse the posterior mediastinum, and empty into the trunks of the azygos veins, the intercostal veins, or the superior vena cava. The veins from the smaller bronchi, and even from the bronchi of the fourth class, empty collectively into the pulmonary veins ; and the anterior bronchial veins also communicate with the pulmonary vessels. The interstitial tissue of the lungs is rich in lymphadenoid tissue and is traversed by a network of fine lymph-channels. A coarser, irregular system of lymph- vessels surrounds the pulmonary lobules, larger bronchi, and blood-vessels. These lymph-channels and vessels become injected when animals are made to inhale powdered, soluble dyes. The coloring-matter penetrates the viscid inter- stitial substance between the epithelium, though according to Klein through small pores that are present. In the walls of the pulmonary alveoli the finest lymph-tubules form a delicate system of canals lying in the spaces between the blood-capillaries. These canals exhibit enlargements at the points of intersection. Lymph- vessels extend along the bronchi, forming a dense, longitudinally meshed network in the mucosa and submucosa, and finally reaching the lymphatic glands at the roots of the lungs. The rapidity with which fluids are absorbed in the lungs, even when introduced in considerable quantities, is remarkable. Landois has often seen this after in- jecting water into the trachea of living animals, and Peiper has demonstrated it for many other substances. Even blood is taken up in like manner, Nothnagel having found blood-corpuscles in the interstitial pulmonary tissue from three to five minutes after injection into the trachea. In the pulmonary pleura, which is exceedingly rich in elastic fibers, the net- works of superficial pulmonary lymph-vessels begin as free stomata. In like manner the lymph-vessels of the parietal pleura communicate by means of sto- mata in many places (on the diaphragm only in certain localities) with the pleural cavity; according to Klein even with the free surface of the bronchial mucous membrane. The lymph-vessels of the veins of the lesser circulation lie between the media and the adventitia. The nerves of the lungs, bronchi, trachea, and larynx have ganglia. It appears that the function of the unstriated muscle^fibers in the trachea and 204 MECHANISM OF THE RESPIRATORY MOVEMENTS. in the entire bronchial tree is to offer resistance within the air-passages to the increased pressure that occurs in all forced expirations, as in speaking, singing, blowing, straining. According to the testimony of many investigators the vagus is the motor nerve; upon it depends the so-called pulmonary tone when the tension within the air-passages is increased. Irritation of the vagus, or of the lung directly, does not induce sudden, expiratory movements (as can be seen by fastening a manometer in the trachea) . The only result of irritation of the vagus is an increase in the resistance of the air passing through the small bronchi that have been nar- rowed by the irritation. Section of the vagus also is said to increase the volume of the lungs. Atropin paralyzes, pilocarpin stimulates, the bronchial muscles of the dog, while reflex stimulation takes place through sensory branches of the vagus. During deepest inspiration the unstriated muscles of the air-passages con- tract, and during forced expiration they are relaxed. Pathological. — Irritation of the unstriated muscles, causing spasmodic narrow- ing of the smaller bronchi, may give rise to asthmatic attacks. If the escape of air from the alveoli is thus made dithcult or obstructed, an acute inflation of the lungs — acute emphysema — may result. According to Sandmann a reflex effect may be produced upon the bronchial muscles from the mucous membrane of the nose and the larynx. This would explain the occurrence of asthma attending nasal affections, such as polypoid growths of the mucous membrane. In addition to the elements of the connective, elastic, and muscular tissues, and of the mucous membrane, the lungs contain lecithin, inosite, uric acid (taurin and leucin in the ox; guanin (?), xanthin, hypoxanthin in the dog), also sodium, potassium, calcium, magnesium, iron oxid, considerable phosphoric acid, also chlorin, sulphuric acid, silicic acid, and carbon. In cases of diabetes sugar has been found; in the presence of purulent infiltration glycogen and sugar; in that of renal degeneration urea, oxalic acid, and ammonium-salts; in that of autointoxications leucin and tyrosin. MECHANISM OF THE RESPIRATORY MOVEMENTS. ABDOMINAL PRESSURE. The mechanism of breathing consists in an alternating dilatation and contraction of the thoracic cavity. The dilatation of the cavity is termed inspiration, and the narrowing expiration. The whole outer surface of both elastic lungs is, by means of its smooth, moist covering of pleura, intimately and hermetically applied to the inner surface of the chest- wall, which in its turn is covered by the parietal pleura. Hence, it is evident that every expansion of the thorax is accompanied by a corre- sponding expansion of the lungs, and every contraction compresses those organs. These movements of the lungs are, therefore, wholly passive, being dependent on the thoracic movements. By reason of their complete elasticity the lungs are able to follow every change in the capacity of the thorax, without causing the two layers of the pleura ever to separate. The cavity of the unexpanded thorax is greater than the volume of the collapsed lungs when removed from the body; therefore, the lungs in their natural position within the chest must be stretched, and they are, to a certain degree, in a state of elastic tension. This tension varies directly with the size of the thoracic cavity. If the pleural cavity be opened by a perforation from without or by a wound of the lungs from within, the elasticity of the lungs causes them to collapse, and there arises an air-space between the outer surface of the lungs and the inner surface of the thorax (pneumothorax). The affected lung is incapacitated for respiration. Double pneumothorax is accordingly fatal. The degree of the elastic traction of the stretched lung may be measured by introducing a manometer through an intercostal space into the pleural cavity of a dead body. The elastic tension here is the same as that in the Ijving body dur- ing a state of quiet expiration, and is equal to 6 mm. of mercury. In a patient RESPIRATORY VOLUMES. 20$ with perforation of an intercostal space Aron found the elastic tension to be from 4.5 to 6.8 mm. If, however, the thorax is, by force applied from the outside, brought into the expanded position assumed during inspiration, the elastic trac- tion will be increased to 30 mm. If the glottis be closed during inspiratory dilatation of the thorax, the elastic lungs also will expand, and there will be produced a rarefac- tion of the air within the lungs, as this air must expand to a greater volume. If the glottis is now suddenly opened, the atmospheric air will enter the lungs, until the density of the air within equals that of the atmosphere. On the other hand, if the chest and the lungs be com- pressed by expiratory efforts, with a closed glottis, the air in the lungs will become denser, that is, compressed into a smaller volume. If the glottis now be opened, air will escape from the lungs, until the internal and external pressures are equalized. As the glottis is open during ordinary respiration, the adjustment of the diminished or increased air-pressure during inspiration and expiration will occur gradually. It is certain, however, that there exists in the air within the lungs a slight negative pressure during inspiration and a slight positive pressure during expiration. This may be measured in the trachea of persons having wounds of this tube, and equals i mm. during inspiration and from 2 to 3 mm. during expiration. According to J. R. Ewald the total figures are only o.i mm. and 0.13 mm. respectively. The so-called abdominal pressure within the abdomen is generally increased during expiration, and declines during inspiration in man and in dogs, while in rabbits it is increased during inspiration. Moderate increase of the abdominal pressure increases somewhat the arterial blood-pressure, as well as the action of the heart; more pronounced increase of abdominal pressure diminishes both. RESPIRATORY VOLUMES. The lungs never completely empty themselves of air. Therefore, in filling and emptying the lungs during inspiration and expiration, only a part of the contained air is subjected to change, the amount depending on the depth of the respirations. Hutchinson in this connection established the following distinctions : 1. Residual air is the volume of air that remains in the lungs after complete expiration. This can be estimated approximately after death by collecting over water the air from the lungs after ligating the trachea. H. Davy and Grehant estimated the amount during life in the following man- ner: The subject makes a forcible expiration, and then breathes for a while from and into a spirometer, filled with a measured quantity of hydrogen. If it can be assumed that the residual air has been completely admixed with the hydrogen, the percentage of air in the spirometer after forced expiration will indicate the quantity of residual air. The observers named found the amount to be from 1200 to 1700 cu. cm. Berenstein, by a similar method, estimated the residual air to be equal to from one-fifth to one-fourth of the vital capacity. The following wholly different method has also been employed to determine the residual air: The amount of an unknown volume of air x can be calculated from the increase in volume that it undergoes when the pressure upon it is lessened, for this increase in volume is directly proportional to the quantity of gas, and to the diminution in the pressure upon it. If Pj is the original pressure to which the gas is exposed, P2 the other, lessened pressure, and d the measurable increase m volume of x, then X = (P2Xd) : (Pi — Po). For carrying out this experiment Pfiuger constructed his pneumometer. The sub- 2o6 RESPIRATORY VOLUMES. ject is placed in a large, hermetically sealed chamber (human cabinet) , in which at first the pressure equals that of the atmosphere (Pi). The contained air is then rarefied by means of a pump, until the pressiire P^ is obtained, as indicated by a manometer inserted in the chamber. In this process a part of the residual air (x) will naturally escape during quiet expiration. This is collected and meas- ured (d) by means of a spirometer connected in an air-tight manner with the air-passages. In this way Pfliiger found x to be from 400 to 800 cu. cm. Gad, working with different apparatus based on the same principle, estimates the residual air to be half the vital capacity; Schenck gives the proportion of the former to the latter as i to 3.7. 2. Reserve air is the additional volume of air that can be forced out after a quiet expiration. It measures from 1248 to 1804 cu. cm. The procedure of H. Davy and Grehant may also be applied to the estimation of reserve air. 3. Respiratory or tidal air is the volume of air that is taken in and given off during quiet respiration. In adults under normal conditions it amounts to about 507 cu. cm. — between 367 and 699 cu. cm., according to Vier- ordt; in the new-born about one-quar- ter of this amount. 4. Complcmental air is the term ap- plied by Hutchinson to the additional volume of air that may be taken in during a forced inspiration immediately succeeding a quiet one. 5. Vital capacity indicates the vol- ume of air that escapes from the lungs between the highest phase of inspiration and the lowest phase of expiration. For Germans it amounts to 3222 cu. cm. on an average, and for Englishmen to 3772 cu. cm. From the foregoing it follows that after a quiet inspiration both lungs contain about from 3000 to 3900 cu. cm. of air (i -f 2 -\- 3); after a quiet expi- ration from 2500 to 3400 cu. cm. (i + 2). From this, as from 3, it follows that during quiet respiration only about one-sixth or one-seventh of the air in the lungs is changed. If, during a series of quiet respirations, a solitary inhalation of hydrogen be made, and if the expired air be examined to determine how long the hydrogen may be detected in it, it will likewise be found that the air in the lungs com- pletely renews itself (becomes free of hydrogen) in from 6 to 10 respirations. Bonders estimates that the combined bronchial tree and trachea contain about 500 cu. cm. of air. The vital capacity is determined by means of Hutchinson's spirometer (Fig. 76). The determination is of importance in persons suffering from disease of the thoracic organs. The vital capacity may be influenced by consolidation, destruc- tion, or emphysema of the pulmonary tissue; by the presence of fluids, blood, air, or new-growths in the thoracic cavity; by diminished mobility of the chest; by weakness of the respiratory muscles ; by enlargement of the heart or pericardium ; or by distention of the abdomen. By means of a large tube provided with a mouth-piece, the subject (holding his nostrils closed) blows his expiratory air into a gradviated gasometer bell- jar that is suspended over water and evenly balanced by a system of weights Jand pulleys. Fig. 76. — Hutchinson's Spirometer. THE RATE OF RESPIRATION. 207 After complete expiration the tube is closed, and the increase of air within the jar indicates the vital capacity, provided the water outside and that inside the jar are at the same level. It is also advisable to allow the expired air to cool, until it is of the temperature of the surrounding air. Of the factors that intluence vital capacity the following are known: 1. Stature. — Every mch of additional height between 5 and 6 feet is accom- panied by about 130 cu. cm. increase in the vital capacit)'. 2. The voliDiic of till' trunk is, on the average, seven times that of the vital capacity. 3. The Body-ivciglit. — An increase in weight of 7 per cent, above the normal is accompanied by a diminution in the vital capacity of 37 cu. cm. for every additional kilogram. 4. Aiic. — The vital capacity reaches its ma.ximum at thirty-five years; from this up to the sixty-fifth year, and backward to the fifteenth year, 23.4 cu. cm. must be deducted for each year. 5. 5t\v. — Arnold found the average to be 3660 cu. cm. for men, and 2550 cu. cm. for women. For the same stature and chest-measurement, the relation of the vital capacity of men to that of women is as 10 to 7. 6. Social position and occupation have a decided influence on the physical condition and nutrition, and hence also on the vital capacity. Arnold established three classes, of which each preceding class exceeds the one following by 200 cu. cm. greater vital capacity: (a) soldiers and sailors; (6) artisans, compositors, police; (t) paupers, the nobility, and students. 7. Miscellaneous. — The vital capacity is greatest in the standing position, and when the stomach is empty. It is diminished after great effort, and also m de- bilitated conditions of the body. It is greater in advanced pregnancy than in the puerperium. To a certain extent practice with a spirometer can increase the vital capacity. THE RATE OF RESPIRATION. The rate of respiration varies in adults between 12, 16, and 24 in a minute. Four pulse-beats on an average thus occur with every respira- tion. Many factors influence the rate: 1. The Position of the Body. — In adults Guy noted 13 respirations to the minute in the recumbent posture, 19 in the sitting posture, and 23 in the standing posture. 2. Age. — In 300 individuals Ouetelet found the rate of respiration to be as follows: .Age. Respirations. Age. Respirations. Up to I year 44 Between 20 and 25 years 18.7 At 5 years 26 " 25 and 30 years 16 Between 15 and 20 years 20 " 30 and 50 years 18. i In the new-born the rate is between 62 and 68. 3. Activity. — In children between two and four years old, Gorham counted 32 respirations to the minute in the standing posture, and 24 during sleep. As a result of bodily exertion the rate of respiration increases before that of the heart-beat. The increase in respiratory movements is incited by metabolic products furnished by the muscles engaged in activity. In connection with violent muscular activity the pulse-rate is increased principally by excitation of the center for the cardio-accelerator nerves. 4. Increase in the surrounding temperature, also febrile elevation of the bodily temperature, will increase the rate of respiration, which may even assume a dyspneic character. THE TIME RELATIONS OF RESPIRATORY MOVEMENTS. PNEUMATOGRAPHY. In order to obtain information with regard to the periodic relations of the various phases of the respiratory movements, it is necessary to 20 8 THE TIME RELATIONS OF RESPIRATORY MOVEMENTS. trace respiratory curves (pneumatograms) by means of recording in- struments. Method. — The graphic method can be appHed in three different waj's: i. The representation of the range of motion in the individual parts of the thorax may- be obtained in the following manner: (a) K. Vierordt and Ludwig arranged an instrument in which the movement of a definite part of the thorax was commtmicated to a lever, whose longer arm traced the curve on a rotating drum. In like manner Riegel constructed his double stethograph on the principle of the lever. It consisted of two levers on the same support, arranged for use on a patient in such way that one lever was applied to a certain spot on the healthy side of the chest, and the other lever to the corresponding spot on the affected side. A sphygmograph may be em- ployed for recording the respiratory curve, the instrument being placed free outside of the chest upon a stand and applied in such manner that only the pad of the elastic stylus touches the chest-wall at one point. J . Rosenthal constructed a lever to register the movements of the diaphragna in animals (phrenograph) ; it Fig. 77. — A, Brondgeest's Air-cushion for Recording the Respiratory Curves. B, A Respiratory Curve of a Healthy Individual, Recorded on a Plate Attached to a Vibrating Tuning-fork (i vibration = 0.016 13 sec), to Deter- mine the Time-relations. was inserted through an opening in the abdomen, and rested against the dia- phragm. (b) The air-cushion of Brondgeest's pansphygmograph (Fig. 77, A) is con- structed on the principle of air-transference. This instrument consists of a saucer- shaped brass vessel (a) , over which is stretched a double-layered rubber mem- brane (b c). Between the layers of this covering there is enough air to make the outer membrane bulge. This cushion is placed on a certain part of the thorax, and fastened with bands (d d) that pass around the chest. Everv enlargement of the thorax presses against the membrane c, producing a diminution of the air- space within the capsule. The latter is connected by means of the tube S with the recording chamber that is pictured in Fig. 44. Instead of this capsular arrangement, Marey, in the construction of his pneu- mograph, uses a piece of thick, cylindrical, elastic rubber tubing. This is fastened by bands like a girdle around the chest, and is connected by a tube with the recording drum. 2. The variations in the volume of the chest or in the exchanged respiratory gases may be graphically recorded as follows: For this purpose E. Hering places an animal in an air-tight, closed chamber, THE TIME RELATIONS OF RESPIRATORY MOVEMENTS. 209 with two openings in its walls. The trachea of the animal having been previously- cut across, a cannula is fastened in the pulmonary end, and is attached to a tube passing through one of the openings in the chamber (respiration being conducted undisturbed through this tube) . Through the other opening passes a manometer- tube, filled with water, and pro- vided with a recording float. The same experiment may be conducted with a human subject, provided the breathing tube be placed in the mouth and the nose be held closed. Gad (Fig. 78) has succeeded in re- cording graphically the variations in the volume of the respired air by means of an apparatus: the expired air lifts a light, balanced box, which is closed off lay water. In rising, this box moves a recording lever. During inspiration the box sinks. 3. "The variations in the rapidity with which the respiratory gases are changed may be recorded as follows : A tube is fastened in the trachea of an animal, or in the mouth of a human subject (holding the nostrils closed), in the same way as with the dromograph (Fig. 69). The pendulum (made broader for this purpose) will swing to and fro during inspiration and expiration, and will record the velocity of the currents of air entering and leaving the lungs. Fig. 78.- -.•\ir-volume Recorder (Pneumoplethysmograph) (after Gad). Fig. 79. — Pneumatograms Recorded by Means of Riegel's Stethograph: /, normal curve; //, curve of a man with emphysema; a. inspiratory limb, b, summit, c, expiratory limb of the curve. The small elevations are due to the pulsations of the heart. The curve in Fig. 77 B was drawn upon a vibrating tuning-fork plate, by- means of the air-cushion of Brondgeest's pansphygmograph, applied to the ensi- form process of a health v man. The inspiration (ascending limb) begins with moderate rapidit}', is accelerated in the middle, and again becomes slower toward 14 2IO TYPES OF RESPIRATORY MOVEMENTS. the end. The expiration begins with moderate rapidity, is then accelerated, and finally becomes much slower in the last part. Inspiration is somewhat shorter than expiration ; in adult males the proportion is 6 17, according to Sibson; in women, children, and old persons it is 6 : 8 or 6 : 9. Vierordt found the relation 10 : 14. i (up to 24.1); J. R. Ewald foimd it ii : 12. Cases in which inspiration and expiration are of equal length, or in which the latter is even the shorter, are observed only exceptionally. Small irregularities may be observed occasionally on various parts of the curve. These are due to the fact that the thoracic movements are at times the result of successive contractions of the respiratory muscles. Now and then power- ftii heart-beats also cause vibrations of the thoracic wall (Fig. 79). If respiration proceeds uninterruptedly and quietly, there is usually no real pause, i. e., complete rest of the thorax. Sometimes the lowest flattened part of the expiratory limb is incorrectly taken for the pause. Of course, a pause may voluntarily be made at any phase of the movement. If the respirations be deep, but slow, an expiratory pause is almost invariably noted; on the other hand, it is always lacking in rapid respiration. An inspiratory pause is never noted under normal conditions, but it may occur under patho- logical conditions. TYPES OF RESPIRATORY MOVEMENTS. Curves recorded from various parts of the thorax throw light upon the so-called type of respiration. Hutchinson was the first to show that women expand the thorax by producing an elevation of the sternum and ribs — costal or thoracic respiration ; while men produce the same effect by depression of the diaphragm — abdominal or diaphragmatic respiration. If the height of the curves taken in men and women from the manubrium, gladiolus, ensiform process, and epigastrium be compared, it will be seen that the excursion of the sternum is most pronounced in women, while that of the epigas- trium (through the diaphragm) predominates in men. This difference between the sexes, in the type of costal and diaphragmatic breathing, holds good only in quiet respiration. In deep and forced respiration the enlargement of the thoracic cavity is brought about in both sexes principally by a pronounced elevation of the chest and ribs. In this case the epigastrium, even in men, is drawn in rather than forced out. During sleep the t>'pe of respira- tion is thoracic in both sexes, and the inspiratory expansion of the thorax precedes the elevation of the abdominal wall. It has recently been again pointed out that the costal type arises principally from compression of the lower ribs by corsets or tight belts, especially as a decided abdominal type is encountered in savage women. It is only a conjecture that the costal type may be a natural tendency, the result of pregnancy, during which abdominal respiration may become obstructive and hannful by exerting pressure on the uterus. Some affirm, while others deny, that the difference in type is evident during sleep with the clothing completely removed, and also in young children. Some investigators maintain that the costal type is found in children of both sexes; they attribute this to a greater flexibility of the ribs in children and women, which thus allows the thoracic muscles to exert a more extensive influence on the ribs. PATHOLOGICAL VARIATIONS IN THE RESPIRATORY MOVE- MENTS. Changes in the Character of tite Movements. — In the presence of affections of the respiratory apparatus the expansion of the thorax may be diminished to the PATHOLOGICAL VARIATIONS IN THE RESPIRATORY MOVEMENTS. 211 extent of 5 or 6 cu. cm. on one or both sides. When the apices are aflected, as occurs so frequently in cases of tuberculosis of the lungs, the subnormal expansion in the upper parts of the thorax is a characteristic feature. Retraction of the intercostal spaces, the ensiform process, and the lower insertions of the ribs occurs during marked inspiratory rarefaction of air in the thorax, such as may take place in the presence of laryngeal stenosis. If this phenomenon be confined princi- pally to the tipper parts of the thorax, it shows that the subjacent part of the lung is diseased and capable of little expansion. In persons suffering from chronic, advanced disease of the respiratory organs, without impairment in the activity of the diaphragm, the insertion of the latter manifests itself on the outer surface of the body by a shallow groove (Harrison's groove), passing horizontally outward from the ensiform cartilage, and due to the marked retraction. The period of inspiration is lengthened in persons suffering from constriction of the trachea or larnyx; that of expiration in those who must call into play all the expiratory muscles, by reason of an emphysematous condition of the lungs (Fig. 72, II). Occasionally, in emphysematous subjects, a short expiratory effort precedes the inspiration. Ckmigcs in the Rkytlim of the Movements. — All disturbances of the respiratory apparatus of any degree of magnitude will produce an increase in the frequency or depth of the respirations, or both together. This phenomenon is termed dysp- nea. The possible causes of dyspnea are various: i. Restriction of the respira- tory exchange of gases in the blood, as a result of (a) diminution of the respiratory surface (pulmonary diseases), (b) contraction of the air-passages, (c) diminution in the number of red blood-corpuscles, (d) disturbances in the mechanism of respira- tion (affections of the respiratory muscles and their nerves, painful affections of the thoracic walls), (e) weakness in the circulation, especially the lesser circulation, principally as a result of various cardiac affections. 2. Febrile conditions are a further cause of increase in the frequency of respira- tion. The febrile blood heats the respiratory center in the medulla oblongata, and thus incites dyspneic respiratory movements up to from 30 to 60 in the minute (heat-dyspnea). If the carotids of animals be placed in hot tubes, the same result is produced. Under the infitience of hysterical irritability, a nervous pathological increase in the respiratory rate may be produced in rare cases. Respirator}'- pauses of considerable duration are uncommon, but they may occur (in one patient with cardiac and renal disease a pause of thirty-seven seconds was observed during sleep). A remarkable change in the rhythm of respiration is known as Cheyne-Stokes' breathing. This manifests itself as a suffocation-phenomenon in affections that alter the normal supply of blood to the brain, or that change the composition of the blood, for example, cerebral affections, cardiac diseases, or uremic intoxica- tion. Under such circumstances pauses of from one-half to three-fourths of a minute alternate with series of from 20 to 30 respirations, likewise extending over from one-half to three-fourths of a minute. The respirations of a single series are first superficial: 'they then becoine deeper and dyspneic, and then again more super- ficial. After this a pause occurs, and at this time the eyeballs roll, the pupils are contracted and do not react, and the blood-pressure falls. In severe cases complete loss of consciousness, analgesia, abolition of the reflexes, and even inability to swallow, rarely, toward the end of the pause, also muscular twitchings have been observed during the pauses. When the respirator}^ movements commence again, the pupils become larger and reactive. It has often been observed that conscious- ness, lost during the pause, has been partially regained whenever the respirations begin. In agreement with Rosenbach and Luciani the cause of Cheyne-Stokes' breathing is referred to variations in the irritability of the respiratory center, which reaches its lowest point during the pause. Luciani compares the phe- nomenon with that of the periodically grouped heart-beats. He observed it to set in after injury to the medulla above the respiratory center, after the apnea in animals profoundly poisoned with opium, and finally in the last stage of as- phyxia attending respiration in a closed space. Cheyne-Stokes' respiration is most readily explained by assuming the pause to be a period of asphyxia, and the series of respirations to be agonal. Under the reviving influence of the latter, the respiratory center recovers from the pre- vious state of exhaustion. During hibernation this form of breathing is normal in the dormouse, the hedge-hog, and the alligator. If frogs are kept immersed in water, or if the 212 MUSCULAR MECHANISM IX IXSPIRATIOX AND EXPIRATION. aorta be clamped, they lose the power of reaction in a few hours. AYhen taken out of the water, or when the clamp is removed, they recover immediately, and they invariably exhibit the phenomenon of Che\Tie-Stokes' respiration. In such frogs the circiilation may be interrupted for a time, dtuing which this form of breathing still continues. Curtailment of the blood-supply in frogs by blood-letting results in periodically grouped respirations. These are followed by a stage of single, infrequent respira- tions, and finally the breathing stops completely. During the pauses between the periods, each mechanical irritation of the skin will give rise to a series of respirations. Periodic respiration, without variations in the depth of the separate respirations (so-called Biot's respiration) , also occurs normally in sleep. While the nervous centers are endeavoring to obtain rest, they forget, to a certain extent, to send out respiraton,- impulses, and the organism takes no notice of these short pauses. Periodic irregularities in respiration also are frequently of reflex origin. Muscarin, digitalin, curare, chloral, hydrogen sulphid, and the toxins of some infectious dis- eases (typhoid fever, diphtheria, scarlet fever) are likewise capable of exciting periodic respirations. SUMMARY OF THE MUSCULAR MECHANISM CONCERNED IN INSPIRATION AND EXPIRATION. A. INSPIRATION. I. During quiet inspiration the following muscles are active: 1. The diaphragm (phrenic nerve, from the third and fourth cervical nerves). 2. The external intercostal and intercartilaginous muscles (intercostal nerves). 3. Long and short elevators of the ribs (posterior branches of the dorsal ner%-es) . In a state of rest the elastic traction of the lungs appears to draw the chest together somewhat with tension on all sides. Accordingly the elastic force thus exerted would act as an aid to the beginning of inspiration. Also Landerer con- siders the thorax at rest to be an apparatus tending toward the attitude of inspira- tion, by means of the elasticity in an upward direction of the six upper ribs. n. Dxiring forced inspiration the following muscles are active: (a) Trunk-muscles. 1. The three scalene muscles (muscular branches of the cervical and brachial plexuses) . 2. Stemo-cleido-mastoid (external branch of the spinal accessory nerve). 3. Trapezius (external branch of the spinal accessory, and muscular branches of the cervical plexus) . 4. Lesser pectoral (anterior thoracic nerves). 5. Posterior superior serratus (dorsal nerve of the scapulse). 6. Rhomboids (dorsal nerve of the scapulae). 7. Extensor muscles of the vertebral column (posterior branches of the dorsal nerves) . The assumption that the greater anterior serratus (long thoracic ner\-e) and the subclavius (brachial plexus) are accessory- muscles of inspiration is unwarranted. (6) Laryngeal muscles. 1 . Stemo-hyoid (descending branch of the hypoglossus) . 2 . Stemo-thyroid (descending branch of the hypoglossus) . 3. Posterior crico-arj-tenoid (inferior lar>-ngeal branch of the vagus). 4. Thyro-ar\-tenoid (inferior lar>'ngeal nerve), (c) Facial muscles. 1. Anterior and posterior dilators of the nares (facial nerve). 2. Levator of the ala nasi (facial nerve) . 3. The muscles that separate the lips and open the mouth during extreme forced respiration — gasping — (facial nerve). {d) Muscles of tlie palate and pharynx. 1. Elevator of the veil of the palate (facial nerve). 2. Azygos of the uvula (facial nerve). 3. According to Garland, the phar\-nx is always narrowed. B. EXPIRATION. I. During quiet expiration the size of the thoracic cavity is reduced essentially by the weight of the chest- walls, together with the elasticity of the Itmgs, costal cartilages, and abdominal muscles. ACTION' OF THE INDIVIDUAL RESPIRATORY MUSCLES. 213 II. During forced expiration the following muscles are employed : 1. The abdominal muscles (internal or anterior abdominal nerves, branches of the intercostal nerves from the 8th to the 12th). 2. Internal intercostal muscles (the parts lying between the ribs), and the infracostal muscles (intercostal nerves). 3. The triangular muscle of the sternum (intercostal nerves). 4. (?) Posterior inferior serratus (external branches of the dorsal nerves). 5. (?) Quadratus lumborum (muscular branches of the lumbar plexus). ACTION OF THE INDIVIDUAL RESPIRATORY MUSCLES. A. Inspiration. — -i. The Jiapliragui arises by six processes from the six lower costal cartilages and contiguovis osseous parts of the ribs (costal portion) , by three processes from the upper four lumbar vertebrae (lumbar portion) , and from the ensi- form process (sternal portion). It presents a double dome, with the convexity toward the thoracic cavity, and contains the liver in its larger, right-sided con- cavity, and the stomach and the spleen in its smaller, left-sided cavity. In a state of rest the intra-abdominal pressure and the elasticity of the abdominal wall press these organs against the under surface of the diaphragm, in such a manner that it bulges into the thoracic cavity. This position is aided by the elastic traction of the lungs. The central part of the diaphragm (central tendon) is, to a great extent, fused on its upper surface with the pericardial sac. This part, which supports the heart and is pierced by the inferior vena cava (foramen quad- rilaterum) , projects downward into the abdominal cavity in a state of rest ; and in casts made of the diaphragm it can be recognized as the lowest part of the middle portion (Fig. 80). During c o n- traction of the dia- phragm the two dome-like projec- tions are flattened, and the thoracic cavity is enlarged downward. At the same time the dis- tal, arched, muscular parts become flatter, and are drawn away from the chest-wall, to which they are closely applied during expiration. The middle part of the central tendon, upon which the heart rests, takes no considerable part in the movement during quiet inspiration; but during forced inspiration it also is depressed to a certain extent. In the recumbent posture (especially in men), with fvdl light on the thorax, the contraction of the diaphragm can often be seen directly in the form of a wave- like movement beginning in the sixth intercostal space and running downward through from one to three intercostal spaces in accordance with the depth of inspiration. The diaphragm undoubtedly plays the most important part in enlarging the thorax. Briicke further maintains that the diaphragm, besides enlarging the thorax in a vertical direction, also expands the lower part in a transverse direc- tion: namely, when it compresses the abdominal organs from above, the latter Fig. 80. — Frontal Secrion of the Thorax at the Extremity of the Twelfth Rib on Each Side (12. C), to Demonstrate the Form of the Diaphragm during Ex- piration (Z e-Z e) and during Inspiration (Z i-Z i) : T e-T e, thoracic wall in a state of expiration; i i, during inspiration; C t, central tendon. The ar- rows indicate the direction of the movements during inspiration. 214 ACTION OF THE INDIVIDUAL RESPIRATORY MUSCLES. endeavor to escape laterally, and thus spread out themselves, as well as the adja- cent thoracic wall. If the abdominal contents be removed from an animal, the lower ribs are seen to be drawn inward with every contraction of the diaphragm; therefore, the presence of the viscera is necessary for the normal action of the diaphragm. In order to obtain some idea as to the extent of thoracic enlargement due to the action of the diaphragm, Landois carried ovit the following experiment: A tracheal cannula was fastened in the body of a well-bixilt, female, newly born child that had died of hemorrhage. The body was completely immersed in water, and the lungs were inflated. The vital capacity was estimated from the amount of water displaced. The abdomen was then opened, the viscera removed, and a wax cast was taken of the under surface of the diaphragm, with uninflated lungs (that is, in the position of expiration). Hereupon, a quantity of air equal to the determined vital capacity was introduced into the kings, and after the air-passages were closed, a second wax cast was taken of the diaphragm in this last position. The difference in volume between these casts was determined, and it was found that the proportion between the expansion due to the diaphragm and that due to all other causes was i : 2J. These figvires are, of course, only approximately correct; for, in the first place, the removal of the abdominal viscera permits of unimpeded descent of the diaphragm (which is, to a certain extent, compensated for by the taking of the wax cast) ; and, secondly, the arch of the actively con- tracting diaphragm presents a form differing from that produced passively by inflation of the lungs. However, there is no other means at hand for determining the thoracic expansion produced by the diaphragm. By increasing the intra-abdominal pressure, each diaphragmatic contraction increases the flow of venous blood from the abdominal organs to the inferior vena cava. The great importance of the diaphragm in the respiratory process can be realized from the fact that bilateral section of the phrenic nerves in young rabbits is followed by death. These nerves contain, as has been shown experimentally, a few sensory fibers for the pleura, the pericardium, and a portion of the peri- toneum. In animals, irritation of the lowest five intercostal nerves causes local, inconsiderable contraction of the marginal part of the diaphragm. The contraction of the diaphragm is not to be regarded as a simple muscular contraction, for its duration is from four to eight times that of the latter. It is, therefore, to be designated as a tetanic movement of short duration. 2. The Elevators of the Ribs. — At their vertebral extremity (which lies at a much higher level than the sternal extremity) the ribs are articulated at their heads and tubercles with the bodies and transverse processes of the vertebrae. A horizontal axis passes through both joints, and upon this axis the rib is capable of rotating upward and downward. If the axes of a pair of ribs be prolonged from both sides until they meet in the middle line, an angle is formed that is large (125°) for the upper ribs and smaller (88°) for the lower ones. An imaginary plane may be passed through the arch of each rib, which inclines, in a state of rest, from behind and inward, fonvard and outward. If the rib turns on its axis, this inclined plane is raised more toward the horizontal. As the axes of the upper ribs pass rather in a frontal direction and those of the lower ribs rather in a sagittal direction, elevation of the upper ribs causes an expansion of the cavity from behind forward, and elevation of the lower ones an enlargement from within outward (as the movements of the ribs inclined downward are perpendicular to their axes). At the same time the costal cartilages undergo slight torsion, which brings their elasticit}' into play. All of the inspiratory muscles that act directly on the walls of the thorax produce the desired result by elevating the ribs. In this con- nection the following points are to be observed : (a) Elevation of the ribs causes a widening of the intercostal spaces, (b) When the upper ribs are elevated, all of the lower ribs and also the sternum are raised at the same time, as all of the ribs are bound together by the soft structures in the intercostal spaces, (c) During inspiration there occurs an eleva- tion of the ribs and a widening of the intercostal spaces. An exception- is made of the lowest rib, which does not actually form a part of the thorax. It moves downward, not upward, at least during deep in- ACTION OF THE INDIVIDUAL RESPIRATORY MUSCLES. 21 5 spiration. ((/) If, on a preparation of the chest, the ribs be elevated, with widening of the intercostal spaces, as occurs during an inspiratory movement, then all those muscles may be regarded as elevators of the ribs whose origin and insertion approach each other. Hence, only these muscles can be designated as muscles of inspiration. From this point of view the scalene muscles, the long and short elevators of the ribs, and the posterior superior serratus are to be recognized as un- doubted inspiratory muscles. They are also to be considered as the muscles having the greatest influence on the ribs during inspiration. Of the intercostal muscles, according to this experiment, only the external and the intercartilaginous portions of the internal can be desig- nated as inspiratory muscles. The remainder of the internal (the parts covered by the external) are lengthened during elevation of the ribs, and shortened when the ribs are lowered. As a muscle always exhibits its activity by shortening, the internal intercostal muscles have been regarded as depressors of the ribs (that is, as expiratory muscles). Fig. 8r, I, shows that when the rods a and b, representing the depressed ribs, are elevated, the interspace (intercostal space) must become wider: ef >cd. On the left side of the figtire it may be seen that when the rods are elevated, the line g h, representing the external intercostal muscles, is shortened (i k <^ g h) , while 1 m, representing the internal intercostals, is lengthened (1 m < o n). Fig. 81, II, shows that the intercartilaginous muscles, designated by g h, and the external intercostal muscles, designated by 1 k, are shortened by elevation of the ribs. The latter position of these muscular filjers may be represented by the shortened diagonals of the dotted rhomboids. The controversy over the mechanism of the intercostal muscles dates back to ancient times: Galen (131-203 A. D.) regarded the external intercostal muscles as inspiratory and the internal as expiratory muscles. Hamburger (1727), fol- lowing Willis' investigations, agreed with this view, and also recognized the inter- cartilaginous muscles as inspiratory muscles. A. v. Haller, who was Hamburger's direct opponent, considered both internal and external intercostals as muscles of inspiration; while Vesalius (1540) regarded them both as expiratory muscles. Masoin and R. du Bois-Reymond admitted the latter view, but only for forced respiration. Finally, Landerer, who observed that the tipper two or three inter- costal spaces became narrower during inspiration, believed that both sets were active during both inspiration and expiration. As they hold the ribs together, they have the sole function of transmitting the traction imparted to them simply through the chest-walls. They would, therefore, remain active even when the distance between their points of insertion becomes greater. After mature consideration of all the conditions, Landois was unable to accept any of these views unconditionally. It is obvious that the external intercostal and intercartilaginous muscles can act together only during inspiration, while the internal can be active only during expiration (the latter statement having been confirmed by Martin and Hartwell in dogs by means of vivisection) ; but elevation and depression of the ribs are not the chief results attained by the action of these muscles. It was rather Landois' opinion that the chief purpose of the external and intercartilaginous muscles is to counteract the inspiratory widening of the intercostal spaces and the synchronous increase in the elastic traction of the lungs. The function of the internal intercostal muscles is to offer resistance to the ex- piratory distention that occurs during forced expiratory efforts, as in coughing. Without muscular resistance the intercostal tissues would be so stretched through the uninterrupted traction and pressure that regular respiratory movements would become impossible. The lesser pectoral (and the greater anterior serratus ?) is capable of assisting in the elevation of the ribs only wtien the shoulders are held in a fixed position, partly through a firm propping up of the arms, and partly by the rhomboid muscles, as is instinctively done by dyspneic patients. 2l6 ACTION OF THE INDIVIDUAL RESPIRATORY MUSCLES. 3. Muscles Acting upon the Sternum, the Clavicle, and the Spinal Col- umn.— If the head be held in a fixed position by the muscles of the back of the neck, the stemo-cleido-mastoid can enlarge the thorax in an upward direction by raising the manubrium, together with the sternal extremity of the clavicle, thus assisting the scalene muscles. In like manner, but to a lesser extent, the clavicular insertion of the trapezius may become efficient. A stretching of the dorsal portion of the vertebral column must result in an elevation of the upper ribs and a widening of the intercostal spaces, by means of which the inspiratory capacity is substantially in- creased. During deep inspiration this stretching is effected involuntaril}'. 4. In forced respiration every inspiration is accompanied by a descent of the larynx and a widening of the glottis. At the same time the palate is raised, in order to allow the air to enter with the least possible resist- ance. 5. Forced respiration is first made evident in the face by an inspiratory dila- tation of the nostrils (horse, rabbit). During marked dyspnea the cavity of the mouth is enlarged with each inspiration by a dropping of the jaw (gasping). B. Expiration. — Quiet expiration is accomplished without muscular effort. It is, first of all, dependent principally upon the weight of the thorax, which has a tendency to fall back from its elevated position to the lower expiratory position. This is assisted b}' the elas- ticity of the various parts. When the costal cartilages are elevated, their lower borders are slightly rotated from below forward and up- ward, and their elasticity is thus brought into play. Hence, as soon as the inspiratory forces are relaxed, the cartilages return to their lower and no longer distorted expiraton." position. At the same time, the elasticity of the distended lungs draws the thoracic walls, as well as the diaphragm, together on all sides. Finally, the tense, elastic ab- dominal walls, which become stretched and pushed forward, especially in men, return to their non-distended state of rest when the pressure of the diaphragm from above is released. It is self-evident that when the body is in an inverted position, the effect of the weight of the thorax is removed, and is replaced by the weight of the abdominal viscera pressing upon the diaphragm. Among the muscles that are brought into action only during forced Fig. 81. — I, II. Diagrammatic Representation of the Mechanism of the Intercostal Muscles. DIMENSIONS AND EXPANSIBILITY OF THE THORAX. 217 respiration, the abdominal muscles stand foremost. They diminish the size of the abdominal cavity, and thus press the viscera upward against the diaphragm. The triangular muscle of the sternum draws downward the sternal extremities of the united cartilages and bones of the ribs from the third to the sixth, which have been elevated during inspira- tion. The posterior inferior serratus depresses the four lowest ribs, the others necessarily following, being assisted by the quadratus lumborum, which is capable of depressing the last rib. According to Henle, how- ever, the posterior inferior serratus fixes the lower ribs so as to with- stand the pull of the diaphragm, thus aiding inspiration. Landerer even asserts that in the lower parts of the chest the movements of the ribs enlarge the thoracic cavity downward. In the erect posture and with a fixed spinal column, deep inspiration and expiration are accompanied by a displacement of the bodily equilibrium. During inspiration the center of gravity is moved slightly forward by the protrusion of the chest and the abdominal walls. In deep inspiration the straightening of the spinal column and the consequent throwing back of the head act as a compensation for the projection of the anterior trunk- wall. DIMENSIONS AND EXPANSIBILITY OF THE THORAX. It is of considerable importance for the physician to know the dimensions of the thorax, as well as the extent of its expansion in various directions. With inspiration the thorax is enlarged in all its diameters. The diameters of the thorax are determined by means of calipers; the circumference is measured by means of the centimeter tape-measure. In well-built men the upper circumference of the chest, close imder the arms, measures 88 cm.; in women it is 82 cm. The lower circum- ference, at the level of the en- siform cartilage, is 82 cm. in men and 78 cm. in women. When the arms are held hori- zontally the measurement taken during expiration just below the nipples and the angles of the scapulse equals half the body-length, that is, 82 cm. in men; during deepest inspira- tion it is 89 cm. At the level of the ensiform cartilage the circumference is about 6 cm. less. In old persons the upper circumference is diminished, being smaller than the lower measurement. Usually the right half of the thorax is some- what larger than the left, on account of the greater muscular de- velopment. The longitudinal diameter of the thorax, from the clavicle to the lowest edge of the ribs, varies considerably. The transverse diameter (distance between the lateral surfaces) is, in men, from 25 to 26 cm., above and below; in women, from 23 to 24 cm. Above the nipples it is about i cm. greater. The antero-posterior diameter (measured from the anterior surface of the sternum to the tip of a spinous process) is 17 cm. in the upper part of the thorax, and 19 cm. Fig. 82. — Cmometer-curve from a Case of Left-sided Retraction of the Thorax in a Twelve-year-old Girl (after Eichhorst). 2l8 RESPIRATORY EXCURSION OF THE LUNGS. Fig. 83. — Sibson's Thoracometer in the lower part. Valentin found that during deepest inspiration in men, the circumference of the thorax at the level of the ensiform carti- lage increased between yV and i; Sibson found this increase to be yV at the level of the nipples. Various instruments have been devised to determine the degree of movement (elevation or depression) made by a definite part of the thorax during respiration. The cyriometer of Woillez is quite useful: A measuring chain with stiffly movable Hnks is appHed to the outer sur- face of the thorax in a definite direction, for example, trans- versely at the level of the epi- gastrium or the nipples, or per- pendicularly through the mam- millary or the axillary line. In two places the links are loosely movable, permitting a removal of the chain without changing its form as a whole. The inner out- line of the chain is traced on a sheet of paper, and the form of the thorax is thus obtained (Fig. 82). If the instrument is first applied in the state of expiration, and then during inspiration, there is obtained a diagrammatic repre- sentation of the extent of move- ment in the various parts of the thorax. The same purpose is served by shadow-diagrams or photograms taken at the various periods of respiration. A compli- cated apparatus has also been constructed of numerous little rods, which rest on the thorax and rise and fall with the respiratory movement and can be fixed in a given position. The thoracometer of Sibson (Fig. 83) measures the elevation of selected parts of the sternum. It consists of two metal rods, joined at right angles, of which one (A) is applied to the spinal column. On B is the movable arm C, which carries at its end the toothed bar (Z) directed perpendicularly downward. The latter is supplied with a spring, and ends below in a ball, which rests upon that part of the sternum to be investigated. The toothed bar, by means of a small cog^vheel, moves the indicator (o) , Avhich shows the excursions of the sternum on an enlarged scale. RESPIRATORY EXCURSION OF THE LUNGS. TJie boundaries and the size of the lungs in a state of rest on the ante- rior surface of the thorax are shown in Fig. 34. The shaded bounda- ries L L indicate the borders of the lungs, while the dotted lines P P show the extent of the parietal pleura (boundaries of the pleural cavity). In the living subject the extent of the lungs can be determined by percussion, that is, by striking the chest-wall (through an interposed thin plate of horn: Piorry's plessimeter) by means of a small cushioned hammer (Wintrich's percussion-hammer). "Wherever pulmonary tissue containing air lies in contact with the chest-wall, a sound is obtained like that produced bv striking a vessel containing air (resonant per- cussion-note). Where the underlying parts contain no air, the sound is like that produced by striking the thigh (flat percussion-note). If the parts containing air are thin, or are partly deprived of their air, the note is dull. Fig. 84 in connection with Fig. 34 shows the boundaries of the lungs RESPIRATORY EXCURSION OF THE LUNGS. 219 on the anterior chest-wall. The apices of the lungs extend above the clavicles anteriorly to a distance of from 3 to 7 cm.; on the posterior surface they extend above the spines of the scapulae to the level of the seventh spinous process. On the right side the lower border of the lung, in a position of rest, begins at the right edge of the sternum at the insertion of the sixth rib, and extends horizontally outward to about the upper edge of the sixth rib in the mammillary line, and the upper edge of the seventh rib in the axillary line. On the left side (apart from the position of the heart) the lower border of the lung extends downward for the same distance. In Fig. 84 the line at b indicates the lower boundary of the lungs in a state of rest. Posteriorly, both lungs extend to the tenth rib. .[Fig. 84. — Topography of the Boundaries of the Lungs and the Heart during Inspiration and Expiration (after v. Dusch). During the deepest possible inspiration the lungs descend anteriorly below the sixth rib as far as the seventh ; posteriorly as far as the eleventh rib. At the same time the diaphragm withdraws from the wall of the thorax. During forced expiration the lower borders of the lungs rise almost for the same distance as they sink during inspiration. In Fig. 84 the line m n shows the limit of the border of the right lung during deep inspiration, and h 1 indicates the same border during complete expiration. The relation between the border of the left lung and the heart de- serves especial attention. In Fig. 34 may be seen an almost triangular space, extending to the left of the sternum from the middle of the inser- tion of the fourth rib to the sixth rib. This space represents that part of the heart which lies in direct contact with the chest-wall when the 220 NORMAL PERCUTORY CONDITIONS IN THE THORAX. thorax is at rest. Within these limits, represented by the triangle t t' t" in Fig. 84, percussion yields the cardiac dulness ; that is, a flat per- cussion-note is obtained here. In the larger triangle d d' d" a relatively thin layer of pulmonary tissue separates the heart from the chest-wall, and a dull note is obtained on percussion. Only outside this triangle is the so-called pulmonary resonance obtained. On deeper inspiration the inner border of the left lung passes completely over the heart, as far as the mediastinal insertion (Fig. 34), and thus the flat percussion-note is confined to the small tri- angle t i i'. On the other hand, during forced expiration the edge of the lung recedes so far that the cardiac dulness embraces the space t e e'. VARIATIONS FROM THE NORMAL PERCUTORY CONDITIONS IN THE THORAX. The investigation of the normal percutory conditions and their pathological variations is of the greatest importance for the physician. Suggestions of percus- sion (also of the abdomen) are found as far back as Aretaeus (Si A. D.). The real discoverer, however, is Auenbrugger (d. 1809), whose fundamental work was elaborated especially by Piorry and Skoda; the latter developed the physical theory of percussion (1839). Over the area of the lungs the otherwise clear, resonant percussion-note is impaired when the lungs have to a greater or lesser extent lost their normal air- content; an airless space of 4 sq. cm. on the outer surface of the lungs will yield a dull note. _ The note is impaired also when the lung is compressed from without. The percussion-note is louder or hyperresonant in lean individuals with thin chest- walls, or after deep inspiration, or in the condition of permanent expansion that occurs in emphysematous persons. It should also be noted whether the percussion-note is of high or of low pitch; this quality being dependent to a certain extent on the degree of tension in the elastic pulmonary tissue, but especially on the tension of the thoracic wall. As this tension is increased during inspiration, and diminished during expiration, there should be recognized a corresponding difference in the pitch of the note. Deepest inspiration produces a higher pitch, on account of the increased tension of the chest-wall and the lungs; but at the same time the note diminishes in dura- tion and intensity, as the more highly stretched parts possess a diminished ampli- tude of vibration. Sometimes in the terminal phase of the deepest possible in- spiration there occurs still another change in the percussion-note, in that there is produced a certain restoration of the depth and intensity, falling short, however, of the original volume. During complete expiration the intensity is lessened and the pitch lowered. Percussion of the larynx and the trachea yields a clear tympanitic note, whose pitch depends upon the size of the cavity. The note is highest when the mouth and the nose are open, or when the tongue is protruded, or when straining efforts are made with closed glottis; it becomes lower when the head is extended back- ward, or during the act of swallowing, as well as during intonation. It is higher at the end of deep inspiration than during expiration. Affections of the lungs that lessen the normal tension lower the pitch of the note. When the percussion-note partakes of a drum-like character, approaching a musical sound, with distinguishable high and low pitch, it is termed tympanitic. If a hollow rubber ball applied to the ear be tapped with the finger, a typical tympanitic sound will result, the pitch of wliich is higher the smaller the diameter of the ball. Tapping the trachea in the neck will also yield a tympanitic note. The tympanitic note consists of a primary tone, together with several harmonic overtones, arising from an air-space surrounded by relaxed and movable walls (the non-tympanitic tone consists of the membrane-tone of a tightly stretched wall). The tympanitic note in the chest is always of pathological origin. It is found in the presence of a cavity within the lung-substance (when the mouth is closed, and especially when the nose is closed at the same time, the note becomes deeper), also in the presence of air in a pleural cavity, as well as in association with dimin- ished tension of the pulmonary tissue. The tympanitic note is closely allied to metallic tinkling, which arises in large, pathological, pulmonary cavities, as well THE NORMAL RESPIRATORY SOUNDS. 221 as when the pleural cavity contains air, when the conditions are suitable for a more uniform reflection of the soimd-wavcs within the cavity. When a percussion- stroke is made over cavities, especially in the upper anterior part of the lung, the air at times escapes with a peculiar ringing and hissing sound — the cracked- pot sound (or coin-sound). In practising percussion it should be observed by the sense of touch whether the underlying parts offer a feeling of greater or lesser resistance to the stroke; and at the same time the vibratory power may be noted. Under normal conditions small vibratory power is associated with a well-developed bony framework, thick soft parts, and tense muscles. Pathologically, lessened vibration always occurs in connection with an airless condition of the lungs, and is associated with a dull percussion-note. Diminution of the resistance to the percussion-stroke is found normally in slender chests. Pathologically, it occurs when there is a considerable amount of air under the chest-wall, hence in the presence of pneumothorax and of abnormal expansion of the lungs by means of air. If the handle of a tuning-fork be placed upon the chest-wall, the fork will sound loud over spaces tilled with air, and will yield a weak note over spaces containing little or no air (Baas' phonometry). THE NORMAL RESPIRATORY SOUNDS. By listening over the chest-wall, either directly or by means of a stethoscope, the vesicular murmur can be heard during inspiration, wherever the lungs are in contact with the walls of the thorax. The character of this sound can be imitated if the mouth be placed in the position necessary for the act of sipping, and a sound between f and v be softly emitted. The sound is a sipping, rustling, hissing one. It is due to the sudden expansion of the pulmonary vesicles by the entrance of inspired air (hence the term vesicular) and also to the friction of the air passing through the alveoli. The sound is at times softer, at times louder. It is constantly louder in children under the age of twelve years, as the air- vesicles are one-third narrower than in adults, and cause greater friction with the entering air. During expiration the air, when leaving the vesicles, gives rise to a weak puffing sound of an uncertain soft character. The cardiopulmonary murmur heard in the vicinity of the heart when the latter contracts during systole likewise has a vesicular character. Bronchial breathing may be heard in the larger air-passages during inspiration and expiration, and resembles the sound of a loud, sharp h or sh. Outside of the neck (larynx and trachea) it may be heard be- tween the shoulder-blades at the level of the fourth dorsal vertebra (point of bifurcation), especially during expiration. It is somewhat louder to the right, on account of the larger caliber of the right bronchus. In all other parts of the thorax it is obscured by the vesicular murmur. The bronchial breathing arises entirely in the larynx, from the forma- tion of air-vortices, by reason of the marked constriction of the air- passage at the glottis. This laryngeal stenosis-sound causes a resonance of the tracheo-bronchial air-column, and thus produces the specific character of bronchial breathing, which the listener hears transmitted along the large tubes of the bronchial tree. It has been maintained that, if the air- filled lungs of an animal be applied to the neck over the larynx or trachea, the bronchial breathing produced there will become vesicular. In that case it must be supposed that vesicular respiration arises from a weakening and acoustic transformation of tubular respiration by its transference through the air-vesicles. Added to this is the fact that it is impossible to produce any sound by forcibly driving air through narrow straws. 222 PATHOLOGICAL RESPIRATORY SOUNDS. During forced respiration rustling sounds often arise at the mouth and nostrils; with these sounds the primary tone of the oral cavity (usually the vowel-soimd ah) is often mingled in mouth-breathing. PATHOLOGICAL RESPIRATORY SOUNDS. The recognition of the succussion-sound, the friction-sound, and many catar- rhal sounds dates back to Hippocrates (460-377 B. C). The actual foundation of auscultation on a physical basis was laid by Laennec (18 16), and its classical development is due to Skoda (1839). Bronchial breathing arises over the entire area of the lungs, either when the air-vesicles have become airless (through exudation) or when the lungs are com- pressed from without. In both cases the condensed pulmonary tissue conducts the bronchial respiration to the walls of the thorax. Bronchial breathing will also be heard over pathological cavities of considerable size that communicate with a large bronchus, provided the cavities lie sufficiently near the thoracic wall and have walls of considerable resistance. If there is no movement of air in the cavity, the sounds may be wholly conducted out through the trachea; or during expiration a stenosis-sound (hke that at the glottis) may arise in the communicating bronchus, and may be rendered amphoric by the resonant cavity. Amphoric breathing resembles the sound produced by blowing across the mouth of a bottle. It may arise when there occurs in the lungs a cavity at least the size of a fist, through which the air passes in such a manner that there is pro- duced the characteristic sound with a peculiar metallic echo. If the lung is partly expansible and contains air, and the pleural cavity also contains air, the resonance of the latter, together with the exchange of air in the lung, will also produce the amphoric sound. If the respiratory sounds have no definite character, so that they oscillate between vesicular and bronchial breathing, they are termed indefinite respiratory sounds. Frequently a deep respiration or expectoration of mucus will make the character of the sound more evident. If the air meets with resistance in its passage through the lungs, various phenomena may result: (a) At times the air- vesicles are not all filled simultane- ously, but intermittently. This occurs (especially at the apices) when partial swelling of the walls of the air-passages obstructs the steady interchange of air; cogwheel respiration is the result. Occasionally this is heard in perfectly normal lungs, when the muscles of the chest contract in an intermittent fashion, {b) If a bronchus leading to a pulmonary cavity is narrowed in such manner that the air meets with a temporary resistance, the inspiratory sound is at first like that of a loud G, and then goes over during the latter two-thirds of inspiration into a bronchial or amphoric sound. This is termed a metamorphosing sound, (c) Rales are produced in the larger air-passages when the air causes bubbling of the con- tained mucus. In the smaller air-spaces rales arise either when the walls of the latter are separated from the fluid contents during inspiration, or when their walls are in contact and are suddenly separated from each other. Rales are distinguished as moist (arising in watery contents) or as dry (in tough, tenacious contents) ; further, as inspiratory or expiratory, or continnous; also coarse, fine, or irregular rales, the high-pitched crepitant rales, and finally the metallic tinkling rales produced by the resonance of large cavities, {d) If the mucous membrane of the bronchi is so swollen or so covered with mucus that the air must force its way through, there arises frequently in the larger passages a deep humming purr — sonorous rhonchus; and in the smaller tubes a clear whistling sound — sibilant rhonchus. In cases of widespread bronchial catarrh a thrill may often be felt in the chest- wall — bronchial fremitus — caused by the numerous rales. When the lung is collapsed and the pleural cavity contains fluid and air, a sound may be heard on shaking the chest, similar to that produced by shaking a large bottle containing water and air— the succussion-splash of Hippocrates. Rarely a higher-pitched similar sound may be heard in pulmonary cavities the size of a fist. When the opposed layers of the pleura are roughened by mflammatory processes, and rub against each other in the act of respiration, a friction-phenomenon is produced. This may be partly felt (often by the patient himself) and partly heard. The sound is usually creaking, and may be compared to that produced by bending new leather. Friction-sounds are produced also by the heart's action between the two layers of the diseased roughened pericardium. PRESSURE IN THE AIR-PASSAGES DURING RESPIRATION. 223 Durins^ loud speaking or singing the chest-wall vil urates — vocal fremitus — as a consequence of the propagation throughout the bronchial tree of the vibrations of the vocal bands. This vibration naturally is most pronounced in the region of the trachea and the large bronchi. If the ear be applied to the chest-wall, the voice can lie heard only as an unintelligible hum. If the pleural cavity contains air or a large effusion, or if the bronchi are occluded by large quantities of mucus, the vocal fremitus is weakened or entirely ab.sent. On the other hand, all factors that cause bronchial breathing will increase the vocal fremitus. Hence, the latter will be more marked also in those localities where bronchial breathing is heard, even under normal conditions. The ear under such circumstances wall hear the sounds conducted to the chest-wall with increased intensity. This is termed bronchopliony. If a pleural effusion or a pulmonary inflammation causes a flattening of the bronchi, the sound of the voice in the chest sometimes assumes a peculiar bleating quality — cgophony. Doubtless the gradations of increased or diminished fremitus could be readily demonstrated by means of the sensitive flame (observed in a rotating mirror) or by the use of the microphone. For the former there should be employed an appa- ratus similar to the gas-sphygmoscope, with the lower part widened in the shape of a funnel. PRESSURE IN THE AIR-PASSAGES DURING RESPIRATION. If a manometer be fastened in the trachea of an animal in such a manner that respiration is not interfered with, the instrument will show a negative pressure ( — 3 mm. of mercury) during inspiration, and a positive pressure during expira- tion. Donders has modified this experiment for man by introducing a U-shaped manometer-tube through one nostril, and instructing the subject to breathe quietly through the other nostril with the mouth closed. He found that during each quiet inspiration the mercury showed a negative pressure of i mm., and during each expiration a positive pressure of 2 or 3 mm. Aron experimented wnth patients having a tracheal fistula as the result of operation, and found during inspiration a pressure of from — 2 to — 6.6 mm. of mercury, during expiration from -1-0.7 to -+-6.3 mm. of mercury. In speaking, the corresponding fluctuation was from — 6 to -f 7 , and when coughing from — 6 to -1-46.1. As soon as the air is drawn in and expelled wdth greater force, the fluctuations of pressure become more marked, especially in the acts of speech, singing, and coughing. If forced respiration be practised with the mouth and one nostril closed, so that the respiratory canal communicates only with the manometer, the greatest inspiratory pressure is — 57 mm. (between 36 and 74), and the greatest expiratory pressure is -f87 (between 82 and 100) mm. Notwithstanding the higher expiratory pressure, it must not be inferred that the expiratory muscles are stronger than those of inspiration ; for during the latter act a series of resisting forces must be overcome, leaving a much diminished supply of force for the aspiration of the mercury. These resisting forces are: (i) The elastic tension of the lungs, which amounts to 6 mm. during complete ex- piration, but reaches 30 mm. during deepest inspiration. (2) The lifting of the weight of the thorax. (3) The elastic torsion of the costal cartilages. (4) The depression of the abdominal viscera and the elastic distention of the abdominal walls. All these resisting forces aid the expiratory muscles during expiration. "With these facts in view, there is no doubt that the combined strength of the inspiratory muscles is greater than that of the expiratory muscles. « As the lungs, by reason of their elasticity, have a tendency to collapse, they naturally exert a negative pressure within the thoracic cavity. In dogs this amounts to from 7.1 to 7.5 mm. of mercury during inspiration, while in expiration it is naturally less, namely only 4 mm. The analogous values obtained by different investigators on the dead body vary; Hutchinson fixes them at 4.5 mm. and 3 mm. The greatest pressure during inspiration and expiration seems small when compared to the blood-pressure in the large arteries. If, ho\vever, the pressure- values obtained for the respired air be 'estimated for the entire superfices of the thorax, considerable results are obtained. To measure the muscular respiratory power in case of illness, a U-shaped mercurial manometer may be employed, provided with an attachment suitable for introduction into a nostril or the mouth (Waldenburg's pneiimatometer) . The in- spiratory pressure alone may be reduced (in the presence of almost all diseases 224 MOUTH-BREATHING AND NASAL BREATHING. impairing the expansion of the lungs), or only the expiratory pressure may fall (in cases of emphysema and of asthma), or both may be weakened (as occurs in feeble persons) . If a forced inspiration rarefies the air in the air-passages, the trachea and bronchi become narrowed and shortened; the reverse occurs during expiration. If a lung be inflated, air will steadily escape through the walls of the alveoli and trachea. The same thing takes place during violent expiratory efforts (cuta- neous emphysema attending whooping-cough) , so that pneumothorax, entrance of air into the blood-vessels, and even death may result. If a dog be made to breathe through Miiller's valve, by means of which the resistance to respiration may be increased at will, it is found that a pressure of 40 cm. of water is still readily overcome, that a higher pressure can be overcome for a short time, and one of 70 cm. not at all. Until birth the airless lungs lie collapsed (atelectatic) in the chest-cavity, and fill it, so that pneumothorax is not produced if the thorax be opened in a dead fetus. Even in children that have lived for eight days and have breathed normally, the lungs do not collapse when the pleural cavity is opened, but remain in contact with the chest-wall. It is only after further growth that the thorax becomes so large that the lungs must expand under elastic tension; only then will opening of the thorax cause the lungs to contract into a smaller volume. Hermann calls attention to the fact that a lung containing air cannot be emptied by pressure from without. The reason for this is that the small bronchi will be closed by the pressure before the air can leave the alveoli. The muscles of expiration, therefore, have not the power to compress the lungs until they are airless; but, on the other hand, the inspiratory muscular power is sufficient to expand the lungs beyond the state of elastic equilibrium. Hence, the physical attributes of the lungs limit, to a certain extent, the mechanism of respiration: the muscles of inspiration expand the lungs and at the same time increase their elastic tension, while the expiratory muscles can only diminish the tension, without being able to abolish it altogether. MOUTH-BREATHING AND NASAL BREATHING. Quiet respiration is usually performed with the mouth closed, pro- vided the nose be unobstructed. The current of air passes through the naso-pharyngeal cavity, and there undergoes certain changes: (i) Its temperature is increased to the extent of f of the difference between its original temperature and that of the body. (2) At this increased temperature it is saturated with aqueous vapor. These changes are made so that the cold, dry air does not irritate the lining of the lungs. (3) Dust-particles may cling to the mucus covering the irregular walls of the air-passages, and are again conveyed outward by the ciliated epithelium. The nasal secretion possesses qualities harmful to many bacteria (for example, anthrax-bacilli), thus demonstrating the salutary effect of nasal breathing when there is danger of contagion. (4) Finally, by means of the sense of smell bad air and air impregnated with injurious admixtures can be recognized. When the mouth is open no current of air passes .through the nose during respiration. Pathological. — Permanent obstruction of the nose, leading to exclusive mouth- breathing, may result in a long series of harmful effects ; namely, catarrhal condi- tions of the pharynx, the air-passages, and the middle ear, abnormal formations in the bones of the mouth and the nose, pains in the facial muscles, changes in speech, disturbances of intellect (difficulty in fixing the attention). Another important phenomenon is the appearance of edema of the lungs; that is, an exudation of serum from the blood into the pulmonary alveoli. The causes of this condition are: (i) marked obstruction to circulation in the aortic system; for example, after ligation of all of the carotid arteries, or of the arch of the aorta in such a position that only one carotid remains pervious ; (2) occlusion of the pulmonary veins; (3) cessation of action in the left ventricle (following mechanical injury), while the right ventricle still continues to beat. All of these causes will produce at the same time anemia of the brain, resulting in anemic MODIFIED RESPIRATORY ACTS. 225 irritation of the vasomotor ct-ntcr, and consequent contraction of the small arteries. This will cause an increased amount of blood to enter the veins and the right heart, whose driving power increases the pulmonary edema. V. Basch believes that an overfilling of the j)ixlmonary capillaries diminishes the elasticity of the alveoli, thus making the latter to a certain extent more rigid. The expansibility, therefore, of the lungs is diminished. MODIFIED RESPIRATORY ACTS. There are a number of characteristic, partly involuntary, partly voluntarv, variations of the respiratory movements, to which the not altogether suitable term abnormal respiratory acts has been applied. Coughing consists in a sudden violent expiratory effort, usually succeeding a deep inspiration and closure of the glottis, during which effort the glottis is sprung open, and any solid, fluid or gaseous substance that may be irritating the respiratory mucous membrane is expelled. The lips are parted during this act. It may be a voluntary or a reflex act, in the latter case being subject to the will only to a certain degree. Hawking consists in a rather long expiratory effort through the narrow space between the root of the tongue and the depressed soft palate for the purpose of removing foreign bodies. If the hawking be accomplished in an intermittent fashion, it is accompanied by a springing open of the glottis (mild, voluntary coughing) . This act is performed only voluntarily. Sneezing consists in a sudden expiratory effort through the nose, accom- panied by a sudden opening of the naso-pharynx, previously closed by the soft palate. The purpose is to expel mucus or foreign bodies. It is very seldom per- formed with the mouth open, and is preceded by a single or by repeated spas- modic inspiration. The glottis is always wide open. This act occurs only as a reflex through irritation of the sensory nerves of the nose, or as a result of a bright light suddenly falling upon the retina. The reflex may be to a certain extent inhibited bj' marked excitation of sensory nerves, such as rubbing the nose, or pressing the hyoid bone forcibly upward. Habitual use of nasal irritants, such as snuff, blunts the sensorv^ nerves against reflex excitation. Coughing and sneezing rarely occur simultaneously. Snorting and Blowing the Nose ; Snuffing ; Sniffing. — Noisy, forced breathing through the nose is designated snorting. Blowing the nose consists in a strong, nois3% expiratory effort made through nostrils that have been narrowed, either by the fingers or by the inuscles of the nose and the upper lip. the object being to remove either foreign bodies or mucus. Snuffing consists of drawing substances up into the nose by a noisy inspiration, the mouth being closed, and the nostrils often being narrowed by the action of the muscles of the nose and the upper lip. Sniffing consists in drawing air up into the nose by a succession of short inspirator}'' efforts, for the purpose of smelling. The act is frequently accompanied by rustling noises and movements of the nostrils, while the mouth is held closed. All these actions are voluntarj-. Snoring results from breathing with the mouth open, the current of air during both inspiration and expiration causing noisy, vibrating movements of the relaxed soft palate. It usually occurs involuntarily during sleep, but it may also be produced voluntarily. Gargling consists in the noisy slow escape of the expired air in the form of bubbles through a mass of fluid held between the root of the tongue and the soft palate, while the head is thrown back. The act is voluntary-. Crying is called forth by the emotions, and consists in short, deep inspira- tions, with prolonged expirations, the glottis being narrowed, and the muscles of the face and jaw being relaxed (with contraction of the zygomaticus minor) ; tears are secreted, and lamenting, inarticulate sounds are often emitted. In conjunction with intense, prolonged crying there often arise sudden, spasmodic: involuntary contractions of the diaphragm, w'hich, when attended with valve-like approxima- tion of the vocal bands, give rise to the inspiratory sound known as sobbing. This act is purely involuntan.^ The sobbing that occurs so frequently during the agonal period may be explained by the electrical influence of the contraction of the heart on the phrenic nerves, which become highly irritable in the act of dying. Sighing is a prolonged respiratory movement, usually accompanied by a mournful sound, often aroused involuntarily by painful emotions. Laughing consists in a quick succession of short expirations through vocal 15 226 CHEMISTRY OF RESPIRATION, bands that are stretched for high notes, and are alternately approximated and separated, while characteristic, inarticulate sounds are emitted from the larynx, with vibrations of the soft palate. The mouth is usually open, and the face is drawn into a characteristic position by the zygomaticus major (not the risorius muscle) . Laughing is usually aroused involuntarily by agreeable conceptions, or by feeble, sensory irritation, such as tickling. It may to a certain extent be repressed by the will, as by forcibly closing the mouth and holding the breath; also by painful irritation of sensory nerves, as by biting the tongue or the lips. Yawning consists in a prolonged, deep inspiration, with the mouth, the palatal arch and the glottis widely open, successively calling into play numerous inspiratory muscles. Expiration is shorter, and both are often accompanied by a prolonged, characteristic sound. There also occurs frequently a general stretching of the bodily muscles. The act is always involuntary, being usually incited by sleepiness or monotony. CHEMISTRY OF RESPIRATION. The problem here is to estimate quaHtatively and quantitatively the gases expelled during respiration. If the results be compared with the gaseous composition of inspired, atmospheric air, a picture may be obtained of the interchange of gases occurring during respiration. QUANTITATIVE ESTIMATION OF THE CARBON DIOXID, THE OXYGEN, AND THE AQUEOUS VAPOR IN GASEOUS MIXTURES. Estimation of the Carbon Dioxid. The volume of carbon dioxid may be estimated bv means of Vierordt's antliracometer (Fig. 85, II). The gaseous mixture is rece'ived and enclosed in a graduated tube r r, previously filled with water, and provided at one end with Fig. 85. — I. Apparatus for the Collection of Expired Air (after Andral and Gavarret). II. Carl Vierordt's Anthracometer. a bulb of known capacity. The bottle n, filled with a solution of potassium hydrate, is then screwed on the end-piece h. The stop-cock is opened, and the potassium-solution is allowed to run up into the tube, the latter being agitated METHODS OF INVESTIGATION. 227 until all the carbon dioxid is absorbed by the [>otassium, with the forma- tion of potassium carboncite. Then the solution is allowed to run back into the bottle, the stop-cock is closed, and the potassium-bottle is removed. The end of the tube is dipped into water, and the latter is allowed to rise in the tube. The volume of water thus admitted is equal to the volume of carbon dioxid removed by the potassitun-solution. Determination by Weight. — A considerable volume of the gaseous mixture is passed through Liebig's bulbs, filled with a solution of potassium hydrate and arranged in a combination such as that of Scharling's apparatus (Fig. 86, e, f, g). Determination by Titration. — A considerable volume of the air to be exam- ined is conducted through a definite quantity of a known solution of barium hydrate. The carbon dioxid combines to form barium carbonate. The solution is then neutralized with a titrated solution of oxalic acid. The quantity of oxalic acid necessary to neutrali.7e the remaining barium hydrate varies inversely with the amount of barium already combined with the carbon dioxid. Estimation of the Oxygen. The volume of oxygen may be determined in two ways: (a) By combining the gas with potassium pyrogallate. Vierordt's anthracometer may be employed for this purpose, svibstitiiting a solution of potassium pyrogallate for that of potassium hydrate. (6) By explosion in an eudioineter. Estimation of the Aqueous Vapor. The volume of air to be examined is allowed to pass either through a bulb- apparatus containing concentrated sulphuric acid, or through a tube filled with pieces of calcium chlorid. In both cases the water is energetically abstracted, and the increase in weight will give the amount of water in the air examined. METHODS OF INVESTIGATION. Collecting the Expired Air. If only the gases exhaled from the lungs are to be collected, the bell-jar of the spirometer (Fig. 76) may be used, suspended in a concentrated solution of sodium chlorid to limit the gas-absorption. Andral and Gavarret permitted several successive expirations to be made into a large bell- jar (Fig. 85. I, C). For this purpose a mouth-piece M was applied in an air-tight manner over the mouth, the nostrils being closed; the direction of the air-current was regulated by Fig. 86. — Respiration Apparatus of Scharling. means of two so-called Miiller's mercurial valves (a, b). which allowed the air to pass only in the direction of the arrows. If the gases given off from the skin during perspiration are to be investigated, as well as those from the lungs, then the subject must be placed in a closed cham- ber, from which the gases mav be withdrawn for experimental purposes. The Most Important of the Respiration Apparatus. — (a) The apparatus of Schar- ling (Fig. 86) consists primarily of a closed chamber A, capable ot containing a human being. The chamber has an afferent opening z, and an efferent opening b. The latter is connected with an aspirating contrivance C, consisting of a good- sized barrel filled with water. It is evident that when the water flows out of the 228 METHODS OF IXVESTIG ATIOX, barrel, an uninterrupted stream of fresh air enters the chamber A, and the air in the chamber, mixed with the respired gases, escapes toward the barrel. Con- nected with the afferent opening z is a set of Liebig's bulbs d, filled with a solution of potassium hydrate through which the entering air passes and is deprived of its carbon dioxid, so that the subject breathes air completely free of carbon dioxid. Upon leaving the efferent opening b the air is first conducted through the tube e, in which the aqueous vapor is absorbed by sulphuric acid, and its amount may be determined by the increase in the weight of the tube. Then the air passes through the potassium-bulbs f, where all the carbon dioxid is absorbed. The tube g, filled with .sulphuric acid, is intended for the purpose of absorbing, the aqueous vapor conveyed by the air from f. The increase in weight of f -(-g represents the weight of the absorbed carbon dioxid. The volume of air inter- changed may be estimated from the contents of the barrel. (6) Regnault and Reiset's apparatus (Fig. 87) consists of a bell-jar R, in which is placed the animal (dog) to be experimented upon. Surrotmding this Koh Fig. 87. — Diagrammatic Representation of Regnault and Reiset's Respiration .\pparatus. jar is a cylinder g g, which may be used for calorimetric observations, a thermometer t being introduced for this purpose. The bell-jar has leading into it the tube c, through which is introduced a measured quantity of oxygen (Fig. 87, O), which (Fig. 87, CO^) has given off to the potassium hydrate any remaining admixture of carbon dioxid. The oxj-gen in the measuring vessel O is forced toward the bell-jar R by a solution of calcium chlorid, coming from a basin pro- vided with large bottles (Ca CU). From R pass the tubes d and e, connected by rubber tubes with the communicating potash-bottles (KOH, koh), which may be alternately raised and lowered by means of the scale-beam w. By these means the air is aspirated from R, and the carbon dioxid is absorbed by the solution of potassium hydrate. At the end of the experiment the increase in weight of the bottles represents the quantity of carbon dioxid expired. The amount of oxygen inspired is measured directly in the measuring vessel O. Finally, the manometer f shows whether there is a difference between the air-presstire within the jar and that on the outside. (c) The most complete apparatus is that of v. Pettenkofer (Fig. 88). A cham- ber Z, made of metal and provided with a door and a window, has an opening for the entrance of air at a. A double suction-pump P P,, driven by steam, renews COMPOSITION AND PROPERTIES OF ATMOSPHERIC AIR. 229 continuously the air in the chamber. This air is first conducted into the vessel b, which is tilled with pumice-stone saturated with water. Here the air becomes saturated with aqueous vapor, and then passes through the gasometer c, which indicates the total volume of the interchanged air; the latter is then discharged into the outer atmosphere. The main tube x, leading from the chamber, carries a mercurial manometer q, for the detection of jiossible variations in pressure within the room. This tube gives off a branch tube n, through which the air passes for chemical examination. The air in this tube is driven b}^ a suction-apparatus M M,, constructed on the principle of Miiller's mercurial valve, and worked by the same steam-engine as .Fig. 88.— Diagram of v. Pettenkofer's Respiration .\pparatus. the pump P Pi. Before entering the pump the air passes through the sulphuric- acid bulbs, from whose increase in weight the amount of aqueous vapor can be estimated. After leaving the pump the air passes through the tube R, filled with barvta-water, \vhich absorbs the carbon dioxid. The quantity of air passing through the branch tube n is then measured by the gasometer u, after which it finally passes into the atmosphere. The second branch tube N provides for an examination of the air before entering the chamber, by an apparatus identical with that placed on the tube n. The excess of carbon dioxid and water found in n over that in N is due to the respiratory activity of the subject placed in the chamber. COMPOSITION AND PROPERTIES OF ATMOSPHERIC AIR. The dry atmosphere contains: Percentage in Percentage in Gas. Weight. Volume. 0 23.015 20.922 Including I per cent, in N 76.985 7902 volume of argon, together CO2 0.029-0.034 with helion, and i part of krj'pton in 20,000 parts of air. The air contains likewise xenon, neon, coronium (lighter than hydrogen), and less than one-millionth part of aetherium (which latter possesses a specific 230 COMPOSITION AND PROPERTIES OF ATMOSPHERIC AIR. gravity only Tcidff that of hydrogen, but a power of heat-conduction 100 times as great as that element, and a density of only x^^ioij^ that of the air). These elements have not been investigated physiologically. ^therium is probably a composite substance, and perhaps plays the role that has been previously ascribed to luminiferous ether. Aqueous vapor is alwaj^s present; its amount usually increases with the height of the temperature. With reference to the humidity of the air there must be distinguished : (a) the absolute humidity, that is, the quantity of aqueous vapor contained in a volume of air; (b) the relative humidity, that is, the quantity of aqueous vapor contained in a volume of air in relation to its temperature. The latter increases with rising temperature. The relative humidity is determined either by means of the hygrometer of Klinkerfues or by the psychrometer of August. The latter consists of two accu- rately graduated thermometers, the bulb of one being kept constantly moistened by means of a wet cloth. As a result of evaporation of the water on the bulb, cooling will take place, and the fall of the thermometer will vary directly with the rapidity of evaporation, that is, with the dryness of the atmosphere. From the difference in the readings of the two thermometers the tension of the aqueous vapor in the air may be calculated according to the formula: e = e' -k X (t -t') Xb; in which e represents the desired tension of the aqueous vapor in the air at the pre- vailing temperature, as indicated by the dry thermometer; e' the tension of the aqueous vapor that prevails when the air is completely saturated with watery vapor at the temperature of the moist thermometer (to be ascertained from works •on physics); b the state of the barometer in millimeters of mercury; t the tein- perature of the dry thermometer, and t' that of the moist thermometer (expressed in degrees Centigrade); and k an empirically obtained constant = o.ooi. Experience has taught that man breathes best in an air that is not completely saturated with watery vapor in accordance with its temperature, but only to 70 per cent, of that amount. Air that is too dry irritates the mucous membranes of the respiratory organs; while air that is too moist arouses a feeling of uncom- fortable oppression, and in warmer air a sensation of oppressive sultriness. At a lower temperature (15° C.) dry air is more comfortable than moist air; at from 24° to 29° C. dry air feels cooler than moist air. With marked dryness of the atmosphere a temperature of 29° C. is well borne; but exceedingly damp air becomes unendurable for any length of time at 24° C. In the living room and in the sick- room attention should, therefore, be paid to the correct degree of atmospheric humidity. (Sprinkling with water, or in winter placing a basin of water on the stove may be resorted to.) Rooms that are too damp, on account of dampness of the walls or the floor, are prejudicial to health. The following factors are known to influence the absolute quantity of aqueous vapor in the air: (i) At the sea-shore during the day the amount is increased with a rising temperature, and diminished with a falling temperature. (2) In the flat, inland country the humidity rises from sunrise to noon, then diminishes until evening; rises again during the first part of the night, and finally falls again. (3) On high mountains the mid-day decrease in humidity does not occur. (4) South- western winds in summer are accompanied by the greatest humidity, while east winds in winter bring the lowest degree of humidity. With reference to the relative amount of moisture it is to be noted: (i) that it is usually greatest at sunrise, and least toward noon; (2) that it is diminished on high mountains; (3) that it is greater in winter than in summer; (4) that it is usually greater with south and west winds than with north and east winds. In the course of the year's changes, that air which is found to be the richest in water absolutely is the poorest relatively. For example, the air in summer contains absolutely about three times as much watery vapor as in midwinter, and still the summer air is relatively drj^er than that of winter. In the course of the seasons the absoktte humidity rises and falls with the mean temperature. The average relative humidity amounts to about 70 per cent, in temperate climates. With increasing elevation above sea-level "the density of the air diminishes. It likewise diminishes with increase of temperature. COMPOSITION OF EXPIRKD AIR. 231 With every increase of about 186 meters in elevation above the surface of the earth, the temperature (irregularly, it is true) falls 1° C. Above a level of 4000 meters the cold increases in greater proportion; at a level of 7000 meters the most severe degree of cold prevails without variation, being the same at all seasons. COMPOSITION OF EXPIRED AIR. The expired air is rich in carbon dioxid, of which it contains on an average 4.38 per cent, by volume (from ^.^ to 5.5 per cent.) during quiet respiration. The amount of carbon dioxid is, therefore, more than 100 times greater than in the atmosphere. The expired air contains less oxygen (on an average 4.782 per cent, less by volume) than inspired, atmospheric air, namely, only 16.033 P^r cent, by volume. ^ Hence, during respiration there is more oxygen taken into the body from the air than there is carbon dioxid expelled; so that the volume of the expired air is from one-fiftieth to one-fortieth less than the volume of inspired air (under the same conditions of temperature, humidity, and pressure). This relation of the expired carbon dioxid to the inspired oxygen (4.38 : 4.782) is termed the respiratory quotient: CO., o" (=S") =°-9'6- A small excess of nitrogen is admixed with the expired air. It has been found that not all of the nitrogen taken up with the food appears again in the excretions (urine and feces). The expired air during quiet respiration is satur- ated with aqueous vapor. It is, therefore, evident that, by reason of the changes in the amount of water contained in the air, a varying quantity of water must be excreted by the body through the lungs. With rapid respirations Moleschott observed the percentage of aqueous vapor to fall. The surrounding tempera- ture also has an influence on the amount of water given off: the minimum occurs at 15° C, while below this point the amount increases moderately, and above the quantity rises rapidly. The expired air possesses a considerable degree of heat (on an average 36.3° C), which at moderate ex- ternal temperatures approaches quite closely that of the body; but even with extreme variations of the surrounding temperature the degree of heat main- tains itself within the same limits. Valentin and Brunner employed the instrument repre- sented in Fig. 89 to determine the temperature of the expired air. It consists of a glass tube A A, with a mouth-piece B and an inserted, delicate thermometer C. Inspiration is made through the nose, and the air is slowly expelled through the mouth-piece into the tube. Temperature of the Air. Temperature of the Expired Air. -6.3° C. -1-29.8° C. + I7°-I9°C. +36.2-37° C. + 44° C. +38.5° C. Fig. 89. — .Apparatus for Measiuing the Temperature of the E.xpired Air. 232 EXTEXT OF THE DAILY INTERCHANGE OF GASES. It wotdd certainly be highh" interesting to determine whether the temperature of the expired air undergoes change by reason of inflammations, disturbances of the circulation, or degenerations in the lungs. Mosso and Rondelli allowed dogs to breathe air at a temperature of from 150° to 160° C, and found that the air in the bronchi was of a higher temperature (39.3° or 37.8° C.) than the rectum. The diminution in volume of the expired air mentioned already is compensated for by the warming of the inspired air in the air- passages, and by the tension of the contained aqueous vapor, so that the volume of the air expired is even one-ninth greater than that of the air inspired. Exceedingly small quantities of ammonia are admixed with the expired air, amounting to about 0.0204 gram in twenty-four hours; they are probably evolved from the blood. Small quantities of hydrogen and marsh-gas (CHJ, both absorbed from the intestines, are likewise exhaled. Reiset observed that in herbiv- orous animals the marsh-gas exhaled in twenty-four hours amounted to as much as 30 liters. The aqueous vapor condensed by low temperature from the expired air of some persons acts as a poison when injected subcutaneoush", in consequence of the presence of a volatile base. These are exceptions, however. EXTENT OF THE DAILY INTERCHANGE OF GASES. As more oxygen is normally taken in than is excreted in the carbon dioxid (equal volumes of oxygen and carbon dioxid containing equal quantities of oxygen), a part of the oxygen taken in must be used for other oxidation-purposes. According to the extent of the latter, there must be considerable variation in the relation of the inspired oxygen to the expired carbon dioxid (the quotient ^', which is given as being on an average 0.916 during normal, quiet respiration). Within the limits of the normal vital processes, not only may the excretion of carbon dioxid be less than the stated average, but it may even be con- siderably in excess of the absorption of oxygen. "With such varia- tions it is evident that the estimation of the amount of carbon dioxid alone cannot be a reliable measure of the total interchange of gases. A complete insight into the gaseous balance can be obtained only by a simultaneous estimation of the oxygen taken in and of the carbon dioxid given off. SUMMARY OF THE GASEOUS IXTERCHAXGE. Absorption in twenty-four hours; Excretion in twenty-four hotirs: Oxygen. 744 gm. =516,500 cu. cm. Carbon dioxid. 900 gm. = 455,500 cu. (Carl Vierordt) . cm. (Carl Vierordt) , hourly 3 1 . 5 - 5 1 1-658 gm. (Speck). ^^ gm. (J. Ranke) ; 32.8-33.4 (The volumes are determined for 0° gm. (v. Liebermeister) ; 34 gm. and the mean barometer.) (Panum) ; 36 gm. (Scharling). Water, 640 gm. (Valentin) ; 330 gm. (Carl Vierordt). FACTORS INFLUENCING THE EXTENT OF THE RESPIRATORY EXCHANGE OF GASES. The process of carbon-dioxid formation consists probably of two separate stages. In the first place, through the presence of oxygen EXTENT OF THE RESPIRATORY EXCHANGE OF GASES. 233 in the tissues, there are formed combinations containing carbon dioxid, which are oxidation-products of substances containing carbon. The second step consists in the separation of this carbon dioxid, which can take place even without the absorption of oxygen. Both processes do not always take place unifomily; at times there is a preponderance in the formation of substances destined for decomposition and carbon- dioxid formation, while at other times the liberation of carbon dioxid predominates, with a diminution in the substances mentioned. The respiratory interchange of gases (also the respiratory quotient) is, within wide limits, independent of the amount of oxygen in the air and the pressure of the atmosphere. According to Schmiedeberg the oxidation in the tissues depends upon a synthesis accompanied by a separation of water, for which purpose the blood supplies the necessary oxygen. The processes under consideration are affected by : 1. Age. — Until the body is fully developed, the output of carbon dioxid increases, while from that point it diminishes with the decline in bodily strength. Hence, in young persons the absorption of oxygen is relatively greater in comparison with the carbon dioxid given ofif. At all other periods of life both values correspond rather closely. For example : Age. Years. CO2 Excreted ii 0.17. 113 8 443 grams 15 766 16 950 I' 18—20, 1003 20—24, 1074 40-60, 889 " 60— So, 810 " In children the excretion of carbon dioxid is absolutely less, but rela- tively greater, than in adults; weight for weight, children excrete almost twice as much carbon dioxid as adults. The new-bom also consumes relatively more oxygen than adults. In the fetus of the sheep the con- sumption of oxygen was found to he only one-sixteenth that in the full- grown animal. 2. Sex. — ^lales from the eighth year to advanced age give off about one-third more carbon dioxid than do females. This difference is still more marked at the time of puberty, when it amounts to about one-half. After the cessation of menstruation there is an increase, and in old age again a decrease in the amount of carbon dioxid given off. Pregnancy progressively increases the output, for evident reasons. Young girls, under otherv\-ise similar conditions, exhale less carbon dioxid than boys; the proportion being 100 : 140. Boys of from nine to twelve years of age exhale from 33 to 34 grams in an hour. In the thirteenth year the excretion of carbon dioxid rises rapidly, and maintains itself at a high level until the nine- teenth year (from 42 to 45 grams in an hour). Then it falls between twenty and thirty years to 38 grams; and, finally, between thirty-five an'd sixty years it is from 34 to 37 grams. Girls between eight and ten years old excrete from 23 to 25 grams; between eleven and thirty years old they exhale from 26 to 32 grams, and at sixty-five years of age 26 grams. Younger and lighter individuals of both sexes, with their greater body surface, give off more carbon dioxid (in propor- tion to their weight) than older, heavier, and more compact persons. 3. Constihition. — As a rule, muscular, active individuals require more oxygen and excrete more carbon dioxid than less muscular In Twenty-four Hours Grams = Carbon. 0 Absorbed in Grams = 121 carbon 375 grams. = 209 652 •' = 259 809 = 274 S54 " = 293 914 " = 242 757 " = 211 689 " 234 EXTENT OF THE RESPIRATORY EXCHANGE OF GASES. and energetic persons of the same size and weight. The consumption of oxygen and the excretion of carbon dioxid are in inverse proportion to the extent of body surface. In this connection the respiratory gaseous interchange pursues a course parallel with that of heat-pro- duction. 4. Diurnal and Nocturnal Variations. — In general there is during sleep a diminution in the excretion of carbon dioxid as compared with the waking state (the proportion being 100 : 145, in the most extreme case 100 : 169). This is proportional to the diminution of the general metabolism resulting from the constant heat of the surroundings (the bed), the darkness, the absence of muscular activity, and the abstinence from food (see 5, 9, 6, 7). According to v. Pettenkofer and C. v. Voit and others a slight accumulation of oxygen seems to take place during sleep. After awaking in the morning the respirations become deeper and more rapid, with at first an increase in the excretion of carbon dioxid. In the course of the morning, however, the excretion diminishes again, until the midday meal causes a fresh increase to the maximum. A falling off takes place again in the afternoon, and finally an incon- siderable increase is produced by the evening meal. During hibernation, in which, together with the taking of food, respiration is entirely discontinued, and the interchange of gases is carried on only by diffusion in the lungs and the cardio-pneumatic movements, the excretion of carbon dioxid falls to 7V. and the absorption of oxygen to 4V of the respective amounts during the waking state. Therefore, much less carbon dioxid is given off than there is oxygen absorbed, so that the body weight may even increase in consequence of the excess of oxygen taken up. 5. Influence of the Surrounding Temperature. — The bodily tempera- ture of cold-blooded animals is easily raised by an increase in the sur- rounding temperature. Under such circumstances the animals give off more carbon dioxid than in a cooler state. For example, a frog exposed to a surrounding temperature of 39° C. excreted almost three times as much carbon dioxid as when the temperature was 6° C. Warm-blooded animals behave in a varying manner with changes in the surrounding temperature, accordingly as the bodily temperature remains constant, or is correspondingly raised or lowered. In the latter case, as in cold- blooded "animals, a considerable decrease occurs in the excretion of carbon dioxid, when the body is cooled under the influence of cold surroundings. Conversely, elevation of the bodily temperature (also in the presence of fever) gives rise to increase in the excretion of carbon dioxid. The behavior is exactly the reverse when the bodily tempera- ture remains constant on exposure to varying surrounding temperature. With increasing cold of the surrounding medium, the consequent reflex stimulation causes an increase in the oxidation-processes of the body, as well as in the number and depth of the respirations. As a result, more oxygen is taken up and more carbon dioxid is given off. The involuntary muscular movement that occurs when the body is cooled has the most obvious influence on the increase in the gaseous inter- change. The season of the year also has an influence on the interchange of gases; in January a man consumed 32.2 grams of oxygen hourly, in July only 31.8 grams. In animals the carbon-dioxid excretion was found to^ be about one-third higher with a surrounding temperature below 8° C. than with a temperature above 38° C. When the tempera- ture of the air increases (without change in the bodily temperature), EXTENT OF THE KKSPI RATORY EXCHANGE OF GASES. 235 the respiratory activity and the excretion of carbon dioxid diminish, while the pulse remains nearly constant. It has been shown that when there is a sudden change from cold to warm surroundings, the carbon- dioxid output diminishes considerably; and, conversely, when the change is from warm to cold, the excretion increases considerably. 6. Muscular Exertion produces a considerable increase in oxygen- consumption and carbon-dioxid elimination, which, for instance, may be three times as great in walking as in a quiet, recumbent position. Every kilogrammeter supplies ^\ milligrams of carbon dioxid; therefore, each additional gram of carbon dioxid formed is the equivalent of 300 kilogrammeters. The establishment of a certain degree of tension in the muscles requires more metabolic change than the maintenance of this tension. The increase in the interchange of oxygen and carbon dioxid begins almost immediately after the work commences. In a few minutes it attains a constant height of at most from seven to nine times the amount during rest. After the work is finished, the consumption of oxygen falls in from 3 to 15 minutes to the rate during rest. The respiratory quotient remains essentially unchanged during work. During light work there is relatively a little more oxygen consumed than during heavy labor. The production of carbon dioxid is diminished with practice, that is, with a more economically applied exertion of the muscles. The gaseous exchange is to a certain extent under the influence of the vagus nerve, which in part inhibits and in part accelerates the heart's activity. Irrita- tion of this nerve may produce a diminution in inetabolism, characterized by a more pronounced fall in the absorption of oxygen than in the excretion of carbon dioxid; or it may call forth an increase in metabolism, distinguished by a greater rise in the output of carbon dioxid than in the oxygen taken in. J. Ingestion of Food causes a not inconsiderable increase in the carbon-dioxid excretion, which is in general governed by the quan- tity of food. Hence, the increase is generally most pronounced (about 25 per cent.) from one-half to one hour after the chief meal (dinner). The increase in the consumption of oxygen that follows the intro- duction of food into the stomach depends in part upon the increased muscular activity of the alimentary canal; nevertheless, the increased exhalation of carbon dioxid cannot be attributed to this alone. It is also, and to a greater extent, dependent on the heat-producing activity of the digestive glands — as in the case of the salivary glands. In addition, some of the carbon dioxid is derived from oxidation, in the course of urea-formation, of a part of the carbon contained in the proteids. The quality of the food also has some influence. According to Magnus-Levy a proteid diet causes a much greater increase in the con- sumption of oxygen (about from 70 to 90 per cent.) than does carbo- hydrate food (which increases the consumption about 39 per cent.), or a fat-diet (which causes an increase of only 15 per cent.), as experiments on dogs show. A fasting adult weighing 50 kilos inspires in one hour eight liters of air for each kilo; he consumes 0.45 gram of oxygen, and forms 0.5 gram of carbon dioxid. The ingestion of food raises these figures to nine liters of air, 0.5 gram of oxygen and 0.6 gram of carbon dioxid. The deposition of fat following a carbohydrate diet, is attended with an increase in the amount of carbon dioxid given off. This results partly from combustion of the carbohydrates, and partly from their trans- formation into fat, during which process carbon dioxid is separated. The respira- tory quotient is also increased as a result of fat-formation following an abundant carbohydrate diet; the quotient under such conditions may even rise above 1.2. The absorption of oxygen is uninfluenced by direct injection into the 236 EXTENT OF THE RESPIRATORY EXCHANGE OF GASES. blood either of non-nitrogenous or of nitrogenous substances. The output of carbon dioxid changes to a certain extent in correspondence with the combustion of these substances by means of a constant quantity of oxygen. Hunger greatl}^ reduces the combustive processes in dogs; but in guinea-pigs it produces at most a small reduction in the consumption of oxygen. 8. The Number and the Depth of the Respirations have practically no influence on the formation of carbon dioxid, or on the oxidation- processes in the body, the latter being regulated rather by the tissues themselves through a mechanism as yet unknown. These factors, however, have been observed to exert an evident influence on the removal of the carbon dioxid already formed in the body. An increase in the number of respirations, the depth remaining the same, as well as an increase in their depth, the number remaining the same, results in an absolute increase in the output of carbon dioxid. The quantity seems relatively diminished, however, when viewed with reference to the amount of gases interchanged. Example: Number of Respirations IN EACH Minute Exchanged Volume OF Air. Contained _ COo _ Per cent. - COo. Depth of Respiration. Contained CO2 Per cent. — COo. 12 6,000 258 cu.cm. =4.3 P-c. 500 21 cu.cm. = 4.3 pc. 24 12,000 420 = 3-5 " 1 1000 36 •' = 3-6 " 48 24,000 744 = 3-1 " 1500 51 " = 3-4 " 96 48,000 1392 " = 2.9 " 2000 3000 64 " 72 •' = 3-2 = 2.4 Deep respirations, and also artificial respiratory movements, increase the absorption of ox^^gen into the blood to the point of saturation. Limitation of the supply of oxygen diminishes its consumption in the body in considerably greater measure tlian does hunger. Naturally, increased activity of the respirator}'' muscles causes in itself a greater interchange of gases. 9. Exposure to Light causes an increase in the excretion of carbon dioxid in frogs, mammals, and birds, even in frogs deprived of their lungs or of their cerebral hemispheres, or in those in which the spinal cord has been divided high up. At the same time the consumption of oxygen is increased. The same processes occur in individuals without eyes, though to a more limited extent. Rodents and birds show the maxi- mum in red light, toads in violet light. According to Aducco starving pigeons lose weight more quickly in the light than in the dark. Quincke demonstrated that certain tissues, such as leukocytes and parts of fresh tissues, attract more oxygen to themselves under the influence of light than in the dark. The nitrogenous metabolism of animals remains unchanged during exposure to light. The increased output of carbon dioxid is, therefore, to be attributed to an increased transformation of fat; hence, animals accumulate more fat when kept in the dark. 10. Blood-letting produces no diminution in the respiratory exchange of gases, but does cause an increase in the nitrogenous excretion. Pro- found anemic conditions diminish the interchange of gases. 11. Changes in the Atmospheric Pressure produce a slight diminu- tion in the interchange of gases if breathing is made easier; but if DIFFUSION OF GASES WITH IX TIIK RESPIRATORY ORGAN'S. 237 breathing is made more difficult, there is a slight increase. By inspira- tion of compressed air the aljsorption of oxygen is increased to an ex- ceedingh' small extent. In order to give off one gram of carbon dioxid, a smaller amount of air is needed at a low atmospheric pressure than with a high barometer. There is no diminution in the excretion of carbon dioxid on high mountains. The effects of artificially rarefied air and of the rarefied atmosphere of high altitudes are not the same. A rare- faction of air to 450 mm. of jiiercury still has no effect, the metabolic changes proceeding unaltered. In the air of high altitudes metabolism is increased, and respiration becomes more frequent and deeper. Ac- cording to A. and J. Loewy and Zuntz the greater amount of light at high altitudes is the exciting factor. 12. In the presence of artificially induced dyspnea, as by tightly compressing the thorax, the proteid metabolism is increased — the amount of urea being increased — and there is an increase in the excretion of oxalic acid, acetone, ammonia, and sulphur in the urine. Pathological. — According to the experiments of Grehant on dogs, it appears that intense inflammation of the bronchial mucous membrane will diminish the output of carbon dioxid, even if there be fever. In cases of diabetes the body is able to take up the necessary amount of oxygen, but the quantity of carbon dioxid given oft" is diminished, and the respira- tory quotient is low. Among the poisons, thebain increases the output of carbon dioxid, while mor- phin, codein, narcein, narcotin, and papaverin diminish it. Curare lowers the metabolism enormously, the absorption of oxygen falling about 35.2 per cent., and the excretion of carbon dioxid about 37.4 per cent. Section of the spinal cord has a similar eft'ect. DIFFUSION OF GASES WITHIN THE RESPIRATORY ORGANS. In the pulmonary alveoli the air is richest in carbon dioxid and poorest in oxygen. Further on, from the smallest bronchioles to the larger ones and then onward to the bronchi and the trachea, the respired air becomes, step by step, gradually more like the atmospheric air. Hence it is that if the expired air of a respiration be collected in two halves, the first half (coming from the larger air-passages) contains less carbon dioxid (3.7 volumes per cent.) than the second half (5.4 volumes per cent.). This inequality in the proportion of the gases at various levels of the respiratory organs necessarily causes a continuous diffusion of gases between the various levels, and also, finally, between the gases in the larynx and nasal cavities and the outside atmosphere. The carbon dioxid constantly diffuses from the depths of the air-vesicles toward the outer air, while the oxygen of the latter diffuses tow^ard the gaseous mixture in the pulmonary alveoli. This diffusion is doubtless assisted materially by the constant shaking of the respiratory gases by the cardio-pneumatic movements. During hibernation, and also in cases of apparent death of long duration, this must be the ^ only means for the exchange of gases within the lungs. Ordinarily, however, this mechanism is insufficient for the respiratory process; so that the ex- change of air produced by inspiration and expiration must be added to it. By this latter means atmospheric air is introduced into those parts of the lungs lying nearest to the large air-passages, from which and into which the diffusion-currents of oxygen and carbon dioxid pass more readily, on account of the greater differences in the tension of the gases. 238 INTERCHANGE OF GASES. If the inspired air contains a diminished quantity of oxygen, the necessary amount of oxygen can still be supplied to a certain extent by more rapid and deeper respirations. INTERCHANGE OF GASES BETWEEN THE BLOOD IN THE PUL- MONARY CAPILLARIES AND THE AIR IN THE ALVEOLI. This interchange of gases is accomplished almost exclusively by chemical processes, independently of the diffusion of gases. For the determination of the gaseous interchange it is first necessary to ascer- tain the tension of the oxygen and the carbon dioxid in the venous blood of the pulmonary capillaries. Pfliiger and "Wolffberg have accomplished this by cathe- terization of the lungs. An opening is made in the trachea of a dog, and an elastic catheter (Fig. 90, a) is introduced into the bronchus leading to the lower lobe of the left lung. In order to have the bronchus fit closely aroimd the catheter, the latter is made to pierce a rubber sac inflated by means of a communicating rubber-ball pump c. In this way no air from that part of the lung can escape at the side of the catheter. The tube is at first closed at its outlet, and the dog is allowed to breathe independently and as quietly as possible. After four minutes the alveolar air in the closed-off part of the lungs is in complete equilibriurn with the blood-gases. By means of a mercurial air-pump the air in the lungs is sucked out of the catheter (at b) and analyzed. The tension of the carbon dioxid and the oxygen in this air will indicate in an indirect way the tension of these two gases in the venous blood of the piilmonary capillaries. For the direct estimation of the gases in various specimens of blood, these gases are removed by shaking the blood with another kind of gas. The composi- tion of the mixture will indicate the proportions in which the blood-gases have been mixed, and will thus serve to determine their tension. It is desirable to use as much blood as possible with a small quantity of gas ; the amount of the latter should be about the same as that supposed to be present in the blood. In the following table are shown the tension and the percentage of oxygen and carbon dioxid in arterial and venous blood, as well as in the atmosphere and the air of the closed-off alveoli : I. V. Tension of O in arterial blood = Tension of O in the alveolar air of 29.6 mm. of mercur\"; increased by the catheterized limg = 27.44 mm. of warming; corresponding to a gaseous mercury; corresponding to 3.6 vol. per mixture containing 3.9 per cent, of O. cent. II. VI. Tension of COj in arterial blood = Tension of CO2 m the alveolar air 21 mm. of mercurv; corresponding to of the catheterized lung = 27 mm. of 2.8 vol. per cent. ' mercury; corresponding to 3.56 vol. per cent. III. Tension of O in venous blood = 22 Y^^- mm. of mercury; corresponding to 2.9 Tension of O in the atmosphere = vol. per cent. 158 mm. of mercur}'; corresponding to 20.8 vol. per cent. IV. Tension of COj in venous blood = VIII. 41 mm. of mercur}-; corresponding to Tension of COj in the atmosphere = 5.4 vol. per cent. ' 0-38 mm. of mercury; corresponding to from 0.03 to 0.05 vol. per cent. If the tension of the oxygen in the atmosphere (VII) be compared with that in venous blood (III) or in the alveoli (V) it will be seen that the absorption of oxygen into the blood during respiration can occur in the form of an equalization of tension. Likewise a comparison of the tension of the carbon dioxid in the atmosphere (VIII) with that in venous blood (IV) or with that in alveolar air (VI) might explain the INTERCHANGE OF GASES. 239 excretion of that gas in a similar manner. Nevertheless, the respiratory interchange of gases is a chemical process. According to v. Fleischl the concussion to which the venous blood is subjected on being pumped into the pulmonary arteries provides for a more ready escape of the carbon dioxid, a point that is of the greatest importance with respect to the respiratory process. The absorption of oxygen from the alveolar air for the purpose of oxidation of the venous blood in the pulmonary capillaries is a chemical process, as the gas-free hemoglobin in the lungs takes up oxygen to form oxyhemoglobin. That this absorption depends, not on diffusion of the gases, but on the atomic combination pertaining to the chemical process, is shown by the fact that the blood does not take up more oxygen when the pure gas is respired than when atmospheric air is respired; further, that animals that are made to breathe in a small, closed space will absorb into their blood all of the oxygen but traces, to the point of suffocation. If the respiratory absorption of oxygen were a diffusion-process, much more oxygen would have to be taken up in the first case in accordance with the partial pressure of the gas; while in the latter case such an extensive absorption could not take place. /^%^ ^~ Fig. 90. — Pulmonary Catheter. Even in highly rarefied air (high balloon-voyages) the absorption of oxygen remains independent of the partial pressure. However, in a space containing rarefied air a longer time and a more vigorous shaking are required for the absorption of oxygen by the blood at the ternpera- ture of the body; that is, the absorption of oxygen is not diminished, but is retarded. ' In this way is explained the death, for example, of the aeronauts Sivel and Croce-Spinelli, during an ascension to a height where the atmospheric pressure is only one-third the normal. The laws of diffusion come into play in connection with the absorption of oxygen onlv to the extent that the oxygen, in order to reach the. red blood-cor- puscles, must, first of all, diffuse into the plasma, where it immediately enters into chemical combination with the erythrocytes. The excretion of carbon dioxid from the blood into the alveolar air could also be well represented in the form of an equalization of ten- sion (diffusion) ; but here again chemical processes are operative, althotigh they have not yet been investigated in many details. The absorption of oxygen by the erythrocytes produces at the same time an expulsion 240 RESPIRATORY GASEOUS EXCHANGE AS A DISSOCIATION PROCESS. of the carbon dioxid. This is proved by the fact that the whole of the carbon dioxid is more easily expelled from the blood if oxygen be at the same time introduced than if all gases are withdrawn. The result is different in the case of the serum, which when subjected to a vacuum will give up only a part of the carbon dioxid, while from 5 to 9 volumes per cent, are still retained ; the latter can be released only by the addition of acids. As this carbon dioxid, which exists in firm chemical combina- tion, also escapes on addition of erythrocytes, the corpuscles must contain a substance that acts like an acid in expelling the carbon dioxid. THE RESPIRATORY GASEOUS EXCHANGE AS A DISSOCIATION PROCESS. Some forms of gas enter into true chemical combination wdth other substances when associated at a certain high degree of partial pressure of the gas in question. This chemical combination, however, is again dissolved as soon as the partial pressure diminishes and reaches a certain low level. Hence, by alternately raising and lowering the partial pres- sure, a chemical combination of the gas can be formed and again broken up. This process is called dissociation of gases. The minimal partial pressure is constant for the various substances and gases in question; but still the temperature, as in the case of the absorption of gases, has a marked influence ; namely, increase in temperature diminishes the partial pressure at which dissociation occurs. Calcium carbonate may be taken as an example to illustrate the dissociation of gases. When this substance is heated in the air to 440° C, carbon dioxid escapes from the chemical combination; but it is gradually taken up again by the calcium, after cooling has taken place. The chemical combinations containing carbon dioxid, and also those containing oxygen, namely, the oxyhemoglobin and the carbon-dioxid compounds, behave in a similar manner within the blood-stream; these also exhibit the process of dissociation. If these gaseous combinations are placed under conditions in which the partial pressure of these gases is exceedingly low (that is, when they are present in small amounts), the compounds are dissociated; that is, they give off carbon dioxid or oxygen, as the case may be, to the surrounding medium. If, however, they are now again brought into a mediuin in which, on account of an abundance of these gases, the partial pressure of the oxygen or the carbon dioxid is high, they are again taken up in chemical combination by these gases. The hemoglobin of the blood in the pulmonary capillaries finds a plentiful supply of oxygen in the alveoli; therefore, it combines with the oxygen, under the high partial pressure of that gas, forming the chemical compound ox3iiemoglobin. On its way through the capil- laries of the greater circulation, the hemoglobin comes in contact with tissues poor in oxygen; the oxyhemoglobin is dissociated, its oxygen passes to the tissues, and the blood, with gas-free or reduced hemoglobin, returns to the right heart and thence to the lungs, in order to take up oxygen anew. The carbon dioxid meets the circulating blood in largest amount in the tissues. The high partial pressure of the gas in this situation causes the constituents of the blood to enter into chemical combination w4th the carbon dioxid. In the lungs, however, the partial pressure for carbon dioxid is low, the gas is dissociated, and it is excreted. It is CUTANEOUS RKSPIRATIOX. 241 thus evident that, as concerns the blood, the giving up of oxygen and the absorption of carbon dioxid in the tissues, and, conversely, the absorption of oxygen and the giving up of carbon dioxid in the lungs, are processes that take place simultaneously. CUTANEOUS RESPIRATION. Method. — If a human being or an animal is placed in the chamber of a respira- tion-apparatus (such as Scharling's or v. Pettenkofer's) , and the gases passing to and from the lungs are conducted through a respiratory tube, so that none of the gaseous interchange of the lungs enters the chamber, but only the transpiration of the skin, information can thus be obtained concerning the cutaneous respira- tion. The procedure of leaving the whole head of the subject outside the chamber, the neck being fixed air-tight in its wall, is less correct. The cutaneous respiration of a circumscribed part of the body — for instance, of an extremity — may be studied by enclosing the part in an air-tight cylinder similar to that used for the arm in employing the plethysmograph. In twenty-four hours a healthy man loses through his skin — which contains the respiratory organ in the moist sweat-glands, richly supplied with blood-vessels — Jy of his entire body- weight, which is greater than the loss through the lungs, since it bears a ratio to the latter of 3:2. Of this large loss of weight only from 8 to lo grams are referable to the carbon dioxid given off. The remainder is comprised in the evaporation of water. Elevation of the surrounding temperature is attended with an increase in the amount of carbon dioxid given off. The excretion at between 29° and 33° C. amounts to 8 grams in twenty- four hours; above ^3° C. it is 20 grams (sweating begins at this point); and at 38.4° C. the amount is 27.5 grams. Active muscular exercise likewise produces an increased excretion. Absorption of oxygen by the skin has also been demonstrated, the amount absorbed being either equal to the volume of carbon dioxid given off, or a little less. As the excretion of carbon dioxid by the skin is only about ^^^ of that by the limgs, and as the absorption of oxygen is only about -^^ of that by the lungs, it is evident that the respiratory activity of the skin is in any event but slight. "It is uncertain whether or not the skin gives off gaseous nitrogen or ammonia. According to Funke the skin secretes hourly 0.0824 gram of soluble nitrogen, this quantity being increased in the presence of renal disease. According to Rohrig, the excretion of carbon dioxid and of water exhibits certain daily variations. It is increased during digestion, after the application of cutaneous irritants, in the presence of obstruction to pulmonar>' respiration, of hyperemia of the skin, and when the blood contains an increased number of erythrocytes. In warm-blooded animals, with thick, dry epidermoid structures, the cuta- neous interchange of gases is still less than it is in man. In frogs and other am- phibia, with a constantly moist skin, cutaneous respiration becomes highly impor- tant. The skin here supplies from two-thirds to three-fourths of the total quantity of carbon dioxid excreted, and in hibernating frogs the proportion is still greater. The skin is, therefore, a more important respirator^' organ than the lungs. Im- mersion in oil will, consequently, kill these animals more readily than will ligation of the lungs. INTERNAL RESPIRATION OR TISSUE-RESPIRATION. The terms iiiternal respiratioi and tissue-respiration are used to desig- nate the interchange of gases between the capillaries of the greater cir- 16 242 IXTERXAL RESPIRATION' OR TISSUE-RESPIRATION. culation and the tissues. Those organic constituents of the tissues that contain carbon are subjected during their vital activity to a process of gradual oxidation, with the formation of carbon dioxid. Hence, the following inferences may be drawn : I. The chief seat for the absorption of oxygen and the formation of carbon dioxid is to be found within the tissues themselves. That the oxygen rapidly penetrates from the capillary blood into the tissues is shown by the fact that this blood rapidly becomes richer in carbon dioxid and poorer in oxygen, while oxygenated blood, kept warm out- side the body, changes much more slowly and incompletely. Further, if fresh pieces of tissue be placed in defibrinated blood rich in oxygen, the oxygen rapidly diminishes. Also, the circumstance that frogs de- prived of their blood exhibit almost as great an interchange of gases as do normal animals indicates that the gaseous interchange takes place in the tissues themselves. Moreover, if the chief seat of oxidation lay, not in the tissues themselves, but in the blood, then, if oxygen were withheld from the blood (during suffocation), those reducing substances that consume the oxygen in the process of oxidation should accumulate in the blood. This is not the case, for even the blood of suffocated animals contains only a trace of reducing substances. The absorption of oxA'gen into the tissues may occur in the form of a temporary storing of the gas, perhaps with the formation of intermediate lower oxida- tion-products. This is followed by a period of more rapid separation of carbon dioxid. Thus, the absorption of oxygen and the excretion of carbon dioxid in the tissues do not necessarily proceed on parallel lines and to the same extent. A clear picture of the development of carbon dioxid in the tissues is furnished by the fact that a larger amount of this gas is found in the cavities of the body and in their gases and fluids than in the blood of the capillaries. Pfliiger and Strassburg found the tension of the carbon dioxid (in millimeters of mercury) as follows ; In arterial blood 21. 28 mm. In bile 50.0 mm. " the peritoneal cavity, ... .58.8 " " hydrocele-fiuid, 46.5 " " acid urine, 68.0 The abundance of carbon dioxid in these fluids, as compared with that in the blood, can arise only from the addition to them of the carbon dioxid generated in the tissues. In the lymph of the thoracic duct the tension of the carbon dioxid (from 33.4 to 37.2 mm. of mercury) is, indeed, greater than in the arterial blood, but it is still considerably less than in the venous blood. This fact does not, however, justify the conclusion that only a small quantity of carbon dioxid is formed in the tissues from which the lymph is collected. It rather permits the inference, either that the lymph possesses less -attraction for the carbon dioxid formed in the tissues than does the capillary blood, where chemical forces are active in the production at least of a partial combination of the gas: or that in the course of the slow lymph-current the carbon dioxid is partiahy given back to the tissues bv equaliza- tion of tension: or, finally, that carbon dioxid is formed independently in the blood. Furthermore, it is to be pointed ovit that those muscles that are known to be the principal producers of carbon dioxid furnish this gas abundantly to the blood, their tissues being relatively poor in lymph- vessels. The amount of uncombined, free carbon dioxid, capable of being pumped out, in the fluids and gases mentioned indicates that the carbon dioxid passes over from the tissues into the blood in an uncombined free state. However, Preyer believes that the gas is carried over into the blood of the veins also in chemical combination. The interchange of oxygen and carbon dioxid varies considerably in the differ- ent tissues. In the first rank belong the muscles, which in a state of activity INTERNAL RESPIRATION OR TISSUE-RESPIRATION. 243 excrete a large amount of carbon dioxid and consume much oxygen. The inter- change of gases in tissues is increased during their activity. The secreting saHvary glands, kidneys, and pancreas are no exception to this rule; for although, in the secreting state, bright red blood flows away from them through the dilated vessels, still this apparently relative diminution in the carbon dioxid of the venous blood is more than compensated for by its absolute increase through the marked increase in volume of the blood passing through these organs. Active reduction-processes take place in most tissues. If coloring-matters, such as alizarin-blue, indophenol-blue, or methylene-blue, be introduced into the blood of animals, the tissues will soon be stained. Those organs that have an especially strong affinity for oxygen (such as the liver, the cortex of the kidneys, and the lungs), abstract oxygen from these coloring-matters, and change them into colorless reduction-products. The pancreas and the submaxillary gland have almost no reducing power. 2. The blood itself, like all of the tissues, is a seat for the consumption of oxygen and the formation of carbon dioxid. This is proved by the fact that blood removed from the body quickly becomes poorer in oxygen and richer in carbon dioxid; further, by the circumstance that in the oxygen-free blood of asphyxiated persons and in the blood-corpuscles there are always found small quantities of reducing agents, which become oxidized on the addition of oxygen. At all events, this gaseous inter- change is but slight as compared with that occurring in all the other tissues. It is incontestable that the walls of the blood-vessels, by means of their contained muscular fibers, also consume oxygen and produce carbon dioxid, although this process is so insignificant that the blood undergoes no visible change in color throughout its arterial course. C. Ludwig and his pupils have proved by specially adapted experiments that transformation into carbon dioxid can actually occur within the blood. If sodium lactate, which is easily oxidized, be mixed with blood, and this mixture be sent through the blood-vessels of a recently excised organ that is still alive (such as the kidnej^ or the lung) , a more abundant consumption of oxygen and formation of carbon dioxid will occur in this mixed blood than would occur in pure blood similarly transfused. 3. It may in advance be concluded as probable that the living pulmonary tissue also consumes oxygen and generates carbon dioxid. By passing arterial blood through lungs that have been deprived of air, C. Ludwig and MuUer succeeded in demonstrating a diminution in the oxygen and an increase in the carbon dioxid. Bohr and Henriques con- cluded further from their experiments, in which they restricted to a considerable degree the circulation of blood through the bodily tissues, and found no significant diminution in the excretion of carbon dioxid from the lungs, that the pulmonary tissue is not limited to a mere excretion and absorption of gases, but that it besides possesses the prop- erty of forming carbon dioxid from substances that are derived from the other tissues. In like manner they assumed that oxygen is actively taken up by the lungs; that is, the lungs secrete carbon dioxid and absorb oxygen like a secreting gland. As the total amount of carbon dioxid and oxygen in the whole volume of blood at any one time is only about 4 grams, while the amount of carbon dioxid excreted daily is 900 grams, and the amount of oxygen absorbed is 774 grams, it is evident that the interchange of gases pro- ceeds with great rapidity, that the absorbed oxygen must be consumed and the carbon dioxid formed must be excreted quickly. As a restilt of an increased introduction of acids into the body there is a diminution in the consumption of oxygen (and in the production of heat), which in a high degree may give rise to an internal asphyxia of the tissues. 244 RESPIRATION IN A CLOSED SPACE. RESPIRATION IN A CLOSED SPACE, OR WITH ARTIFICIAL CHANGES IN THE AMOUNTS OF OXYGEN AND CARBON DIOXID IN THE RESPIRED AIR. Respiration in a closed space results in (i) a gradual diminution of the oxygen, (2) a simultaneous increase of the carbon dioxid, and (3) a diminution in the volume of gas. If the space is only of moderate size, the animal consumes the oxygen almost completely, the blood becomes almost free of oxygen, and death finally results, accompanied by asphyxial convulsions. The absorption of oxj^gen occurs, therefore, through chemical combination, independently of the laws of absorption. In larger closed spaces considerable accumulation of carbon dioxid takes place before the oxygen is diminished to such an extent that life is threatened. As the carbon dioxid can be excreted from the body only when its tension is greater in the blood than in the surrounding air, there will be retention of the gas as the amount expired into the enclosed space increases; and, finally, a return of the carbon dioxid into the body may take place. This occurs while the oxygen is still sufficient to support life. Death results, therefore, directly from poisoning by carbon dioxid, with the symptoms of dyspnea of short duration, to which are added stupor and subnormal temperature. This manner of death has been ob- served in rabbits, after they had reabsorbed some of the carbon dioxid that had been excreted previously by them. In pure oxygen, or in an atmosphere rich in oxygen, animals breathe in a per- fectly normal manner. A little more oxygen is absorbed, but still the amount of carbon dioxid excreted is not increased. In closed spaces filled with oxygen, animals finally die through the reabsorption of their excreted carbon dioxid. Rabbits have thus been observed to die after they had absorbed an amount of carbon dioxid equal to half the volume of their body, although the enclosed air still contained over 50 per cent, of oxygen. Human beings and animals can still breathe an air-mixture containing only 9 per cent, of oxygen; deepened respirations set in at 10 per cent., and discomfort at 8 per cent. Animals breathe with difficulty and lose consciousness at 7 per cent.; pronounced dyspnea makes its appearance at 4.5 per cent., and quite rapid suffocation at 3 per cent. The air expired by man under normal conditions still contains between 14 and 18 per cent, of oxygen. Mammals placed in a gaseous mixture poor in oxygen consume slightly less oxygen. The metabolism of animals is unchanged by variations in the amount of oxygen in the respired air between the limits of 10.5 and 87 per cent. If the oxygen falls below 10.5 per cent., there is an increase in the excretion of nitrogen, carbon dioxid, lactic acid, and oxalic acid through the urine. If the amount of carbon dioxid in the inspired air be increased, the respiratory movements are increased, but the excretion of carbon dioxid and the absorption of oxygen are diminished. Inspiration is actively stimulated by a deficiency of oxygen, as well as by an excess of carbon dioxid. The dyspnea that is induced under the condition first stated is prolonged and severe, while under the second condition the respiratory activity soon diminishes. A deficiency of oxygen further causes a greater and more prolonged rise in the blood-pressure than does an excess of carbon dioxid. Finally, the consumption of oxygen by the body is less restricted b}" a diminution of the oxygen in the air than by an excess of carbon dioxid. Death from limitation in the supply of oxygen is preceded by violent irritative phenomena and convul- sions, which are absent in case of death from excess of carbon dioxid. Finally, in conjunction with poisoning by carbon dioxid, the excretion of this gas is greatly diminished. If animals be supplied with a gaseous mixture similar to the atmosphere, but in which the nitrogen is replaced by hydrogen, they breathe quite normally; the hydrogen of the mixture does not vmdergo any noteworthy change in volume. Increase or diminution in the amount of nitrogen in the air simply causes a greater or lesser absorption of the gas by the fluids of the body. CI. Bernard found that if an animal be made to respire in a closed space, it became, up to a certain point, accustomed to the successive deterioration of the air. If he placed a bird under a glass bell-jar, it lived for several hours; but if, before its death, another bird were added from the fresh air, the latter imme- diately died in convulsions. RESPIRATION OF FOREIGN GASES. 245 It is remarkable that frogs, when placed in air free from oxygen, will for several hours give off just as much carbon dioxid as in air containing oxygen, and this without any obvious disturbances. Hence, the formation of carbon dioxid must be independent of the absorption of oxygen, and the carbon dioxid must be set free in the decomposition of other compounds. Finally, however, complete motor paralysis sets in, while the circulation for a time remains undisturbed. RESPIRATION OF FOREIGN GASES. No gas is able to support life without a sulficient admixture of oxygen. Hence, without oxygen, all other gases will quickly cause suffocation (in two or three minutes) . even though they be in themselves harmless and indifferent. Completely indifferent gases are represented by nitrogen, hydrogen, and marsh-gas (CH4). The blood of an animal breathing any of these gases yields no oxygen to it. Poisonous Gases. (a) Tliose displacing oxygen: (i) Carbon monoxid (CO). (2) Hydrocyanic acid (CNH) displaces(?) oxygen from the hemoglobin, with which it forms a more stable compound, and it thus kills with great rapidity. Further, it prevents the forma- tion of ozone from the oxygen in the blood. Blood-corpuscles charged with hydro- cyanic acid lose the property of decomposing hydrogen dioxid into water and oxygen. (b) Narcotic gases: (i) Air containing o.i per cent, of carbon dioxid has been designated as "bad air"; still, the discomfort experienced in such an atmosphere (for example, in overcrowded rooms) arises rather from offensive exhalations of unknown character than from the carbon dioxid itself. Air containing i per cent, of carbon dioxid produces marked discomfort; with 10 per cent, life is endangered, and with a higher percentage death ensues, accompanied by symptoms of coma. (2) When nitrous oxid (NjO) is respired, mixed with one-fifth its volume of oxy- gen, it causes in from one and one-half to two minutes a short, evanescent, especially pleasurable state of intoxication (laughing-gas), which is followed by an increased excretion of carbon dioxid. (3) Pure ozonized air produces similar effects; it also causes short, agreeable excitement, then drowsiness and rapidly transient sleep. (c) Reducing gases, (r) Hydrogen sulphid (HjS) rapidly deprives the erythro- cytes of all oxygen, forming sulphur and water by oxidation; death occurs qtiickly, even before the gas can effect any change in the hemoglobin, with the formation of sulphur-methemoglobin. In addition, hydrogen sulphid forms in the blood sodium sulphid from sodium carbonate, the new compound rapidly causing death. (2) Hydrogen pJwsphid, phosphin (PH3) , is oxidized in the blood to form phosphoric acid and water, with decomposition of the hemoglobin. (3) Hydrogen arsenid, arsin (AsHj), and hydrogen antimonid, stibin (SbHj"), act like hydrogen phosphid, but in addition they allow the hemoglobin to pass out of the stroma, so that the excreta, as the urine, contain hemoglobin. (4) Cyanogen (C2X2) withdraws oxygen and further decomposes the blood. Irrespirable gases cannot be inspired at all, as they cause reflex spasm of the glottis on entering the lar\-nx. If introduced forcibly into the air-passages, they give rise to violent inflammatory processes, followed by other disturbances and death. Included in this class are hydrochloric acid (HCl), hydrofluoric acid (HFl), sulphurous acid (SO,), nitrous acid (N'204) , nitric acid (N2O5), ammonia (XH3), chlorin, fluorin, iodin, bromin, undiluted ozone, and pure carbon dioxid. OTHER INJURIOUS SUBSTANCES IN THE INSPIRED AIR. Particles of dust are among the impurities of the atmosphere that are ham;iful in large quantities and after long-continued action. Most of these particles are expelled externally by means of the ciliated epithelium of the respiratory organs, whose cilia wave toward the larynx. Some of the dust-particles, however, pene- trate the epitheHum of the air- vesicles, and thus reach the interstitial pulmonary tissue, from which they frequently pass through the lymph- vessels to the lymphatic glands of the lungs. For this reason coal-dust is found deposited in the lungs of all elderly persons, blackening the alveoli. In moderate amounts these sub- stances are harmless in the tissues; but if the deposits become large, they may cause pulmonan.' diseases that may finally lead to disintegration of the lungs. The particles penetrate between the alveolar epithelium into the interstitial pul- monary- tissue, and then into the lymphatic vessels and glands. In many trades 246 RENEWAL OF THE AIR IN LIVING-ROOMS. the work must be done in a dusty atmosphere, and they are thus rendered detri- mental to heahh. Charcoal-burners, grinders, stone-cutters, file-cutters, weavers, spinners, tobacco-workers, sawyers, millers, bakers, and others suffer from various affections of the lungs, induced by the dust of their trades. During a year's work a workman in a horse-hair mill inhales 15 grams of dust, in a saw-mill 27 grams, in a woolen mill 30 grams, in a grinding mill 37.5 grams, in an iron-foundry 42 grams, in a snuff-factory loS grams, in a cement-factory 336 grams. The ciliated epithelitim is exceedingly sensitive to mechanical excitation. The coordinated, continuous movement of the cilia on a larger surface does not depend wholly upon an external (mechanical) conduction of the stimulus, but also upon an internal conduction (as in the nervous system). There is no doubt that with the inspired air the germs of infectious diseases are often taken into the respiratory organs, whence they gain entrance into the body. Thus, the diphtheria-bacillus becomes localized in the pharynx and the larynx, the glanders-bacillus in the nose, the germ of whooping-cough in the bronchi, the microbes of hay-fever and ozena in the nose, the influenza-bacillus in the air- Ciliated epithelium Squamous cells J « Intermediary' forms S^U$'^^^Y^' I^Jier layer Fig. 91. — Stratified Ciliated Cylindrical Epithelium of the Larynx (Horse) (after Toldt). passages, the pneumonia-bacillus in the air-vesicles. The cause of tuberculosis, the bacillus tuberculosis, enters the air-fllled pulmonary tissue with the dust of tuberculous sputa, and may spread from that focus through all of the tissues. In a similar manner leprosy arises from the bacillus leprse. The cause of malaria, the plasinodium malariae possessed of ameboid movement, reaches the blood partly through the respirators' organs, changes the hemoglobin within the red corpuscles into melanin, and causes their destruction. In the same way the blood is invaded by the exciting agents of smallpox (micrococcus vaccinas) , the spirillum of relapsing fever, the still little known microbe of measles, and the as yet undiscovered germ of scarlet fever, etc. Many disease-germs enter the mouth with the air, others with the food, and are swallowed, so that they undergo development in the intestinal tract. This is true of cholera (comma-bacillus), dysentery, typhoid fever (bacillus typhosus), and amebic enteritis (amoeba coli; the amoeba coli mitis is less virulent, and the amoeba intestina vulgaris is harmless). In cattle, anthrax arises in the same way from bacterium anthracis. RENEWAL OF THE AIR IN LIVING-ROOMS (VENTILATION). EXAMINATION OF THE AIR. Fresh air is one of the most necessary conditions for salutarj' existence on the part both of the healthy and of the sick. It may be assumed that a sufficient renewal of the air in living-rooms will be assured, if 800 cu. ft. of space be allowed for every inmate of a room, and about 1000 cu. ft. for everj' sick person. The neces- sary space for the inmates of dwellings, schools, barracks, penal institutions, and hospital-wards should be measured accordingly, and the allotment of space to the individuals should be made only in this proportion. However, this standard has been materially departed from in various countries. In overcrowded spaces the amount of carbon dioxid at first increases. The normal amount in the air (0.5 in 1000) has been found increased in comfortable living-rooms to from 0.54 to 0.7 in 1000; in badly ventilated sick-rooms to 2.4 in 1000; in overcrowded auditoriums to 3.2 in 1000; in pits to 4.9 in looo; in school-rooms to 7.2 in 1000. Although it is not the amount of carbon dioxid RENEWAL OF THE AIR IN' LIVING-ROOMS. 247 that makes the air of crowded spaces injurious, but rather the exhalations from the outer and inner surfaces of the body, which at the same time render the air offensive to the sense of smell, still the amount of carbon dioxid is an indication of the degree of vitiation of the atmosjihere. To determine whether or not the ventilation is sullicient in spaces crowded with individuals, the carl)on dioxid of the air should be estimated ciuantitatively at the time of occupation; hence, in school-rooms, if possible, shortly Ijcfore the close of the school-session, or in sick- wards or dormitories (barracks) shortly before daybreak. As a good, comfortable room-atmosphere contains less than 0.7 of carbon dioxid in 1000, the ventilation of a space must be considered insuflicicnt if more than 1.0 in 1000 is found. The atmosphere contains only 0.0005 cubic meter of carbon dioxid in 1 cubic meter of air, and an adult produces hourly 0.0226 cubic meter of carbon dioxid. Therefore, it will be found on calculation that ventilation must supply 113 cubic meters (for a child 60 cubic meters) of fresh air hourly for each person if the carbon dioxid in the living-room is to be kejjt below 0.7 in 1000 — -0.7 : 1000 = (0.0226 -f- x X 0.0005): x; hence, x = 113. If the amount of carVjon dioxid in the air of a room be allowed to reach i.o in 1000, then an hourly ventilation of 45 cubic meters is sufficient for an adult, and 24 cubic meters for a child. The following method is employed to determine whether a living-room has sutTficient ventilation. A large quantity of carbon dioxid is generated in the room, as much as i or 2 liters hourly for every cubic meter of space. The burning of stearin-candles may be employed as the source of carbon dioxid, each candle producing 12 liters of gas in one hour: a gas-burner supplies 100 liters an hour; an adult man produces 22.6 liters by respiration, and a school-child 12 liters hourly. If suflicient carbon dioxid has been produced at the end of an hour, the generator is removed, and the first estimation of carbon dioxid in the air is made, according to the method described later on. At the end of another hour, during which the windows and doors are kept closed, the second estimation of carbon dioxid is made. The amount of fresh air that has entered by ventilation during this hour is calculated by the following formula: C = 2.3 X m X log. ^^^^, in q a which C represents the volume in cubic meters of fresh air that has entered by- ventilation in one hour, m the volume of room-space in cubic meters, p the amount of carbon dioxid contained in i cubic meter of the air in the room at the first estimation, expressed in cubic meters, q the amount of carbon dioxid in each cubic meter, found at the second estimation and expressed in cubic meters, a the carbon dioxid in atmospheric air = 0.0005 cubic meter in i cubic meter of air. Example: In a school-room, containing 40 children, the first estimation of car- bon dioxid is made shortly before the close of school. If the result be 2 in 1000, it will indicate the presence of 0.002 carbon dioxid in i cubic meter of air. After the children have gone, the windows and doors are again closed, and the second analogous estimation is made at the end of an hour. If the restilt be i in 1000, there will be 0.00 1 carbon dioxid in i cubic meter of air. The size of the school- room is 600 cubic meters. The quantity of fresh air that has entered the space during the hour can be estimated according to the foregoing formula: C = 2.3X 600 X log. ^:^^j:^^:22Sls = 1380 X log. °-^^^ =1380 X log. 3 = 1380 X o.ooi — 0.0005 0.000s 0.477 12 13 = 658.3 cubic meters. Hence, 658.4 cubic meters of fresh air have entered the school-room by ventilation. As one child requires 60 ctxbic meters of fresh air hourly, the 40 pupils require 40 X 60 = 2400 cubic meters of fresh air in one hour; but, as a matter of fact, the ventilation of this space amounts to only 658.4 cubic meters; therefore, 1741.6 cubic meters are still wanting. Hence, either a better ventilation must be provided, or fewer children should be allowed to attend the school. A ventilation that amounts to more than three times the room-space hourly will be found to give rise to an unpleasant draft, and is, there- fore, often directly harmful in winter. For the school-room in question containing 600 cubic meters of space, only 1800 c^ibic meters of ventilation hourly would be permissible; hence, there is only space in that room for at most 30 pupils (30 X 60 = 1800). As the space receives only 658 cubic meters of ventilation hourly, provision must be made by better ventilation for the addition of 1 142 cubic meters more of fresh air; but without further ventilation place could be found in the school for only 11 children (658 -r- 60). In ordinary living-rooms, in which the necessary space (800 cu. ft.) is allowed for every inmate, the air is sufficiently renewed by the numerous pores possessed by the walls of the rooms, as well as by the going in and out, and further, in win- 248 REXEWAL OF THE AIR IX LI VIXG-ROOMS. ter, by stoves (a well-heated stove providing a ventilation of from 40 to 90 cubic meters of air hourly). That this ventilation is sufficient is proved by the fact that the amount of carbon dioxid in the room remains constant. When there is a more considerable difference between the temperature in the room and that outside (as in winter), the ventilation is more than sufficient. If. however, the cubic space allotted to each inmate is too small, as in over- crowded hospitals, narrow ship-quarters, etc., then the necessary change of air must be provided for by means of contrivances for artificial ventilation. The same must be done if noxious exhalations are given off by the sick. Above all, however, it is to be noted that the natural ventilation through the pores of walls is greatly limited if they be damp. At the same time, damp walls are prejudicial to health by reason of their greater conduction of heat, and also because the germs of infectious diseases can develop in them, as in moist ground generally. Ventilation maj' be accomplished either by aspiration, the exchange of air being brought about by suction-power; or by pulsion, the fresh air being pumped into the room. The carbon dioxid contained in the air of a living-room ma}^ be estimated as follows: A baryta-solution is prepared, containing 10 grams of crystallized barium hydrate and 0.5 gram of barium chlorid in i liter of water. A large, dry. accurately graduated, 6-liter flask is filled with air from the room to be in- vestigated, by blowing the air for some time down to the bottom of the flask by means of a bellows. Then, by means of a pipet 100 cu. cm. of the baryta-solution are allowed to nin into the flask, naturally displacing 100 cu. cm. of the air. The flask is then closed with a rubber cap, and is allowed to stand for two hours, being shaken occasionally. In this way all the carbon dioxid is absorbed by the baryta-solution. Then, 25 cu. cm. of the clear, supernatant flmd are withdrawn into a medicine-bottle, and are titrated with a normal oxalic-acid solution from a graduated buret, until a drop of the mixture, when placed upon turmeric paper, does not form a brown stain, that is until the reaction is neutral. A few drops of a solution of 0.2 gram of rosolic acid in 100 cu. cm. of dilute alcohol may also be added to the bar^'ta-solution in the medicine-bottle, producing a red coloration. When oxalic acid is added, the mixture is decolorized b}' the slightest excess of this acid. To prepare the normal oxalic-acid solution, 2.8636 grams of pure, cry-stallized. undecomposed oxalic acid, dried by having stood over concentrated sulphuric acid under a glass bell-jar for four hours, are dissolved in i liter of water; I cu. cm. of this solution is equivalent to i mgm. of carbon dioxid. The number of cubic centimeters of acid-solution added to the baryta-solution is noted. Now, 25 cu. cm. of the original bar\'ta-solution, with which nothing has been done, are titrated in like manner with the normal acid-solution to the point of neutralization; here also the amount of the acid-solution added is noted. By subtraction the dift'erence is found between the amounts of normal acid-solution added in both titrations. Each cubic centimeter of this dift'erence is equivalent to i mgm. of carbon dioxid, and the resulting value must be multiplied by 4, in view of the fact that only 25 cu. cm. of the 100 cu. cm. of bar\-ta-solution were titrated. The result gives the milligrams of carbon dioxid in six liters minus 100 cu. cm. of air. The milligrams of carbon dioxid thus determined are converted into cubic centimeters by mtdtiplying them by 0.508 (as 0.508 cu. cm. of carbon dioxid, at 0° C. and 760 mm. of barometric pressure, weighs i mgm.). The volume of the air is further reduced to 0° C. and 760 mm. of barometric pressure. This is done according to the formula V, = ; — ^^ , in which V, represents the re- ^ 760. (i + 0.003665.1) ' ^ duced volume desired, V the volvmae of air taken in the flask for the experi- ment, B the barometer-reading taken at the time of the experiment, and t the temperature in the investigated room. By this reduction-procedure the results can be obtained in percentages for possible comparisons. Example: Twenty-five cu. cm. of the bar>-ta-solution are neutralized by means of 24.6 cu. cm. of the oxalic-acid solution: 25 cu. cm. of the bar^^ta-solution after the absorption of carbon dioxid (taken from the experiment-flask) are neutralized by means of only 21.5 cu. cm. of the oxalic-acid solution. The dift'erence between them. 24.6 — 21.5 =3.1, represents 3.1 mgm. of carbon dioxid, which have been absorbed in the 25 cu. cm. of baryta-solution. Accordingly, there are contained in the 100 cu. cm. of bar>'ta-solution employed 12.4 mgm. of carbon dioxid (4 X 3.1) • If it be assumed that the large flask of air contains 4100 cu. cm., of which 100 cu. cm. have been displaced by an equal volume of barj'ta-solution that has been run in, so that there remains a volume of air equal to 4000 cu. cm.; NORMAL FORMATION OF MUCUS IN THE AIR-PASSAGES. 249 and if, at the time of the experiment, the temperature of the Uving-room was 20° C, and the barometer-reading 750 mm., then the reduced volume of air corre- sponding to the 4000 cu. cm. is V, = 4000 X 75° _ . = ,6^3 cu. cm., in which ' 760 X (l -r 0.00366s X 20) are contained 12.4 mgm. carbon dioxid. One mgm. of carbon dioxid, how- ever, equals 0.508 cu. cm.; hence, there were in 3678 cu. cm. of air 6.299 cu. cm. of carbon dioxid (12.4 X o-5o8). In 1000 cu. cm. air this amounts to 1.7 cu. cm. (according to the formula x : 1000 = 6.299 : 3678), or r.7 of carbon dioxid in 1000. NORMAL SECRETION OF MUCUS IN THE AIR-PASSAGES. THE EXPECTORATION (SPUTUM j. The mucous membrane of the respiratory tract is covered by a thin layer of mucus. This mechanically hinders further formation of mucus by preventing the usual irritation of the air and dust. Additional mucus is secreted only in so far as it is rendered necessary to replace that lost by evaporation. As a rule, increased circulation of blood in the tracheal mucous membrane is attended with increased secretion. Division of the nerves on one side (in the cat) gives rise to redness on the same side, with increased secretion. On "catching cold" (for instance, as a result of covering the abdomen with ice) the mucous membrane first becomes completely pale, and then deep red, with marked increase in the secretion. Injection of sodium carbonate and ammo- nium chlorid restricts the secretion. The local application of aliim, silver nitrate, or tannic acid dries the mucous membrane, so that the epithelium is cast off. Apomorphin, emetin, and pilocarpin actively stimulate the secretion; atropin and morphin limit it. Even under normal conditions hawking and coughing will cause the expectoration of slimy, viscid material, which may be derived from the entire respirator}^ tract, and is always mixed with a little saliva. In the presence of catarrhal conditions or of more serious disease the expectoration becomes more profuse, and is often mixed with charac- teristic products. It contains: 1. Epithelial cells, especially squamous cells from the mouth and the throat (Fig. 92, 8), more rarely alveolar epithelium (2), still more rarely ciliated epithelium (7) from the larger air-passages. Not rarely changes are found in. the epithelium as a result of maceration, including the cylindrical cells that have already lost their cilia (6) and contain swollen nuclei. Alveolar epithelium (2), with a diameter from two to four times that of a leukocj'te, is found especially in the morning-sputum, but only in that from per- sons over 30 years of age. In younger persons its presence indicates diseased conditions of the pulmonary parenchyma. Alveolar epithelium is found also in a state of fatty degeneration and filled with pigment-granules (3); also in the form of myelin-degenerated cells (4), that is, cells filled with clear refractive droplets of varying size, some being colorless, and some having absorbed pigment- granules (dust -particles). Also mucin in myelin-forms, that is, in the form of coagulated nerve-substance, is found constantly in the sputum (5). Mucus is stained yellow by safranin, while albumin is stained red. 2. Leukocytes (9) are present in large number in yellow sputum, and in smaller number in clear sputum. They are to be looked upon as white blood-corpuscles that have wandered from the blood-vessels. They also are often found in changed forms and in a state of dissolution ; they may be shrivelled up, filled with fat-granules, or they may appear as conglomerations of granules; and, finally, isolated nuclei indicate the destruction of their cell-bodv. 250 NORMAL FORMATION OF MUCUS IN THE AIR-PASSAGES. Eosinophile cells are found in the sputum from cases of asthma, and also in the nasal secretion from cases of acute coryza and of nasal polyps. Leukocytes containing hemosiderin are found after capillary hemorrhages in the air-passages. The fluid substance of the sputum contains much mucus, derived from the mucous glands and the goblet-cells, also some nuclein and lecithin, and the constituents of the saliva, according to the amount mixed with the sputum. Albumin is found in the sputum only in cases of inflammation of the air-passages; its amount increases with the degree of inflammation. Urea has been found in the sputum in cases of advanced nephritis. Pathological. — In the presence of catarrhal conditions the sputum is usually at first glairy and slimy (sputa cruda) ; later, it becomes more consistent and yellow (sputa cocta) . Fig. 92. — Objects Found in the Sputum: i, detritus and dust-particles; 2, pigmented alveolar epithelium*, 3, fatty degenerated and partially pigmented alveolar epithelium; 4, alveolar epithelium showing myelin-de- generation; 5, free myelin-forms; 6, 7, desquamated ciliated epitheUum, partly changed and deprived of its cilia; 8, squamous epithelium from the mouth; 9, leukocytes; 10, elastic fibers; 11, fibrinous cast of a small bronchus; 1 2 leptothrix buccalis, together with cocci bacilli, and spirochetse; o, fatty-acid crystals and free fatty granules; b, hematoidin; c, Charcot's crystals; d, cholesterin. Under pathological conditions there may be found in the sputa: (o) Erythrocytes, always from rupture of a blood-vessel. (b) Elastic fibers (10) from destroyed pulmonary alveoli. Usually they occur in small bundles of delicate fibers, which at times suggest the rounded walls of the alveoli by their curved arrangement. Naturally, they always indicate destruction of pulmonary tissue. (c) Much more rarely, in the presence of rapid and extensive disintegration of the lungs, there occur larger fragments of pulmonary debris, embracing several alveoli; likewise small pieces of fibro-cartilage or unstriated muscle-fibers from the small air-passages. (d) Colorless coagula of fibrin (11) may be found, and are usually to be recog- nized as casts of the smaller or larger air-passages. They are formed in connection with inflammatory processes in the lungs or bronchi that are attended with a fibrinous exudation into the tubules. They are thus found frequently in cases of pneumonia in adults, in cases of bronchial croup, and also, rarely, in cases of severe influenza. EFFECTS OF ATMOSPHERIC PRESSURE. 251 (e) Crystals of various kinds: Fatty-acid crystals (a), arranged in bundles of fine needles, usually lying in whitish, cheesy, fetid lumps of sputum. They indi- cate a more profound process of decomposition aflfecting the stagnating secretion and the underlying tissue. Crystals of leucin and tyrosin arc rarely found as decomposition-products of the allniminates. Tyrosin is found more aVjundantly after rupture of an old abscess into the lungs. Colorless, octahedral or rhomVjic platelets with elongated points — Charcot's crystals (c) — -have been found in the expectoration in cases of asthma, Iving in and on peculiar, spirally wound plugs of exudate from the narrow air-passages; they have also been found in connection with other exudativ>i affections of the bronchi. These structures, also called Curschmann's spirals, are produced when the respiratory air, in passing by, draws out parts of the secretion into threads, and rolls them spirally to and fro. Hema- toidin-crystals (b), from old effusions of blood in the lungs, occur rarely; likewise cholesterin-crystals (d) , arising from broken-up collections of pus. (/) Fungi and other low organisms are found in the sputum, being taken in during inspiration. The threads of leptothrix buccalis (12) occur frequently, having been detached from deposits on the teeth. Mycelial threads and spores are found in the sputvim in cases of thrush, which occurs frequently in the mouths of nursing infants as white, spreading deposits (oidium albicans). Among the bacteria, the mucous-membrane streptococci (mostly diplococci) are constantly found, and frequently the micrococcus albus liquefaciens and harmless saprophytes; pyogenic cocci usually occur only in cases of pulmonary tuberculosis. In the presence of gangrene of the kings monads and cercomonads have been found, in cases of pneumonia at times the bacillus pneumoniae of Friedlander, in cases of influenza the influenza-bacillus of Pfeiffer and Canon, in cases of whooping-cough a minute diplococcus (according to Czaplewski and Hensel a non-motile bacillus), in cases of mumps a bacterium similar to the gonococcus, in cases of measles the bacillus causing that disease, in cases of pulmonary tuberculosis without exception the tubercle-bacillus. Rarel}^ the sarcina is found; this is encountered more fre- quently in the stomach in the presence of gastric catarrh, and also in the urine. With regard to its external appearance sputum may be described as mucous, muco-purulent, or purulent. When heated at 60° C. all sputa are reduced to a uniform degree of fluidity. The sputum may have an abnormal coloration. Thus, it may be red from blood-pigment; if it remains long in the lungs, the blood-pigment may run through a whole scale of colors (as in external, visible blood-tumors), and it may thus give the sputa a dark-red, bluish-brown, brownish-yellow, deep-yellow, yellowish-green, or grass-green color. The sputum is sometimes yellow in cases of jaundice. Colored dust, if accidentally inspired, may also color the expectoration. The odor of the sputa is usually stale, and more or less unpleasant. It be- comes ill-smelling when it has remained for some time in pathological cavities in the lungs; it is stinking in the presence of gangrene of the lungs. EFFECTS OF ATMOSPHERIC PRESSURE. At the normal pressure of the atmosphere, with the barometer regis- tering 760 mm. of mercury, a pressure is exerted on the entire surface of the body amounting to from 15,000 to 20,000 kilos, corresponding to the extent of surface — 103 kilos to each square decimeter. This pressure acts on the body equally from all sides, and in those internal air-spaces as well which are in direct communication with the outer air either constantly — as the respiratory tract, the sinuses of the frontal, superior maxillary, and ethmoid bones — or only temporarily — as the digestive tract and the tympanic cavity. If an air-filled space, for example the tympanic cavity, be closed off from the outer air for some time, a rarefaction of the gases in the space occurs, as a result of the consumption of oxygen and its replacement by a smaller volume of carbon dioxid. As the fiuids of the body (blood, lymph, secretions, parenchymatous juices) are practically incompressible, their volume may be regarded as unchanged by the prevailing pressure. These fluids, however, absorb gases from the atmosphere in accordance with the pre- 252 EFFECTS OF ATMOSPHERIC PRESSURE. vailing pressure — that is, the partial pressure of the several gases — and also with their temperature. The solid constituents of the body are composed of innumerable and minute elementary parts, such as cells and fibers, of which each presents only a microscopic extent of surface to the influence of the pressure. Hence, the prevailing atmospheric pressure for every cell can be estimated only at a few milligrams, a pressure under which even the most delicate histological structures develop with ease. As an example of the action of atmospheric pressure on larger masses, attention may be called to the fact that, as a result of the adhesion of the smooth, sticky, articular surfaces of the shoulder- joints and the hip-joints, the arm and the thigh are supported without the aid of muscular activity; so that, for example, the thigh is still held in the acetabulum after all of the soft parts around the neck of the femur, including the articular capsule, are divided. An ordinary increase in barometric pressure has an influence on the respiratory activity in that it stimulates slightly the respiratory movements, while a fall in barometric-pressure has the opposite effect. The absolute amount of carbon dioxid remains the same; but in connection with the lessened frequency of respiration attending a low barometer, the percentage is naturally somewhat increased. Marked diniiniition in the atmospheric pressure, such as occurs in ascending mountains or in balloon-voyages (the highest known ascension, without loss of con- sciousness having been made by Berson of Berlin, to a height of 9145 meters at a temperature of — 47-7° C), causes a series of characteristic phenomena: (i) As a resiilt of great diminution in the pressure on surfaces in direct contact with the air, they undergo marked congestion. Hence, there occur redness and swelling of the skin and exposed mucous membranes, even to the extent of causing hemor- rhages from the more delicate parts, as the nose, the lungs, the gums; turgidity of the cutaneous veins, profuse sweating, marked secretion from the mucous mem- branes. The arteries become more empty; at one-half the atmospheric pressure the blood-pressure in the radial artery begins to fall. (2) Other direct effects of diminished pressure are a feeling of weight in the legs, as the atmospheric pres- sure alone is not sufficient to keep the head of the femur in the acetabulum; bulg- ing of the tympanic membrane by the air in the tympanic cavity, until the differ- ence in tension is equalized through the Eustachian tube, and as a consequence pain in the ears and even impairment of hearing. (3) The diminution in the tension of oxygen in the surrounding air causes difficulty in breathing and oppres- sion of the chest, as a result of which the respirations become more rapid (also the pulse), deeper, and irregular. At an elevation of from 3000 to 4000 meters the respiration and pulse are increased one-fourth ; when the atmospheric pressure is reduced from one-third to one-half, the blood loses oxygen, and in consequence there is incomplete removal of the carbon dioxid from the blood and a considerable diminution in the oxidation-processes in the body. When the atmospheric pres- sure is one-half or less, the amount of carbon dioxid in the arterial blood is dimin- ished, and the amount of nitrogen decreases in proportion to the diminution in atmospheric pressure. Rabbits kept under a pressure of from 300 to 400 mm. of mercury die on the third day, and present widespread fatty degeneration, espe- cially of the heart. In men and in animals, residence in high, mountainous regions appears to increase in the course of a few days the amount of hemoglobin in the blood and the number of red corpuscles. This effect should be favorable for the absorption of oxj-gen. A noteworthy phenomenon is the appearance of numerous microcytes in the first few days. Dyspnea from various causes also has a similar effect in man. (4) In consequence of the diminution in the density of the air, the latter is not able to produce loud tones in the larynx through the vibrations of the vocal bands; hence, the voice appears faint and altered. (5) In consequence of the determination of blood to the external parts in contact with the air, the internal parts become relatively poor in blood; hence result diminution in the secretion of urine, muscular weakness, digestive disturbances, dulness of the senses, fainting spells, all of which phenomena are intensified by the conditions mentioned in EFFECTS OF ATMOSPHERIC PRESSURE. 253 paragraph (3) . According to the observations made by Whimper on himself during the ascent ot the highest peak in the Andes, the body can, to a certain extent, accustom itself with respect to these latter phenomena. At an elevation of from 7000 to 8000 meters loss of consciousness occurs at times; the aeronauts Croce- bpinelli and Sivel lost their lives at a height of 8600 meters, where the rarefied air contains only 72 per cent, of oxygen (the air-pressure being 241 mm. of mer- cury). In dogs a marked fall in the blood-pressure occurred hrst at 200 mm. of mercury, accompanied by a small, slow pulse. The inhabitants of high, mountainous regions are sometimes attacked by an illness (mountain-sickness) , which consists essentially of symptoms similar to those described, especially anemia of the internal organs, and which is accompanied by a diminution in the amount of hemoglobin in the blood. Alexander von Hum- boldt found remarkable roominess of the thorax in the inhabitants of the high Andes. This phenomenon has been attributed to a diminution in the carbon dioxid of the blood, which serves as a stimulant to the respiratory center. At an elevation of from 6000 to 8000 feet above the sea, water contains only about one- third the amount of air absorbed; therefore fish cannot longer live in it. Animals can be subjected to a still greater rarefaction of the atmosphere under the receiver of an air-pump. Under such conditions birds die when the air-pressure is reduced to 120 mm. of mercury; mammals at 40 mm. of mercury. Frogs endure repeated evacuation, and as a result they become much distended by escaping gases and aqueous vapor; after the entrance of air, however, they col- lapse completely. Hoppe-Seyler ascribes the cause of death in warm-blooded animals to the development of gas in the blood, the bubbles obstructing the capil- laries. Landois has often been able to confirm this phenomenon, and as far back as 1879 he suggested that the development of gas-bubbles in the parenchymatous juices, especially of the nervous system, might act injuriously through mechanical laceration of the tissues. Sudden reduction of a previously high air-pressure may act in a similar manner. The free gas that fo:-ms in the blood is almost pure nitrogen. The presence of air in the arteries of the spinal cord produces anemic paralysis, and later local destruction of the nerve-elements. Redi and Wepfer, in 1685, were the first to observe death from blowing air into the veins, as a result of mechanical obstruction to the circulation. Local diminution of the air-pressure results in marked congestion and swelling of the tissues in the affected part ; this is shown in the simplest manner by cupping. Under the name of the "cupping-boot" Junod described an apparatus for the rare- faction of air, made to include a whole extremity; this apparatus rendered possible a reduction to one-third in the air-pressure surrounding the leg. By this means from 2 to 3 kilos of blood may be aspirated into the leg, thus producing a temporary withdrawal of blood from other parts of the body, without causing a permanent loss of blood to the body. The energetic application is exceedingly painful, and the after-effects persist for 48 hours. Marked increase of the atmospheric pressure is accompanied by phenomena that may for the most part be explained as the reverse of those described in the dis- cussion of diminution of the air-pressure. They have been observed many times, partly in so-called pneumatic cabinets, in which, for therapeutic purposes, the pressure is gradually increased to one and one-lifth, two and two-fifths atmos- pheres and more; partly in closed reservoirs used in construction under water, and out of which the water is forced by pumping air in. Under such conditions men work at times even under a pressure of four and one-half atmospheres. The fol- lowing phenomena are worthy of attention: (i) Pallor and drjmess of the external surfaces, collapse of the cutaneous veins, reduction in perspiration and the secretions from mucotis membranes, greater supply of blood to the abdominal organs. (2) Pressing inward of the tympanic membrane (until the Eustachian tube allows the compressed air in the tympanic cavity to escape, often with a noise) ; considerable pain in the ears and even impairment of hearing. (3) A feeling of lightness and freshness during respiration. The respirations become slower (from 2 to 4 in a minute), inspiration is made easier and shortened, expiration is lengthened, and the pause is distinct. The capacity of the lungs is increased, owing to freer move- ment of the diaphragm, in consequence of diminution in the gases contained in the intestine. G. v. Liebig has noted an increase in the absorption of oxygen; Panum found that with the same volumes of air interchanged, the excretion of carbon dioxid is increased; the venous blood appears to be reddened. (4) Diffi- culty in speaking, a nasal metaUic tone to the voice, inability to whistle. (5) In- creased secretion of urine; on account of the more rapid oxidation in the body, 254 COMPARATIVE. HISTORICAL. there is increased activity of metabolism, increase in muscular energy, increased appetite, subjective feeling of warmth. The pulse is slower, and the pulse-curve lower. On account of the invigorating and stimulating effect of a sojourn m moder- ately compressed air, the employment of the latter has been practised for thera- peutic purposes; and it has been found that repeated applications have produced favorable after-effects of considerable duration. Unduly rapid increase of pressure is to be avoided and likewise unduly rapid removal of the pressure. Waldenburg and others have constructed apparatus in the form of a spirom- eter; either compressed air maybe inspired from its bell-jar, or the bell- jar may be filled with rarefied air, into which the expirations are made. Both methods are used in suitable cases for therapeutic purposes. Paul Bert has found at an excessively high, artificial atmospheric pressure, over 30 vol. per cent, oxygen in the arterial blood of animals (investigated at 700 mm. of mercury). If the amount of oxygen reaches 35 vol. per cent., death occurs, accompanied bv convulsions. At a somewhat lower point the bodily tem- perature falls, the oxidation-processes in the body are reduced, strange to say, and as a result of this the formation of carbon dioxid and urea is diminished. Greatly compressed oxygen also produces the effect of a relative deficiency of oxygen; animals die in it, exhibiting signs of suffocation with greatly reduced metabolic processes. Frogs exhibit in compressed oxygen (up to 14 atmospheres) the same phe- nomena as they w^ould in a vacuum or in pure nitrogen. There occurs paralysis of the central nervous system, at times preceded by convulsions. Then the heart stops beating (but not the lymph-hearts) , and at the same time the motor nerves lose their irritability; finally, the direct muscular irritability disappears. Under exceedingly high pressure of oxygen (thirteen atmospheres) an excised frog's heart beats scarcely one-fourth the time that it remains active in the air. If the quiet heart be brought into the air, the pulsations may return. Under a pressure of 100 atmospheres the frog's muscles still contract normally, and only at 400 atmospheres do they become paralyzed. Phosphorus ceases to be huniniferous under high pressure of oxygen, but not, however, the phosphorescent organisms, — for example, the lamprey, — or the phos- phorescent bacteria, such as those of meat (micrococcus Pflugeri). Exceedingly high atmospheric pressure is injurious to plants also. COMPARATIVE. HISTORICAL. Mammals have lungs similar to those of man. Those of birds exhibit a spongy structure; they are fused with the inner surface of the chest-wall, and have, on their outer surface, openings that lead into large, thin-walled air-sacs, lying among the viscera. These air-sacs further communicate with the cavities in the bones, which contain air instead of marrow, in order to provide greater lightness (pneu- maticity of the bones) . There is no diaphragm. In reptiles the lungs are divided into larger and smaller divisions of vesicles; in snakes one lung atrophies, while the other becomes greatly drawn out and elongated, in accordance with the form of the body. Frogs pump air into their lungs by contraction of the pharyngeal sac, the nostrils being closed and the larynx opened. Turtles fill their lungs with air by a sucking movement. Amphibia (frog) possess two simple lungs, each of which in its structure to a certain extent represents an enormous infundibulum with its alveoli. When young (until their metamorphosis) they live as aquatic animals, and breathe by means of gills; the perennibranehiates (proteus) indeed, like the fishes, breathe in this manner throughout life. Among fishes the dipnoi, besides their gills, possess a swimming-bladder, abundantly supplied with afferent and efferent vessels, constituting an internal respiratory organ remotely comparable to the lungs. By the term "gills" is meant an organ for respiration in water, constructed in the form of numerous, vascular, plate-like diverticula. Among the fishes, the mud-fish (cobitis) exhibits an intestinal respiration, when there is lack of water and it buries itself in mud; in this process air is swallowed on the upper surface of the water, the oxygen is abstracted in the intestines, and carbon dioxid is discharged through the anus. Insects and centipedes respire through tracheas, which consist of numerous air-canals distributed throughout the body and com- municating with the atmosphere on the outer surface of the body by means of openings (stigmata) that can be closed. As insects possess no true circulatory movement of the blood, the air conducted through tubes penetrates from all sides COMPARATUi:. HISTORICAL. 255 into the blood-liUed huily-cavitics; while in the hin^-breathing vertebrates the blood conducted through tubes is brought from the whole body to the respiratory organ. The stigmata on the outer surface of the body, constituting the entrances to the tracheas, are provided with j)cculiar contrivances for closing, and can be employed for the einission of sounds. Arachnids respire by means of tracheas and lung-like air-sacs (tracheal pouches) ; crabs, by means of gills. Mussels and cephalo- pods possess fully developed gills; snails have partly gills, partly lungs. Among the lower animals, gill-like formations are still found ainong the round worms and in the echinoderms; intestinal respiration occurs in the tunicatcs and many of the mites. Respiration by means of a water-vascular system, a system of canals through which water Hows, is peculiar to the medusae and the Hat worms. The lowest animal forms — protozoa, sponges, polyps — do not possess a special respiratory organ; in them the surfaces in contact with water carry on the respiratory interchange of gases. Historical. — Aristotle (384 B. C.) regarded the object of respiration to be the cooling of the body, in order to moderate the internal heat. He observed cor- rectly that the warmest animals also respire most actively, but in the interpretation he reversed cause and effect; for the warm-blooded animals do not respire on account of their heat (for cooling purposes) , but they are warm as a result of their more active respiration (combustion). Galen (203-131 B. C.) already observed the pvirifying action of the respiratory organ, assuming that the "soot" was removed from the body with the expired air, together with the expired water. The most important experiments concerning the mechanics of respiration date from Galen. He maintained that the lungs passively follow the movements of the thorax, that the diaphragm is the most important respiratory muscle, that the external intercostals are inspiratory mus- cles, and the internal intercostals expiratory. He divided the intercostal nerves and muscles, and observed that loss of voice followed. After dividing the spinal cord at progressively higher levels, he found that successively higher thoracic muscles became paralyzed. Theophilus Philaretus taught that the circulation could be improved by loud crying, singing, or speaking. Oribasius (360 A. D.) observed that both lungs collapsed in the presence of double pneumothorax. Vesalius (1540) first described artificial respiration as a means of reanimating and stimulating the heart's action. Malpighi (1661) described the peculiar structures of the lungs. Lower (1669) saw the blood become bright red in the lungs. Borelli (died 1679) first explained most thoroughly the mechanism of the respira- tory movements. The chemical processes attending respiration were already suspected by Mayow (1679): "Ignis et vita iisdem particulis aereis sustinetur." However, more accurate knowledge could be obtained only after the discovery of the several gases coming under observation. J. B. van Helmont (died 1644) discovered car- bon dioxid, and found that the air was vitiated by respiration; but Black (1757) first discovered the excretion of carbon dioxid during respiration. In 1774 Pristley and Scheele discovered oxygen. Lavoisier, in 1775, foimd the nitrogen, and at the same time ascertained the composition of the atmosphere. The same investi- gator also represented the formation of carbon dioxid and water during respiration as being the result of combustion within the lungs. J. Ingenhousz (1779) dis- covered the respiration of plants — the absorption of carbon dioxid and the giving oflf of oxygen during that process. Senebier (1785) found that this exhaled oxygen arose from decomposition of the carbon dioxid. Vogel and others definitely proved the existence of carbon dioxid in venous blood. Hoffmann and others demon- strated the presence of oxygen in arterial blood. Lavoisier with Scguin, in 1789, made the first communication concerning the quantitative absorption of oxygen and excretion of carbon dioxid during respiration. More complete insight into the interchange of gases during respiration could be obtained only after Magnus ex- tracted and analyzed the gases from arterial and venous blood. PHYSIOLOGY OF DIGESTION. THE MOUTH AND ITS GLANDS. The mucous membrane of the mouth contains sebaceous glands at the red edge of the hps. It consists of fibrillar connective tissue intermixed with fine elastic fibers. Toward the free surface it forms papillae, of which the largest (0.5 mm.) are found on the lips and the gums, including some with double points — twin papillas. The smallest are on the palate and in the fold-like duplica- tures of the mucosa. The submucous tissue, which passes directly over into the mucosa, is thickest and most dense where the mucous membrane is immovably attached to the periosteum of the maxilla and the palate, and also in the vicinity of glandular involutions; while it is most delicate over movable and folded parts. The surface is lined by stratified nucleated squamous epithelium (Fig. 92, 8), and it is, as a rule, strongest and consists of the largest number of layers in regions where the papillae are longest. A diplosoma is found in the deeper cells of the surface of the tongue. All of the glands of the mouth, in- cluding the salivary glands, are divided, with reference to their secretion, into three groups: (i) albuminous or serous glands, whose secretion contains albumin; (2) mucous glands, whose ropy secretion contains mucin, together with some albu- min; (3) mixed glands, whose acini secrete partly albumin and partly mucin, as, for example, the submaxillary gland in man. For a description of their structure refer- ence may be made to page 258. Numerous mucous glands — termed buccal, palatine, lingual or molar muciparous glands, in accordance with the region in which they occur — are present in the tisstie of the mucosa, their bodies appearing macroscopically as tiny white nodules. They represent the type of simple branched tubular glands. The con- tents of their secreting cells are partly mucus, which is expelled at the time of secretion. The excretory duct, formed of connective and elastic tissues, with a narrow outlet, is lined by a single layer of cylindrical epithelium. One duct often receives that of a neighboring gland. The labial glands are mixed glands. The small glands of the tongue deserve special consideration. Two morpho- logically and physiologically distinct glands can be distinguished, namely (i) mucous glands (E. H. Weber's glands), situated especially near the root of the tongue- compound alveolar glands, with bright, transparent, secreting cells and mural nuclei, and a rather thick membrana propria; and (2) serous glands (von Ebner's o-jands) , situated about the circumvallate papillae (and the foliate papillae in animaTs) and consisting of convoluted and branched tubules, characterized by small narrow cells, filled with droplets of secretion, containing a centrosome and yielding an albuminous secretion. Halfwav up between the cells the intercellular secretory ducts are found. (3) The Blandin-Nuhn glands, within the tip of the tongue consist of glandular lobules secreting mucus and saliva, and are, therefore, mixed glands. Delicate varicose nerve-fibers pass up to the cells. 256 Fig. 93. — Section through Lymph-folli- cles of the Root of the Tongue (after Schenk): B, lymph-follicles; V, depression; A, adenoid connec- tive tissue; S, mucous glands; E, epithelium. THE SALIVARY GLANDS. 257 Of the blood-vessels, which are abundant, the larger he in the submucosa, while the smaller penetrate into the papilhe, in which they form either capillary networks or simple loops. Of the iyniph-vesscls the larger trunks, which form a coarse meshwork, lie in the subinucosa, while the smaller, forming a finer network, pass through the mucous membrane itself. The cutaneous follicles or lymph-follicles constitute a part of the lymphatic apparatus. Tlicy form an almost coherent layer on the back of the tongue at its root. Several of these lymph-follicles always collect into a round mass, surrovinded by connective tissue, and raising the mucous membrane somewhat. In the center of every such collection is a depression (Fig. 93) into the bottom of which mucous glands empty and fill the small crater with mucous secretion. The ioiisils exhibit on the whole the same formation, — crypt-likc depressions, into the sinuses of which small mucous glands empty, and surrounded by masses of from 10 to 20 lymph-follicles. Layers of firm connective tissue form a sheath aVjout the ton.sils. The pharyngeal and tubal tonsils exhibit a similar structure. Many medullated nerve-fibers, coming from the submucous tissue, ramify in the mucous membrane and terminate in part in separate papilla in the form of Krause's end-bulbs, in larger number on the lips and the soft palate, in smaller number on the cheeks and the floor of the mouth. Probably the nerves also spread out in the form of fine terminal nodules between the epithelial cells, accord- ing to the Cohnheim-Langerhans mode of distribution. Functionally these are sensor}^ nerves and nerves of touch. THE SALIVARY GLANDS. The salivary glands and also the pancreas are compound tubular glands. The excretory ducts, formed of connective and elastic tissues (Wharton's duct contains also unstriated muscle-fibers) are lined with ^"onal dental ledge, which has also been found in birds and turtles as the last rudiment of a former den- tition. MOVEMENTS OF THE TONGUE. The tongue keeps the tood between the opposing surfaces of the teeth during mastication: it collects the finely divided particles of food, held together by the saliva and forms them into a bolus, and finally it trans- fers the bolus along its dorsal surface into the pharynx at the time of deglutition. The course of the muscle-fibers in the tongue is three-fold: longitudinal, from the tip to the root of the tongue; transverse, originating mainl\^ from the septum of the tongue stretched longitudinally; and vertical, traversing the thickness of the organ. The muscles of the tongue are in part confined to this organ alone; in part they pass to the tongue from other fixed points, namely, the hyoid bone, the lower jaw, the styloid process and the palate. Microscopically the muscle-fibers are striated transversely, surrounded by deli- cate sarcolemma, and frequently divided Hke a fork at their extremities. The bundles interlace with one another to a considerable extent, and small deposits of fat are found in the spaces between them. The movements of the tongue give rise in part to changes in form, in part to changes in position. 1. Shortening and widening, through the longitudinal lingual muscle, aided by the hyoglossus. 2. Elongation and narrowing, through the transverse lingual muscle. 3. Excavation of the dorstun of the tongue in the form of a longitudinal furrow, through contraction of the transverse Ungual muscle, with simultaneotis action of the median vertical fibers. 4. Arching the dorsvun of the tongue: (a) transversely, through contraction of the lowermost transverse fibers; (b) longitudinally, through the action of the lowermost longitudinal muscles. 5. Protrusion of the tongue, through the genioglossus , aided somewhat by the geniohyoid, passing from the hyoid bone toward the chin; at the same time the tongue'usually becomes elongated and narrowed. 6. Retraction of the tongue through the hyoglossus, chondroglossus and stylo- glossus; also as a rule with shortening and widening of the tongue. 7. Depression of the tongue upon the floor of the mouth is ettected in the median line by the genioglossus; at the sides by the hyoglossus. By depression of the hyoid bone the floor of the mouth can be made even much deeper. 8' Elevation of the tongue to the palate: (a) at the tip, through the anterior portions of the upper longitudinal fibers; (6) in the center, through elevation of the entire hyoid bone by the mylohyoid muscle (trigeminal ner\-e) ; and (c) at the root, through the styloglossus and palatoglossus muscles, as well as indirectly by the stylohyoid muscle (facial nerve) . 9. Lateral deflection of the protruded tongue is effected by the genioglossus (toward the opposite side) ; while similar deflection of the tongue, lying in the mouth, is effected by the styloglossus, hyoglossus, chondroglossus and palato- glossus muscles. Further lateral deflection of the tongue, so that the tip comes to he behind the last bicuspid tooth, is effected through the combined action of the styloglossus and hyoglossus muscles on one side and the genioglossus on the other side. The motor nerve of the tongue is the h\-poglossal. In case of unilateral paralysis the tip of the tongue lying at rest in the mouth is directed toward the unaffected side, because the tone of the vmparalyzed longitudinal fibers shortens the unaffected side to some extent. If, however, the tongue is protruded, the tip deviates toward the paralyzed side. This is dependent on the direction pursued by THE ACT OF SWALLOWING. 277 the genioglossus muscle from the middle line (internal mental spine) backward and outward, the direction of whose traction the tongue must naturally follow. The tongue in killed animals sometimes exhibits librillary twitchings for an entire day. THE ACT OF SWALLOWING (DEGLUTITION). The propulsion of the contents of the alimentary canal is effected by a motor process whereby the canal contracts upon the contained mass; and as this contraction progresses throughout the entire length of the tube, the contents are pushed on before it. This movement is called peristalsis. The first and most complicated act of this movement is deglutition, in which the following stages can be distinguished : 1. The mouth is closed by the orbicularis oris muscle (facial nerve). 2. The jaws are pressed together by the muscles of mastication (trigeminal nerve); in this way the lower jaw becomes a fixed point, permitting the action of the muscles passing from the lower jaw to the hyoid bone. 3. The tip of the tongue, the back of the tongue, and the root of the tongue are successively pressed against the hard palate, and in this way the contents of the mouth (bolus or fluid) are forced toward the pharynx. 4. When the bolus has passed the anterior palatine arches, having been made slippery by the mucus of the tonsillar glands, its return to the mouth is prevented by the contraction of the palatoglossus muscles lying in the anterior palatine arches, which bring these arches firmly in contact with each other, like the scenes in a theater, and by the back of the tongue, which is elevated by the styloglossus muscle. 5. The bolus now lies behind the anterior palatine arches and the root of the tongue, within the pharynx and exposed to the succes- sive action of the three constrictor muscles of the pharynx, which push it onward. The action of the superior constrictor muscle, which contracts first, is always combined with horizontal elevation, through the elevator of the veil of the palate (facial nerve), and tension of the soft palate, through the tensor of the veil of the palate (trigeminal nerve; otic ganglion). The superior constrictor, through the pterygo- pharyngeal muscle, presses the posterior and lateral pharyngeal wall firmly against the posterior edge of the veil of the palate horizontally elevated and made tense like a cushion (Passavant's cushion), while the edges of the posterior palatine arches are at the same time approximated through the palatopharyngeal muscles. In this way the nasopharyngeal cavity is closed, so that food is prevented from passing readily upward into the nasal cavity. In persons with congenital or acquired defects of the soft palate, food can enter the nose during the act of deglutition. The elevation of the veil of the palate can be readily demonstrated by intro- ducing a fine probe through one nostril, along the floor of the nasal cavity, until its posterior extremity rests upon the veil of the palate. With every movement of deglutition the anterior extremit}' of the probe, projecting from the nostril, is depressed. A sensitive flame may also be employed, a T-shaped tube being in- troduced into one nostril, the other being closed. One arm of the tube is con- nected with a gas-pipe, the other with a burner. Every movement of deglutition is attended by mov^ement of the flame. 278 THE ACT OF SWALLOWING. 6. Responding to the successive contractions of the superior, middle, and inferior constrictors of the pharynx and the esophageal muscles, the bolus is forced downward. During this time the entrance to the larynx must be kept closed, to prevent food from passing into the trachea. 7. According to Kronecker and Falk, semisolid foods and fluids in the mouth are forced through the pharynx and the esophagus by vigorous contraction of the muscles closing the mouth, particularly the mylo- hyoid muscles. If the act of swallowing is repeated several times in rapid succession, as in drinking, only the last is followed by movements of contraction in the pharynx and the esophagus, for every act of swallowing in the mouth exerts an inhibitory effect upon the lower portions of the esophagus, through stimulation of the glossopharyngeal nerve. That solid and semisolid articles of food are, however, pushed slowly through the esophagus, by peristalsis alone, has been demonstrated by the Rontgen rays on admixture of bismuth subnitrate with the bolus. According to Meltzer and Kronecker, the duration of the act of deglutition in the mouth is 0.3 second. Then the constrictors of the pharynx contract; 0.9 second later the superior, 1.8 seconds later the middle, and 3 seconds later the inferior constrictor of the pharynx. The constriction of the cardiac orifice, after the food has passed into the stomach, is the final movement of the series. On auscultation of the stomach two sounds are heard during deglutition: (i) the squirting sound, which is due to the fact that the material swallowed is forced into the stomach, and (2) the squeezing sound, due to peristalsis occurring at the end of deglutition forcing the contents of the esophagus through the cardia. The latter is a rale and, as such, is dependent on the presence of air in the mass swal- lowed. Closure of the larynx is brought about as follows: (a) The lower jaw being fixed, the larynx is drawn upward and forward beneath the root of the tongue, which is arched over it. This is effected by a movement of the hyoid bone forward and upward through the action of the geniohyoid, the anterior belly of the digastric, and the mylohyoid muscles together with an approximation of the larynx to the hyoid bone, through the thyro- hyoid muscle, (b) While the tongue, besides, is drawn somewhat backward by the styloglossus muscles, it presses the epiglottis over the entrance to the larynx, so that food can now slide over it. (c) The epiglottis, further, is pulled down over the entrance to the larynx by the action of the reflector epiglottidis and the aryepiglottic muscle. Intentional injuries of the epiglottis in animals, or destruction of the epiglottis in human beings, cause choking readily from the entrance of liquids into the larynx, while solid foods can be swallowed with scarcely any troulDle. In dogs, however, colored liquids pass directly from the back of the root of the tongue downward into the pharynx, without necessarily staining the upper surface of the epiglottis, hidden under the overhanging root of the tongue. (d) Finally, closure of the glottis by the constrictors of the larynx prevents the entrance of swallowed substances into the larynx. This closure is brought about through reflex influences. In order that the pharynx itself shall not be drawn down with the de- scending bolus it is drawn upward by the stylopharyngeal, salpingo- pharyngeal and basopharyngeal muscles during the activity of the pharyngeal constrictors. Nervous Supply.— The nerves of the pharynx are comprised in the pharyngeal plexus, formed by branches from the pneumogastric, the glossopharyngeal and the sympathetic. The act of deglutition is voluntary only in so far as it takes THE ACT OF SWALLOWING 279 place in the mouth. The passage of the bohis through the palatine arches on past the tonsils into the pharynx is involuntary, and entirely reflex in character. The pharynx takes up the movement only if its contents (food or saliva) mechani- cally excite reflex action. The sensory branches that excite this mechanical stimulation of the deglutition-reflex are, according to Schroder van der Kolk, the palatine branches of the trigeminal nerve, from the sphenojsalatine ganglion, and the pharyngeal branches of the pneumogastric nerve. The center for the nerves in question for the striated muscles lies in the medulla oblongata. Degluti- tion is still possible in the state of unconsciousness, as well as after destruction of brain, cerebellum and pons. Irritation of the ninth cranial nerve prevents the deglut it ion-reflex. Within the esophagus (Fig. 107), the stratified squamous epitheHum of which is kept slippery by the mucus from small mucous glamls opening at the edges of the folds of mucous membrane, the downward movement takes place also involuntarily through a coordinated muscular act, a peristaltic movement of the external (longitu- dinal) and the internal (circular) unstriated muscle-fibers. In the upper part of the esophagus, in which lie striated muscle-fibers, peris- talsis is much more rapid than in the lower portion. The movements of the esophagus never originate spontaneously, but they al- ways follow on a previous act of deglutition. Thus, if a bolus be introduced into the esophagus through an external woimd, it re- mains where it was placed; it is carried downward only when movements of deglu- tition are initiated above. The peristalsis extends throughout the entire length of the esophagus, even if this be ligated or a portion has been excised. The peristalsis, likewise, continues downward in a dog, even after meat is with- drawn from the esophagus, though it has been halfway down. Exceedingly large and exceedingly small masses of food are swallowed with greater effort than those of medium size. Dogs are able to swallow a bolus weighing 450 grams. Deglutition becomes difficult in consequence of great dilata- tion of the thorax, as in Miiller's experiments ; likewise in consequence of con- traction of the thorax, as in Valsalva's investigations. The motor nerve of the esophagus is the pneumogastric — after division of which on both sides food remains in the esophagus, particularly its lower part. Goltz discovered the remarkable fact that the ganglionic plexuses situated in the esophagus and the stomach of the frog acquire greatly increased irritabiUty when the brain and spinal cord or both pneumogastric nerves are destroyed. Esophagus and stomach contract vigorously like a string of pearls, even after slight irritation, while animals with an uninjured central nervous system swallow fluid introduced simply by peristalsis. It should be borne in mind that human beings with an enfeebled nervous system (hysteria) not rarely exhibit similar spas- modic contraction of the esophagus (globus hj^stericus) . Schift" observed spas- modic contraction of the esophagus in dogs also after section of both pneumo- gastric nerves. The heart-beats are accelerated with each act of swallowing, while the blood- pressure falls, the need of respiration diminishes and some movements, such as labor-pains and erection, are inhibited. All of these movements are brought about through reflex influences. Fig. 107. — Transverse Section through the Esophagus. E, epithe- lium ; St, mucous membrane ; Se, mucous gland ; Mc, circular muscle-fibers ; Ml, longitudinal muscle-fibers ; G, capillaries ; B, connective tissue; S, submucosa. 28o THE MOVEMENTS OF THE STOMACH. THE MOVEMENTS OF THE STOMACH.— VOMITING. Three methods are employed for determining the position of the stomach: (a) the introduction of a rubber bougie through the esophagus, whose passage along the greater curvature of the stomach can be palpated; (b) electric transillumina- tion of the stoinach by means of a small round incandescent light attached to the extremity of a stomach-tube. The stomach is previously suitably dilated by the development of carbon dioxid from sodium bicarbonate administered; the interpretation requires great care; (c) the Rontgen rays have also been em- ployed after filling the stomach with meat mixed with bismuth subnitrate, the latter being impervious to the ar-rays. For registering the gastric movements, a rubber bulb, introduced through an external gastric fistula in animals, and applied in various situations in the in- terior of the stomach, is employed. The bulb is connected with a writing-ap- paratus by means of a column of air. Einhorn has used the gastrograph in human beings. This consists of a metallic capsule attached to the extremity of a rubber tube, which is swallowed. With every movement of the stomach the metallic parts in the interior of the capsule are brought into contact, and thus employed to eftect an electrical registration. A series of photographs taken with Rontgen rays also affords information as to the course of the movements and the evacuation of the gastric contents. The anterior surface of the empty stomach lies in a frontal position, with a slight tendency to the right and upward, while the posterior surface accordingly occupies the opposite position. When the stomach is moderately distended, the anterior surface rises about the lesser curvature as an axis, so that it forms an angle of from 45° to 48° with the horizon. When the distention is more marked, the stomach comes progressively to occupy inore nearly the horizontal position, so that its anterior surface gradually becomes the superior surface. The muscular coat of the stomach consists of an external or longitudinal layer of fibers, a middle or circular layer, and an internal or oblique layer, one layer passing over into another in many places. At the pylorus the musculature forms a circular sphincter-muscle (sphincter of the pylorus) , whose fibers continue into the pyloric valve. At the cardiac orifice also the muscle-fibers are grouped into a sphincter muscle. The movements of the stomach are of two kinds: i. The rotatory- rubbing movement, by means of which the walls of the stomach lying in immediate contact with the ingesta move to and fro with a slow displacing action. These movements succeed one another periodically, each cycle occupying several minutes. These movements can be imitated by slowly rolling or molding a ball between the palms of the hands by means of rotatory movements of the hands in opposite directions. Indeed, hair swallowed by cattle and dogs is formed into a regular ball in the stomach. The object of this rotatory movement is thoroughly to moisten the surface of the stomach-contents with the secretion of the gastric glands, and at the same time to favor its escape by the pressure and the continu- ous passage of ingesta, as well as to detach the already loosened and softened superficial layers of the food. Further, the admixture of the ingesta with the gastric juice is effected in this way. This movement may be either diminished, in the presence of gastric disease, such as gastric ulcer, or increased, as when there is stenosis or dilatation. 2. The other kind of movement is a peristalsis of periodic recur- rence, in conjunction with rhythmic opening and closure of the pylorus, as a result of which the partly dissolved gastric contents are little by little propelled into the duodenum, commencing after an interval of fif- teen minutes and ending at about the fifth hour. Each wave lasts twenty seconds, with an interval of from fifteen to twenty seconds between waves. This peristalsis is most active from the pyloric antrum toward the pylorus. According to Rtidinger, the longitudinal fibers passing toward the pylorus, in contracting, especially when the pyloric antrum is full, cause dilatation of the pylorus. THE MOVKMEXTS OF THE STOMACH. 201 Evacuation of the stomach occurs only when the intestine is free from con- tents. The followinjj experiment will serve to determine when the ingcsta enter the intestine. In the presence of an alkaline reaction in the intestine, salol is decomposed into carbolic acid and salicylic acid; the latter can be recognized in the urine from the violet color i)roduced upon adding ferric chlorid. In healthy persons this reaction begins in from half an hour to an hour and disappears after twenty-four hours; while in the presence of motor insufhciency of the stomach it is delayed from three to twenty-four hours. Liquids are rapidly propelled from the stomach into the intestine. The thick, muscular walls of the stomach in many grain-eating birds aid in triturating the ingesta. The energy of muscular action necessary for this purpose has often been measured by earlier investigators, who found that glass balls were broken, and lead pipes that could be flattened only by a pressure of 40 kilograms Avere compressed, in the stomach of the turkey. The masticating stomach of many insects also is capable of similar activity. Mechanical stimulation causes contraction of the muscular layers directly affected ; as does also application of potassium-salts, segmentary contraction of the circular muscles often taking place at the same time. Sodium-salts, on the con- trary, usually cause semicircular contractions or contractions progressing toward the cardiac orifice. At the pyloric antrum the stimulations as a rule spread more rapidly. Electrical stimulation of the internal surface of the stomach causes no movement. The contraction induced by stimulation of the intestinal mucous mem- brane is always less than that due to stimulation of the external surface of the in- testine. In human beings both endogastric and percutaneovis electrical stimulation are without demonstrable effect on the evacuation and the secretion of the stomach. XervoHs Activity. — Openchowski and his pupils make the following statements with respect to the influence of the nerves upon the movements of the stomach: The cardia contains automatic ganglion-cells, which are connected with the pneu- mogastric and the sympathetic nerves. A center for the contraction of the cardiac orifice is situated in the posterior quadrigeminal bodies, whence the paths pass downward, mainly through the pneumogastric, and in lesser degree through the splanchnic nerves. The center for opening the cardia lies in the corpus striatum. and in connection therewith one in the cruciate sulcus of the central cortex, in the dog; the pneumogastric nerves constitute the conducting paths. Dilatation centers are situated also in the upper portion of the spinal cord, whence the path passes through the sympathetic nerve (aortic plexus, lesser splanchnic nerve). Reflex opening of the' cardiac orifice can be induced by irritation of the sensory splanchnic nerves, and of the sciatic also. The body of the stomach contains also automatic ganglia, connected with the pneumogastric and the sympathetic nerves. A center for contraction is situated in the corpora quadrigemina, whence paths pass through the pneumogastric nerves and the spinal cord, and from the latter into the sympathetic. The upper cord contains inhibitory centers; the paths pass through the sympathetic and the splanchnic nerves. The pylorus contains automatic ganglia. It exhibits a certain, varying degree of tone during closure: the splanchnic nerve may more fully open the pylorus, while the pneumogastric tends to close it. The center for opening the cardiac orifice inhibits the movement of the pylorus; the path passes through the spinal cord and the splanchnic nerves. Inhibitory pyloric centers are situated in the corpora quadrigemina and the olivary bodies; the path passes through the spinal cord. The cortical center for opening the cardia causes simultaneous contraction of the pylorus; the path passes through the pneumogastric nerves. Centers for the contraction of the pylorus are situated in the corpora quadrigemina; the path passes through the pneumogastric nerves, a few fibers through the spinal cord and the svmpathetic nerve. Stimulation of the peritoneum and also of the skin causes reflex immobility of the p3-lorus and of the small intestine. Stimulation of the central stump of one pneumogastric, the other being intact, gives ri.se to immobility of the pylorus, contraction of the stomach and dilatation of the cardiac orifice. Elevation of the temperature to 25° C. causes movements in the excised empty stomach. Vomiting takes place in consequence of contraction of the walls of the stomach, the pvloric sphincter being at the same time closed. It occurs most readily when the stomach is distended. Dogs usually distend the stomach greatly before vomiting, by swallowing air. There is no doubt that in infants vomiting is due principally to contractions of the walls of the stomach, though without 282 THE MOVEMENTS OF THE INTESTINES. the slightest spasmodic cooperation of abdominal pressure. When the act of vomiting is attended with straining, abdominal pressure comes energetically mto ^ ^^The contractions of the walls of the stomach that cause a general diminution in the size of the viscus can be recognized when the stomach is exposed, i he pylorus contracts ; then wave-like contractions appear from the pyloric extrernity upward to the body of the stomach. The uppermost portion of the stomach, including the cardia, does not contract, but the cardiac orifice is opened by the con- traction of the longitudinal muscle-libers, which pass toward the esophageal opening, and therefore must act as dilators when the stomach is full. The actual ejection of the contents of the stomach is immediately preceded by an eructation-like movement, dilating the intrathoracic portion of the esopha- gus. This takes place in such a manner that, with the glottis closed xnolent. Jerky inspiration suddenly occurs, causing the esophagus to be distended by gas rising from the stomach. At the same time the larynx and the hyoid bone are drawn forcibly forward bv the combined action of the geniohyoid and sternohyoid, together with the sternothyroid and thyrohyoid muscles, with obliteration ot the laryngeal angle. As a means of support the lower jaw is even moved horizontally forward; as a result air passes from the pharynx downward to the upper portion of the esophagus. At the same time the projection and the inclination of the head favor dilatation of the esophagus. If, now, sudden abdominal pressure is exerted, supported by the intrinsic movements of the stomach, the contents of the yiscus will be ejected. If the vomiting be long continued, there may even be antiperis- talsis of the duodenum, as a result of which bile enters the stomach and becomes admixed with the vomited matters. Children, in whom the fundus of the stomach is not sacculated, vomit more readily than adults, in whom the fundus must contract forcibly. The center for the act of vomiting is situated in the medulla oblongata. It is connected with the respiratory center, as experience teaches that attacks of nausea can be overcome by rapid, deep respiration. The act of vomiting can be inhibited likewise in animals by means of artificial respiration. On the other hand, the administration of emetics does not permit the development of apnea. _ The act of vomiting may be excited by chemical or mechanical irritation of the centripetal nerves of the mucous membrane of the palate, the pharynx, the root of the tongue and the stomach; also, under certain conditions (pregnancy) by irritation of the uterus, of the intestines (peritonitis) , and also of the genito-urinary apparatus; finally by direct stimulation of the vomiting center. The act of vomiting excited by repulsive conceptions appears to result from the transmission of stimuli from the cerebrum through conducting fibers to the vomiting center. The act of vomiting is also common in connection with cerebral disease. Irritation of the central stump of the pneumogastric nerve is capable of inducing vomiting. _ _ . , • The ruminating process in ruminants resembles the -act of vomiting. Also m human beings eructation of food resembling morbid rumination has been observed as the expression of a gastric neurosis. There exists under such circumstances relative insufliciency of the cardiac orifice of the stomach : with the glottis closed, the contents of the stomach on attenuation of the air in the thorax rise into the mouth. Forced expiratory pressure is capable of preventing this phenomenon. Emetics SiCt (i) directly upon the vomiting center (as, for instance, apomorphin). Central vomiting ceases after destruction of the corpora quadrigemina, or division of the anterior columns of the spinal cord or destruction of all the spinal sympa- thetic fibers that pass to the stomach. (2) Other emetics act upon the vomiting center through reflex influences from the stomach or the intestine (copper sulphate, tartar emetic) . The irritation reaches the gastric musculature through the pneu- mogastric nerves. (3) Both of these modes of action may be combined. Emetics may also remove mucus from the respiratory organs. It would appear that emetics exert a favorable infliience upon the respiratory movements, through irritation of the respiratory center, as, for instance, in small children. THE MOVEMENTS OF THE INTESTINES. For observing the peristaltic movements in animals, the abdominal cavity is opened under a 0.9 per cent, sodium-chlorid sohition at blood-temperature in order to avoid the entrance of air ; or the observations may be made through the shaved and uninjured abdominal walls. THE EVACUATION OF FECES. 283 The small intestine exhibits peristaltic movements in a classical manner. The progressive constriction of the canal, which forces the contents before it, always passes from above downward. After death and on exposure of the coils of intestine to the air, peristalsis is often seen to develop in several parts of the intestine at the same time, and as a result the intestinal loops acquire the appearance of a mass of crawling worms. In addition to these movements, pendulum-like movements of the intestine also occur, by which the contents are moved some distance first in one direction and then in the other. The advance of new intestinal contents and the resulting increased distention of the tube due to solid contents or gas causes renewed movement. The large intestine exhibits less active and less extensive move- ments. When the abdominal walls are thin, or in the sac of a hernia, peristalsis may be felt and even seen. Herbivora exhibit more active peristalsis than camivora. Perhaps the transmission of peristalsis takes place directly through the musculature, as in the heart and the ureter. The ileo-cecal valve, as a rule, does not permit the usually more con- sistent contents of the large intestine to pass back into the small intes- tine. During sleep, at night, the movements of the stomach and the intestines cease. If fluid material is gradually introduced into the rectum from a height of one meter of \vater-pressure through an intestinal tube, it may pass upward through the ileo-cecal valve into the small intestine, and, with great care, it may reach the stomach and esophagus, and even escape from the mouth and nose. In this way the entire intestinal tract in the living subject can be irrigated, and with cura- tive results ; as, for instance, in cases of cholera (i or '2 per cent, solution of tannic acid in 7.5 per cent, solution of sodium chlorid). Eight or nine liters are sufficient to fill the entire alimentary canal. A crystal of sodium chlorid applied externally to the intestine causes con- traction at that point, with upward peristalsis, while potassium chlorid induces only local contraction. Particles saturated with sodium-chlorid solution and in- troduced into the rectum are carried upward, in part even to the stomach, through the mediation of nervous irritation, perhaps of the muscularis mucosae. Pathological. — If an inflammatory^ or catarrhal condition of the intestinal mucous membrane develops rapidly in consequence of an acute inflammatory irritation, contractions of the inflamed portion, at first marked, occur in the full intestine. When the affected portion has been emptied the movements are no longer more marked than normal. If further contents reach the inflamed portion, the peristaltic downward movement takes place more rapidly than normal and diarrhea results. At times a greatly contracted piece of the intestine is pushed into a neighboring portion (invagination, intussvisception) . Reduction in the bodily temperature is followed by a decrease in the peristalsis. That antiperistalsis, that is a movement upward toward the stomach, occurs was formerly considered proved by the appearance of fecal vomiting in connection with intestinal obstruction due to stenosis in human beings with occlusion of the bowel. The investigations of Nothnagel, however, throw doubt upon this con- clusion, as he failed to observe effective antiperistalsis after artificial occhision of the bowel. The fecal odor of the vomited matter may also depend upon its pro- longed sojourn in the duodenum, whence, as the well-known bilious vomiting shows, ingesta may be returned into the stomach. THE EVACUATION OF FECES (DEFECATION). The contents of the intestine remain in the small intestine about three hours, and for a further twelve hours in the large intestine, where they become inspissated, and in the lower portion formed into the fecal mass. Through the peristaltic movement, the feces are forced onward to a point somewhat above that portion of the rectum which 284 THE EVACUATION OF FECES. is surrounded bv both sphincter-muscles, of which the upper or internal is formed of unstriated and the external of striated muscle-fibers. Immediately after the act of defecation the external sphincter (Fig. 108, S; Fig. 109) usually contracts, and remains contracted for some time. When the muscle relaxes, the elasticity of the parts surrounding the anal opening, particularly of both the sphincter-muscles, is sufficient to insure closure of the anus. In the interval of rest or until the pressure of the feces again occurs, there is no evidence of a permanent contrac- tion (tonic innervation) of the anal sphincters. As long as the fecal matters lie above the rectum, they give rise to no conscious sensation. Pjc ijjg The Perineum and its Muscles: i, anus; 2, coccyx; 3, ischial tuberosity; 4, tuberososacral ligament; ' s acetabulum; B, bulbocavemosus muscle; Ts, superficial transverse perineal muscle; F, fascia of the deep transverse perineal muscle; J, ischiocavemosus muscle; O, internal obturator muscle; S, external sphincter ani muscle; L, levator ani muscle; P, pyriformis muscle. It is only their descent into the rectum that causes the feeling of tenesmus. At the same time the stimulation of the sensory nerves of the rectum causes reflex stimulation of the sphincters. The center for this reflex (Budge's anospinal center) is situated in the lumbar cord. In animals, after division of the spinal cord above this center, the anal opening closes actively when touched; but soon after this reflex contraction the sphincters relax, and the anus may thus remain open for a time. This is due to the fact that the active voluntary contraction of the external sphincter-muscle, already mentioned, under the control of the will (cerebrum), which keeps the anus closed for some time after each evacuation of the bowel, is absent. Ih dogs, in THE EVACUATION OF FECES. 285 which the posterior roots of the lower lumbar and the sacral nerves were divided, Landois observed that, while recovery was otherwise normal, the anus remained open. Not rarely a portion of the fecal mass protruded for a considerable time, as the sensibility in the rectum and anus was lost in such animals. Neither was reflex contraction of the sphincters possible, nor could voluntary closure of the anus, induced by the sense of feeling alone, take place, although this would other- wise have doubtless been possible. An excitomotor as well as an inhibitomotor influence may be exerted upon the external anal sphincter, as upon any voluntary muscle, from the cerebrum. Nevertheless, closure can be maintained only for a certain time if the pressure from above is considerable. Finally ener- getic peristalsis overcomes even the strongest voluntary stimulation. Fig. 109.— The Levator Ani and External Sphincter Ani Muscles. The evacuation of feces, which takes place habitually in human be- ings at a definite interval, once or twice daily, rarely oftener, begins with active peristalsis in the large intestine which passes downward to the rectum. In order that the sphincter muscles may not be excited to reflex activity by the advancing column of feces, it appears that an inhibitory center for the sphincter-reflex, capable of voluntary stimula- tion, must become active. This is situated in the brain (Masius sup- poses in the optic thalamus), whence its fibers pass through the cere- bral peduncles to the anospinal center. During stimulation of this inhibitory apparatus, the column of feces passes through the anus without causing its reflex closure. 286 NERVOUS IXFLUENCES AFFECTING INTESTINAL MOVEMENTS. The active peristalsis necessary to cause defecation may be favored and to a certain extent excited, partly by pressure, partly by short voluntary movements of the external sphincter and the levator ani muscles, whereby the myenteric plexus of the lower portion of the large intestine is stimulated mechanically, with the result that active peris- taltic movements of the large intestine are soon set up. The expulsion of feces is favored by active, voluntary abdominal pressure, principally with inspiratory depression of the diaphragm. The soft parts of the •pelvic floor are forced downward conically with a strong effort at stool, whereby the anal mucous membrane, which coincidently becomes filled with venous blood, is at times everted. It is the function of the levator ani muscle (Figs. loS and log) voluntarily to elevate the soft parts forming the pelvic floor and thus, in elevating the anus, in a measure to slide it over the descending column of feces. At the same time it prevents relaxation of the soft parts of the pelvic floor, particularly the pelvic fascia. As the fibers of both levator ani muscles converge down- ward, and mix with those of the external anal sphincter, they coinci- dently aid the sphincter when energetic contraction takes place, as they bear approximately the same relation to the anus that the strings of a tobacco-pouch bear to its opening. When the desire for stool is marked the closure of the anus can be made more secure by pressure from without through forcible rotation of the thighs outward and the action of the gluteal muscles. During the normal interval between evacuations of the bowel, the feces appear to descend only to the lower extremity of the sigmoid flexure. From this point to the anus the rectum normally is usually free from feces. The strong circular fibers of the muscularis, which Ndlaton termed the third anal sphincter, appear, b}* their contraction, to arrest the further advance of the fecal matter. NERVOUS INFLUENCES AFFECTING THE INTESTINAL MOVE- MENTS. The automatic center for the movements of the intestinal canal is the greatly developed myenteric plexus, which is embedded between the longitudinal and circular layers of the muscular coat. It is this that is responsible for the movements that continue for some time in an excised portion of intestine, just as they occur in the heart. This plexus, constituted mainly of non-medullated nerves, distributes fibers that, after again forming a network, pass to the unstriated muscle-fibers. The cells of the plexus possess an axis-cylinder process and several protoplasmic pro- cesses. Nerve-fibers pass through the mass of ganglia, while others surroiind the ganglion-cells with their extremities. Special nerve - plexuses, containing ganglia, are found upon the blood-vessels and lymph- vessels of the intestinal wall. When this center is free from all stimulation, the intestine remains in a state of rest, resembling the apnea that occurs with absence of stimu- lation of the medulla oblongata. This occurs during intra-uterine life, as it does also with respect to respiration, in consequence of the large amount of oxygen in the fetal blood. This condition may be termed intestinal rest — aperistalsis. It is observed also during sleep, perhaps in consequence of the greater amount of oxygen in the blood. The circulation through the intestinal vessels of blood containing NERVOUS INFLUENCES AFFECTING INTESTINAL MOVEMENTS. 287 the usual amount of gases gives rise to the quiet peristaltic movement of the healthy individual — euperistalsis. All stimuli transmitted to the myenteric plexus increase peristalsis, which finally may progress to violent movement, with rumbling in the intestines (borborygmus), and may even cause involuntary discharge of feces and spasmodic contraction of the intestinal musculature. This condition, which corresponds to dyspnea, may be designated dysper- istalsis. This condition may be caused (a) by interruption of the circulation in the intestines, I'c matters not whether anemia, as after compression of the aorta, or venotis hyperemia is thereby induced. The exciting agent here is the deficiency of oxygen, or the excess of carbon dioxid. Even shghter circulatory disturbances in the intestinal blood-vessels, as, for instance, venous stasis in connection with abundant transfusion into the veins, whereby transitory overdistention of the venous system, and therefore stasis in the portal system occurs, give rise to in- creased peristalsis. This takes the form of noises and rumbling in the intestines, together with involuntary defecation, if, in consequence of transfusion of hetero- geneous blood, stasis becomes marked, as a result of thrombosis of the intestinal blood-vessels. Landois explains in this way the irresistible inclination to stool and the increased peristalsis that attend certain forms of cardiac weakness of acute onset and sclerosis of the coronary arteries, in consequence of which the circulation in the intestines suddenly ceases. A similar state of affairs is observed even under normal conditions. Landois believed that the persistent pressure in constipated individuals induces the evacuation that eventually takes place, as much by exciting peristalsis through the venous stasis in the intestines as by mechanical pressure upon the intestinal canal. Also the increased peristalsis that constantly attends approaching death depends, undoubtedly, upon circulatory- disturbances and thus upon an alteration in the amount of gases in the blood in the intestines. The same statement is applicable to the increased intestinal movement that attends certain emotional disturbances, as, for instance, fear. Here the stimulation of the brain passes through the medulla oblongata (containing the center for the vasomotor nerves) to the intestinal nerves and causes circulatory disturbances in the intestines (coincidently with pallor). Restoration of the normal circulatory condition restores the intestines to quiet peristalsis. Salvioli caused blood to flow artificially through excised pieces of intestine by means of cannulas intro- duced into the" blood-vessels, and found that blood rich in oxygen caused intestinal rest, while interruption of the circulation caused contractions of the intestines. B6kai was able to overcome the dysperistalsis induced by the introduction of carbon dioxid into the intestines by introducing oxygen into the intestinal cavity. (6) Direct irritation of the intestine causes movement not only of the part directly affected, but also of the neighboring part of the intestines, especially that Iving toward the pylorus. The cumulative effect of stimuli is shown here ; that is feeble stimuli, which are too weak to excite movement when applied but once, do so on persistent repetition, as exposure of the intestines to the air, in more marked degree in the presence of carbon dioxid and chlorin, the introduction of certain irritating substances into the intestine, marked distention of the intestinal canal, especially with coincident difficulty in or obstruction to defecation (which occurs frequently in human beings), or direct irritation of different kinds, also inflammatory processes involving the intestine either from within or from without. In this connection, the observation is of interest that induced currents applied to a hernial sac containing intestine excite active peristalsis in the hernia. Local irritation of a portion of the intestine with a tetanizing induced current causes a circular constriction, which advances especially toward the stomach when the current is of considerable strength. The shortening of the longitudinal fibers that are stimulated at the same time extends in both directions. With increasing temperature intestinal rest first results-— from irritation of the splanchnic nerves; when the temperature reaches 43° C. intestinal movement is resumed. All persistent stimuli of moderate strength cause cessation of dys- peristaltic intestinal movement from overstimulation. This condition may be designated intestinal exhaustion or intestinal paresis. 288 NERVOUS INFLUENCES AFFECTING INTESTINAL MOVEMENTS. This State of rest of the intestine is thus widely different from that attending the condition of aperistalsis. Persistent stasis of blood in the intestinal vessels leads finallv to intestinal exhaustion, as, for instance, when thrombosis occurs m the intestinal vessels after transfusion of blood from a different species. Distention of the vessels with indifferent fluids, after compression of the aorta had previously excited active peristalsis, likewise causes cessation of peristaltic movement. In the same category belongs also the condition of rest noted after the temperature of the intestine has been reduced to 19° C. Severe intestinal inflammation also has a similar effect. Under favorable conditions the intestine may recover from this stage of exhaustion after the irritation has ceased. This takes place, as a rule, through a transitional stage attended with active peristalsis. Thus the intro- duction of arterial blood into the vessels of the exhausted intestine causes at first active peristaltic movements, followed by normal peristalsis. The continuous application of strong stimuli finally causes complete paralysis of the intestine in human beings as seen after inflammations, traumatisms, incarcerations, and the like. The intestine becomes greatly distended, as the paralyzed muscularis is no longer able to offer any resistance to the gases expanded by the heat (meteorism). The Peripheral Intestinal Nerves. — Of the nerves passing to the intestine the pneumogastnc nerve increases the movements of the small intestine and the upper portion of the large intestine, either by conveying the stimuli applied to it to the myenteric plexus, or by causing contractions of the stomach, which, in turn, as true mechanical impulses, excite the intestine to movement. The pneumogastric nerves also contain several inhibitomotor fibers. The splanchnic nerve — the greater derived from the sixth to the ninth, and the lesser from the tenth and eleventh dorsal ganglia — is (i) the inhibitory nerve for the intestinal movements, but only so long as the blood in the capillaries has not become venous while the circulation in the intestine remains undisturbed. _ If the latter condition has arisen, irritation of the splanchnic causes increased peristalsis. If arterial blood be introduced, the inhibitory action is prolonged. Irritation of the origin of the splanchnic nerve in the dorsal cord also produces the inhibitory effect under analogous circumstances, even in the presence of irritation of the spinal cord as a result of strychnin-poisoning, with the occurrence of general tetanic convulsions. O. Nasse believes that it may be concluded from the experi- ments that, in addition to these readily exhausted inhibitory fibers, paralyzed by venosity of the blood, there are present (2) motor fibers that are excitable for a longer time, inasmuch as stimulation of the splanchnic nerve after death always causes peristalsis of the stomach and intestines, as does stimulation of the pneu- mogastric nerve. (3) The splanchnic nerve is also the vasomotor nerve of all of the arteries and veins of the intestines, including the portal vein, thus controlling the largest vascular area of the body. Stimulation of the splanchnic nerve causes contraction, its division dilatation, of all of the intestinal blood-vessels possessing muscle-fibers. In the latter event an enormous accumulation of blood takes place in the intestinal vessels, so that anemia of other parts of the body results, and in consequence even death may take place from anemia of the medulla oblon- gata. (4) The splanchnic nerve is, finally, the sensory nerve of the intestines, and, as such, it is extremely sensitive. Almost all the cells of th6 solar plexus are included in the course of the fibers of the splanchnic nerve. Nicotin paralyzes these cells, while the peripheral fiber retains its irritability. Stimulation of the nervi erigentes causes contraction of the longitudinal mus- cular fibers and relaxation of the circular fibers of the rectum; while irritation of the hypogastric nerves has the opposite effect according to FcUner. Stimulation of the sigmoid gyrus on the cerebral cortex of the dog, as well as of parts lateral to and behind it, excites intestinal movements through the pneumogastric nerves, as does likewise stimulation of the optic thalamus. Inhibi- tory fibers pass from both of these situations through the spinal cord, from which they make their exit near the middle of the dorsal cord. The dinigs that affect the intestine are (i) those that diminish the irritability of the myenteric plexus, and thus decrease peristalsis, even to the point of intes- tinal rest, like belladonna; (2) those that stimulate the nerves inhibiting peris- talsis, and paralvze in large doses, like opium or morphin. The drugs of these two classes caus'e constipation. Elevation of temperature (also during fever) THE STRUCTURE OF THE GASTRIC MUCOUS MKMBKAXE. •89 diminishes intestinal i)cristalsis through irritation of the splanchnic nerve. (3) Other drugs stimulate the motor apparatus; such as nicntin, to the point of intestinal crumps, muscarin, calTcin and some laxatives, whicli thus act as evacu- ants. The movement excited by muscarin can be neutralized by atropin. As. in consequence of the rapid movement of the intestinal contents, the contained fluid can be absorbed in but small measure, the frequent evacuations that follow are at the same time liquid. (4) Among purgatives, mention should be made of those that irritate the intestines directly, such as colocynth and croton-oil. It is supposed that agents of this kind cause' a watery transudation from the blood- vessels into the intestine, just as croton-oil also causes vesicles on the external skin. (5) Certain laxative salts, sodium sulphate, magnesium sulphate and others, liquefy the intestinal contents by retaining for their solution in the intestine the water of the intestinal contents; if, therefore, they are injected into the blood- vessels of an animal, constipation may even result. (6) Calomel (mercurous chlorid) restricts the absorptive power of the walls of the intestine, and also putrefactive decomposition in the bowels. Therefore the fecal evacuations are thin, with little odor, and of a greenish color from admixture of unchanged bili- verdin. THE STRUCTURE OF THE GASTRIC MUCOUS MEMBRANE. The surface of the mucous membrane of the stomach exhibits numerous small depressions, the gastric crypts (foveoke gastrica?. Fig. no), lined by a single layer of mucous goblet cells (Fig. 112, d). These cells are sharply delimited at the cardiac oritice from the stratified squamous epithelium of the esophagus; and at the pyloric extremity from the true cylindrical epithelium of the duodenum. The cells with almost homogeneous contents are provided with elliptical nuclei containing nucleoli. Between their narrowed, lower ends are scattered oblong or spindle-shaped, unencapsulated, nucleated elements, exhibiting mitosis, which are intended to replace desquamated cells. All cells are completely open upon their free surface, so that nothing prevents the escape of the mucus elaborated by mucous metamorposis from the cell-protoplasm. The simple tubular gastric glands, generally several in num- ber, empty into the bottom of the gastric crj'pts. They occur in two different forms : 1 . As true gastric glands, peptic glands of the fundus (Fig. 114), which number about five millions, the largest being present in the fundus. The structureless membrana propria of simple tubular form, has, on its internal surface, two different kinds of cells : (a) the chief cells (Fig. 1 1 1 , II, a), the adelomorphous ceils of RoUett; small, unencapsulated, nucleated, pale cells lying close together, lining the inner lumen of the glands, and (6) larger, mainly scattered, plainl}^ projecting parie- tal cells (Fig. Ill, II, h), the delomorphous cells of Rollett, ovoid or crescentic, without a membrane, darkly granular, readily stained with osmic acid and aniline-blue, containing, at times, several nuclei. They cause bulbous projections of the mem- brana propria. In human beings the parietal cells are thought to reach to the lumen of the spaces within the gland. They are even found scattered under the epithelium of the crypts and the surface of the mucous membrane, as well as in isolated pyloric glands. Between the chief cells secretory spaces are present, and likewise between neighboring parietal cells, while, at the same time, with the latter delicate branching and anastomosing passages in part lead from the excretory duct of the gland into the interior of the parietal cells and in part form a network surrounding them. 2. Only in the vicinity of the pylorus, where the mucous membrane has a 19 Fig. 1 10. — Sectioniil View of the Gastric Mucous Membrane, Showing the Crater-like Depres- sions of the Gastric Crypts: a, a, the most prominent projections of the mucous mem- brane (from a dog). 290 THE STRUCTURE OF THE GASTRIC MUCOUS MEMBRAXE. rather yellowish- white appearance, are the pyloric glands (Fig. 112, A) found, in general in smaller number. At their lower extremity their ducts are not rarely divided into two or more blind sacs. Their cellular contents consist, as a rule, Fig. III.— I. Transverse Section through the Duct of a Fundus-gland : a. membrana propria; b, goblet-cells; c, reticular connective tissue. II. Section through the Glands of the Fundus: a, chief cells; h, parietal cells; r, reticular tissue of the mucous membrane between the glandular tubules; c, dirided blood-vessels. Fig. 112. — d, Isolated goblet-ceUs; A, pyloric gland of the stomach. Fig. 113. — M, Portion of a gastric gland with chief cells (h h) and parietal cells (b b); the latter exhibit intracellular secretory canals. Between the chief cells interceUular secretory ducts (z z) penetrate for some distance; a, excretory duct of the gland. THE STRUCTURE OF THE GASTRIC MUCOUS MEMBRANE. 291 of a variety of finely granular secreting cells, which tjiost nearly resemble the chief cells of the lab-g!ands. 3. At the cardiac orifice, also, there lies a circular layer of tubules without parietal cells, which secrete diastatic ferment. The scanty supporting structure of the gastric mucous membrane consists of reticular connective tissue with leukocytes, mixed with fibrillar}^ connective tissue and elastic fibers. The mucous membrane possesses a special muscular layer, the muscularis mucosae. This passes as a rather thick stratum under the base of the gland, often exhibiting an inner circular and an outer longitudinal layer. From Fig. 114.— Vertical Section through the Gastric Mucous Membrane: g g, the crj'pts of the surface; p. the mouths of the peptic tubuses (fundus glands) with parietal cells (x) and chief cells (y); avc c .artery, vein and capil- laries of the mucous membrane; i, capillarv network for the passage of the mouth of the gland-duct; d d, the lymphatic vessels of the mucous membrane, passing over, at e, into a large trunk (senudiagrammauc representation). this stratiim a number of bundles of fibers pass upward between the glands and around them. They appear to be intended for active evacuation of the glandular tubules. Numerous blood-vessels (Fig. 114) enter from the fibrillary connective tissue of the submucosa (a) , spread out into a longitudinal capillary network (c c) between the glands, and reach the free surface, where they again form a fine meshwork (1 1) just under the epithelium, and through the meshes of which the mouths of the ducts (g) make their appearance. Collecting at this point the vems unite m the submucosa to form trunks of considerable size (v) . 292 THE GASTRIC JUICE. The lymphatic vessels of the gastric mucous membrane begin rather close beneath the epithelium as bulbous or loop-like formations (d d) , then pass per- pendicularly to the submucosa, where they attain a considerable size (e) through the union of adjacent branches. The nerves are the same as those of the intestine. The submucosa consists of bundles of connective tissue with elastic fibers and embedded fat-cells. THE GASTRIC JUICE. The gastric juice is a fairly clear, colorless, levorotatory, readily filtered fluid, with a strongly acid reaction, an acid taste and a character- istic odor. From the presence of free hydrochloric acid, it counteracts putrefaction and, in part, fermentation. Its specific gravity, when the stomach is empty (fasting), ranges between 1004 and 1006.5; after the ingestion of food, from loio to 1020, and more than 1020 when the production of acid is diminished. Its amount was said by Beaumont, in 1843, from observations upon a human being with a gastric fistula, to be only 180 grams daily. According to Griinewald, in 1853, it was estimated in a similar case to be 26.4 per cent, of the body- weight in twenty-four hours. Finally it was placed by Bidder and Carl Schmidt, after comparative observations upon dogs, as 6.} kilograms in the day, corresponding to yV of the body-weight. The gastric juice contains : 1. Pepsin, the characteristic, nitrogenous, hydrolytic ferment or enzyme that dissolves proteids: from 0.41 to 1.17 per cent. 2. Hydrochloric acid occurs free in the gastric juice: from 0.2 to 0.3 per cent. 3. Lactic acid may also be found, either from fermentation of carbo- hydrates (fermentation lactic acid) or from being dissolved out of the meat of the food (sarcolactic acid). Reactions. — Hydrochloric acid alone, and in the free state, is identified by Gunzburg's reagent: To a few drops of filtered gastric juice an equal number of drops of a solution of 2 grams of phloroglucin and i gram of vanillin in 30 grams of alcohol are added, and the mixture is evaporated in a porcelain dish over the water-bath, with the development of a rose-red color. Resorcin, 2.5 grams, dis- solved in 50 grams of dilute alcohol, with addition of 1.5 grams of cane-sugar, may be employed in a manner analogous to the foregoing reagent, likewise giving rise to a red color. Reaciion for Lactic Acid. — A freshly prepared blue mixture of 10 cu. cm. of a 4 per cent, solution of carbolic acid, with 20 cu. cm. of distilled water and one drop of ferric chlorid, is colored yellow by lactic acid. To 5 cu. cm. of the gastric juice to be tested i or 2 drops of hydrochloric acid are added, and the mixture is evaporated over a free flame to the thickness of sirup. The residue is extracted with a little ether, is then poured into a reagent glass containing 5 cu. cm. of water, one drop of a 5 per cent, solution of ferric chlorid is added, and the mixture is shaken. A greenish-yellow color appears even when i part of lactic acid in 1000 is present. The gastric contents, evaporated to the consistency of sirup, to expel the alcohol, are extracted by shaking with ether. The filtrate, on addition of an alcoholic solution of iodin arid being heated, yields iodoform, in consequence of the formation of acetaldehyd from the lactic acid. Hydrochloric acid and organic acids together yield the following reactions. To demonstrate the total free acids (those not combined with albumin), Congo- red is used, also in the form of reagent-paper. It indicates the presence of free hydrochloric acid or a considerable amount of free organic acids by becoming blue in color. The same information is aftorded by dark-red benzopurpurin, which is changed to a violet color, and also by tropaeolin OO. A little of a concentrated alcoholic solution of the latter, heated'with 4 drops of gastric juice in a dish, yields a bluish- violet stain. THE SECRETION' OF THE GASTRIC JUICE. 293 4. For a consideration of the milk-ferment, reference may be made to page 300. 5. The large amount of mucus adherent to the surface of the mucosa is a secretion of the mucous goblet-cells. 6. Inorganic matters are present in percentages for human beings (and for dogs, in parenthesis) as follows: Water, 994.40 (973.06); hydro- chloric acid, 0.20 (2.84); calcium chlorid, 0.06 (0.96); sodium chlorid, 1.46 (2.82); potassium chlorid, 0.55 (1.09); ammonium chlorid (0.5); calcium, magnesium, and iron phosphates, 0.125 (2.7). Organic matters, principally pepsin, are present to the amount of 0.32 per cent. (1.7 1). Of foreign substances, the following appear in the gastric juice after introduction into the body: potassium sulphocyanid, iron lactate, potassium ferrocyanid, sugar, etc. Ammonium carbonate is found in the presence of uremia. THE SECRETION OF THE GASTRIC JUICE. During the course of digestion characteristic changes take place in the chief cells, and in the parietal cells of the fundus glands and in the cells of the pyloric glands. The chief cells contain granules that are consumed during the process of secretion. The granules contain the pepsin-forming substance, which is transformed into pepsin. The size of the chief cells diminishes also during secretion. At rest these cells take from the lymph, material for the production of the granules. The parietal cells, during the period of secretion, appear first to be swollen, then to become smaller. All of the cells, further, are darker, and the nucleus of the cells of the pyloric glands moves toward the center. The secretory ducts become more distended. In some animals the chief cells, during secretion, bear a fringe of short, hair-like processes (Tornier's "brush-fringe"!), directed toward the lumen of the gland. The pepsin is formed in the chief cells. If these are swollen, they produce much pepsin; if shrunken, they produce but little. The pyloric glands also secrete pepsin, though in much less amount. During the first stage of hunger the pepsin accumulates; while during the period of digestive activity it is eliminated, as it is also when hunger is pro- tracted. Klemensiewicz removed the pyloric portion of the stomach of a dog with two incisions; sutured the duodenum to the stomach, and allowed the pyloric portion, still in communication with its blood-vessels, to heal in the abdominal wound, after closure of its lower extremity by sutures. The secretion of this portion of the stomach was viscid and alkaline, containing 2 per cent, of solid matters, including pepsin. The glands themselves contain no pepsin, but only a zymogen, namely, the pepsinogenic substance or propepsin, which occurs in the granules of the chief cells. The zymogen, of itself, exerts no influ- ence upon proteids. If, however, it be treated with hydrochloric acid or sodium chlorid, it is transformed into pepsin. In addition to pepsin, the pepsinogenic substance may be extracted from the mucous membrane of the stomach by means of water free from acid. The milk-ferment also originates in the chief cells. The hydrochloric acid is formed by the parietal cells. It is found 294 THE SECRETION OF THE GASTRIC JUICE. on the free surface of the mucous membrane, as well as in the excretory ducts of the gastric glands. In the depth of the glandular tubules, however, the reaction is generally alkaline. The acid must, therefore, be advanced rapidly from the depth to the surface. Sarcolactic acid can be rapidly extracted as such from the chyme. For the production of lactic acid through fermentation in the stomach it is necessary that the carbohydrates have been present for a consider- able time. This does not occur in the healthy individual, but in asso- ciation with great diminution in the production of hydrochloric acid, stagnation of the ingesta in the stomach, and interference with gastric absorption, particularly in the presence of gastric carcinoma. Lactic-acid bacteria are always present in the stomach, though they exhibit no activity in the presence of healthy gastric juice on account of the anti-fermenta- tive influence of the hydrochloric acid. Lactic acid develops, however, only in the absence of free hydrochloric acid, which is particularly often the case in the presence of gastric carcinoma. The hydrochloric acid first secreted at once combines in the stomach with the proteids to form acid albuminates. These do not yield the color-reactions of free acid. As the secretion progresses free hydro- chloric acid makes its appearance. If the secretion of gastric juice be enfeebled it may, therefore, happen that the production of hydrochloric acid is not sufficient to permit of the appearance of free hydrochloric acid. When the tests for hydrochloric acid in the stomach-contents are distinctly, even though feebly, positive, sufficient hydrochloric acid is present; an unusually strong reaction is indicative of abnormally increased production. If the reaction is wanting, a decinormal hydrochloric-acid solution is added to a measured amount of gastric contents until a distinct reaction is obtained by Giinzburg's test. The am.ount of hydrochloric acid consumed is then proportional to the degree of the hydrochloric-acid insufficiency present. In regard to the production of free acid, the following appears to be established. The parietal cells secrete hydrochloric acid from the chlorids that the mucous membrane takes up from the blood. There- fore, the production of hydrochloric acid ceases when the chlorids are withdrawn from the food, as well as in the state of hunger. The active agent in this connection has not been discovered; yet it is established that, if carbon dioxid acts continuously on the chlorids, nevertheless, hydrochloric acid is expelled by the much weaker carbon dioxid. Maly and others assume that the production of hydrochloric acid takes place within the parietal cells as follows: 2Na2HPO,+3CaCl2=Ca3(PO,)2+4NaCl4-2HCl. The bases set free by the separation of the hydrochloric acid are excreted in the urine, with the development of a slightly acid reaction. When the stomach is empty the gastric juice contains some hydro- chloric acid, but a more abundant secretion is, according to Pawlow, brought about in a most striking manner by the appetite, and also by the stimulation of the food under natural conditions, as w^ell as by water, meat-extractives, and even by indigestible matters when intro- duced into the stomach. Under these circumstances the mucous mem- brane is reddened from increased activity of the circulation, so that the outflowing venous blood is lighter in color. The excitation of the secre- tion is a reflex process. The sensory nerves of the pharynx and the METHODS OF OBTAINING THE GASTRIC JUICE. 295 Stomach excite, in a centripetal direction, the medulla oblongata, which contains the center for this reflex. The centrifugal path to the mucous membrane traverses the pneumogastric nerves, after the division of which the reflex is abolished. The mucous membrane subsequently furnishes a moderate amount of a feebly active, paralytic secretion. During sleep in the stage of digestion, the amount of acid increases. Heidenhain found in experiments upon dogs — in which, in the same way as the pylorus, he isolated the fundus for the formation of a blind sac — that mechan- ical irritation induced only local secretion. If, however, absorption of digested substances took place at the point of irritation, the secretion spread out over a larger surface. Small quantities of alcohol, introduced into the stomach, increase the secretion of the gastric juice, while large amounts abolish it and enfeeble the movements of the stomach. Fat inhibits the secretion of the gastric juice. Artificial digestion is somewhat disturbed by alcohol up to 2 per cent., and in greater degree by 10 per cent, alcohol; 20 per cent, alcohol retards, while still larger amounts abolish it. Beer and wine retard digestion, and undiluted they prevent artificial diges- tion. The administration of large amounts of sodium chlorid diminishes the secre- tion of hydrochloric acid, while the ingestion of much sugar only delays it. After two days of fasting the secretion of hydrochloric acid ceases (in the dog) . Gastric ulcers cause reflex increase in the production of hydrochloric acid; jaundice, nervous gastric aft'ections and anemias, a reflex diminvition. The gastric juice, which passes into the duodenum after digestion is completed, is neutralized by the alkalis of the intestinal and of the pancreatic juices. The pepsin is absorbed as such, and can be found in small amounts in the urine and in the muscle-juice. If the gastric juice is removed completely through a gastric fistula, the alkalies in the intestines become so abundant that the urine is ren- dered alkaline. The acid gastric juice in the new-born is quite intensely active. It most readily digests casein, and next in order fibrin and other proteids. In consequence of excessive acidity of the gastric juice, large masses of casein, difficult of digestion, form in the stomach of infants, and are especially tough after the ingestion of cow's milk. The following drugs are excreted by the gastric juice after introduction into the body-juices: Morphin, veratrin, caffein, quinin, aritipyrin, chloroform, chloral hydrate, methyl-alcohol, ethyl-alcohol and acetone. Comparative. — According to Klug, the parietal cells of grain-eating birds pre- pare also pepsin, in addition to hydrochloric acid. The gastric glands of the frog, which possess only parietal cells, likewise secrete pepsin; the pyloric glands of the dog, which contain only chief cells, nevertheless secrete acid. Accordingly both kinds of cells secrete hydrochloric acid. METHODS OF OBTAINING THE GASTRIC JUICE. THE PREPARATION OF ARTIFICIAL DIGESTIVE FLUIDS; DEMONSTRA- TION AND PROPERTIES OF PEPSIN. To obtain the gastric juice Spallanzani had fasting dogs swallow bits of sponge enclosed in perforated leaden capsules, and withdrew them after they had become saturated with the gastric juice. In order to prevent admixture with the secre- tions of the mouth, the sponge is best introduced through an opening made in the esophagus ligated above. Beaumont (1825-1833), an American physician, was the first to obtain gastric juice from a human being, in the case of the Canadian hunter, Alexis St. Martin, whose stomach had been opened by a bullet-wound, with the formation of a per- manent gastric fistula. Various substances were introduced directly into the stomach through the opening, and examined from time to time as to their digestion. Guided by this, Bassow, in 1842, was the first to estabUsh an artificial gastric fistula in a dog. The wall of the stomach is opened below the xiphoid process, and the margins of the gastric opening are united by suture to the margins^ of 296 METHODS OF OBTAINING THE GASTRIC JUICE. the wound in the abdominal walls. A short tube with a terminal plate is placed in the fistula in such a manner that the plate lies in contact with the margin of the mucous membrane. The tube possesses a screw-thread, upon which an appro- priate cannvila can be so screwed that the terminal plate lies upon the abdominal wall outside of the margins of the wound. The parts are joined in the following manner I- H. As a rule the opening of the cannula is corked. If in such dogs the excretory ducts of the salivary glands are additionally ligated, unmixed gastric juice is secured. According to C. A. Ewald and Leube, dilute gastric jttice can be obtained from human beings by introducing water into the empty stomach through a tube that acts like a siphon, and withdrawing the fluid by siphonage after a short time. An important advance was made by Eberle, in 1834, who taught that artificial gastric juice could be prepared by extracting pepsin from the gastric mucous membrane by means of dilute hydrochloric acid. Dilute hydrochloric acid serves for the extraction of the triturated gastric mucous membrane — 0.088 per cent, for the digestion of fibrin, 0.16 per cent, for the digestion of coagulated albumin — being added anew, in quantities of a half liter every six or eight hours. The later extracts are even more active than the first. The fluid collected is filtered and in it are placed, at the temperature of the body, the substances to be digested. It is, however, necessary to add more hydrochloric acid from time to time. That degree of acidity affects digestion most favorably that most causes the proteids to swell. According to Klug, gastric j\iice containing 0.6 per cent, of hydro- chloric acid and o.i per cent, of pepsin is most effective. Pepsin from dogs is especially active. Digestion pursues a favorable course between 37° and 40° C. ; while it ceases in the cold, as well as at higher temperatures. The hydrochloric acid employed may be replaced, to a certain extent, by other halogen-acids, whose activity is inversely proportional to their molecular weight; further by from six to ten times as much lactic acid; by nitric acid; in a much less effective manner, finally, by oxalic, sulphuric, phosphoric, acetic, formic, succinic, tartaric, and citric acids. In general, the acids with greater acidity act more powerfully, with the exception of sulphuric acid. The action of the different acids varies, however, accordingly as fibrin, casein, solid or liquid albumin is employed. V. Wittich showed that pure pepsin can be extracted from the gastric mucous membrane by means of glycerin also. After cleaning the mucous membrane, it is left in alcohol for twenty-four hours, then dried, pulverized and sifted, and then extracted for a week in glycerin. On addition of alcohol to the filtered extract pepsin is precipitated, and this, dissolved in dilute hydrochloric acid, yields active gastric juice. The preparation of perfectly pure pepsin has been effected by W. Kuhne by exposing commintated pigs' stomachs to autodigestion with dilute hydrochloric acid at the temperature of the body. The mass, which is for the most part liquefied, is saturated with ammonium sulphate, by which pepsin and albumoses still present are precipitated. The residue collected on the filter is again — and if necessary repeatedly— digested in the incubator, after addition of dilute hydrochloric acid. If, finally, all of the albumin has been converted into peptone, the pepsin alone is precipitated by repeated satttration with ammonium sulphate, and is collected on the filter. It is dissolved in water, its salts are removed by dialysis and it is finally precipitated in a pure state by alcohol. Briicke had previously prepared pure pepsin by causing a voluminous precipitate in the digestive mixture including the pepsin, and separating the latter. Pekelharing found that a strongly active arti- ficial gastric juice, on dialysis with water, caused the separation of a precipitate of pepsin. In all the processes of extraction, the yield of pepsin is greatest when the mucous membrane, protected from putrefaction, is exposed to the air for some time, as subsequently propepsin and pepsin are formed in the gland-cells. Pure pepsin is a colloid substance. It does not yield the reactions of albumin to the following tests: It does not respond to the xantho- proteic test, is not precipitated by acetic acid and potassium ferrocyanid, by tannic acid, mercuric chlorid, argentic nitrate or iodin. In other respects it is to be included among the albuminoid substances. Pepsin, when heated to a temperature of from 55° to 60° C. or above, in acid solution, is rendered inactive. THE PROCESS AND THE PRODUCTS OK GASTRIC DIGESTION. 297 THE PROCESS AND THE PRODUCTS OF GASTRIC DIGESTION. The mixture of finely divided food and gastric juice is designated chyme. Upon this the gastric juice exerts its action. ACTION UPON PROTEIDS. The pepsin and the free hydrochloric acid are capable of transforming the proteids, at the temperature of the body, into a readily soluble modification that has been designated peptone. In this process the proteids are changed first into bodies possessing the character of synto- nins, and in this condition the solid proteids are swollen. Syntonin is an acid-albuminate. By neutralization, with cautious addition of an alkali, the albumin is precipitated. Then, by combination with water and division into numerous small molecules, a product results, which is, to a certain extent, an intermediary body between albumin and peptone — the albumose of W. Kiihne and Chittenden (propeptone of Schmidt-Mulheim). This is soluble in water, readily soluble in dilute acids, alkalies and salts. These solutions are not precipitated by boiling, but by acetic acid and potassium ferrocyanid, as well as by acetic acid and saturation with sodium chlorid or magnesium sulphate. Albumose is precipitated by nitric acid, but it is redissolved, with the production of an intense yellow color when heated, and it is again precipitated on cooling. Some albumoses possess diffusibility. With the continued action of the gastric juice, the albumose passes over into soluble and readily diffusible peptone. The unchanged pro- teids behave toward the peptones as anhydrids with a large albumin- molecule. The production of peptone and its solution result, therefore, from decomposition with the taking up of water, brought about by the hydrolytic ferment, pepsin. This action takes place best at the tem- perature of the body. According to W. Kuhne, the proteid molecule contains two different substances, namely hemi-albumin and anti-albumin. By the action on these of hydrochloric acid syntonin is produced. This is next broken up into the two primary albu- moses: protalbumose, soluble in water, and hetero-albumose, soluble in salt- solutions. Both are then transformed into deutero-albumoses, which, in contra- distinction to the primary albumoses, are not precipitated in neutral solution by saturation with sodium chlorid. Deutero-albumose in contradistinction to pro- talbumose is not precipitated by copper sulphate. The deutero-albumoses are then decomposed into peptones: hemipeptone and antipeptone. The pepsin enters into intimate relations with the proteid molecule. The greater the amount of pepsin present, the more rapidly, to a certain degree, does digestion take place. The pepsin itself undergoes almost no change, and if care is taken to keep the amount of hydrochloric acid always the same, it is able to digest new amounts of albumin (one part to about 500,000 parts). Nevertheless some pepsin is consumed in the process of digestion. The proteids are introduced into the stomach either in a liquid or in a solid form. Of the liquid proteids only casein is at once coagulated in solid form and precipitated and then redissolved. The other liquid proteids remain liquid, are converted into the condition of syntonins, and then immediately into albumoses and finally into peptones, that is, actually digested. Uncoagulated and coagulated proteids, globulins, fibrin, some forms 298 THE PROCESS AND THE PRODUCTS OF GASTRIC DIGESTION. of vitellin, chondrigen, collagen, and elastin, though with difficulty, are in the same way converted into albumoses and peptones ; while neuro- keratin, keratin, and nuclein remain undigested. During the digestion of albumin, absorption of heat takes place, demonstrable by the thermometer. Accordingly the temperature of the chyme in the stomach falls, in the course of two or three hours, from 0.2° to 0.6° C. The coagulated proteids may be designated the anhydrids of the liquid proteids and the latter in turn the anhydrids of the peptones. Thus the peptones represent the highest possible stage of hydration of the proteid bodies. Peptones may also be obtained from proteids with the aid of such agents as usually cause hydration, particularly by treatment \vith superheated steam vapor, through the action of strong acids, caustic alkalies, ferments of putrefaction and some other ferments, as ^yell as by ozone. The proteid anhydrids may be reconverted from this stage of hydra- tion by the abstraction of water. By heating with acetic-acid anhydrid at a temperature of 80° C. peptone is transformed into svntonin. Also by heating to a temperature of 170° C, through the action of the galvanic current in the presence of sodium chlorid, and through the action of alcohol together with salts, peptone is retransformed into albumin. Albumose was thus first seen to result from fibrin-peptone. Properties of Peptones. — (i) They are readily and completely soluble in water. (2) They diffuse readily through membranes, more readily than propeptones. (3)" They also filter much more readily than albumin through the pores of animal membranes. (4) From a mixture of pep- tone, propeptone, albumin and pepsin, first neutralized and then feebly acidulated with acetic acid, neutral ammonium sulphate added in excess precipitates everything except peptone. (5) Peptones are not precipi- tated by boiling, or by nitric acid, or acetic acid and potassium ferro- cyanid, or by acetic acid or by saturation with sodium chlorid. (6) They are precipitated by phosphotungstic, by phosphomolybdic acid, and by biliary acids; precipitated by tannic acid, they are redissolved in an excess. Other precipitating agents are mercuric chlorid and nitrate, • mercuric iodid, potassium iodid. (7) They yield all of the color-reactions of albumin. (8) With sodium hydrate and copper sulphate in the cold, they give a purple-red color (biuret-reaction). The biuret-reaction is yielded also by propeptone, as well as by a proteid body, the so-called alkophyr, formed coincidently in the process of artificial digestion and soluble in strong alcohol. Gelatin-peptone and gelatin are precipitable by tri- chloracetic acid, while albiamin-peptone is redissolved in an excess of this acid. This is a useful means of differentiating these peptones. The peptones of the various proteid bodies are distinguished by the amount of sulphur they contain, with some of which this substance is but loosely combined, while with others it is firmly united. All have a disagreeable and bitter taste. In order to demonstrate the rapidity with which fibrin is digested by the gastric juice, Grunhagen places in a funnel the fibrin that has been saturated with 0.2 per cent, hydrochloric acid, moistens it with digestive fluid and notes the rapidity with which the fibrin gradually melts away, drop by drop, and finally is entirely dissolved. Grutzner stains the fibrin with carmine, saturates it with o.i per cent, hydrochloric acid, and places it in the digestive fluid. The more rapidly the latter becomes stained tmiformly red, in consequence of digestion of the fibrin, the more energetic, natiirally, is the digestive action. QuantiiaUve Estimation of the Activity of Pepsin.— -Oi a solution of egg- albumin (3 grams in 160 cu. cm. of 0.4 per cent, hydrochloric acid) two specimens of 10 THE PROCESS AND THE PRODUCTS OF GASTRIC DIGESTION. 299 cu. cm. are taken, 5 cu. cm. of gastric juice being added to the one and 5 cu. cm. of water to the other. The mixtures are poured into Esbach's tubes up to the mark U. Both tubes are then kept for one hour at a temperature of 37° C, after which Esbach's reagent is added up to the level of the mark R, and the amount of the precipitate in both tubes is noted after the lapse of twenty-four hours. Pep- tone is not precipitated. Chronic gastric catarrh and carcinoma yield low digestive values, while hypersecretion of the gastric juice may increase the digestive in- tensity. Preparation of Pure Peptone. — The diluted digestive solution, freed from albu- minates by boiling, and with an almost neutral reaction, is first saturated, while boiling, with ammonium sulphate, filtered when cool, again heated, after beginning to boil made strongly alkaline by adding ammonia and ammonium carbonate, again saturated in the heat with ammonium sulphate, filtered after cooling, again heated vmtil the odor of ammonia has disappeared, again saturated with the salt, hot, and acidulated with acetic acid. The fluid, filtered in the cold, contains pure peptone. The peptones are undoubtedly those modifications of proteids that are intended, after absorption from the digestive tract, and later through the blood, to be employed to replace the proteids consumed by the pro- cess of metabolism in the living organism. If much albumin has already been digested by the gastric juice, the pepsin is precipitated and becomes inactive if some hydrochloric acid is not again added from time to time. Admixture with bile in the test-tube impairs the activity of pepsin; nevertheless the entrance of bile into the stomach causes no permanent derangement, as renewed amounts of pepsin are at once secreted by the gastric mucous membrane. The stomach digests less well food that has not been thor- oughly masticated or properly insalivated. The presence of blood or of serum prevents the action of pepsin, as well as of trypsin and of the lab-ferment. Heated to a temperature of 65° C. the pepsin in the gastric juice becomes inactive, pure pepsin even at a temperature of 55° C. Concentrated acids, alum and tannic acid abolish the process of peptic digestion. Alkalinity of the gastric juice, as, for instance, from the presence of large amounts of saliva, also concentrated solution of alkaline salts, such as sodium chlorid, magnesium sulphate and sodium sulphate, have the same effect, as do also sulphurous and arsenous acids, and potassium iodid; while small amounts of sodium chlorid increase the secretion and favorably influence the action of the pepsin. The salts of the heavy metals, which form precipitates with pepsin, peptones and mucin, disturb gastric digestion. According to Langley and Eakins, alkalies rapidly destroy pepsin, and propepsin less rapidly. Acids (as lactic, acetic and hydrochloric) precipitate the gastric mucus and stimu- late the secretion of pepsin, while the salts of the alkalies have exactly the opposite effect. Alcohol precipitates the pepsin, although this is redissolved on addition of water, so that digestion can then proceed again undisturbed. Agents that hinder thorough saturation of proteids, as, for instance, binding them tightly, or concen- trated solutions of astringent salts, retard digestion. The ingestion of half a liter of cool water does not disturb gastric digestion in the healthy individual, though it does when the function of the stomach is de- ranged, while the ingestion of a larger amount impairs the digestive activity of the stomach. The same eiTect is brought about by strong muscular action. In the horse moderate movement (trotting) assists the digestion of starches in the first hour. Warm compresses over the epigastric region favor gastric digestion. According to Penzoldt, the digestibility of various proteid articles of food by the stomach is given in the following order. Easily digestible: boiled brain and thymus, pike, sea-fish, carp, oysters, chicken, boiled pigeon, raw scraped beef or veal, wheat-bread, cauliflower, soft-boiled egg (casein, alkali-albuminate) . Digest- ible with moderate ease: boiled beef and veal, duck, goose, pork, salt potatoes, rye- bread, rice, tapioca, asparagus, rape-cole, carrots, raw egg, pur6e of legumes. Digestible ivith difficiilty: salmon, salt fish, highly salted caviare, string beans, hard- boiled egg. The digestibility of the different meats, from the more to the less readilv digestible, is as follows: veal, lamb, mutton, pork, beef, rabbit, horse. 300 ACTION" UPON' OTHER FOODS. ACTION UPON OTHER FOODS. iililk coagulates in the stomach, with the Hberation of heat, as a result of precipitation of the casein, which encloses the fat globules. The free acid of the stomach is alone sufficient for precipitation, the alkali being withdrawn from the casein, which it holds in solution. Hammarsten, in 1872, discovered a special rennet-ferment in the gastric juice, which coagulates the casein in either neutral or alkaline solutions. On this fact depends the preparation of cheese by means of calf's stomach rennet. The rennet is formed in the chief cells of the gastric glands from a rennet-forming substance, bj^ the action of an acid. The rennet-forming substance is present in the mucous membrane in much larger amount than rennet itself. One part of rennet-ferment is capable of precipitating 800,000 parts of casein. The addition of calcium chlorid hastens, while water retards, coagulation. An excess of alkali impairs the activity of rennet. The rennet-ferment is best assisted by hydro- chloric acid, followed, in order, by lactic, acetic, sulphuric and phosphoric acids. The casein, as well as the nucleo-albiimin, is converted in the process of diges- tion, mainly into peptone rich in phosphorus; a residue poor in phosphorus, para- nuclein, remaining as an insoluble product. The rennet-ferment is destroyed by long-continued artificial digestion. To obtain rennet, Hammarsten agitates artificial gastric juice prepared from the calf 's stomach, and after neutralization, with magnesium carbonate. The filtrate contains only rennet, which, after acidulation with acetic acid, is precipitated by the in- troduction of liquid stearic acid, to which it adheres. The acid is dissolved in ether, which can then be readily separated. Finally, sugar of milk is converted in the gastric juice into lactic acid, by fermentative activity — lactic-acid ferment. Further, the milk- sugar in the stomach and intestines is, in part, transformed into grape- sugar. Cane-sugar is gradually converted into grape-sugar, in which process, according to Uffelmann the gastric mucus, according to Leube the gastric acid, plays the most important part. ACTION ON THE DIFFERENT TISSUES AND THEIR CONSTITUENT MATERIALS. (i) The gelatin-yielding substance of the various supporting structures — connec- tive tissue, fibrous cartilage and the matrix of bone as well as glutin itself, is pep- tonized and digested in the gastric juice. (2) The structureless membranes (mem- branae propriae) of the glands, sarcolemma, the nerve-sheath of Schwann, the capsule of the crystalline lens, the elastic layers of the cornea, the membranes of the fat-cells, are likewise digested, but scarcely the elastic, fenestrated membranes and fibers. (3) Striated muscular tissue forms after digestion of the sarcolemma and breaking up of the transversely striated contents into discs and fragments of fibrils, as well as iinstriated muscular tissue, a true digested peptone, in consequence of hydration and the decomposition of the myosin. Remains of meat, however, always pass over into the intestine. (4) The proteid elements of the soft cellular structures of the glands, stratified epitheUum, endothelium and lymphoid cells, are converted into peptone, while the nuclein of the nuclei cannot, apparently, be digested. (5) The homy portions of the epidermis, nails, hairs, as well as the chitin and the wax of lower animals, are indigestible. (6) The erythrocytes are digested, the hemoglobin decomposed into hematin and a globulin-like substance. The latter is peptonized; the former remains unchanged, and in part appears in the feces, and in part is absorbed and transformed into the coloring-matter of the bile. (7) The fibrin is easily digested into propeptone and fibrin-peptone by the taking up of water and the breaking up of the molectile. Mucin is digested in the stomach. (8) Of vegetable articles of food, vegetable fats are not changed by the gastric juice. The vegetable cells give up their protoplasmic contents for the production of peptone, while the cellulose of the cell-walls is undigestible in the stomach of human beings. THE GASES OF THE STOMACH, 3OI That the stomach is also capable of digesting parts of a living body is shown by the fact that the thigh of a living frog or the ear of a rabbit, introduced into a gastric fistula in a dog, will be partly digested. The edges of gastric ulcers and hstulae in human beings are also eroded by the digestive activity of the gastric juice. The question was early asked, Why does the stomach-wall not digest itself? As, after death, the mucous membrane is, in fact, often rapidly softened by autodigestion (gastric softening), the opinion is justified that, so long as the circulation is maintained, the tissues are constantly protected against the action of the acid by the alkalinity of the blood. If the reaction of the gastric juice be alkaline, digestion cannot be inaugurated. Ligation of the blood-vessels of the stomach resulted, according to Pavy's investigations, in digestive softening of the gastric mucous membrane. In human beings morbid occlusion of the vessels causes, in an analogous manner, the development of gastric ulcers. Also the thick, firmly adherent layer of mucus may help to protect the uppermost layer of the mucous membrane against autodigestion. In general, however, the conditions, with respect to all peptonizing ferments, are such that fully living protoplasm, therefore also that of the epithelial cells of the stomach, possesses the property of being able to resist the action of enzymes, as it is capable of decomposing all, even the most complicated, molecules of inanimate substances. Armu^ba;, bacteria, worms, larvt-e and embr>'onal vegetable cells are not affected by artificial digestive juices, not even by trypsin. After extirpation of the stomach, digestion is continued by the pancreas, the liver and the intestines. The stomach is a protective apparatus with respect to the intestine, as it removes various injurious influences, particularly of bacterial origin. THE GASES OF THE STOMACH. The stomach always contains gases, derived in part from air directly swallowed, as, for example, with the saliva, and in part from gases that pass backward from the duodenum. If the larynx and the hyoid bone are suddenly drawn forcibly forward (as in vomiting), a considerable amount of air enters the space behind the larj-nx and when the latter returns to its position of rest, is carried down by the peristalsis of the esophagus. One can feel distinctly the downward passage of such a quantity of air. At times, even without any movement of deglutition, a number of small air-bubbles enter the stomach. These masses of air constantly undergo change, owing to the absorp- tion of oxygen into, and the elimination of carbon dioxid from, the blood. The rather abundant production of carbon dioxid in the stomach depends, however, on chemical processes resulting from the admixture of the pyloric secretion, containing sodium carbonate, with the secretion of the fundus, containing acid. According to Planer, the amount of oxygen is extremely small, while that of carbon dioxid is considerable. A portion of the carbon dioxid in the saliva is set free by the acid of the gastric juice. The quantity of nitrogen is indifferent. GASES OF THE STOMACH. VOLUMES IN PER CENT. {According to Planer.) Human Cadaver .\iter Vegetable Diet. Dog. I. II. I. After a Meat diet. II. After a Diet of Legumes. CO2 .... H N 0 20.79 6.71 72.50 33-83 27-58 38.22 0-37 25.2 32-9 68.7 6.1 66.3 0.8 302 STRUCTURE OF THE PANCREAS. Abnormal development of gases, in cases of gastric catarrh, occurs only when the reaction of the gastric contents is neutral. Thus, in the presence of butyric- acid fermentation, hydrogen and carbon dioxid are produced, while acetic-acid and lactic-acid fermentation generate no gases. Marsh-gas (CH4) also is found; though this can reach the stomach only from the intestine, as it can be produced only in the absence of oxygen. Traces of hydrogen sulphid generated by the bacterium coli commune are formed at times in connection with benign dilatation of the stomach and motor insufficiency. Yeasts and various bacteria are also found in the stomach. STRUCTURE OF THE PANCREAS. The pancreas is a compound tubular gland with terminal alveoli which constitute the chief portions of the gland. On the internal sur- face of the membrana propria, formed of fibrillar tissue, lie the some- what cylindrical-conical secreting cells, which consist of two layers: (i) the smaller, parietal layer, which is transparent, lamellated, stri- ated, and can be deeply stained by carmine, and (2) the internal layer (Bernard's granular Jayer), which is deeply granular, and stains but slightly. Between the two layers lies the nucleus. During the process of secretion a visible transformation takes place continually in the cell- substance ; the granules in the granular layer undergo solution and form constituents of the secretion, while in the external layer the homo- geneous substance is renewed, and is later again transformed into granu- lar matter. This, in turn, again moves inward toward the lumen of the alveolus. In detail there takes place in the first stage of digestion (from the sixth to the tenth hour) a consumption of the granular inner zone and a growth of the Fig. 115. — Changes in the Cells of the Pancreas in the Different Stages of Activity: i, in the state of hunger; 2, in the first stage of digestion; 3, in the second stage; 4, with paralytic secretion. striated outer zone (Fig. 115, 2). In the second stage (from the tenth to the twentieth hour) the inner zone of the swollen gland has increased greatly in size, while the outer zone is much diminished (Fig. 115, 3). In the state of hunger the latter again increases in size (Fig. 115, i). In the pancreas, yielding a para- lytic secretion, and reduced in size, the inner zone of shrunken cells is almost entirely lost. In consequence of increased secretion, some of the secreting cells undergo a change, so that the acini form irregular collections containing many granules, and have lost all resemblance to glandular acini. Entire cells are also destroyed during the activity of the gland and new ones are again formed. The finest excretory ducts of the acini begin as intercellular secretory spaces. With the alveolus there is connected an intercalary portion, constituted of flat cells, and which develops in the center of every acinus. Then a sort of salivary duct follows, without striated epithelium, as in the salivary glands. From the micro- center of the cells of the excretory-duct system a ciliated flagellum, the "outer thread," projects free into the lumen of the canal. The pancreatic duct, which possesses an axial cotarse and as a rule empties into the duodenum in common with the bile-duct, while a smaller branch of the duct makes its entrance at a special papilla at a higher level, consists of an inner, denser, and an outer, looser, wall of connective and elastic tissue, together with THE PANCREATIC JUICE. 303 un.slriatcil muscular iihcrs mainly pursuing a circular course, and lined inlernally by a sinj^le layer of cylindrical epithelium. Small mucous glands lie in the main duct and in its larger branches. Mcdullated and non-medullated nerves, which in their course arc connected with ganglia, pass to the glandular acini; but their terminations are unknown. Blood-vessels surround the acini, in part of large size and in abundance, in part isolated. The fresh jjancrcas contains water, albuminates, ferments, fats and salts. The resting gland contains much leucin, isoleucin and tyrosin; further, biitalanin, often xanthin and guanin; lactic acid, formic acid, fatty acids; most of these from autodecomposition. THE PANCREATIC JUICE. To obtain the pancreatic juice Regner de Graaf, in 1664, tied in the excretory duct of a dog a cannula provided with an emptj'- bag at its extremity, in which the juice collected. Others passed the tube through the abdominal walls exter- nally and thus made a transitory cannula-fistula, which closed in the course of a few days, with inflammatory expulsion of the extremity of the cannula that had been tied in place. In order to establish a permanent fistula, either a duodenal fistula is made, like a gastric fisttila, through which the duct of Wirsung is cathe- terized by means of a thin tube; or the duct is o])ened in a dog and drawn toward the abdominal wound and an attempt is made to unite the wound in the duct with the abdominal wound so as to form a fistula. Heidenhain eliminates the portion of the duodenum in which the duct opens from the continuity of the intestine, incises it, and fixes it outside of the abdominal wound. From such a permanent fistula an abundant, feebly active, watery secretion, rich in sodium carbonate, is collected. From a freshly made opening and before the onset of inflammatory processes, a scanty viscid fluid is obtained which exerts energetic and characteristic physiological actions. Obviously, the scanty, viscid secretion is normal, while the watery, abundant secretion is abnormal and derived from the dilated blood-ves- sels, perhaps in consequence of paralysis of the vasomotor nerves, and as a result of increased transudation. The latter would thus in a cer- tain sense be a paralytic secretion. ' The amount must vary greatly, accordingly as viscid or watery secretion is produced. During digestion a large dog secreted from i to 1.5 grams of viscid secretion; Bidder and Schmidt obtained from a permanent fistula from 35 to 37 grams of watery secretion in twenty-four hours, for each kilogram of weight. While the resting, inactive gland is flabby, yellowish red in color, the secreting gland is turgescent and reddened from the dilatation of its blood-vessels. Normal pancreatic juice is transparent, colorless and odorless, with a salty taste, and a strongly alkaline reaction from the presence of 0.4 per cent, sodium carbonate, and therefore effervescent from escape of car- bon dioxid on addition of acid. It contains albumin and potassium albuminate (9.2 per cent.); like watery egg-albumin, it is viscid, flows with difficulty and coagulates at a temperature of 75° C. into a white mass. On standing in the cold a gelatinous coagulum of albumin sepa- rates, in which concentrated mineral acids, metallic salts, tannic acid, chlorin-water and bromin-water cause a precipitate; the precipitate produced by alcohol can be redissolved by water. The total solids in the pancreatic juice of human beings equal 13.6 per cent. Among the salts are sodium chlorid, 7.3; sodium bicarbonate, 0.4; sodium phos- phate, 0.45; sodium sulphate, i.i in 1000, together with some lime and traces of magnesia, potassium sulphate and ferric oxid. The more rapid and the more profuse the flow of the pancreatic 304 THE DIGESTIVE ACTIVITY OF THE PANCREATIC JUICE. juice, the more deficient is tlie secretion in organic constituents, the inorganic components remaining almost the same. Nevertheless, the total amount of solid constituents secreted is greater under such circum- stances than when the secretion is scanty. The freshly discharged juice contains traces of leucin and soaps. • In pancreatic juice that is no longer fresh, chlorin induces a red color, as does crude nitric acid in the putrefying juice, by the production of indol. Rarely the juice forms concretions in the pancreas, principally of calcium carbonate. In cases of diabetes dextrose has been found in the pancreatic juice; in cases of jaun- dice, \irea. THE DIGESTIVE ACTIVITY OF THE PANCREATIC JUICE. The presence of four hydrolytic ferments, or enzymes (an amj^loly- tic, a proteolytic, a lipolytic, and a milk-curdling ferment), makes the pancreatic juice a most important digestive fluid. The amylolytic activity is due to the ferment amylopsin, which ap- pears to be identical with the ptyahn of the saliva, though it acts more energetically, both upon raw and upon boiled starch and glycogen. At the temperature of the body almost immediately, but more slowly at a lower temperature, it converts the substances named into maltose, isomaltose and dextrin, as does the saliva. Even cellulose itself is said tc be digested and gum to be transformed into sugar, but inulin remains unchanged. The amylopsin is precipitated b}'^ alcohol and it remains dissolved in glycerin without material enfeeblement. All agencies that disturb the diastatic activity of the saliva also abolish that of the amylopsin, although admixture of acid gastric juice, as its hydrochloric acid is in combination, or of bile, is without injurious effect. The ferment is isolated by the same method as that by which salivarj' ptyalin is obtained, but in this process the peptic ferment is at the same time precipitated with it. In addition to this diastase, the pancreatic juice contains a second diastatic ferment, by which maltose and isomaltose are transformed into dextrose. Saliva contains hardly a trace, and blood-serum more of this ferment than of diastase. The addition of bile, as well as of various neutral salts (in about 4 per cent, solution), increases the diastatic activity, and in the following order: potassium nitrate, sodium chlorid, ammonium chlorid, sodium nitrate, sodium sulphate, potassium chlorate, ammonium nitrate and ammonium sulphate. The proteolytic activity is due to the ferment trypsin, which at the temperature of the body transforms the albuminates, in the presence of an alkaline medium, without previous swelling, first into albu- moses (hemi-albumose and anti-albumose), also designated propeptones, and finally into true peptones, also designated tryptones. Previous swelling of the proteids by means of hydrochloric acid, as well as an acid reaction in general, have a tendency to prevent this transformation. The albumoses of tryptic digestion have the character of the deutero- albumoses. Two kinds of peptones are formed, namely hemi-peptone^ which later breaks up into the amido-acids, and antipeptone, which does not undergo further decomposition. Trypsin peptonizes all proteids, casein, vitellin, elastin, mucin, and nuclein, while neurokeratin, keratin and amyloid remain insoluble. Glutin and the gelatin-yielding substance, swollen by acids are changed into gelatin-peptone, and the latter is not further changed. Oxyhemo- globin decomposes into albumin and hemochromogen. Pancreatic ex- THE niOESTIVR ACTIVITY OF TIIK 1>A NC 1< IC ATIC JLMCK. 305 tract first affects milk-casein in such a manner that it is coagulated by heat, after which it is peptonized. In other respects, trypsin lias an action like that of pepsin upon tissues containing albumin. Casein is almost wholly dij^csted by trypsin. The tryptic ferment, which is also present in the pancreas of new-born infants, is carried down mechanically from the pancreatic juice diluted with water, by the production of a voluminous precipitate, with collodion. The precipitate is washed and dried, and then the collodion is dissolved out in a mixture of ether and alcohol. The residue is soluble in water, and represents the ferment. Kiihnc further separates with especial care the albumin still combined with the ferment in the aqueous extract of the gland, and thus secures the ferment in a purer form. It is soluble in water, insoluble in alcohol and in pure glycerin. As trypsin is destroyed by hydrochloric acid, it is not advisable, as in the presence of weakened digestion, to administer trypsin by the mouth. In a dried state it can be heated to a temperature of 140° C. without injury; in a moist state, if pure, to 50° C; and mixed with salts or with albumoses and peptones, to 60° C. Method: For testing trypsin, gelatin is especially usefid, being liquefied in a test-tube at the temperature of the body: 7 grams of gelatin boiled with 93 grams of an aqueous solution of thymol. For antiseptic purposes thymol should be added also, after filtration, to the fluid to be tested for the presence of the ferment. Trypsin results through the taking up of oxygen within the pan- creas, from a mother-substance, zymogen, which collects in the interior of the secreting cells in smallest amount between the sixth and the tenth hour, and in largest amount, on the other hand, sixteen hours after eating. It can be extracted from fresh glands by glycerin or by water. In aqueous solution this body yields the ferment. Within the excised pancreas the same result occurs on treatment with strong alcohol. The addition of bile, sodium chlorid. sodium glycocholate and carbonate, as well as carbon dioxid, increases the activity of the ferment, while magnesium sid- phate and sodium sulphate enfeeble its action. With continued action of the trypsin upon the hemipeptone pro- duced, this is converted in part into the amido-acids: leucin (CgHigNOz), tyrosin (CaHnNOg), aspartic or amidosuccinic acid (C4H7NO4) in the diges- tion of fibrin and glutin, glutamic acid (C5H,,N0J, and butalanin or amidovalerianic acid (C5H11NO2). Gelatin-peptone, according to Nencki, on further decomposition yields glycin and ammonia. The amido-acids produced may be partly absorbed as such and may be consumed in the circulation. The following bases also occur: xanthin-bases, lysin, lysatinin, argi- nin, together with ammonia and a body that becomes reddened by chlorin-water or bromin-water. If the action be continued still further, matters having a fecal odor result, and with especial rapidity when the reaction is alkaline, also indol (CgHyN), skatol (CgHyN), and phenol (CgHgO), volatile fatty acids with the development of hydrogen, carbon dioxid, hydrogen sulphid, marsh- gas and nitrogen. These products of decomposition, however, result wholly from putrefaction of the preparations. This can be prevented by the addition of salicylic acid or thymol, which destroys the putre- factive organisms that are always present. Prolonged boiling of the albuminates with dilute sulphuric acid, Hke the action of trypsin, produces first peptone, then leucin and tyrosin, and glycin from gelatin. Hypoxanthin and xanthin result in this way on boiling fibrin, the former also from long-continued boiling of fibrin with water. Leucin, tyrosin, glutamic and aspartic acids, together with xanthin-bodies, 20 306 THE DIGESTIVE ACTIVITY OF THE PANXREATIC JUICE. result also in the germination of certain plant?, by reason of which there is a resemblance between the transformation and the consumption of mitritive mate- rials in seeds and the digestive effects of ferments. The lipolytic activity depends on the presence of a ferment termed steapsin or pialyn, which exerts its action more especially on the neutral fats. This action is two-fold: (i) they are transformed into a fine, permanent emulsion, and (2), by taking up water, they undergo a cleav- age into glycerin and fatt}' acids. C„H„oO, -f 3H2O = C3H3O3 -^ sCCisHseOs) Tristearin + Water = Glycerin -r Stearic .-Vcici. The addition of bile increases this action in the rabbit very consid- erably. This cleavage action is due to a ferment, especially decomposed bv acids, but which has not yet been isolated. Lecithin is split up by this ferment into glycerinphosphoric acid, neurin and fatty acids. After decomposition is complete, the fatty acids are in part united with the alkalies of the pancreatic juice and the intestinal fluid to form fatty-acid alkalies, or soaps; and in part emulsified in the alkaline in- testinal juice. Both the emulsion and the soap-solution are capable of being absorbed. After extirpation of the pancreas in the dog, the digestion and absorption of fats are correspondingly diminished. If the fat to be emulsified contains free fatty acids, as is the case with all of the fats of the food, and if the fluid at the same time has an alkaline reaction, emulsification takes place with extraordinary rapidity. A drop of cod-liver oil, which likewise always contains some free acid, placed in a 0.3 per cent, soda-solu- tion, is at once broken up into fine emulsion-granules. First a hard soapy mem- brane is formed on the surface of the oil-drop; this, however, is quickly dissolved and small drops are thereby torn away. The fresh surface becomes again covered with a layer of soap and the process is continvially repeated. The soaps produced themselves in turn act as emulsifiers. If the amount of oleic acid contained in the oil and the concentration of the soda-solution are increased, so-called "myelin- forms" are produced, that is, forms like those that appear when fresh nerve-fibers are teased in aqueous liquids. Animal fats furnish an emulsion more readily than vegetable fats, castor-oil not furnishing any at all. The fatty acids also may undergo still further decomposition through the action of the fat-splitting ferment, with the production of carbon dioxid and hydrogen even, in the absence of microorganisms. Danilewsky isolated the four pancreatic ferments in the following manner: If an acid infusion of dog's pancreas is super-saturated with magnesium oxid, the precipitate carries the fat-ferment down with it. Collodion added to the filtrate precipitates the trypsin; the precipitate is collected; and the collodion is dissolved out by a mixture of ether and alcohol. The diastatic ferment is contained in the filtrate from the collodion-precipitate. For testing the digestive activity of the pancreas an extract of the swollen and reddened gland may be prepared after trituration with the aid of concentrated solution of sodium chlorid. Triturated pancreas, which has lain for a day, can also be extracted with glycerin or chloroform-water. Alcohol precipitates the fer- ments in these extraction-fluids. Kiihne renders the minced pancreas free from water and fat by means of alcohol and ether, and pulverizes it. The powder, to which 10 parts of o.i per cent, salicylic acid sokttion at blood-heat are added, exhibits the activity of the ferments. An extract of the pancreas, prepared rapidly and at a high temperature with a 0.7 per cent, sokition of sodium chlorid, contains almost alone the sugar-forming ferment, which is absent from the gland in the state of hunger. After long-continued maceration at a later period trypsin prin- cipally is obtained. To demonstrate the effects of the pancreas Setschenow proceeds as follows: I^Iinced calf's pancreas is infused with less than double its volume of water and is kept at a temperature of 38° C. for five hours. The decanted fluid is strained, shaken with ether, and alcohol is added tmtil a precipitate forms. The latter is spread uniformly upon filter-paper by filtration, and the paper is dried at a tem- THE SECRETION OF THE PANCREATIC JUICE. 307 pcrature of 40° C. A strip of this papt-r about tlie length of a finger immersed in 3 or 4 cii. cm. of water yields a fluid capable of acting upon starches, albumin and fat. The pancreas of new-born infants contains no diastatic ferment, but both peptic and fat-splitting ferments. Diseases of infants, diarrhea at times, appear to have a marked effect on the activity of the pancreas. Slight diastatic power is exhibited after the second month of life, complete activity only after the lapse of the tirst year. The milk-cnrdliug activity depends on the presence of a ferment, according to W. Kiihne and W. Roberts, which can be extracted by means of a concentrated solution of sodium chlorid. The pancreas also prepares a sugar-splitting ferment. If a solution of sugar is digested with an aqueous or glycerin extract of pancreas, the amount of sugar diminishes. THE SECRETION OF THE PANCREATIC JUICE. In the case of the pancreas, a resting stage, in which the gland is flabby and pale yellow, and a stage of secretory activity, in which the organ appears swollen and pale red, can be distinguished. The latter occurs only after the ingestion of food, and results probably in consequence of reflex excitation through the nerves of the alimentary canal, and ap- parently in consequence of the moistening of the intestinal mucous mem- brane with the acid gastric contents, for acids are the most powerful excitants of this secretion. W. Kiihne and Lea found that all the lobules did not take part in the secretory activity at the same time. The pan- creas in herbivora secretes continuously. According to Bernstein and Heidenhain, the secretion begins to flow with the entrance of the food into the stomach, the quantity reaching its maximum in the second or third hour. After this the amount de- creases between the fifth and the seventh hour; then, in consequence of the passage of all of the dissolved matters into the duodenum, it rises again between the ninth and the eleventh hour, and finally falls gradually between the seventeenth and the twenty-fourth hour, to the point of complete cessation. During the act of secretion the blood-vessels behave like those of the salivary gland after stimulation of the facial nerve; they are dilated, the venous blood being bright red. It is, therefore, probable that a similar nervous mechanism is active here. In general, the activity of the gland is in large measure dependent upon an adequate blood-supply; anernic conditions impair the secretory processes. The secretion, in the rabbit, is under a secretory pressure of over 17 mm. of mercury. The nerves are derived from the hepatic, splenic and superior mesenteric plexuses, to which the pneumogastric and splanchnic nerves send branches. The secretion of the gland is excited by stimulation of the medulla oblongata, of the splanchnic nerves (feebly), of the peripheral stump of the pneumogastric nerve, in consequence of which the amount of ferment in the juice is increased, as well as of the gland itself by means of induction-currents. Reflex increase in the secretion is brought about by stimulation of the central stump of the lingual nerve, at times also by that of the central stump of the pneumogastric nerve. The secretion is suppressed by atropin, by excitation through the act of vomiting, as well as by stimulation of the pneumogastric nerve or its central stump, as well as of other sensory nerves, as, for example, the crural and sciatic nerves. Destruction of the accessible nerves of the pancreas surrounding the blood-vessels renders the stimulation mentioned ineffective. On the other hand the secretion of a watery, paralytic, slightly active secretion becomes permanent; and the amount is then no longer moditied by the ingestion of food. 3o8 THE STRUCTURE OF THE LIVER. Fat and water, further pilocarpi:! and physostigmin, excite pancreatic secre- tion. Solutions of neutral and alkaline salts of the alkahne metals exert an in- hibitory action. Animals tolerate lis^ation of the pancreatic duct. It is a remark- able fact that the duct mav regenerate spontaneously. This operation may, how- ever, be followed by cvst-formation in the ducts and atrophy of the glandular structure. After total 'extirpation of the pancreas, the digestion of albumin, tat and starches is impaired. The severe diabetes that develops immediately after extirpation of the pancreas and which has been observed also in human beings after degeneration of the pancreas, is of obscure origin. THE STRUCTURE OF THE LIVER. The liver is included among the compound tubular glands. Its development -shows that with its excretorv ducts it evolves in the form of a reticulated tubular gland. The globular, polvgonal hepatic acini (lobules, islands), flattened one ao-ainst the other, from i 'to 2 mm. in diameter, are considered as the ultimate naacrosco])ic units of the gland. Thev show the following histological peculiarities: The liver cells (Fig. r 16, II, a) , 34 or 3 s /^ in diameter, are irregularly polyhedral, consisting of soft, friable protoplasm, filled with pigment-granules. They have no membrane, and contain one or more spherical nuclei, with nucleoli, and are so arranged that thev radiate from the centre of the acinus in longer or shorter con- nected lines toward the surface of the lobule. Thus arranged they are m part surrounded by the more delicate bile-ducts (Fig. 116, I, x), m part separated one from the other in rows by the coarse network of blood-capillaries (d d) . In the state of hunger the liver-cells are finelv granvilar and deeply clouded (Fig. 117, _i). About thirteen hours after suitable nourishment the cells contain coarse, glistening flakes of glycogen (2). At the same time the protoplasm is condensed on the surface, whence a network extends toward the center of the cells, in which the nucleus is suspended. The liver-cells often contain fatty granules. The Blood-vessels of the Lobule.— (a) Ramifications of the venous system. If the branches of the jiortal vein, well supplied with muscular fibers, and entering through the transverse fissure, be followed, small vessels will finally be found, after free dendritic branching, that, approaching from various directions, converge at the limits of the acini, and here enter into communication through capillary anasto- moses, forming the interlobular veins (Fig. 116, V, i). From these veins capillary vessels (c c) pass from the entire periphery of the acinus toward its center. They are relatively large (from 10 to 14 /z in diameter) and form a longitudinal network in a radiating direction; and between them rows of connected hepatic cells, liver-cell columns (d) , are always lodged. The capillaries are so arranged that they run along the edges of the rows of cells, and never between the surfaces of two adjacent Irows. The radiating course of the capillaries necessarily brings it about that these vessels must unite at the center of the acinus to form the beginning of a larger vessel. This is the central or intralobular vein (V. c) which, in turn, piercing the lobule vertically, makes its exit at one point and, reaching the surface unites, as the sublobular vein (V. a), with similar vessels from neighboring acini, to form larger trunks that (100 n in diameter) represent the roots of the hepatic veins. The trunks of this great system of venous radicles leave the gland at the blunt edge of the liver. (6) Ramifications of the Hepatic Artery. — The branches of the hepatic artery, throughout their entire course, accompany the larger branches of the portal vein, to which, as well as to the adjacent larger bile-ducts, they supply nutrient capillaries. These branches enter into numerous anastomotic communications among them- selves. The small capillaries pass mainly from the periphery of the acinus into the capillaries of the portal system (Fig. 116, i i). Those arterial capillaries, how- ever, that he in the thicker connective tissue upon the larger venous and biliary branches (rr) pass over chiefly into two venous trunks that, accompanying the corresponding arterial branches for some distance, empty into branches of the portal vein. Individual arterial branches pass up to the surface of the liver, where they form a wide-meshed nutritive network, particularly under the peritoneal covering. The small venous radicles collecting from this point also reach the ramifications of the portal vein. The Biliary Passages. — The finest biliary passages, bile-capillaries, originate from the center of the acinus, and likewise wi'thin its entire interior, as membrane- less, regularly anastomosing straight ducts, i or 2 // in diameter. They form a THE STRUCTURE OF THE LIVER. 309 polygonal mesh about each liver-ccU (Fig. 117, 3). The ducts almost always lie midway between the surfaces of two adjacent liver-cells (Fig. 116, II, a) as true intercellular passages or secretory spaces. When the cells fall ai:)art in the process of maceration, they retain only semicircular depressions. The finest ducts of the bile-capillaries have been observed to penetrate the interior of the liver-cells and to communicate here with round, secretory vacuoles containing bile (Fig. 117, 3). As the blood-capillaries run along the edges of the rows of liver-cells, while the biliary ducts rtm along the surfaces of the cells, both systems of ducts are always at a deiinite distance from one another (Fig. 118). In human beings individual bile-ducts sometimes run also along the edges of the cells, so that they must then act as intercellular ducts of 3 or 4 cells. This arrangement is said to predominate in the cmbrj'onal liver. In addition to in- jection, the capillaries can be made visible by staining by Golgi's method. n Fig. 116.— I. Diagrammulic Representation of an Hepatic Lobule: \ i., \ . i, mterlobular veins; V. c, central vein, c, capiUarv between the two; V. s, sublobular vein; V. v, vascular vein; A .\, branches of the hepatic artery, approaching the capsule of Glisson and the larger blood-vessels at r r, and forming the ^•ascular vein further onfentering the capillaries of the interlobular veins at i i; g. branches of the bile-duct, dinding at .x x between the liver-cells; d d, situation of liver-cells in the capillary network. IL Isolated liver-ceUs, at c lying upon a capOlary blood-vessel and forming a fine bile-duct at a. Within the peripheral, cortical portion of the lobule the ducts, without walls, increase in size bv anastomosis of neighboring ducts. They then leave the acinus, in order from this point, uniting between the lobules (Fig. 116, g) with adja- cent ducts to form larger bile-ducts, with numerous anastomoses. These, m com- panv with the branches of the hepatic arterj- and the portal vein, hnally leave the transverse fissure of the liver as a collecting duct, the hepatic duct, ihe hner interlobular bile-ducts possess a structureless membrana propria with low epithe- lium The larger (Fig. 119) exhibit a double membrane constituted of connective tissiie and elastic fibers, the internal layer being especially supplied with blood- capillaries and bearing a single laver of cylindrical epithelium. Only m the largest branches, and in the gall-bladder, does this internal layer become an independent mucous membrane, with submucosa. Unstripcd muscle-fibers are found m isolated 3IO THE STRUCTURE OF THE LIVER. Fig. 11*7. — A, Liver-cell, in the state of hunger; 2, filled with masses of glycogen; 3, sux- ronnded by bile-capillaries. bundles in the main ducts (longitudinal and circular especially in the lower portions of the bile-ducts), as well as in a delicate longitudinal and circular layer in the gall-bladder. The movements here are slowly rhythmic and peristaltic. The mucous membrane of the gall-bladder is provided with folds and comb-like de- pressions. The epithelium is a single layer of cylindrical epithelium with a basal membrane and inter\'cning mucous goblet-cells. Small mucous glands are found in the mucous membrane of the large bile-ducts and of the gall-bladder. The connective tissue of the liver enters the portal fissure as a sheath (capsule of Glisson) for the vessels, and, mixed with elastic tissue, finally reaches the periphery of the acini, where in the pig, the camel and the polar bear it forms a clearly demonstrable cap.sule, but in human beings is in- conspicuous. Delicate elements can, however, be followed even into the acinus, nucleated star-cells and a network of delicate reticular fibers, which effect the fixation of the elements. The connective tissue of the acini not rarely undergoes considerable increase in drunkards, and its hyperplasia may even cause destruction of the contents of the acinus by pressure (cirrhosis of 'the liverj. In this thickened, interacinous connective tissue newly formed bile-ducts have been fotmd, and likewise in the cicatricial connective tissue of the "corset-liver." The l;)inph-vessHs begin as pericapillary ducts in the interior of the acinus. Further on they run within the walls of the hepatic veins and the branches of the portal vein; then they surround the venous branches. The larger vessels, formed from the union of the inter- lobular passages, leave the organ in part at the trans- verse fissure, in part with the hepatic veins, and in part at different points on the surface. At the blunt edge of the liver they form a close meshwork and pass through the triangular, he- pato-rena] and suspensory ligaments. The nervesoi the hepatic plexus, constituted in part Fig. iiS. — Blood-capillaries. Finest Biliary Ducts, and Liver- cells, in Their Mutual Relations in the Rabbit's Liver (after E. Hering): B, blood-vessel; D, finest biliary duct, in cross-section; F, finest biliary duct; K, nucleus of liver-cell. Fig. 1:9. — Interlobular Bile-duct from the Human Liver (after Schenk) : R. circular fibrous layer; C, cylindrical epitheUum. of Remak's fibers, in part of meduUated fibers fiom the sympathetic and pneu- mogastric nerves, follow the ramifications of the hepatic arter\-. Ganglia are placed in their course in the interior of the organ. The nerves are in part vasomotor in nature. According to Pfluger, other nerve-fibers enter into direct connection with the liver-cells, as is the case in the salivary- glands. The muscle-cells of the bile-ducts contain motor filaments. CHEMICAL COXSTITUEXTS OF TIIH LIVER-CELLS. 31I The celiac plexus sends trophic and vasomotor nerves to the liver. Destruc- tion of this plexus therefore causes degeneration of the liver-cells, and dilatation of the hepatic artery. The pneumogastric nerve .supplies dilator-fibers to the vessels, and the greater splanchnic motor branches to the muscles of the bile- ducts. CHEMICAL CONSTITUENTS OF THE LIVER-CELLS. Proteids. — The fresh, soft liver-parenchyma has an alkaUne re- action. After death, coagulation takes place, with cloudiness of the cell-contents; the tissue becomes friable and gradually acquires an acid reaction. This process is suggestive of rigor mortis, and is due to a myosin-like, post-mortem coagulating albuminous substance. The liver contains, further, a proteid body coagulable at 45° C, another coagulable at 70° C, and one slightly soluble in dilute acids and alkalies. The nuclei contain nuclein. The connective tissue yields gelatin. Glycogen, 6C6H10O5-I- H2O, or animal starch, from 1.2 to 2.6 per cent., is a carbohydrate closely allied to inulin, soluble in water, and diffusible with difficulty, which surrounds the nuclei of the liver-cells in ainorphous granules (Fig. 117, 2), though not always present and not always found in equal amounts in all parts of the liver. The glycogen in the liver represents the excess of carbohydrate material, which, after the ingestion of suitable foods, is temporarily stored like the starch in the plants. It is subsequently transformed into sugar and consumed by the tissues. , Qualitative Deterntination. — Glycogen is stained deeply red by iodin (best dis- solved by means of potassium iodid in a concentrated solution of sodium chlorid), like inulin, even in microscopic sections hardened in alcohol. Organs containing glycogen, boiled with an excess of sodium sulphate, yield an opalescent filtrate. If the organs, as, for example, the liver, still contain diastatic ferment, the glycogen, after being kept warm for several hours, will be converted into sugar, and, as already stated, the resulting filtrate, remains clear. Quantitative Estimation. — According to Kiilz's modification of Briicke's method, the coarsely minced liver is thrown into boiling water immediately after death and boiled for half an hour. It is then crushed and potassium hydrate (4 grams to roo grams of liver) is added. Evaporation over a water-bath to double the weight of the piece of liver employed is permitted to take place until in the course of three hours all is dissolved. After cooling, the mixture is neutral- ized with hydrochloric acid, and the albumin, together with the lime, is precipitated by means of hydrochloric acid, and potassio-mercuric iodid. Filtration is now practised, the precipitate being taken from the filter four times, mixed with a few drops of hydrochloric acid and potassio-mercuric iodid in water to the consistency of broth and filtered. All of the glycogen is now contained in the filtrate, to which, with stirring, double the volume of 96 per cent, alcohol is added. The glycogen deposited in the course of twelve hours is placed upon the filter, washed with 62 per cent, alcohol, then with absolute alcohol, with ether, again with absolute alcohol and dried at 110° C. Should the fluid remain cloudy after addition of hydrochloric acid and potassio-mercuric iodid, two parts of 98 per cent, alcohol are added and the filtered precipitate is dissolved in 2 percent, potassium hydrate, then neutralized with hydrochloric acid and now all of the albumin can be precipitated by repeated addition of hydrochloric acid and potassio-mer- curic iodid again. According to Seegen, dextrin is present in the liver in addition to glycogen. Rabbit's liver contains about three times as much glycogen in winter as in summer. The following are to be considered as the sources of glycogen in the liver: (i) The carbohydrates of the food, after they have been con- verted into dextrose in the alimentary canal; only the sugars ferment- able by yeast form glycogen, and not those incapable of fermentation; 312 CHEMICAL COXSTITUEXTS OF THE LIVER-CELLS. and (2) the proteids, including gelatin. If the proteids are a source of glycogen, it must result from a non-nitrogenous derivative of them. Pfluger considers the formation of glvcogen from albumin a synthetic process. The molecular group CHj, found in albumin, as well as in the fatty acids, must be transformed bv oxidation into CHOH. The cells taking part in the formative process may, however, also utilize this group CHOH wherever it is found already prepared, as in sugar or in glvcerin. Also fats (olive-oil), glycerin, taurin and glycin (the latter through decomposi- tion into glvcogen and urea) , have been designated as the source of glycogen. In rabbits, the production of glycogen is increased by the adrninistration of asparagin, ammonium carbonate or urea. The excessive production of acid in cases of diabetes, demonstrated by Stadelmann, fixes the ammonia and thus materially diminishes the production of glycogen. Ligation of the common bile-duct results in diminution of the glycogen in the liver. The liver after this operation appears to have lost the property of form- ing glycogen from suitable material brought to it. Also ligation of the hepatic arters' renders the liver free from glycogen. After excluding the portal circtilation the amotmt of sugar contained in the blood decreases. "With reference to the occur- rence of glycogen elsewhere reference may be made to p. 466. If large amounts of starch, grape-sugar, cane-sugar, levulose and maltose are added to the proteids of the food, the amount of glycogen in the liver is greatly increased, while on a pure albuminous or fatty diet it is considerably decreased: the state of hunger may cause it to dis- appear entirely. Injection of grape-sugar or of glycerin into a mesen- teric vein of a fasting rabbit causes the appearance of glycogen in a liver previously free from it. The living liver-cell is capable of producing glycogen in considerable quantities only from the two kinds of sugar capable of direct fermentation, namely dextrose and levulose. The non-fermentable sugars are not converted into glycogen, and cane-sugar and maltose only in so far as they are transformed in the intestine into dextrose. As the infant consumes milk-sugar, it must form glycogen from albu- min. Forced muscular movement rapidly renders the liver of the dog free from glycogen. Reduction of temperature diminishes the amount of glycogen in the liver. The rigid liver after death contains dextrin and grape-sugar. Glycogen is also present in the liver for a considerable time after death, as well as in the muscles. Under normal conditions, the glycogen in the liver is gradually transformed in small amounts into grape-sugar. The amount of sugar normalh^ present in the blood is from 0.5 to i in 1000. The blood in the hepatic veins may contain somewhat more. Increased transforma- tion into sugar occurs only in connection with marked circulatory dis- turbances in the liver, as a result of which the blood of the hepatic veins comes to contain a larger amount of sugar. The glycogen undergoes this transformation, likewise, soon after death, when the liver is always found to contain a larger amount of sugar and a smaller amount of gly- cogen. The active ferment necessary for this process can be obtained from an extract of the liver-cells, by the method employed to obtain ptyalin. Nevertheless, it is said not to be formed in the liver-cells, but only reaches the Hver to be quickly stored up, through the blood, within which the ferment is always formed with rapidity so soon as the move- ment of the blood undergoes marked disturbance. This transforming ferment develops also as a result of the solution of red blood-corpuscles ; and as a constant slight destruction of red blood-corpuscles must surely be assumed to take place within the liver, a source is thus provided DIABETES MELLITUS. 313 for the production of the ferment through the action of which small quantities of sugar are continually fonned in the liver. As the liver is thus the seat for the production of sugar, extirpation of this organ or ligation of its vessels is followed by disappearance of the sugar con- tained in the blood. The grape-sugar formed in the liver is destroyed in part in the blood- stream, on its way through the tissues, in part by a special ferment, which appears to be derived principally from the pancreas, and to be carried by the blood-corpuscles. A portion of the sugar in the blood is converted in the muscles into glycogen. According to Kiilz and Vogel, the same process takes place in the hver in the formation of sugar from glycogen as results from the action of the saliva and the pancreatic juice, with the production likewise of maltose and isomaltose. According to E. Cavazzani, irritation of the celiac plexus causes the production of sugar in the liver, in connection with which the li\'er-cells undergo morphologic change. Further, fats are observed in the liver-cells, in the form of granules, as well as free in the bile-ducts; occasionally when the diet is rich in fat (in greater amount in drunkards and tuberculous patients), olein, pal- mitin, stearin and volatile fatty acids are found. Further, sarcolactic acid, traces of cholesterin, jecorin, finally small amounts of urea (in increasing amount in the warm, "surviving" liver), uric acid; and leucin, tyrosin (guanin?), sarcin, xanthin, and cystin pathologically in conjunction with putrefactive disorders, may be present. The liver-cells contain pigments, which are partly soluble in feebly alkaline water, partly in chloroform. The pigment soluble in water, designated ferrin. varies from yellow to red in color and contains almost all ot the iron of the liver. The latter can be demonstrated directly by means of potassium ferrocyanid or ammonium sulphid. The pigment soluble in chloroform, designated cholechrome. can be extracted from pulverized dried liver. It stands midway between bile-pigment and the lipochromes. The inorganic constituents of the liver are potassium, sodium, calcium, magnesium and manganese. Iron in organic combination with albumin (in ferratin) is present in the liver to the amount of about 6 per cent. Abstraction of blood together with albumin-hunger causes its disappear- ance. It is utilized in the production of new blood. Chlorin, phosphoric, sulphuric, carbonic and silicic acids may also be present ; and copper, zinc, lead, mercury and arsenic have been found deposited in the liver acci- dentally. DIABETES MELLITUS. The formation of large amounts of grape-sugar by the liver and their entrance into the blood and into the urine (glycosuria, diabetes mellitus) have been brought into relation with the normal conditions already mentioned. Extirpation of the liver in the frog or destruction of the liver-cells (fatty degeneration from phos- phorous or arsenical poisoning) does not cause the appearance of this phenomenon. It occurs a few hours after injurv to a particular spot (center for the vasomotor nerves of the liver) on the floor of the lower portion of the fourth ventricle (CI. Bernard's sugar-puncture, piqure) ; further, after division of the vasomotor paths in the^ spinal cord from above downward to the exit of the nerves for the liver, that is to the lumbar portion, in the frog to the fourth vertebra. Division or paralvsis of the vasomotor conducting paths from the center to the liver results in glvcosuria. According to recent researches by Fran9ois Franck and Hallion, the vasomotor nerves of the liver (for the hepatic artery and the portal vein) arise between the sixth dorsal and the second lumbar nerves and 314 DIABETES MELLITUS. pass through the communicating branches into the splanchnic nerves. According to the opinions of earlier investigators, aU of the paths, however, do not pass through the spinal cord alone. A number of vasomotor fibers for the liver leave the spinal cord at a higher level, and pass further on in the course of the sym- pathetic ner\-e to the liver. Thus, destruction of the uppermost, as well as of the lowest, cer\-ical ganglion, and of the first dorsal ganglion, of the abdominal ganglia, often also of the splanchnic ner\-es. is followed by glycosuria. The paralyzed, dilated vessels render the liver exceedingly vascular, and the blood-stream in them is slowed. This disturbance of the circulation gives rise to the presence of a large amount of sugar in the liver, as the blood-ferment has time to effect transformation of the glycogen. Irritation of the sj-mpathetic nerx^e at the last cer\'ical and first dorsal ganglia causes contraction of the hepatic vessels at the -periphery of the acini, with anemia. It is a remarkable fact that glycosuria when present can be removed by division of the splanchnic nerves. This is explained by the cir- cumstance that the enormous hyperemia of the intestines occurring after this operation renders the liver anemic. Also a nvunber of poisons that paralyze the vasomotor ner\-es of the liver cause diabetes in the same manner, namely ctu-are, when artificial respiration is not maintained: carbon monoxid, amyl nitrite, orthonitrophenyl-propionic acid and methyldelphinin : less constantly morphin, chloral hydrate and others. The toxic products of some of the infectious diseases also act in the same way at times. Blood-stasis of other sort in the liver also appears capable of caus- ing glycosiiria. as. for example, after mechanical stimulation of the liver. In this category- probably belongs the glycostiria following the injection of dilute saline solutions into the blood, as a restilt of which the changes in the shape of the red corpuscles cause stasis. Also the fact that repeated venesection makes the blood richer m sugar may, perhaps, be explained by the slowing of the circulation. Persistent irritation of peripheral ner\-es may also be active through a reflex influence upon the center for the vasomotor ner\-es of the liver. The appearance of sugar in the vu:ine has sometimes been observed as a result of irritation of the central stump of the pneumogastric ner\"e. likewise after irritation of the central stump of the depressor ner\'e. Even division and central irritation of the sciatic ner%-e may cause the appearance of sugar from the urine; in this way is explained the occurrence of glycosuria in cases of sciatica and other nervous disorders. According to Schitt. stagnation of the blood in various extensive portions of the body is said to increase the development of the ferment in the blood to such a degree that diabetes results. Of this character must be considered the glycosuria that occurs after compression of the aorta or the portal vein, although the pressure exerted under such circumstances may. perhaps, paralyze ner\'e- paths concerned. According to Eckhard. injury to the vermis of the cerebellum, in the rabbit, is said to bring about diabetes. In human beings, also, affections of the nen'ous structures mentioned may cause diabetes. Various explanations have been assigned in elucidation of the ultimate cause of these symptoms: (o) The glycogen of the Uver may without interference be converted into sugar, as ferment may be conveyed to the liver-cells from the blood-mass, in consequence of its stagnation. Therefore the normally ftmctionating vasomotor system of the liver, and especially its center, is, in a certain sense, to be designated an inhibitory sj'stem controlling the production of sugar. (6) If it be assumed that, under normal conditions, a certain, even though small, amoimt of sugar flows continual!}- from the liver into the blood, through the hepatic veins, diabetes might be explained as depending on the aboHtion of those metabolic processes (deranged combustion of sugar) that constantly remove this sugar from the blood vmder normal conditions. The following experiments appear to confirm this latter view: Independently of one another, v. Mering and Minkowski, as well as de Dominicis, obser\ed that dogs become diabetic after total removal of the pancreas. According to Min- kowski, it is the function of the pancreas to consume the sugar of the blood. Lepine and Barral state that a ferment is produced in the pancreas that destroys the sugar in the blood; so that after extirpation of the pancreas, sugar must accord- ingly accumulate in the blood. The ferment is contained in abvmdance within the leukoc>"tes in the portal vein; some is derived from the lymph, perhaps also from other abdominal glands. After extirpation of the pancreas, the blood con- tains little sugar-destroying ferment. Kolisch and von Stejskal found much jecorin. THE CONSTITUENTS OF THE BILE. 3x5 Pfl tiger expresses himself as follows as to the development of diabetes mellitus: The sugar formed by the liver in excessive amount, in consequence of abnormalyl increased nervous excitation, stimulates the pancreas— for it is possible that this gland takes part in the synthetic production of fat from sugar — or the fat-forming organs to the production of an increased amount of fat, so that often fat-formation takes place at the beginning of the disease. As soon as the fat-producing organs, exhausted and paralyzed from over-activity, arc no longer capable of disposing of the sugar wholly or in part (which may also be the result of excessive ingestion of sugar), this is excreted by the kidneys, because even the healthy body cannot assimilate the greater portion of the sugar as such, but only after it has been transformed into fats or into soaps. The living body strives to make good the resulting great loss in nutritive material by the assimilation of larger amounts of albtunin and fat. Naturally a variety of diabetes is conceivable without hepatic disease as the result of paralysis of the pancreas, or of the fat-producing organs. Lepine's discovery of a glycolytic ferment yielded to the blood by the pancreas, which decomposes the sugar in the blood in some as yet unknown manner, and which is absent or diminished in cases of diabetes, would readily accord with the foregoing hypothesis. In the presence of pancreatic diabetes, puncture of the floor of the fourth ventricle increases the excretion of sugar; Hkewise, remarkably, the addition of raw pancreas to the food. (c) Phloridzin, a glucosid from the bark of the roots of cherry-trees and apple- trees, after ingestion causes the sugar normally present in the blood to pass rapidly over into the urine, so that the latter contains a larger and the former a smaller amount of sugar. (d) According to Biedl, diabetes occurs after ligation of the thoracic duct in the dog. The enormous need of food and drink, together with the signs of consumption of the bodily tissues, is characteristic of diabetic patients. Not rarely, in severe cases, collapse-like coma is observed, which has been designated also diabetic coma, and during the existence of which the breath often smells of acetone, which can also be demonstrated in the urine. Diabetic patients living on an exclusive meat- diet exhibit diacetic acid in the urine, in addition to acetone. Neither acetone nor its antecedent, diacetic acid (which can be recognized bj^ the reddening of the urine when dilute ferric chlorid is added drop by drop), after the administration of which the virine contains much acetone, is, as direct feeding-experiments show, the cause of this coma; which is perhaps the result of excessive acid-production in the body, therefore an acid intoxication. To neutralize the acid, increased elimination of ammonia takes place from the body. The urinary tubules often ex- hibit signs of coagulation-necrosis, which can be recognized by a bright and swollen appearance of the necrotic cells of the tubules, v. Frerichs found, further, glyco- genic degeneration in Henle's loops, in the liver, the heart, the leukocytes and the lungs. The urine of diabetic patients is discussed on p. 501. THE CONSTITUENTS OF THE BILE. The bile is a transparent fluid varying from yellov^'ish brown to dark green in color, of a sweetish, bitter taste, feeble musk-like odor, and feebly acid or neutral reaction. The specific gravity of human bile from the gall-bladder is between 1026 and 1032, while that collected from a fistula varies from loio to loii. The constituents of the bile are as follows : Mucus, and in addition a considerable amount of mucoid nucleo- albumin, which together make the bile ropy, are products of the mucous glands and the goblet-cells of the mucous membrane of the bile-ducts. They are precipitated by alcohol, or dilute hydrochloric acid or dilute acetic acid. They cause rapid putrefaction of the bile. The two biliary acids : glycocholic acid and taurocholic acid, the so- called conjugate acids, combined with sodium (and with potassium in traces) to form sodium glycocholate and taurocholate, have a bitter taste and are dextrorotatorv. In human bile, as in that of cattle, 3l6 THE CONSTITUENTS OF THE BILE. glycocholic acid predominates; in carnivora, the sheep, the goat, tauro- cholic acid. (a) Glycocholic acid, CoeH^jNOg, is decomposed by boiling with potas- sium or barium hydrate or with dilute mineral acids, and by taking up water splits into — C3H5NO2 + C2,H,o05 = C2„H,3NO„ + H2O Glycin (glycocoU, + Cholalic or = Glycocholic Acid -h Water, gelatin-sugar, amido- cholic Acid acetic acid) (b) Taurocholic acid, C20H45NSO7, decomposes with similar treatment and addition of water into — C2H7NSO3 + C,4H,„05 = C^eH^^NSO, + H,0 Taurin (amido-ethyl- + Cholic Acid = Taurocholic Acid + Water, sulphuric acid, pris- matic crystals) Demonstration of the Biliary Acids.— The bile is evaporated to one-fourth its vol- ume, triturated to a pasty mass with animal charcoal to remove the coloring- matter, and dried at 100° C. The black mass is extracted with absolute alcohol, which passes colorless through the filter. After a portion of the alcohol has been driven off by evaporation, the addition of an excess of ether causes at first a resinoid precipitate of salts of the biliary acids, which later pass over into a crys- talline mass of brilliant needles (Platner's crystallized bile) . The alkaline salts of the biliary acids obtained in this way are readily soluble in water or alcohol, but are insoluble in ether. From the solution of both salts neittral lead acetate pre- cipitates a portion of the glycocholic acid as lead glycocholate. The latter is collected on a filter, dissolved in hot alcohol, and lead sulphid is precipitated by hydrogen sulphid. After removal of the precipitate, the addition of water causes separation of the isolated glj^cocholic acid. If, after precipitation of the lead glycocholate, basic lead acetate is added to the filtrate, a precipitate of lead taurocholate forms, uncontaminated, however, by lead glycocholate, from which the free acid is subsequently obtained by analogous treatment. According to Schotten and others, human bile contains, in addition to cholic acid, still another acid, fellic acid (CjsHggO^) ; the bile of cattle contains cholic acid (C^^H^oOs). Of the products of decomposition of the biliary acids, glycm does not occur as such in the body, but only in the bile in combination with cholic acid, in the urine in combination with benzoic acid as hippuric acid, and finally. in gelatin in complete combination. Cholic acid is dextrorotatory, insoluble in water, soluble in alcohol; it is sokxble with difficulty in ether, separating out in prisms. Its crystalline alkaline salts are readily soluble in water, like soap. With iodin, in direct light, it yields a yellow, in transmitted light a blue, crystalline combination. It occurs free only in the intestine. Cholic acid is replaced in the bile of some animals by a related acid, as, for example, in the bile of swine, by hyocholic acid; in the bile of geese, chenocholic acid is present. By boiling with concentrated hydrochloric acid or heating, dry, to 200° C, cholic acid is changed into an anhydrid dyslysin. Dyslysin is only an artificial product and never occurs in the intestines. When fused with potassium hydrate, it is changed back to potassium chelate. Pettenkofer's Test. — The biliary acids, the cholic acids and their anhydrids, when dissolved or broken up in water, and on addition of two-thirds concentrated sulphuric acid (drop by drop, without permitting the temperature of the fluid to rise above 70° C.), and a few drops of a 10 per cent, solution of cane-sugar, yield a ptirplish-red transparent color, which shows two absorption-bands in the spec- trum, at E and F. Before examining a solution for the presence of biliarj^ acids, the albumin inust always be first removed, as the latter yields a similar reaction, although the red solution here is characterized by only one absorption-band. If only small amounts of biliary acids are present, the fluid must first be concentrated by evaporation. Cholesterin, stearic and oleic acids, as well as phenol and pyrocatechin, exhibit a similar reaction. Pettenkofer's test, therefore, is absolutely reliable only when THE CONSTITUENTS OF THE BILE. 317 the salts of the bihary acids in alcoholic extract arc precipitated and thus isolated. It depends on the production, from the reaction h>etween sugar and sulphuric acid, of furfurol, which is stained red in the presence of the biliary acids. Instead of sugar a 0.1 per cent, aqueous solution of furfurol may be employed with advan- tage for this reaction. The biliary acids are formed in the Hver, as extirpation of this organ is not followed by their accumulation in the blood. The manner in detail in which the production of the nitrogenous biliary acids takes place, is unknown, although they are supposed to result from albumin. A generous protcid diet increases the secretion of bile. Taurin contains the sulphur of the protcid; the biliary acids contain from 4 to 6 per cent, of sulphur. Probably the substance of the red blood-corpuscles broken up in the liver takes part in their production. The Biliary Pigments. — Fresh human bile and that of some animals is yellowish brown in color, due to the hiliriihin present which is combined with an alkali. Under the influence of oxygen, heat and light, bilirubin is transformed by oxidation into a green pigment, biliver- din. This predominates in the bile of herbivora and of cold-blooded animals, and likewise often in the state of hunger. (a) Bilinibiii, Cj^HgeX^Oe, from 0.15 to 0.25 percent, in human bile, according to Stadeler and Maly in combination with an alkali, crys- tallizes in transparent, sorrel, clinorhombic prisms. It is insoluble in water, but soluble in chloroform, by means of which it can be separated from biliverdin, which is insoluble in chloroform. It combines w'ith alkalies as a monobasic acid and is thus soluble. It is identical with hematoidin. It is most easily prepared from red gall-stones formed of bilirubin and lime, which are triturated, the lime being dissolved out by means of hydrochloric acid. On agitation with chloroform the bilirubin is taken up. The derivation of bilirubin from hemoglobin is not to be doubted, on account of its identity with hematoidin. Probably red blood-corpuscles are broken up in the liver, and their hemoglobin is converted into bilirubin. In normal bile from a dog, a pigment is not rarely present having the spectral properties of methemoglobin, and which perhaps represents a body intermediate be- tween the hemoglobin and the coloring-matter of the bile. (6) Biliverdin, C32H36N4O8, is an oxidation-stage of bilirubin, from w^hich it can be obtained by various oxidizing processes. It is readily soluble in alcohol, wnth great difficulty in ether, and not at all in chlo- roform. It is present in large amount in the placenta of the dog. It has not as yet been possible to reconvert it into bilirubin by means of reducing agents. Gmelin's Test. — Bilirubin and biliverdin, which, in addition to the bile, are occasionally found also in other fluids, at times in the urine, are demonstrated by Gmelin's test. If to the fluid containing the substances named are added several cubic centimeters of nitric acid and one drop of nitrous acid, which are permitted to flow carefully from the edge down the sides of a conical glass, without agitation, a play of colors results as follows: green (biliverdin), blue, violet, red and yellow. (c) If the addition of acid is stopped when the color becomes blue, thus pre- venting further oxidation, a stable transformation-product remains, namely bili- cyanin. This has a blue color in acid solution, a violet color in alkaline solution, and it exhibits two ill-defined absorption-bands at D. Haycraft and Schofield were able to change this back by reduction with ammonium sulphid. Fluids containing biliary pigment, if boiled for from three to five minutes with one-third formalin, acquire "an emerald-green color, which is changed to amethyst violet on addition of hydrochloric acid. {d) Small amounts of bilijuscin (bilirubin -f water) have also been found in gall-stones and putrid bile. 3l8 THE CONSTITUENTS OF THE BILE. (e) Biliprasin (bilirubin + water + oxygen) has also been found under like conditions. (/) The yellow pigment finally obtained by the continued oxidizing effect of the nitric-acid mixture upon all of the biliary pigments is the choleiclin pi Maly, CieHigNjOf,; it is amorphous, and soluble in water, alcohol, acids and alkalies. (g) With addition of hydrogen and water in the intestine through the agency of bacteria biUrubin passes over into the hydrohiliruhin of Maly, C32H40N4O7. The same result can be brought about artificially by treating "an alkaline aqueous solution of bilirubin with actively reducing sodium-amalgam. Hydrobilirubin is but slightly soluble in water, more readily in salt-solutions or alkalies, alcohol, ether and chloroform, and it exhibits an absorption-band at F. This body, which, according to Hammarsten, occurs even in normal bile, is a constant pigment of the feces, from which, after acidulation with sulphuric acid, it pan be extracted by absolute alcohol. Probably it is identical with the pigment of the urine, the urobilin of Jaffe. HydrobiHrubin is formed in the intestine from ingested bile, being in part absorbed and excreted from the portal circulation through the bile. Hydrobilirubin to which a drop of sulphuric acid and some potassium nitrate are added again yields Gmelin's reaction. Fresh fecal matter, broken up in a porcelain dish in a concentrated solution of mercuric chlorid, yields a red color as the reaction of hydrobilirubin, while admixture of bilirubin causes a green color. Cholesterin forms transparent rhomboid plates (Fig. 92, d), is in- soluble in water, but soluble in hot alcohol, in ether or chloroform. In the bile it is kept in solution by the salts of the biliary acids. Choles- terin is not a secretory product of the liver, but a product of the disinte- gration of the epithelial cells of the biliary passages. It is most easily obtained from the so-called white gall-stones, wdiich not rarely consist principally of almost pure cholesterin, by boiling the triturated cal- cvili with alcohol. The crystals that separate on evaporation of the alcohol become red in color from the edges on addition of sulphuric acid (five volumes to one volume of water), and blue, like cellulose, on addition of sulphuric acid and iodin. Dissolved in chloroform, one drop of concentrated sulphuric acid produces a deep-red color. Moistened with a deep wine-yellow, alcoholic solution of iodin, the crystals exhibit green, blue and red coloration after addition of sulphuric acid. Dissolved in glacial acetic acid, addition of sulphuric acid produces first a rose- red, then a blue color. Other Organic Substances. — Lecithin, or its decomposition-products, neurin and glycerin-phosphoric acid; palmitin, stearin, olein, as well as their sodium-soaps; diastatic ferment; traces of urea, at times ethereal sulphuric acids ; acetic and propionic acids and traces of myris- tinic acid in the bile of cattle. Fat reaches the bile from the liver and, conversely, fat is in turn absorbed from the bile in the biliary passages (epithelial cells of the gall-bladder). Fresh unboiled bile decomposes hydrogen dioxid. Bacteria introduced into the blood- stream are in part eliminated by the bile. The inorganic constituents of the bile (from 0.6 to i per cent.) include sodium chlorid, potassium chlorid, 0.2 per cent, soda, alkaline sodium phosphate, calcium and magnesium phosphate, and an abundance of iron. The last yields the usual reactions of iron even in fresh bile, so that iron must be present in the bile in one of its oxygen-combinations. Finally, some manganese and silica are present. Freshly secreted bile from the dog contains more than 50, from the rabbit 109, volumes per cent, of carbon dioxid, in part combined with alkalies, in part absorbed, the latter being almost completely absorbed within the bladder. SECRETION' OF BILE. 319 Analysis of Human Bile. — "Water, from 82 to 90 per cent., salts of the biliary- acids, from 6 to 1 1 per cent., fats and soaps, 2 per cent.; cholesterin, 0.4 per cent.; lecithin, 0.5 per cent.; mucin, from i to 3 per cent.; ash, 0.6 per cent. The amount of sulphur contained in dr>^ bile from a dog is from 2.8 to 3.1 per cent.; the amount of nitrogen, from 7 to 10 per cent. The sulphur of the bile is not oxidized into sulphuric acid, but it appears in sulphur-containing compounds in the urine. SECRETION OF BILE. The secretion of bile is not a simple filtration of already prepared materials from the blood through the liver, but a chemical production, attended with oxidation, of the characteristic biliary matters in the liver-cells, which exhibit histological change during the process of diges- tion, and to which the blood of the gland only supplies the raw material. It takes place continuously, the bile being in part temporarily stored in the gall-bladder, and only discharged in considerable amount at the time of digestion. The higher temperature of the blood in the hepatic veins, as well as the large amount of carbon dioxid in the bile, indicates the occurrence of oxidation-processes in the liver. Even the water of the bile is not simply filtered out, since the pressure in the biliary pas- sages may exceed that in the portal vein. It appears that the bile is derived from proteid onl}', and that the excretion of carbon dioxid in the act of respiration bears a certain relation to its production. In animals (birds) deprived of their livers the constituents of the bile are not produced. After an albuminous diet the liver-cells undergo increase in size, and in still greater degree after administration of carbohj-drates, in connection with which they contain glycogen; while after ingestion of fat they likewise become larger and contain fatty granules, principally at the peripherj' of the liver-lobules. Irritation of the celiac plexus causes reduction in the size of the cells, with, deficiency in glycogen, and it appears to spur them on to secretion. The experiments of Kallmeyer and Jul. Klein, performed under the direction of Alex. Schmidt, have yielded the interesting result that a paste of fresh, "sur- viving" liver-cells produces the glycin and the taurin of the bilian.' acids from a mixture of hemoglobin (or serum) and glycogen (or dextrose) and that addition of soda or 0.6 per cent, sodium-chlorid solution favors this production. In addition to this production, a body resembling urea is formed. It is now established that the source of the latter is to be referred to the liver. Anthen, under Alex. Schmidt's direction, found that "surviving" liver-cells possess the ability to take up dissolved hemoglobin in their cell-bodies, and, in the presence of glycogen, to transform this into a pigment closely related to the biliary coloring-matter. The Amount of Bile. — Copemann and "Winston found the amount of bile to be from 700 to 800 cu. cm. in twenty-four hours, in a small woman with a biliary fistula, in whom the common bile-duct was completely closed, so that no bile could flow into the intestine; Mayo Robson found the amount to be 862 cu. cm. in a similar case; Paton found it to be as much as 680 grams, with 2.2 per cent, solid matter. Older estimates are: 533 cu. cm. by v. Wittich ; from 453 to 566 grams by Westphalen; 652 cu. cm. by Ranke, in 24 hours. Analogous estimates for animals are, to one kilogram of dog 32 grams (1.2 per cent, solid matter); to one kilogram of rabbit 137 grams (2.5 per cent, solid matter); to one kilogram of guinea-pig 176 grams (5.2 per cent, solids). The flow of bile into the intestine exhibits two maxima during a digestive period, one from the second to the fifth, and the other from the thirteenth to the fifteenth hour after the meal. The cause resides in reflex stimulation of the hepatic vessels, which in consequence become greatly distended with blood. 320 SECRETION OF BILE. The influence of the food is most striking. The most abundant secre- tion takes place after free ingestion of meat ; on addition of fat or carbo- hydrates scarcely any more is formed. In a state of hunger the quantity is reduced from one-third to one-half, and even more with a pure fat-diet. The ingestion of water increases the amount, with simultaneous relative reduction in the solid constituents. The influence of the circulation. The portal vein furnishes especially the material for the production of the bile, and in greater degree than the hepatic artery. The latter is at the same time the nutrient vessel of the tissues of the liver. This is shown by the following observations : (a) Simuhaneous ligation of the hepatic artery (diameter, 5^ mm.) and of the portal vein (diameter, 16 mm.) abolishes the secretion of bile. (b) If the hepatic artery is ligated, the portal vein alone maintains the secre- tion. According to Kottmcicr, Betz, Cohnheim and Litten, ligation of the artery or of one of its branches is said, further, to result in necrosis of the parts supplied, and possibly of the entire liver, as the artery is the nutrient vessel of this organ. After ligation of the artery the production of urea diminishes greatly; while after ligation of the portal vein this is said to remain almost normal. (c) If the branch of the portal vein for a lobule of the liver is ligated, only slight secretion takes place in this lobule through the agency of the artery. Thus neither exclusive ligation of the hepatic artery nor exclusive gradual obliteration of the portal vein (rarel}" observed as a morbid condition) results in cessation of the secretion. Only diminution in the secretion takes place. The observation that the secretion ceases after sudden ligation of the portal vein (which, besides, is rapidly fatal) is to be explained by the fact that, in addition to the diminution in the secretion, the enormous blood-stasis in the abdominal viscera after this operation makes the liver intensely anemic and therefore unsuited for secretion. (d) If the blood of the hepatic artery is introduced directly into the lumen of the opened portal vein, ligated peripherally, the secretion continues. (e) The passage as rapidly as possible of large amounts of blood through the liver acts most favorably upon the secretion. In this connection the pre- vailing blood-pressure is not of primary importance, for after ligation of the in- ferior cava above the diaphragm, in consequence of which the highest degree of blood-pressure due to stasis develops, the secretion ceases. The transfusion of considerable quantities of blood always increases the production of bile, although excessive pressure in the portal vein, from the introduction of blood from the carotid artery of another animal restricts the production. (f) Profuse loss of blood has a tendency to cause cessation of bile-production before the function of the muscular and nervous apparatus is abolished. A more abtmdant blood-supply to other organs, as, for example, to the muscles of the body engaged in hard labor, diminishes the secretion. (g) The influence of the nerves. All procedures that cause contraction of the arteries of the abdomen, such as irritation of the valve of Vieussens, of the inferior cervical ganglion, the hepatic nerves the splanchnic nerve, the spinal cord, whether directly, as by strychnin, or reflexly, by irritation of the sensory nerves, diminish the secretion. All procedures that induce stagnation of blood in the hepatic vessels, such as division of the splanchnic nerves, diabetic puncture, divi- sion of the cervical cord, have a like effect. Paralysis (ligation) of the hepatic nerves is said at first to increase the secretion of bile, with reddening of the liver. (h) With regard to the raw material brought to the liver by the blood-vessels for the production of bile, the difference in tlie composition of the blood in the hepatic veins and that in the portal vein is noteworthy. The blood in the hepatic veins contains somewhat more sugar, lecithin, cholesterin, and blood-corpuscles, but, on the contrary, it is deficient in albumin, fibrin, hemoglobin, fat, water and salts. The liver is capable of excreting unchanged in the bile biliary pigments circulating in the blood. The production of bile is dependent preeminently upon the trans- formation of the red blood-corpuscles, as they furnish the material for the formation of some of the constituents. EXCRETION OF BILE. 321 All procedures, therefore, that induce increased destruction of red blood- corpuscles make the liver rich in hemoglobin and, as a result, cause increased production of bile, also pathologically, as, for example, in the presence of malaria and blood-degenerations. Naturally, a normal condition of the liver-cells is necessary for normal secretion. For observing the secretion of bile in animals, a biliary fistula is established, the fundus of the gall-bladder being opened somewhat to the right of the xiphoid process, and then being sutured into the abdominal wall, with the aid of a cannula kept constantly open. As a rule, all of the bile will then be discharged externally. If absolute certainty in the latter connection be desired, the common bile-duct should be ligated in two places and divided. Soon after the establishment of a fis- tula, the secretion of bile diminishes. This is dependent upon the removal of the bile from the body. Introduction of bile in the body from some other source again increases the secretion. Various investigators have been able to observe directly biliary fistuUe developed pathologically in human beings. In dogs regeneration of the divided bile-duct may take place. EXCRETION OF BILE. This takes place : 1. Through the constant advance of fresh amounts of bile from the seat of production toward the excretory ducts. 2. Through the periodic compression of the liver by the diaphragm from above, with each inspiration. In addition, each inspiration accel- erates the blood-current in the hepatic veins ; each respiratory increase in abdominal pressure hastens the blood-current in the portal vein. Whether the diminution in the secretion of bile following bilateral division of the pneumogastric nerves is to be explained in this manner has been decided in the affirmative. Nevertheless it is to be borne in mind that the pneumogastric nerve sends branches to the hepatic plexus. Whether the excretion of bile is also decreased after paralysis of the phrenic nerves and relaxation of the abdom- inal pressure is undetermined. 3. By the peristaltic contraction, every fifteen or twenty seconds, of the unstriped muscle-fibers of the large biliary ducts and the gall-bladder, the secretion is forced onward. Stimulation of the region of the spinal cord, from which the motor nerves for these structures are derived (through the splanchnic nerves), for this reason induces acceleration of the discharge, which is later followed by retardation. Under normal circumstances this stimulation appears to be due to reflex action, ex- cited by the entrance of the ingesta into the duodenum, in conjunc- tion with stimulation of the movement of this portion of the intestine. The movement of the biliary ducts can be in part excited, in part inhibited reflexly by stimulation of the central end of the pneumogastric or of the sciatic nerve. According to Oddi, the common bile-duct is provided with a sphincter at its duodenal orifice, which is affected by reflex influences: gastro-intestinal irritation is believed to cause spastic contraction, which would not be unimportant in the explanation of attacks of jaundice of nervous origin. 4. Direct stimulation of the liver or reflex stimulation of the spinal cord retards the excretion. On the other hand, extirpation of the hepatic plexus, as well as injury to the floor of the fourth ventricle, has no dis- turbing influence. The splanchnic nerve is the motor nerve of the bile- ducts and the gall-bladder. Stimulation of its central extremity causes relaxation of ducts and bladder, while stimulation of the central end of the pneumogastric nerve causes their contraction, together with relaxa- tion of the sphincter of the duodenal orifice. 322 RESORPTION' OF BILE. 5. Stasis of bile occurs in the bile-ducts even from relatively slight resistance. A manometer fastened in the gall-bladder of a guinea-pig balanced a column of water more than 200 mm. high. Up to this pressure, therefore, secretion took place. If this pressure were increased or maintained for an excessively- long time, absorption of the water of the bile into the blood took place on the part of the liver, up to about four times the weight of the liver, as a result of which solution of red blood-corpuscles by the bile absorbed took place at the same time, with the passage of hemoglobin into the urine. Various substances that enter the circulation readily pass over into the bile, particularly the metals, which are also deposited in the hepatic tissue. _ Further, potassium iodid, bromid, and ferrocyanid, potassium chlorate, arsenic, oil of turpentine, bile injected into the blood (also that from other animals), indigo- carmine and xanthophyllin pass over; less readily, cane-sugar and grape-sugar, sodium salicylate and carbolic acid. Sugar has been foiind in cases of diabetes, leucin and tyrosin in cases of typhoid fever, altered hemoglobin in the presence of blood-degeneration, lactic acid and albumin under other pathological con- ditions. Some substances promote the secretion of bile, olive-oil most intensely; further, oil of turpentine, sodium salicylate, alkalies and laxatives, bile and salts of the biliary acids (particularly from other species of animals), which, after ab- sorption, are again secreted by the liver. Pilocarpin and atropin diminish the secretion. The so-called lymphagogues induce marked secretion of bile in conse- quence of increased hepatic activity; the increase of lymph, on the part of the liver, is thotight to depend upon the latter. RESORPTION OF BILE. Symptoms of Jaundice (Icterus; Cholemiaj. — If an obstruction occurs to the dis- charge of bile into the intestine, — as, for example, a plug of mucus or a gall-stone occluding the common bile-duct, or a tumor or pressure from without, rendering the duct impervious, — the biliary passages become distended, and, through their distention, cause enlargement of the liver. The pressure in the biliary passages is naturally increased under such conditions. As soon as this pressure has reached -a certain point, in the dog up to 275 mm. of a column of the excreted bile — as must soon take place with the continued production of bile — resorption of the bile from the greatly distended bile-ducts of larger size into the lymph-vessels (not into the blood-vessels) of the liver occurs. In this way the biliary acids and the biliary coloring-matter enter the blood. Ligation of the thoracic duct therefore prevents the entrance of the substances into the blood. Also when the pressure within the portal vein is abnormally low, it is thought that bile can pass over into the blood without occlusion of the bile-ducts. This is said to be partly the case in the presence of icterus neonatorum, as blood no longer enters the portal vein from the umbilical vein after the umbilical cord has been tied; further, in the presence of the " hvmger - icterus " observed during the state of hunger, as in the stage of inanition, the distribution of the portal vein is relatively empty, on account of deficient absorption from the intestine. Cholemia may, however, result also from the excessive production of bile (hypercholia) , which cannot be completely discharged into the intestine, and thus is resorbed. This takes place when erythrocytes, which furnish the material for the manufacture of the bile, are destroyed in excessive amount. From this material only the liver can elaborate bile. Under such circumstances a plug •of inspissated secretion at times forms in the bile-ducts, as a result of which, in consequence of the stagnation of the bile, its resorption is in turn favored. The transfusion of heterogeneous blood acts in this way, in consequence of destruction of the red blood-corpuscles. Therefore icterus is a frequent symptom under such conditions. The author has encountered the same phenomenon after excessive transfusion of blood from the same species, the blood being in part likewise dis- solved later. Such a solvent effect upon the erj-throcytes is exerted also by the injection of some heterogeneous sera, of salts of the biliarj^ acids, of water, of vari- ous acids, as, for example, phosphoric acid, and by the administration of large amounts of chloral, chloroform and ether. Further, injections of hemoglobin in solution into the blood-stream or into the intestine, from which it is absorbed, have the same effect. (The subject is further considered on p. 34 1 .) RESORPTION OF BILE. 323 If, as a result of compression of the placenta in the uterus, too much blood has been carried to the new-born infant, a portion of this excess of blood in the body may be dissolved during the first days of life, the hemoglobin being trans- formed into bilirubin, with symptoms of icterus. Under such circumstances also there is excessive destruction of erythrocytes, as, indeed, of all of the tissues, because in the new-born infant, with insufficient nourishment the metabolic processes must be more active for the maintenance of respiration, heat-production and digestive activity. The jaundice that is exemplified by the foregoing symptoms is also designated hepatogenic, or resorption-icterus, because it is due to the absorption of bile already prepared in the liver. Cholemia is accompanied by a series of characteristic symptoms: 1. Biliary coloring-matter and the biliary acids enter into the tissues of the body, giving rise to the most striking objective symptom (and therefore designated also jaundice). The external integument, particularly the sclera, ac- quires an exquisitely yellow color. In pregnant women the fetus also is discolored. Hematoidin-crystals have been found in the kidneys, the blood and the fatty tis- sue of icteric children. In exceptionally rare cases, as in the presence of hemi- plegia, only one-half of the body has been found jaundiced. 2. The biliary acids and the biliary coloring-matters appear in the urine, though not in the saliva, the tears or in mucus. When the coloring-matter is present in large amount the urine acqmres a deep yellowish-brown color, while its foam is intensely lemon-yellow. Immersed strips of paper or linen are stained the same color. Occasionally crystals of bilirubin are present. 3. The feces become clay-colored, because of the absence of hydrobilirubin derived from the bile-pigment; extremely hard, because the diluting bile does not reach the intestine; rich in fat, because the fats, particularly the more solid, are not sufficiently digested in the intestine in the absence of bile (so that even as much as 78 per cent, of the fat ingested passes out in the feces; principally fatty acids and soaps appear in the feces, and but little neutral fats) ; and highly offensive, because, under normal conditions, the bile poured out into the intestine inhibits putrid decomposition of the intestinal contents. The evacuation of the feces takes place sluggishly, partly on account of their hardness, partly because of the absence of bile, which excites peristaltic movements in the intestines. 4. The heart-beats are reduced to about 40 in the minute. This is due to the salts of the biliary acids, which at first stimulate the heart and then enfeeble it. Injection of the salts of the biliary acids into the heart causes, therefore, at first, transitory increase in the heart-beats, followed by slowing. The same result is brought about if these substances are injected directly into the blood, although under such circumstances the brief stage of stimulation is much less marked. Division of the pneumogastric nerve has no influence on this phenom- enon. In addition to the action on the heart, there is marked dilatation of the smallest blood-vessels, slowing of the respiration and lowering of the tem- perature. 5. An influence on the nervous system, either through the salts of the biliary acids or through the cholesterin accumulated in the blood, perhaps also upon the muscles, is shown by the great general relaxation, fatigue, weakness and somnolence, finally deep coma; at times by insomnia, pruritus, even delirium and convulsions. In experiments on animals Lowit observed symptoms, after injections of bile, indicative of stimulation of the respiratory, cardio-inhibitory and vasomotor centers. Direct application of bile or its salts to the cerebrum causes convulsions. 6. Jaundice of marked degree is attended with yellow vision, in consequence of impregnation of the retina with yellow biliary coloring-matter. 7. The biliary acids in the blood dissolve the erythrocytes, and this leads to the further formation of bile. The dissolved hemoglobin is transformed into new bile-pigment, while the globulin-body of the disintegrated hemoglobin may form casts in the renal tubules, which later are washed into the urine. Should dissolution not take place, the erythrocytes become swollen and exhibit increased solubility. After ligation of the bile-duct, the protoplasm of the liver-cells disappears, and according to some observers partial necrosis of the hepatic tissue occurs, with secondary reactive inflammation, connective-tissue hyperplasia, cell-multiplica- tion of the epithelial cells of the biliary passages. The stagnating bile diminishes in amount and exhibits further an increase of mucus and cholesterin, but on the other hand a reduction in taurocholic acid (in the dog). 324 ACTIOX OF THE BILE. ACTION OF THE BILE. The bile is a metabolic product largely destined for excretion, and participating in but small measure in the digestive process. Bile plays an important part in the absorption of fat. It fonns a fine emulsion of the neutral fats, in consequence of which the fatty granules, in addition to chemical division, are especially rendered capa- ble of passing through the cylindrical epithelium of the small intes- tine. It does not effect the chemical decomposition of the neutral fats into glycerin and fatty acids, as does the pancreatic juice, but it is capable of dissolving the fatty acids through the salts of the biliar}^ acids. . The soaps present in the intestine are soluble in the bile and are capable in turn of greatly increasing the emtilsifying power of the bile. The bile itself, however, is capable of converting the fatty acids directly into an acid solution that exerts an active emtdsifying influence. As the bile, like a soap solution, bears a certain relation to aqueous fluids as well as to fats, it may conduce to diffusion between the two, as the membrane can be moistened and can imbibe both fluids. From the foregoing it follows that the bile is of great importance for the preparation and absorption of fats. This can also be demonstrated b)- experi- ments on animals, in which the bile is entirely conve\-ed externally through a fisttda. Dogs thus treated absorb, at the most. 40 per cent, of the fat ingested, while normal dogs absorb 99 per cent. The chyle of such animals is, accord- ingly, deficient in fat, and is not white, but transparent. The feces, however, contain more fat and are greasy. The animals eat greedilj-; the tissues of the body show great deficiency of i'at, even when the nutrition in general has not suffered much. In htunan beings suftering from derangement in the secretion of bUe, a diet rich in fat is, for this reason, contraindicated. Fresh bile contains some diastatic ferment, as starch and glycogen are converted into sugar. This ferment is, however, absorbed from the walls of the alimentary canal and is then excreted as ptyalin by the bile, as by the urine also. The bile acts as a stimulant to the intestinal musculature and thus contributes to absorption in general. Perhaps through its biliary acids, acting as irritants, it causes the muscles of the intestinal villi to contract from time to time, in consequence of which these propel the contents of their lymph-spaces into the larger lymph- trtmks, and thus are capable of absorbing renewed amounts. Also the musculature of the intestinal wall itself appears to undergo excita- tion, probably through the agency of the myenteric plexus. In favor of this view is the fact that intestinal peristalsis is greatly impaired in animals with biliar}- fistulae and in the presence of obstruction of the bilian.- passages, as well as the fact that the salts of the biHar\- acids, administered by the mouth, cause diarrhea and vomiting. As, however, intestinal contractions aid absorption, the bile is, in this connection also, active in taking up the dissolved food. The presence of bile is necessan,^ for the normal vital activity of the intestinal epithelium in the absorption of the fatty globules. Through its excretion the bile supplies a sufficient amount of water for the feces. Animals with biliar}' fistulae and human beings with obstnicted biliary' passages are markedly constipated. Besides, the slipper}^ mucus of the bile facilitates the advance of the rngesta through the intestinal canal. FIXAL FATE OF THE BILE IX THE IXTESTIXAL CAXAL. 325 The bile diminishes putrefactive decomposition of the intestinal con- tents, especially with a fatty diet. On the entrance of the strongly acid gastric contents into the duo- denum, the glycocholic acid is precipitated by the acid of the stomach and carries the pepsin with it. Further, the albumin and the gelatin, still in solution, but not the peptones and propeptones, are precipitated by the taurocholic acid, salts of the biliary acids having already been de- composed by the acid of the stomach. If, however, the mixture is again rendered alkaline by the pancreatic and the intestinal juice and the alkali of the bases derived from the salts of the biliary acids, the pancreatic ferments enter energetically into action. If bile enters the stomach, as, for instance, in the act of vomiting, the acid of the gastric juice combines with the bases of the salts of the biliary acids. There thus results principally sodium chlorid and free biliar\^ acids. At the same time the acid reaction is diminished. The bilian,' acids are not effective as acids in gastric digestion, in place of the combined hydrochloric acid, the neutralization causing also precipitation of the pepsin and the mucin. As soon, however, as the wall of the stomach secretes additional acid, the pepsin is again dissolved. The bile entering the stomach has a disttirbing effect on gastric digestion also, by causing contraction of the albximinates, as these can be peptonized only when swollen. FINAL FATE OF THE BILE IN THE INTESTINAL CANAL. Of the constituents of bile, some are evacuated with the feces, while others are again absorbed through the intestinal walls. The mucin passes into the feces unchanged. The biliary coloring-matters are mostly reduced in the large in- testine and are partly evacuated with the feces as hydrobilirubin ; a small portion of them is absorbed and finds its way into the urine as urobilin. The reduction may proceed beyond the formation of hydro- bilirubin to that of a colorless material, which may, however, upon ad- mission of oxygen, be again oxidized to hydrobilirubin. Hydrobilirubin is absent from meconium, but bilirubin and biliverdin are present together with an unknown red oxidation-product derived from them. Therefore the process that takes place in the fetal intestine is not a reducing but an oxidizing one. Cholesterin is in part evacuated with the feces; in part it is re- duced to the form of hydrocholesterin (coprosterin), crv'stallizing in needles. The biliary acids are. for the most part, again absorbed through the walls of the jejunum and the ileum, and are utilized anew in the pro- duction of bile. Tappeiner found them in the thoracic duct; small amounts find their way from the blood into the urine. Only a small portion of glycocholic acid appears unchanged in the feces. Taurocholic acid, in so far as it is not absorbed, is readily decomposed in the intestine by putrefactive processes into cholic acid and taurin. The former is found in the feces, the latter is not infrequently absent. Cholic acid is, however, in part resorbed and may again unite in the liver with glycin or taurin. As putrefactive decomposition is absent from the fetal intestine, unchanged taurocholic acid is accordingly present in the meconium. Glycocholic acid, when administered, is found again in the bile from animals (dog) which nor- mally excrete but little thereof. The feces certainlv contain merelv traces of lecithin. 326 THE IXTESTIXAL JUICE. As, therefore, the largest part of the bihary acids is returned to the blood, it is clear that animals from which all the bile is lost through a biliary fistula, without their licking it up, lose considerably in weight. This is due partly to the impaired digestion of fat, in part to the direct loss of the biliary acids. If dogs are nevertheless to maintain the same weight, they must consume almost double their former nourishment. Under svich conditions, carbohydrates are especially serviceable as a substitute for fat in the diet. If their digestive ap- paratus is in other respects intact, the animals may, by reason of their voracity, even gain in weight. Under such circumstances, however, it is the muscles almost alone and not the fat that is increased. The fact that bile is secreted during fetal life, while none of the other digestive fluids are produced, indicates that the bile is in part a product of retrogressive tissue-metamorphosis, and is intended for the constant elimination of certain excrementitious matters. The cholic acid, which is absorbed through the intestinal wall, is finally burned up in the body into carbon dioxid and water. The glycin gives rise to the production of urea, as well as hippuric acid, as, after the ingestion of that substance, the amount of urea is greatly increased. The fate of the taurin is not known. Considerable amounts administered to human beings by the stomach appear again in the urine principally as taurocarbamic acid, together with a small amount of unchanged taurin. When injected subcutaneously into a rabbit, it almost all appears in the urine. THE INTESTINAL JUICE. The human intestine is ten times as long as the length of the body from the vertex to the anus. In this it resembles that of fructivorous apes. It is relatively longer than that of omnivora. Its minimum length is 507 cm.; its maximum length, 1 149 cm. Its capacity is relatively greatest in children, in whom also it is relatively longer. The intestine is somewhat longer in males than in females. The intestinal juice is the digestive fluid secreted by the numerous glands of the intestinal mucous membrane. The largest amount is fur- nished by Lieberkiihn's glands; the duodenum receives, besides, the scanty secretion of the compound alveolar grands of Brunner. Brunner's glands, which occur singly in human beings, but in the sheep constitute a continuous layer in the duodenum, are present, in part, at the pylorus. Their cylindrical cells have a middle, darker zone; the flat nucleus lies near the base of the cell, with a diplosome nearer its free surface. During the state of hunger, the cells are turbid and small, and, like the pyloric glands of the stomach, they contain fatty granules, while during digestive activity they are large and clear. The glands contain nerve-filaments from Meissner's plexus in the mucous membrane. The Secretion of Brunner's Glands. — The usually granular contents of the secretory cells consist, in addition to albuminous materials, of mucin and ferment-substances of unknown nature. It is not improbable that these glands are related to the pancreas, and peirhaps are even to be regarded as detached portions of the pancreas. Their activity seems to favor this view. An aqueous extract (i) dissolves albumin slowly and feebly, at the temperature of the body. (2) It possesses diastatic activity. The secretion appears to have no effect on fats. It should be especially emphasized that, as on account of the small size of the glands they must be viewed individually, with a magnifying glass, from the under surface of the intestinal mucous membrane, digestive experiments are exceedingly difficult. Lieberkiihn's crypts or glands are simple tubular glands, resembling the finger of a glove, that lie close to one another in the intestinal mucous membrane, and in greatest number in that of the large intestine (on account of the absence of villi). They possess a membrana propria, constituted of most delicate fibrils, THE INTESTINAL TUICE. 327 and a single layer of cylindrical protoplasmic cells, between which goblet-cells also occur, in small number in the small, and in large number in the large intes- tine. The glands in the small intestine yield a watery secretion principally; those of the large intestine, from their numerous goblet-cells, ropy mucus. Both kinds of gland-cells multiply by mitosis, and the new products move from situ- ations where active division is going on to places where the production is less active. The mucus in the goblet-cells encloses usually a single central body. The secretion of Lieberkuhn's glands is, from the duodenum down- ward, the chief source of the intestinal juice. The intestinal juice is obtained, ATX. /^ 1 c^ l>i-- ■- r. -V* is- - ■ ' '_-P mr ^ 1 '^y iM^ :^x2^^ L.l Mm. by Thir>''s method, in the following manner: From a loop of the in- testine of a dog. withdrawn from the abdomen, a piece of the length of a hand is so divided by two inci- sions that only the continuity of the intestinal canal is severed but not the mesentery. Then one end of this piece is ligated; the other, left open, is sutured in the abdominal woimd, after the ends of the intestine, be- tween which the piece has been re- moved, have been carefully united by suture. Vella permits both ends of this horseshoe-shaped portion of intestine to open on the abdominal wall. In this way, after the opera- tion has been completed, the animal can continue to live with its but slightly abbreviated intestine. The intestinal fistula, with a free exter- nal opening, yields, however, an in- testinal juice that is not contamin- ated by any other digestive secretion. The intestinal juice derived from such a fistula flows spon- taneously in very small amount ; during digestion it is largely increased. Mechanical, chemi- cal and electrical stimulation increase the secretion, especi- ally of mucus, with reddening of the mucous membrane, so that 100 square centimeters yield from 13 to 18 grams of juice in an hour. The adminis- tration of pilocarpin also in- creases the secretion. The juice is light yellow in color, opal- escent, water}', strongly alkaline, effervescing on addition of acids, and has a specific gravity of loio. It contains, in human beings, proteid (0.80 per cent.), ferments, mucin, especially in the large intestine (0.73 per cent.), and salts (0.88 per cent.), of which 0.34 per cent, is soda and 0.5 per cent, sodium chlorid. The amoimt of intestinal juice secreted is least with the presence of dissolved grape-sugar in the intestines, greater with the presence of cane-sugar, and still greater with the presence of starch and peptone. It increases in the second hour of digestion. ifc. MI. Fig. 120. — Longitudinal Section through the Small Intestine of a Dog: B, connective-tissue layer; Z, intestinal ^-iili covered with cylindrical epithe- lium; L, Lieberkuhn's glands; ^Sim, muscularis mucosa: G, crowded h-mph-follides; Mc, circular muscular layer; Ml, longitudinal muscular layer. 328 THE INTESTINAL JUICE. Biedermann found the production of mucus in the goblet-cells of the intestine, in the frog, to take place in such a manner that droplets of mucus first appear in the cell-contents. These enlarge into vacuoles, which soon become confluent; then the mucus escapes from these and is discharged from the cell. The digestive activity of the juice of the small intestine is still in many respects unexplained. The juice has been found most active in the dog, while it is more or less inactive in other animals. It possesses less diastatic activity than the saliva and the pancreatic juice. It forms maltose, which rapidly passes over into dextrose. The glands of the large intestine are said to be wanting in this property, von "Wittich has extracted the ferment by means of glycerin diluted with water. The intestinal juice is capable of transforming maltose into grape- sugar. It, therefore, continues the diastatic action of the saliva and the pancreatic juice, which principally are active only up to the pro- duction of maltose. According to Bourquelot, this action is due to intestinal bacteria, and not to the intestinal juice as such, nor to the saliva, the gastric juice or the invertin. The larger part of the maltose, however, seems to undergo absorption tonchanged. No action upon proteids is recognizable, or, at least, only traces. The peptonizing properties described are in part dependent upon putre- factive processes. According to earlier statements, fibrin is slowly peptonized by trypsin and pepsin; albumin, fresh casein, raw or cooked meat and vegetable albumin less readily. Gelatin is probably also brought into solution by a special Fig. 121. — Transverse Section through Lieber- lermenc. kuhn's Glands: H, caWty of the glandular 'p^g intestinal juicC is Capable Of tubule; D, glandular epitheuum; B, connec- -!,.,. ^ . ,, live tissue; G, blood-vessels. actmg ou tat, which it partially emulsifies in the presence of free acid. AVhether the neutral fats are also decomposed, in small measure, has not as yet been determined with certainty. The intestinal juice contains invertin, an unorganized ferment, which decomposes disaccharids (cane-sugar, milk-sugar and maltose) into monosaccharids (dextrose, le^'ulose and galactose), with the taking up of water and the production of heat : CnH,,On - H,0 = CeHijOe + CeHijOg Cane-sugar — \\ ater = Dextrose — Le\-ulose. Milk (casein) is coagulated. With regard to the ferments of the alimentary canal, Langley upholds the view that they undergo destruction: the diastatic ferment of the saliva is de- stroyed by the hydrochloric acid of the gastric juice ; pepsin and the rennet-ferment succumb to the action of the alkaline salts of the pancreatic and intestinal juices and the tr\-psin ; the diastatic and peptic ferments of the pancreas are rendered inert by the acid fermentation in the large intestine. Nevertheless some ferment is absorbed and passes over into the urine. Of the influence of the nenes upon the secretion of the intestinal jtiice but little has been ascertained with certainty. Stimulation or division of the pneumo- gastric nerves is without apparent effect. On the other hand, destruction of the nerve-filaments passing to the intestinal loops and accompanying the blood-ves- sels is followed by distention of the intestinal canal ^^-ith an abundance of watery BACTERIAL FERMENTATION IN THE INTESTINES. 329 flxiid. This result is explained in part by paralysis of the vasomotor nerves of the intestinal tract. As the nerve-filaments for a limited portion of intestine, ligated in two places, can be completely separated, the watery intestinal contents will be found only in the corresponding loop of intestine. According to Hanau, the condition in this experiment of Moreau is one of paralytic secretion, which, with regard to time, pursues a typical course. The following substances are after ingestion excreted by the intestinal mucous membrane of isolated fistuke : iodin, bromin, lithium, metallic ferrocyanogen, salts of iron and others. FERMENTATIVE PROCESSES IN THE INTESTINES DUE TO MICROBES; INTESTINAL GASES. "Wholly different from the peculiar digestive processes just described, which are brought about by definite unorganized ferments or en- zymes, are those processes which are to be considered as fermentative or putrefactive decompositions. These are caused by microbes, the so- called excitants of fermentation or putrefaction, or organized ferments; and they may, therefore, take place outside of the body, in suitable media. Lower forms of organisms, which maintain fermentative pro- cesses in the intestinal tract, are often swallowed with food and drink, as well as with the buccal fluid. Upon the introduction of these the processes of decomposition begin, with simultaneous production of gas. On a pure milk-diet intestinal putrefaction is much less marked. Fermentation, therefore, cannot occur in the intestine during fetal life. For this reason gases are always absent in the intestine of the new-bom. The first bubbles of air reach the intestine through frothy saliva swallowed, even before food is taken. As, however, micro- organisms may enter the intestinal tract with the air swallowed, the development of gas by fermentation must soon follow. The development of the intestinal gases thus goes hand in hand with the fermentative processes. As, however, gases from the air swallowed are exchanged in the intestinal canal, the composition of the intestinal gases will be found to be dependent upon various factors. Kolbe and Ruge collected intestinal gases from the human anus and found in 100 volumes: Food. COo. H. CH4. N. H;S. Milk 16. S 43-3 0-9 38-3) Amoimt Meat 12.4 2.1 27.5 57.8^ Amount r> .. ^ in ^ \ unknown. Peas 21.0 4.0 55.9 ii>-9 J Moreover, it should be noted : i . That oxygen is rapidly absorbed by the walls of the canal from the air-bubbles swallowed with the food, so that, in the lower part of the large intestine, even traces of oxygen are absent. In exchange the blood-vessels of the intestinal wall give up into the intestine carbon dioxid, so that, therefore, a portion of the car- bon dioxid in the intestines is derived from the blood by diffusion. 2. Hydrogen, carbon dioxid and ammonia, as well as marsh-gas, are also developed from the intestinal contents by fermentation, which may take place even in the small intestine. Bacteria as Excitants of Fermentation. The organisms that especially cause fermentation, putrefaction and other forms of decomposition are bacteria (schizo- mycetes), namely, minute, unicellular structures, chiefly having the shape of a sphere (micrococcus) , or a short rod (bacteritun) , or a long rod (bacillus) , or a spiral thread (vibrio, spirillimi, spirochsta). Their power of reproduction is bevond all conceotion. Through their vital phenomena they cause profound 33° BACTERIAL FERMENTATION" IN THE INTESTINES. chemical changes in the matters containing them. As for their growth and metaboHsm, they abstract certain substances from the nutritive fluid in which they live, they decompose the chemicals contained therein. In this process sonie of them "form certain substances that may subsequently act as ferments upon matters in the nutritive fluid. The microbes are destroved by antiseptics, such as carbolic acid, salicylic acid, etc., although the ferments are not destroyed. Therefore, these substances afford a means of distinguishing and separating the fermentative from the micro- biotic decompositions. The bacteria consist of a capsule and protoplasmic contents. Some possess fiagella as organs of locomotion, which, perhaps, are possessed by all capable of motion. The organisms multiplying by division are sometimes collected together in extensive colonies, united by a gelatinous mass, often visible to the naked eye, and which are designated zoogleas. These appear in the form of nodules,' branches, patches, flakes, layers of mold, or ropy, creamy or greasy deposits. In the case of some micro-organisms, principally bacteria, multiplica- tion takes place by spore-formation, especially if the nutritive fluid becomes deficient in nutrient material. The rods then grow into threads of considerable size, which become jointed: and globvilar, strongly refractive granules, from i to 2 " in size, develop in the individual parts (Fig. 122, 8, 9}. In the case of some, as 3 ^ff I i ^ e« ^ <^ .J Fig. 122. — A, baaerium aceti, in the form of coed (i), diplococd (2), short badlli (3), and jointed threads U.s)- B, badllus butyricus: i. isolated spore; 2, 3, 4, germinating stage of the sp)ore; 5, 6, short and long badlli; T, 8, 9, spore-formation in the bacteria. the butyric-acid germ, the bacilli, before spore-formation, acqture the shape of an enlarged spindle, within which the spores form. After death of the mother- cells, the spores become free, and from them, transplanted to a suitable soil, the newly formed cells of the microbes again germinate. The processes of spore- formation (7, 8, 9) and of germination of the butyric-acid micro-organism (1,2, 3, 4) are illustrated in Fig. 122. B. The spores are extremely resistant, being capable, in the dr\' state, of surviving for a long time, and some even withstanding boiling. Among bacteria, a distinction is made between those that exhibit their vital activity in the presence of oxygen, aerobes, and others that thrive only when oxygen is excluded, anaerobes. In accordance with the products to which they give rise bv decomposition in their nutrient media, they may be divided into those that induce decomposition in the form of fermentations (zymogenic schizo- m^-cetes), those that form pigments (chromogenic) , those that generate bad odors, as in the putrefactive processes (bromogenic) , and, finally, those that, developing in the Uving tissues of other organisms, cause morbid conditions, even death itself (pathogenic) . Some also elaborate poisons (toxicogenic) . All of these have been fotmd in and upon the human body. If it be borne in mind that a large number of bacteria are introduced into the alimentary- canal with foods and drinks, as well as, in part, also with the in- spired air; that, further, the temperature of the intestine is especially favorable BACTERIAL FERMENTATION IN THE INTESTINES. 331 to their development: and, finally, that sufficient material of the most varied kind, not entirely disposed of by the digestive processes, furnishes nutrient matter for the vegetation of the germs, it is not surprising that a rich formation of these organisms is found in the alimentary canal and that they cause numerous forms of decomposition in the intestinal contents. Knowledge of these processes is, at the present time, still highly deficient; and the formulce proposed for the de- compositions can. therefore, only approximately explain the processes. For this reason, the following statements can only be considered provisionally as aphorisms in the study of the mycotic intestinal decompositions. Fermentation of Carbohydrates, which takes place principally in the small intestine, i. Bacillus acidi lactici (bacterium lacticum), whose biscuit-shaped cells, from 1.5 to 3 /^ in length, are arranged in groups or rows or are isolated, causes fermentative decomposition of sugar into inactive lactic acid: C,H,A = 2(C3He03) I Grape-sugar = 2 Lactic add. Milk-sugar (CisHojOu) may be decomposed by the same bacterium, with the addition of water, first into two molecules of grape-sugar, 2(C6Hi206), and this in turn into four molecules of lactic acid, 4(C3H803). This micro-organism, whose germs fioat in the air every-v\^here , causes the spontaneous souring and curdling of milk. It develops further in sour-crout, sour pickles, and the like. It induces fermentation of cane-sugar, mannite, inosite, and sorbite, as of the sugars mentioned. In addition to lactic acid, carbon dioxid also results. There are, besides, other lactic-acid-producing bacteria that are capable further of transforming starch into sugar, van de Velde obtained lactic, butyric and succinic acids as products of the fermentative activ- ity of the bacillus subtilis (Fig. 123), and mannite as a reduction-product. 2. Bacillus butyricus, which is often stained blue by iodin in a starch-containing medium, transforms lactic acid into butyric acid, together with carbon dioxid and hydrogen. 2(C3He03) = C4H,02 -r 2CO2 4- 4H. 2 Lactic Acid = i Butyric .■\cid — 2 Carbon Dioxid — 4 Hydrogen. This bacterium (Fig. 122, B) is a true anaerobe, which vegetates only in the absence of oxygen. The lactic-acid bacillus, which actively consumes oxygen, is therefore its natural predecessor. Butyric-acid fermentation completes the transformation of many carbohydrates, chiefly starch, dextrin and intdin. It takes place constantly in the feces. There are a number of other bacteria with similar activity. The butyric-acid bacillus produces also dextrin from starch. 3. Certain micrococci are capable of developing alcohol as the chief product from sugar. In the human small intestine there are present besides: bacterium Bischleri (short rods) . which produces alcohol, inactive lactic acid and acetic acid from sugar; bacterium ilei (short rods), which transforms sugar into alcohol, succinic acid and some active paralactic acid, together with carbon dioxid and hydrogen; bacterium ovale ilei (almost spherical), which transforms sugar into alcohol, paralactic ■ acid and traces of the fatty acids; bacillus gracilis ilei (delicate long rods), which has a similar action; bacterium lactis aerogenes, which transforrns sugar into alcohol and succinic acid, together with lactic acid and some acetic acid. The presence of yeast also may result in the production of alcohol in the intestine, in both instances likewise from milk-sugar, which at first passes over into dextrose. Only traces are found in the intestine. 4. Bacterium aceti (Fig. 122, A) is capable, outside of the body, of transforming alcohol into acetic acid. QHeO _ O = C,H,0 + HjO Alcohol - Oxygen = Aldehyd + Water. 332 BACTERIAL FERMENTATION IN THE INTESTINES. Aldehyd is changed by oxidation into acetic acid (CoH^Oj). Accord- ing to Nageli, the same micro-organism is capable of producing small amounts of carbon dioxid and water. As acetic fermentation ceases at 35° C, it will not take place in the intestine, so that the acetic acid con- stantly met with in the feces must result from other fermentative pro- cesses. Thus, it is produced in considerable amount in herbivora as a product of the fermentation of cellulose; being, after absorption, burned up in the fluids of the body. Acetic acid is formed also as a result of the putrefaction of albuminates with exclusion of air. 5. Also partial solution of starch and of cellulose is caused by schizo- mycetes (bacillus butyricus, bacterium termo, vibrio rugula) in the intestines; for cellulose, mixed with cloacal discharge or the intes- tinal contents, is transformed into a sugar-like carbohydrate, which then breaks up into equal volumes of carbon dioxid and marsh-gas. The neurin produced by the pancreas also yields marsh-gas (CH4), in addition to carbon dioxid. The solution of the cellulose of the cell-walls then permits the action of the digestive juices upon the enclosed digestible portions of the 0 0 -J 1234 Fig. 123. — Hay-bacillus (Bacillus subtilis): i, spore; 2, 3, 4, germination of the spore; 5, 6, short bacilli; 7, jointed filament \vith spore-formation in each cell; 8, short bacilli, in part with spore-formation; 9, spores in indi\idual short bacilli; 10, bacteria with flagella. vegetable food. In human beings the metabolism of cellulose is always slight, while in herbivora it is digested in considerable amounts. 6. Bacillus subtilis, cheese-spirilli and others are capable of trans- forming starch into sugar. 7. Micro-organisms (lactic-acid bacilli?) that produce invertin also occur in the intestinal canal. This substance can be obtained also from brewer's yeast by agitation with water and ether and subsequent fil- tration. Fermentation of Fats. Putrefaction is capable, with the aid of as yet unknown micro-organisms, of decomposing neutral fats into glycerin and fatty acids, after taking up water. Glycerin is susceptible of varied fermentations with different microbes, as, for example, the bacillus Fitzianus. When the reaction is neutral, hydrogen and carbon dioxid are formed, together with succinic acid and a mixture of fatty acids. Fitz observed alcohol, together with caproic, butyric and acetic acids, develop as a result of the action of the hay-bacillus (bacillus subtilis. Fig. 123J, while in other cases butj'l-alcohol principally resulted, van de Velde found butyric and lactic acids, together with traces of succinic acid, and also carbon dioxid, water and nitrogen. BACTERIAL FERMENTATION IN THE INTESTINES. 333 The fatty acids yield, chiefly as calcium-soaps, material suitable for fermentation. Calcium formate, in fermentation with cloacal discharge, yields calcium carbonate, carbon dioxid and hydrogen; calcium acetate yields calcium carbonate, carbon dioxid and marsh-gas. Of the oxy- acids, the fermentation of lactic, glyceric, malic, tartaric and citric acids is known. According to Fitz, lactic acid, in combination with calcium, yields propionic acid, acetic acid, carbon dioxid and water. Valerianic acid in cons derable amount is produced by other excitants of fermentation. Glyceric acid yields especially acetic acid, in addition to alcohol and succinic acid. Malic acid forms succinic acid and some acetic acid; as a result of other fermentative processes, propionic acid, and of still other fermentative processes, butyric acid, together with hydrogen; or it is decomposed into lactic acid and carbon dioxid. Tartaric acid breaks up into acetic acid, propionic acid, carbon dioxid and water; as a result of the action of other microbes, into butyric acid; and of that of still others, into acetic acid, together with some butyric and succinic acids and alcohol. Citric acid yields finally acetic, with some butyric and succinic acids. Fermentations of Proteids. In the fermentation of the undigested proteids in the intestine and their derivatives, which takes place princi- pally in the large intestine, micro-organisms likewise appear to take part. In the first place it should be emphasized that some schizomycetes are capable of producing peptonizing ferment, as, for example, the bacillus subtilis, bacillus liquefaciens ilei, the cheese-spirilli, the micro-organisms of pickled herring, etc., so that assistance to the peptic enzyme, even though slight, on the part of these microbes appears to be not wholly ex- cluded. It has been found that pancreatic digestion of albuminates does not proceed beyond the production of amido-acids : leucin, tyrosin and others. Putrefactive fermentation in the large intestine causes still further and more profound decompositions. Leucin (CgHjjNO,), by taking up two molecules of water, forms valerianic acid (C5H10O2), ammonia, carbon dioxid and four molecules of hydrogen. Glycin behaves in a similar manner. Tyrosin (C9H11NO3) breaks up into indol (CgH^N), which is constantly encountered in the intestine, together with carbon dioxid, water and hydrogen. If the admission of oxygen is possible, still other decompositions take place. These products of putrefaction are wanting in the intestine of the fetus and the new-born. In the putrefactive de- compositions of proteids, as well as upon boiling them with alkalies, carbon dioxid and hydrogen sulphid develop, together with hydrogen and marsh-gas. Under such circumstances, gelatin yields, in addition to abundant leucin, much ammonia, carbon dioxid, acetic, butyric and valerianic acids and glycin. Mucin and nuclein undergo no decomposi- tion. Artificial digestive experiments with the pancreas disclose an extraordinary tendency to putrefactive decomposition. The body giving rise to the fecal odor, which likewise results from putre- faction, has not as yet been discovered. It is intimately related to indol and skatol, but these are odorless when prepared in the pure state. Among the solid matters in the large intestine produced only by putrefaction, iiidol (CgHyN) is especially to be pointed out. This is a substance that results also from heating albuminates with alkalies, or in small amount by superheating them with water to 200° C. It is the forerunner of indican in the urine. If the products of the digestion of albuminates, the peptones, are rapidly absorbed in the intestine, only a 334 BACTERIAL FERMEXTATIOX IN THE INTESTINES. small amount of indol is formed. If, on the other hand, with a lesser degree of absorption, the putrefactive process can exert a profound effect chiefly upon the products of pancreatic digestion still present in large amount, considerable indol will be formed, and much indican subse- quently appears in the urine. Thus Jaffe found an abundance of indican in the urine in the presence of in- carcerated hernia and obstruction of the bowel. After transfusion with hetero- geneous blood, in connection with which the walls of the intestine are often the seat of extravasation of blood and thrombosis, and paralytic conditions of the intes- tinal vessels and musculature itself are not rarely encountered, the author has often found the amount of indican contained in the urine to be large. Test for indol: The fluid to be tested is acidulated with considerable hydrochlo- ric acid and is well shaken after addition of a few drops of oleoresin of turpentine. If an intense red color results, the pigment is removed by agitation with ether. The pigment resulting from fibrin in the process of tryptic digestion, and becom- ing violet with bromin-water, can be isolated by agitation with chloroform. In addition to the latter pigment, there is still a second pigment that passes over in the process of distillation, and can be extracted from the distillate by ether. Both appear to belong to the indigo-group. A. V. Bayer was able to produce indigo-blue artificially from orthonitrophenol- propionic acid by boiling with dilute sodium hydrate and after addition of some grape-sugar. From indigo-blue he obtained skatol, in addition to indol. G. Hoppe-Seyler observed an abundance of indican in the urine after feeding rabbits upon sodium orthonitrophenol-propionate. Further, some phenol (CgHgO) is formed in the intestine by the putre- factive process. Baumann observed the same substance as a result of the putrefaction of fibrin with pancreas outside of the body, and Brieger found it constantly in the feces. It appears to undergo an increase under conditions analogous to those attending an increase in the amount of indol, as an increase in the amount of indican in the urine is accompanied by an increase in the amount of phenyl-sulphuric acid. Amidophenyl-propionic acid also can be obtained from putrefying meat and fibrin as a product of the decomposition of tyrosin. Part of this is changed by putrefactive ferments into phenylpropionic acid (hydrocinnamic acid) , which is com- pletely oxidized in the organism to benzoic acid, and appears in the urine as hippuric acid. In this way is explained the formation of hippuric acid when a pure proteid diet is taken. Skatol (C9H9N, methylindol), a constant constituent of human feces, has been prepared artificially by Nencki and Secretan by protracted putrefaction of egg-albumin under water. In this way results skatol- carbonic acid, which, when heated, readily decomposes into skatol and carbon dioxid. Skatol also appears in the urine in combination with sulphuric acid. Milk inhibits the decomposition of albumin and intestinal putrefaction through the presence of casein and thus also diminishes the amount of ethereal sulphates in the urine. According to the brothers Salkowski, both skatol and indol result from a common substance preformed in albumin, which, when decomposed, at one time yields a larger amount of indol, and at another time a larger amount of skatol, accordingly as to whether the h^'pothetical indol-bacterium or the skatol-bac- terium active under such conditions prevails in the development. It is of great importance in the process of putrefactive fermentation whether this takes place with the exclusion of oxygen or not. In the former case reduc- tion occurs: oxy-acids are reduced to fatty acids, and there are developed, especially hydrogen, but also marsh-gas and hydrogen sulphid; the hydrogen, in turn, may cause further reduction. If, however, oxygen is still present, the nascent hydrogen divides the molecule of ordinary free oxygen into two atoms of active oxygen; there forms, thus, on the one hand, water, and on the other hand, the second atom of oxvgen brings about active oxidation. PROCESSES IN THE LARGE INTESTIXE. 335 The remarkable fact should yet be mentioned here that the putrefactive processes, after the development of phenol, indol, and skatol, and also of cresol, phenyl-propionic and phcnylacetic acids, are again inhibited, and after a certain concentration in their pi-oduction cease completely. Thus, the putrefactive pro- cess itself generates antiseptic substances even to the point of causing the death of the micro-organisms; for, as with highly organized beings, the excremen- titious products of the bacteria themselves are poisons for them. It is, there- fore, to be inferred that, in the intestinal canal also, the formation of the sub- stances mentioned in turn inhibits the putrefactive decompositions to some ex- tent. Ptomains are not formed normally in the intestines. The reaction of the contents of the small intestine is alkaline, due principally to carbonates, and in less degree to phosphates. The con- tents are, however, rich in carbon dioxid, the presence of which causes, on one hand, the acid reaction of the indicators reacting to carbon dioxid, while, on the other hand, it ensures the maximum efficiency on the part of the ferments in the intestine. In the large intestine the reaction is generally acid, in consequence of the acid fermentation and decomposition of the ingesta and the feces. PROCESSES IN THE LARGE INTESTINE. FORMATION OF THE FECES. Within the large intestine the putrefactive and fermentative decom- positions of the ingesta greatly exceed the fermentative or tnie digestive transformations, as only small amounts of the ferments of the intestinal juice are found in it. In addition, the absorptive activity of the walls of the large intestine is greater than the secretory activity, whence the consistency of the contents, which at the commencement of the large intestine are still semi-liquid, but become more consistent in the further course of the intestine. The absorption includes not only the water and the products of digestion in solution, but also, under certain circum- stances, even unchanged fluid proteids. Also toxic substances are de- cidedly more readily absorbed here than from the stomach. The feces begin to be formed only in the lower portion of the large intestine. The cecum in some animals, as, for example, the rabbit, is of considerable size ; fermentative decompositions appear to take place in it with great activity, with the development of an acid reaction. In human beings the cecum is principally an organ of absorption, as the abundance of lymphatic follicles indicates. From the lower portion of the small in- testine and from the cecum onward, the ingesta acquire the fecal odor. Observations on Thiry's intestinal fistulae permit the conclusion that a considerable portion of the feces is derived from the secretion of the mucous membrane and from epithelial desquamation. The amount of feces evacuated equals, on an average, 170 grams in twenty-four hours (from 60 to 250 grams), although, when large amounts of food, especially if difficult of digestion, are taken, even more than 500 grams may be discharged. After a diet of animal food the amounts of feces and of solid residue therein are less than after a vegetable diet. The consistent feces are broken up by the development of gas, and there- fore float on water. The consistency of the feces depends on the amount of water con- tained in them, which usually reaches 75 per cent. A pure meat- diet causes rather dry feces; food rich in sugar, rather watery feces; while the amount of fluid ingested is without influence. The more 35^ PROCESSES IX THE LARGE INTESTINE. rapidly peristalsis takes place, however, the more watery are the feces, because there is not sufficient time for the absorption of fluid from the rapidly advancing ingesta. Paralysis of the intestinal blood-vessels and lymph-vessels, after transection of the nerves, is likewise accompanied by liquefaction of the feces. The reaction of the feces is often acid, particularly in consequence of lactic-acid fennentation of large amounts of carbohydrates ingested. Numerous other acids generated by fermentation are also present. If, however, considerable amounts of ammonia are produced in the lower portion of the intestine, a neutral and even an alkaline reaction may preponderate. The secretion of large amounts of mucus in the intestine favors a neutral reaction. Mm. Fig. 124. — Longitudinal Section through the Large Intestine: E, epithelium; St, mucous membrane; G, blood- capillaries; Sl, solitary follicles; C, circular muscular layer; Ms, muscular layers; Lm, longitudinal muscular layer; Ld. Lieberkiihn's glands; Mm, muscularis mucosae; B, connective tissue. The odor of the feces, w^hich is more pronounced with a meat-diet than with a vegetable diet, is dependent upon the fecal-smelling products of putrefaction not yet prepared in an isolated state ; further upon the volatile fatty acids, as well as upon traces of methylmercaptan. The last-named substance can be prepared from proteid bv means of fused potassium hydroxid, and it develops in traces on boiling varieties of cabbage, and it is also formed from hydrogen sulphid (as from eggs). The color of the feces varies in accordance with the amount of altered biliary pigment present, hence shades vary from light vellow to dark brown. PROCESSES OF THE LARGE INTESTINE. 337 In addition, the color of the food has consideral)le effect. Thus the presence of much blood in the food renders the feces almost brownish black, from hematin; green vegetables render them brownish green, from chlorophyll; Ijones, in dogs, render the feces white, from the calcium contained; bluish-red vegetable juices render them bluish black; iron-preparations stain them black in part, from the production of iron sulphid. The feces contain (Fig. 125): I. The secreted juice of the intestinal mucous membrane, together with desquamated and digested epithelial cells. After almost complete absorption of the digested food, the feces still contain from 8 to 9 per cent, of nitrogen, from 12 to 18 per cent, of ethereal extract and from II to 15 per cent, of ash. Certain articles of food stimulate these excre- tions more vigorously than others. If a loop of the lower portion of the small intestine and the upper portion of the large intestine be excluded, as in a Thiry's fistula, and it be replaced in the W^". '^C ■'l\ i V \': : ^CJ^::©,>.;-. ■: \ Fig. 125. — Feces: a, muscle fibers; b, tendon; c, epithelial cells; d, leukocytes; e-i, various forms of plant-cells, among which everywhere large numbers of bacteria (i) are scattered; between h and b are yeast-celJs; k, ammoniomagnesium phosphate. abdominal cavity after being closed by a circular suture, a mass of fecal char- acter will be found in it. A loop of colon, thus excluded, will contain only a watery transudate, rich in salts. 2. The indigestible residue of the tissues of animal or vegetable food: hairs, homy tissue, elastic tissue; most forms of cellulose, wood-fibers, fruit-stones, spiral vessels from plant-cells, gum. 3. Fragments of otherwise readily digestible substances, particularly when they were ingested in excessive amount, or when not sufficiently comminuted by mastication; thus, the remains of meat (up to i per cent.), pieces of ham, shreds of tendon, bits of cartilage, flakes of fatty tissue, small pieces of hard albumin; further, plant-cells, starch in vegetable cells, firm- walled cells of ripe pulses, unground adhesive cells of grain, and the like. The presence of meat and starch is suggestive of an existing intestinal catarrh. Of all articles of food certain remnants pass over into the feces: of wheat- bread, 3.7 per cent.; of rice, 4.1 per cent.; of meat, 4.7 per cent.; of potatoes, 9.4 per cent.; of cabbage, 14.9 per cent.; of rye bread, 15 per cent.; of carrots, 20.7 per cent. ■ . 22 33S PROCESSES OF THE LARGE IXTESTINE. 4. The metabolic products of the biliary coloring-matter, which are especially abundant in all diseases that cause increased destruction of erythrocytes, and which now no longer yield the Gmelin-Heintz reaction, as well as the altered biliary acids. In diarrheal stools, as, for example, the green stools, the reaction, however, can often be readily demonstrated. It indicates accelerated peristalsis. The meconium contains unaltered bilirubin, biliverdin, glycocholic and taurocholic acids. 5. Unaltered mucin and nuclein and, as a metabolic product of the latter, xanthin -bases; nuclein especially after a diet of bread ; in addition, cylindrical epithelial cells from the alimentary tract in various stages of digestion ; further, fat-globules at times. Crystals of cholesterin and of coprosterin are rare. The less intimately the mucus is admixed with the feces, the lower down in the intestine is its source. 6. After the ingestion of a large amount of milk, as well as after a diet of fat, crystalline needles of calcium-salts of the fatty acids, thus calcium-soaps, are found constantly in the feces, even in infants. When courses of treatment with milk have been pursued undigested masses of casein and fat have besides been observed to be present. Further, com- binations of ammonia with the acids resulting from putrefaction already mentioned are among the substances constantly present in the feces. Larger masses of fat in the feces indicate accelerated peristalsis. 7. Among the inorganic residue, the readily soluble salts, which, therefore are readily diffused, are rare in the feces; thus sodium chlorid and other alkaline chlorids, the phosphoric as well as the sulphuric com- binations. On the other hand, the insoluble combinations, principally ammoniomagnesium phosphate, neutral calcium phosphate, yellow- colored calcium-salts, calcium carbonate and magnesium phosphate, constitute 70 per cent, of the ash. The large amount of alkalies and earths contained in the feces is noteworthy, three-quarters of which are in combination with carbon dioxid and organic acids. These are derived only in smallest part from the secretions of the intestinal mucous mem- brane. By far the greatest part of the ash, however, is derived from the constituents of the food. According to Rey, from 20 to 50 per cent, of solutions of calcium-salts, injected into the blood or subcutaneously, is excreted by the glands of the large intestine in the dog; 0.2 gram of iron is present daily. In the presence of a fistula in the large intestine, Kobert and Koch observed, in the feces: sodium, calcium, magnesium, iron; phosphoric, sulphuric, hydro- chloric acids; soaps, neutral fat, fatty acids, mucin, albumin, epithelium, traces of ethereal sulphates, together almost one gram daily. At times the excretion of inorganic substances is so abundant as to form incrustations upon other fecal matter. Under such circumstances either ammoniomagnesium phosphate is present alone, in large crystals, or magnesium phosphate is mixed with it. Par- ticularly the ingestion of rye-bran, in bread, which contains these substances in large amount, causes this result. Charcot's crj-stals are found in the presence of entozoa. 8. Bacteria are present in abundance; yeasts are seldom absent. For the identification of the individual bacteria, Escherich has developed pure cultures from the intestinal contents of infants. Bienstock from those of adults. In the intestine of infants, fed upon mother's milk exclusively, the bacterium lactis aerogenes (Fig. 126, 2) produces, particularly in the upper portion, where milk-sugar is still unabsorbed, acetic acid, together with carbon dioxid, hydrogen and marsh-gas. Lactates are transformed into but3-rates. The bacterium also produces acetic acid from starch. A characteristic feature of the MORBID ALTERATION'S IN* DIGESTIVE ACTIVITY. 339 feces is the slender bacterium coli commune (Fig. 126, i), provided with from one to three flagella, which forms lactic and formic acids, together with acetic acid, and at times exerts a pathogenic action. In the feces of adults Bienstock found first of all two varieties of large bacilli (Fig. 126, 3, 4) resembling the bacillus subtilis in size and appearance, differing from the latter only in the form of its pure culture, by its manner of sporulation and by an absence of independent movement. These two bacilli are distinguish- able macroscopically only by the form of this culture, which takes the shape either of a grape, or of a mesentery. Neither possesses any fermentative activity. A third, micrococcus-like, small, slowly multiplying bacillus (bacillus coprogenus parvus) was present in three-quarters of all of the stools. The fourth variety is the specific bacterium of proteid decomposition (bacillus putrificus coli), which is wanting in the feces of infants, and which with the production a fecal odor gives rise to the putrefactive products of proteids. Only this and no other causes these processes in the intestine; yet it does not decompose casein and alkali- 3 Q 0 e / \'x> Fig. 126. — I, Bacterium coli commune; 2, Bacterium lactis aerogenes; 3, 4, the two large Bienstock bacilli with ptartial endogenous spore-formation; 5, the various stages of development of the bacillus of proteid putre- faction. albuminate. The evolution of this bacterium is represented in Fig. 126, 5, a-g; of which the stages c and g are, however, wanting in the feces and are encoun- tered only in artificial ctiltures. If the feces are simply examined microscopically, without special precautions, the following are found as normal saprophytes: the bacterium coli commune, the staphylococcus aureus: frequently, also, varieties of proteus, at times with infective properties; in addition, other bacteria, whose entrance in part through the anus is possible: the bacillus butyricus, often staining blue with iodin, in feces rich in starch, and other small, spherical and rod-shaped schizomycetes, staining similarly. After the ingestion of uncooked food of various kinds, Lembke was able to verify the presence of as many as 73 different bacteria in the intestine. In human beings, with accidentally acquired intestinal fistulae or an artificial anus (intestinal fistula involving the colon), opportunity is afforded to study the changes in the intestinal contents with greater precision. MORBID ALTERATIONS IN DIGESTIVE ACTIVITY. The ingestion of food may be prevented by spasm of the muscles of mas- tication (usually as a symptom of general convulsions), b}- strictures of the esophagus, either from corrosive cicatrices (after the swallowing of caustic fluids) or from neoplasms, especially carcinoma. Inflammatory affections of any kind in the mouth and phar\'nx may also seriously interfere with the ingestion of food. Inability to swallow occurs as a symptom of disease of the medulla oblongata, in consequence of paralysis of the center for the motor nerves (facial, pneumogastric and hypoglossal) and of that for the sensory nerves through which pass reflex impulses (glossopharj-ngeal , pneumogastric and trigeminal). Irritation or ab- normally heightened stimulation of this area may cause spasmodic swallowing and a feeling of constriction in the throat (globus hystericus). The secretion of saliva is diminished in conjunction with inflammation of the salivary glands, occlusion of their ducts by concretions (salivary calculi) , etc.; further, under the influence of atropin and daturin, in consequence of which the secretory (not the vasomotor) fibers of the chorda tympani appear to become paralyzed. Slight fever may increase the amount of saliva, though the amoimt of ferment may be lessened; fever of more marked degree diminishes both, while 34° MORBID ALTERATION'S IX DIGESTIVE ACTIVITY. in the presence of high fever no saHva at all is secreted. The saliva secreted with lower grades of fever is cloudy, viscous and it usually becomes acid. With increase in fever the inertness of the diastatic action also increases. After the crisis the amount of saliva and the activitv of the ferment become subnormal; likewise in the presence of diseases of the kidneys. After chronic illness of long standing the production of ferment frequently diminishes. The secretion of saliva is increased by morbid irritation of the nerves of the mouth, as from in- flammations, ulcers, trigeminal neuralgia, so that enormous quantities may be poured out. Mercury and jaborandi-leaves cause salivation, the former with the simultaneous occiirre'nce of a stomatitis that induces reflex secretion of saliva. Diseases of the stomach also may increase the secretion of saliva, in conjunction with paroxysms of nausea and retching. Viscid, ropy saliva, due to irritation of the sympathetic nerve, is secreted, together with some vascular disturbance, in consequence of active sexual excitement, but also as a result of certain ps^xhical impressions. The reaction of the buccal secretion becomes acid in the presence of catarrhal conditions of the mouth and. further, as a result of the decomposition of accumulated epithelial cells in the mouth during the prevalence of fever, as well as in cases of diabetes mellitus. in consequence of acid fermentation of the sugar contained in the saliva. Diabetic patients therefore sufter frequently from carious teeth. The secretion of the mouth in infants also has a slightly acid reaction unless the greatest cleanliness is obser\-ed. Disturbances in the activity of the gastric musculature may appear, as a paral>'tic phenomenon, with distention of the stomach, and a protracted sojourn of the ingesta. With more marked grades of the disorder decomposition and the production of gas take place. Diminution in muscvdar activitj* may give rise to dilatation of the entire stomach. Incompetency of the pylorus represents a special form of gastric paralysis. Derangement of inner\-ation. central or periph- eral in nature, may be the cause; further, actual paralysis of the pyloric sphinc- ter or anesthesia of the mucous membrane of the pylorus, which exerts a reflex effect upon the sphincter muscle; finally, also, interference with the transmission of the reflex within the center. Abnormally increased activity of the gastric musculature will, as gastric diarrhea, hasten the ingesta into the intestine; often vomiting occurs. In nerv-ous individuals so-called peristaltic unrest of the stomach is at times present, in conjunction with dyspeptic disorders. Spasm of the cardiac orifice or paresis of the inhibitor^' ner\'es of the cardia also occurs. Rarely, in the presence of stricture of the pylorus, true antiperistalsis of the stomach has been observed. Gastric digestion is delaj-ed by all severe physical and mental exertion and, if this be of more marked degree, digestion may even be inhibited. Also sudden emotional disturbance, as well as reflex influences from other organs (uterine dyspepsia), may have this eff^ect. Probably these factors exert an influence upon the vasomotor nerves of the stomach. Impairment and abolition of the secretion of the gastric juice may, under certain conditions, be purely nervous in nature, as in cases of nervous dyspepsia and gastric neurasthenia. Complete absence of the gastric juice is found in connection with atrophy of the mucous membrane, prin- cipallv in cases of pernicious anemia. Also excessive secretion of ihe gastric juice, continuous flow of the juice, and likewise excessive production of acid may depend upon derangement of ner\-ous activity: ner\-ous gastroxynsis, chiefly observed in women. Excessive production of hydrochloric acid occurs in asso- ciation with round ulcer of the stomach. Inflammator\- or catarrhal affections of the stomach, as well as ulcers and neoplasms, distvu-b normal digestive activity, as does also the excessive ingestion of foods difficult of digestion, of sharp spices in considerabl ■ amount, or much alcohol. Griitzner obser\-ed in a dog that the mucous membrane secreted con- tinuously under the influence of a chronic gastric catarrh, but the gastric juice was deficient in pepsin, cloudy, viscous, less acid, even alkaline. The introduc- tion of food did not modify the secretion; the stomach, therefore, never actually comes to rest. At the same time the chief cells of the gastric glands are turbid. Accordingly it would seem o" advantage for patients suffering from gastric catarrh to eat frequently, but only a little at a time, and in addition use a 0.4 per cent, hydrochloric-acid solution as a beverage. Small doses of sodium chlorid appear to aid gastric digestion. In the presence of enfeebled digestion, the cause may be deficien: formation either of hydrochloric acid or of pepsin. Both substances may therefore be administered as remedial agents. In the presence of enfeebled gastric digestion MORBID ALTERATIONS IN DIGESTIVE ACTIVITY. 341 and motor insufficiency decom])()siti()n of the contents of the stomach into lactic, butyric and acetic acids often takes place as a result of the action of lower organ- isms. Small doses of salicylic acid arc advisable under such circumstances, together with some hydrochloric acid (notwithstanding possible heart-l)urn or acid eructation). The administration of pepsin probably is Init rarely imperative, as this ferment is only seldom absent even from the diseased gastric mucous membrane. In the presence of" marked dilatation and a protracted .sojourn, the f)roteids in the stomach, notwithstanding the hydrochloric acid, undergo putre- action, which, however, does not as a rule have an injurious effect. In cases of gastric catarrh and cholera, albumin has been observed to appear in the gastric juice. Gastric Digestion in Patients with Fever and Anemia. — Beaumont, from obser- vations made upon the man with the gastric fistula examined by him, found that only scanty secretion of gastric juice takes place in the presence of fever. The mucous membrane was deficient in secretion, red and irritable. Dogs, which Manassein had made febrile from septicemia or profoundly anemic by venesection, elaborated a fairly active gastric juice, characterized especially by a deficiency of hydrochloric acid. Hoppc-Seyler examined the gastric juice from a patient with typhoid fever — in which disease van de Velde found no free hydrochloric acid (for the parietal cells are destroyed under such conditions) ; as well as in cases of gastric carcinoma also, in which disease there is, as a rule, no excess of free hydrochloric acid — and found it absolutely inactive for artificial digestion, even after hydrochloric acid had been added. This investigator properly emphasizes the fact that the diminution in hydrochloric acid after such conditions favors the development of a neutral reaction of the gastric contents, by reason of which, on the one hand, digestion in the stomach can no longer take place; while, on the other hand, abnormal fermentative processes must take place, with the aid of developing micro-organisms and sarcinae ventriculi (?). Uf^elmann found that, in patients with fever, the secretion of a peptone- forming gastric juice ceases if the fever sets in violently, if a condition of great weakness develops, or if a high temperature persists for a long time. In any event, also the amount of gastric juice secreted is diminished. In the presence of fever the irritability of the mucous membrane is increased, so that vomiting is readily induced. Also the increased excitability of the vasomotor nerves of patients with fever is evidently detrimental to the secretion of active digestive juices. Gluzinski found an absence of hydrochloric acid in the acute febrile infectious diseases. Beaumont observed that fluids were rapidly absorbed from the stomach of a febrile patient, while, on the other hand, the absorption of pep- tones was diminished, on account of the frequently accompanying gastric catarrh and the disturbed activity of the muscularis mucosae. Many salts disturb gastric digestion, if added in considerable amount, par- ticularly the sulphates. Of the alkaloids, morphin, strychnin, digitalin, narcotin and veratrin likewise have a disturbing influence. A small amount of quinin ac- celerates gastric digestion. As the digestive activity of the stomach can be replaced by the pancreas, it is evident that dogs may continue to live without profound disturbance of nutrition after extirpation of the stomach. Langenbach observed a similar result in human beings after operation. The secretion of bile undergoes a change in the presence of acute disease, as, for example, fever, in that it becomes scanty and at the same time more watery, and that it is poorer in its specific constituents. Should the liver undergo profound structural changes as a result of the morbid process, the secretion of bile may cease completely. As a result of the decomposition of bile (acid fermentation ') gall-stones form within the gall-bladder or biliary passages. These calculi may be white or brown. The former consist almost entirely of laminated cholestcrin-crystals. They are generally about i cm. in diameter, but they may be the size of a walnut or even larger. The brown gall-stones consist of bilirubin-limes together with biliverdin, bilicyanin and choletelin, and also calcium carbonate and phosphate, often mixed with iron, manganese, copper and other precipitated heavy metals. All gall-stones, like urinary^ calculi, possess an organic supporting structure. Some are rather spherical, often studded with midberrv-shaped nodules. Those packed together in the gall-bladder become polished, from mutual attrition in consequence of the contraction of the walls of the gall-bladder. The white gall- stones often contain lime and biliary coloring-matter as a nucleus, together with 342 MORBID ALTERATIONS IN DIGESTIVE ACTIVITY. a nitrogenous residue, probably derived from desquamated epithelium, mucus, salts of biliary acids and some fat. Gall-stones may cause obstruction of the bile-ducts and then give rise to symptoins of cholemia. Smaller stones, impacted in the ducts, may cause intense pain (biliary colic) and, by means of their sharp edges, they may even bring about fatal rupture of the ducts. The formation of biliary calculi is probably due ultimately to local stagnation and decomposition of bile in the gall-bladder, caused, for example, by tight lacing, in consequence of which kinking of the gall-bladder takes place. Cholemia and jaundice have already been discussed. In the presence of high fever the pancreatic secretion appears to be dimin- ished and its activity enfeebled. Cessation of secretion is attended with the appearance of fat in the form of globules and crj-stalline fatty acids in the feces. Degeneration of the pancreas may cause diabetes. Among the disturbances in the activity of the intestinal tract, constipation (obstipation) is first to be considered. The causes of this condition may reside in: (i) Obstructions that occlude the normal passage. In this category belong constrictions of the intestinal canal, due to cicatricial strictures, as, for example, in the colon often after dysenter}-; neoplasms; further, axial torsion of a loop of intestine (volvulus) , or invagination of one portion into another (intussuscep- tion) , or into a hernial sac (hernia) ; also the pressure of tumors or exudates from without. Finally, congenital absence of the anus may constitute the cause. (2) Excessive dryness of the intestinal contents may cause obstipation. Under such circumstances the following factors may be operative: Excessive drjmess of the food; further, diminution of the digestive juices, as, for example, of the bile in cases of icterus ; or in consequence of great loss of fluid through other organs of the bod^^ as after profuse perspiration or secretion of milk, or, finalh', during fever. (3) Derangement of the activity of the muscles and of the motor nerve- apparatus of the intestine ma}' induce constipation through insvifficient peristal- sis. This is caused especially by parah^ic conditions, as in the presence of in- flammation, degeneration, chronic catarrh and peritonitis. Spinal paralysis is generally attended with sluggish defecation; central affections often also. Whether the phenomena of mental impairment and hypochondriasis are the ac- companiment or the sequel of constipation has not yet been demonstrated. Spasmodic contraction of certain portions of the intestine ma}- give rise to transi- tory retention of the intestinal contents, with great pain (colic) ; as may also spasm of the anal sphincter, which may also take place reflexly, from irritation of the lower portion of the intestine. The feces are almost always hard and deficient in Avater, when constipation exists, because during their long sojourn in the in- testines fluid is absorbed from them. In consequence, the fecal masses form large pieces (sc3^bala) within the large intestine and these may, in turn, constitute a new obstacle to the onward movement (coprostasis) . Diminution in the intes- tinal and gastric secretion occurs also as a sign of general nervous affections (hys- teria, hypochondria, mental disorders), although increased secretion may also take place under such circumstances. The agents that cause constipation are, in part, those that paralyze the motor apparatus temporarily, such as opium or morphin; and, in part, those that dimin- ish the secretions of the intestinal mucous membrane, and exert a constringent effect upon the blood-vessels and the mucous membrane, such as tannic acid, alum, lime, lead acetate, argentic and bismuth nitrates. Increase in the intestinal discharges is usually accompanied by a greater degree of fluidity of the feces (diarrhea). The causes are as follows: 1. Unduly rapid propulsion of the contents through the intestinal canal, particularly through the large intestine, so that absorption from this part cannot take place in a normal manner. The increased peristalsis is due to irritation of the motor-nerve apparatus of the intestine, and is principally reflex in character. Rapid passage of the ingesta through the intestinal canal results in the presence in the discharges of substances that could not be completely or at all digested in the short time afforded (lientery). This will also occur if portions of the in- testine, situated high up, communicate with lower portions of the intestine, through abnormal openings. 2. The feces may be of the consistency of paste from the admixture of water, mucus and fat, in considerable amount; further, from the residue of fruits and vegetables. In rare cases in which the feces contain a good deal of m.ucus, so- called Charcot's crystals are present (Fig 92, c). In the presence of ulceration of the intestine, leukocytes (pus-cells) are found. COMPARATIVE PHYSIOLOGY OF DIGESTION. 343 ,3. Diarrhea may develop in consequence of disturbances of the processes of diffusion through the intestinal walls. Affections of the epithelial cells should be mentioned in this connection: swelling in association with catarrhal or in- flammatory conditions of the mucous membrane. As, further, in the process of absorption independent activity on the part of the cylindrical cells is to be taken into consideration, controlled, perhaps, by the nervous system, it is plain how sudden agitation, from fright, anxiety, etc., may cause diarrhea. 4. Diarrhea may be the result of increased secretion. In its simplest form this occurs through cajnllary transudation, when salts, as, for example, magne- sium sulphate, introduced into the intestine, remove water from the blood by endosmosis. In this category belong the copious watery discharges that take place in consequence of alteration of the intestinal epithelium, as in cases of cholera, in which such excessive transudation takes place into the intestine that the blood becomes inspissated and may even stagnate in the veins. In addition, transudation into the bowel may take place in consequence of paralysis of the vasomotor nerves of the intestine. The diarrhea due to cold appears to belong in this group. Certain substances appear directly to irritate the secretory organs of the intestine or their nerves; among these are the drastic purgatives. Pilocarpin injected into the blood also induces marked secretion. In the presence of febrile disorders, the secretion of the intestinal glands appears to undergo quantitative and qualitative changes, with simultaneous derangement in the activity of the intestinal musculature and the organs of absorption and increased irritability of the mucous membrane. With respect to fermentations in the intestine, the fact should be emphasized that all, in excess, as, for example, the butyric or the acetic, give rise to patho- logical manifestation. With regard to the pathogenic schizomycetes acting from the intestinal canal (cholera, typhoid, dysentery, and others) reference may be made to p. 246 Flagellated trichomonads are exceedingly rare. Finally, attention should be directed to the fact that, in consequence of abnormal "decompositions in the intestinal canal, substances may be forrned that exert a toxic effect upon the organism and thus give rise to auto-intoxications. COMPARATIVE PHYSIOLOGY OF DIGESTION. Among mammals, herbivora possess larger salivary glands than camivora, while omnivora occupy an intermediate position. Whales have no salivary glands at all; the pinnipeds have a small parotid, the echidna none at all. The dog, like some camivora, has an additional zygomatic gland situated in the orbit. In birds the salivar\^ glands empty at the angle of the mouth; the parotid gland is wanting. Among snakes "the parotid glands are in some species transformed into poison-glands; tortoises have sublingual glands; in addition, reptiles have labial glands at the margin of the lips. Amphibia and fish have only small, disseminated buccal glands. In insects the salivary glands are widely distributed, partly unicellular (as, for example, two pairs in lice), partly com- pound; several pairs of them are usually present. In some the secretion contains formic acid, for which reason the stings of these animals cause burning and in- flammation; in others the secretion is strongly alkaline, as that from the large salivary glands of the bed-bug. In bees and ants the lower salivary glands secrete a sort of cement-substance. The web-glands on the lower lip of caterpillars secreting the silky material, principally those of the silk-worm, should not be confounded with the salivarv glands. Among vermes, leeches have unicellular salivarv glands. In snails the salivary glands are also widely disseminated, and the saliva from dolium galea contains more than 3^ per cent, sulphuric acid, which also is present in murex. cassis, and aplysia. Cephalopods have a double set of salivary glands. In the octopus the saliva digests fibrin, but not starch, and it is poisonous. Crop-like formations are wanting in all mammals; the stomach appears to be single, as in human beings, or divided into halves, as in maiiy rodents, into a cardiac portion and a pvloric portion. The stomach of ruminants consists of four portions: the first and largest is the paunch (rumen) , the next the honeycomb-bag (reticulum) . In these two portions, principallv in the paunch, the ingesta undergo maceration and fermenta- tion. Thev are now returned to the mouth by the action of the voluntary' mus- cular fibers passing to the stomach, again thoroughly masticated, and, by the closure of a special semicircular groove (esophageal groove), the bolus is earned 344 COMPARATIVE PHYSIOLOGY OF DIGESTION. into the third stomach, the manypHes (psalterium) , which is absent in camels, and thence to the true, fourth stomach, the rennet-stomach (abomasurn). In the two tirst stomachs starch and cellulose are digested, the sugar formed in part passing over into lactic acid. The third stomach performs chiefly mechanical work, while the fourth really digests albtimin. In the small intestine proteids and carbohydrates are further digested. The intestine is divided into the small and the large intestine. It is short in carnivora, and considerably longer in herbivora. The cecum, which in her- bivora attains considerable size as the most important organ of digestion, a,nd in some rodents is even multiple, represents in human beings an insignificant, typical remnant, and is wholly absent in carnivora. In birds the esophagus, especialh^ in birds of prey and granivora, often possesses a diverticular appendix, the crop, for the maceration of the food. In the crop of pigeons there occurs, at the breeding-season, the secretion of crop-milk, the product of a special gland, which is also used as food for the young. The stomach consists of the proven- triculus well supplied with glands, and the thick-walled muscle-stomach, which, with the aid of the inner homy plates, effects the crushing especially of grain. In the intestine, at the junction with the short large intestine, there is almost con- stantly present a pair of ccca shaped like a glove-finger. The intestinal mucous membrane exhibits principally longitudinal folds. The alimentary canal of fish is usually simple. The stomach frequently represents only a dilatation. Less commonly the pylorus possesses one, more frequently a large number of divertic- ular appendices, containing a large number of glands (appendices pyloricte, as, for example, in the salmon). The mucous membrane of the usually short intes- tine exhibits longitudinal plication, as a rule, or the so-called spiral valve, as in the sturgeon, resulting from a spiral arrangement. The alimentary canal of fish, from the esophagus to the rectum, possesses peptonizing power. The short rectum is provided, in sharks and rays, with a diverticular appendage (bursa entiana). In amphibia and reptiles the stomach is generallj^ a simple dilatation. The intestine is longer in herbivora than in carnivora. Especially interesting in this connection is the fact that the vegetable-eating frog-larv£E acquire a much shorter intestine with the metamorphosis that makes them carnivorous, terrestrial animals. The intestinal mucous membrane of reptiles exhibits numerous plications. The liver is not wanting in any vertebrate, and is especially large in fish. The amphioxus has onh' a diverticulum indicative of the liver. The gall-bladder is wanting occasionally in all classes, in accord with which is the experimental observation that extirpation of the gall-bladder is unattended with appreciable influence on digestion and absorption. The pan- creas is wanting only in some fish. One opening (in the amphioxus) or two open- ings (in the shark, the ray, the sturgeon, the eel and the salmon) lead from with- out freely into the abdominal cavity; the same conditions prevail also in crocodiles. Among the molluscs, snails and cephalopods only have true organs of mastication. Some herbivorous land-snails have a movable, homy grinding plate situated in the upper pharyngeal wall. Horizontal maxillary plates, with hard edges working one upon the other, are present particularly in carnivorous snails with uncovered gills. A homy grinding plate, placed like a tongue, whose peculiar form serves for the systematic differentiation of various snails, is fre- quently present in others. Cephalopods possess a strong biting apparatus in the form of a large, horny pair of jaws, resembling a parrot's beak in shape. They also have a grinding plate upon a tongue-like prominence, studded with spines. The alimentarj^ canal is divided into esophagus, stomach and intestine, at times provided with diverticula. In many mussels the rectum pierces the heart and the pericardium. In snails the anus is usually in the vicinity of the respiratory organs. The liver is, as a rule, large. The vineyard-snail has a cellulose- splitting ferment in the secretion of the liver. In the cephalopods the ink-bag opens into the rectum or near the anus. Among vertebrates crustaceans have a masticating apparatus transformed from feet; in some, true masticating feet are still present; in parasitic crabs there are also sucking mouth-organs. Among arachnids the mites have sucking mouth- organs; in true spiders, there are, in addition to the sucking inouth-organs, horizontally acting clutching jaws, in part connected with poison-glands. Centi- pedes possess a strong pair of jaws, acting horizontally. Of insects, those provided with masticating mouth-organs possess, between the upper and lower lips, two pairs of jaws, acting horizontally against each other, of which the upper (man- Ccmi'ARATIVH PHYSIOLOGY OK DIGKSTIOX. 345 dibuhf) cxcLvd the lower (maxilUf) m slivn^lh. In suckin-msects the four iaw" are transformed into a long tube with a longitudinal sht (he stinging pn.- boscis of the bed-bug), which lies in the semicircularly grooved lower lip as m a case T e proboscis of the butterfly consists of the great y prolonged lower faws lying side by side, and capable of being rolled up while the development of the upper jaws has been arrested. Bees have a sucking tongue, which lies m a gr3> formed in the lower jaws; in addition, the feeble upper jaws still per- sist as orerans of mastication. ,., In crustaceans the esophagus is short; in some the stomach is a simple dila- tation ^n others it possesses diverticula, in which are situated the bile-producmg IbSs The freslvwater crab and its relatives possess a strong chitinized m- t'ima in the stomach, which is capable of acting as a masticatmg "^gan^ Ihis membrane is expelled when the skin is shed. Among arachnids, scorpions have r s Se aUmentary canal. True spiders possess a narrow esopha.gus and a eircZr stomach; in' addition diverticula on all f ^es, at the base of wh^ch iver- tissue is present, and which mav extend even down into the feet, in insects, n iddUcm to the esophagus and the chyle-stomach, generally rich m glands^ and at mes serrated,^there are present various portions, such as the crop m ?he ercSffor instance, the sucking stomach in the butterfly,, the n^f^ticaUng stomach m the beetle, in varying manner. The intestinal canal is usual y shorty in carnivorous than in herbivorous insects. In the intestine of the flour-worm (?enebrio) ferments are present resembling those of ^^^ P^"-^^^^^\^^,"\^;^,, is remarkable that in the larval state, as, for example, of most bees, the tract is closed below the chvle-stomach. The rectum, with its auxiliary apparatus exists bvftself and empties, as an excretory duct, into the anus. Pecuhar long, tubular excretorv organs, the Malpighian vessels, several of which are present, open at the iunction of the small and the large intestine. , , / , ■ -u t, \ Of the vermes, tape-worms, as well as the acanthocephala (echinorhynchus) amon- roimd worms, have no special digestive organ, but are nourished by endos- SSS" trough Absorption on the part of the skin The anus is wantmg m S?matodes (distomum), thread-worms, and almost all turbellana. In the hrst, «s well as in leeches (sanguisuga) , the buccal orifice is surrounded by a suckmg- S; which in leeches, posses'ses, in its depth, three ^^f ^^^.^ -"^^S- ^S, Some leeches, as well as the planaria, have a protrusile P^°^f^^ , J^^^^^J^^/'^Tt of turbellaria unprovided with an anus, is shaped simply hke ff^^ ^-hnger. it ?s Siouslv branc^hed m liver-flukes (distomum). In the ^""^'^^^^^^ both testine extends from the anterior to the posterior extremity of the body, both moulh Ind anus are present. Among them, the earth-worms possess a muscular ?rr':^nx thnrSh^es have a highly. distensible ^^tomach provided w.thm^^^^^ lateral d verticula, which, when the animal has sucked itself full can be "c sea thrott^h the skin of the back, so that the blood flows continuously from the ^Nound, whS" the animal continues to take up blood through its suckmg mouth (bdel- ^°^°5?ecl5^=^lSSS^St?^S caiir The mc.th . often ^ vide d with a biting mechanism, which appears in ^^^-Y^^'^'^XZl lu"'ra^^^^ teeth connected with a movable, complicated "2^^^^11^5> ^^^PPJ^f^^^ike ^e^^^^^^^^^ i^„+„^„\ Manv of the starfish are unprovided with an anus, a Due-UKe becieuun Is foiSd in d^^^erticl!:ia of their stomLh. Salivary glands have been found m "'"The aquatic celenterates possess no intestinal tract P^^f a^j'anufaTeTep^^^^^ walls. The abdominal cavity is the digestive cavity; mo"th and anm a^e r^re sented by the same central orifice, which often ^^^X' wf fmedusS and^on- uss, polyps) . A system of canals, passmg through the ^""^y}"^^^^^^ nected with the digestive cavity, conveys the "^f^^^ive flmd and^ a^^^^ time the oxygen -containing water. It is, therefore, the water-\ ascular s> stem, a at the same time the nutritive, respiratory and excretory P^J^J"- ■ through Among the protozoa, the gregannes are nourished by .e"^°^"^°f^^ ^^^J?,,"^^^ the skin, infusoria possess mouth and anus although their abdommal^c^^^^^^^ ^-^^i S ^^£S^&n-^?S- r m^ ^^ ?-s^?hS^s?eJS:s^s,^x^^^^;^oL^^^ 346 HISTORICAL. (drosera) possesses, tipon the surface of its leaves, numerous tentacle-like processes, provided with glands. As soon as an insect lights upon the leaf, the former is suddenly seized by the tentacles. The glands discharge a juice of acid reaction and digest the animal with the exception of its insoluble chitinous remains. The juice contains a pepsin-like ferment and formic acid. The secretion, as well as, later, the absorption of the dissolved substances, takes place in conjunction with movement of the protoplasm of the leaf-cells. Venus' fly-trap (dionea) and butter- wort (pinguicula) exhibit similar processes, as well as the cavities of the transformed leaves of the nepenthe. Altogether, about 15 species of such carnivorous dichotyles are known. The juice escaping from incisions in the green fruit of the papaw-tree (carica papaya) possesses peptonizing properties due to a ferment closely allied to trypsin. The milky sap from the fig-tree is likewise active, exerting a diastatic effect and also coagulating milk at 50° C. Albumin is dissolved also by some fungi (boletus, tuber), lichens (parmelia) and the sap of taraxacum, lactuca, agave and portulac. Artichokes, yellow or lady's bedstraw and other plants contain rennet-ferment. The sap of aloes and of sugar-cane, as well as dried figs, coagulates milk and has a peptonizing action; as does also ordinarv flour-dough on admixture: further, the juice (containing peptone at the same time) from the seed of wheat, barley, poppy, beets and corn, after the addition of organic acids. Potatoes and rice have feeble, flour, grain and corn marked sugar-forming activity. HISTORICAL. Digestion in the Month.^The vessels of the teeth were known to the Hippo- cratic school. Aristotle ascribed an uninterrupted growth to the teeth. In addition, he directed attention to the fact that those animals that exhibit a devel- opment of horns and antlers, cloven-hoofed animals, possess an imperfect denture (absence of the upper incisor teeth) . It is a remarkable fact that, in human beings with excessive formation of horny substance, in consequence of the presence of superfluous hair, imperfect development of the teeth (absence of the incisors) has also been observed. The muscles of mastication were recognized early. Vidius (died 1567) described the maxillary articulation, with the meniscus. The epiglottis, according to Hippocrates, prevents the entrance of food into the larynx. The ancients considered the saliva only a solvent and a means for moistening the food. In addition, in consequence of a knowledge of the saliva of rabid animals and the parotid secretion of venomous snakes, various poisonous properties were ascribed to the saliva, especially from fasting animals — a view that Pasteur again confirmed in part, referring the action to pathogenic bac- teria in the secretions of the mouth. Areteeus (81 A. D.) emphasizes the muscular nature of the tongue. The salivary glands had been discovered in ancient times. Galen (131-203 A. D.) was familiar with Wharton's duct and .i^tius (270 A. D.) with the submaxillary and sublingual glands. Regner de Graaf established salivary fistulae in dogs in 1663, by tying tubes in Stenon's duct. Hapel de la Chenaye obtained in 1780 for examination large amounts of saliva from a salivary fistula established in a horse. Spallanzani in 1786 stated that insalivated articles of food are more readily digested than those moistened with water. Hamburger and Siebold investigated the reaction, consistency and specific gravity of the saliva and found mucus, proteid and salts present. Ber- zelius introduced the term ptyalin for the characteristic substance in the saliva, though Leuchs in 183 1 first discovered its diastatic fermentative action. Gastric Digestion. — -The ancients compared digestion to cooking, through which solution is effected. Aristotle supposed that, through this "'pepsis" chyle (ichor) first developed from the food, and then reached the heart. He also knew of the rennet-action of the stomach. According to Galen, only dissolved masses pass through the pylorus into the intestine. He described the movement of the stomach and the peristalsis of the intestines. JEliaxi recognized the four stomachs of ruminants and gave their names. Vidius (died 1567) observed the numerous small glandular openings in the gastric mucous mem- brane, van Helmont (died 1644) expressly mentions the acid of the stomach. He as well as Sylvius (died 1672) compared the action of the stomach with fermentation, in connection with which, according to Descartes (died 1650) and Willis (died 1675), the action of the acid predominates. Reaumur (1752) recognized that a juice was secreted by the stomach that eft'ects solution and with which, together with Spallanzani (1777), he undertook digestive experi- HISTORICAL. 347 merits outside of the stomach. Carminati (1785) then found that the stomach of carnivora, especially when engaged in digestion, secretes an actively acid juice. Prout discovered in 1S24 the hydrochloric acid of the gastric juice and Sprott and Boyd in 1836 found the glands of the gastric mucous membrane, among which Wassmann and Bischoff distinguished the two different kinds. After Beaumont (182 5-1 833) had made his observations upon a man with a gastric fistula, Bassow (1842) and Blondlot (1843) estabhshed the first artificial gastric fistulas in animals. Eberle subsequently (1834) prepared artificial gastric juice. Mialhe designated the albumin modified by digestion as albuminose; while Lehmann, who examined this more thoroughly, introduced the name of peptone. Schwann (1836) first prepared pepsin and defined its activity in com- bination with hydrochloric acid. Pancreas, Bile, Intestinal Digest-ion. — ^The pancreas was known to the Hip- pocratic school. Moritz Hofmann demonstrated in 1641 its excretory duct in the turkey to Wirstxng, who (1642) described it in human beings as his dis- covery. Regner de Graaf collected in 1663 pancreatic juice from fistulas, and which Tiedemann and Gmelin found to be alkaline, while Leuret and Lassaigne found it to resemble saliva. Bouchardat and Sandras in 1845 discovered its diastatic, Eberle in 1834 its emulsifying, Purkinje and Pappenheim in 1836 its peptic, and CI. Bernard in 1846 its fat-splitting properties, to the last of which Purkinje and Pappenheim had already directed attention. Aristotle designates the bile as a useless excrement itious product. Ac- cording to Erasistratus the bile is conveyed from the liver to the gall-bladder through most minute, invisible ducts. Aretaeus attributed the cause of icterus to occlusion of the bile-ducts. Benedetti in 1493 described gall-stones. According to Jasolinus (1573) the gall-bladder is emptied by its own contraction. Sylvius de le Boe (1640) observed the hepatic lymph-vessels, Walaeus (1641) the connective tissue of the so-called capsule of Glisson. Albr. v. Haller pointed out the utility of the bile in the digestion of fat. Henle, Purkinje and Dutrochet (1838) de- scribed the liver-cells. Heynsius discovered urea, CI. Bernard (1853) sugar, in the liver, and with Hensen (1857), he found glycogen in the liver. Kieman (1834) described the blood-vessels more thoroughly. Beale injected the lymph- vessels, Geriach (1854) the finest biliary passages, Schwann (1844) established the first biliary fistula. Gmelin discovered cholesterin, taurin and the biliary acids. Demarcey pointed out the combination of the biliary acids with sodium (1838). Strecker found the sodium-combinations of both biliary acids and isolated them. Com. Celsus mentioned nutritive enemata (3-5 A.D.). Laguna (1533) and Rondelet (1554) knew of Bauhin's valve. Fallopia (1561) de.scribed the folds and villi of the intestinal mucous membrane, as well as the nerve-plexuses of the mesentery. J. Conrad Brunner (1687) discovered the duodenal glands that bear his name. Severinus (1645) knew of the agminated follicles (Peyer's patches, 1673) and Galeati (1731) knew of Leiberkiihn's (1745) glands in the intestine. PHYSIOLOGY OF ABSORPTION. STRUCTURE OF THE ORGANS OF ABSORPTION. The mucous membrane of the entire intestinal tract, so far as it is lined by a single layer of cylindrical epithelium, that is, from the cardiac orifice to the anus, is capable of absorption. The buccal cavity and the esophagus can take part in this process only to an exceedingly limited extent, on account of their thick, many-layered squamous epithelium. Nevertheless, poisoning, as, for example, with potassium cyanid, may take place by absorption from the mouth alone. The capillary blood- vessels, as well as the chyle- vessels, of the mucous membrane act as the absorbing channels of the intestinal tract. The former convey the materials absorbed almost wholly through the portal vein to the liver, while the latter, uniting in their further course with lymph- vessels, dis- charge the absorbed chyle or milky juice through the thoracic duct into the blood at the junction of the subclavian and internal jugular veins. From the stomach are absorbed aqueous salt-solutions (within six minutes), sugar (namely, grape-sugar, milk-sugar, cane-sugar and mal- tose) in aqueous solution in moderate amount, in alcoholic solution in. somewhat larger amount; dextrin and peptone, chiefly in concentrated solutions, in lesser amount; and poisons, especially when dissolved in alcohol. Klemperer and Scheurlen observed that, in the dog, neither fat nor the fatty acids were absorbed. The empty stomach absorbs more rapidly than that filled with food. Diseases of the stomach and fever cause delayed absorption. In addition to absorption, an active secretion of water into the stomach, takes place, in general, in greater degree in proportion as the amount of absorbed substances is greater. The small intestine constitutes the principal field of absorption, pre- senting, especially in its upper half, through its many folds of mucous membrane and through the innumerable cone-shaped villi projecting from them, an extraordinary expanse of surface for absorption. The villi are close together at their bases, so that the entire surface of the mucous membrane appears to be covered with them. In the spaces between their bases the numerous simple tubules of Lieberkiihn's glands empty. Each villus is to be regarded as a projection of the entire mucous mem- brane, for it contains all of the elements comprised within it. The cloak-like covering of the villi consists of a single layer of cylin- drical epithelium with intervening isolated mucous goblet-cells. The surface of the cells directed toward the lumen of the intestine is poly- gonal (Fig. 127, D) and, viewed from the side (C), exhibits a broad seam-like outline, which was formerly considered the thickened wall of the cell-membrane and was designated by the term "lid-membrane." This seam exhibits a delicate longitudinal striation, which was inter- preted in part as the expression of the constitution of the lid, of rods 34S STRUCTURE OF THE ORGANS OF ABSORPTION. 349 arranged as a mosaic, in part as pore-canaliculi, intended for the passage of the finest fat-granules. As a matter of fact, however, this seam belongs only to the longitudinal surfaces of the epithelial cells and is comparable to the thickened edge of a cylindrical vessel, open above. The protoplasmic cell-contents, which enclose a large elliptical nu- cleus with nucleolus in the lower portion of the cell, end approximately on a level with this edge, although at the same time, they contain, at the level of the thickness of this marginal seam, many pseudopod-like proto- plasmic processes, which, standing side by side, and arranged in bundles, are surrounded by the edge of the marginal border. Thus, when viewed from the side, the lid-membrane appears striated, while, as a matter f ;#ih Fig. 127. — Structure of the Absorption-apparatus of a Villus: A, transverse section of a villus, in part; a, cylindrical epithelium, with thickened border (b); c, a goblet-cell; i, i, framework of the adenoid tissue of the \illus; d, d, cavity within this, in which lie lymphoid cells (e, e); f, central lymph-space in transverse section. B, two cyUndrical epithelial cells with extended pseudopod-like processes of the cell-protoplasm, participating in absorption of the fat-granules. C, cylindrical epithelium after absorption of the fat-granules has been com- pleted. D, cylindrical epitheUum of the villus, viewed from the surface, with a goblet-cell in the center. of fact, neither the lid nor the mosaic plates or pores attributed to it exist. The cells are, therefore, open toward the intestinal surface. The protoplasmic processes, standing close together, and resembling the cilia of ciliated epithelium, are directed from the interior of the cell toward the periphery of the intestine. In their midst, near the free sur- face, lies a diplosoma. These protoplasmic processes are rapidly extended from the cell-body beyond the edge of the cell-membrane, and in a manner comparable to the pseudopods of amoebae, they seize the finely granular fat and draw it into the cell-bodv. Moistening with bile appears especially to promote their activity, as the movement is not observed in villi not moistened with bile. 35° STRUCTURE OF THE ORGANS OF ABSORPTION. CI. In addition, the medulla oblongata, the spinal cord or the dorsal nerves must have been divided for about a day previously. This apparently depends upon the fact that, in the preparation of an uninjured animal (frog), the fresh division of nerves that becomes necessary acts as an irritant, as a rcstilt of which the cells settle down to rest, like irritated amoeba; or like the corneal cells after irrita- tion of their nerves. This fact points to an influence of the nerves upon absorp- tion. When the epithelial cells are filled with fat -granules, the processes are withdrawn into the interior of the cell. The border then appears unstriated, and a transparent zone lies between it and the cell-proto- plasm. The goblet-cells appear to be engaged principally in the secre- tion of mucus; although small fat-granules are also occasionally seen within them. Pathological: In cases of cholera, as well as after poisoning with arsenic and muscarin, enormous desquamation of intestinal epithelium takes place. According to the views of Eimer, Heidenhain, v. Than- hoffer and others, the con- stricted root-ends of the epithe- lial cells communicate with anastomosing connective-tissue corpuscles of the villous tissue. Into these the fat-granules are believed to migrate from the interior of the epithelial cells. The soft connective-tissue cells, finally, are thought to com- municate with the central lymph-vessel; and in this man- ner a communication is estab- lished between the epithelium and the latter. Thus, the fat- granules would migrate through the body of the connective- tissue cells, as through lymph- canaliculi, to the central lymph- vessel. The author is able to agree with this conception with a modification, which approaches the views of His, Brficke and v. Basch. As a result of his investiga- tions he believes that the epithelial cell narrows toward its lower extremity, like a funnel; the cell-membrane entering, in various direc- tions, directly into communication with the supporting cells of the adenoid tissue of the villus, as well as with the subepithelial branching layer of the villus, which, accordingly, must be perforated in many places. The supporting cells of the villous tissue surround a spongy system of cavities within which lie protoplasmic, nucleated strom'a-cells (Fig. 127, A) of varying appearance. The latter at times contain fat- granules in suspension. According to v. Davidoff, these ceils are formed by constriction from the lower extremities of the epithelial cells, which, in time, develop a nucleus within themselves. These cells, like ameboid cells without capsules, communicate with one Fig. 128. — Blood-vessels of an Intestinal Villus: Cn, capillaries; A, artery; CI, cylindrical epithelium; O, surface of the epithelium; V, vein. ABSORPTION OF THE DIGESTED FOOD. 35 1 another and with the protoplasm of the epithelial cells, and in them, through active movement of the protoplasm, wander the fat- granules, which the cells take up and again give up within the villus. Thus, the epithelial sheath, with the connective-tissue corpuscles of the villus, forms the supporting apparatus; the -contents of the epithelial cells and the numerous stroma-cells are the active propellers of the fat-granules taken up. Through appropriate interstices in the tissues the cavities containing the stroma-cells communicate with the axial lymph-vessel, which is lined by endothelial cells. It is not improbable that leukocytes frequently migrate from the capillary blood-vessels of the villus into the tissue of the villus and, in part containing absorbed fat-granules, pass over into the central lymph-vessel. According to Schafer, Zawary- kin, Wiedersheim, Stohr, Preusse, Heidenhain and others, the ameboid cells probably migrate from the parenchyma of the villi toward the epithelial layer and perhaps even between the epithelial cells, and return toward the axis of the villus, laden with the substances absorbed. A small artery enters every villus and, lying excentrically, passes to the summit of the villus without division, to give off branches from this point. In human beings this division begins at the middle. The ramifications form a dense capillary network, which lies superficially in the parenchyma of the villus, almost directly beneath the epithelial layer, and from which, either at the apex of the villus or further downward, a vein, running backward, is constituted. The villus is provided with unstriated muscular fibers, both deep- seated, their bundles accompanying the central lymph- vessel longitu- dinally, and also superficial, running rather transversely. The connective tissue of the small intestine has two layers, a deeper, composed of thick, interwoven, mainly collagenous fibers (stratum fibrosum) , and lying above this a reticular layer intermixed with elastic fibers (stratum granulosum), entering into the villi also. Nerves enter the villi from Meissner's mucous-membrane plexus, are provided with small, granular ganglion-cells in their course, and end in part in the muscles of the villi and of the arteries, while in part they appear to communicate with the contractile protoplasm of the epithelial cells. Nerve-filaments pass from Meissner's mucous-membrane plexus to the vessels of the submucosa. Meissner's plexus communicates, by numerous fibers, with a nerve-plexus that spreads throughout the entire thickness of the mucous mem- brane, extends into the villi and supplies the muscularis mucosa, the vessels of the mucosa and Lieberkiihn's glands. The epithelial cells of the large intestine possess no seam-like mar- ginal thickening. The serous coat of the alimentary tract is provided with special lymph- vessels, at first distinct from the chyle-vessels. ABSORPTION OF THE DIGESTED FOOD. PHYSICAL FORCES: ENDOSMOSIS, DIFFUSION, FILTRATION. Endosniosis and diffusion take place between two liquids that are capable of admixture, as, for example, hydrochloric acid and water, but never between two fluids that are opposed to admixture, as, for instance, oil and water. If two miscible dissimilar liquids are separated from each other by a membrane provided with physical pores, stich as may be present even in apparently homo- geneous membranes, an interchange of the constituent parts takes place through the pores of the membrane, until finally both fluids have the same composition. This process is designated endosmosis' or diosmosis. The endosmotic passage of a substance through the membrane takes place if a solvent liquid having an attraction for the substance is present on the other side of the membrane. 352 ABSORPTION OF THE DIGESTED FOOD. If both miscible fluids are simply placed over one another in a vessel, without the intervention of a porous septum, an interchange of particles of the liquids also takes place, until the entire mass has undergone homogeneous admixture. This interchange is designated diffusion. The rapidity of diffu.sion is influenced: i. By the nature of the fluids. Acids pass over most rapidly, alkaline salts more slowly; liquid albvmiin, gelatin, gum, dextrin, and starch-solutions most slowly. The latter, in part, do not crystallize, and also in part do not represent true solutions, but only su.spensions. 2. The more concentrated the solutions, the greater is the diffusion. 3. Heat promotes, cooling retards, diffusion. 4. If the solution of a body difficult of diffusion is mixed with a readily diffusible solution, the former diffuses with even greater difficulty. 5. Dilute solutions of various substances diffuse into one another without difficulty, while concentrated solutions mutually retard diffusion. 6. Double salts, of which one constituent diffuses more readily, and the other with greater difficulty, may even be separated chemically b}- diffusion. In the endosmoti'c interchange of fluids, the passage of the fluid-particles takes place independently of the hydrostatic pressure. Fig. 129 is a simple illustration of endosmotic exchange. A glass cylinder is filled with distilled water (F). A flask (J) is kept immersed in the water to a suitable height, and closed by a membrane (m) replacing its broken bottom. From the neck of the flask, in which it is tightly corked, projects a glass tube (R) . The flask is filled with concen- trated salt-solution up to the level of the lower extremity of the tube. The flask is introduced into the glass cylinder to such a distance that both fluids stand at the same level (x). In a short while the fluid rises in the tube (R), because particles of water pass through the membrane into the concentrated salt-solution in the flask, and independently of the hydrostatic pressure. The fluid rises in the tube as high as the attraction of the water causes it to. The height of the fluid thus indicates the osmotic pressure. Conversely, also, particles of the concentrated salt- solution pass from the flask into the interior of the cylinder, mixing with the water (F). This interchange of current continues until an entirely uniform mixture is present in the flask and in the cylinder. Under these circumstances the level of the fluid will to the last always have risen higher in the tube (to y). The circumstance that the level of the liquid within the tube can rise so high and be kept at such a height depends tipon the fact that the pores of the membrane are too fine to permit of the action of hydrostatic pressure through them. Therefore endosmosis is defined as an interchange of par- ticles of fluid independently of the hydrostatic pressvire. Reflection will show that if, in an endosmosis-experi- nient of similar kind, the water in the cylinder is renewed from time to time, the solution in the flask must become progressively more dilute, until, finally, the flask (J) and the cylinder (F) contain only pure water. Endosmotic Equivalent. — It has been found that in endomosis-experiments, equal parts by weight of dift'erent fluids or soluble substances (which soon coalesce on the moist surface of the membrane within the flask to form concentrated solu- tions, as, for example, sodium chlorid) being present in the flask, a varj'ing amount of distilled water passes through the membrane, so that, finally, if the water in the cylinder is constantly renewed, a variable amotmt of distilled water will be pre- sent in the flask. In other words, it has been found that a definite part by weight of a soluble substance in the flask has been exchanged by endosmosis for a definite part by weight of distilled water. The figure that indicates how many parts by weight of distilled water pass over in the endosmosis-flask for a definite part by weight of a soluble substance has been designated b}^ Jolly as the endosmotic equivalent. For i gram of alcohol. 4.2 grams of water are exchanged; for I gram of sodium chlorid, 4.3 grams of water. The endosmotic equivalents for the following substances are: V- Fig. 129. — .Apparatus for Diosmosis. ABSORPTION' OF THE DIGESTED FOOD. 353 Acid potassium sulphate = 2.3 Magnesium sulphate = 11.7 Sodium chlorid = 4.3 Potassium sulphate = 12.0 Sugar = 7.1 Sulphuric acid = 0.39 Sodium sulphate = 11.6 Potassium hydrate = 215.0 The amount of the substance passing through the membrane into the water of the cylinder within an equal time is proportional to the degree of concentra- tion of the solution. If, therefore, the water within the cyhnder is frequently renewed, the course of the endosmotic equalization is the more rapid. Further, the larger the pores of the membrane and the smaller the molecules of the sub- stance in solution, the more quickly endosmosis takes place. It thus results that the rapidity with which endosmosis takes place varies for different substances. Thus the rapidity for sugar, sodium sulphate, sodiimi chlorid and urea is, as I : I.I : 5 : q.5. The endosmotic equivalent for each substance, however, is not constant. It is influenced by: i. The temperature, with increase in which, in general, the endosmotic equivalent increases. 2. C. Ludwig and Cloetta have demonstrated that the endosmotic equivalent varies with the degree of concentration of the penetrating solutions; it is larger for dilute solutions of substances. Should a solution of another substance be present in the cylinder instead of water, an endosmotic current takes place from both sides, until complete equaliza- tion is effected. In this process it is seen that these covmter-currents of concen- trated solutions have a disturbing influence on each other. If, however, two sub- stances in. solution are present in the flask at the same time, both diffuse toward the water, without interfering with each other. 3. The endosmotic equivalent varies with the employment of different membranes of different porositv. Sodium chlorid, which has an endosmotic equivalent of 4.3 when pig's bladder is used, possesses an equivalent of 6.4 when a cow's bladder is employed; 2.9 with a swimming-bladder, and 20.2 with a collodion membrane. There are a number of fluids that, on account of the considerable size of their molecules, are capable of passing with difficulty, if at all, through the pores of a membrane impregnated with gelatinous substances, diffusible with difficvdty. These consist in part of fluids that contain substances, not in true solution, but in a greatly diluted state of imbibition. Among such substances are the liquid albuminates, solutions of starch, dextrin, gum, mucus and gelatin. They are capable of gradually passing over into and mixing with other fluids by diffusion, in the absence of an intervening porous membrane-wall ; they pass by endosmosis with difficulty, if at all, through the pores of membranes impregnated with gelatin. Nevertheless, the nature of the outside liquid must be taken into consideration; egg-albumin, it is true, passes through membranes into salt-solutions, but not into water; the transudate, under such conditions, becomes more concentrated. Graham has designated the substances in question colloids, because in consider- able concentration they become gelatinous. They also possess the property of not crystallizing, as a rule, while crj-stalline substances, designated crj-stalloids, are exchanged by endosmosis. The endosmotic apparatus thus constitutes a mechanism for effecting a separation from mixtures of cr\-stalloids and colloids, which by Graham is designated dialysis. If mineral salts are added to the colloid substances, their ability to pass through membranes is increased. That endosmosis takes place within the ahmentary canal, through its mucous membrane and the delicate membranes of the capillary blood-vessels and lymphatics, cannot be denied. On the one side of the membrane, within the tract, there are relatively concentrated aque- ous solutions of salts, sugar, soaps, and peptones, all of which possess slight diosmotic power. On the inner side of the vessels is the colloid, albuminous solution of the blood and the lymph, practically incapable of osmosis, and deficient in the matters in solution within the ali- mentary canal, particularly in the state of hunger. The vital proper- ties, however, probably in consequence of the motility of the proto- plasmic structure within the membranes, also appear to exert some influence upon endosmosis. Thus, Reid observed that the exfoliated frog's skin is less permeable than living skin, and the latter, in turn, more so after irritation had been applied. 23 354 ACTIVITY OF THE WALL OF THE ALIMENTARY CANAL. Filtration is the passage of fluid through the coarser intermolecular pores of a membrane dependent upon pressure. The higher the latter and the larger and more numerous the pores, the more rapidly will the filtrate pass through the pores of the membrane. Increase in temperature likewise accelerates filtra- tion. Further, those fluids filter most readily that most rapidly soak into the membrane in question. Therefore, different fluids vary in the readiness with which they pass through difterent membranes. Further, the greater the con- centration of the solutions, the more slowly, in general, is their passage. The filter has the property of retaining in part matters from the solutions passing through, either substances dissolved in the fluid (particularly colloid substances) , or water (from dilute solutions of potassium nitrate) . In the former case the filtrate is more dilute, in the latter more concentrated, than the fluid was before its passage through the filter. Other substances pass through without material change in concentration. Should the filtrate enter another fluid, the concen- tration of the transudate increases with the pressure under which filtration takes place. Some membranes exhibit a difference according as filtration takes place from their difterent surfaces; thus the membrana testacea of the egg per- mits of filtration onh?- in the direction from without inward. The mucous mem- brane of the stomach and intestine also exhibits a difference in this respect. It was formerly believed that filtration of substances in solution could take place from wdthin the digestive canal into the vessels: i. If the intestine contracted and thereby exerted pressure directly on the contents. This alone, however, could scarcely have any noteworthy influence, even in case the canal were contracted in two places and the intervening musculature, through contraction, compressed the fluid intestinal contents. 2. Filtration under negative pressure may be effected through the villi, which on contracting forcibly evacuate the contents of the blood-vessels and lymphatics in a centripetal direction. The latter particularly will remain empty, as the chyle in the fine lacteals is prevented from passing backward by numerous valves. When the villi are again relaxed, they will by suction be able to fill themselves with the fluids of the digestive tract capable of filtration. On the other hand, the fact must especially be emphasized that, according to Spee and Heidenhain, the muscles of the villus actively dilate the central lymph-vessels. ABSORPTIVE ACTIVITY OF THE WALL OF THE ALIMENTARY CANAL. The process of digestion prepares from the food in part true solutions, in part finely divided emulsions, whose small globules are surrounded by an albuminoid capsule. Absorption of Solutions. — It cannot be denied that true solutions can pass over into the blood and the lymph of the intestinal canal by endosmosis, but some observations indicate that the cellular elements of the digestive tract also participate in the process of absorption through the functional activity of their protoplasm. It has not as yet been possible to refer the forces effective in this connection to simple physical or chemical processes. When Heidenhain introduced methylene-blue in solution into the intestine, he was convinced that the path of its absorp- tion was in part through, in part between, the epithelial cells. The Inorganic Substances: Water, and the dissolved salts necessary for nutrition, are generally easy of absorption, and in large measure by the blood-vessels. In the absorption of salt-solutions by endosmosis, water must naturally pass from the intestinal vessels into the intestine, while the salt-solutions enter the vessels. The amount of water, how- ACTIVITY OF THE WALL OF THE ALIMENTARY CAN'AL. 355 ever, is but slight on account of the small endosmotic equivalent of the salts to be absorbed. Salts are absorbed in larger amount from con- centrated than from dilute solutions. If, however, considerable amounts of salts with a high endosmotic equivalent are introduced into the in- testine, as, for example, magnesium or sodium sulphate, these salts retain the water for their solution, and in addition more fluid escapes from the vessels of the intestinal wall, and diarrhea results. Conversely, it is evident that, on injecting these substances into the blood, a large amount of water passes from the intestine into the blood, so that con- stipation results, in consequence of the great dryness of the interior of the intestine. It should, however, especially be pointed out that the absorption of solutions of various salts, isotonic with one another, takes place differently. The epithelial cells of the intestine behave like the erythrocytes with respect to the permeability of the solutions. Water is absorbed from the stomach only in small amount. The absorption of fluids takes place best at moderate pressure within the intestinal canal (from 80 to 140. cm. of water-pressure), in connection with which the surface of the mucous membrane is best smoothed out. A greater degree of pressure would compress the intestinal vessels and would accordingly allow absorption to diminish. During digestion, on account of the dilatation of the blood-vessels, absorption takes place rapidly. For this reason warm solutions also are more quickly absorbed from the stomach than cold, the latter causing contraction of the vessels. The fact that a 0.5 per cent, sodium-chlorid solution is better ab- sorbed than water, further a potassium-solution less well than sodium- solutions, and also the extensive absorption of dog's serum in the dog's intestine, are opposed to the view that only physical forces (endosmosis) are concerned in absorption. Some other inorganic substances also, which are not, as such, constituents of the body, are absorbed by endosmosis: potassium iodid, potassium chlorate, potassium bromid; further, iron-salts, as well as dilute sulphuric acid, etc. Carbohydrates in solution have their chief representatives in the different varieties of sugar — and principally in dextrose and maltose, which have relatively high endosmotic equivalents, as cane-sugar is gen- erally transformed by a ferment into invert-sugar. Absorption appears to take place relatively slow^ly, as, at this time, only small amounts of grape-sugar are found in the intestinal vessels and in the portal vein. According to v. Mering, the sugar is absorbed from the intestine by the portal vein. Dextrin is also present in the blood of the portal vein, as boiling with dilute sulphuric acid increases the amount of sugar in this blood. The amount of sugar absorbed depends upon the concen- tration of its solution in the intestine. Therefore, the amount of sugar contained in the blood is increased after a diet rich in sugar, so that it may even pass over into the urine. To this end approximately a 0.6 per cent, solution of sugar in the blood is necessary. Also cane- sugar in small amount has been found in the blood. When a large amount of sugar-solution is present in the intestine, a portion also enters the lymph-vessels. In a girl with a fistula of the receptaculum chyli, not more than h per cent, of the sugar introduced into the alimentary canal was found to be absorbed by the lacteals. The sugar is in part consumed in the blood and in metabolism, perhaps principally in the muscles. 356 ACTIVITY OF THE WALL OF THE ALIMENTARY CANAL. Peptones have an endosmotic equivalent, more than four times smaller than that of dextrose. They can be rapidly absorbed, on account of their ease of diffusion and filtration. Absorption takes place through the blood-vessels, unless excessive amounts are present in the intestine, as after ligation of the thoracic duct, ingested proteids are as well absorbed as under normal conditions. Peptones have been recovered from the blood, with certainty, in small amounts only. It is, therefore, to be inferred that they are quickly retransformed into true proteids. The mucous membrane possesses the property of retrans- forming peptone into albumin. Heidenhain regards the epithelial cells of the villi as the seat of this transformation. Peptone gains entrance into the blood unchanged only in minimal amount and it disappears from this after its passage through the tissues. If blood containing peptone is kept warm in the presence of a small piece of small intestine, while air is passed through the mixture, the peptone soon disap- pears from the blood. The peptones undoubtedly represent the principal contingent of the albuminates destined for absorption. Of all the proteids they alone suffice to maintain the body equilibrium, as animals fed upon peptone only (in addition to the necessary fat or sugar) are able to maintain their nutrition. They can do the same when fed with propeptone. According to Pfeiffer, the diffusion of the peptones is promoted by a i per cent, solution of sodium chlorid or sulphate. The absorption of grape-sugar and peptone in the stomach and intestine is increased by the addition of certain sub- stances, as, for example, sodium chorid, pepper, alcohol or ethereal oils. In dogs a peptone-solution (5 cu. cm. of a 20 per cent, solution in 0.6 per cent, sodium- chlorid for an animal weighing 8 kilograms) introduced into the blood, causes death. Unchanged Proteids. — In spite of their slight power of filtration and (on account of their great endosmotic equivalent) of diffusion, it has been demonstrated with certainty that unchanged proteids, such as liquid casein and the proteids of milk, meat-juice, dissolved myosin, alkali-albuminate, egg-albumin mixed with sodium chlorid, syntonin, gelatin, can be absorbed; their absorption takes place, in part, even from the mucous membrane of the large intestine. The amount of absorbed unaltered albumin is, however, smaller than that of the peptones. Egg- albumin without sodium chlorid, serum-albumin, hemoglobin and fibrin are not absorbed. Many j^ears ago the author made the observation in a j'oung man that after the ingestion of the white of between 14 and 20 raw eggs, with sodium chlorid, albumin was excreted in the urine after from 4 to 10 hours. The amount of albumin thus excreted increased up to the third day, then becoming less and ceasing on the fifth day. The more albumin ingested, the earlier the albuminuria appeared and the longer it lasted. In this case the condition was evidently one in which considerable absorption of tinchanged egg-albumin took place into the circulation. If egg-albumin be injected directly into the blood- stream of animals, it likewise passes, in part, into the urine. The soluble soaps form only a part of the fats absorbed, the largest portion of the fat being taken up in the form of a finely granular emulsion. Absorbed soaps have, on the one hand, been found in the chyle; on the other hand, from the circumstance that the blood of the portal vein is richer in soaps at the time of absorption than during the state of hunger, it has been inferred that absorption of the soaps takes place, to some extent, through the intestinal capillaries. Nevertheless, only a small portion of the soaps enters the blood. ACTIVITY OF THE WALL OF THE ALIMENTARY CANAL. 357 The experiments of Lenz, Bidder and Schmidt render it probable that the organism can take up only a limited amount of fat within a certain time, and this may, perhaps, bear a definite relation to the cjuantity of bile and pancreatic juice. Beyond that amount no more fat is absorbed. Thus, in cats, 0.6 gram of fat an hour was found to be the greatest amount absorbed for every kilogram of body weight. I. Munk and Rosenstein found the absorption of fat greatest from 5 to 8 hours after ingestion, and earlier or later accordingly as the fat was more or less readily liquerialile. The greater part of the soaps in the intestine, transformed into neutral fat, passes over into the chyle. It seems as if the soaps are capable of uniting with glycerin in the parenchyma of the villus to form neutral fat. Perewoznikoff and Will found neutral fat after the injection of both of these ingredients into the intestinal canal, and also C. A. Ew^ald observed fat to form when he brought soap and glycerin in contact w4th the fresh, living intestinal mucous membrane. Blood and chyle contain no free fatty acids. In the blood the fat is subsequently decom- posed in the presence of oxygen. Of other organic matters in solution that are introduced into the intestinal tract, some are absorbed, as, for example, alcohol, and many others. Other bodies may be in part absorbed, in part fermented: tartaric acid, citric acid, malic acid, lactic acid, glycerin and inulin ; gum and vegetable mucin, which give rise to the formation of glycogen in the liver ; and it is probable that unknown products of metabolism are also absorbed. Of pigments, alizarin, alkanna and indigo-carmine are absorbed: others are in part absorbed, such as hematin; chlorophyll is not absorbed. Metallic salts appear, in part, to be held in solution by an excess of albuminates, and to be absorbed at the same time with these (iron sulphate has been found in the chyle) , and. in part, to be conveyed to the liver through the blood of the portal vein. Numerous poisons undergo rapid absorption, prussic acid in the course of a few seconds; potassium cyanid has been found in the chyle. Moreover, the purely physical conception of the absorption even of true solutions by endosmosis and filtration alone is not sufficient. Here, also, the protoplasm of the cells takes at least an active part, for only in this way is it possible to explain how even a slight derangement in the activity of these cells, as, for example, after cold or excitement, may be followed by sudden serious disturbances of absorption, even the escape of fluid into the intestine. Only in this way, also, can the fact be explained that the presence of different spices, in small amount, actively increases absorption in the stomach. If, further, absorption took place solely and alone by endosmosis, water would pass over into the intestine after the injection of alcohol; but this never occurs. Further, salt is absorbed in the intestine from a solution that has less osmotic energy than blood-plasma. Moreover, Brieger observed, after the injection of from 0.5 to i per cent, solutions of metallic salts into ligated loops of the intestine, that transudation of water into the bowel failed to take place; although this occurred w^hen injections of 20 per cent, solutions were made. Absorption of the Smallest Granules. — The largest amount of the neutral fats and at the same time also of the fatty acids is absorbed in the form of a milky emulsion prepared by the bile and by the pancreatic juice and composed of minute granules. The individual fat-granules appear to be surrounded by a delicate albuminous membrane, the hap- togenic membrane, which is derived in part from the pancreatic juice. In the absorption of fat-emulsions, the villi of the small intestine par- ticipate primarily and in greatest degree; but the epithelial cells of the 358 ACTIVITY OF THE WALL OF THE ALIMENTARY CANAL. Stomach also, as well as those of the large intestine, take part in this process. In the villi the fat-granules are seen: (i) Within the epithe- lial cells, the protoplasm of which is dotted with them. The nucleus remains free from them, yet it is so beset by the innumerable fat-granules as to escape observation. (2) Within the tissue of the villus itself, the granules traverse in large numbers the intercommunicating course of the spaces in the reticular tissue. Not rarely, when absorbed in smaller amount, the granules arrange themselves in connected reticular paths. At times they appear to be collected in undivided, band-like lines; at other times, the entire parenchyma of the villus is completely filled with innumerable granules. (3) At a later period the central lymph- vessel in the axis of the villus appears filled with fat-granules. The amount of fat in the chyle varies in the dog, after generous feeding of fat, from 8 to 10 per cent. The fat disappears from the blood within thirty hours. If chyle, rich in fat, is mixed with blood (even if lake-colored), and is agitated with air, the amount of fat in the mixture diminishes as a result of the action of a lipolytic substance present in the blood, in consequence of which a body, insoluble in ether, is formed. The fat-granules are taken up out of the blood by the various tissues, particu- larly by the liver, and in smallest measure by the muscles. The consumption of fat in the tissues begins with a division into glycerin and fatty acids, which is followed by the final combustion. With regard to the forces that effect absorption of the fat-gran- ules, it appeared conceivable from observations made by v. Wisting- hausen that moistening of the porous membranes with bile is capable of facilitating the passage of fat-granules ; but this does not adequately explain the abundant and rapid absorption. It appears most probable that the protoplasm of the epithelial cells of the alimentary tract seizes the fat-granules by an independent movement, and then actively draws them within itself. The protrusion of delicate protoplasmic filaments from the cell-body would take place in a manner similar to that in which the absorption and the inclusion of granular articles of food takes place in the lower organisms, the amoebae. Absorption is possible on the part of the goblet-cells also, because the entrance to the cell remains open. The protoplasm of the epithelial cells communicates directly with the protoplasmic lymphoid cells present in large number within the reticulum of the villus. Thus, the granules may be conveyed to these cells and finally from them, through the stomata between the endothelial cells, into the central lymph-vessel of the villus. The process of the absorption of granules — and perhaps the same is in part true of proteids — is thus established as a wholly active, vital one. This view receives adequate support from the investigations of Brucke and of V. Thanhoffer and others, as well as the observation of Griinhagen that the absorption of fat-granules in frogs takes place most rapidly at a temperature at which the motile phenomena of the protoplasm are most active. In fact, the conception of a simple physical filtration of the granules into the tissue of the villus is scarcely any longer permissible. This is to be concluded also from the fact that the number of fat-granules present in the chyle is independent of the amount of water present in it. If absorption took place essentially through filtration, the constancy of a direct relation between the amount of fat and the amount of water INFLUENCE OF THE NERVOUS SYSTEM. 359 present would at least be highly probable. The fatty acids, in their passage through the intestinal wall, are retransformed with fixation of glycerin into neutral fats. They pass, in part, through the blood-vessels. The intestine of distomum hepaticum may be considered as a truly classical object-lesson for a study of the cells of the intestine in their functional activity and of the manner in which they accomplish the absorption of solid substances by means of their pseudopod-like processes. Sommcr has admirably depicted the conditions, and the author convinced himself of the accuracy of the represen- tation by personal observation of the preparations. Metschnikoflf noted similar conditions in celenterates, Du Plessis in turbellaria, Greenwood in earth-worms. If carmine or India-ink is mixed with the food of rabbits, a deposition of either ^anular pigment takes place in Peyer's patches and in the lymph-cells. Pathological. — In the presence of severe intestinal disease, injury to and al- teration in the epithelial cells of the intestine appear to be caused by a poison elaborated in the bowel, as, for exaniple, in cases of cholera and cholera infantum. INFLUENCE OF THE NERVOUS SYSTEM. Little is known with certainty concerning the influence of the nervous system upon the processes of absorption in the intestinal tract. After division of the mesenteric nerve-filaments, the intestinal contents be- come abundant and watery. This may be due, in part, to deficient absorption, as well as to an increased, paralytic secretion of the intestinal juice, although it is as yet impossible to determine with certainty to what extent transudation into the intestine on the part of the vessels participates in this process. After extirpation of the sympathetic ganglia of the abdomen, symptoms of paralysis of the intestine appear, with exhausting diarrhea, finally terminating fatally; acetone is also present in the urine. Of especial interest is the observation of v. Than- hoffer, who noted the protrusion of filaments from the protoplasm of the epithelial cells of the small intestine only when the medulla oblongata or the dorsal nerves had been divided some time previously. NOURISHMENT BY MEANS OF "NUTRITIVE ENEMATA." In those desperate cases in human beings in which administration of food by the mouth is impossible, r. g., in the presence of stenosis of the esophagus or of persistent vomiting, resort has been had to the procedure adopted by Com. Celsus, namely, rectal alimentation. As the large intestine is capable of scarcely any digestive activity it is best to introduce fluid material capable of absorption, which is permitted to flow slowly, by its own weight, into the anus, preferably through a long tube provided with a funnel. The recipient must endeavor to retain the material for as long a time as possible. Bj^ means of slow and gradual injection, the fluid at times maj^ even pass beyond the ileo-cecal valve. Particles of proteid substances, saturated with a solution of sodium chlorid, may even pass through the small intestine into the stomach, where they may be digested. Nitrogenous substances are to be recommended for this purpose : eggs rubbed up into an emulsion with an aqueous solution of sodium chlorid, peptone or pro- peptone; less well, milk and egg-albumin with sodium chlorid. The commercial preparations of peptone are made by digestion with pepsin, by vegetable ferments or by superheated water, and they often contain much propeptone. An adult should receive daily 120 grams, a child 50 grams of meat-peptone; Leube ad- vises from 50 to 80 grams dissolved in 250 cu. cm. of water. In addition, as a stimulant and as food-sparer, tea with wine may be given. Leube introduces into the rectum a pasty mixture consisting of 150 grams of meat with 50 grams of reddened pancreatic tissue and 100 grams of water, and it is beheved that proteids.are peptonized and absorbed here. In addition, as much as 50 grams of grape-sugar dissolved so as to make 300 cu. cm., or starch-paste and dilute lake- colored blood may be employed; also fat-emulsions (not more than 10 granis of fat daily) ; mixed'with pancreatic paste, as much as 50 grams of fat can be given. 360 SYSTEM OF LACTEAL AND LYMPHATIC VESSELS. Whether thin soap-solutions are advisable, however, has not as yet been deter- mined. This mode of administering nutriment by means of nutrient enemata, must, however, always remain imperfect; at best only one-quarter of the amount of proteids necessary for the maintenance of the metabolic equilibrium is absorbed. SYSTEM OF LACTEAL AND LYMPHATIC VESSELS. Within the tissues of the body, and even in those without special blood-vessels (cornea) or with but a poor supply, there is present a system of vessels conveying fluid, and within which the movement is only centripetal. These vessels begin within the parenchyma of the organs in widely different ways, and unite in their course to form delicate, then thicker tubes, which empty into two trunks of considerable size at the junction of the common jugular and subclavian veins: the tho- racic duct on the left side, the lymphatic trunk on the right. The importance of the lymph and of its movement in the various organs is apparent in different ways at different points, (i) In some tissues the lymphatics represent the nutrient channels through which the nutrient fluid given off by adjacent blood-vessels is distributed, as in the cornea particularly and often within the connective tissues. (2) In some tissues, as in the glands, for example the salivary glands and the testicles, the lymph-spaces constitute the chief reservoirs for fluid, from which, at the time of secretion, the cellular elements derive their necessary fluid. (3) In addition, the lymphatic vessels everywhere have the task of collecting the fluid with which the tissues are saturated and of conveying it back again to the blood. If the network of capillary blood-vessels be regarded, from this standpoint, as an irrigation-system, which supplies the tissues with nutrient fluid, the lymphatic system can be considered as a drainage-mechanism, which, in turn, conducts away the excess of the transuded fluids. Metabolic products from the tissues, the products of retrogressive metamorphosis, are added to this return- current. The lymph-channels are thus, at the same time, absorbent vessels: substances that would otherwise be carried to the parenchyma of the tissues are thus also absorbed by the lymphatic system. A consideration of these circumstances shows that the system of the lymph-channels represents in reality an appendix to the blood- vascular system ; therefore, further, the lymphatic system cannot be active at all if the circulation of blood is totally interrupted; it operates only as a part of the whole and with the whole. If the lacteals are contrasted with the true lymph- vessels, this is done chiefly for anatomical reasons, because the important and con- siderable paths of the former, which are derived from the entire intes- tinal tract, have especially attracted the attention of investigators since antiquity and are to a certain extent an almost independent division of the lymphatic system, with conspicuous absorptive activity. In addi- tion their contents, of white color from the generous admixture of fat- granules, as chyle or lacteal fluid, appeared at first sight to be essen- tially distinct from the clear and watery fluid of the true lymphatics. From the physiological standpoint, however, the lacteals cannot be given an independent position. They are, functionally and structurally, lym- phatics, and their contents are true lymph, mixed with a large amount of absorbed materials. ORIGIN OF THE LYMPH-CIIA WELS. LYMPHATICS. 361 ORIGIN OF THE LYMPH-CHANNELS. LYMPHATICS. Development by Means of Secretory Spaces. Witliin the supporting sub- stances (connective tissue, bone) numerous star-shaped or polymorphous spaces are found that are connected with one another by means of delicate tubular processes. This system of communicating spaces contains the cellular elements of the tissues. The cells, however, by no means completely fill the spaces, an interval often existing between the cell-body and the wall of the space, Fig. 130. — Origin of the Lymph-channels: I, from the central tendon of the rabbit (semi-diagrammatic) •."'s, secretory spaces, communicating with the lymphatic at x; a. commencement of the lymphatic froml the confluence of secretory spaces. II, perivascular lymphatics. Ill, lymph-stomata. and varying in size, in accordance with the state of motility of the protoplasmic cells. These spaces are the so-called secretory spaces, or secretory canals, and they represent the commencement of the lymphatics. As adjacent spaces inter- communicate, the proptilsion of the lymph is provided for. The cells lying in the secretory spaces are capable of ameboid movement. In part they remain permanently in their spaces (fixed connective-tissue cells, bone-corpuscles) ; in part they are capable of engaging in active migration through the secretory canal- 362 ORIGIN OF THE LYMPH-CHANNELS. LYMPHATICS. system (wandering-celLs) . At greater or lesser distances, these secretory clefts are connected with minute tiibular lymphatics, which are designated lymph- capillaries (Fig. 130, I, L). Their commencement results from the more intimate approximation of secretory spaces (I, a). The lymph-capillaries, generally exceeding the capillary blood-vessels m caliber, lie principally in the space midway between the arched loops of the blood- capillaries (B). They are composed of delicate nucleated endothelial cells (e), whose characteristic sinuous edges can be stained black by means of a solution of silver nitrate. Between the endothelial cells scattered spaces, stomata, are present. The endothelial cells constituting the wall are often united by bridges of protoplasm. According to Kolossow, the cells may recede from one another at their edges, and thus form spaces between them, while the connecting bands of protoplasm are capable, subsequently, of drawing them together again. Thus, the stomata would develop temporarily and again close. It is to be inferred that the blood-vessel system communicates with the lymph-spaces ; that the blood-plasma finds its way into the lymph- spaces from the thin-walled blood-capillaries through their stomata. In the lymph-spaces this fluid maintains the nutrition of the tissues, inasmuch as the necessary constituents are taken up independently by the tissues. The materials consumed are returned to the lymph- spaces and later reach the lymph-capillaries, which finally deliver them to the venous system. To what extent the cellular elements within the lymph-spaces exert any action upon the discharge of blood-plasma and later upon its propulsion into the lymphatics can only be surmised. It can be conceived that, through con- traction and diminution in size of their cell-bodies, as well as through partial change in position from the group of secretory spaces closer to the blood-vessel to that directed toward the lymph-capillary, they might exert suction upon the blood- plasma transuded. If the cells, themselves, then take up the transuded fluid, the conception is permissible, further, that by subsequent contraction they ex- press this fluid in a certain direction, namely from secretory space to secretory space, toward the lymph-capillaries. In consequence of the independent migra- tion of the cellular elements through the secretory spaces into the larger lymph- paths, small particles that may be contained in the secretory spaces (as, for ex- ample, pigment-granules that have been rubbed into the tissue of the irritated, horny skin in the process of tattooing, and also minute fat-granules, bacteria and the like), and which the lymph-cells are capable of taking up through ameboid movement, may be propelled onward. After what has been said concerning the migration of leukocytes from the blood-stream through the stomata between the endothelial cells of the capillaries, or through the walls of smaller vessels, the migra- tion of cellular elements from the blood-vessel system into the com- mencement of the lymph-channels may be regarded as a normal process. Granular pigments pass from the blood into the protoplasmic bodies of the cells in the lymph-spaces. Only when the granular substance is present in large amount is it distributed into the ramifications of the lymph-spaces as a granular injection. The origin of the lacteals within the villi has been outlined in their descrip- tion as organs of absorption. Commencement of the Lymphatics in the Form of Perivascular Spaces. — In the tissue of bony substance, of the central nervous system and of the liver, the smallest blood-vessels are surrounded by wider lymph- vessels, so that the blood-vessels lie in the lymph-vessels like a finger in a glove. In the brain these lymph-vessels are in part constituted of delicate connective-tissue fibrils, which, partly traversing the lumen of the lymph-canal, are supported upon the sur- face of the blood-vessel. Fig. 130 II, B represents in transverse section a small blood-vessel (B), with a perivascular lymph- vessel, from the brain; p is the tra- versed lumen of the lymph- vessel. In addition to these so-called perivascular spaces of His, the cerebral vessels are provided also with lymph-spaces within THE LYMPH-GLANDS. 363 the adventitia (Virchow-Robin spaces). In part these possess a well-developed endothelium. In their further course, where the vessels increase in caliber, the blood-vessel penetrates the wall of the lymph-vessel at one spot, and both continue separately side by side. Wherever the lymph- vessels serve as perivascular sheaths, the passage of blood-plasma and lymph-cells into the lymph-stream is greatly facilitated. It should be especially mentioned that, in tortoises, even the larger vessels are often covered by the lymph-vessels as a sheath. In Fig. 130, II, A, the bifurcation of the aorta, with the perivascular lymph-vessels, is shown according to Gegenbaur. The animals referred to exhibit macroscopically the same relations that warm-blooded animals present microscopically; and thus the illustration inay serve also as the microscopical picture of small peri- vascular lymph-vessels in warm-blooded animals. Commencement in the Form of Interstitial Spaces Within the Viscera. — In the testicles the lymphatics commence simply in the form of numerous spaces, which occur between the multifarious coils and convolutions of the seminiferous tubules. They will, therefore, here present the form of spaces bounded by the arched, cylindrical surfaces of the tubules. The limiting surfaces are, however, lined with endothelium. The lymphatics acquire independent tubular walls only beyond the parenchyma of the testicle. Similar conditions are found in the kidneys. In many other glands the glandular substance is likewise sur- rounded by lymph-spaces. Into these the blood-vessels first pour lymph, from which the secreting cells remove the material for the formation of the glandular secretion, as, for example, the salivary glands. Commencement by Means of Free Stomata upon the Walls of the Larger Serous Cavities (Fig. 130, III). Ft-om the investigations of v. Recklinghausen, C. Ludwig, Dybkowsky, Schweigger-Seydel, Dogiel and others, it has been found that the old view of Mascagni, that the serous cavities communicate freely with the lymphatics, is correct. Upon examining serous membranes (most readily the peritoneal lining of the large lymph-cavity in the frog) , best after moistening them with argentic nitrate, followed by exposure to the action of light, disseminated, relatively large, free openings of the stomata are found lying between the endo- thelial cells. Groups of the latter include a stoma among them. A portion of motile protoplasm lies in the cells surrounding the stoma, close to the edge of the opening. Upon the state of contraction of this protoplasm appears to depend the fact whether the stomata are widely open (a) , half closed (b) , or com- pletely closed (c). These stomata are thus the beginnings of the lymph-capil- laries. Fluids, introduced into the serous cavities, therefore readily reach the path of the lymphatics. The cavities of the peritoneum, the pleurae, the peri- cardium, and the serous covering of the testicle, further the arachnoid space, the chambers of the eye, and the labyrinth of the ear have shown themselves to be true lymphatic cavities; the fluid in them is thus to be designated lymph. Fluids in the peritoneal cavity are absorbed, in part, also by the veins. The endothelial cells of the serous membranes are capable of movement and communicate with one another by means of connecting bridges of protoplasm. In the animal king- dom the free surfaces of the cells are frequently provided with cilia. Even upon the free surface of a number of mucous membranes, it is stated, open pores have been observed as the commencement of the lymphatics: in the bronchi, in the nasal mucous membrane and in the larynx. The larger lymphatics arising from the lymph-capillaries closely resemble veins of equal size in the structure of their walls. Especial stress is to be laid upon the presence of a large number of valves, which are placed so closely behind one another that the distended lymphatic is not unlike a string of pearls. THE LYMPH- GLANDS. The so-called lymph-glands are peculiar to the lymphatic apparatus. They are inappropriately designated glands, because they really represent only many- branched, lacunar, labyrinthine spaces, constituted of adenoid tissue, interposed in the course of the lymphatics. Simple and compound lymph-glands can be distinguished. The simple lymph-glands, more correctly designated simple lymph-folhcles or cutaneous follicles, are present either isolated (solitary follicle) , as in the intes- tine, the bronchi, the spleen; or collected in masses (conglobate follicle), as in the tonsil, Peyer's patches, the follicles of the tongue. They are small, spherical vesicles, attaining approximately the size of a pin's head, and they consist through- 364 THE LYMPH-GLAXDS. out of delicate elements of the reticular connective tissue intermixed with elastic fibrils and arranged in a network (Fig. 131, C). In the meshes of this network, lymph and h-mph-ceJls are present in abimdance. Upon the s^l^face the tissue becomes condensed into a somewhat more independent, conspicuous sheath, which, however, is variously traversed by small spong\' spaces in the reticular tissue. Small lymphatics advance ever\'where directly up to these lymph-follicles, often keeping considerable areas of their s^arface covered with a rich network. Fre- quently, also, the surface of the follicle is incorporated into the wall of the vessel, at times throughout a slight, at other times throughout a considerable, extent, so that the surface of the follicle is directly irrigated by the lymph of the vessel ; and, if no direct canal-orifice of considerable size leads from the lumen of the lymphatic into the interior of the spherical follicle, a communication must, never- theless, be assumed to exist between the small h-mphatic and the lymph-follicle, and this is adequately provided by the innumerable spaces between the fol- licles. Thus, the h-mph-follicle is a true lymphatic structiire, whose fluid and lymph-cells can pass over into the stream of the adjacent 13-mphatics. The foUicles are provided, upon their surfaces, with a network of blood-vessels, which also send numerous delicate ramifications and capillaries through the interior of the follicle (A), within which they are supported by the retictilum (B). It is to be inferred that leukocj-tes can pass from these capillaries into the follicle. It should be mentioned as of special importance in connection with these follicles that, in the lymph-glands, the solitary as well as the Fig. 131. — A, blood-vessels of the ioIMde; B, the reticulum and a branch of a blood-vessel; C, lymph-follicle with retfcoluin aitd sheath. conglobate glands, an enormous migration of the leukocytes normally takes place uninterruptedly during life through the epithelium be- tween the cells. The leukocytes insinuate themselves between the epithelial cells, but, by their enormous migration, as well as by the divisions that take place during this process, they impair the functions of the epithelium and may even destroy it. Thus, in a measure, physio- logical injuries result, which prepare the wa}'" for invading microorgan- isms. The cells that have tlius migrated later undergo disintegration. The compound lymph-glands (incorrectly designated lymph-glands) repre- sent to a certain extent an aggregation of lymph-folhcles of altered shape. Every lymph-gland is surrounded externally by a connective-tissue capsule traversed by numerous unstriaed muscle-fibers, and from whose inner surface numerous septa and bands (Fig. 132, a a) penetrate into the interior of the body of the gland, and divide it into a large number of small compartments. The latter possess within the cortical s^abstance of the gland a rather rounded shape (alveoli), in the medulla, a rather longitudinal sausage-shaped form (medullar},- spaces) . All, however, are of the same significance and all are connected by commvinicating orifices. Thus, a rich network of cavities, connected in all directions, is formed within the lymph-gland by the septa. These spaces are traversed by the so- THE LYMPH-GLANDS. 36; called follicular bands (f f) . The latter represent to a certain extent the inner- most contents of the spaces, but in such a manner that they are smaller than the spaces and nowhere touch the walls of the cavities themselves. If the cavities of the gland be conceived as injected with a substance that at lirst has filled them all. but later, by contraction, is reduced to half its size, one will have an approxi- mate picture of the spatial relations of the follicular bands to the cavities of the gland. The follicular bands contain the blood-vessels (b) of the gland within them. About these there is deposited a rather thick cortex of reticular connective tissue, whose meshes (x) are extremely delicate and fine, whose spaces are rich in lymph-cells and whose surface (o o) is so constituted of the condensed reticulum- cells that a communication between the narrow meshes is still possible. Between the surface of the follicular bands and the inner wall of all the cavities Flo. 132. — Part of a Lymph-gland: .■\, afferent vessel; B, B, lymph-path within the cavity of the gland; a, a, column and septa bounding the ca\ity of the gland; f, f, foHicular band of the cavity; x, x, its reticulum; b, its blood-vessels; o, o, deUcate reticular junction between the follicular band and the Ijinph-paths. of the glands lie the paths of the lymphatics (B B) . Perhaps they are lined by an endothelium; their lumina are traversed by a rather coarse reticulum. The afferent-vessels (A), which spread out upon the surface of the gland, penetrate the external capsule and pass over into the lymph-paths of the glandular cavities (C). The efferent vessels, which exhibit large, almost cavernous anasto- moses and dilatations in the vicinity of the gland, arise at other parts of the gland directly from the Ivmph-paths. The latter, thus, to a certain degree represent a dense interlacing network of capillar}^ vessels, Ij-ing within the glandular cavi- ties, arranged between the afferent and efferent vessels. The movement of the Ij-mph on its way through the many-branched and tortuous lymph-paths of the gland will be retarded and. on account of the resist- ance to the current that the cellular elements, arranged in the paths, must offer, will possess feeble propulsive power. The lymph-corpuscles, lying in the meshes 366 PROPERTIES OF THE CHYLE AND THE LYMPH. of the reticulum, are carried onward by the lymph -stream, so that, after flowing through the glands, the lymph is richer in cells. The lymph-cells lying in the range of the follicular bands may again migrate through the narrow meshes of the reticulum (o) into the lymph-paths, to make good the loss. The formation of the lymph-cells in the follicular bands either takes place locally by division, or new cells migrate from the capillary blood-vessels into the follicular bands. Further on, the muscular activity of the capsule and of the trabeculae should not be underestimated in the movement of the lymph through the glands. Such muscular contraction will express the gland like a sponge. The direction of the fluid thus discharged is governed by the presence of valves within the related lymphatics. Of the chemical substances in the lymph-glands, in addition to those of the lymph, leucin and the xanthin-bodies are worthy of mention. PROPERTIES OF THE CHYLE AND THE LYMPH. Both chyle and lymph are colorless, albuminous, clear fluids, contain- ing lymph-cells. The latter are in reality the same elements that enter the circulation with the lymph-stream, and within the former are desig- nated white blood-corpuscles. The source of the lymph-cells is dis- cussed on p. 370. As, in rare cases, isolated red blood-corpuscles also pass out through the walls of the vessels and into the commencement of the lymph-vessels again, the presence of erythrocytes in the lymph, rarely in the chyle, is readily explained. Red blood-corpuscles can also pass over from the veins into the central extremities of the large lymph- trunks when the pressure in the veins is high. Lymph and chyle con- tain also molecular granules, and fragments of disintegrated leukocytes; chyle contains, in addition, numerous fat-granules. In the lymph a distinction is made between the lymph-plasma and the contained lymph-cells or leukocytes, whose chemical constituents are considered on p. 64. The lymph-plasma contains both of the fibrin- factors, derived from disintegrated lymph-cells. They cause coagulation of the lymph after withdrawal from the body, and in this process the soft, gelatinous, scanty lymph-clot, which forms but slowly, includes the still surviving lymph-cells within it. The fluid remaining, the lymph-serum, contains alkali-albuminates, serum-albumin and some diastatic ferment derived from the blood. Of the coagulable albumi- nates about 37 per cent, consist of paraglobulin. The chyle, which is the sole fluid contained in the lymphatic vessels of the digestive tract (lacteals), can be obtained only in small amounts, before its admixture with the lymph, and it can, therefore, be examined only with great difficulty. A small number of lymph-cells are already present in the first beginnings of the lacteals in the villi; beyond the intestinal wall and, still more, after passing through the mesenteric glands, their number increases. On the other hand, the amount of the solid constitu- ents of the chyle, which is increased after abundant good digestion, is decidedly diminished after the chyle has become mixed with lymph. After the ingestion of food rich in fat the chyle contains many fat-drop- lets (from 2 to 4 !>■ in diameter), which, however, decrease conspicuousl}'- in the further course of the current. The amount of fibrin-factors in the chyle increases with increase in the number of lymph-cells. In addi- tion, chyle contains sugar (up to 2 per cent.), glycogen, peptone adherent to the leukocytes, diastatic ferment absorbed from the intestine, and lactates after ingestion of starches, traces of urea and leucin. PROPERTIES OF THE CHYLE AND THE LYMPH. 367 The chyle from the body of an executed person contained, together with 90.5 per cent, of water: ( fibrin a trace t- . . ■ Carl Schmidt found the following inorganic constituents in 1000 parts of chyle from a horse: Sodium chlorid 5.84 Sulphuric acid 0.05 Magnesium phosphate 0.05 Sodium 1. 17 Phosphoric acid. . . .0.05 Iron a trace Potassium 0.13 Calcium phosphate. 0.20 The lymph, at the beginnings of the lymphatics, is likewise deficient in cells, and clear and colorless. The fluid from the serous cavities and synovial fluid exhibit similar features. A variation in the lymph, in accordance with the tissues from which it is derived, can with certainty be assumed, although, up to the present time, this has not been estab- lished. After passing through the lymph-glands, the lymph becomes richer in cellular elements and, probably in consequence of this, also richer in solid constituents, particularly proteid and fat. In one cu. cm. of lymph from a dog, 8200 lymph-corpuscles were counted. Hensen and Dahnhardt succeeded in collecting for examination pure lymph in considerable amount from a lymphatic fistula on the thigh of a human being. It had an alkaline reaction and a salty taste. The relative composition of pure lymph, cerebrospinal fluid and pericardial fluid is as follows : Pure Lymph. Cerebrospinal Fluid. Pericardial Fluid. (Hensen and Dahnhardt.) (Hoppe-Seyler.) (v. Gorup-Besanez.) Water 98.63 98.74 95-5i Solids 1.37 1.25 4.48 Fibrin o.ii — 0.08 Albumin 0.14 0.03 — 0.06 2.46 Alkali-albuniinate 0.09 — — Extractives — 1.26 Urea, leucin 1.05 Salts 0.88 Absorbed carbon dioxid, The cerebrospinal lymph contains a substance to 70 per cent, by volume, that reduces Fehling's solution, and that Naw- of which 50 per cent, could ratzki determined to be dextrose. This, how- be obtained by extraction ever, disappears soon after death, and 20 per 'cent, was ob- tained by addition of acid. 100 parts of lymph-ash contain: Sodium chlorid. . . .74. 48 Calcium 0.98 Sulphuric acid 1.28 Soditun 10.36 Magnesia 0.27 Carbon dioxid 8.21 Potassium 3.26 Phosphoric acid. . . . 1.09 Iron oxid 0.06 Just as in the case of the blood, potassium and phosphoric acid, of the inorganic constituents, predominate in the cells; while in the lymph-serum, sodium preponderates, principally as sodium chlorid. Only in the cerebrospinal fluid are the potassium-combinations and the phosphates said to predominate. The amount of water in the lymph rises and falls in correspondence with that in the blood. Of gases, dog's lymph contains carbon dioxid in abundance (over 40 per cent, by volume, of which 17 per cent, can be pumped out and 23 per cent, can be removed by acids), traces of oxygen and 1.2 volumes per cent, of nitrogen. 368 QUANTITATIVE RELATIONS OF LYMPH AND CHYLE. QUANTITATIVE RELATIONS OF LYMPH AND CHYLE. It is estimated that the total amount of lymph and chyle introduced into the circulation through the large lymph-trunks in twenty-four hours equals the total volume of the blood. Of this one-half will be contributed by the chyle, the other half by the lymph. The secretion of lymph in the tissues takes place without interruption. From a lymphatic fistula on a woman's thigh, about 6 kilograms of lymph were collected in twenty- four hours. In voung horses, the amount of lymph collected from the large l5^mph-trunk of the neck in from one and one-half to two hours measured between 70 and more than 100 grams. The following influ- ences affect the amount of chyle, as well as that of lymph. _ The amount of chyle increases considerably during digestion, espe- cially if the quantity of food taken has been large, so that the vessels of the mesentery and the intestine will at this time be constantly found filled with white chyle. In the state of hunger the vessels are collapsed and can be recognized with difficulty. The amount of lymph increases especially with the activity of the organ from which it flows. Thus it was found that active and passive muscular movements increase the amount of lymph considerably, almost five-fold in the horse. Lesser obtained more than 300 cu. cm. of lymph in this manner from fasting dogs, in consequence of which, with inspis- sation of the blood, the animals became exhausted, to the point of death. All agencies that increase the pressure to which the parenchymatous fluids of the tissues are subjected increase the amount of lymph secreted, and conversely. Of this the following observations are illustrative: (a) An increase in blood-pressure, not alone in the entire blood-vessel system, but also in the vessels of the part in question, causes increase in the amount of lymph, and conversely. (b) Ligation or compression of the efferent veins causes considerable increase in the amoimt of Ij^mph given off by the parts in question, even more than double, because the escape of fluid is confined to the lymphatic vessels. The applica- tion of tight bands is also a cause for swelling of the parts to the peripheral aspect of the application, as copious effusion of lymph takes place into the tissues — hypo- static edema. (c) An increased supply of arterial blood acts in a similar manner, but less powerfull3^ In this connection paralysis of the vasomotor or irritation of the vaso- dilator fibers ma}^ cause an increase in the amount of lymph b}^ creating marked hyperemia. The process of dilatation favors the production of lymph in greater degree than permanent distention of the blood-vessels. Contraction of the arterial paths as a result of irritation of the vasomotor nerves or from other causes will naturally have the opposite result; but even after ligation of both carotids, the lymph-current in the large cervical tnmk of the dog by no means ceases, as the head is still supplied with blood in small amount by the vertebral arteries. If, after unilateral division of the sympathetic nerve, the blood-vessels of the ear are dilated, indigo-carmine, injected into the blood, enters earliest and in greater degree into the lymph of this ear; the latter also becomes decolorized earlier than the healthy ear. In this way the rare instances of tmilateral or partial icterus are to be explained. An increase in the total volume of blood as a result of injection of blood or serum into the veins causes increased formation of lymph, as, in consequence of the increased tension thus induced, blood-plasma passes over into the tissues in large amount. If water or a hypotonic salt-solution be infused, water passes out into the tissues. After death and complete rest of the heart, the formation of lymph still goes on for some little time, although in slight degree. If fresh ORIGIN OF LYMPH. 369 blood be then passed through the ainnial's 1)od3^ still warm, mcreased lymph will in turn flow from the large lymph-trunks. It thus appears that the tissues are still capable of taking up plasma from the blood for the production of lymph for some time after cessation of the circula- tion. This fact may explain the circumstance that some tissues, as, for example, the connective tissue, appear to contain more fluid after death than during life, while, at the same time, the blood-vessels have after death given up much of the plasma from their interior. Under the influence of curare an increase in the secretion of lymph takes place ; the amount of the solid constituents of the lymph increasing. In the frog large amounts of lymph collect in the lymph-sacs, and this may be due in part to the fact that the lymph-hearts are paralyzed by curare. The production of lymph is increased also in the tissues of inflamed parts. ORIGIN OF LYMPH. SOURCE OF LYMPH-PLASMA. The lymph-plasma is, in part, a filtrate from the blood-vessels, passing over into the tissues, in accordance with the prevailing blood-pressure. In this process, the salts (penetrating membranes most readily) pass through admixed in approximately the same proportions as the salts in the blood-plasma; the fibrin-factors, to about two-thirds; the albumin, about one-half. As in the case of filtration in general, the filtration of lymph also must increase with increased pressure. C. Ludwig and Tomsa were able to demonstrate this by permitting blood- serum to pass through the blood-vessels of an excised testicle under varj'ing pressure, with the result that the transuded fluid from the lymph- vessels was increased or diminished in amount. This artificial lymjjh exhibited a composi- tion similar to that of natural lymph. The albumin contained in the lymph also increased with increasing pressure. In addition, the metabolic products of the tissues, concerning whose qualitative and quantitative conditions little is known, naturally undergo admixture with the lymph-plasma in the different tissues. In part, however, the formation of lymph must be regarded as a secretory process of the cells of the blood-capillaries. In favor of this view is the fact that materials injected into the blood (sugar, egg-albumin, peptone, urea and sodium chlorid) jjass in concentrated form into the increased Ij-mph ; further, that the blood is capable of maintaining the osmotic tension of its plasma. As a result of this secretory property on the part of the endothelium of the vessels, substances that would disturb the isotonia between the blood-corpuscles and the blood-plasma are quickly eliminated from the blood, including superfluous water. After the injection of peptone, the blood-pressure falls enormously, so that the passage into the lymph cannot be dependent upon this pressure. With increase in the lymph-current, the secretion of urine also is later increased. The lymph-paths may thus be considered as a reservoir that temporarily takes up out of the blood the substances to be eliminated, whence they are then gradually further consumed or excreted. According to Heidenhain, there are materials that increase lymph-production, lymphagogucs, which are in part effective by causing the passage of fluid from the blood into the lymphatic radicles. Among such agencies are injections into the blood of a decoction of leeches, crab-muscles, mussels, solution of nuclein, tuberculin, bacterial extracts, bile, physostigmin, pilocarpin and extract of helian- thus. In part they increase the amount of lymph by causing the passage of water from the tissues into the lymph. In this' category belong injections into the blood of sugar, urea and salts. Atropin diminishes lymph-production. 24 37© SOURCE OF THE LYMPH-CELLS, Muscular activity causes increased lymph-production, as well as a more rapid escape of the lymph. The tendons and fasciae of the skeletal muscles, which possess numerous small stomata, absorb lymph from the muscular tissue. With alternate contraction and relaxation of these fibrous tissues, their lymph-ducts suck themselves full and propel the lymph onward. Even passive movements are effective in this direction. If solutions are injected beneath the fascia lata, they can be propelled onward by passive movements, contraction and relaxation, into the thoracic duct. SOURCE OF THE LYMPH-CELLS. A considerable portion of the lymph-cells are derived from the lymph- glands, out of which the lymph-stream washes them into the efferent ves- sel. Therefore it happens that the lymph-stream, after passing through the lymph-glands, is always found richer in lymph-cells. Within the lymph-glands there are large and small lymphocytes, the latter being the daughter-cells of the former, and arising by mitosis. In addition, new leukocytes are constantly migrating from the blood-capillaries of the follicular bands into the reticulum. The lymphatic follicles permit cellular elements to enter through the meshes of their limiting layer into the adjacent small lymph- vessels. A second seat of lymph-cell production is found in the organs contain- ing adenoid tissue as a basis, in the meshes of which lymph-cells are found in large number, such as the entire mucous membrane of the intestinal tract, the bone-marrow and the spleen. The cells reach the radicles of the lymph-vessels in these organs by ameboid movement. Just as the lymph-cells reach the circulation through the large trunks and are there encountered as white blood-corpuscles, so, likewise, numerous leukocytes migrate in turn from the blood-capillaries into the lymph- vessels, especially in their small beginnings, and partly by active ameboid movement, partly by being forced by filtration-pressure exerted by the blood-column. In rare cases even a return movement of lymph- cells from the lymph-spaces into the blood-vessels has been observed. Also particles of cinnabar or milk-globules introduced into the blood reach the lymph- vessels from the blood-capillaries in a short time; the nerves of the vessels having no influence in this condition. In case of venous stasis, in analogy with the processes attending diapedesis, this passage takes place more freely than when the circulation is unembarrassed. Inflammatory changes in the vessel- wall also favor the passage. The vessels of the portal system prove especially permeable. New lymph-cells result also through multiplication by division of the lymph-corpuscles, and likewise of the so-called fixed connective-tissue cells, as has been demonstrated with certainty especially in the pres- ence of inflammation of certain organs. If irritants which excite inflam- mation are applied to the excised cornea, kept in a moist chamber, a large increase in the wandering cells in the anastomosing lymph- passages of the cornea will be noted; and as, in the inflamed cornea, the corneal cells permit the recognition of a reproduction of their nuclei by division, the conclusion is probably justified that a division of the corneal corpuscles (fixed connective-tissue cells) is responsible for the increase in the wandering cells. That a new-formation of leukocytes must take place by division, as well as by the setting free of divided connective-tissue cells, is shown by their often CIRCULATION OF CHYLE AND LYMPH. 371 enormous production in the presence of inflammations (pus-formation), particu- larly in the case of extensive phlegmons and purulent effusions in the serous cavities, when by reason of their enormous number, they cannot be regarded as having resulted solely by migration from the circulation. The destruction of the lymph-cells appears to take place in part at the seats of origin of the vessels and in the vessels themselves. The occurrence in the lymph of the fibrin-factors, which are derived from disintegrated leukocytes, tends to support this view. Particularly in the presence of severe inflammation, especially in connective tissue, the new-formation of numerous lymph-cells appears to be attended with their increased destruction. Therefore the lymph under such circum- stances becomes especially rich in fibrin, and, naturally, also the blood, through the lymph. According to Hoyer, the lymph-glands are also filtering apparatus in which degenerating leukocytes are intercepted and subjected to a destructive meta- morphosis. CIRCULATION OF CHYLE AND LYMPH. The cause for the movement of the chyle and the lymph depends ultimately on the difference in pressure prevailing between the lymphatic radicles and the points at which the lymphatics empty into the venous system. In detail the following facts are noteworthy : In the onward movement of the lymph, forces are primarily active that are of influence at the points of origin of the lymphatics. These forces must vary in accordance with the character of the points of origin, (a) The lacteals receive the first motile impulse through the contraction of the muscles of the villi. Inasmuch as these grow shorter and smaller, they constrict the axial lymph-space, whose contents must m.ove in a centripetal direction. With the succeeding relaxation of the villus, the numerous valves prevent the chyle from flowing backward. With con- striction of the lumen of the intestine, through contraction of the in- testinal muscles, the villi are forced more closely together longitudinally, the evacuation of the central lymph- vessel being likewise favored, (b) Within those lymph- vessels that originate as perivascular spaces, every dilatation of the blood-vessels must cause a movement of the surrounding lymph-stream in a centripetal direction, (c) Lymph enters the open lymph-pores of the pleura with each inspiratory movement, which excites suction upon the thoracic duct. A similar condition exists at the orifices of the lymph-vessels on the abdominal aspect of the diaphragm- atic peritoneum. The blood-vessels participate principally in absorption from the abdominal cavity, the lymphatics relatively little. If serous fluid or a solution of salt or sugar is introduced into the abdominal or pericardial cavity, it will be absorbed, and, if isotonic with the blood- plasma, without change; if it is not isotonic, it will first be made isotonic by elimination from the blood. Accordingly, osmosis cannot be alone the active agency in the process of absorption, as imbibition contributes some influence. If the intra-abdominal pressure increases, the blood-vessels absorb more freely, but with excessively high pressure less freely, in consequence of compression of the abdominal veins. In this manner is explained the clinical observation that, in the presence of ascites, absorption is often promoted after the abdominal tension is 37 2 CIRCULATION OF CHYLE AND LYMPH. diminished through removal of a moderate amount of fluid, (d) In those vessels that arise by means of fine secretory canaliculi, the move- ment will depend directly on the tension of the parenchymatous fluids, and the latter, in turn, upon the tension in the blood-capillaries. Thus the blood-pressure will still be active as a force from behinde ven into the lymphatic radicles. In the lymph-trunks themselves, the contractions of their mus- cular walls propel the current onward. Heller noted, in the lymphatics of the mesentery of the guinea-pig, that this movement was peristaltic in an upward direction. The large number of valves prevent a back- ward current. In addition, the contractions of the surrounding muscles, further, any pressure upon the vessels and the tissues as the seat of origin of the lymphatic radicles will force the current onward. If the escape of blood from the veins is rendered difficult, lymph is poured out more abundantly from the tissues in question. The interposed lymph-glands offer considerable resistance to the current, as the lymph must flow through numerous spaces, traversed by fine meshes and partially filled with cells. Nevertheless the obstacles thus presented are in part compensated for by the numerous unstriated muscles that are present in the sheath and the trabeculse of the glands. By means of these, compression of the glands (as of a sponge) can take place, the presence of the valves again determining the centripetal direction of the current. From this point of view electrical stimulation of swollen lymph-glands might be successful. With the union of the vessels into a few of considerable size, and finally to form the main trunk, the sectional area of the current becomes diminished, and the velocity of the current correspondingly increased. Nevertheless, the velocity under such circumstances is always low, reaching only from 238 almost to 300 mm. in a minute in the main cervical lymph-trunk in the horse, a fact that is indicative of the exceedingly slow movement of the lymph in the small vessels. The lateral pressure in the same situation was from 10 to 20 mm.; in the dog only from 5 to 10 mm. of a dilute soda-solution, but in the tho- racic duct of a horse it was 12 mm. of mercury. The time required for the passage of the lymph through the walls of the capillaries of the abdomen or of the lower extremity, is about 2 minutes in the dog; for the propulsion of the lymph through the lymphatics of the lower ex- tremity and of the trunk, 3.2 seconds. The respiratory movements have an important influence upon the lymph-stream in the thoracic duct and the right lymphatic duct, as each inspiration conveys the current of lymph, together with venous blood, to the heart, and as a result the tension in the thoracic duct may even become negative. Lymph-hearts.— The lymph-hearts containing valves found in some ani- mals, particularly cold-blooded animals, are deserving of consideration. The frog possesses two axillary hearts (above the shoulder near the vertebral column) and two sacral hearts (above the anus near the apex of the sacrum). They beat, though not synchronously, about 60 times in the minute and contain about 10 cu. cm. of lymph. They contain striated muscle-fibers and are provided with special ganglia. The posterior hearts pump the lymph into the branches of the communicating iliac vein, the anterior into the subscapular vein. Their pulsation depends in part on the spinal cord, for, as a rule rapid de- struction of the cord causes cessation of the heart-beat, but pulsations are not rarely observed to continue after removal of the cord. A second normal source ABSORPTION OF PARENCHYMATOUS EFFUSIONS. 373 of excitation of the l\in])h-hcarts is to be souj^ht in Waldeyer's ganglia. Irrita- tion of the skin, ihv intestine and the blood-heart gives rise to a reflex influence, partly acceleration, partly retardation of the beat, which does not affect the sacral heart if the coccygeal nerve, which connects the posterior lymph-heart with the spinal cord, is divided. Strychnin-convulsions accelerate the Deat, as does also irritation of the spinal cord by heat, while it is diminished by cold. The heart that has ceased to beat in consequence of exposure or of the action of muscarin, l)ut not resting in consec^uence of destruction of its nerves, can be excited to renewed pulsation by increased lilling. Antiar paralyzes the lymph-hearts and the blood- heart: curare, the former only. In other amphibians, two lymph-hearts have been found: and one or two in the ostrich and the cassowary, in some web-footed birds, as well as in the chicken-embryo; in fish they have been found in the tail, as, for exainplc, in the eel, where their pulsation visibly affects the adjacent veins. The nervous system has a direct influence upon the movement of the lymph through innervation of the muscles of the lymphatics, the lymph-glands, and, when they exist, the lymph-hearts. In addition, there are still other special effects of the nerves upon the absorptive activity of the lymphatic radicles. Kiihne noted, after irritation of the corneal nerves, that the corneal cells contracted within their secretory canaliculi. The following observation by Goltz is also interesting in this connection. When this investigator injected a dilute solution of sodium chlorid subcutaneousl}' into the lymph-spaces, he saw that it was rapidly absorbed; it remained unabsorbed, however, after destruction of the central nervous system. Division of the nerves to the extremities also resulted, temporarily, in retarding the absorption. If inflammation was excited in both posterior extremities of a dog, marked edema, together with acceleration of the lymph-stream, appeared in the one in which the sciatic nerve had been divided. If the thigh of a frog is tightly constricted until the circulation ceases, the nerve being preserved, and the part is immersed in w^ater, it becomes greatly swollen (the dead thigh does not swell) ; whence it follows that absorption takes place independently of the existence of the circulation. Division of the sciatic nerve or crushing of the spinal cord (though not mere transverse section or separa- tion of the brain) abolishes absorption. ABSORPTION OF PARENCHYMATOUS EFFUSIONS. Fluids that transude into the tissue-spaces from the blood-vessels, or those that are injected into the parenchyma through a needle, undergo absorption. In this process the blood-vessels participate primarily, and the lymphatics also secondarily. Into the latter, there pass from the clefts and secretory spaces in the connective tissue, even small particles, as, for example, granules of cinnabar and India ink after tattooing of the skin, blood-corpuscles from hemorrhagic extravasations and fat-droplets from the marrow of fractured bones. If all the lymphatics of a part be ligated. absorption still takes place just as rapidly as before. Therefore, the absorbed fluid must have passed through the delicate membranes of the blood-vessels. The opposite observation, that no absorption of parenchymatous fluids takes place after ligation of all the blood-vessels, does not exclude a participation of the lymphatics in the process of absorption, because, after ligation of all of the blood-vessels, naturally all formation of lymph in the tissues, and consequentlv any lymph-current, must cease. The absorption of fluids introduced into the tissues artificially, particularly in the subcutaneous cellular tissue (parenchj-matous and subcutaneous injection), generally takes place rapidlv, as a rule more rapidlv than after administration by the mouth. There- fore, s'ubcutaneous injections of drugs in solution are much employed for thera- peutic purposes. Naturally the substances to be injected should not have a destructive, corrosive or coagulating effect upon living tissues. In addition to the great rapiditv of absorption, subcutaneous injection has the further advantage over the adminis'tration of a drug bv the mouth that some agents that are ingested undergo decomposition in the stomach and intestine as a result of the digestive 374 LYMPH-STASIS AND SEROUS EFFUSIONS. process, so that they cannot at all be absorbed unchanged. Thus, particularly poisons that act through ferments, such as snake-venoin, ptomains and putrid poisons, are destroyed by the stomach. Emtxlsin also behaves in the same manner. If this ferment is introduced into the stomach while amygdalin is injected into a vein of the same animal, poisoning by hydi-ocyanic acid does not take place, because the emulsin is destroyed by the digestive process. If, however, emulsin is injected into the blood and amygdalin into the stomach, h3-drocyanic-acid poison- ing takes place rapidly, because amygdalin is absorbed unchanged from the stomach. Amygdalin is a glucosid (CjnHjjNOii) that breaks up as a result of the fermentative activity of fresh emulsin with the taking up of water, 2(H;0), into hydrocyanic acid (CHN), oil of bitter almonds (CtHcO) and sugar, 2(C6Hi20(,). For observations on animals on the absorption of solutions from the parenchyma- tous structitres, either poisons whose action gives rise to conspicuous tonic symp- toms, or such harmless substances as are readily discoverable in the blood and subsequently especially in the urine are employed, as, for example, potassium ferrocyanid. The author, in 1878, demonstrated that serum, injected into the subcuta- neous tissue, is rapidly absorbed. The serum, which must be obtained from an animal belonging to the same species or at least as indifferent as possible, undergoes decomposition in the circulation, so that the production of urea in- creases. Infusions of serum may, therefore, be given for nutritive purposes. Febrile reaction is observed after such injections, as in the case of transfusion. Solutions of albuinin and peptone, oil, butter, dextrose, levulose, galactose and maltose in solution have also been observed to midergo absorption. LYMPH-STASIS AND SEROUS EFFUSIONS. If obstruction to the efferent venous and lymphatic paths of an organ arises, stasis results, and later abundant effusion of lymph into the tissues. This is most distinctly recognizable in the skin and the subcutaneous tissue, where the soft parts become swollen; while, without redness and pain, tumefaction develops, with a doughy feeling, and pressure with the finger causes pitting. These are the signs of lymph-stasis, which, if the fluid is especially rich in water, is designated by the term edema. Also within the serous cavities, under like conditions, a similar collection of lymph takes place. If numerous leukocytes inigrate from the delicate blood- vessels into such serous cavities and undergo multiplication, the fluid, richer in cells, becomes more and more like pus. The multiplication of these cells gives rise to the presence of a considerable amount of albumin, which may subsequently be increased by absorption of water from the effusion. The latter will be made particularly easy when the pressure in the fluid exceeds that in the small blood- vessels. These sero-piirulent effusions not rarely tmdergo a change in constitu- tion later on, for which no reason has been found. The substances present are in part prodticts of the decomposition of albumin, such as leucin and tyrosin, in part products of the retrogressive metamorphosis of nitrogenous substances, such as xanthin, kreatin, kreatinin (?), uric acid (?) and urea. Further, endo- thelial cells from the serous cavities; sugar in pathological serous and chylous effusions and edematous fluid have been fotmd; in the latter also diastatic fer- ment, often cholesterin; and in the fluid of serous hydrocele and echinococcus- cysts, succinic acid. Not only the pressure from without upon the Ij-mphatics, but, in general, resistance of any kind that is present in the lymph-path may give rise to l^-mph- stasis and serous effusions. Thus, Ij^mph-stasis results from occlusion of the lymph- atics in consequence of inflammation and thrombosis (lymph-coagulation) ; further, as a result of impermeable, swollen, inflamed or degenerated lymph-glands. In these cases, however, the formation of new 13'mph-vessels is frequently ob- served, reestablishing the former communication. An effusion of h-mph may also take place into the serous cavities of the abdomen or the thorax, from rup- ture of large lymph-paths, especially of the thoracic duct — chylous ascites or chylothorax. Interference with or even removal of all those factors that have been found active in propelling the lymph onward will be capable of inducing lymph-stasis. If stagnation of lymph can develop in this manner also on the part of the lymphatic apparatus, the appearance of considerable amounts of watery lymph, in the form of edema or anasarca, as well as of serous effusions, is often at the same COMPARATIVE. 375 time due to the fact that a copious transudate is furnished on the part of the blood- vessels. Obstruction in the distribution of the lymph-stream may then further increase such a collection of fluid. Particularly the vessels of the abdomen and, further, those that furnish a watery exudation also under normal circumstances appear, aliove all others, to be especially adapted to transudation. Such increase in transudation is favored by (i) any considerable degree of venous stasis. These hypostatic transudates are, as a rule, deficient in albumin and leukocytes, but, on the other hand, the richer in erythrocytes the greater the interference with the flow of venous blood. Ranvicr induced hypostatic edema artificially in the lower extremity by ligatioii of the inferior vena cava and simultaneous division of the sciatic nerve. The paralytic dilatation of the vessels of the posterior extremity, induced by the latter, causes an increase in the amount of blood present and a rise in the blood-pressure, which, in turn,. promotes edematous exudation. (2) Further, as yet unknown physical changes in the protoplasm of the endothelial cells of the blood-vessels and capillaries may render these capable of permitting the abnormal passage of albu:nin, heinogloljin and even blood-cells. This takes place when foreign matters are present in the blood in considerable amount, as, for example, hemoglobin in solution; further, when the blood is deficient in oxygen or albumin. Also after exposure to abnormal heat, a similar condition has been observed, and the tumefaction of the soft parts in the vicinity of inflamed tissues likewise appears to be due to an exudation of lymph through altered vessel-walls. Perhaps a nervous influence, which makes itself felt in a certain vascular area (by contraction or relaxation of the protoplasm of the blood-capil- laries ?), may even be capable of catising such a transitory change in the vessel- walls. Lymphatic transudates of this character are generally rich in cells and consequenth'' also in albumin. (3) Further, the presence of a large amount of water in the blood will increase its capacity for transudation. Nevertheless, the fact should be considered in this connection that the large amount of water contained in the blood acts, in turn, by inducing changes in the protoplasm of the endothelium of the blood-vessels and capillaries, so that it is itself, when long continued, a factor that increases the permeability of the vessel-walls. Debilitated, poorly nourished, flabby individuals particularly exhibit watery lymphatic exudations from watery blood — cachectic edema. There is no doubt that lymph-stasis (hydrops) may develop also under cer- tain circumstances, and even through the action of microorganisms (bacterium lymphagogum) , in consequence of the fact that irritation of the cells of the blood- capillaries (as by the products of metabolism of that organism) gives rise to increased exudation of fluid. COMPARATIVE. Extensive lymph-spaces, lined with endothelium, are present in the frog, beneath the entire external integument. In addition, a large lymphatic space, the cysterna lymphatic magna of Panizza, extends in front of the vertebral column, separated from the abdominal cavity by the peritoneum. Tailed amphibia, as well as many reptiles, have large lymph-spaces beneath the skin, occtipying the entire length of the trunk in the lateral regions of the back. Further, all reptiles and the tailed amphibia possess, in the covirse of the aorta, large, longi- tudinal lymph-reservoirs. Tortoises likewise have an extensive lymphatic ap- paratus (Fig. 130, A, II). The bony fish have longitudinal lymph-trunks in the lateral regions of the back, from the tail to the anterior fins, and these are connected u-ith dilated lymph-spaces at the root of the tail and the fins of the extremities. Within the interior of the body the extensive lymph-sinuses attain their greatest development in the region of the gullet. Many birds possess a sinus-like dilatation of a lymph-space in the region of the tail. In the caniivora the mesenteric lymph-glands are united to form a large, compact mass, the so- called pancreas of Aselli. Naturally the lymph-spaces (provided with valves) always communicate with the venous system, and usually with the territory of the superior vena cava. HISTORICAL. Although the lymph-glands were known to the school of Hippocrates, espe- cially through their morbid enlargement, and although Herophilus and Erasistratus had observed the milk-white chyle-vessels in the mesentery, Aselli (1623) was the 37^ HISTORICAL. first to study the mesenteric ch^ie-vessels more thoroughly, together with their valves. Pecquet (1648), as a student, found the receptacle for the chyle, Rudbeck and then Thorn. Bartholinus the clear, watery lymph-vessels (1650-1652). Eus- tachius (1562) was familiar with the thoracic duct, which Gassendus (1654) later claimed to have been the first to discover. Lister noticed that chj'le was colored blue after the injection of indigo into the intestine (167 1). Rudbeck (1652) observed the separation of fibrin in the lymph; Reuss and Emmert(iSo7) were the first to obser^-e the lymph-corpviscles. The chemical examinations date from the first quarter of the nineteenth centur}-, and were made by Lassaigne, Tiedemann, Gmelin and others, of whom the latter also recognized the fact that the white color was dependent upon the fat-granules. PHYSIOLOGY OF ANIMAL HEAT. SOURCES OF HEAT. The heat of the body is a form of kinetic energy appearing without interruption and must be conceived as depending upon vibrations of the atoms of the body. In the last analysis every source of heat is contained in the mass of potential energy taken into the body as food, in combination with the oxygen obtained from the air in the act of respiration. The amount of heat liberated depends upon the amount of potential energy transformed. The potential energy of nutrient matters may be appropriately desig- nated as latent heat, inasmuch as it may be conceived that in their consumption in the body, which is essentially a process of combustion, kinetic energy is transformed only in the form of heat. As a matter of fact, mechanical energy and electricity are also developed from the potential energy supplied. However, in order to obtain a uniform measure for the forces transformed, it is advisable to express all potential energy in terms of heat-units. The calorimeter is an apparatus with the aid of which the amount of potential energy contained in food-stuffs can be converted experimentally into heat and the units of the latter can at the same time be measured. Favre and Silbermann employed the so-called water-calorimeter (Fig. 133). A cylindrical box, the so-called combustion-chamber (K), serves for the recep- tion of the substance to be burned. This box is suspended in a larger, cylindrical vessel (L), which is filled with water (w), so that the combustion-chamber is completely surrounded thereby. Three tubes enter into the upper portion of the chamber: one (O) is intended for the passage of air containing oxygen, which is necessar}^ in the process of combustion. The second tube (a) in the middle of the cover is closed above with a thick glass plate, upon which is mounted at an angle a mirror (s) , which permits the observer (B) to look into the interior of the chamber from a lateral point of view in the direction b b. in order to observe the process of combustion at c. The third tube (d) is employed only when it is desired to consume combustible gases in the chamber and through it these are then passed. Generally this tube is closed by a cock. A lead pipe (e e) also passes out of the upper portion of the chamber and in a convoluted arrangement traverses the volume of water, finally reaching the surface at g. Through this the gases of combustion escape, being cooled in the convoluted tube to the tem- perature of the water. The cylindrical vessel containing the water is covered with a lid having open- ings for the four tubes that pass through it. The water-cylinder stands upon legs within a larger cylinder (M) , which is filled with a poor conductor of heat. Finally this is placed in a still larger cylinder (N), which again contains water (W) . This last layer of water is intended to prevent any heat from the exterior from raising the temperature of the water in the interior. A definite amount of the material to be examined is burned in the combustion-chamber. After com- bustion has been completed, during the progress of which the water in the interior is repeatedly stirred, the temperature of the water is determined by means of a delicate thermometer. If the amount of increase in temperature is noted, and if the amount of water in the inner cvlinder is known, the number of heat-units furnished by the combustion of the' measured amount of the substance under examination can be readilv estimated. 377 378 SOURCES OF HEAT. Instead of the water-calorimeter the ice-calorimeter may be employed. Iri this instrument the inner container is surrounded with ice instead of with water. Around this in a second container is still more ice, which prevents any heat from without acting upon the ice in the interior. The body in the interior cham- ber gives off heat and causes a portion of the surrounding ice to melt, while the ice-water passes off below through a tube and is measured. In this connection it should be noted that 79 heat-units are required to melt i gram of ice into i gram of water at a temperature of 0° C. For animal experimentation the calor- imeter has probably reached the highest grade of perfection at the hands of Rubner. The air-calorimeter of d' Arson val permits of measurement in human beings within a few minutes. A rigid cylinder of woolen material, within which a man may stand, is provided above with a chimney. If the man heats the air in the interior, this will escape through the chimney and set in motion a small wind- mill contained therein, whose revolutions can be counted. The amount of heat given oft" is proportional to the square of the velocity of the escaping cur- rent of air. A man in the nude state yielded 124, and in the dressed state 79 calories in an hour. Just as in the calorimeter, though much more slowly, nutrient mat- ters are consumed in the human body with a supply of oxygen, and as a consequence there takes place a transformation of potential into kinetic energy, which in a person at rest appears almost wholly as heat. Favre and Silbermann, Frankland, Rechenberg, Stohmann, B. Danilewsky, Rubner and others have made calorimetric observations as to the amount of heat yielded by the combustion of many nutrient substances. One gram of water- free substance yields in heat-units as follows: CARBOHYDR.\TES. Proteids on the average 57 n Galactose, 3722 Serum-albumin, 5918 Cane-sugar, 3955 Egg-albumin, 5735 Milk-sugar 3952 Syntonin, 5908 Maltose, 3949 Hemoglobin, 5885 Glycogen 4191 Milk-casein, 5858 Starch 4183 Yolk of egg, 5841 Cellulose 4185 Vitellin, 5745 Cow's milk, 5613 ]VIgat ^^ 5663 Woman's milk 5786 ' t 5641 Rye-bread, 4471 Peptone, 5299 Wheat-bread, 4351 Fibrin, 5637 Peas 4889 Vegetable fibrin, 5942 Buckwheat, 4288 Legumin 5793 Maize, 5188 Conglutin 5479 Alcohol, 6980 Muscle-extractives, 4400 Animal fats on the average 9500 Liebig's meat-extract, 3216 Butter 9231 (Prmcipally according to Stoh- Olive-oil ( 9467 mann). I 9608 Rape-oil \ 9627 Urea 2537 ^ I 9759 Glycm, 3128 Stearic acid, 2712 Leucin, 6533 Oleic acid, 2682 Hippuric acid 5678 Palmitic acid, 2398 Kreatinin, 4275 Glycerin, 397 Uric acid, 2741 Alcohol, 7100 As the proteids in the body are not transformed beyond urea the amount of heat resulting from the combustion of urea is to be deducted from that resulting from the combustion of the proteids. As one gram of proteids (average calories 57 11) yields 0.3428 gram of urea, and i gram of urea yields 2537 calories, S70 calories are to be deducted. Isodyiiamic food-stuffs, namely, those that yield the same amount of heat in the process of combustion, are as follows: 100 grams of animal proteid, after deduction of the heat resulting from the combustion of urea, equal 52 grams of fat, 114 grams of starch, 128 grams of dextrose. One hundred grams of fat are SOURCES OF HEAT. .379 isodynamic with 243 grams of dry meat or 225 grams of dry syntonin, or with 256 grams of dextrose. According to Pfluger, i gram of nitrogen in meat equals 2.79 grams of fat; i gram of animal fat equals 0.364 gram of nitrogen in meat; I gram of starch equals 0.424 gram of fat or 0.154 gram of nitrogen in meat; i gram of grape-sugar equals 0.390 gram of fat or 0.42 gram of nitrogen in meat; 100 grams of vegetable albumin likewise equals 55 grams of fat or 121 grams of starch or 137 grams of dextrose. Rubner estimates in human beings on a mixed diet the available heat-pro- ducing energy for i gram of proteid at approximately 4100 calories, for i gram of fat 9300 calories, for i gram of carbohydrate 4100 calories. For the dog Rubner determined that i gram of nitrogen in the excreta of the fasting animal had caused the production of 25,000 calories; further, that i gram of nitrogen in the excreta with a meat-diet had produced 26,000 calories; and i gram of carbon, formed from 1.3 grams of fat, had yielded 12,300 calo- ries. If it be known, therefore, how many parts by weight of the foregoing substances a human being takes up with his food during twenty-four hours, the calculation can be made as to how many heat- units he may generate there- from through oxidation. In this connection the utiliza- tion of the nutrient materials must be taken into consider- ation, in accordance with which a certain, even though small, percentage of the food cannot be disposed of by the digestive and absorptive or- gans, and therefore is ex- creted unused. Rubner found that, however abtmdant the administration of food, a larger amotint of heat can be shown to be produced immediately on the first day of feeding, as compared with the preceding days of fasting. The bodily temperature under such circumstances remains unaltered. The greatest amount of heat is produced as a result of excessive administration of proteids, less from carbohydrates and least from fats. In detail the sources of heat are as follows : I. The transformation of chemical coinbinations of foods with high potential energy into those of lesser or completely exhausted potential energy. As the organic articles of food, exclusive of the inorganic accompaniments, consist of C, H, N and 0, it is especially through (a) the combustion of C into CO2 and of H into H,0 that heat is produced. In this connection it is to be noted that the combustion of i gram of C into CO2 yields 8080 heat-units, while that of i gram of H into HoO yields 34,460 heat-units, though the C and H in the molecules of the food-stuffs must not already be saturated with O. The amount of O necessary for this purpose is taken up in the act of respiration. There- Fic. 133. — Water Calorimeter (after Fa\Te and Silberir.ann). 380 SOURCES OF HEAT. fore an approximate estimate may be made as to the quantity of heat produced by an organism from the amount of oxygen consumed in a unit of time. An equal consumption of O corresponds with an equal production of heat, whether it served for the oxidation of H or of C. As a matter of fact, a relation exists between heat-production in the animal body and the consumption of 0, as between cause and efifect. Thus, cold-blooded animals, which consume little O, have a low bodily temperature. Among warm-blooded animals i kilogram of living rabbit takes up 0.914 gram of O within an hour and by this means maintains its bodily temperature on the average at 38° C; i kilogram of living hen, on the other hand, consumes 1.186 grams of O in an hour and maintains as a result an average temperature of 43.9 C. The amount of heat produced is equally large whether the combustion takes place slowly or rapidly. The activity of metabolism has, accordingly, an in- fluence only upon the rapidity, but never upon the absolute amount, of heat-formation! Also, the combustion of inorganic substances in the body, such as that of sulphur into sulphuric acid, that of phosphorus into phosphoric acid, constitutes a source of heat, although it be but slight. According to Rubner this amounts to but 0.47 per cent, of the heat. (b) In addition to the processes of combustion, however, all of those chemical processes in the human body, as a result of which the total amount of potential energy present is diminished, in consequence of greater saturation of affinities of the atoms previously present, are attended with the development of heat. Wherever the atoms combine with saturated affinities for greater stability in their ultimate position of rest, chemical potential energy is transformed into kinetic thermal energy, as, for instance, in the alcoholic fermentation of grape-sugar and other similar processes. Heat is produced also in the following chemical process: ('() The union of bases with acids. Here the character of the base determines the amount of heat formed, while the character of the acid is without any influence. Only when the acid, as, for instance, carbon dioxid, is not capable of neutraliz- ing the alkaline reaction, is the production of heat smaller. Also, the forma- tion of chlorin-combinations, as in the stomach, generates heat. (3) The transformation of a neutral into a basic salt. In the blood the sulphuric and phosphnric acids resulting from the combustion of sulphur and phosphorus combine with the alkalies of the blood to form basic salts. The decomposition of the carbonates of the blood by lactic and phosphoric acids constitutes a double source of heat, namely through the formation of a new salt, as well as through the release of carbon dioxid, which is in part absorbed by the blood. ()) The combination of hemoglobin with oxygen. According to Berthelot the amount of heat produced in this way is equal to one-seventh of the total amount formed in the body. In the chemical processes through which the body is provided with heat there not rarely occur heat-absorbing intermediate transformations of the bodies. At times, in order to bring about more complete saturation of the aftinitics, inter- mediary atom-groups in themselves firmly united must first be broken up. In this process thermal energy is consumed. Also in the breaking up of stable aggregate states in processes of retrogressive metamorphosis heat is bound up. All of these intermediary losses of heat, however, are extremely slight as compared with that due to the development of the end-products. 2. Physical processes may be mentioned as a second source of heat, (a) The transformation of the kinetic mechanical energy of the viscera furnishes heat, as the work done cannot be conveyed to the outside. AXIMALS WITH CONSTANT AND VARIABLE TEMPERATURE, 381 Thus, all of the kinetic energy of the heart is transformed into heat through the resistance opposed to the blood-stream. The same may be said of the kinetic energy of certain muscular viscera. Thus, the torsion of the costal cartilages and the friction of the current of air in the respiratory organs and of the contents of the digestive tract yield a certain amount of heat. Small amounts of the mechanical energy of the heart are transmitted through the apex-beat and the superficial pulse to surrounding parts, but these are ex- ceedingly small. Also, in the respiratory movement, in the expulsion of the respiratory ga.ses, the expectorated and other matters, a small amount of energy is conveyed to the outside, which is not converted into heat. Joule has attempted to determine the amount of heat generated in consequence of the kinetic energy lost by a flowing fluid. According to him the amount of heat produced in this way as a result of the friction must stand in a relation to the product of the difference between the initial and the terminal pressure in the weight of the flowing fluid mass. If it be assumed that the daily work of the circulation equals more than 86,000 meter-kilograms, it will be seen that the resulting amount of heat in 23 hours will be about 204,000 calories, which is suffi- cient to raise the temperature of the body of a medium-sized person about 2° C. (6) If the body through muscular activity does work transmitted to the outside, as, for instance, if an individual throws a heavy weight or ascends a tower, a portion of the kinetic energy is converted into heat through the friction of the muscles, the tendons, the articular surfaces, further through concussion and pressure of the ends of the bone upon one another. (c) The electrical currents generated in muscles, nerves and glands, apart from the small amounts that pass outside of the body with suitable conduction, are most probably transformed into heat. Thermogenic chemical processes also generate electricity, which likewise is trans- formed into heat. This source of heat is, however, quite insignificant. (d) As a further slight source of heat from physical causes there should yet be mentioned heat-production through absorption of carbon dioxid. through the condensation of water in its passage through membranes, and in the process of imbibition, the formation of stable aggregate states, as, for instance, of cal- cium in the bones. It is true, heat is again in part lost through the involution of solid parts at advanced age. After death, at times also under pathological conditions during life, coagulation of blood and the rigidity of muscles constitute in this manner a source of heat. ANIMALS WITH CONSTANT AND WITH VARIABLE TEMPERATURE. Instead of the older division of animals into cold-blooded and warm- blooded (mammals and birds), it is advisable to base their classification upon another characteristic, namely, the uniformity or the variability of the bodily temperature with respect to external influeiices. For the class of warm-blooded animals the name homoiothermic animals has been introduced by Bergmann, because they are capable of maintaining their bodily tempeVature with remarkable uniformity notwithstanding consid- erable variations in the surrounding temperature. He designated cold- blooded animals poikilotherjuic anijiials because their bodily temperature rises and falls within wide limits in accordance with the temperature of the surrounding medium. Accordingly, heat-production must be in- creased in homoiothermic animals if exposed for a long tirne in a cold atmosphere and diminished on exposure for a long time in a warm atmosphere. 382 METHODS OF ESTIMATING THE TEMPERATURE. An instance of this great constancy of the temperature in the human body was furnished by Fordyce, who died in 1792. After a man had been for ten minutes in a room filled with hot, dry air, the temperature of the interior of his closed hand, the cavity of his mouth beneath the tongue, as well as the urine, was raised only a few tenths of a degree. When Becquerel and Brechet were inves- tigating by means of the thermo-electric needle the temperature in the middle of the biceps muscle in a man whose arm had been immersed for a whole hour in ice-water, they found the temperature of muscular tissue reduced only 0.2° C. The same muscle exhibited either no increase in temperature or a reduction of only 0.3° C. after the man had immersed the arm in water at a temperature of 42° C. for a quarter of an hour. If marked alteration in temperature be brought about by powerful agents, namely, by vigorous abstraction of heat or by considerable addition of heat, great danger to the continuance of life results. Poikilothermic animals react differently, the bodily temperature following in general the surrounding temperature, though with varia- tions. On the basis of numerous observations Soetbeer therefore states that the poikilothermic vertebrates have no special temperature in the ordinary sense of the term, but their bodily temperature, like that of inanimate objects, is dependent upon that of the physical conditions of their surroundings. The following may suffice as illustrations of the bodily temperature in the animal kingdom; Birds: sea-gull, 37.8° C; swallow and titmouse, 44.03°; mam- mals: dolphin, 35.5°, motise, 41.1°, echidna from 26.5° to 36°; arthropods; from 0.1° to 5.8° above the surrounding temperature; in bees aggregated in the hive from 30° to 32°, and in bees in swarms as high as 40°. The following animals raise their temperature above the surrounding temperature; cephalopods 0.57°, molluscs 0.46°, echinoderms 0.40°, medusse 0.27°, polyps 0.21° C. METHODS OF ESTIMATING THE TEMPERATURE: THERMOMETRY. Thermometry. — By means of thermometric apparatus information is obtained as to the temperature of the body subjected to examination. For this purpose there are employed; The thermometer (Galileo, 1603). Sanctorius was the first in 1626 to make thermometric measurements in human beings. It is advantageous to employ instruments graduated in 100 parts according to Celsius, each degree being subdivided into ten parts. The apparatus should be compared with a nor- mal thermometer before being used. The column of mercury should be slender and the spindle neither too small nor too large, and preferably cylindrical in shape. A large bulb increases the sensitiveness and also the period of observation, because the large amount of mercury is influenced through and through by heat with greater difficulty. If the spindle be smaller the observation can be made more rapidly, but it is less trustworthy. The scale should be of porcelain. All thermometers acquire an error after use for a considerable time, regis- tering too high. Therefore, they should be compared from time to time with a normal instrument. At every observation the bulb should be completely sur- rounded and kept at rest for at least fifteen minutes and during the last five minutes no movement in the column of mercury should be noticeable. Minimal and particularly maximal thermometers, for the measurement of febrile tempera- ture, are of the greatest convenience to the physician. For delicate comparative measurements Walferdin's metastatic thermometer (Fig. 134) is especially useful. The tube is exceedingly narrow in proportion to the bulb. In order that on this account the instrument should not be drawn out to an extraordinary length, an arrangement is provided by which the necessary amount of mercury can be increased or diminished at will. So much mercury is taken that at the expected temperature the column reaches about to the middle of the tube. This end is attained by having at the upper extremity of the tube an expansion in which the superfluous mercury is received. If, for instance, a temperature is to be taken that is likely to be between 37° and 40° C, the bulb METHODS OF KSTIMATIXG THE TEMPERATURE. 383 is first heated to somewhat above 40° C; then it is cooled quickly and at the same time shaken, so that the column of mercury is broken below the upper expansion. Thus the play of the column is /-^ from about 40° downward. The tube is so ime that 1° C. com- W/ prises about 10 cm. in length, and |,',u° C. is still i mm. long. f\ A reading of even as little as ,,,',,,1° C. has been made possible. The scale is graduated arbitrarily. The value of the graduation must be determined by comparison with a normal thermometer, and also the temperature when the column of mercury reaches a certain level. Kronecker and Mayer caused small maximal thermometers to be passed through the digestive canal or through vessels of considerable size. The small instruments are so-called outflow thermometers, whose mercury escapes through the short open tube, and in greater amount naturally when the temperature is highest. After removal, examination is made by comparison with a normal thermometer for the purpose of determining the tem- perature at which the mercury rises exactly to the free extremity of the tube. The thermo-electric apparatus permits rapid and accurate measurement of the temperature (Fig. 135, I). The thermo-elec- tro-galvanometer of Meissner and Meyerstein employed for this purpose contains a circular magnet (m) suspended from a silk thread (c) to which by means of a hook a small mirror (s) is attached. Near this magnet another bar-magnet is fixed, with its poles similarly directed, and in such proximity that the free magnet is capable of turning to the north with the slightest de- gree of force. About the latter a thick copper wire (b b) is wound several times (in the diagrammatic representation but one turn is shown) , and with the prolonged extremities of this two needle-like thermo-elements (a f , f a) made of different metals — German silver and iron — and soldered together, are connected. The free ends of these needles of similar name are, further, con- nected by means of a wire (b) . Thus the two thermo-elements are incorporated into the closed circuit. At a distance of three meters from the mirror a horizontal scale (K K) is fixed, the numbers on which are reflected in the mirror. The scale itself is supported upon a telescope (F), which is directed toward the mirror. The observer (B), looking through the telescope, sees in the mirror the figures of the scale, which can be accurately adjusted. If the magnet swings out of the magnetic meridian, and with it the mirror, other figures on the scale appear to the observer in the mirror. If one of the thermo-elements is heated, an electric cur- rent results, which is directed in the warmer element from the German silver to the iron, and at the same time causes deflection of the movable magnet. If the observer conceive that he is swimming in the direction of the current within the conducting wire the north pole of the magnet is deflected to the left. The tangent of the angle, through which the freely movable magnet is deflected from its position of rest in the magnetic me- ridian by means of a galvanic current passed before it, is equal to the relation of the galvanic energy G to the magnetic energy. Therefore, the tangent is as G is to D. In order, thus, to keep the tangent as large as possible, while G remains the same, the magnetic energy must be reduced as much as possible. If the magnetism of the swinging magnet be designated m and the mag- netism of the earth T the magnetic energy D equals Tm. From this it appears that D can be diminished in two ways, namely (i) by reduction of the magnetic force of the swinging magnet, as may be done through the astatic pair of needles of the Nobili multiplicator, and (2) by lessening the magnetism of the earth by means of a fixed auxiliary magnet (Hauy bar) applied in the neighborhood of the swinging magnet with the same object. Of importance for the rapid and accurate adjustment of the magnet is the employment of the so-called damping arrangement of Gauss, which is not indicated in the illustration. This consists of a thick w Fig. 134. — Wal- ferdin's Me- tastatic Ther- mometer. 384 METHODS OF ESTIMATING THE TEMPERATURE. copper, hollow cylinder, upon which the wire of the coil is wound. This mass of copper may be considered as a closed multiplicator of a single winding with a large cross-section. The magnet set into oscillation induces in this closed copper mass a current whose intensity is greatest when the rapidity of oscillation of the magnet is greatest, and which takes the opposite direction as soon as the mag- net is reversed. In lesser degree the multiplicator itself as soon as it is closed operates in the same manner as a damper. The currents thus induced cause a reduction in the oscillations of the magnet in such a way that the arc of move- Fic. 135.— Diagrammatic Representation of Thermo-electric Apparatus for the Measurement of Temperature. ment diminishes in rapid and almost geometric progression. The induced, damp- ing current is the stronger the less the resistance in the closed circiut, m the presence of the damper therefore the greater the transverse section of the copper ring By means of this damping arrangement the monotonous oscillation of the magnet to and fro is limited and the latter comes to rest rapidly and promptly after three or four small oscillations while the observation is sharp and made without loss of time. , • i So-called Dutrochet needles (II) are introduced as thermo-electric elements. These consist of German silver and iron and are soldered together longitudinally TEMPERATURE-TOPOCKAPHY. 385 at their points. Bccquerel needles (III) also may be emjjloycd. These are made of the same metals, whieh are soldered together i'n continuity. The needles mvist be well covered upon their surface with brown varnish in order that the currents resulting from the moistening of dilTerent metals with the parenchymatous fluids may not interfere with the thermo-currents obtained. Before the investigations are undertaken the extent of deflection on the scale to which a definite difference in temperature in the needles gives rise, thus about 1° C, must further be deter- mined. In order to do this a sensitive thermometer is fastened by means of a loop to each of the thermo-needles, which are placed in separate oil-baths of a constant temperature, though differing by 1° C, as can be seen from the ther- mometers. If the circuit is now^ closed the deflection on the scale will naturally correspond to 1°. If, thus adjusted, the instrument exhibited a deflection of 150 mm., every displacement of the scale of i mm. would equal , l„ ° C. If this has been determined, either the two thermo-needles can be introduced into the different tissues or organs of animals at the same time, and in this way information be gained as to the prevailing differences in temperature in these portions of the body ; or one of the thermo-needles is placed in a bath of constant temperature — approximately that of the body^in which at the same time there is a sensitive ther- mometer, while the other needle is introduced into the viscus to be examined. In this event the difference in temperature between the tissue and the constant source of heat is learned. For slight differences in temperature, such as usually exist in the tissues of the body, the thermo-electric energy is always proportionate to the dift'erence in temperature between the two needle-elements. It is obviovis that instead of one pair of needles a multiplicity may be em- ployed. By this means the delicacy of the apparatus naturalh^ is materially in- creased. Thus, v. Helmholtz was able to increase the delicacy of the apparatus to the detection of differences of ;foV" ° C. by the employment of 16 antimony- bismuth elements. Schift'er constructed a thermopile of four pairs of needle- elements in a simple manner (Fig. 135, IV) by soldering together alternately wires of iron and German silver. It is intended that four such elements should be introduced into tw^o substances (A and B) to be examined for differences in tem- perature. Thermo palpation is the name given by Bencziir and Jonas to the following method of examination: If the finger be moved over an uncovered portion of the trunk it will be found that the skin is warmer over parts containing air, such as lungs and intestines, than over parts, normal or pathological, not containing air. The boundaries are said to agree with those determinable by percussion, but this has been disputed. Naturally this difference can be established also by therrnometric examination. TEMPERATURE-TOPOGRAPHY. Although a powerful influence must be ascribed to the blood, on account of its constant movement, in the equalization of the temperature in the different parts of the body, nevertheless an exact equalization is never attained, but noteworthy differences exist in different parts of the body. The temperature of the skin has been found to be as follows: In the middle of the sole of the foot . . . .32.26° C. J. Davy made these measure- In the vicinity of the Achilles tendon. . .33.85° C. ments immediately on In the middle of the anterior aspect of arising without dressing, the leg 33-05° C. with the temperature of In the middle of the calf 33. S5°C. the room at 21°. Only In the popliteal space 35° C. the inferior surface of the In the middle of the thigh 34.40° C. bulb of ^ a thermometer In the inguinal fold 35.80° C. otherwise covered came in Over the apex-beat of the heart 34.40° C. contact with the different On the face in a man 31° C. portions of the skin. At the tip of the nose and on the lobule of the ear from 22° to 24° C. In the closed axillary cavity, the temperature ranges, according to Wunderlich, from 36.49° to 37.25°; according to C. v. Liebermeister it is 36.89° C. 386 TEMPERATURE-TOPOGRAPHY. The skin overlying muscles is warmer than that covering bones and tendons. The cutaneous temperature is somewhat lower in the aged, while in children it ranges between 25° and 2q° C. The skin of the cranial vault has a higher temperature in the frontal and parietal regions than in the occipital region. Further, the left side is warmer than the right. The temperature of the skin is increased by dyspnea. V. Liebermeister employs the following method in taking the temperature of free cutaneous surfaces: The btilb of the thermometer is heated to a point slightly above that of the temperature expected. Then the fall of the column of mercury is observed as the instrument is held in the air, and then at the apparently appro- priate moment the bulb is applied to the stirface of the skin. If the skin has the same temperature as the bulb, the mercury must remain stationary for a time. For the measurement of the cutaneous temperature, it is useful to employ a spe- cially constructed thermometer with a flat vessel. The temperature of the cavities of the body : Cavitv of the mouth beneath the tongue 37-i9° C. Rectum 38.01° C. Vagina 38.03° C. The temperature of the uterus is somewhat higher, while that of the cervical canal is somewhat lower. Urine 37-3o° C. The temperature of the stomach falls during the process of digestion. Cold rectal injections (11° C.) rapidly lower the temperature of the stomach 1° C. The temperature of tJie blood is on the average 39° C. In the internal portions of the body venous blood is warmer than arterial blood, wdiile the reverse condition prevails in the peripheral portions. Blood of the right heart 38 Blood of the left heart 38 Blood of the aorta 38 Blood of the hepatic veins 39 Blood of the superior vena cava 36 Blood of the inferior vena cava 38 Blood of the crural vein 37 8° C. 6° c. 7° 7° 78° c. c. c. 11° c. 20° c. Claude Bernard. G. v. Liebig. The lower temperature of the blood in the left heart is due to the fact that the blood is cooled in the lungs in the process of respiration. According to Heiden- hain and Korner the temperature of the right heart is somewhat higher because it lies upon the warm liver, while the left heart is surrounded by the air-containing lung. This fact, observed by Malgaigne in 1832 and by Berger and G. v. Liebig, is disputed by others, who attribute the somewhat higher temperattire of the left heart to the fact that more active processes of combustion take place in arterial blood and that heat is generated in the formation of oxyhemoglobin. In adjacent veins or in those of the same name the temperature of the blood is generally lower than in the corresponding arteries, on account of the greater amount of heat given off in the slower movement. Thus, the temperature of the blood of the jugular vein is from 0.5° to 2° lower than that of the carotid; that of the blood of the crural vein is from 0.75° to 1° lower than that of the crural artery. Super- ficial veins, particularly in the skin, give off much heat and therefore the contained blood has a lower temperature. The hepatic veins contain the warmest blood, 39.7° C, not alone on account of the glandular activity of the liver, but also on account of the extraordinarily protected situation of the organ. Tlie Temperature of the Tissues. — The temperature of the individual tissues is the higher: (i) the more they contribute to the production of heat through the transformation of potential energy, that is, the greater their metabolic activity; (2) the more blood they contain; and (3) the more protected their situation. The muscles are the chief seat of heat-production, principally during contraction, but also during rest. The temperature of the blood in the TEMPERATURE-TOPOGRAPHY. 387 aorta is from o.i° to 0.6° lower than that of muscle at rest. In tlie second place, the glands generate heat, especially during activity, par- ticularly the liver, the salivary glands, the glands of the stomach and the intestines. Berger took the temperature of different tissues in the sheep and obtained the following results : Subcutaneous connective tissue 37-35° C. Brain 40.25°C. Liver 41. 25° C. Lungs 41.40° C. Rectum 40.67° C. The right heart 4 1 .40° C. The left heart 40.90° C. In man, Becquerel and Brechet found the temperature of the subcutaneous connective tissue 2.1° C. lower than that of the adjacent muscles. The temperature of the cornea and of the aqueous humor depends in part upon the state of the iris. The smaller the pupil, the more heat must they receive from the vessels of the iris. INFLUENCES AFFECTING THE TEMPERATURE OF INDIVIDUAL ORGANS. The temperature of the individual organs is by no means constant, but there are numerous influences that at times cause it to rise and at other times cause it to fall. I. The more heat a portion of the body generates independently within itself, the higher will be its temperature. As the production of heat depends upon the metabolic changes in the organs, it follows that with the activity of the latter the degree of heat-production must keep pace. (a) The glands during secretion produce much heat, which they impart either to their secretion or to the outflowing venous blood. C. Ludwig found the temperature of the escaping saliva on irritation of the tympanico-lingual nerve 1.5° C. higher than that of the blood passing through the glandular artery to the secreting organ. The temperature of the venous blood in the secreting kidney is higher than that of the arterial blood. The secreting liver in particular produces a large amount of heat. Claude Bernard studied the temperature of the blood in the portal vein and of the blood in the hepatic veins during hunger, at the beginning of digestion and at the height of digestion, and found Temperature of portal vein 37 hepatic veins. . . .38 Temperature of portal vein 39 hepatic veins 39 Temperature of portal vein 39 hepatic veins 41 8° C. ) After fasting for four days. Blood ot 4° C. ) right heart during fasting 38.8° C. "^o p' , At the beginning of digestion. 5 ^- ' 7° C. ) At the height of digestion. Blood of 3° C. I right heart during digestion 39.2° C. In dogs feeding or chemical or mechanical irritation of the gastric mucous membrane, and even the holding of food before the animal, brought about elevation of temperature in the stomach and the intestines. (6) The muscles produce heat in their contraction. J. Davy found the temperature of active muscle higher by 0.7°. Becquerel observed in 1835, by means of the thermo-galvanometer, an increase of i °C. in the temperature in the interior of a contracting muscle in man after five minutes. 388 TEMPERATURE-TOPOGRAPHY. Therefore the temperature in fast runners may rise above 40°. The increase in temperature following vigorous muscular activity disappears about one and a half hours after the commencement of rest. The lower temperature of par- alyzed muscles is due only in part to the absence of muscular contractions. (c) With reference to the influence of the sensory nerves upon the temperature it should in the first place be noted whether the circu- lation is increased or diminished as a result of their stimulation, whether respiration is slowed or accelerated, and whether the muscula- ture of the body is relaxed, or is stimulated to activity through reflex influences. In the first place the temperature, in the interior of the body and the rectum, will be increased, and in the latter diminished. From this point of view the conflicting statements not rarely made can be reconciled. (d) The bodih^ temperature rises also (about 0.3°) as the result of mental activity. The brain itself acquires a higher temperature in consequence of sensorial or sensory stimulation. {e) The parenchymatous fluids, the serous fluids and the lymph generate but little heat within themselves by reason of the slight metabolic changes that take place in them, and accordingly their tem- perature is that of their environment. The epidermoidal and homy tissues produce no heat at all, and therefore maintain their temperature from the subjacent tissues. 2. The temperature of an organ depends upon the amount of blood it contains, as well as upon the time within which the volume of blood is renewed. This is seen most distinctl}^ in the differences in temperature between cold, pale skin, and warm, reddened skin. When Becquerel and Brechet compressed the axillary artery in a man, the temperature in the interior of the biceps mviscle of the arm fell several tenths of a degree. After ligation of the crural artery and vein in dogs Landois observed the temperature decline several degrees. Long-continued elevation of the ex- tremities deprives them of blood and causes them to become colder. Attention should be called at this point to a difference between the internal and external portions of the body, which is especially emphasized by v. Lieber- meister. The external portions of the body give off more heat to the exterior than they generate within themselves. They will, therefore, be the cooler the more slowly the blood flows into them; and the warmer the more rapid the blood- current. Acceleration of the blood-current, therefore, will cause greater uniformity in temperature between the peripheral portions and the interior of the body, while retardation of the blood-current causes greater uniformity in temperature between the peripheral portions of the body and the surrounding medium. The internal portions of the body react in exactly the opposite manner. Here active production of heat takes place, while heat-dissipation occurs almost solely through the blood-current. The temperature in these parts must, therefore, fall when the blood-current is accelerated, and the reverse. From this it follows that the greater the difference in temperature between the periphery and the interior of the body, the less is the rapidity of the circulation. 3. If the situation of an organ causes it to lose much heat by con- duction and radiation, or if other conditions bring about the same result, the temperature of the organ declines. In the first place the skin is again to be mentioned in this connection, as it must exhibit a different temperatiire accordingh* as it is exposed to colder or warmer surroundings, or is covered or not, or is dry or moistened by perspiration (in the evaporation of Avhich heat is lost) . The ingestion of considerable amounts of cold food and drink must cause the temperature of the stomach, and the inhala- tion of cold air must cause that of the respiratory tract down to the bronchial tree, to fall. MEASURE.MEXT OF THE VOLUME OF IIRAT: CALOKIMETRY. 389 MEASUREMENT OF THE VOLUME OF HEAT: CALORIMETRY. The calorimeter furnishes information as to the amount of lieat that the body to be examined possesses or is capable of producing. The heat- unit or calory, that is the amount of kinetic energy that is capable of raising the temperature of one gram of water i° C, is employed as the unit of measure. Experiment has shown that equal amounts of different bodies require unequal amounts of heat in order to attain the same temperature. For instance i kilo of water requires nine times as much heat as i kilo of iron to attain the same temperature. Wherever, therefore, different materials with equal temperatures are found, each will be endowed with different amounts of heat. The same amount of heat iinparted to different bodies will, thus, also produce different temperatures in them. On the other hand, bodies naturally of different tempera- ture may possess equal amounts of heat. The amoimt of heat that a definite ainount (as, for instance, i gram) of a body requires in order to have its tempera- ture raised a definite amount (as, for instance, 1° C), is designated the specific heat of that body. The specific heat of water, which possesses the greatest of all bodies, is placed at i. Heat-capacity is the term applied to that property of bodies by means of which they are required to take up a varjang ainount of heat in order to maintain the same temperature. Calorimetry is employed : For the determination of the specific heat of the different organs of the body. But few observations in this connection have as yet been recorded. The specific heat of a number of animal parts, as compared with that of water as i, is as follows: Blood froin man, on the average . 1.02 (') Meat from man, on the average . . .0.741 (it is in proportion to the num- Compact bone 0.3 ber of erythrocytes) Spongy bone 0.71 Arterial blood, on the average. .1.031 (?) Fat 0.712 Venous blood, on the average . .0.892 (r) Striated muscle 0.825 Cow's milk, on the average . . . .0.992 Defibrinated blood 0.927 The specific heat of the human body as a whole is thus only ap- proximately that of an equivalent weight of water. For the method of determining the specific heat of solid or liquid bodies works on physics should be consulted. More important is the employment of calorimetry for the estima- tion of the amount of heat that either the entire body or an individual portion is capable of producing in a definite period of time. Lavoisier and Laplace made the first calorimetric observations on animals in 1780, with the aid of the ice-calorimeter. A guinea-pig melted 13 ounces of ice in 10 hours. Crawford in 1779 and later Dulong and Despretz in 1822 employed for this purpose the water-calorimeter of Rumford — after which that of Favre and Silbermann (Fig. 133) is modeled. Small animals were placed in the interior chamber (K) made of thin copper and this was immersed in a large volume of water surrounded by a poor conductor of heat. The amount of the surrounding water and its initial temperature were known. From the elevation of temperature at the termination of the experiment, which lasted several hours, the number of calories furnished could be directly estimated. The air for breathing was supphed to the animal through a special tube from a gasometer. The expired gases were examined chemically for carbon dioxid. According to Despretz, a small bitch generated 14,610 heat-units in an hour — 393,000 in twenty-four hours. The taking of the temperatm-e of the animal before and after the experiment was carelessly omitted. Assuming equal metabolic activity, a human being about seven times heavier would, on the basis of this observation, produce in the neighborhood of 2,750,000 calories in twenty-four 39° HEAT-CONDUCTION OF ANIMAL TISSUES. hours. Senator found that a dog weighing 6330 grams i)roduced 15,370 calories, with a loss of 3.67 grams of carbon dioxid. An adult man produces at rest in twenty-four hours 2,400,000 calories, therefore 100,000 in an hour. One kilogram of body-weight produces in twenty-four hours approximately 34,000 calories, therefore 141 7 in an hour. These figures increase with increase in the total metabolism and also with functional activity. The first calorimetric observations on man were made by Scharling in 1849. Leyden introduced the leg alone into the chamber of the calorimeter. This raised the temperature of 6600 grams of water 1° C. in an hour. If it be assumed that the total superficies of the body is about fifteen times as great as that of the leg the human body, assuming equal loss, would produce 2,376,000 calories in twenty- four hours. HEAT-CONDUCTION OF ANIMAL TISSUES. EXPANSIBILITY OF ANIMAL TISSUES BY HEAT. The heat-conduction of animal tissues is principally of importance in relation to the arrangement of the external integuraent and the sub- cutaneous fatty tissue. The latter especially serves as a protecting shield in warm-blooded animals living in cold water (whale, walrus, seal) and through this abstraction of heat by means of conduction from the interior of the body is practically impossible. Few investigations have been made upon this question. Greiss in 1870 determined the con- ductivity of the following tissues by noting the distance from a central source of heat introduced into the tissues at which was melted a layer of wax. He studied the stomach of sheep, the bladder of oxen, the skin of cattle, calves' feet, the hoofs of oxen, the bones of oxen, the horns of buffaloes, the antlers of deer, ivory, mother of pearl and haliotis-shell (sea-snail). He found that fibrous tissues conduct better in the direction of their fibers than at right angles to their course. The figures formed by the melting wax upon tissues spread out over a wide area were therefore generally elliptical. Landois has made observations upon a number of human tissues by determining the melting-distance of a layer of paraffin from a thin test-tube filled con- stantly with boiling water and applied intimately to tissues in layers of equal thickness, and subsequently applied on the fiat and supported by threads. Desiccation was avoided, and also the effect of radiant heat, Landois was able to confirm the fact of the better conduction in the direction of the fibers. Next to bone the best conductor was found to be blood-clot; then there followed successively spleen, liver, cartilage, ten- don, muscle, elastic tissue, nails and hair, anemic skin, gastric mucous membrane, washed fibrin-fibers. The great thermic conductivity of the blood as compared with the much lower conductivity of bloodless skin is of particular interest. In this way is explained the fact that but little heat is dissipated by anemic skin, while hyperemic skin conducts and gives off a much larger amount of heat. Like all bodies the human body undergoes expansion at elevated temperatures. A man, weighing 60 kilos, will expand about 62 cu. cm. with an increase of his bodily temperature from 37° C. to 40° C. Of the different tissues, connective tissue (tendon) is expanded by heat, while elastic tissue and skin are contracted like rubber. VARIATIONS IN THK MEAN BODILY TKMPERATURE. 391 VARIATIONS IN THE MEAN BODILY TEMPERATURE. (lOicral Cliiiiatic am! Soiiuitit Injluciucs. — The bodily temperature remains on the whole constant within different climates. This is note- worthy if it be considered that a human l)eing at the equator and in the polar regions is exposed to surrounding temperatures that differ from each other by more than 40° C. Further, it has been observed that when a person passes from a warm to a cold climate his temperature declines but little, but that when an individual passes from a cold to a hot region his temperature rises relatively in more considerable degree. In the temperate zone the bodily temperature in the cold winter-season is usually from o. 1° to 0.3° C. lower than on hot summer days. The elevation of a region above the level of the sea has no demonstrable influence upon the temperature. Race and sex cause no difference. Persons of vigorous constitution are believed to have a somewhat higher tempera- ture in general than debilitated, flabby, anemic persons. Influence of the General Metabolism. — As the production of heat is related to the breaking up of chemical combinations, from which, in addition to the formation of water, carbon dioxid and urea finally result as the most important excrementitious products, the amount of heat generated will keep pace with the total production of those bodies formed. The increased metabolic activity that sets in after a heavy meal causes an elevation of several degrees in temperature. As the general metabol- ism is naturally much less on days of fasting than on days on which a normal amount of food is taken, it is clear that in human beings the temperature will be found to be on the average 36.6° on fasting days and 37.17° C. on ordinary days. Also Jurgensen found in human beings on the first day of inanition a reduction in the temperature, although on the second day a transitor}^ elevation occurred. In experiments on fasting animals it was found that the temperature declined much at first, then for a considerable time remained pretty constant, and finally in the last days declined still further. Schmidt subjected a cat to starvation, and found that up to the fifteenth day the temperature was 38.6° C; on the six- teenth dav it was 38.3°, on the seventeenth, 37.64°, on the eighteenth, 35.8°, on the nineteenth, the day of death, 33° C. Chossat found the temperature of mammals and birds 16° C. lower on the day of death from starvation than under normal conditions. Influence of Age. — The activity of the general metabolism must be in part responsible for the temperature of the body at different ages, but other influences of undetermined origin may also in part be contributory. Age. New-born. . 5- 9 years 15-20 " 21-25 II 26-30 31-40 41-50 51-60 " Mean Tempera- TURE AT Room- NoRiLAi. Limits. temperature. 37-45° C. 37-35°-37-55°C. 37 72° c. 37.87°-37-62°C. 37 37° C. 36.i2°-38.io°C. 37 22° C. 36 9i°C. 37 10° C. 36.25°-37-5° C. 36 87° C. 36 83° C. 37 46° C. Place of Measurement. Rectum. Mouth and rectum. Axillary cavity. Mouth. According to Chelmonski the bodily temperature is somewhat lower in the old. and the evening temperature lower than the morning temperature. 392 VARIATIONS IX THE MEAN' BODILY TEMPERATURE. The temperature in the new-bom exhibits special pecuHarities, such as would be readily explicable from the sudden change in the conditions of life. Immediately after birth the temperature of the child is on the average 0.3° higher than that of the vagina of the mother, namely 37.86° C. In the first hours after birth the temperature declines about 0.9° C, in conjunction with the reduction in gaseous interchange. After from nine to thirty-six hours it will again have risen to the average temperature of the infant, which is about 37.45° C. Certain irregular fluctuations occur during the first week of life. During sleep the tem- perature in infants declines between 0.34° and 0.56° C. Persistent cr\'ing may cause the temperature to rise several tenths of a degree. Less heat is produced in the aged on account of their lesser activity of metabolism, so that they suffer more readily from cold and therefore need warmer clothing. Periodic variations in the course of the day are constant at all periods of life. In general, it may be stated that the temperature rises continuously by day, the maximum being reached between 5 and 8 p. m. ; while it declines continuously by night, the minimum being reached between 2 and 6 a. m. The mean temperature of the body is found in the third hour after breakfast. The average level of all the temperatures observed in a person in the course of a day is designated the daily mean, which, according to Jager, is 37.13° in the rectum. If the daily mean is above 37.8° it must be considered as febrile, and if below 37° as an evidence of collapse. As the daily variations in temperature occur also during the state of hunger, although the elevations are somewhat less after the time for meals, the ingestion of food cannot alone be the cause of the variations, but these appear to reside essentially in the varying degree of muscular activity. Hoot. V. B.iRZN- SPRUNG. J. Davy. Hallm.\nn. GlERSE. JURGESSEX. Jager. a. m. 5 36.7 36.6 36.9 6 36.68 36.7 36 4 37 I 7 36.94* 36.63 36.98 36.7* 36 5* 37 5* 8 37.16* 36.80 37.08* 36.8 36 7 37 4 9 36.89 36.9 36 8 37 5 10 37.26 loi = 37.36 37-23 37 37 37 5 II 36.89 37.2 37 2 37 3 m. 12 36.87 37-3* 37 3* 37 5* p. m. I 36.83 37.13 37-3 37 3 37 4 p. m. 2 37.05 37-21 37.50* 37.4 37 4 37 5 3 37-15* 37-43 37.4* 37 3* 37 5 4 37-17 37.4 37 3 37 5* 5 37-48 37-05* Sh = 37-31 37-43 37-5 37 5 37 5 6 H = 36.83 37-29 37-5 37 6 37 4 7 37-43 7i = 36.50* 37-31* 37-5* 37 6* 37 3 8 37-4 37 7 37 I* 9 37.02* 37.4 37 5 36 9 10 3729 37-3 37 4 36 8 II 36.85 36.72 36.70 36.81 37-2 37 I 36 8 m. 12 37-1 36 9 36 9 a. m. I 36.85 36.44 37 39 9 36 9 2 36.9 36 7 36 8 3 36.8 36 7 36 7 4 36.31 36.7 36 7 36 7 * Indicates ingestion of food. VARIATION'S IN THE MEAN BODILY TEMPERATURE. 393 The excretion of carbon dioxid from hour to hour, also the daily variation in the pulse-frequency, almost coincides with the temperature, v. Barensprung found that the mid-daj' maximum temperature somewhat preceded the maxi- mum pulse. If a person sleeps by day and performs all of his other daily duties by night, the typical course of the temperature-curve described may be inverted. The variations are, therefore, dependent upon the state of activity. With respect to the state of activity or of rest of the individual, the temperature of persons active during the day appears in general higher and during the night in general lower than in a person at rest. The peripheral portions of the body also exhibit more or less regular variations in temperature. In the palm of the hand the course is somewhat as follows: After a relatively high temperature during the night a rapid fall sets in in the morning at six o'clock, which reaches its lowest between 9 and 10 o'clock. Then there follows a slow ascent, which reaches its maximum after the midday meal. Between i and 3 o'clock the temperature begins to decline, and the lowest level is reached in the course of two or three hours. Between 6 and 8 there is again a rise, and finally a decline toward morning. A rapid fall of the temperature at the periphery corresponds with a rise in the interior of the body. Fig. 136. — Variations in the Bodily Temperature during Health within Twenty-four Hours. L according to V. Liebermeister. J according to Jiirgensen. Certain operations upon the body cause variations in temperature. After venesection the temperature at first falls. Then it rises several tenths of a degree with chilliness. In the first days it falls again to the previous level and even somewhat below this. Profuse acute hemor- rhage causes a reduction in temperature of from 0.5° to 2° C, while long-continued, extensive hemorrhage may cause in dogs a reduction to as low as 31° and 29° C. Here the reduction in oxidation-processes in the tissues the seat of lessened metabolic activity in consequence of the hemorrhage and the enfeebled circulation obviouslv constitute the cause of the reduction in temperature. Analogous condi- tions of diminished metabolism can be brought about if the peripheral extremity of the divided vagus is irritated for about an hour, so that the heart-beat becomes extremelv slow, and in conjunction with it the entire circulation. Thus Landois was able 'to reduce the temperature in rabbits several degrees within a short time. After everv transfusion of any considerable amount of blood, begin- ning about half an hour after the operation, the temperature rises to a marked febrile attack, which will have subsided in the course of several 394 REGULATION OF THE TEMPERATURE. hours. Direct transfusion from an artery to an adjacent vein in the same animal excites the same phenomenon. Certain poisons, particularly chloroform, chloral and other anes- thetics, as well as alcohol; further, digitalis, quinin and others, cause reduction in temperature. These substances appear in part to render the tissues less suited for the molecular decomposition necessary for the generation of heat. In the case of the anesthetics it is possibly a con- dition of the latter kind within the structure of the nerve that furnishes the cause. In part, however, they may also have an influence upon those processes that control the dissipation of heat from the body. Other poisons cause elevation of temperature from opposite causes. Strj'-chnin, nicotin, picrotoxin. veratrin, laudanin, cause elevation of the bodily temperature. The lowest temperature terminating in recovery observed was 24° (!) C. in the rectum of a profoundly intoxicated individual. Reduction in temperature in connection with disease is due either to diminished heat-production (reduction in metabolic activity), or to increased heat-dissipation. Marked reduction in temperature in individual instances (between 31° and 27.5° and down to 22° C. in the anus) has been observed particularly in cases of paralysis, in one of which Reinhard found a rectal temperature of as low as 22.5° C. four and one-half hours before death. The lowest temperature observed one day before death was 23° C. in the anus in a case of hemorrhage into the medulla oblongata. Also in cases of diabetes a reduction in temperature below 30° C. has been observed. Elevation of temperature is exhibited as a rule in connection with fever, the highest temperature being observed by Wunderlich before death, 44.65° C. REGULATION OF THE TEMPERATURE. As human beings and other homoiothermic animals are capable of maintaining their bodily temperature at the same level under varying conditions, the body must possess special mechanisms by means of which the heat-economy is subjected to constant regulation. The latter can obviously make itself effective in two directions: either by control of the amount of molecular transformation through which potential energy is transformed into the kinetic energy of heat, or by influencing the dissi- pation of heat from the body in accordance with the production or the effects of external agencies. Regulatory Mechanisms Governing Heat-production. C. V. Liebermeister estimated the heat-production of a medium- sized person as 1800 calories per minute. It is in the highest degree probable that mechanisms are operative in the body upon whose stimula- tion the amount of heat-producing molecular transformation is depen- dent. It should especially be borne in mind that this stimulation is of reflex origin. Irritation from the peripheral extremities of the cutane- ous nerves, through thermic excitation, or of the nerves of the intes- tines and of the digestive glands, through mechanical or chemical stimulation during the process of digestion or during inanition, may be transmitted to a heat-center, from which an influence is exerted through centrifugal fibers upon the reservoir for potential energy, for the purpose of stimulating either increased or diminished metabolism. Little is as yet known, however, concerning the nervous apparatus and chan- VARIATIONS IN THE MEAN BODILY TEMPERATURE. ;^95 nels necessary for the maintenance of this hypothesis. Nevertheless, numerous phenomena indicate tliat such a view is not unjustiliable. Investigation has as yet furnished no adequate evidence as to the existence of a heat-center. Tschetschechin and Naunyn, as well as Ott and Wood recently, assunu' the existence in the l)rain (acconhniij to Ott in the anterior portion of the optic thalannis) of a center that is sup])()sed to exert an inhil>itory effect upon the coml)ustion-pi-ocesses in the body through fibers that descend through the pons, medulla and cord; and accordingly destruction of this center or its con- ducting paths would cause increased heat-production. Aronsohn and Sachs ob- served transitory rise of temperature, with increased metabolism, after deep inincture of the rabl)it's brain several millimeters to one side of and behind the anterior fontanel. Injuries of the caudate nucleus, optic thalamus, corpus cal- losum, septum lucidum and trigone also cause similar phenomena. Confirmatory evidence is given by Richct, who attributes this elevation of temperature to in- creased heat-production. The animals cat more, yet lose Hcsh. Repeated cerebral puncture eventually induces marasmus, reduction in temperature, as low as 26°, and death. Centers with an opposite function, namely, stimulating heat-produc- tion, arc said to be situated in the caudate nucleus, in the gray substance of the septum lucidvim and in the gray matter in front of and below the caudate nucleus and in the tuber cinereum. After high division of the spinal cord heat- regulation, heat-production and heat-dissipation are disturbed. The regulatory mechanisms governing heat-production can be recog- nized from the follov^ing phenomena: 1. As a result of the moderate, transitory influence of cold the bodily temperature rises, while as a result of the like influence of heat upon the external integument the temperature declines. 2. Heat-production is increased by reduction of the surrounding temperature, while the excretion of carbon dioxid and the consump- tion of oxygen are at the same time increased. Heat-production is diminished by increase of the surrounding temperature. The produc- tion of carbon dioxid takes place principally in the muscles, without contraction necessarily taking place at the same time. Human beings generate at 0° C. about twice as much heat as at a surrounding temperature of 30° C. D. Finkler found in experiments on guinea-pigs that the production of heat is inore than doubled in vigorous animals in consequence of a reduction in the surrounding temperature of about 24° C. Thus, during the winter the metabolism of the guinea-pig was increased about 23 per cent, as com- pared with the summer. It thus caused an alteration in heat-production in general that is entirely analogous to that resulting from lowering of surround- ing temperature of shorter duration. C. Lvidwig and Sanders-Ezn have observed in rabbits, when the surrounding temperature was reduced from. 38° C. to 6° or 7°, a rapid increase in the elimination of carbon dioxid. Conversely, this was diminished in animals as the surrounding temperature was raised from between 4° and 9° to from 35° to 37°. The thermic stimulation of the surrounding temperature must thus have had an effect also upon the combustion-processes. In accordance with this fact is the observation of Pfliiger, who found increased consumption of oxygen and increased elimination of carbon dioxid in rabbits that had been immersed in cold water. When the influence of the cold was so profoimd that the bodily temperature fell as low as 30°, the gaseous interchange also diminished, and if the exposure continued until the temperature fell to 20° the interchange became only half of the normal. If mammals are placed in a warm bath whose temperatvire exceeds, that of the body by 2° or 3° the elimination of carbon dioxid and the consumption of oxygen increase in consequence of a stimulation of the metabolic processes. The elimina- tion of urea also increases from the same cause. 3. The application of cold to the external integument causes in part involuntary muscular movement (shivering), in part voluntary muscular movement. As a result of both heat is produced. 396 VARIATIONS IN THE MEAN BODILY TEMPERATURE. Cold thus stimulates muscular activity, which is attended with oxidation- processes. In human beings muscular activity induces, in addition to increased heat-production, also increased heat-dissipation. The latter, however, becomes less on conclusion of the activity than it had been before. After administration of curare, which paralyzes the voluntary muscles, this regulation of temperature falls to a minimum. Strychnin increases heat-dissipation and heat-production, and the bodily tem- perature may be either increased or diminished in accordance with the prepon- derance of production (convulsions) or of dissipation. Cocain increases the bodily temperature, while the anesthetics have the reverse effect. 4. Change in the surrounding temperature has an influence upon the need for food. Ingestion of food increases the elimination of carbon dioxid, principally in consequence of increased activity on the part of the digestive glands. In winter, as well as in cold regions, the sense of hunger and the need for fats, whose combustion yields much heat, are increased. Regulatory Mechanisms Governing Heat-dissipation. The average dissipation of heat from the skin of a human being weighing 82 kilos is between 2,092,000 and 2,592,000 calories in twenty- four hours — therefore, between 1450 and 1798 calories in the minute. I. Elevation of temperature causes dilatation of the cutaneous ves- sels. The skin becomes vividly reddened, soft, and full of fluid, so that it serves as a better conductor of heat and is swollen. The epithe- lium becomes moistened and sweat exudes from the surface. In this way provision is made for augmented heat dissipation, evaporation of the sweat playing an important part in the abstraction of heat. The greater the increase in the moisture of the air, the less becomes the evapora- tion from the skin. Accordingly, heat-dissipation must be increased by conduc- tion and radiation. The same amount of heat that is capable of transforming I gram of water at a temperature of 100° C. into steam is equal to that which will raise the temperature of 10 grams from 0° to 53.67° C. The sweat secreted is of the same temperature as the body; if it be completely converted into vapor it will require first sufficient heat to raise it to the boiling-point and then addi- tionally the amount of heat that will convert it from this point into steam. For purposes of more precise determination there would be required a knowledge of the heat-capacity and of the boiling-point of the sweat. The action of cold is to cause contraction of the cutaneous vessels. The skin becomes pale, less soft, deficient in fluid and collapsed. The epithelium becomes dry and permits the escape of no fluid for evapora- tion. In this way dissipation of heat through the skin is diminished. Through the contraction of the muscles of the skin and of the cutaneous vessels, with the displacement of well-conducting fluid and blood from the skin and the subcutaneous connective tissues, loss of heat from the periphery is diminished and heat-conduction transversely through the tissues is rendered difficult. The cooling of the body is lessened through the marked interference with the flow of blood through the skin, in the same way as is the case with a cooling apparatus made of convoluted tubing if the current passing through it is greatly lessened. If, however, the cutaneous vessels undergo dilatation, the temperature of the surface of the body rises, and the difference in temperature between it and the surrounding cooler medium is increased, and thus the loss of heat is aug- mented. Tomsa has shown that anatomically the arrangement of the fibrillation of the skin is such that every stretching of the fibers effected by the muscles of the skin gives rise to a reduction in the thick- ness of the skin, as a result of which an influence is exerted principally VARIATIONS OF THE MEAN BODILY TEMPERATURE. 397 upon the readily displaceable blood present. When the author, in con- junction with Hauschild, ligated in dogs either the arteries alone or at the same time the axillary and crural arteries and veins, the carotids and the jugular veins, the temperature of the interior of the body rose several tenths of a degree within a short time. Chlorotic and anemic individuals, with pale, bloodless skin, at times exhibit, for the same reason of failing circulation through the skin, elevation of the bodily temperature. By means of systematically employed stimuli, which, like cold baths and cold sponging, cause contraction of the muscles and vessels of the skin, the latter may be so invigorated and be maintained in such a state of irritabiHty as to oppose vigorously loss of heat when the body or individual parts thereof are threatened with sudden abstraction of heat. Thus, cold spongings and baths constitute in a measure gy^mnastics for the muscles of the skin, which under the conditions indi- cated are capable of protecting the body against cold. 2. Elevation of temperature accelerates the heart-beat, while reduc- tion of temperature diminishes the number of contractions of the heart. Through the action of the heart the blood that is relatively the warmest is pumped from the interior of the body to the surface of the skin; and in this way it may readily give off heat upon the extensive surface. The oftener the same amount of blood courses through the skin, the more will be the amount of heat given off, and the reverse. Therefore, the frequency of the heart-beat is in direct relation to the rapidity with which cooling takes place. Thus, the pulse has been observed to rise to more than i6o per minute in air of an excessively high tem- perature— above ioo°C. This is true not alone of the range of normal conditions, but also of the pathological variations in temperature during the febrile state. C. v. Liebermeister records the following figures for the pulse and the temperature respectively in adults : Pulse — in the minute: 78.6, 91.2, 99.8, 108.5, ^'^°- ^37-5- Temperature in °C.; 37°, 38°, 39°, 40°, 41°, 42°. If the number of heart-beats is permanently diminished it might be anticipated that elevation of temperature would occur. When the author, in conjunction with Ammon, caused reduction for about one and one-half hours in the number of heart- beats by irritation of the peripheral extremity of the vagus in rabbits, the tem- perature in the rectum fell on the average from 39° to 34.5° C. The enfeebled circulation diminishes also metabolism and oxidation in the body; in fact, this diminution must therefore even over-compensate for the accumulation of heat resulting from the diminished circulation. 3. Elevation of temperature increases the number of respirations, so that a much larger amount of air passes through the lungs in a given time and in them is raised almost to the temperature of the body. In addition a certain amount of water undergoes evaporation in the expired air with every respiration, and in this way heat is taken up. Therefore, it is to be borne in mind that vigorous respiratory movement materially sustains the circulation, so that the respiration operates indirectly in the manner outlined in 2. Forced respiratory movement exerts a cooling effect even if air heated to a temperature of 54° C. and saturated with watery vapor is inhaled. 4. Nature provides many animals with furs during the winter and with lighter covering in the summer. Many animals living in air and water of a low temperature are protected against excessive heat-dissipa- tion by heavy layers of fat. In the same manner man provides for a more uniform dissipation of heat on the part of the skin by means of a difference in clothing for winter and summer. The attitude of the body 398 CLOTHING. also is not without influence upon the temperature. Thus, a cowering position and drawing together of the head and the extremities help to retain heat, while spreading of the extremities, erection of the hair, ruffling of feathers, permit the escape of a greater amount of heat. Landois found that in rabbits suspended in air with their extremities spread out the rectal temperature declined from 39° C. to 37° C. in the course of three hours. Exposure in heated or cooled rooms, ingestion of hot or cold food and drink, hot or cold baths, exposure to a quiet atmosphere or to air in active motion (fanning) are measures employed by man for regulating the temperature at will. In the cooling of the body from its surface, radiation, conduction (also through the air) and convection (as the layer of air in contact with the body is constantly being displaced by the heat) take part in addition to evaporation. The radiating power of the skin has been carefully studied by Eichhorst and Masje. It is in- creased after irritation and friction of the skin, after muscular effort, and in still greater degree — up to three or four times the initial amount — through the action of cold air or after a cold bath. After marked abstraction of heat radiation be- comes small, while it is increased during the febrile process and after the employ- ment of antipyretics. The amount of heat radiated by a naked man from each square centimeter of superficies is equal to 0.00 1 calon.^ in the second. This would make for the entire body, weighing 82 kilos, approximately 1.7S2.000 calories in twenty-four hours. Stewart found the loss of heat through radiation for a clothed man. weighing 70 kilos. 700.000 calories: for a man, weighing 82 kilos, 820.000 calories. In a clothed person the radiation, according to Rubner, with a weight of 82 kilos and a superficies of 22.430 square centimeters, is 1,181.000 calories. In estimating the influence of climate upon the regulation of heat of the body chief importance is to be attached to the rapidity of evaporation, which is pro- portional to the square root of the velocity of the wind. CLOTHING. The effect of the clothing is yet to be taken into consideration. A warm dress is an equivalent for food, for as the dress is intended to preser\"e the heat of the body generated by the latter from the combiistion of food, it may be stated that the body has a direct income through the food, while by means of clothing it protects itself against unnecessarv- expenditure. The clothing thus at room- temperature saves 20 per cent. From this its importance in the heat-economy is obvious. Summer-clothing weighs from 3 to 4 kilos and winter-clothing from 6 to 7 kilos. The radiation of heat from the body through a full suit of clothing is only about one-third of that from the naked skin. At a low temperature this re- duction in heat-radiation is greater than when the surrounding temperatiore is high. With respect to the usefulness of clothing the following considerations are to be borne in mind: (i) Its condiiciivity. Those materials that are the poorest con- ductors of heat keep the body the warmest. The following is a list of conductors arranged successively from the poorest to the best: Hare-skin, down, beaver-skin, raw silk, taffeta, sheep's wool, cotton, flax, twisted silk. (2) The radiating power. Rough substances radiate heat more readily than smooth substances. The radi- ating power is. however, equal for different colors. (3) The relation to the sun's rays. Dark materials absorb more heat from the stm than light materials. (4) The degree in which materials are hygroscopic is of great importance, that is whether they are capable of taking up much moisture from the skin, and at the same time yield this up gradually by evaporation, or the reverse. Wool of the same weight takes up twice as much water as linen, but the latter permits its more rapid evaporation. Wool upon the skin, therefore, less readily permits accumulation of moisture and also the development of cold through rapid evapora- tion, and therefore affords protection against catching cold. (5) The degree of permeability for air— ventilation — is of importance with respect to clothing, but it bears no relation to heat-conduction. Thus the application of a coat of varnish to materials increases the heat -conduction, but destroys the ventilation. The perme- ability depends — apart from the thickness of the material — upon the specific gravity and the character of the thread. The following is a list of substances beginning with the more permeable and passing to the less permeable: Flannel, buckskin. HEAT-BALANCE. 399 linen, silk, leather, oil-cloth. (6) Clothing that is in direct contact with the skin natvirally also takes up the excrementitious i)roducts of the skin, linen and cotton in greatest amount, and wool least of all transmitting the waste matters to the overlying clothing. The drawers take up the least material, the shirt twice as much, the socks eight times as much. The temperature of the surface of the body beneath winter-clothing is on the average 18° C. and beneath summer-clothing 20° C. Heat is given off principally by conduction when clothing is worn. Clothing appears comfortable when the temperature of its surface is 5° or 6° C. higher than that of the air. HEAT-BALANCE. As the temperature of the body is capable of remaining constant within narrow limits, it is obvious that the amount of heat taken up must be equivalent to the amount of heat given off, that is exactly so much potential energy must within a given time be converted into heat as heat is given off from the body. Attempts have been made from different points of view to set up heat-balances which while partly at least without a reliable foundation, are nevertheless of great inter- est in the elucidation of the heat-economy of the animal organism. An adult produces on an average enough heat to raise the temperature of his body almost i° C. in half an hour. If no heat were given off, the body would in a short time become enormously heated — in thirty-six hours to the boiling-point — providing the production of heat continued uninterruptedly. HEAT-BALANCE ACCORDING TO H. v. HELMHOLTZ. Hermann von Helmholtz was the first, in 1846, to determine numerically the amount of heat produced by man. I. Heat-income. — (a) A healthy adult, weighing 82 kilos, expires in twenty-four hours 878.4 grams of carbon dioxid. The combustion of the carbon thereof into carbon dioxid generates 1,730,760 calories (6) The man, however, takes up more oxygen than is present in the carbon dioxid given off. This excess is em- ployed for purposes of oxidation, particularly for the forma- tion of water through the combustion of hydrogen. In conse- quence of the excess of oxygen thus taken up 13.615 grams of hydrogen can be additionally burned up, yielding 318,600 2,049,360 calories (c) About 25 per cent, of heat must be derived from other sources than combustion-processes, so that in round figures there will be 2,732,000 calories This amount would in fact suffice to raise the temperature of a human body weighing from 88 to 90 kilos from an average temperature of 10°, 28°or29°C.. thus to 38° or 39° C, that is the normal temperature. 2. Heat-expenditure. — According to v. Helmholtz the following debits must be set against the heat-income: (a) For the heating of food and drink, which have an average temperature ofi2°C.... 70.157 calories = 2.6 per cent. (6) For heating the inspired air = 16,400 grams, assuming the temperature of the air to be20°C 70,032 ■' = 2.6 per cent. [If the temperature of the air were 0° the number of calories would be 140,064 = 5.2 per cent.] (c) 656 grams of water evaporated through the lungs 397. 53^ " = 14.7 Pt^r cent. (d) The remainder through radiation and evaporation from the external integument . . . from 77.5 percent, to So.i percent. 400 VARIATIONS IN HEAT-PRODUCTION. ESTIMATION OF HEAT-INCOME ACCORDING TO FRANKLAND'S METHOD. Frankland in 1866 burned food directly in the calorimeter (Fig. 133) and obtained the following results: I gram of proteids yielded 4998 heat-tmits ^. These figures may be " grape-sugar yielded 3277 " [ compared with Rub- " beef-fat yielded 9069 " J ner's results, p. 379. The proteids are decomposed only to the stage of urea; therefore the heat yielded by the combustion of the latter is to be deducted from 4998, thus leaving 4263 heat-units for i gram of proteids. If the number of grams of the individual foods taken by inan has been determined by weight the number of heat-units taken up can be readily estimated. When the amount of food is sufhcient the production of heat, under otherwise like conditions, is always the same. If the amount of food is insufficient, the amount of heat produced is but little diminished, as the body inust then consume some of its own tissues. This is naturally the case in' the state of hunger especially. The character of the food, providing it is sufficient in other respects, is of subor- dinate importance. VARIATIONS IN HEAT-PRODUCTION. According to v. Helmholtz the average heat-production in a healthy adult, weighing 82 kilos, in twenty-four hours is 2,732,000 calories. Influence of the Superficies of the Body. — Rubner found that heat- production is dependent not upon the weight of the body, but upon its size and the related superficies. Small, and also young, animals have a relatively larger superficies than larger, and also older, animals. As, however, the dissipation of heat takes place principally from the external surface, accordingly greater heat-production will have to take place in animals with a greater superficies — heat-dissipating surface. Thus a relatively greater consumption of oxygen was accordingly ob- served in smaller animals. Rubner's investigations have shown that for dogs of various sizes the heat-production for each square meter of body- surface uniformly equaled 1,143,000 calories. If the body-weight was compared with the body-surface in different animals, he found that for every kilogram of weight there was in the rat 1650, in the rabbit 946, in man 287 square centimeters of surface. According to J. Rosenthal the production of heat is to be estimated in the following manner: If n represents the amount of heat produced in an -animal in one hour, gthe body-weight, and A a factor that remains nearly constant in the same species and under like nutritive conditions (for the body of the child, 11.97; for that of the adult, 12.31; for that of the dog' 49; for that of the rabbit, 33), then n = A] g- . Age and Sex. — In the earliest period of life, as well as in old age, the production of heat is less than at mature age. It is likewise so in women as compared with men. Daily Variation. — The production of heat exhibits a course similar to that of the bodily temperature at different hours of the day. Bodily Functions. — During waking, with physical and mental exertion, as well as during digestion (on account of the greater glandiilar activity), the pro- duction of heat is greater than under the opposite conditions. RELATION OF HEAT-PRODUCTION TO THE WORK PERFORMED BY THE BODY. The potential energy supplied to the body can be transformed by the latter into heat and into kinetic energy. In the resting body almost the RELATION OF HEAT-PRODUCTION TO BODY WORK. 401 entire amount of potential energy is transformed solely into heat, ftjr the work of the muscles of the circulatory, digestive, and respiratory organs is transformed within the body into heat, and therefore is not work transmitted outward. A man at work, however, in addition to the production of heat, transforms potential energy into work. An equiva- lent measurement will serve for the comparison of both activities, namely, i heat-unit, that is, the energy that will raise the temperature of I gram of water i° C, which equals 425.5 grammeters. The following illustration will scrv'e, first of all, to make clear the relation between heat-production and work. If a small steam-engine, in which a given amount of coal is burned, is placed within the inner chamber of a capacious calor- imeter, heat alone will be produced from the coal so long as the engine is not brought into working activity. The water in the calorimeter will indicate exactly- through the elevation of its temperature the number of heat-units furnished by the burning coal. If this has been determined, the same amount of coal is burned in the steam-engine in a second experiment, but at the same time by means of a suitable device outside of the calorimeter work is performed by the engine, such as the raising of a weight. This work must naturally be furnished by the potential energy of the fuel and be transformed. If now the elevation of temperature at the end of the experiment is noted it will be found that a smaller number of heat- units have been transmitted to the water than in the first experiment, in which the engine was heated, but performed no work. Comparative experiments of this kind have demonstrated beyond doubt that in the second experiment the useful working effect is almost proportional to the heat-deficit observed. If the processes in the organism be compared with this illustration it will be seen that the resting human being generates between 2^ and 2f million calories from the potential energy contained in the ingested food, while the amount of work performed by a laborer is estimated at 300,000 kilogram-meters. If the organism were exactly comparable wdth the engine, just so much less heat would have to be formed within the body as corresponds to the amount of work done. As a matter of fact, the organism naturally can transform only a lesser amount of heat from the same measure of potential energy wdien work is performed. One point, however, should be taken into consideration in which the laborer differs from the working engine. The laborer consumes in the same time a far larger amount of potential energy than the resting indi- vidual. A greater amount of combustion takes place in his body, and it therefore comes about that the loss through the increased combustion is not alone made good, but is even over-compensated. The laborer is, by reason of his greater muscular activity, warmer than the resting individual. The following may serve as an example of the relation in- dicated: Him in 1858 took up at rest in the calorimeter-chamber 30 grams of oxygen in an hour, and produced 155,000 calories. When subsequently he undertook in the chamber work transmitted outward, to the amount of 27,450 kilogram-meters, he consumed 132 grams of oxygen and furnished only 251,000 calories. In estimating the amount of work done only that transmitted outward as heat- equivalent is to be considered, as, for instance, the lifting of a load, the throwing of w-eights, the displacement of masses. Also the lifting up of the body is to be included here. In ordinary walking the overcoming of the resistance of the air and the activity of the muscles must be taken into consideration. In descending from a height an increase in heat of the body is not to be looked for, for muscular activity is required to prevent the body from falling down and from collapsing, and to avoid a too precipitate descent. 26 402 ACCOMMODATION' TO ^■ARIATIO^'S IX TEMPERATURE. The organism is superior to the engine in the fact that more work in proportion to heat is transformed from the same measure of potential energy. While the best gas-engine is capable of converting 10.82 per cent, of the potential energy of illuminating gas into work and the remainder into heat, the human being is capable of furnishing 35 per cent, of work — in making ascents and in doing work of other character only 25.4 per cent. — froin the chemical transformation in its muscular tissue, Pfiiiger's experimental dog as much as 48.7 per cent., and an excised bit of frog's muscle even 50 per cent. "Work alone, without simultaneous production of heat, can never be transformed from chem- ical potential energy in an inanimate or animate motor. ACCOMMODATION TO VARIATIONS IN TEMPERATURE. All bodies possessing great heat-conductivity, when brought in contact with the skin, appear much cooler or warmer respectively than poor conductors. The reason for this lies in the fact that they abstract more heat from the bod}^ or supply more heat to the body than the latter. Thus the water of a cold bath will always feel colder than the air at the same temperature, because it is a better conductor of heat. In the temperate zone, for example : Air Water At 18° C. feels moderatelv warm, Up to 18° C. appears cold, From 25° to 28° C, hot, ' From 18° to 29° C, cool. Above 28° C., extremely hot. From 34° to 35° C, indifferent, Above 35.5° C., warm, At 37.5° C. and above, hot. So long as the temperature of the body is higher than that of the surrounding medium, the body gives off heat, and in greater amount and more rapidly the better the conductivity of the surrounding medium. As soon, however, as the surrounding temperature becomes higher than that of the body, the latter takes up heat and in greater amount and more rapidly as the meditim is a better conductor. Therefore, hot water appears to be of a higher temperature than air at the same tem- perature. A human being may remain for eight minutes in a bath at a tempera- ture of 45 . 5° C. , but not without risk to life. The hands tolerate immersion in water of a temperature of 50.5^ C, but not of a temperature of 51.65° C. At a temperature of 60^ C. intense pain is felt in the integument. On the other hand, a human being may tolerate air at a temperature of 127° C. for eight minutes. Girls have remained for as long as twenty minutes in air at a temperature of 132° C. Under these circumstances the bodily temperature rises but little, namely, to 38.7° or 38.9° C. This depends upon the fact that the air, acting as a poorer conductor of heat, does not convey so much heat to the body as does water. Fur- ther, and this is the most important fact, the body exposed to hot air is capable of losing heat at its surface through abundant sweating and evaporation, and to this end the increased evaporation of water due to the increased activity of the lungs contributes. The enormous accel- eration of the heart -beat — up to above 160 — causes constantly renewed volirmes of blood to be sent to the skin through its greatly dilated blood- vessels, for the secretion of sweat and evaporation. In the degree in ACCUMULATION OF HEAT IN' THE BODY. 4O3 which these diminish the body becomes less capable of withstanding the surrounding heat, and thus is readily explained the fact that the human being is by far less able to withstand air rich in watery vapor than dry air at the same temperature, as heat must, under such circum- stances, accumulate within the body. Thus in the Russian steam-bath at a temperature of from 53° to 60° C. the normal rectal temperature rises to between 40.7° and 41.6° C. A human being is just able to work in an atmosphere at a temperature of 31° C. almost completely saturated with watery vapor. In water at the temperature of the body the normal bodily temperature rises 1° C. in one hour; about 2° C. in one and one-half hours . Gradual elevation of the temperature of the water from 38.6° to 40.2° C. caused an increase in the axil- lary temperature to 39° C. within fifteen minutes. ACCUMULATION OF HEAT IN THE BODY. As under normal conditions the constancy of the bodily temperature is the result of a constant relation between heat-production and heat- dissipation it is obvious that heat must be stored up in the body when heat-dissipation is lessened. The chief organ regulating heat-dissipation is the external integument. Contraction of the skin and its vessels diminishes heat-dissipation, while relaxation with dilatation of the ves- sels increases heat-dissipation. Accumulation of heat may, accordingly, be effected : (a) By intense and extensive cutaneous irritation, through which a transitory influence is exerted, causing contraction of the skin and its vessels, (b) Also through other forms of restriction of loss of heat through the skin, (c) Through increased activity of the vasomotor center, as a result of which contraction of all vessels, and naturally also those of the external integument, is brought about. In this way the elevation of temperature following transfusion of blood from an animal of the same species is to be explained — direct transfusion of arterial blood from the crural artery into the adjacent vein in the same animal will suffice, as Landois was able to confirm by experiments on the carotid and the external jugular vein — as well as that following venesection after a preceding decline in temperature. In both events abnormal blood-distribution takes place. In the first the venous system is abnormally overloaded, in the second abnormally empty. For the restoration of the normal distribution vigorous activity on the part of the musculature of the vessels is necessary, excited through the vaso- motor center. The marked contraction of the cutaneous vessels hereby brought about exerts an inhibitory influence on heat-dissipation and heat-accumulation thus takes place. The elevation of temperature observed after sudden abstraction of water from the body must appa- rently be explained in the same way. The inspissated blood requires less vascular space and the contracted vessels permit the escape of little heat into the skin, (d) If the circulation through the cutaneous vessels in considerable areas is retarded by mechanical means, as by occlusion of small vessels by viscous masses of stroma or coagula, which form after transfusion of blood from an animal of a different species, accumu- lation of heat takes place likewise in consequence of diminished dissipa- tion. Perhaps a number of other pyrogenic agents act in the same manner. In dogs in which both carotids and both axillary and crural 404 FEVER. arteries were ligated at one time, with or without the related veins, the temperature was observed to rise almost i° C. within two hours. It is obvious that increased heat-production in the presence of normal heat-dissipation must give rise to accumulation of heat. In this categorv belongs the elevation of temperature following muscular and mental activity, and attending digestion. Finally, the elevation of temperature that appears several hours after a cold bath and is brought about by increased heat-production through reflex influences from the cooled skin is probably of the same character. If the temperature of the body as a whole is raised about 6° C. death results, as in the case of heat-stroke or sunstroke. At this tem- perature molecular decomposition of the tissues appears to take place. With long-continued, though less marked, elevation, distinct fatty de- generation of many tissues occurs. If animals whose temperature is raised artificially to 42° or 44° C. are subsequently placed in a cooler atmosphere, the temperature at first becomes subnormal (36° C.) and it mav remain so for days. FEVER. In many ways related to the accumulation of heat largely confined -svithin the limits of physiological phenomena fever occurs as the most common patho- logical derangement in the bodily economy and to it some reference may be made. Fever consists essentially in increased metabolism, chiefly in the muscles, together with elevation of temperature. Under these circumstances a disturbance in the regulation of the heat -balance must naturally take place, for if provision be made that with the increased heat-production also increased heat-dissipation shall take place, there can then be no elevation of temperature, or accumulation of heat. According to v. Liebermeister heat-regulation is placed upon a higher temperature- level during the febrile process. As in the state of fever the body appears to be in large measure incapacitated for mechanical activity, the transformation of this larger amount of decomposing potential energ\- in the body almost wholly into heat, and the failure to utilize this for mechanical activity, must moreover be especially emphasized as characteristic. Malarial intermittent fever may be considered as the prototype of fever. It is attended with severe paroxysms of fever lasting several hours in alternation with wholly afebrile periods, so that its symptoms may be readily analyzed. Among the individual phenomena of fever there are encountered: 1. Elevation of bodily temperature (to 38° or 39° C. constitutes mild, and from 39° to 41° C. and above, severe fever) . Not only the febrile patient with a burning, reddened skin (calor mordax). but also the shivering patient in a chill with an apparently cold skin may exhibit elevation of temperature. The reddened skin, however, is a good conductor, the pale skin a much poorer conductor of heat. Therefore, the former appears the warmer to the touch. 2. Increased heat- production, which had already been assumed by Lavoisier and Crawford, can be recognized indubitably by calorimetric measurement. This can be attributed only in smallest part to transformation of the increased circulatory activity into heat, but in largest part it is dependent upon heat generated in the processes of combustion. 3. Increased metabolism, to which the wasting character of fever is due. This was known to Hippocrates and Galen and was thus described by v. Barensprung in 1852 : "All so-called fever-symptoms indicate that during the febrile process tissue- consumption is abnormally increased. The increased metabolism is evidenced by augmented carbon-dioxid elimination (from 70 to 80 per cent.). In addition to carbon-dioxid elimination there is increased absorption of oxygen, at most 20 per cent, in a patient with acute fever, while the respiratory quotient remains unchanged. According to D. Finkler the production of carbon dioxid is susceptible of greater variation than the consumption of oxygen. The state of the nutrition is an index of the size of the respiratory quotient. The increase in gaseous interchange is not the result, but the cause, of the increased bodily tem- perature. The former takes place also when the bodily temperature is reduced by FEVER. 405 a cold bath. The elimination of urea is increase^ and heat, but not if bodily tissue is to be replaced. Under such circumstances two parts of gelatin take the place of one part of proteid. The carnivora, which can maintain their metabolic equilib- rium with large amounts of meat, are capable of doing this with less meat and a corresponding addition of gelatin. According to Munk the dog is capable for a few days of replacing ,■; of its proteid requirement by gelatin. A diet of gelatin exclusively is, however, inadequate. In addition the animals soon lose their appetite for such food. In consequence of its solubility the addition of gelatin (calf's-foot jelly) to the food of convalescents has been recommended. The absorbed products of the digestion of gelatin are conveyed to the connective tissues, which constitute a re- pository for it. After a long-continued diet of chondrin, together with meat, glucose has been found in the urine. LAWS GOVERNING METABOLISM. 443 AN EXCLUSIVE DIET OF FATS OR CARBOHYDRATES. If jat alone is supplied, the body is vinablc to maintain itself. In consequence of the deficiency of nitrogen, the animal must necessarily perish. The symptoms occurring with this form of diet are as follows: The animal in question secretes less urea than in a state of hunger. Therefore, the consumption of fat must restrict that of the flesh of the animal itself. This is due to the fact that the fat, being a readily combustible substance, is more readily oxidized in the body than the less readily combustible nitrogenous albuminates. If the amoimt of fat taken is exceedingly large, not all of the carbon of the fat can be recovered in the excreta, or as carbon dioxid in the expired air. Accordingly the body must accumu- late fat, while naturally it destroys protcids in corresponding amount. The animal thus becomes fatter and at the same time poorer in flesh. The result of administration of carbohydrates alone, which must first be con- verted into sugar by the digestive processes, exhibits marked similarity to that obtained with a pure fat-diet. It should, however, be noted that the sugar in the body more readily undergoes destruction than the fat, and, further, that with reference to the nutritive value, 256 parts of glucose are the equivalent of 100 parts of fat. Accordingly, a carbohydrate-diet restricts the decomposition of proteids even more readily than a pure fat-diet. Just as it is necessary outside of the body for the fermentation of disaccharids and polysaccharids that these be first decomposed into monosaccharids, so also the combustion of sugar in the body can occur only on condition that a trans- formation into monosaccharids has previously taken place. LAWS GOVERNING METABOLISM ON A MIXED DIET OF MEAT AND FAT OR CARBOHYDRATES. If a dog in a state of metabolic equilibrium be given an amount of fat and starch exceeding its requirements, elimination through metabolism is not in- creased, but the excess of these non-nitrogenous foods administered is deposited in the body of the animal as fat. If a dog fed with the leanest possible meat, and in a state of metabolic equilib- rium, be given an additional amount of meat exceeding its requirements, the elimination through metabolism increases almost proportionately to the addi- tional amount administered beyond the requirements. Only a small portion of the addition is conserved and increases the body-weight as a deposition of flesh. This augmentation of metabolism not only causes an increase in the nitrog- enous excretion in general proportional to the supply of proteid, but also the carbon contained in the supply of proteid is again excreted, for of the proteid fed no portion is deposited in the body as fat or carbohydrate. From both of these statements it follows that neither fat nor carbohydrate is capable of in- creasing metabolism beyond the requirements, although proteid is. The seat of active proteid metabolism after a diet rich in proteids is. according to Pfliiger, not in the increased flow of fluid, but within the proteid- containing cells which have undergone a marked alteration (saturation) as a result of the entrance of the proteid into them. This view is confirmed by the experiments of Schondorft", who found that if the blood of a fasting animal be forced through the tissues of a generously nourished animal the urea in the blood of the latter increases, while, on the contrary, if the blood of a well-nourished animal be forced through the tissues of a fasting animal the urea in the blood of the latter diminishes. As, on providing an adequate amount of proteid, mus- cular activity takes place only at the expense of proteid, and as in the decomposi- tion of this proteid neither fat nor carbohydrate results, fat or carbohydrate cannot be the source of muscular activity (Pfliiger). Other investigators are of the opinion, however, that with adequate nitrogenous nourishment energy as well as heat can be generated from fat and carbohydrate. Nourishment with Carbohydrates and Meat. — The organism is capable of gen- erating fat from carbohydrates. A deposition of fat in the body thus brought about takes place only if in addition to the proteid of the meat a nutritive excess of carbohydrates is present. Such an excess of starch may be present even when the supply of starch itself is small, while the excess may even be wanting when the supply of starch is large. The result depends upon the character of the food that is supplied in addition to the starch. The larger the amovmt of proteid, in 444 ORIGIX OF THE FAT IX THE BODY. addition to the starch, contained in the food, the more readily is an excess of starch to be attained without the necessity of supplying too much starch. If this condition of such an excess is not fulfilled, fat does not result even with generous administration of carbohydrates. The newly formed fat possesses the same potential energy as the nutritive excess resulting from the carbohydrates administered. Deposition of fat in the body does not take place, however large the excess of proteid food, if carbohydrates or fat be not supplied at the same time. On feeding with meat and starch, or in general with a mixed diet, the amount of newly formed fat depends in no wise upon the amount of proteid decomposed, but onl}' upon the amount of nutritive excess due to carbohydrates. Deposition of fat from carbohydrates takes place even when no proteid at all is supplied and the metabolism, therefore, must be maintained in part at the expense of a portion of the body-proteid. While for the maintenance of the metabolic equilibrium on a pure meat-diet an enormous consumption (from r.^ to ,,\ of the body -weight in the dog) is required, a third of the amount of meat suffices with an adequate addition of fat or carbo- hydrate. For loo parts of fat, added to the meat, 245 parts of dry meat or 227 of syntonin can be conserved. If carbohydrates are selected instead of additional fat, 100 parts of fat correspond to from 230 to 250 parts of carbohydrate. It should, however, be borne in mind that, at least for a short time, the carbohy- drates are superior to fat as a proteid-sparer, as the fat is less completely utilized in the process of metabolism than the carbohydrates. It appears that, instead of fat, a corresponding amount of fatty acids has the same effect in the process of metabolism. Glycerin is not capable of lessening the destruction of bodily proteid, although recently I. Munk has stated that moderate amounts of glycerin introduced into the circulation are consumed in the body and through their oxidation protect a portion of the bodily fat against oxidation. Accordmg to Lebedeff, v. Voit and Arnschink, glycerin, however, diniinishes the decomposition of bodily fat and is therefore a food-material. ORIGIN OF THE FAT IN THE BODY. A portion of the bodily fat is derived directly from the food, being simply deposited in the tissues after absorption. In favor of this view is the observation that with a scantv proteid diet a generous addition of meat causes the deposition of large amounts of fat in the body. The administration of fatty acids alone may also contribute to the formation of fat, inasmuch as glycerin, formed by the body, must combine with them in the process of metabolism. As a result of fattening experiments with different warm-blooded animals (pig, goose, dog), in which, in addition to a large excess of starch, only a small amount of fat and proteid is supplied, the conclusion has been reached that a direct transformation of the absorbed carbohydrates, rich in oxygen, into fatty tissue, poor in oxygen, takes place. Pfluger found that the sugar-molecule of the food, given in excess of the requirements for the development of fat in the animal, is in part oxidized and in part reduced, so that, on the one hand, carbon dioxid, and, on the other hand, the group of atoms concerned in the formation of fat, result, inasmuch as the molecular groups CH OH are reduced to CH3. The carbon dioxid that is exhaled when fat-formation takes place in consequence of the administration of starch is thus derived from two sources, namely, in part from the process of decomposition described, and in part from the total combustion of starch. The excessive elimination of carbon dioxid in this process of fat- formation in consequence of an excessive starchy diet mu.st naturally cause an increase in the respirator}^ quotient, even above 1.2. If the carbohvdrates be considered as decomposing into fat, carbon dioxid and water, 100 grams of starch or iii.i grams of sugar will yield at most 41.1 grams of fat, 47.5 grams of carbon dioxid and 11.4 grams of water. Also the circumstance that bees vitilize the sugar of honey in the formation of wax is in favor of the production of fat from carbohydrates. According to Pasteur and E. Voigt, glycerin can be formed from carbohydrates. Does fat result from proteid metabolism? v. Pettenkofer and v. Voit reached the conclusion, as a result of their experiments, that fat can be formed in the ani- mal body from proteids. They fed a dog with large amounts of meat, and although all of the nitrogen thereof was excreted in the urine and the feces, a portion of DEPOSITION OK FAT AM) I'LKSH IN THE KOUV. 445 the carbon of I ho meat could not he recovered from the excreta. They concluded, therefore, tlial this carbon had been transformed into fat for accumulation in the body. This statement is contradicted by Pfliiger on the basis of his own investiga- tions, which lead him to the conclusion that the doctrine of the development of fat from proteids in the bodies of animals is entirely groundless. If it were assumed that fat covild be formed from proteid, such formation is not possil)le through simple decomposition of the proteid molecule, but rather it would be necessary for decomposition first to take place and then synthesis of the decom- posed parts. Earlier investigators, who accepted the formation of fat from proteids, be- lieved that the proteids administered broke up into a non-nitrogenous and a nitrogenous atom-complex. The former, in case it did not leave the body com- pletely decomposed into carbon dioxid and water when a rich proteid diet was taken, was believed to furnish the material for the formation of fat, while the latter was supposed to leave the body oxidized principally into urea. The following experiments support the view that fat can develop from proteid fxirnished as food: (i) Ssubotin and Kemmerich fed nursing bitches with meat almost free from fat, and fovuid that the greater the amount of meat eaten, the greater was the amount of milk produced and thus also of fat. In these experi- ments, however, the possibility is not excluded that the bitches utilized the fat of their own bodies m the preparation of the milk. (2) Radziejewski gave a lean dog meat almost free from fat and in addition pure rape-oil, one of whose constituents, erucic acid, does not occur normally in the animal body. When the animal, aifter a period of feeding of considerable length, had accumulated fat, chemical examination demonstrated that the tissues contained, in addition to erucin, also fat which otherwise is normally present in the dog. In an analogous manner Lebedeff found in a dog after feeding with lean meat and linseed-oil con- siderable amounts of linoleic acid, together with normal dog's fat. In both experi- ments, however, the normal dog's fat could have been derived from the fat of the meat fed. (3) The fat found within organs in a state of pathological fatty degenera- tion had previously often been considered as derived from the proteid protoplasm of the tissues. Even though it be admitted, says Pfliiger, that the fat of the de- generated organs has developed within them, and has not gained entrance from without, it would still first be necessary to believe that the cells everywhere con- tain carbohydrates or their derivatives, which it is known with certainty can be transformed into fat by synthetic processes. Also the fatty degeneration produced in the animal body by phosphorus-poisoning affords no support for the view that fat is developed from proteid, for although a small amount of fat is found in the body after such poisoning, its development from proteid has not yet been demon- strated. In the case of fatty degeneration, there is primarily an injury of proteid bodies and in place of these fat from other sources appears in the cells in a certain measure as a reparative procedure. (4) Nageli showed that lower forms of fungi, like other plants, are able to form proteid, fat and carbohydrates synthetically from various matters, in part exceedingly simple. Thus, for example, fungi generate fat synthetically in ripening cheese probably from the products of de- composed proteid. In the decomposition of entire cadavers and their transforma- tion into a mass consisting almost wholly of palmitic and stearic acids (adipocere) in the presence of ftmgi, it cannot be concluded that a simple transformation of albumin into these fats takes place. DEPOSITION OF FAT AND FLESH IN THE BODY (HYPER- NUTRITION). CORPULENCE AND THE MEANS FOR ITS CORRECTION. Hypernutrition results if more food is supplied than the body is capable of decomposing and again eliminating. The digestive apparatus (collectively and in common activity) is probablv capable of digesting twice as much as the re- quirements demand. The absorbed excess of food that is not decomposed is accumtdated and forms the superfluous tissue. Higher animals are capable, although not in the strict sense, of surviving on an almost exclusively proteid diet. Pfliiger was able to keep a dog engaged in' hard work alive for an indefinite time on a diet exclusively of meat and almost free from fat. All of the vital phenomena, therefore, can be carried on by means of proteid alone. Albumin may, accordingly, 446 DEPOSITION OF FAT AXD FLESH IN THE BODY. wholly replace fat in the process of metabolism. The smallest amount of lean meat that thus maintains the metabolic equilibrium is designated by Pfliiger as the nutritive requirement. The supply of fat or carboh^'drates exclusively is never capable of maintaining life, as the animal under such circumstances is compelled to consume its own flesh. Therefore, a certain indispensable amount of proteid must absolutely be present in every diet. If an amount of proteid be added to the food that is suflicient in itself to fulfil the requirement and if any desired amount of fat is added, almost all of the proteid will be decomposed and almost all of the fat will be deposited as such. The conditions are much the same if carbohydrate is supplied instead of fat, except that in this case the carbohydrate is transformed in the body into fat and is deposited as such. The greater the amount of non-nitrogenous food that is supplied in addition to the nutritive requirement of proteid the more favorable are the conditions for fattening, because all of the non-nitrogenous matters are transformed into bodily fat. If proteid is not supplied in sufficient amount the deficiency may be made good by fat or carbohydrate, and in such proportion that two-thirds of the nutritive requirement may be supplied by non-nitrogenous matters. Under such circum- stances the latter replace the deficiency of proteid in accordance with the amount of their potential energy as indicated by the number of calories yielded in their combustion. From these facts it follows that the greater or smaller amount of albumin supplied with such food is decomposed almost wholly in the process of metabolism, indifterently whether much or little fat or carboh^^drate is sup- plied at the same time. In direct contrast to the proteid, the amount of fat or carbohydrate that is consumed in the process of metabolism is in nowise dependent upon the amount thereof contained in the food. Generally, the amount of carbo- hydrate or fat that undergoes decomposition is the smaller the larger the amount of proteid supplied. The nutritive requirement is satisfied first and foremost by proteid, but if the amount of proteid supplied is not sufficient, the fats and the carbohydrates are also utilized in so far as the requirements demand. In order to comprehend the laws of fattening by means of proteid and starch, it should be borne in mind that for the satisfaction of the nutritive reqtiirement, in addition to almost the entire amotnit of proteid supplied, so much carbohydrate is decom- posed as will wholly suffice for the nutritive requirement. The amount of carbo- hvdrate left over is deposited as fat. In accordance with the foregoing statements, on supplying equal amounts of carbohydrate a proportionately larger amount will be conserved the larger the amount of proteid furnished. The amount of nutritive requirement, that is, the smallest amount of fat-free meat that alone establishes metabolic equilibrium, is governed by the flesh-weight of the animal and increases in direct proportion to this. A fat animal has, there- fore, apparently a smaller nutritive requirement only because the total amount of fat, acting as a similar amount of dead matter, consumes nothing. The decomposition in the process of metabolism of the proteid taken with the food increases with the supply, even when this far exceeds the requirement, but a portion of the excess is always conserved. In this manner there is a gradual deposition of flesh in the body. As the amount of proteid supplied with the food has practically no influence upon the deposition of fat in the body, and the carbohydrates are generally not so useful as proteid, fat will be produced most advantageously with the smallest amount of proteid possible, but with the largest possible amount of starch in the food. If an animal on a mixed diet in a moderate state of fattening be given a further supply of proteid, this will at once satisfy a portion of the nutritive requirement, which theretofore had been satisfied by non-nitrogenous matters. These therefore can be dispensed with and are deposited as fat. With a diet of meat exclusively deposition of flesh is possible only when the proteid of the food exceeds the requirement. The largest portion of the excess of proteid is decomposed and some is deposited. With increase in the weight of flesh, the consumption of proteid soon increases, and, accordingly, the amount of excess diminishes. It is, therefore, one of the properties of proteid food that it tends speedily to neutralize the conditions necessary for the deposition of flesh if these are present. With a mixed diet deposition of flesh can be attained only if the supply of proteid exceeds the amount indispensable. Under such circumstances only from 7 to 9 per cent, on the average, at most i6 per cent., of the proteid supplied, is conserved by the non-nitrogenous articles of food. The deposition of flesh is then the greater the larger the amoimt of proteid contained in the food. Of the proteid CORPULENCE AND THE MEAN'S FOR ITS CORRECTION. 447 consumed the body can deposit only one part of proteid, while nine parts are decomposed. In addition, for two parts of decomposing proteid one part of fat is formed from the carbohydrate supplied in excess. Excessive deposition in the body of man, corpulence, is to be considered an abnormal manifestation of metabolism, which to the subject may be a source not alone of inconvenience, but also of disorders or even of serious danger. With reference to the causes of obesity, a certain degree of congenital predisposition (in from 33 to 56 per cent, of the cases) cannot be denied, inasmuch as members of certain families increase more readily in weight (as is likewise true of certain breeds of animals), while others, even when supplied with an abundance of food, which may reach enormous amounts, remain thin. The principal cause, however, is an habitually excessive supply of food beyond the normal metabolic average, although almost every corpulent person will with complacent self-deception main- tain that he really eats remarkably little. The mistake should be avoided of considering the corpulent individual as always excessively fat. The process of overfeeding results at hrst in the deposition both of fat and of flesh. On continuance of the process the development of muscular tissue diminishes, because in consequence of his clumsiness and helpless- ness the corpulent individual is rendered inactive. As a result, the nutrition of the muscular structures is secondarily impaired. Some active corpulent individ- uals, however, retain their large deposition of flesh throughout life. If, however, those factors become especially operative later on that favor the production of fat, corpulence may be transformed into obesity exclusively, as, naturally, is fre- quently the case. The following influences favor the development of corpulence: (i) An excessive diet of proteid, with a corresponding addition of fat or carbohydrate. The proteid of the food serves for the deposition of albuminates in the bod3^ while the fat is produced by the ingestion of fat and carbohydrates. (2) Diminished consump- tion of nitrogen in the body, in consequence of (a) lessened muscular activity (little movement, much sleep), (b) Enfeeblement of the sexual functions, as shown by the fattening of castrated animals, as well as the circumstance that women readily become corpulent after cessation of menstruation, probably in consequence princi- pally of withdrawal of the stimulating influence of vascular activity, (c) Dimin- ished mental activity (obesity of idiocy), phlegmatic temperament, probably for the foregoing reason. Conversely, vigorous mental activity, an excitable tem- perament, anxiety and grief counteract the fattening process, (d) The corpu- lent individual need consume relatively less material for the generation of heat in his body, partly because his compact body, in consequence of the greater concentration of mass, gives off less heat from the external integument than a delicate slender body, and partly because of the thick layer of fat as a poor con- ductor of heat prevents direct loss of heat by conduction. As a result of the relatively lessened production of heat in the body thus required, there may be an increased deposition of tissue. (N, and irymethalamin, CHiiVN, known only as decomposition-products of CH3 ) CHs ) cholin (neurin) and of kreatin. Neurin occurs in lecithin in complex combination. The lecithins are described on p. 463 and the diamins are discussed on p. 305. 2. Amids, that is derivatives of acids in which NH, is substituted for the hydroxyl (HO) of the acids. U rca . CO {'I'iYi^) 2. the diamid of CO^ is the principal end-product of the tissue-metamorphosis of the nitrogenous constituents of the body. Carbon dioxid containing water is CO (OH),, in which both OH-atoms are replaced by NH,, thus C0(NH2),. 3. Amido-acids, that is nitrogenous combinations exhibiting partly the character of an acid, and partly that of a feeble base, in which H-atoms of the acid-radicle are replaced by NH, or substituted ammonia- groups. (a) Giycin (amido-acetic acid, glycocol, gelatin-sugar) results on boiling gelatin with dilute sulphuric acid. It is present in the cornea, which contains, besides, chondrin. It has a sweet taste (gelatin-sugar), behaves like a feeble acid, but unites also as an amin-base with acids. It occurs as giycin -\- benzoic acid = hippuric- acid in the urine (it has also been prepared artificially) , and as giycin -I- cholic acid = glycocholic acid in the bile, {b) Leucin (amidocaproic acid) has been found pathologically in pus and in the atheromatous matter of sebaceous cysts, generally in combination with tyrosin. (c) Serin (amidolactic acid) is obtained from silk- gelatin, {d) 5/ooules. From these capillaries there collect throughout the entire extent of the medulla loops curving upward and downward, representing the beginning of the veins. The latter pass back toward the junction between the medullary and the cortical structure and gradually constitute the straight venules (c), which empty into the lower portion of the interlobular veins. On the papilla; the capillaries of the medulla communi- cate with vascular branches in garland-like arrangement surrounding the papil- lary ducts. The vessels of the fibrous capsule of the kidney are derived in part from pene- trating branches arising from the extremity of the interlobular arteries and in part from branches of the suprarenal, phrenic and lumbar arteries, between which anastomoses take place. The capillary network is a simple mesh-arrangement. The venous radicles pass over in part into the stellate veins and in part into veins of the same name as the arteries. A number of venous radicles also pass out of the cortex. The communication between the distribution of the renal artery and other arteries in the capsule explains the fact that after ligation of the renal arter}' within the kidney the blood-stream may enter from the capsule. Arterial blood also is sent to the kidney and this may even give rise to a slight secretion. Lymphatics are present within the fibrous capsule as a wide-meshed network and beneath the capsule in the form of spaces of considerable size. In the parenchyma of the kidney itself the lymph is said to circulate between the urinary tubules and the blood-vessels, in tissue-spaces without walls which are found in larger number around the convoluted tubules than around the straight tubules. The spaces reach to the surface of the kidney and are dis- tributed extensively beneath the capsule. Marked distentioji of the lymph-spaces compresses the urinary tubules and the vessels. Large lymphatics, provided w-ith valves, are visible at the hilus of the kidney, while others pass through the fibrous capsule, both communicating with the' lymph-spaces of the capsule of the kidney. Of the nerves, branches provided with ganglia accompany the afferent vessels. Non-meduUated fibers penetrate to the surface of the capsule and between the urinary tubules. It is establi.shed physiologically that motor libers are present for the unstriated muscular fibers, also vasomotor fibers and sensor}^ branches in the capsule and the pelvis of the kidney. The existence of vasodilator and secretory fibers is also probable. The connective tissue of the kidney forms in the papilte fibrillated, con- centric layers about the excretory ducts (VI). Further upward star-shaped cells of reticular tissue appear in addition and these are found alone in the cortex. The outer layers of the fibrous capsule of the kidney are formed of dense bundles of fibrils, while the inner layers are looser and send processes into the cortical layer. The fatty capsule of the kidney is connected w'ith the organ itself, in part through vessels and in part through bands of connective tissue. Unstriated muscular fibers are contained in the kidney in three forms: (i) A sphincter-like layer surroimding each papilla; (2) a wide-meshed net- work on the surface of the kidney; (3) libers that arise from the depth of the pelvis of the kidney and pass through the pyramids with the blood-vessels 472 THE URINE. H. Kostjurin found at the junction of the cortical and the medullary structure, in the dog, a layer of muscle-fibers from which bundles pass in each direction. THE URINE.- THE PHYSICAL CHARACTERS OF THE URINE. The amouyit of urine in men is between looo and 1500 cu. cm. in twenty-four hours; in women between 900 and 1200. There is a min- imimi between 2 and 4 a. m., a maximum in the morning and a second maximum between 2 and 4 p. m. The amount of urine is diminished by profuse perspiration, diarrhea, thirst, food deficient in nitrogen, reduction in the general blood-pressure, after profuse hemorrhage, as a result of the action of certain poisons, such as atropin and mor- phin, and in the presence of certain diseases of the structure of the kidney. The minimum that may still be considered normal is between 400 and 500 cu. cm. The amount is increased by increase in the blood-pressure in general, or in the distribution of the renal artery alone, by copious drinking, contraction of the cutaneous vessels from the action of cold, the elimination of soluble diuretic substances, such as urea, salts, and sugar through the urine, a diet rich in nitrogen, as well as by certain medicaments, such as digitalis, juniper, squill, alcohol, etc. Carbonated beverages increase the urine in the succeeding hour. The direct influence of the nervous system upon the amount of urine is also familiar. In this categorA- belongs the poh'uria suddenly developed after nervous perturbation, as, for instance, in hysterical persons, following epileptic attacks, and also after pleasurable excitement, and finally the remarkable increase in urinan.- secretion after injurs" of the floor of the fourth ventricle of the brain. Nocturnal polyuria occurs in persons suffering from disease of the heart and the kidneys, in cachectic states and in the presence of arterio-sclerosis. Neurasthenic anuria of neurotic origin lasting from twelve to fifty-six hoiirs is extremely rare. The urine can be measured in graduated cylinders or flasks. The specific gravity of the urine varies between 1015 and 1025. The minimum is observed after abundant ingestion of water, 1002; the maximum after profuse sweating and marked thirst, 1040. In the new- bom the specific gravity falls considerably in the first few days, in conformity with the progressive increase in the amotmt of nourishment taken. The adult discharges per diem on the average i gram of solids through the urine for every kilogram of body-weight. The determination of the specific gravity is made, with the urine at a tem- perature of 16° C, bj- means of the urinometer (Fig. 144). If but a small amount of urine is obtainable and it does not sufficiently fill the urinometer-cylinder the urine is diluted with twice or thrice its volume of distilled water, and then the last two figures on the urinometer are multiplied by two or three respectively. By means of the formula of Trapp or Haeser the amount of solids contained in 1000 parts of urine can be estimated approximately from the specific gravity. Of the number indicating the specific gravity, as, for instance, 10 18, the last two figures are taken, in this instance therefore iS, and multiplied by 2.33. The estimation of the total solids can be made in a more trustworthy manner by evaporating about 15 cu. cm. of urine in a weighed porcelain-dish over the water-bath and subsequent complete dr\-ing in the air-bath at a temperature of 100° C. and cooling over concentrated sulphviric acid. In this way some urea is decomposed into carbon dioxid and escaping ammonia, in consequence of which the result is some- what too low. The specific gravity depends naturalh^ upon the amount of water in the urine. The urine of the morning (urina noctis) is most concentrated, that is, heaviest, because water is absorbed from the bladder after the urine has been * The illustrations are taken in part from Ultzmann and Hoffmann's Atlas of Urinarj' Sediments. THE PHYSICAL CHARACTERS OF THE URINE, 473 .1010 .1080 present for a considerable time during sleep and the urine thus becomes in- spissated. The most dilute urine is encountered after copious drinking (urina potus). Hunger and laxatives diminish, while jihysical exertion increases, the amount of solids in the urine. Among pathological conditions, highlj' concentrated and copious tirinc, up to lo.ooo cu. cm., is observed in ca.ses of diabetes mellitus (p. 313), when the specific gravity may be from 1030 to 1060. Concentrated, scanty urine is encountered in the presence of fever. Simple, for instance, ner- vous, polyuria is characterized by ex- tremely dilute and copious urine, and the specific gravity may be as low as looi. The color of the urine exhibits various gradations principally in accordance with the amount of water contained. Highly diluted urine is likely to be pale yellow in color. Urine of watery clearness has even been observed in associa- tion with sudden polyuria — as, for instance, the spastic urine of the hysterical. Concentrated urine, particularly after a generous meal, varies from dark yellow to brown- ish red in color. Urine of similar tint in association with fever is commonly designated high-colored. Fetal urine, as well as that passed immediately after birth, is as clear as water. Admixture of blood gives rise, in accordance with the degree of disinte- gration of hemoglobin, to a color vary- ing from red to deep brownish-red; bili- ary pigment to a deep yellowish-brown color, with an intense yellowish foam; senna, taken by the mouth, causes the urine to have a deep-red color, rhubarb a brownish-yellow color, carbolic acid a black color. Urine in a state of am- moniacal decomposition maj^ present a dirty-blue appearance from the forma- tion of indigo. For uniform estimation of the color of the urine a urinary color- scale has been devised empirically. The urine, especially if in a state of ammoniacal decomposition, exhibits fluorescence, which disappears on addi- tion of acid, and reappears on addition of alkali. Normal urine precipitates in the course of a few hours a cloud or nubecula of vesical mucus that settles slowly. The froth of normal urine is white and it disappears rather quickly, though persist- ing for a longer time when albumin is present. Not rarely the urine contains a number of epithelial cells. Xormal urine flows in a limpid stream like water. The presence of considerable amounts of sugar, albumin or mucus diminishes its fluidity. So-called chylous urine from patients in the tropics may even present a white, gelatinovis appearance. The taste of urine is saline and bitter, the smell characteristically aromatic, approximating that of beef-broth, particularly after the inges- tion of roast meat. Fig. 14.^. — Graduated cylinder and Flask, for measuring the .Amount of Urine. Fig. 144. — Urinometer. 474 THE PHYSICAL CHARACTERS OF THE URINE. Urine in a state of ammoniacal fermentation exhibits the odor of ammonia. Of substances taken by the mouth, turpentine gives rise to the odor of violets, copaiba and cubebs to an aromatic odor, and asparagus to a disgusting odor due to methylmercaptan. Valerian, garlic and castor yield up some of their odorous constituents to the urine. The reaction of normal urine is acid from the presence of acid salts, especially acid monosodium phosphate (PO^HoNa). The latter re- sults from alkaline disodium phosphate (PO^HNaj), uric acid, hippuric acid, sulphuric acid and carbon dioxid each taking up one atom of so- dium, so that the phosphoric acid must be displaced to form the acid salt. After a meat-diet acid potassium phosphate especially causes the acid reaction. That the urine contains no free acid is shown by the fact that no precipitate takes place on addition of sodium hyposulphite. Night-urine exhibits the highest, morning-urine the lowest degree of acidity. Sometimes the reaction of the morning-urine is alkaline. The acid reaction becomes increased after ingestion of acids, such as hvdro- chloric acid and phosphoric acid; as well as of ammonium-salts, which are trans- formed in the body into nitric acid; after active mtiscular exercise; after a milk- diet; and pathologically in the presence of hyperacidity of the gastric juice. The absolute elimination of acid is increased by marked diuresis, while the relative elimination is diminished. The acidity of the urine is lessened and its reaction may even be rendered alkaline: (i) By the ingestion of caustic alkalies, alkaline carbonates, or alkaline salts of the vegetable acids — the last being oxidized in the body into alkaline carbonates. (2) By the presence of calcium or magnesittin carbonate. (3) By admixture of blood or pus of alkaline reaction. (4) By drainage of the acid gastric juice outside the body through. a fistula; further, in from one to three hours after digestion, in consequence of the formation of acid in the stomach. (5) By the absorption of alkaline transudates, such as serum or blood. (6) In con- sequence of profuse secretion of sweat and hot baths. If the surface of the body is kept at a temperature of 31° C. and 30 per cent, of relative humidity, alkaline urine will be excreted in the morning-hours, on account of the fixed alkaline carbonates, while the evening-urine exhibits a strongly acid reaction. (7) The urine has rarely been observed to be alkaline in anemic persons, from deficiency of phosphoric and sulphuric acids. The reaction is tested by means of strips of violet litmus-paper, which become red when dipped in acid urine and blue in alkaline urine. In order to determine the degree of acidity of the urine it is necessary to learn the amount of sodium hydroxid required to render exactly neutral the reaction of 100 cu. cm. of urine. For this purpose a solution of sodium hydroxid is employed of which each cubic centimeter contains 0.0031 gram of sodivim; i cu. cm. of this solution neutralizes exactly 0.0063 gram of oxalic acid. From a graduated buret (Fig. 145) the sodium- solution is permitted to escape drop by drop into a beaker containing 100 cu. cm. of urine, with constant stirring, until violet litmus-paper no longer becomes either red or blue. The amount of sodium-solution in cubic centimeters is read from the scale of the buret, and as each cubic centimeter corresponds to 0.0063 gram of oxalic acid, the amount of oxalic acid that is the equivalent of the acid in the 100 cu. cm. of urine can be readily estimated. The degree of acidity of the urine is therefore expressed in terms of the equivalent amount of oxalic acid that is fully neutralized by the same amount of sodium hydrate. The urine of carnivora varies in color from pale to golden yellow. It has a high specific gravity and exhibits a strongly acid reaction. The urine of herbivora has an alkaline reaction and therefore exhibits precipitates of earthv carbonates (so that it effervesces on addition of acid) and of earthy basic phos- phates. In the state of htinger it acquires the character of the urine'of carnivora, as under these conditions the animal in a certain measure lives upon its own tissues. THE ORGANIC CONSTITUENTS OF THE URINE. 475 THE ORGANIC CONSTITUENTS OF THE URINE. UREA: C0(NHn)2. Urea, the diamid of CO^ or carbamid must be considered as the principal end-product of the oxidation of the nitrogen-containing consti- tuents of the body. It has the following extremely simple composi- tion: I atom of carbon dioxid + 2 atoms of ammonia — i atom of water. It crystallizes in silky-glistening, four-sided prisms, with oblique ends, be- longing to the rhombic system (Fig. 146. I, 2), without water of crystallization; when rapidly crystallized it forms delicate, white needles. It has no in- fluence upon litmus, is odorless, and of a feeble bitter, cooling taste like that of potassium ni- trate. It is readily soluble in water and in alcohol, but almost insoluble in ether. It is isomeric with ammonium cyanate, from which it develops on evapora- tion through atomic displace- ment. Numerous other modes of artificial preparation are known. Heated to a temperature above 120° it is decomposed, with the de- velopment of vapors of ammonia, and leaving a vitreous mass of biuret and hydrocyanic acid. In the pro- cess of ainmoniacal putrefaction and as a result of treatment with strong mineral acids, of boiling with alka- line hydrates and of heating with water at a temperature of 240° C, it takes up two atoms of water and vields ainmonium carbonate: COCNHj), + 2H,0 = CO(ONH^j). Brought in contact with nitrous acid it is decomposed into water, carbon dioxid and nitrogen. The last two forms of decomposition have been employed for the quantitative estimation of urea. The amount of urea in normal urine is between 2.5 and 3. 2 percent. Adults excrete daily about from 30 to 40 grams; women less; children relatively more. In accordance with the more active metabolism in the latter, the amount of urea furnished by the weight-unit of the child's body, as compared with that of the adult, is as 1.7 to i. If the body is in a condition of metabolic equilibrium almost as much nitrogen is eliminated in the form of urea as is introduced into the body with the food. The amount of urea increases with the amount of proteids in the food, Fig. 145. — Graduated Buret. 476 UREA. as well as with the degree of disintegration of the nitrogen-containing tissues in the body. As the latter is increased by withholding oxygen and by hemorrhage, these also cause an increase in the amount of urea. The administration of large amounts of water — by more thorough washing out of the tissues — and also of salts, frequent micturition and exposure to compressed air likewise increase the amount of urea. In diabetics who partake of large amounts of food, the amount of urea occasionally exceeds loo grams daily, while in the state of hunger it falls to 5.6 grams. In the state of inanition a maximum of elimination has been observed toward noon, and a minimum toward morning. Daily variations in the amount of urea pursue a course parallel with the amount of urine. Three or four hours after digestion begins the forma- tion of urea reaches its maximum, subsequently falling again and reaching its minimum during the night. The excretion of urea, and in the same proportion that of the total nitrogen, with the urine is materially aug- mented in consequence of increased muscular activity. This excretion Fig. 146. — I, 2, Prisms of pure urea; 3, rhombic f)lates; 4, hexagonal tablets; 5, 6, irregular scales and plates of urea nitrate. is less on the first working day, as observed in dogs, than on the second and third, but it is still increased on the two resting days succeeding the work. Pathological. — In the presence of acute febrile inflammatory processes and of fever in general, the excretion of urea increases to the height of the morbid process, in association with which it again declines. After the cessation of the process the excretion is often subnormal. At times the formation of urea may be in- creased in association with high fever, but the excretion may be checked and retention of urea takes place. In the further course of the disorder the excretion may be greatly increased. In chronic diseases the ainount of urea varies with the state of the nutrition, the metabolism of the patient and in accordance with the height of the accompanying fever. Degenerative disorders of the liver, as, for instance, from phosphorus-poisoning, may be attended with diminished excre- tion of urea and increased excretion of ammonia. Substances that increase the proteid disintegration in the body, as, for instance, arsenic, antimony-combinations, and small amounts of phosphorus, increase the formation of urea; while those that conserve proteids, as, for instance, quinin, diminish the production. Increased formation of bile in the liver gives rise at the same time to increased formation of urea. UREA. 477 Urea rei)rcscnts the end-product of the metabolism of proteids. Next in order there stand, as lower stages of oxidation, uric acid, guanin, xanthm. hypo- xanthin alloxan and allantoin. Uric acid administered as urates appears in the urine as urea being transformed by the liver, with increase m the secretion of bile Muscle-extractives have tlie same effect, and in general increased formation of bile is attended with augmented formation of urea. After administration of leucin, glycin, aspartic acid or of ammonium-salts an increase m the excretion of urea takes place. The liver is the principal, but not the sole seat of the formation of urea. The correctness of the supposition of Schmiedeberg that the urea is derived from ammonium carbonate through loss of water was demon- strated by V. Schroder, who found urea in large amount in blood to which ammonium carbonate had been added, and made to pass through a recently removed liver. It is, therefore, to be concluded that am- monium-combinations derived from nitrogen-containing tissues as meta- bolic products pass over into the circulation, through which they are conveyed to the liver for the formation of urea. The organism is capable of converting considerable amounts of ammonia, as, for instance, in the form of lactate or acetate, into urea. The liver forms urea also from the ammonia in the blood of the portal vein. In the metabolism especially of proteids there is formed in many organs by oxidation car- bamic acid, CO2NH3, which likewise is transformed principally m the liver into urea, and also the amido-acids. If acids are taken into the body before the ammonium-combinations are transformed into_ urea, there result ammonium-salts, with a corresponding reduction m the amount of urea in the urine. Under pathological conditions the urea-forming activity of the liver may be diminished. \fter extirpation of the liver, the urine no longer contains urea, and likewise after exclusion of the hepatic circulation, but on the other hand large amounts of amnionium-salts. , . ,. ^, • , ^i. • r • Eck in the dog, diverted the blood of the portal vein directly into the inferior vena cava, by establishing an artificial communication between the two vessels and then igated the portal vein close to the liver. The dogs w-ere seized with severe nervous attacks and convulsions. As, according to v. Schroder, ammonium- salts are transformed in the liver into urea, this transformation is thus almost wholly prevented, and the substances named now exert a toxic effect upon the nervous system. ^ , , . -j • ^ ^u i 1 i «. Bv iniection of a 6.2 per cent, solution of sulphuric acid into the bile duct, in the dog, all of the liver-cells became necrotic, and the animal died in one or two days with signs of prostration, mental derangement, loss of sensibility central narcosis and finally convulsions. From this it has been concluded that the liver serves the purpose of converting a toxic metabolic product, carbamic acid, into an innocuous one, urea. ^ r ■ ^-a f^r.,^ ti-.^ in birds the liver thus produces the largest amount of uric acid from the ammonium supplied. As birds readily tolerate ablation of the liver, Minkowski observed after this operation reduction in the amount of unc acid and in- crease in the amount of ammonium-salts m the urine. u,^r.Vi Urea is present in the following parts ot the body: Blood (i . 10,000 , lyniph, chyle (2 : 1,000); liver, lymphatic glands, spleen, lungs bram eye, bile saliva amnLtic fluid; by Schbndorff it was found m the muscles and the erythrocytes a^d in almost all of the organs of the dog; besides, pathologically, m the sweat asforSance, in cases 0I cholera, as well as in the vomitus and m dropsical ^"^^ThlpTeprat^o'n'o'f'urea can be accomplished directly from dogs' urine after c^enerous^Sfg w?tS meat, the fluid being evaporated to a syrupy consistency Extracted with alcohol, the filtered extract agam ^^^P°7^^^,^',^^,\'^^^f J^^^'S,"^ separated freed of the adherent extractives by means of alcohol and then dis Sowed in absolute alcohol. Filtration is practised again and evaporation is per- initted to take place until crystallization occurs. A given volume of human urine 47S QUALITATIVE AXD QUANTITATIVE ESTIMATION OF UREA. is evaporated to one-sixth of its original volume, is reduced to a temperature of 0° and an excess of strong, pure nitric acid is added. Urea nitrate contaminated with coloring-matter is precipitated. The precipitate is filtered, expressed, dis- solved in a little boiling-water, mixed with animal charcoal for the removal of the coloring-matter, and filtered hot. On cooling, decolorized crs'stals of urea nitrate separate from the filtrate. These are again dissolved in hot water, and barium carbonate is added so long as effervescence takes place. Barium nitrate and free urea are thus formed. Evaporation to dn.mess is now practised, fol- lowed by exhaustion with absolute alcohol, filtration and evaporation, after which the urea separates in cr\-stals. Combinations of Urea. — Urea is capable of entering into combination with acids, as nitric, oxalic or phosphoric, or with bases, or with salts, as sodium chlorid, mercuric nitrate. The most important combinations are: 1. Urea nitrate: CH^XoO.NOjH, whose mode of preparation from the urine has just been described. The preparation of urea nitrate is employed with advant- age for the microscopic demonstration of urea. If there are but a few drops of water}' fluid in which the presence of urea is suspected — and this must be so prepared' that the urea present is in concentrated watery solution — one drop of this fitiid is placed upon a glass slide, a thread is laid through the middle of the drop and over both is placed a cover-slip. From the extremity of the thread a drop of concentrated nitric acid is permitted to find its way beneath the cover-slip. The characteristic cr}-stals appear upon either side of the thread (Fig. 146, 3, 4, 5, 6). Urea nitrate is readily soluble in water, soluble with difficulty in water acidtilated with nitric acid. Less commonly, when crystallization takes place slowly, it yields six-sided prisms. 2. Mercuric-nitrate urea is obtained in the form of a white, cheesy precipitate, Avhen mercuric nitrate is introduced into a solution of urea. If, on the develop- ment of the precipitate, the nitric acid set free is neutralized by sodium carbonate, all of the urea eventually combines with the mercuric salt. When this point has been reached, all excess of mercuric nitrate gives rise, on addition of sodium carbonate, to the production of sodium nitrate and yellow basic mercuric carbo- nate. The titration-method of J. v. Liebig for urea is based upon this reaction. QUALITATIVE AND QUANTITATIVE ESTIMATION OF UREA. The qualitative estimation of urea aims (i) at the preparation of this substance directly as such. If its presence be suspected in an albuminous fluid mixed with blood or pus, the following course is pursued: Three or four times its volume of alcohol are added to the fluid, and filtration is practised after the lapse of several hours. The filtrate is evaporated over the water-bath, and the residue is dis- solved in a few drops of water. (2) This aqueous solution is employed for the microchemic preparation of urea nitrate, which has important diagnostic signifi- cance. (3) By means of a solution of sodium hypobromite, the urea in the fluid submitted to examination is decomposed into carbon dioxid, water, and nitrogen. The nitrogen rises in the mixture in the form of small bubbles. The Knop- Hiibner method of quantitative estimation is based upon this reaction. (4) A cn.-stal of urea is cautiously fused in a dry test-tube, and yields an odor of am- monia. On cooling, it is dissolved in a small amount of water, and sodium hy- drate, together with one drop of dilute copper sulphate, is added, with the develop- ment of a red-color— biuret-reaction. Quantitative estimation of urea in the urine, according to the method of Momer and Sjoqvist: To 2.5 cu. cm. of urine are added 2.5 cu. cm. of bar\'ta-mixture (1 volume of a cold saturated solution of barium hydrate and 2 volumes of cold saturated barium nitrate) and 75 cu. cm. of ether- alcohol (the alcohol must be 70 per cent.). The mixture is preserved for a day sealed. It is now filtered, and the filtrate, which contains of the nitrogenous substances only the urea, is evaporated at a temperature of 55° C. after the addition of 0.5 gram of magnesium oxid. After the addition of 10 cu. cm. of sulphuric acid it is further evaporated upon a boiling water-bath, until no further reduction in volume takes place. Then it is placed in a Kjeldahl boiling-flask, and the examination is continued according to the Kjeldahl method. The method of Kjeldahl is employed for the estimation of the total amount of nitrogen in the urine. It is based upon the fact that all of the nitrogen is transfonned into ammonia, and this is estimated quantitatively. Five cu. cm. of urine of inoderate concentration are measured by means of a pipet and intro- URIC ACID. 479 duccd into a llask liaving a cajiacity of about 200 cu. cm., with 20 cu. cm. of pure English sulphuric acid (to one liter of which 200 grams of phosphoric anhydrid are added), and one drop of metallic mercury; and this is boiled over the sand- bath until the fluid, which at first was dark, is entirely decolorized. On cooling, the fluid is rin.sed with about 200 cu. cm. of water into a flask having a capacity of half a liter, and 100 cu. cm. of sodium hy- drate (of a sp. gr. of 1.34), a few cu. cm. of an aqueous solution of potassium sulphid, and some powdered zinc are added. The flask is then quickly closed with a stojiper and the ammonia set free is distilled into a receiver containing 50 cu. cm. of one- tenth normal sulj^huric acid. The extremity of the tube from which the ammonia escapes must be immersed in the normal sulphuric acid. In order to determine whether all of the am- monia is present in the receiver, the stopper of the receiver is cautiously removed, a strip of litmus-paper is placed by means of a pair of forceps in front of the tube conveying the ammonia, and note is made whether the escaping distillate causes the strip to turn blue. The amount of sulphuric acid in the receiver not saturated by ammonia is determined by titration with one-tenth normal sodium hydrate. According to Pfiiiger and Bohland, the amount of nitrogen in the urine can be estimated approximately by the following simple method: To 10 cu. cm. of urine, Liebig's urea-titrating solution is added from a buret, and the mixture is tested upon a dark glass plate with sodium bicarbonate drop by dro]:), as in the estimation of urea. If the stirred stain remains yellow, the number of cubic centimeters of titration-fluid employed is mul- tiplied by 0.04 and in this w^ay the percentage of nitrogen present is obtained. The total amount of nitrogen in the urine is to the nitrogen in the urea approximately as 5 to 4. URIC ACID— CjH.N.Oj. Next to urea, the greatest amount of nitrogen is eliminated as uric acid, namely, 0.5 gram in 24 hours (in the state of hunger, 0.24 gram ; after a generous meat- diet, 2.1 1 grams). The amount of uric acid is to that of urea on the average as i to 46, though with many varia- tions. In the mammahan body the uric acid is formed from the nuclein of the disintegrating leukocytes. With increase in the latter, there is increase in the amount of uric acid formed. . Ingestion of nuclein — as, for instance, after the eating of thymus gland — increases the number of leukocytes in the blood and the excretion of uric acid. Xanthin-bases (guanin, xanthin, hypoxan- thin) occur in the intestines as products of the digestion of nucleins. If they be increased in amount, an increase in the amount of uric acid results. Fig. 147. —Gradu- ated Pipet. In birds, reptiles and insects, uric acid is the principal nitrogenous excrementi- tious product; while it appears in but small amount in the urine of herbivora. The products of the decomposition of leukocytes present in surviving splenic pulp (nuclein) yield, w^hen treated with fresh blood at the temperature of the body, an abundance of uric acid, together with xanthin and hypoxanthin. Also the nuclein of the nuclei of many other tissues has also shown itgelf to be a source of i:ric acid. In addition to uric acid, xanthin-bodies are formed in the same way. When animals are fed with nucleinic acid and hypoxanthin, the elimination of uric acid is increased. Uric acid fed to mammals passes into the urine in part further oxidized into urea, together wdth an increase in the amount of oxalic acid. In hens there is increased elimination of uric acid after the administration of leucin, glj'^cin, aspartic acid, hypoxanthin, or ammonium carbonate. The urea administered to hens is, however, eliminated chieflj^ reduced to uric acid. 48o URIC ACID. Uric acid is dibasic, tasteless, odorless, and colorless, soluble with great difficulty in water (in 15,000 parts of warm, or 18,000 parts of cold water, though in 2,000 parts of a 2 per cent, solution of urea), insoluble in alcohol or ether. It crystallizes in various forms (Fig. 148), the basic type of which is the rhombic plate (i). Enlargement of the op- posed larger angles causes the formation of the whetstone-shape fre- quently observed (2). If the longer sides of the latter are flattened, six-sided plates result. Large, golden-yellow crystalline rosets (6, 8) often separate spontaneously from diabetic urine. Precipitated by addition of hydrochloric acid (25 cu. cm.) to urine (one liter) or of acetic acid, the crystals usually assume the form of a barrel (9) or a bundle of spears that are tinged brownish violet by adherent urea. Uric acid is readily solvible in alkaline carbonates, borates, phosphates, lactates, and acetates. Removing a portion of the base from these salts, there restdt, on the one hand, acid urates; and on the other hand, acid salts from the neutral Fig. 148. — Different Forms of Uric .\cid: i, rhombic plates; 2, whetstone-shape; 3, quadratic .shape; 4, 5. elon- gated forms with two pointed extremities; 6, 8, arrangement of several crystals in the form of a roset; 7, crystals drawn out into the shape of a lance; p, so-called barrel-shape obtained from human urine by means of hydrochloric acid, in part darkly discolored. salts. Among alkalies, lithium (citrate) is especially noteworthy as a solvent of uric acid. According to v. Noorden and Strauss, a favorable coniposition of the urine will be obtained if calcium carbonate or calcium-salts of the vegetable acids (from 2 to 10 grams) are administered. Phosphoric acid leaves the body with the cal- cium through the intestines. In consequence, the monosodium phosphate in the urine is diminished, as it gives up the phosphoric acid and thus disodium phos- phate results. The latter, however, is capable of dissolving uric acid, inasmuch as sodium urate and monosodium phosphate are formed. Uric acid is soluble in concentrated sulphuric acid, from which it is reprecipitated by water. Plumbic oxid converts it into urea, allantoin, oxalic acid and carbon dioxid; ozone pro- duces the same substances, together with alloxan. Reduced by hydrogen in a nascent state, xanthin and sarcin are produced. Horbaczewski has prepared uric acid synthetically by fusing one part of glj^cin and seven parts of urea. In the urine, the uric acid is dissolved principally in the form of acid sodium and potassium urate. These salts are present also in urinary URIC ACID. 481 sediments, urinary sand, and urinary calculi. Ammonium urate is con- tained in lateritious sediment in but small amount, being formed in large amount only as a result of ammoniacal decom])osition of the urine (Fig. 154). Free uric acid occurs in normal urine only in the smallest amount. It is, however, not rarely precipitated subsequently on standing (Fig. 153), and it is present, further, also in urinary sand and calculi. De- ficiency of neutral phosphates in the urine favors the formation of uric- acid sediment. The urine of the new-born is rich in uric acid (uric-acid infarct of the kidneys) . The uric acid, together with its salts, is increased by marked muscular activity attended with perspiration, also in the presence of catarrhal and rheumatic fevers and such as are attended with derangement of respiratory activity; further, in cases of leukemia with increased leukocyte-destruction and splenic tumor, granular liver; and, linally, quite generally in connection with gastric and intestinal catarrh following excessive indulgence in alcohol, after generous ingestion of cheese and salt fish or salt ineat, after administration of glycerin, and a diet containing nuclcin. Hypoxanthin fed to birds is eliminated in part transformed into uric acid. The amount of uric acid is diminished after generous ingestion of fresh fruits (strawberries, cherries, grapes) or of quinic acid or alkaline salts of the vegetable acids contained in them; further, after hot baths; also after ingestion of proteids in large amount and after the administration of caffein, potassium iodid, sodium chlorid, sodium carbonate, lithium carbonate, sodium sulphate, inhalations of oxygen, gentle muscular exercise, though not after copious ingestion of water. In cases of gout in which uric acid is deposited in the gouty nodules, its elimination is slight. In the presence of chronic splenic tumor, anemia, and chlorosis, it is diminished, particularly if no respiratory disorder is at the same time present; and likewise in cases of epilepsy in advance of an attack. TJie Urates.— With various bases uric acid forms principally acid urates, which are soluble with difficulty in cold water and readily in hot water. Neutral urates are transformed by carbon dioxid into acid salts. Hydrochloric and acetic acids dissolve the combinations and the uric acid separates in the form of crystals. Acid sodium urate, sodium biurate, has a neutral reaction, and ap- pears as a uratic sediment (lateritious sediment) generally of a brick- red color from uroerythrin (according to Hoppe-Seyler from urobilin) — less commonly it is between light gray and whitish in color — in the presence of catarrhal digestive disorders and of rheumatic and febrile affections. Microscopically it appears as amorphous granules (Fig. 153, h). The sediment is dissolved by heating the urine. Not rarely the sediment contains also the potassium-salt, which is entirely similar Acid ammonium urate is soluble with difficulty in water, is always present, as a sediment, in ammoniacal urine, appears in reflected light in the form of yellowish spheres of thorn-apple or morning-star shape — in transmitted light of a darker color — and is frequently accompanied by triple phosphates (Fig. 154, a). Acid sodium urate and acid ammonium urate are recognized by the separation of free uric-acid crystals in microscopic preparations, after addition of a drop of hydrochloric acid. Acid calcium urate, occasionally present in urinary calculi, is a white amorphous powder soluble with difficulty in water. Fused upon a platinum plate, it leaves a residue of calcium carbonate. Rarely magnesium urate occurs in urinary calculi. 482 QUALITATIVE AND QUANTITATIVE ESTIMATION OF URIC ACID. QUALITATIVE AND QUANTITATIVE ESTIMATION OF URIC ACID. Qualitative Estimation. — i. The microscopic deiiioiistralion of uric acid and the urates is based upon the characteristics that have been described. Uric acid is precipitated from urine by addition of acetic or hydrochloric acid. 2. The niurexid test. Uric acid or urates are heated in a shallow dish with nitric acid at a low temperature. Decomposition takes place, with the develop- ment of a yellow color. Nitrogen and carbon dioxid escape, while urea and alloxan (C4H2N2O4) remain behind. Evaporation is now cautiously carried further, and the resulting yellowish-red stain is permitted to cool. The addition of a drop of dilute ammonia produces a purple-red color (murexid = ammonium purpurate: alloxantinamid) . This red color becomes blue on further addition of potassium hydrate. If, at the outset, potassium or sodium hydrate is added to the stain, instead of ammonia, a violet color results. 3. If upon a strip of filter-paper saturated with a solution of silver nitrate is dropped uric acid or urate dissolved in an alkaline carbonate, a black stain at once appears through reduction of the silver. Quantitative Estimation. — i. The method of Hopkins, by means of which the uric acid is precipitated as ammonium urate. If 100 cu. cm. of urine are thor- oughly saturated with ammonium chlorid (about 30 grams are necessary), all of the uric acid is precipitated as ammonium urate, particularly if some ammonia is added besides. After the lapse of two hours the precipitate is collected upon a filter, where it is washed several times with a saturated solution of ammonium chlorid. The precipitate is now rinsed from the filter with boiling water, and exposed to the action of hydrochloric acid with heat. The uric acid that sepa- rates is collected upon a dry filter, and is again dried and weighed. 2. The method of Salkowski, modified by E. Ludwig, is based upon the pre- cipitation of the uric acid by silver nitrate and its subsequent separation and weighing. The following solutions are necessary: A. Twenty-six grams of silver nitrate dissolved in water, and admixed with ammonia, until complete solution takes place; then addition of water to make i liter. B. Magnesia-mixture: 100 grams of crystallized magnesium chlorid dissolved in water; ammonia added until a strong odor is developed; then ammonium chlorid to the solution; and, finally, addition of water to make i liter. C . Ten grams of pure sodium hydrate dissolved in i liter of water. One-half of this is completely saturated with hydro- gen sulphid, and then both halves are mixed. Mode of Procedure. — -One hundred cubic centimeters of filtered non-albumin- ous urine (if necessary freed of albumin) are placed in a beaker. In another glass, 10 cu. cm. of the solution A are mixed with 10 cu. cm. of the solution B, and ammonia is added, if necessary also ammonium chlorid to the point of complete saturation. This solution is poured with stirring into the urine, and the mixture is permitted to stand for one hour. The precipitate is then collected upon a filter, is washed with water containing ammonia, and is brought, by means of a pipette and a glass rod, without injury to the filter, back again into the beaker. Now 10 cu. cm. of the solution C, diluted with 10 cu. cm. of water, are heated to the boiling-point, and this solution is passed through the used filter into the beaker which contains the silver-precipitate; the filter is then washed with hot water, and the beaker is heated for some time over the water-bath with stirring. On cooling, the solution is filtered into a dish; the filter is washed with hot water; the filtrate is acidulated with hydrochloric acid; and the product is evaporated to about 15 cu. cm., when 15 drops of hydrochloric acid are added, and the solution is permitted to stand for twenty-four hours. The uric acid separated out is col- lected upon a previously weighed filter, washed with water, alcohol, ether, and hydrogen sulphid; dried at a temperature of 100° and weighed. For every 10 cu. cm. of the watery filtrate, 0.00048 gram of uric acid are to be added. KREATININ, XANTHIN-BASES, OXALURIC, OXALIC, AND HIPPURIC ACIDS. Kreatinin (C4H9N3O,) is derived in part from the kreatin present in the muscles b}^ loss of water, and in part from the meat in the food. Its amount daily is from 0.6 to 1.3 grams. The amount of kreatinin is diminished in cases of progressive muscular atrophy, of tetanus, and of marantic, anemic, or paralytic conditions of the musculature. kri:ati.\ix, xantiiix uases, oxaluric axd oxalic acids. 483 It is increased particularly l)y greatly augmented muscular activity, after the ingestion of food rich in nitrogen. It is wanting in the urine of infants. Kreatinin yields an alkaline reaction, is readily soluble in water and in hot alcohol, and it forms colorless, oblique rhombic columns. It combines with acids, but also with salts. Kreatinin-zinc chlorid is prepared for the detection of krea- tinin. Demonstration. — A few drops of a slightly brown, watery solution of sodium nitroprussid and then dilute sodium hydrate' added to 5 cu. cm. of urine cause a Burgundy-red color that soon disappears. Addition of acetic acid changes the color to yellow. Acetone yields a similar reaction, though in the case of this substance the red color becomes still darker, almost purple, after addition of acetic acid. Acetone can tirst be driven off from the urine by boiling, and then the reaction of kreatinin is certain. Xanthin-bases : Alloxuric Bases. — Under the names xanthin-bases or nucleiti- bases, or alloxuric bases, are comprised a group of bodies, including xanthin, hypoxanthin, adenin, guanin, camin, which are related genetically to uric acid', and, together with it, are also designated alloxuric bodies. The mother-substance of all alloxuric bodies, including uric acid, is purin (C5N4H4), from which are derived: hypoxanthin, as oxypurin; xanthin, as dioxypurin; uric acid, as trioxy- purin; adenin, as 6-aminopurin ; guanin, as 2-amino-6-oxypurin. By the en- trance of one methyl-group into the xanthin-moleculc, there result the isomers, i-methylxanthin, 3-methylxanthin, 7-methylxanthin (heteroxanthin) . If two methyl-groups enter, there are formed theobromin, paraxanthin, and theophyllin. If 3 methyl-groups enter, caffein is formed. Salomon and Kriiger found in the urine hypoxanthin, xanthin, adenin, hetero- xanthin, paraxanthin, i-methylxanthin, 7-methylguanin; and of the foregoing, respectively, in 10,000 liters of urine, 8.5 grams, 10. i grams, 3.5 grams, 22.3 grams, 15.3 grams, 31.3 grams, 3.4 grams. Alloxuric bases are prepared from the urine as combinations with silver or copper, and these are decomposed by hydrogen sulphid. The crude bases, treated with dilute hydrochloric acid, exhiVjit varying solubility. The vegetable alkaloids of coffee, tea, and cocoa are the antecedents of heteroxanthin. Paraxanthin is derived from caffein. Studies of the alloxuric bodies, therefore, are of value only after protracted abstinence from the beverages named. Xanthin, C5H4N4O,, is present in small amounts only; according to E. Sal- kowski, it may, however, under some circumstances, be as much as one-eighth of the weight of uric acid. It is an amorphous, yellowish-white powder, quite readily soluble in boiling water. It is said to be present in the urine in somewhat greater amount after courses of treatment with sulphur, in leukemic patients and in conjunction with nephritis in children. Rarely it forms urinarv calculi. It represents an intermediate link between sarcin and uric acid. Guanin and hypo- xanthin can be converted into xanthin. In contact with water and ferments, xanthin is transformed into uric acid. Evaporated with nitric acid, it leaves a yellow stain that becomes yellowish red with potassium and violet red when further heated. Hypoxanthin, sarcin, CjH^X^O, can be prepared in the form of needles or exfoliating scales from meat, milk, bone-marrow, liver, blood from the cadaver. It is present in normal urine in smaller amount. Hypoxanthin exhibits great resemblance to xanthin, into which it can be transformed by oxidation. Hydrogen in the nascent state conversely reduces uric acid to xanthin and hj^poxanthin. Evaporated with nitric acid, it yields a light-yellow stain, which becomes more intense on addition of sodium hydrate, but not reddish yellow. It is more readily soluble in water than xanthin, and a means of differentiating the two is thus af- forded. Guanin is wholly insoluble in water. Paraxanthin has proved toxic in moderate amount to dogs. Rachford found it in the urine in considerable amount in cases of severe migraine with convulsive conditions. Oxaluric acid, C3H4N2O4, occurs in the urine in but small amount as an ammo- nium-salt, is but slightly soluble in water and appears as a loose white powder. Ammonium oxalurate can be prepared from uric acid. Perhaps there is a physio- logical connection between uric acid and oxaluric acid. Oxalic acid, CoHoO^, occurs, though not constantly, as calcium oxalate, to an amount varying from 10 to 25 mg. daily. It is recognizable from its envelop- shaped clear octahedra (Fig. 153, huric acid, a violet-red color results, which is particularly pretty in transmitted light. SUGAR IN THE URINE: GLYCOSURIA. Normal urine contains traces of dextrose. Small amounts of sugar are present after ingestion of sugar in large amounts (alimentary glycosuria) , and also in the presence of fever, after the drinking of beer supplemented by alcohol, occasionally in the exceedingly obese, in neurasthenics, in association with cerebral disease, and in advanced age. Glycosuria occurs also as a result of failure in intestinal activity in ill-nourished individuals; and, artificially, after ligation of the mesen- teric arteries. Dextrosuria of considerable degree is a sign of diabetes mellitus. In this connection, the large amount of urine, up to 10,000 cu. cm., as well as the high specific gravity, from 1030 to 1040, are striking. The diabetic patient excretes a relatively larger amount of water through the kidneys; and, on the other hand, a relatively smaller amount throtigh the skin (and the lungs?) than a healthy person. Also the elimination of the water ingested takes place later and more uniformlj' than in health. The urine is pale yellow in color, although the amount of coloring-matter is, in the aggregate, by no means diminished; and the nitrogenous matters are increased. A diet of carbohydrates generally in- creases the excretion of sugar; while a proteid diet may reduce it. Uric acid and calcium oxalate are often found increased at the commencement of the disease. On standing for a considerable time yeast-cells constantly develop in the urine. For quantitative estimation the tests for sugar already described (p. 2 68) are appropriate, althotigh the urine must be free from albumin or be rendered so. The following tests are most to be recommended: (a) The fermentation-test is the most reliable. A test-tube inverted over mercury is filled with the saccharine urine and a piece of yeast, living and free from sugar, as large as a pea, and also one drop of tartaric acid, are added, and the mixture is kept in a wann place. Carbon dioxid collects at the bottom of the inverted tube, and disappears after the introduction of potassium hydrate. (b) A 2.5 per cent, solution of copper sulphate and a solution containing 10 parts of sodiopotassic tartrate in 100 parts of a 4 per cent, solution of sodium hydrate are employed. Five cubic centimeters of urine are boiled in a test-tube, and from i to 3 cu. cm. of the copper-solution and 2.5 cu. cm. of the tartaric- acid solution in a second test-tube. The boiling of both fluids is interrupted simultaneously, and after the lapse of from 20 to 25 seconds, the contents of the one tube are poured without agitation into the other; reduction then takes place spontaneously. (c) Bottger's test with Nylander's modification (p. 267). ((i) In the application of the phenylhydrazin-test, 5 cu. cm. of urine are diluted with 5 cu. cm. of water, and 0.5 of phenylhydrazin hydrochlorate and 1 gram of sodium acetate are added. The mixture is boiled for two minutes over the water-bath, is permitted to cool slowly and to stand for fdur hours in the cold. Combinations of glycuronic acid form similar, though plumper, crystals, more like thorn-apples. (e) In applying Molisch's test, «-naphthol dissolved in chloroform, instead of in alcohol, is employed. The test discloses the presence of all of the carbohy- drates in the urine, under normal circumstances 0.96 per cent, altogether, of which o. I is grape-sugar. Urine containing sugar should be diluted 100 times. (/) If to 10 cu. cm. of diabetic urine in a test-tube 0.5 mg. of powdered gentian- violet are added, the urine is colored, while normal urine is not. 502 SUGAR IN THE URINE. Quantitative estimation is made by fermentation or by the titration-method. The estimation by circumpolarization is, according to Worm-Miiller, ahnost value- less for the estimation of the amount of sugar in diabetic urine, as the urine often contains in part as yet unknown optically active substances. If, however, it be desired to employ this method, the urine must be previously agitated with commercial animal charcoal and filtered, in consequence of which it becomes colorless. Small amounts of glycogen derived from urinary tubules that have undergone glycogenic degeneration have been found by Leube in diabetic urine. After ingestion, the sugars that are most readily decomposed pass with greatest difficulty, while those that are not at all decomposable pass most readily, into the urine. If, therefore, considerable amounts of dextrose are administered, a portion thereof passes into the urine; and a larger amount in cases of diabetes than in health. Ingested levulose does not increase the amount of sugar in the urine of a diabetic patient. The use of starch in considerable amounts never gives rise to the presence of sugar in the urine in health, although it increases the amount of sugar in cases of diabetes. The ingestion of cane-sugar or of milk- sugar in considerable amount causes the passage of small ainounts of each into the urine during health. The diabetic, under such circumstances, excretes an increased amount of dextrose. According to Kiilz, the cane-sugar ingested by a diabetic patient is decomposed into grape-sugar and fruit-sugar; the latter is consumed in the body, the former in part excreted. The same takes place with milk- sugar. Levulose is rarely present in the urine, constituting lev^l- losuria. In severe cases of diabetes mellitus, Kiilz found levoroia- tory ;^-oxyhutyric acid, the next higher analogue of lactic acid, in the urine, from the oxida- tion of which diacetic acid is produced. The latter, in its turn, is readily decomposed into carbon dioxid and acetone. f3-oxybutyric acid is never wanting when diabetic coma is present. .4c^/o"^ is present in the urine of diabetics often in considerable amount, princi- pally in association with pro- gressive loss of strength, and often even in spite of admin- istration of carbohydrates. From oxybutyric acid there results, by dehydration, o-cro- tonic acid, which Stadelmann found in diabetic urine. As albuminuria results from administration of acetone, the complication of albuminuria with diabetes is clear. Milk-sugar — lactosuria — is present in the urine of puerperal women, together with glucose and isomaltose, chiefly in connection with milk-stasis. The condition is thus due to absorption from the breasts. Milk-sugar likewise appears in the urine of infants with derangement of digestion. Pentose has, on several occasions, been observed in the urine: pentosuria. This substance contains 5 atoms of carbon, is not susceptible of fermentation, and is capable of causing reduction. It may possibly be due to disease of the pancreas. Phloroglucin and hydrochloric acid yield a red color. Pentose is present in coffee, in many wines, and in varieties of milk and sugar. Ingested pentoses — arabinose, xylose — pass over into the urine. Reichart has called attention to the simultaneous appearance of dextrin in urine containing sugar. Inosite has been found both in cases of diabetes and in cases of polyuria and albuminuria. Traces of it are contained even in normal urine. Occasionally, "sugar-puncture" in animals is followed by the appearance of inosite instead of dextrose in the urine. For the detection of inosite, the dextrose is removed by fermentation, and albumin by boiling after addition of a few drops of acetic acid and sodium sulphate. Of the filtrate, a few cubic Fig. 162.- -A, crystals of cystin; B, of calcium oxalate; c, hour- glass shaped crystals of calcium o.xalate. CYSTIN, LEUCIN, TYROSIN. 503 centimeters are evaporated in a porcelain dish down to a few drops; then 2 drops of a solution of mercuric nitrate (titration-solution according to J. v. Liebig) are added. A vellow precipitate takes place. If this is spread out and further carefully heated to a point beyond desiccation, a dark-red color appears, which on cooling gradually disappears. The sugar may, in rare cases, also give rise to pneumaturia, fermentation by microbes causing the development of carbon dioxid. CYSTIN. Cystin, CgHijNoS^O^, is a levorotatory body that occurs normally in ^traces in the urine and" but rarely in considerable amount. It appears in the form of colorless, six-sided plates (Fig. 162, .4), in children also forming concretions. Cystin is insoluble in water, alcohol, and ether; readily soluble in ammonia, after the evaporation of which it crystallizes out. According to Baumann and Preusse, there exist intermediary products of metabolism that contain the material necessary for the forma- tion of cystin. When the metab- olism is normal, these, however, undergo further change; and their sulphur appears in the urine ox- idized as sulphuric acid. In rare cases this oxidation fails to take place; and then the sulphur ap- pears in the urine as cystin. In cases of phosphorus-poisoning the cystin is increased. LEUCIN, C,Hi,NO., AND TY- ROSIN, C.HiiNOg. Both of these bodies, whose development has been referred to in the consideration of pancreatic digestion, are present in traces in normal urine. They occur to- gether in somewhat larger amount in association with derangements in the function of the liver-cells (acute yellow atrophy of the liver, phosphorus-poisoning) . As the elimination of urea is generally diminished at the same time, it may be concluded that the liver is the seat of the formation of urea. Leucin, which separates either spontaneously in the precipitate or only after evaporation of an alcoholic extract of the inspissated urine, appears in the form of yellowish-brown spheres (Fig. 163, a a) , occasionally with concentric radiation or provided with fine points at the periphery. When heated dry leucin sublimes without fusing. Tyrosin forms silky, colorless sheaves of needles (Fig. 163, bb). If a solution of tyrosin be boiled with Millon's reagent, there results at first a pretty red color, and shortly afterward a deep brownish-red precipitate. If tyrosin is gently heated with a few drops of concentrated sulphuric acid, it is dissolved Avith the development of a transitory deep-red color. If it now be diluted with water, and barium carbonate be added to the point of neutralization, the mixture boiled and filtered, and dilute iron chlorid added to the filtrate, a violet color appears. Dissolved in hot water, addition of quinone produces a red color. Fig. 163. — a a, Leucin-spheres; b b, tyrosin-sheaves; c, double spheres of ammonium urate. SEDIMENTS IN THE URINE. Both in normal, as well as in pathological urine, precipitates may form at the bottom of the vessel; and these are designated sediments. They are either organized or unorganized. S04 ORGANIZED SEDIMENTS. ORGANIZED SEDIMENTS. (A) Sediment of blood: derived from erythrocj'tes and leukocytes (Figs. 157, 158, 159, 160), occasionally also shreds of tibrin (Figs. 6, 7). (B) Pus-corpuscles, in gi-eater or lesser amount in association with catarrhal or inflammatory^ processes in the urinary passages, entirely resemble the leukocytes (Figs. 6, 7). Marked, persistent admixture of pus is indicative of profound parenchymatovis suppuration: numerous mononucleated leukocytes, of disease of the kidneys. Demonstration, — If the supernatant fluid be poured oft' and a l;.it of potassium hydrate be dissolved in the sediment, the pus is converted into a vitreous, ropy mass, later becoming more consistent (alkali-albuminate) , Mucus treated in this manner is dissolved into a thin fluid admixed with flakes. (C) Epithelial cells of varied shape and not always distinguishable as to the source whence they are derived. They are more abundant in the presence of catarrhal conditions in the parts in qviestion. In the urine of women, pavement epithelial cells from the vagina are also present. The spermatozoids likewise are included among epithelial structtires. (D) Lower forms of organisms. The freshly collected ^uine from healthy Fig. 164. — e, Molds; /, budding-fungi (yeast); d g. bacteria (micrococci and bacilli); a b c, uric acid (after v. Jaksch). Fig. 165. — Epithelial Tube-casts. persons always contains inany microorganisms, which, however, have probabh' been washed away from the urethral mucous membrane. Thej' are principalh^ large or small diplococci. In cases of gonorrhea, gonococci thus gain entrance into th$ urine. Lower forms of organisms may also appear in the urinary pas- sages, as, for instance, in the bladder, when their germs have been introduced by means of unclean catheters. The following varieties may be distinguished: 1. Schizoinycetes (fission-fungi). In pathological' cases bacteria may gain entrance into the urinary tubules and the urine from the blood. Bacterial cul- tures injected artificially into the vessels are in part eliminated through the kidneys. In urine undergoing alkaline fermentation, both micrococci and rod- shaped bacteria or bacilli appear (Fig. 164). The sarcin.-e are further included among schizomycetes. 2. SaccJiaromycetcs (fermentative germs): (a) The germ of acid fermentation of urine (saccharomyces urina?) : small vesicular cells, arranged partly in groups, partly in rows (Figs. 153,11; Fig. 164,/). (i>) Yeast (saccharomj'ces fermentum. Fig. 140) is present in diabetic urine. 3. Phycomycetes (molds) appear in putrid urine as mold-formations (Fig. 164, c) . They are without significance. (E) Of great significance in the diagnosis of certain diseases of the kidnc}' is the occurrence of so-called urinary cylinders, that is, casts of the urinary tubules. If these structures are relatively thick and father straight, they are probably ORCIANIZED SEDIMENTS. 505 derived from the coUectinsj; tubules of the kidney; while if they are thinner and tortuous, their source is suspected to be the convoluted tubules. Various kinds of tube-casts can be distintjuished: i. Epithelial casts (Fig. 165), which consist of coherent and desquamated cells of the urinary tubules. They indicate that no profound change has as yet taken place within the kidney, but that, as in catarrhal inflammatory states of mucous membranes, the epithelial cells are in process of desquamation. 2. Hyaline tube-casts (Fig. 171) are com- pletely homogeneous and transparent. Thev are most readily demonstrated by addition of a solution of iodin to the preparation. They are generally long and narrow; occasionally, they present fine disseminated points, or fat-granules (finely granular tube-casts, Fig. 169). They appear not to be derived from a transuda- tion from the blood, but as a result of the secretory activity of the eiMthehal Fig. 166. — Blood-casts. Fig. 167. — Casts of I.eukocyles (after v. Jakscli). Fig. ifiS. — Acid Sodium Urate in the Form of Tube-casts. Fig. 169. — Finely Granular Tube- casts. Fig. 170.— Coarsely Granular Tube-casts (after v. Jaksch) Fig. 171. — a. Hyaline tube-cast; b, hyaline tube-cast with leukocytes; c, hyaline tul)e- cast with renal epithelium (after v. Jaksch). cells of the urinary tubules. 3. Darkly gramilar tube-casts (Fig. 170), brownish yellow, opaque, and consisting wholly of a granular mass, are usually somewhat wider than hyaline tube-casts. Marked variations of the latter occur. Not rarely, they exhibit fattilv degenerated or atrophic epithelial cells of the urinary tubules 4 Amyloid tube-casts occur in cases of amyloid degeneration ot the kidnevs. Thev have a waxy luster, are completely homogeneous (Fig. 171, a) and yield, with sulphuric acid and solution of iodin, the blue ^ color of amyloid reaction. 5. Blood-casts, consisting entirely of coagulated blood, with distinct blood-corpuscles, occur in association with capillary hemorrhage into the tissue of the kidnev (Fig. 166). These are allied to the casts found m connection with hemoglobinuria; as, for instance, after transfusion of heterogeneovis blood ihey consist of hemoglobin or of its globulin tinged with hematm. The tube-casts stained yellow that have been observed in conjunction with icterus probably also result from the albumin of dissolved blood-corpuscles. Urine containmg tube- casts is always albuminous. 5o6 SEDIMENTS IN THE URINE. Tube-casis of leukocytes are obser\-ed in connection with suppurative pro- cesses in the urinarj- tubules (Fig. 167). Urates arranged in the shape of tube- casts are without significance (Fig. 168); as well as cylindroids, formed of mucus, with which short strands of mucus arising in the ureter, the bladder, the prostate, the uterus, and the vagina, may be confounded. UNORGANIZED SEDIMENTS. The tmorganized sediments, in part crj'stalline, in part amorphous, have already received consideration in the discussion of the individual constituents of the SCHEMATIC RESUME FOR THE RECOGNITION OF ALL OF THE SEDIMENTS IN THE URINE. I. In acid urine there may be foimd — I. An amorphous crumbling sediment, (a) Which is soluble in the heat and is again precipitated in the cold, and which, on addition of a drop of acetic acid to the microscopic preparation, forms crystals of uric acid, which often has a reddish color (brick-dust powder). This sediment consists of sodium or potassium biurate (Fig. 153). (b) The sediment is not dissolved by heat, but on addition of acetic acid, and without effervescence. This is probably tribasic calcium phosphate. {c) Highly refracting graniiles, occurring occasionally and soluble in ether. Fig. 172.— a, Finely granular calcium carbonate; b and c, cnstalline neutral calcium phosphate. are fat-globules. Fat occurs in the urine particularly in conjunction with the presence of a round-worm (filaria sanguinis hominis) in the blood (onlv in for- eigners or travelers) ; further, occasionally together with sugar in the urine, in tuberculous patients ; in cases of phosphorus-poisoning, of yellow fever, of pyemia ; after protracted suppuration; and. finally, after injections of fat or milk into the circulation. Fatty degeneration in some portion of the urinar\' apparatus, ad- mixture of pus from old abscesses, and severe injuries to bones, should further be taken into consideration. In this connection, attention should be given also to cholesterin and lecithin. Rarely, the amount of fat in the urine may be so marked as to give rise to a creamy appearance — chyluria. 2. A sediment consisting of crystals: (a) Uric acid (Fig. 14S and Fig. 153 — whetstone-shaped crv^stals). (6) Calcium oxalate (Fig. 153, Fig. 162, B) — envelop-shaped crj'stals, insolu- ble on addition of acetic acid. (c) Cystin — extremely rare (Fig. 162, .4). (d) Leucin and ty rosin — of great rarity (Fig. 163). II. In alkaline urine there may be present: 1. The sediment is wholly amorphous and crumbling; it consists of tribasic calcium phosphate. It is soluble on addition of acids without effervescence. 2. The sediment is crystalline, or, at least, of characteristic form. URINARY CONCRETION'S. 507 (a) Amnwiiio-iiiagnesiuDi phosphate (Figs. 173, 160, 154): Large coffin-lid crystals, immediately soluble on addition of acids. (b) Small globules, yellowish in reflected light, dark in transmitted light, often provided with points; thorn-apple or morning-star shaped, together with amorphous granules (Figs. 154 and 175). These consist of acid ammonium urate. (c) Calcium carbonate: Small whitish globules, biscuit-shaped or arranged side by side in irregular masses, together with amorphous granviles. EfTerves- FlG. 173. — .\innionio-magnesium Phosphate. Fig. 174. — Imperfectly Developed Crystals of Am- monio-magnesium Phosphate. ^^v Fig. 175. — Acid Ammonium Urate (after v. Jaksch). '^ Fig. 170. — Basic Magnesium Phosphate. cence takes place on addition of acids, also in the microscopic preparation (Fig. 172, a). (d) Leucin and tyrosin are extremely rare (Fig. 163). Crystals of neutral calcium phosphate (Fig. 172, c) , with their spear-shaped extremities in contact, are also rare, as well as plates of basic magnesium phosphate (Fig. 176). Organic sediments may occur both in acid, as well as in alkaline, urine. Among them, pus-corpuscles are present especially in alkaline urine, and the lower forms of vegetable organisms likewise predominate under such circumstances. URINARY CONCRETIONS. Urinarj' concretions varv in size from that of a grain of sand or a pebble to that of a fist. They are encountered in the bladder, also in the pelvis of the kid- ney, in the ureters, and in the prostatic sinus. All urinary concretions contain a framework of organic structure uniting the particles of the formation into a coherent mass. The v are divided, according to Ultzmann, as follows: 1. Concretions wliose nucleus consists of the sediment formed in acid urine — primary calculus-formation. All of these arise primarily in the kidney and pass thence into the bladder, where they undergo enlargement in accordance with the development of the crystals in the urine. 2 . Calculi that have for a nucleus either the sediments found in alkahne urine So8 URINARY CONCRETIONS. or a foreign body — secondary calculus-formation. These develop in the bladder itself. Primary calcnlus-jormation takes place from free uric acid in the form of sheaves as a nucleus (Fig. 148, 7), and surrounded by layers of calcium oxalate. Sedondary calculus-formation takes place in neutral urine from calcium carbonate and crystalline calcium phosphate, in alkaline urine from acid ammonium urate, ammonio-magnesium phosphate, and amorphous calcium phosphate. Chemical examination next determines whether or not the particles of the concretion are combustible upon a platinum plate. I. Combustible concretions can consist only of organic matter. (o) If the murexid-test yields a positive reaction, the concretion contains tiric acid. Uric-acid calculi are common, often of considerable size, smooth, rather hard, and in color from yellow to reddish brown. (6) If another specimen on boiling Avith potassium hydrate yields an odor of ammonia, and if moist turmeric-paper held in the vapor becomes brown, or a glass rod moistened with hydrochloric acid and held over the vapor yields fumes of ammonium chlorid, the concretion contains anunonium urate. If this test yields a negative result, the concretion contains pure uric acid. Calculi of ammonium urate are rare, generally small, of earthy consistence, and in color between clay-yellow and whitish. (c) Should the xanihin-reaction be positive, this substance is present, though it is rare. In one instance, indigo has been found in a calculus. {d) If cystin-crystals (Fig. 162, .4) are developed after sohttion in ammonia and evaporation of the latter, the presence of this rare substance is demonstrated. {e) Concretions composed of blood-coagula or fibrinous flakes, without any crystallization whatever, are rare. If burned, they 3-ield an odor of singed hair. They are insoluble in water, alcohol, and ether. They are soluble in potas- sium hydrate, out of which they are reprecipitable by acids. (/) Urostealith is the name that has been given to the substance composing rarely found concretions which in the fresh state are soft and elastic, re- sembling India rubber. On drying, they become brittle and hard, and in color between brown and black. Warmth causes them to become softer again, and they melt when heated. Solution takes place in ether, the residue of the evapo- rated ethereal solution becoming violet in color on further heating. Urostealith is dissolved by heated potassium-hydrate solution, with saponification. Concre- tions containing jat or cholcstcrin are rare. II. If concretions are only in part combustible, with a residue, they contain organic and inorganic matters. (a) A portion of the calculus is reduced to powder, and this is boiled with water and filtered hot. Urates that ma}^ be present undergo solution. In order to determine whether the uric acid is combined with sodium, potassium, calcium, or magnesium, the filtrate is evaporated and fused. The ash is examined spectro- scopically (flame-spectra), and by this means sodium and potassium are recognized. Magnesium urate andcaicium urate are transformed by fusing into carbonates. In order to separate the two, the ash is dissolved in dikite hydrochloric acid, and filtration is practised. The filtrate is neutralized with ammonia; then again dis- solved with a few drops of acetic acid. Addition of ammonium oxalate precipi- tates calcium oxalate. Filtration is now practised, and to the filtrate are added sodium phosphate and ammonia. By this means the magnesia is separated as ammonio-magnesium phosphate. (b) Calcium oxalate occurs principally in children, either as small, smooth, pale hempseed-calculi. or in dark, nodular, hard mulberry-calculi. It is not affected by acetic acid, is soluble in mineral acids, without cftervescence ; and is reprecipitated by ammonia. When fused upon a platinum plate, the specimen becomes black; it is then burned white to calcium carbonate, which undergoes effervescence upon addition of acid. (c) Calcium carbonate occurs generally in whitish-gra}', earthy, chalk-like, rather rare calculi that usually are multiple. It is sokible in hydrochloric acid with effervescence. When fused, it becomes at first black, from admixture of mucus; but soon afterward white. (d) Ammonio-magnesium pliosphatc and basic calcium phosphate are usually united in soft, white, chalky stones, which at times attain qtiite considerable size. Such calculi imply a long sojourn in ammoniacal urine. The first substance yields an odor of ammonia when heated, and more distinctly when heated with potassium hydrate. It is soluble in acetic acid without effervescence, and is precipitated in crystalline form from this solution on addition of ammonia. When PHYSIOLOGICAL PROCESS OF UKIXARY SECRETION. 509 fused, the specimen melts to a white, porcelain-like mass. Basic calcium phos- phate does not elYervesce with acids. The solution in hydrochloric acid is pre- cipitated by ammonia. The solution in acetic acid yields calcium oxalate on addition of ammonium oxalate. In order to isolate calcium and magnesium from such stones, the process described in paragraph ((/) should be folIf)\vcd. {e) Xcutral calcium phosphate is rarely found in calculi, but, on the other hand, not rarely in urinary sand. Such concretions resemble the earthy phos- phates in physical and chemical properties, except that they contain no magnesia. THE PHYSIOLOGICAL PROCESS OF URINARY SECRETION. The two older and most important theories of secretion will be mentioned: (i) Bowman held that the glomeruli secrete only water, and that the epithelial cells of the urinary tubules through their glandu- lar activity furnish the specific urinary elements, which the onfiowing urinary water washes out of the cells. (2) C. Ludwig assumed that a dilute urine is secreted in the capsules. Passing through the urinary tubules, this, by endosmosis, returns water to the blood, which is more deficient therein, and to the lymph of the kidney, and thus becomes reduced to normal consistence. The secretion of the urine in the kidneys depends, however, not alone upon physically definable influences, but it must rather, in accordance with a series of acquired facts, be assumed that in addition the vital activity of special secretory cells plays a prominent role. The physical or chemical forces obviously underlying the latter have not as yet been determined. The secretion includes (i) the urinary water, and (2) the urinary elements dissolved therein. Both together constitute the totality of the secretion. The amount of urinary water secreted in the glomeruli determines principally the amount of urine, while the amount of substances dissolved in the urinary water determines the concen- tration of the urine. The amount of urinary water, which is secreted principally in the capsules, depends, in the first place, upon the blood-pressure in the distribution of the renal artery; and, accordingly, is governed by the laws of filtration. The amount of urinary water furnished is, however, not dependent upon the hydrostatic pressure alone, but the functional activity of the cells lining the glomerulus is also of influence. In ad- dition to the water, a certain amount of the salts occurring in the urine is secreted in the glomerulus; albumin, however, is retained. In consideration of the functional activity of the cells, the amount of urinary water must depend also in part upon the rapidity with which new blood conveying the material for secretion passes to the glomeruli; and, in part, upon the amount of urinary elements and water contained in the blood. The independent activity of the secretory cells is present only when their vitality is intact. It is paralyzed in consequence of transitory occlusion of the renal artery. For this reason, the kidney no longer secretes under such circum- stances, even when the circulation is restored after removal of the compression. The observation that the urine is not rarely found to have a higher temperature than the arterial blood is also indicative of this activity. The dependence of the secretion upon the blood-pressure will be made clear by the following observations : I. Increase of the total contents of the vessels, in consequence of which the tension in the vascular svstem must increase, increases the 5IO PHYSIOLOGICAL PROCESS OF URINARY SECRETION. amount of filtered urinary water. Injections of water directly into the vessels, or the ingestion of considerable quantities of fluid, operates in this direction. If the increase in blood-pressure exceeds a certain level, albumin may even pass into the urine. Conversely, loss of water in consequence of profuse sweating or diarrhea, or copious venesection, as well as prolonged thirst, will cause diminution in the amount of urinar}' secretion. The circumstance that the blood-pressure does not rise constantly after free drinking is evidence of the functional activitv of the cells of the glomeruli, as is also the fact that the amount of urine is not increased after large transfusions. 2. Diminution in the vascular capacity will operate in a similar manner: contraction of the cutaneous vessels under the influence of cold, stimulation of the vasomotor center or of considerable areas of the vasomotor nerves, ligation or compression of arteries of large size, envelopment of the extremities in tight bandages. Naturally the op- posite conditions will be followed by a reduction in the amoimt of urine : the influence of heat upon the skin to the point of redness and dila- tation of the vessels, enfeeblement of the stimulation of the vasomotor center, or paralysis of considerable areas of the vasomotor nerves. 3. Increased cardiac activity, in consequence of which the tension and the rapidity of the current in the arterial distribution are increased, augment the amount of urine. Conversely, enfeeblement of the heart's action (paresis of the motor nerves of the heart, disease of the heart- muscle, valvular lesions) diminishes the amount of urine. Artificial irritation of the vagi, in consequence of which, with slowing of the heart- beats, the average blood-pressure fell in animals from 130 to 100 mm. of mercury, with slowing of the pulse, was followed by a reduction in the amount of urine to about one-fifth. At 40 mm. of aortic pressure the secretion of urine ceases. 4. The amount of urine secreted rises or falls with increasing or diminishing fulness of the renal artery. Even moderate compression of the artery in animals is followed by distinct reduction. Pathological. — In the presence of fever, there is diminished fulness of the renal vessels, with consecutive reduction in the amount of urine. The observation is of especial significance for the pathogenesis of certain diseases of the kidney that ligature of the renal arter\-, even if continued for only two hours, causes necrosis of the epithelium of the urinary tubviles. In case of arterial anemia of longer duration, necrosis of the entire renal structure takes place. Ribbert fotmd the epithelial cells of the convoluted tubules greatly altered after compression of the renal arter\- for some time. ]\Iost diuretic medicaments act in one or another of the directions indicated. In case of increased diuresis, the lumen of the urinary tubules is increased. The pressure within each afferent vessel must be relatively large, because (i) the duplicate capillary arrangement in the kidney offers considerable resistance, and because (2) the efferent vessel has a much narrower lumen than the afferent vessel. In accordance with these facts, an excretion from the blood into the capstiles of the urinar}^ tubules will take place from the capillar}' loops of the glomerulus in consequence of the filtration-pressure. Dilatation of the aft'erent vessels, as, for instance, from the action of the nerves upon the unstriated muscular fibers, will increase the filtration-pressure; while constriction will diminish the secretion. If the reduction in the pressure has become so considerable that the blood-current in the renal vein is distinctly slowed, the secretion of urine begins to diminish. It is a remarkable fact that occlusion of the renal veins completely suppresses the secretion. C. Ludwig has concluded from this that the secretion PHYSIOLOGICAL PROCESS OF URINARY SECRETION 51I of fluid accordingly can not take place from the true renal capillaries, because the blood-pressure in these must be increased by occlusion of the veins, and this would cause increased filtration. On the other hand, the observation mentioned would indicate that the secretion takes place from the capillaries of the glomerulus. The venous stasis in the efferent vessel distends this vessel, which arises in the center of the convolution, to such a degree that the capillary loops are pushed together against the wall of the capsule and compressed, so that no filtration can take place from them. Whether some fluid is given off through the urinary tubules, especially the convoluted tubules, is as yet undecided. The amount of urine and the amotmt of contained urea are diminished by venous stasis in the kidneys. The amount of sodium chlorid remains constant, while that of albumin in pathological urine increases. As the blood-pressure in the renal artery equals between 120 and 140 mm. of mercury, and the urine in the ureter is propelled under exceedingly slight pressure, so that it is no longer capable of escaping against a counter-pressure of from 10 to 40 mm. — provided by a manome- ter introduced into the ureter divided transversely — it must be clear that the blood-pressure is also capable, as a vis a tergo, of forcing the stream of urine through the ureter. The degree of concentration of the urine depends upon the amount of the constituents in solution passing out of the blood into the urinary water. The cells of the convoluted urinary tubules appear to take up these substances from the blood by means of an independent activity. The urinary water passing through the urinary tubules from the glomerulus, and containing only readily diffusible salts, later takes up these substances out of the cells of the convoluted tubules by a pro- cess of extraction. The independent activity of the cells is indicated by the following facts : I. Sulphindigotate of sodium (indigocarmin), which, when injected into the blood, passes into the urine, can be recognized in the interior of the cells of the urinary tubules, but not in the capsules. Further on, this substance is visible in the lumen of the urinary tubules, whither it is washed by the current of urinary water from the glomerulus. If, in such an experiment, the cortical layer containing the capsules has been removed two days previously by cauterization or with the knife, the blue pigment will have remained in the convoluted tubules. It will not have advanced onward, as the current of water from the de- stro^'ed glomeruli is wanting. This observation thus indicates that the glomeruli furnish principally the urinary water, and the convoluted tubules the specific urinary elements. Heidenhain and Sauer observed also urates (injected into the blood) secreted by the convoluted tubules. Nussbaum has also demonstrated that urea is not secreted by the cap- sules, but by the urinary tubules. Mobius found the same with respect to the biliary pigment, Glaevecke with respect to the iron salts of the vegetable acids when injected subcutaneously, and Landois first described the same condition with respect to hemoglobin. After in- fusion of milk into the vessels, Landois encountered numerous fat- globules within the cells of the urinary tubules. It appears that the capsules may also take part in the process only after abundant secretion. After infusion of large amounts of sodium sulphindigotate and after the observation has been continued for some time, the epithelium of the Malpighian capsules also exhibits the blue discoloration. Likewise in the presence of albuminuria, the abnormal elimination of albumin takes place first in the urinary tubules and later in the capsules. Also hemoglobin occurs in part in the capsules. Egg-albumin is believed by Nussbaum to be excreted through the capsules. 512 PHYSIOLOGICAL PROCESS OF URINARY SECRETION. Disse studied the alterations in the secretory cells during their activity. With the commencement of this activity the cells become larger, and bright areas of the protoplasm, infiltrated with secretion, appear as halos about the nucleus. The discharge of the secretion into the lumen of the tubules takes place through filtration. The brush- border indicates only the empty cell; it disappears while the cell is being filled with secretion. Henle, H. Meckel, Le3^dig, and Bial observed in snails constituents of the urine (guanin) within the cells of the kidney. 2. Also when, either after ligation of the ureter or in consequence of marked reduction in blood-pressure in the renal artery (after division of the cervical cord or venesection), urinary water is no longer secreted, the substances named are, nevertheless, after introduction into the blood, seen to pass over into the urinary tubules. Injection of urea likewise again stimulates the secretion. This indicates that the secre- tory activity takes place independently of the filtration-pressure. The independent vital activity of the glandular cells of the urinary tubules not explainable by physical processes makes it impossible to consider the glandular tubules as a simple apparatus resembling physical membranes. This is shown also by the following experiment: Abeles permitted the circulation of arterial blood to continue artificially through fresh, living, extirpated kidnej^s. Pale urinotis fluid escaped frotn the ureter drop by drop. If urea or sugar were added to the circulating blood, the vessels became dilated and the secretion contained the admixed substances in greater concentration. Thus, also the surviving kid- ney excretes, in concentrated form, stibstances that circulate in the blood in a dilute state. The saine observation was made by I. Munk in analogous experi- ments with sodium chlorid, potassium nitrate, caffein, grape-sugar, and glycerin, with an increase in the total amount of the secretion. Addition of caffein or theobromin to the circulating blood induces an increase in the secretion, stimu- lates, thus, the secretory cells themselves to increased activity. The assumption of vital activity alone explains, also, why the serum-albumin of the blood does not pass into the urine, although egg-albumin or dissolved hemoglobin, intro- duced into the blood, does so rapidly. Among the salts that occur in the total blood, also in the blood-corpuscles, naturally only those in solution can pass over into the urine. Those that are united to proteids or in the cellular elements cannot pass over, or at least only after decomposition. This fact explains the difference between the salts of the total blood and those of the urine. The urine can, likewise, take up only the gases absorbed into the blood; and not those in chemical combination. Should stagnation of the secretion take place in the ureter, as after ligation, and, later, in the urinary tubules, a return of the secretion into the tissue of the kidney and, later, into the blood will be observed. The kidnev becomes edem- atous, in consequence of distention of its lymph-spaces. The secretion is altered, inasmuch as, tirst, water is reabsorbed into the blood; then the sodium chlorid in secretion is diminished, likewise sulphuric acid and phosphoric acid, and, finally, also the urea. Kreatinin will still be present in considerable amount. A true secretion of urine, later on, no longer takes place. The circumstance, ftirther, is noteworthy that the two kidnevs never secrete symmetrically. The condition is one of alternation in activitv and hyperemia. The one kidnej- secretes a fluid containing a larger amount of water, and, at the same time, more sodium chlorid and urea. It mav even be more acid. v. Wittich observed that the excretion of uric acid in the kidneys of birds does not take place uniformly in all of the urinary tubules, but only in varying areas. The extirpation of one kidne}- or its morbid destruction in human beings does not diminish the secretion. There occurs increased activity, with enlargement of the remaining organ; and this is due to the increased functional demands upon the secretory cells of this kidney. THE PRKPARATION OF THE URINE. 513 THE PREPARATION OF THE URINE. The question has often been raised, whether the urine is really se- creted through the kidney, or whether the urinary constituents are not in part prepared l)y the kidney itself. The following experiments will shed light upon this sul)ject: 1. The l:)lood already contains one part of urea in from 3000 to 5000 parts; but the blood in the renal vein contains less urea than that of the artery. This fact indicates that urea is excreted from the blood. 2. After extirpation of the kidney — nephrectomy — or ligation of its vessels, urea accumulates in the blood and progressively with the lapse of time to between :f^^ and 3-^^. At the same time, fluids containing urea and ammonia are vomited and discharged with the stools. Ani- mals die after such profound operations, moreover, within from one to three days. 3. If the ureters are ligated, the actual secretion of the kidneys soon ceases. After this, the accumulation of urea in the blood likewise in- creases, and, indeed, as it appears, not in greater amount than after nephrectomy. Nevertheless, it is possible that the kidney, in its meta- bolic activity, does, like other portions of the body, prepare some urea in its tissues. 4. The blood of birds contains uric acid even under normal con- ditions. Ligation of the ureters, as well as of the renal vessels, or gradual destruction of the secreting renal epithelium by means of subcutaneous injections of neutral potassium chromate, is followed in birds by a deposition of uric acid in the joints and tissues; so that the serous membranes particularly acquire a whitish incrustation there- from. The brain remains free. Also acid combinations of uric acid with ammonia, sodium, and magnesium are thus deposited. Extir- ])ation of the kidneys in serpents gives rise to the same phenomena in lesser degree. From these experiments it may be concluded that the urea, and with it probably inost of the organic constituents of the urine, are excreted ])rincipally through the kidneys, but are not prepared in them. The seat for the formation of all of these substances is probably to be re- ferred to the tissues. The urea is formed from decomposed proteid, and principally in the liver. As a result of experiments with birds and serpents, v. Schroder and Colasanti come to the conclusion that the formation of uric acid cannot be assumed to take place exclusively in any definite organ. Urobilin is formed from hemoglobin. Little is known concerning the physiological-chemical processes in the kidneys themselves. Hippuric acid is formed in part in the kidney, for the blood of herbivora contains no trace thereof; but the synthesis of this substance in rabbits takes place also in other tissues. If blood to which sodium benzoate and glycin have been added is passed through the vessels of a fresh kidney, hippuric acid is formed. If, further, phenol and pyrocatechin are digested with fresh renal tissue, the corresponding sulphuric-acid combinations that occur in the urine are formed. The latter, it is true, are formed also by similar digestion with hepatic and pancreatic tissue and with muscle. From these observations it may be con- cluded that in the body the substances in question are prepared within the kidneys and the organs named. The kidneys are extremely rich in water, and they yield an alkaline reaction. In addition to serum- albumin, globulin, nucleo-albumin, albumin soluble in sodium carbonate, a gelatin-yielding substance, fat in the epithelial cells (principally after 33 514 PASSAGE OF VARIOUS SUBSTANCES IXTO THE URINE. the ingestion of milk and meat), the elastic sarcolemma-like substance of the membrana propria of the urinary tubules, and the tissue-elements of the vessels and their unstriated muscles, the kidneys contain leucin, xanthin, hypoxanthin, kreatin, taurin, inosite, cystin (the last is present in no other tissue) ; and of these, the majority pass into the urine either not at all or only in small amount. The presence of these substances indicates, probably, active metabolism in the kidneys; and this is suggested also by the great vessels of the kidney. During the secretion of the kidneys, the blood of the renal vein is said to become bright red, and to be deprived of its fibrin. If alkaline blood-serum be filtered through a layer of nucleo-albvimin or lecithin-albumin, an acid filtrate passes through. Liebermann explains in a similar manner the development of acid urine on passing blood- plasma through the renal epithelium containing lecithin-albumin. THE PASSAGE OF VARIOUS SUBSTANCES INTO THE URINE. The following substances pass tuichangcd into the urine: Alkaline sulphates, borates, silicates, nitrates, carbonates; alkaline chlorids, bromids, and iodids; potassium sulphocyanate, potassium ferrocyanid; salts of the biliary acids; urea, kreatinin; cumaric, oxalic, camphoric, pyrogallic, sebac\'lic acids; further, many alkaloids, as, for instance, morphin, strj-chnin, curarin, quinin, cafifein; among the pigments, sodium sulphindigotate, carmine, gamboge, madder, logwood, the color- ing-matter of huckleberries, mulberries, cherries, rhubarb; further, santonin; and, finally, the salts of gold, silver, mercur^^ arsenic, bismuth, antimony, iron (but no lead), which, however, pass in largest amount into the bile and into the feces. Inorganic acids appear in human beings and camivora as neutral ammo- nium-salts; in herbivora. as neutral alkaline salts. Certain substances that generally undergo decomposition, even when they gain entrance into the blood in small amounts, pass in part into the urine when thej' accumulate in the blood in considerable amount, because they are not com- pletely decomposed, such as sugar, hemoglobin, egg-albumin, alkaline salts of the vegetable acids, alcohol, chloroform. Many substances appear in the urine as oxidation-products: moderate amounts of alkaline salts of the vegetable acids as alkaline carbonates; uric acid in part as allantoin; sodium sulphite acid and hyposulphite in part as sodixim sulphate; potassium sulphid as potassium sulphate. Many oxids appear as sub- oxids, benzol as phenol. Those bodies, such as glycerin and the resins, that are completely con- sumed, exhibit no special derivatives in the urine. Some substances undergo synthesis with metabolic products, and appear in the urine as conjugated combinations. In this category belongs the develop- ment of hippuric acid by conjugation, the formation of the conjugate sulphates, as well as the formation of urea by sj-nthesis from carbamic acid and ammonia. After administration of camphor, or of chloral and butj-l-chloral, a conjugated combination wdth glycuronic acid, an acid closely allied to sugar, appears in the urine. Taurin and sarcosin undergo conjugation with sulphamic or carbamic acid. Phenyl bromid, when administered, enters into conjugation with mercapturic acid, a body allied to cystin. Tannic acid, CnHi^Og, takes up water, and is thus decomposed by hydro- lysis into two molecules of gallic acid — 2C7H8O5. Potassium iodate and bromate are reduced to potassium iodid and bromid; malic acid, CiHjOj, in part to succinic acid, C4He04; indigo-blue, CisHjoNjOj, takes tip hydrogen to fonn indigo-white, C,6Hi2N,0,. Finally, many substances do not pass into the urine at all. such as serum- albumin, oils, insoluble metallic salts, and metals. INFLUENCE OF THE NERVES UPON THE SECRETION OF THE KIDNEYS. As yet, only the influence of the vasomotor nerves upon the fil- tration of the urine from the renal vessels is known, and these nerves appear to be derived from both halves of the spinal cord for each kidney. In general, it should be borne in mind that dilatation of the branches of INFLUENCE OF NERVES UPON SECRETION OF KIDNEY. 515 the renal arteries, particularly of the afferent vessels, must increase the pressure in the glomeruli, and therefore the amount of filtered fluid increases. The greater the measure in which the dilatation of the vessels is confined to the distribution of the renal artery alone, the greater will be the amount of urine. The lower dorsal nerves, in the dog principally the twelfth and thirteenth, contain the largest number of the vasomotor fibers for the kidney. Division of the renal plexus is, as a rule, followed by increase in the amount of urine. Occasionally, in consequence of the increased pres- sure, albumin is observed to pass into the Malpighian capsules; and with rupture of the vessels of the glomeruli even blood may appear in the urine. The center for these renal vasomotor fibers is situated on the floor of the fourth ventricle, in front of the origin of the vagus. In- jury, as by puncture, in this situation is, therefore, followed by increase in the amount of urine (diabetes insipidus), occasionally with the simul- taneous appearance of albumin and blood. Naturally, any injury of the active nerve-path from the center to the kidney has a similar effect. The center for the vasomotor nerves of the liver is situated close to this center, and injury of the former gives rise to the production of sugar in the liver. Eckhard observed hydruria develop after irritation of the vermiform process of the cerebellum lying upon the medulla. A similar result is brought about in human beings also as a result of irrita- tion in this situation by tumors, inflammatory processes, and the like. If, in addition to the distribution of the renal artery, an adjacent extensive vascular area be paralyzed simultaneously, the blood-pressure in the distribution of the renal artery will be less liigh; as, at the same time,, much blood finds its way into the other paralyzed area. Under such conditions, therefore, either a slight or only a transitory polyuria will be observed. In this way, there results a moderate increase in the amount of urine for a few hours after division of the splanchnic nerve, which contains the vasomotor fibers for the kidney. These leave the spinal cord in part through the first dorsal nerve, and pass into the sympathetic nerve. The splanchnic contains, at the same time, also the fibers for the extensive distribution of the intestinal vessels. Irritation of this nerve is, naturally, attended with the op- posite effect. If, with parah'sis of the renal nerves, the overwhelming majority of all of the vasomotors of the body are at once paralyzed, the pressure throughout the entire arterial distribution falls in accordance with the extensive dilatation of all of these vascular paths. In consequence, the secretion of urine diminishes, even to the point of complete cessation. This last eft'ect is seen after division of the cervical cord down to the seventh cervical vertebra. This fact explains the observation that the polyuria that occurs after injury to the floor of the fourth ventricle dis- appears as soon as the spinal cord down to the twelfth dorsal nerve is divided. The presence of a large amount of urea in the blood causes con- traction of the vessels of the body, but dilatation of the renal vessels. Contraction of the vessels, and, therefore, at the same time of the volume of the kidney, are caused by asphyxia and strychnin-poisoning; also irritation of sensory nerves has a similar reflex effect. Extirpation of the nerves of the kidney has the opposite effect. During fever, the vessels of the kidney are contracted, probably in consequence of irritation of the center by the abnormally heated blood. SI 6 uremia; am.moxiemia; uric-acid dvscrasia. Repeated inhalation of carbon monoxid is said occasionally to be attended with polyuria, perhajis in conseqvience of paralysis of the center for the vasomotor nerves of the kidneys. According to CI. Bernard, irritation of the vagus at the cardia causes increased secretion of urine, with reddening of the blood in the renal veins. Possibly this nerve contains vasodilator libers that behave similarly to the corresponding fibers in the facial nerve for the salivary glands. The vagus innervates the intrinsic unstriated musculature of the kidney. According to Arthaud and Butte and others, irritation of a peripheral ex- tremity of the vagus, conversely, diminishes the secretion of urine and the circu- lation in both kidneys. Atropin renders the experiment impossible. The vagus thus appears to be the vasomotor nerve of the kidney. According to Boeri, it possesses trophic functions, as albuminuria occurs after division of the vagus. Irritation of the cervical sympathetic likewise diminishes the secretion. This irritation appears to be reflex, being transmitted through the spinal cord to the splanchnic nerve. UREMIA; AMMONIEMIA; URIC-ACID DYSCRASIA. After extirpation of the kidneys, nephrectomy, or ligation of the ureters, which renders further secretion of urine impossible; further, also, in human beings, as a result of extreme urinary stasis, as well as in consequence of morbid alterations in the kidneys (inflammation, fatty degeneration, and desquamation of the epithe- lial cells of the urinary tvibules, cicatricial contraction of the kidney, amyloid degeneratioTi) , there develop a series of characteristic phenomena tha't resemble an intoxication, and, if of marked degree, cause death, with degeneration of the ganglia in the cerebral cortex and the spinal cord. This condition is designated uremic intoxication or uremia. Among the phenomena, the following are con- spicuous: Mental prostration, somnolence, even loss of consciousness to the point of deep coma, and, in addition, from time to time, the occurrence of twitching or even widespread, severe convulsions. Occasionally, there are delirium and general excitement. At the same time, the occurrence of the so-called Cheyne- Stokes respiratory phenomenon is often observed. Occasionally, transitory, in- variably bilateral, blindness occurs, from toxic paralysis of the psycho-optic center. There may, however, take place, quite independently, hemorrhagic extravasations into the retina, causing, rarely permanent, blindness — apoplectic retinitis. Also impairment of hearing is observed. Vomiting and diarrhea are common. Ammonium carbonate, formed in the digestive tract from urea, as well as kreatin, causes uremic diarrhea. Also the breath and the emanation from the skin may exhale the odor of ammonia. The alkalinity of the blood and the amount of oxygen in the blood are diminished. The retention of substances that are normally excreted by the urine must be considered as the cause of these symptoms, although it has not, as yet, been possible to designate with certainty the substances that must be considered as the agents upon which the toxic phenomena depend. Suspicion was first directed to urea. v. Voit observed that even healthy dogs exhibited uremic manifestations when they partook of urea for a considerable time with their food if, at the same time, the use of water, which would have carried oft" the urea rapidly through the kidneys, was prevented. Fvirther, Meissner found that death amid uremic manifestations could be hastened in nephrectomized animals, if urea was at the same time injected into the blood. An injection of moderate amounts of urea into the blood of entirely healthy animals was not, it is true, followed by uremic symptoms, although one or two grams caused a comatose state in rabbits. Dogs died after subcutaneous injection of urea to an amount equaling one per cent, of the bodily weight. Hippurie acid is said to have an entirely similar efl'ect in frogs. Although urea, when introduced into the blood in large amounts, causes death with convulsions, this condition should not be confounded with uremic attacks of intermittent occurrence. As injection of ammonium carbonate causes symptoms similar to those of uremia, v. Frerichs and Stannius believed that the decomposition of urea in the blood causes the intoxication — ammoniemia. However, after nephrectomy or ligation of the ureters, even on simultaneous injection of urea into the blood, careful chemical investigation fails to disclose the presence of ammonia in the blood. Therefore, spontaneous formation of ammonia in the blood cannot be the cause of the uremic symptoms. STRUCTURE AXD FUNCTION'S OF THE URETERS. 517 As in birds and reptiles, which eliminate principally uric acid, ligation of the ureters likewise induces a comatose state, it was necessary to think of other sub- stances as possibly causing the toxic symptoms. Meissner observed prostration and twitchings develop in dogs after injection of kreatinin. CI. Bernard, Traube, Ranke, Astaschewsky, Feltz and Ritter, and others attribute the phenomenon to an accumulation of the neutral potassium-salts; Schottin and Oppler suggest the accumulation of normal or abnormally decomposed extractives, Thudichum that of the oxidation-stages of the urinary pigment. Possibly many substances and their decomposition-products act in conjunction. R. Fleischer found a reduc- tion in the elimination of sulphuric and phosphoric acids in advance of the ure- mic attack m man. On placing various substances occurring in the urine — kreatinin, kreatin, acid potassium phosphate, uratic sediment from human urine — directly upon the sur- face of the cerebrvmi, Landois observed the development of all signs of uremia. There occurred, particularly, fully developed convulsive seizures, with intervals of rest, in dogs, with subsequent coma. Also, many other secondary phenomena of uremic eclampsia could be thus induced. Urea is inactive in this direction, ammonium carbonate, leucin, sodium carbonate, sodium chlorid, potassium chlorid, feebly active. After long-continued excessive ingestion of food, together with the use of spirit, and slight activity, there occurs, principally in conjunction with respiratory disorders, derangement of metabolism, and not rarely a marked accumulation of uric acid in the blood. The latter is deposited in the joints and their ligaments and cartilages, principally of the foot and the hand, and gives rise to inflammatory and painful attacks — gouty nodules, uric arthritis. Rarely, the kidneys, the heart, and the liver are involved. In the vicinity of the foci, the tissues undergo necrosis. Food containing nuclein is to be avoided; also meat -broths, meat- extract, sodium chlorid; while cheese, peptone, legumins, and aleuronat are to be commended. As to the amins, piperazin, lysidin, lycetol, urotropin, the in- vestigations are not as yet concluded. As uric acid is more readily soluble in solutions of urea, the administration of this substance has been advised. Uric acid introduced into the blood or into the lymphatic system causes changes in the renal epithelium, in the form of uric-acid spheroli'ths between and within the cells of the convoluted tubules. Administration of adenin, while it does not increase the excretion of uric acid, favors its deposition in the kidney amid in- flammator}- symptoms. In birds, long-continued administration of oxalates, sugar, acetone, phenol, gives rise to deposition of urates in the urinar}' tubules, as well as in the serous and the s\movial membranes, and these have disappeared after administration of piperazin. Human urine, when injected beneath the skin or into the veins of animals, has a toxic and even fatal elifect, particularly in the case of infectious diseases, diseases of the liver, carcinoma, exophthalmic goiter, and, in accordance herewith, after extirpation of the thyroid gland. The toxic properties are due to organic (toxins) and inorganic constituents, principally potassium-salts. Pregnant ani- mals are especially susceptible to this poison. STRUCTURE AND FUNCTIONS OF THE URETERS. The pelvis of the kidney and the ureter possess a mucous membrane con- stituted of delicate connective-tissue fibers with many embedded cells, upon which a laminated transitional epithelium is situated. The deepest layer of the latter is provided with small, round, soft cells. Then follows a layer of more nearly vertical, club-shaped and bulbous cells, whose attenuated extremities ramify between the cells of the deepest layer; the free surface is covered bv cubical cells, which finally are surmounted by a homogeneous cuticular border. Beneath the epithelium there is a layer of adenoid tissue, containing disseminated lymph- follicles. In the pelvis of the kidney, the mucous membrane contains isolated small grape-like mucous glands, which are present also in the ureter. The muscular coat consists of an internal somewhat thicker longitudinal laver and an external circular layer, to which, in its lower third, a number of disseminated bundles of longitudinal fibers are added. All of these layers are rather freely intenvoven with connective tissue. The external connective-tissue sheath forms a sort of adventitia, in which the larger vessels and the nerves, together with the ganglia, are situated. The layers of the ureter may be followed upward to the pelvis of the kidney and to the calices. They finally line the pelvis itself only with mucous 5i8 STRUCTURE AXD FUNCTION'S OF THE URETERS. membrane, passing over upon the base of the pyramids, while the muscle-fibers cease at the foot of the pyramids, where they form a. sort of sphincter about the pyramids by means of circular bundles. The blood-vessels supply the various layers and form a capillary network beneath the epithelium. The relatively scanty medullated nerves, in the vicinity of which ganglia are found, in part supply the muscles as motor fibers, while in part they penetrate toward the epithe- lium. These are reflex and sensor\-, as indicated by the severe pain attending impaction of calculi. The ureter penetrates the thickness of the bladder-wall, passing obliquely through it for a considerable distance. The internal opening is a slit in the mucous membrane directed obliquelj- inward and downward, and provided with a sharp, valve-like process (Fig. 177). The propulsion of the urine through the ureter takes place (i) in consequence of the fact that the urine constantly secreted in the kidney under considerable pressure forces on- ward the urine in the ureter, which is under lower pressure. (2) In the erect posture, the urine flows by gravity down the ureter. (3) The muscles of the ureter through their peristaltic movement propel the urine into the bladder. This movement occurs on- ly as a reflex phenom- enon in response to the entrance of the urine, a few drops every three-quarters of a minute, or in con- sequence of direct ir- ritation. It always passes downward with a velocity of from 20 to 30 mm. in a second. The greater the distention of the ureter by the urine, the more rapidly does this peristaltic movement take place. Asphyxia, venous hyperemia, and irritation of the splanchnic increase the number of contractions; while rapid ligation of the renal vessels, as well as ligation of the ureter, diminishes them. In case of local irritation, the contraction takes place in both directions. As Engelmann observed these movements also in excised portions of ureter in which neither ner\-e-fibers nor ganglia were visible, he believes that the move- ments are due to direct muscular conduction in the unstriated muscles, just as takes place in the heart. The stagnation of urine toward the kidney is prevented (i) by the fact that the secretion collecting in the pelvis of the kidney and in the calices under high pressure presses upon the pyramids from all sides, so that the urine cannot pass back into the urinary tubules closed by pres- sure. (2) If when the urine has accumulated in the ureter in consid- erable amount, as from occlusion by concretions, the musculature en- Fic. 177.— Lower Portion of the Male Rladder, with the Commencement cf the Ureter, Opened through a Median Incision in the .\nterior Wall, and spread out (after Henle). The clear lines of the trigone, the slit- like openings of the ureters, the ureters di\-ided above and the seminal vesicles can be recognized. On the colliculus seminalis there appear in the middle the large opening of the prostatic sinus, and on either , side the small circular orifice of the ejaculatory duct, and below both the numerous punctate openings of the excretory ducts of the prostate gland. STRUCTURE ( > 1- L K ! .\ A K V BLADDER AXD URETHRA. 519 gages in increased activity for the propulsion of the urine, the portion of the muscular fibers surrounding the pyramids so compresses the urinary tubules that the urine cannot pass back into the excretory ducts of the tubules. The return of urine from the bladder into the ureter is ren- dered difficult in part by the fact that with marked stretching of the bladder-wall the ureter, in so far as it is contained therein, is likewise com- pressed ; and in part by the fact that the stretching of the mucous mem- brane of the bladder firmly approximates the margins of the slit-like openings of the ureters (Fig. 177). In case of retention of urine in the bladder, a return of urine into the ureters may, it is true, take place. STRUCTURE OF THE URINARY BLADDER AND THE URETHRA. The mucous membrane of the bladder is not unlike that of the ureter. The laminated epithelium exhibits flatter cells in the upper layer. When the bladder is distended, the epithelial cells become stretched and thinner. The unstriated muscular fibers are arranged in bundles that form an external longitudinal layer and an internal circular layer. In addition, fibers pass in various directions and cross one another, forming a wide-meshed trabecular network. Between the mus- cular coat and the mucous membrane there is a layer of delicate, fibrillar, cellular connective tissue, with an intermixture of elastic fibers. An excessively minute dissection of the individual layers and bands of the musculature of the bladder has given rise to erroneous physiological interpretations. In this category- belongs the establishment of a special detrusor urinse muscle, which is said to consist of fibers pursuing a vertical direction from the vertex to the fundus, principally upon the anterior and posterior surfaces. The conception of a special internal sphincter vesicae is likewise unjustified as constituted of a circiilar layer of un- striped muscles, from 6 to 12 mm. thick, surrounding the commencement of the urethra, and in its form helping to give rise to the funnel-shape of the outlet of the bladder. This layer, also designated annulus urethralis vesicae, is no sphincter at all. In the trigone of Lieutaud there are, at times, between the orifices of the ureters, numerous muscular bundles, attached in part to the circular, in part to the longitudinal fibers of the wall of the bladder. Waldeyer believes, par- ticularly of the trigone, that it facilitates the distention of the bladder, favors its complete evacuation and aids its closure. From the physiological standpoint, it should be borne in mind that the entire musculature of the bladder represents a continuous hollow muscle whose sole function it is, in contracting, to diminish the cavity of the bladder from all directions and to expel its contents. The vessels of the bladder resemble those of the ureter in their distribution. The nerve-fibers are provided with ganglia, as is the case generally at all parts of the urinary passages outside the kidney. These are situated in part in the mucosa, in part in the muscularis, and the}^ communicate Avith one another by means of filaments. In the mucous membrane and its epithelium, the nerves terminate in end-bulbs. In accordance with their functions, the nerves are motor, sensory, reflex, and vasciilar. In women, the urethra serves only as the excretory- duct of the urinary bladder. The mucous membrane, formed of a large amount of fibrillar}- con- nective and elastic tissue and supplied with papillae, is lined by laminated pavement epithelitun. In addition, a number of Littre's mucous glands are embedded in it. Next to the mucous membrane is a layer of longitudinal vmstriated muscular fibers, and next to the latter a layer of circular fibers. These layers contain an abundance of connective-tissue and elastic fibers, and, besides, extensive venous plexuses, suggestive in their structure of cavernous spaces. The true sphincter muscle of the bladder is a striated muscle, which undergoes contraction and relaxation under the influence of the will, and consists in part of transverse, completely circular fibers, which extend 520 EVACUATION OF THE URINE. downward to the middle of the urethra and lie next to the unstriated cir- cular fibers, and in part of longitudinal fibers, which pass upward to the base of the bladder only on the posterior wall of the urethra, and down- ward between the circular fibers. Additional circular fibers are situated below the middle of the urethra, and only in isolated distribution on its anterior surface. In the male urethra, the cpitheHum of the prostatic portion still resembles that of the bladder, in the membranous portion it becomes laminated, and in the cavernous portion a simple cylindrical epithelium. The mucous membrane beneath the laminated epithelium, provided with papilhe, contains, principally in the posterior portion, the mucus-secreting glands of Littre. Unstriated muscle- fibers are present in the prostatic portion as a longitudinal layer, especially at the colliculus seminalis; while the membranous portion contains principally cir- cular fibers, with intervening longitudinal fibers. The cavernous portion contains posteriorly delicate circular fibers, anteriorly only isolated insignificant oblique and longitudinal fibers. With respect to the mechanism for closure of the male urethra, it should be pointed out that the so-called internal sphincter vesicge of the anatomists, which consists of unstriated muscular fibers, and, as an integ- ral portion of the musculature of the bladder surrounds the commencement of the urethra down to within the prostatic portion of the urethra, above the colliculus seminalis, is not a sphincter muscle at all. The true striated sphincter of the urethra, or external sphincter of the bladder, is situated below the former. It is a completely circular muscle, surround- ing the urethra, just above the entrance of the urethra into the urogen- ital septum, at the apex of the prostate gland, where its fibers anasto- mose with those of the subjacent deep transverse peroneal muscle. This sphincter muscle includes, also, longitudinal fibers, which pass downward from the bladder along the upper border of the prostate. Isolated transverse bimdles are derived anteriorly from the surface of the neck of the bladder. The sphincter muscle includes, besides, certain transverse fibers that lie within the prostate even opposite the apex of the colliculus seminalis, passing like a thick transverse column in advance of the commencement of the urethra into the structure of the prostate — prostatic muscle. In the male urethra, the blood-vessels form a rich capillarv network beneath the epithelium, in the midst of which a wide-meshed lymphatic vascular net- work is situated. COLLECTION AND RETENTION OF THE URINE IN THE BLADDER. EVACUATION OF THE URINE. After the evacuation of the bladder, urine reaccumulates, with grad- ual distention of the viscus. As long as the amount of urine is but mod- erate, the elasticity of the elastic fibers surrounding the urethra and of the sphincter muscle of the urethra — in men, in addition, that of the prostate — suffices perfectly to retain the urine in the bladder. This is indicated by the fact that in the cadaver the urine does not escape from the bladder. The movements for the evacuation of the bladder, as well as for the retention of the urine in the bladder, exhibit, in many respects, an agreement with the motor mechanism at the rectum. In the first place, it should be pointed out that the walls of the bladder are capable of independent contraction. Whether these are due to the ganglion-cells in the bladder that are found in the course of the nerves has not been demonstrated. It is rather more likely that the muscula- ture of the bladder is capable of rhythmic movement without nervous aid. EVACUATION' OF THE URIXE. 521 The urinary bladder, especially when consideral)ly distended, exhibits the occurrence of intermittent slight contractions, which can be compared with the peristaltic movements of the intestines. Even the excised frog's bladder, and even portions thereof without ganglia, exhibit similar rhythmic contractions, which can lie increased by heat. After division of all of the nerves f)f the bladder, bleeding with asphyxia is still followed by contractions as a result of direct stimu- lation of the muscles of the bladder. The contractions occur, further, more actively in the ])resence of derangement of the circulation in the bladder, or of venositv of the blood, in the same way as the movements of the intestine are brought about in marked degree by like influences. In this category belongs the evacuation of the urine when the action of the heart ceases in cases of sudden asphvxia or protracted suppression of respiration. As emotional disturbances also influence the contraction of the walls of the bladder, the evacuation of the urine in connection with sudden fear can be explained in this manner. In the state of apnea, as well as in apneic intervals after persistent deep respiratory movements, the independent contractions of the bladder cease. In order to comprehend the mechanism of the retention of the urine in the bladder, as well as of its evacuation, a description is necessary of the following nervous apparatus which participates in these processes : T. The sensory nerves of the walls of the bladder are derived from the first, second, third, and fourth posterior sacral roots. A number of sensory fibers pass into the spinal cord through the intermediation of the hypogastric plexus. The sensory nerves pass upward in the cord to the cerebral cortex. 2. The center for reflex stimulation of the unstriated musculature of the wall of the bladder — vesicospinal center — is situated in the neigh- borhood of the fourth lumbar vertebra, in the dog. 3. The motor tracts pass from this center to the unstriated muscula- ture of the wall of the bladder through the nerves between the second lumbar — by way of communicating branches of the sympathetic — and the fourth sacral by way of the nervi erigentes. Irritation of the sensory nerves of the wall of the bladder causes reflex contraction of the bladder-wall. In addition to the sensory nerves of the bladder, the reflex described may be excited also by irritation of other sensory nerves; thus, active tickling, or warming of the region of the knee during sleep at times causes evacuation of urine, likewise the hearing of splashing and whistling sounds. In animals, stimulation of certain sensory nerves likewise causes contractions of the bladder. Omitting consideration of the sphincter muscle of the urethra, the sensation of a distended bladder will become apparent as soon as the bladder is moderately distended. Then the mechanical irritation of the sensory nerves of the bladder in the mucous membrane excites in the vesicospinal center the reflex through the motor nerves of the unstriated musculature of the bladder, and in consequence of this the walls of the bladder undergo contraction. This constitutes the process as it takes place, for instance, normally always in infants, who do not as yet have control of the urethral sphincter. Also voluntary evacuation of the bladder, whatever the degree of distention, is always effected only through exci- tation of the reflex described. The will is incapable of influencing di- rectly the unstriated musculature of the bladder; and this is emphasized particularly by the author, in opposition to the statements of many other observers. To induce reflex stimulation of this movement of the bladder, principally in the presence of considerable degrees of distention, the direction of the attention to the sensations in the urinary apparatus 522 EVACUATION OF THE URIXE. alone suffices. "When the distention of the bladder is only moderate or slight, the sensory, excito-reflex nerv'es of the bladder must first be stimu- lated, and either through irritation of the sensory nerves -by voluntary contraction of the striated muscles of the urethra and the floor of the pelvis, or of the nerves of the bladder as a result of abdominal pressure. As electric stimulation from the cerebral peduncle downward through the motor paths of the spinal cord to the motor nerves of the unstriated musculature of the bladder causes contraction of the bladder, many investigators have concluded that the will is capable of exciting spon- taneous contractions of the bladder directly in this way. The author con- siders this view as incorrect. In his opinion, voluntary- evacuation of urine is always induced by reflex influences, in the excitation of which the will participates only in a secondary manner. With the vesical center situated in the spinal cord still other nervous apparatus cooper- ates. As painful irritation of sensor}^ nerves in different parts of the body also is capable of causing reflex contraction of the bladder — the involuntary discharge of urine that occurs frequently in children suffer- ing from disorders of dentition may be of this character; as, further, as has already been pointed out, senson,^ ner\^es situated at a higher level, even cerebral nerv^es, are capable of exciting the vesical reflex, it must be concluded that the vesical center extends for a considerable distance up- ward, perhaps to the anterior portion of the optic thalamus, and that from these higher levels descend motor paths that are susceptible of — possibly reflex — stimulation in the spinal cord. Irritation of the medulla from the cerebral peduncle downward causes contraction of the walls of the bladder. With respect to the mechanism for the retention of the urine in the bladder through the sphincter muscle of the urethra, consideration should be given to the following facts: 4. The motor ner\'es for the striated sphincter muscle are con- tained in the pudendal ner\'e, derived from the anterior roots of the third and fourth sacral nerves. Irritation causes contraction of the muscle; paralysis, inability to close the urethra, with the resiilt that dribbling or incontinence of urine takes place. Thenerv^es maybe both stimulated — voluntary interruption of the stream of urine — and in- hibited through the action of the will. 5. The sensory- nerves of the urethra pass into the spinal cord through the posterior roots of the third, fourth, and fifth sacral nerves. These stimulate, on the one hand, the reflex for the urethral sphincter, so that as soon as urine escapes from the bladder into the commencement of the urethra the sphincter muscle contracts; as, for instance, in adults, during sleep, when the bladder becomes distended. On the other hand, they transmit sensory impressions from the urethra, particularly also when urine forces its way into the canal. 6. The center for the urethral-sphincter reflex — urethrospinal cen- ter— is situated, in the dog, at the level of the fifth, and, in the rabbit, at the level of the seventh lumbar vertebra. 7. From the cerebral cortex the voluntary motor paths course down- ward through the spinal cord to the sphincter muscle of the iirethra, within the pyramidal tracts. 8. The inhibitory paths for this muscle likewise pass from the brain through the spinal cord, and through them the muscle may voluntarily DKKAN'GEMKNT OF URIXARV R i: T i: X T K.) \ AND MICTURITION. 523 be relaxed into inactivity. It has not yet been possible to stimulate this center experimentally. With respect to the mutual relations between the activity of the mus- culature of the bladder — expulsion of urine — and of the sphincter of the urethra — retention of urine — the action of the sphincter muscle pre- ponderates, as a rule, when the distention of the bladder is not excessive. In other w'ords, as soon as urine is forced into the urethra by ccfntraction of the musculature of the bladder, reflex closure of the urethra takes place. The action of the sphincter muscle, how^ever, predominates only to a certain degree; and neither the reflex nor the voluntary con- traction of the sphincter is capable of resisting strong pressure by the urine. In the act of micturition, as it takes place w^hen the bladder is moderately distended, the sphincter of the urethra must always be vol- untarily inhibited in its contraction during the contraction of the walls of the bladder. The foregoing description of the innervational conditions of the bladder is based upon the published experiments of Budge, all of which were performed in collaboration with Landois. Division of the sacral nerves, in the dog, causes degeneration of the nerves of the bladder and of the rectum, but not of the internal genitalia — some fibers of the urethral and vulvar nerves undergo degeneration. Bilateral division renders micturition and defecation impossible, Avhile unilateral division renders these difficult. In addition, there is complete anesthesia at the anus, of the vagina, and on the posterior aspect of the thigns, together with weak- ness at the ankle-joint. Normally, the bladder is completely evacuated. The residual urine that col- lects abnormally in greater or lesser amount is a source of danger, on account of the tendency to decomposition. The urine undergoes alterations during its sojourn in the bladder. According to Kaupp, retention is attended with an increase in the amount of sodium chlorid, and a diminution in the amount of urea and of water. The reduction in the latter is much more marked in con- junction with simultaneous sweating. The question whether the mucous mem- brane of the bladder absorbs soluble matters has been answered in the affirmative by CI. Bernard, for the dog. Under such circumstances, water is again excreted into the bladder. Maas and Pinner noted absorption also on the part of the urethral mucous membrane, Lewin and Goldschmidt also on the part of the ureter, and the pelvis of the kidney, as well as the prostatic vesicle (strychnin). As the ureters empty rather toward the base of the bladder, the urine most recently secreted is always the lowermost. Under varying conditions of secretion the urine may therefore (in a resting posture) form layers in the bladder, so that when evacuated the different la\-ers may be clearly distinguishable. In quiet dorsal decubitus, the pressure in the bladder is from 13 to 15 cu. cm. of a column of water. The pressure is naturally increased by increase of the intra-abdominal pressure, especially in consequence of coughing and expulsive efforts. The erect posture has a similar eft'ect, in consequence of the pressure of the viscera from above. In the evacuation of the urine, the amount expelled is at first small; this increases later in the same interval of time, and toward the end of the act it again diminishes. In men, the last portions are expelled from the urethra through voluntary contraction of the bulbo-cavernous muscle. Adult dogs constantly accelerate the stream of urine rhythmically through the action of this muscle. MORBID DERANGEMENT OF URINARY RETENTION AND OF MICTURITION. Derangement in the mechanism of retention and evacuation of urine may be referred by the physician to its cause from a consideration of the physiological conditions described. Retention of urine — ischuria — results (i) from occlusion of the urethra by foreign bodies, concretions, strictures, prostatic enlargement; (2) from paralysis or exhaustion of the musculature of the bladder, the latter also following parturition in consequence of the pressure of the child's parts against the bladder; (3) primarilv, after division of the spinal cord. Under such circum- 524 COMPARATIVE. HISTORICAL. stances, retention of urine takes place (a) because the division of the spinal cord gives rise to increased reflex activity on the part of the urethral sphincter, and (b) because inhibition of this reflex cannot take place. If, with increasing distention of the walls of the bladder, the urethral orifice is finally dilated mechanically, dribbling of urine takes place. Nevertheless, the urine' escapes only drop by drop, as it overcomes the maximum tension at which the urethra still closes. Therefore, the bladder becomes more and more distended, as the tone of the continuously stretched walls lessens progressively, and the bladder may be distended to an enormous size. In consequence of the entrance of bacteria into the bladder, ammoniacal decomposition of the long-retained urine may readily take place; and, as a result, catarrhal and inflammatory conditions of the bladder may be excited. (4) From interference with the "voluntary control of the inhibition of the reflex of the urethral sphincter, as well as from increased reflex excitability of the urethral center. Incontinence of «rnt^— stillicidium urinse — occurs as a result (i) of paralysis of the urethral sphincter; (2) of anesthesia of the urethra, in consequence of which the reflex of the sphincter must be lost; (3) incontinence of urine is, sec- ondarily, always a result of division of the spinal cord or of abnormal degeneration. Strangury is observed as an excessive reflex of the walls of the bladder and the sphincter muscle, in consequence of irritation of the bladder and the urethra, as observed in association with inflammation, irritation, and neuralgia. So-called nocturnal enuresis, nocturnal involuntary discharge of urine, mav be a result of increased reflex activity of the walls of the bladder, or of enfeeblement of the reflex of the sphincter muscle. Nothing of a definite nature is known as to the influence of deranged action of the will, principally in connection with unilateral injury, apoplexy, and the like. In patients suffering from disease of the spinal cord, there is impairment of the sensation of a distended bladder, as well as of the contractile power of the walls of the bladder. In neurasthenic patients, the latter is diminished, while the sensation of distention is increased. In patients with prostatic disease, there is, at first, likewise increased sensitivity with a dis- tended bladder. COMPARATIVE. HISTORICAL. In vertebrates, with exception of the bony fishes, there is often a union of the urinary and the generative organs. The primitive kidney (Wolffian body) , which serves during the first period of embryonic life as an excretory organ, assumes this function throughout life in fish and amphibia. The myxenoids (cyclostomata) possess the simplest kidneys: On either side there is a long ureter, upon which are situated capsules with short pedicles containing glomeruli, and arranged in rows. Both ureters empty into the genital pore. In the remaining fishes, the kidneys often extend longitudinally, lying as more compact masses on either side of the vertebral column. The two ureters unite to form the urethra, which always opens behind the anus, either united with the genital orifice or behind this. In the sturgeon and the shark the anus and the urethral orifice together form a cloaca. Bladder-like formations, which, however, do not resemble the urinary bladder of mammalia morphologically, occur in fish, either at each ureter (ray, sh^rk) or at the junction of the two. In amphibia, the eft'erent vessels of the testicles unite with the urinary^ tubules. The testicular-renal duct unites, in the frog, with that of the other side; and both, united, open into the cloaca, while the capacious urinary bladder opens through the anterior wall of the cloaca. From the reptiles upward, the kidney in all vertebrates is no longer the per- sisting Wolffian body, but a newly formed organ. In reptiles, it is generally flattened longitudinally. The ureters open separately into the cloaca. Saurians and tortoises possess a bladder opening into the anterior wall of the cloaca. In birds, the ureters remain separate and open into the urogenital sinus emptjang into the cloaca internally to the excretory ducts of the generative glands. The bladder is constantly wanting. In mammalia, the kidnej-s often consist of many small lobules, reniculi, as, for instance, in the seal, the dolphin, the ox. Among invertebrate animals, molluscs possess excretory organs in the form of canals provided with an external opening and an internal opening, communi- cating with the cavity of the body, and occasionally functionating also as oviducts. In mussels, this canal is expanded into a spongy organ (organ of Bojanus), situated at the base of the gills, often possessing a central cavity of considerable size, and FUXCTIOXS OF THE EXTERNAL IXTEGUMEXT. 525 jirovidcd with ciliated secretory cells. The internal (ciliated) excretory duct opens into the pericardial cavity; the outer, occasionally united with the sexual orihces, opens upon the external surface of the body. In the analogous, generally un- paired, often contractile organ of snails, guanin has been demonstrated. The organ is capable, in a remarkaljle manner, not alone of excreting water from the blood, but also of conveying water into the blood. Cephalopods possess sacculated ex- cretory organs, provided with glands and opening into the mantel-cavity lying on the vascular trunks of the gills. Insects, spiders, and centipedes have so-called Malpighian vessels, partly as uric-acid forming excretory organs; partly, also, as biliary organs. The.se vessels are long tubes that open into the commencement of the large intestine. In crabs, the blind tubes of the digestive tract probably have similar functions. In cestodes, the excretory organs are longitudinal tubes; in tape-worms two that extend throughout the entire chain, in the tenia- anastomosing at the junction of the segments by means of a large communication. In trematodes (distomum) the branching organ opens at the posterior extremity of the body. Also in most round- worms the excretory organ is formed of tubes, which, united, open at a pore in the abdominal line. Earth-worms possess, almost in all segments of the body in pairs, the so-called nephridia-canals, that is, tubes, often much con- voluted, that commence in the abdominal cavity with an inner, ciliated orifice, and communicate upon the ventral aspect of the body with the external surface. In the sea-urchin, the star-fish, and the medusse, the water-vascular system is, at the same time, the excretory organ. Also in sponges, the canals passing through the body and conveying water may be considered as such. Historical.— According to Aristotle the urine is derived from the blood passing through the kidneys, and then flows through the ureters into the bladder; the venous blood of the kidneys does not undergo coagulation. He pointed out the relatively large size of the human bladder. Berengar (1521) observed, on injecting water into the renal vessels, that fluid escaped from the papillae. Massa (1552) discovered lymphatic vessels in the kidneys. Eustachius (died 1580) ligated the ureters and subsequently found the bladder empty. Cusanus (1450) studied the color and the specific gravity of the urine. Rousset (15S1) pointed out the muscular nature of the walls of the bladder, in which Sanctorius (163 1) was un- able to recognize any special sphincter muscle; while Vesling (1641) had already described the trigone of Lieutaud (1753). The first more important chemical investigations were made by van Helmont in 1644. He demonstrated the solid constituents of the urine, and found among them sodium chlorid. He noted the higher specific gravity of febrile urine, and explained the development of urinarv calculi from the solid constituents of the urine. With respect to the discover)- of individual urinary constituents, it may be noted that Scheele, in 1776, dis- covered uric acid; Bergmann calcium phosphate; Brand and Kunckel phosphorus; Rouelle, in 1773, urea, which was named by Fourcroy and Vauquelin in 1799; Berzelius lactic acid; Seguin albumin in pathological urine; J- v. Liebig hippuric acid; Heintz and v. Pettenkofer kreatin and kreatinin; WoUaston, in 18 10, cystin; Marcet, in 181 7, xanthin; Lindbergson magnesium carbonate. The more recent histological, physiological, and chemical investigations are discussed in the text. FUNCTIONS OF THE EXTERNAL INTEGUMENT. STRUCTURE OF THE SKIN. The external integument, from 2.3 to 2.7 mm. thick, with a specific gravity of 1057, is constituted of the cutis vera, corium, cutis, and the overlying epidermis. The corium (Fig. 178, I, C) forms upon the entire surface numerous papillae, from 0.1 to 0.5 mm. high, of which the largest are encountered upon the palmar aspect of the hand and the plantar aspect of the foot, as well as upon the nipple and the glans penis. The majority of the papillae contain loops of capillary blood-vessels (g), and in circumscribed areas of the skin also so-called tactile corpuscles (Fig. 179, a). The papillae are arranged upon the skin in groups in the small areas bounded by the delicate furrows in the skin that are still macro- scopically visible. On the palmar aspect of the hand and the plantar aspect of the foot thev follow the characteristic cutaneous lines. The hornv skin consists 526 STRUCTURE OF THE SKIX. of a dense, uniformly woven network of elastic fibers, more delicate in the papilljE, and coarser in the deeper layers, with which fibrillary connective tissue, with connective-tissue corpuscles and lymphoid cells, are intermixed. In the deepest layers, the connective tissue predominates, and, by the interlacing of its bundles, forms longitudinal-rhombic reticular spaces (a a), generally filled with fatty tissue, whose longitudinal expansion corresponds with that of the greatest degree of ^ x^r ifi Fig. 178. — Histology of the Skin and the Epidermoidal Structures: I, transverse section through the skin, with hair and sebaceous glands (T), corium and epidermis are shown in reduced size; i, external, 2, internal fibrous layer of the hair-follicle; 3, cuticula of the hair-foUicle; 4, external root-sheath; 5, Henle's layer of the inner root-sheath; 6, Huxley's layer of the inner root-sheath; p, hair-root attached to the vascular hair-papUla; A, arrector pili muscle; C, corium: a, subcutaneous fatty tissue; b, horny layer; d, Malpighian mucous layer of the epidermis; g, vessels of the cutaneous papilla;; v, lymphatics of the cutaneous papillae; h, homy substance; i, medullary canal; k. epidermis of the hair; K, sudoriferous gland; E, epidermal scales from the homy layer, viewed partly from the side, partly from the surface; R. prickle-cells from the Malpighian layer; n, superficial, deep nail-cells; H, hair, more highly magnified; e. epidermis; c. medullary canal with medullary cells; f f, fiber cells of the hair-substance; x, cells of Huxley's layer; i, cells of Henle's layer; S. transverse section through a sudoriferous gland of the axillary cavity; a, adjacent unstriated muscular fibers; t, cells of a sebaceous gland, in part with fatty contents. tension of the skin at the part of the body in question. Beneath the corium lies the subcutaneous connective tissue, which, however, is without fat-cells in some places. At certain points, firm fibrous bands of connective tissue unite the skin to the underlying fascia, ligaments, or bones (tenacula cutis). In other situations, principally over projecting bony parts, there are subcutaneous mucous bursae filled with a synovial-like fluid, their interior partly lined by endothelium. THE XAILS AND THE HAIR. 527 Unstriated muscle-fibers are present in the uppermost layers of the corium, principally on the extensor aspects; further, particularly on the nipple, the mam- millary areola, the prepuce, the perineum, and in especial abundance in the tunica dartos of the scrotum. The arteries of the skin in the palm of the hand and the sole of the foot, which must sustain the greatest amount of pressure, possess the thickest walls for the propulsion of the i)lood-stream. In silver-workers, the elastic libers of the skin of the hands are discolored black in places from the deposition of reduced silver, and the same condition exists in cases of medicamentous argyria. The epidermis is a layer of pavement epithelium, from 0.08 to 0.12 mm. thick, tmited by cement-substance. The deepest layer, the mucous layer (d), rete Mal- pighii, consists of several layers of protoplasmic nucleated prickle-cells (R) , without membrane, pigmented in the colored races, as well as on the scrotum and at the anus, and of which the deepest are rather cylindrical and vertical. Among these cells scattered lymphatic wandering cells are encountered, which convey important constructive and nutrient material to the epithelial cells. On high magnification the cells are found to be provided with a fibrillar structure. The interstices between the prickles serve as lymph-paths. The more superficial layers (b), stratum corneum, consist of fiat, homy, non-nucleated, epidermic scales (E) that swell up in sodium hydrate. The division between these two layers is constituted by a layer especially distinct when the epidermis is thick — of bright transitional forms of cells — stratum lucidum (between b and d) . The uppermost layers of the epidermis are being continually desquamated, while new layers of cells resulting from division of the rete cells are constantly brought up from the depth. In this process, the cells that are elevated acquire the microscopic and chemical character of the horny layer, inasmuch as the nucleus un- dergoes atrophy. Wherever pigment is present in the epidermis itself and likewise in the epidermoidal structures, it is conveyed, in many situations, from the underlying connective tissue by the stellate wandering cells. In this way is explained the fact that pieces of epidermis trans- planted from a white person to a negro soon become dark. In cer- tain other situations, however — as, for instance, on the mam- milla—it can be shown that the pigment is formed in the deep epidermal cells themselves. Finally, the pigment in connective-tissue cells is said to be derived in part from that formed in the epidermal cells. In the layer of the epidermis in which the process of comification takes place, therefore, from the upper layers of prickle-cells down to the actual comified epidermis, the cells contain two varieties of granules — the albuminoid, intracellular, hyaline granules, and the fat-like, extracellular granules of eleidin, which are exhibited in an analogous manner by all homy structures at the boundary of the process of comification. The granules of eleidin can be stained with henna, the hyaline granules with hematoxylin. Both structures are said to be allied to chitin. Between the prickle-cells of the epidermis, and between the laminated epithelial cells of the mucous membrane, Herxheimer observed peculiar, spiral, solid fibers, which appeared to consist of fibrin-like masses. The elastic fibers of the homy skin undergo hyaline swelling and scaly or granular disintegration as a phenom- enon of age. Fig. T79. — Cvitani'ous P.ipilUc Dtpri'-L-J of ihcir Epidermis and the Vessels Injected : a a a, tactile papillae, each con- taining a Meissner corpuscle. THE NAILS AND THE HAIR. The nails consist of numerous layers of firmly united comified prickly epi- dermal cells, which can be isolated by caustic alkalies, and at the same time undergo swelling and display a nucleus (Fig. 178, n, m). The entire inferior surface of the nail rests upon the nail-bed. The posterior and the lateral borders are situated in a deep groove, the nail-fold (Fig. 180, e). The corium beneath 528 THE XAILS AND THE HAIR. Fig. i8o. — Transverse Section of One-half of a Xail, through the True Nail-bed (after Biesiadecki) : a, nail-substance; b. subjacent loose homy layer; c, mucous layer; d. nail-ridge divided transversely; e, nail-fold' whhout papillae; /. the horny layer of the nail-fold, which has pushed itself over the nail; g, papilla; of the skin of the dorsum of the finger. the nail is provided throtighout the entire extent of the nail-bed with longitudinal rows or bands of papillce (Fig. i8o, d). Immediately above these, as upon the skin in other situations, is fhe laminated, prickle-cell layer of the Malpighian mucous network (Fig. i8o, c). Over this the nail is spread, thus representing the horn}- layer of the nail- bed (Fig. iSo.a). The pos- terior nail-foM and the semilunar, brighter portion of the nail, the lunula, con- stitute the root of the nail. With the exception of a small surrovxnding area. they form at the same time the matrix, from which the growth of the nail takes ])lace. The whitish cres- cent, present also on iso- lated nails, is due to the lessened translucence of this posterior portion of the nail, and this is a result of the special thickness and the uniform distribution of the cells of the mucous layer in this situation. Growth and Develop- ment.— According to Unna, working vinder Waldeyer, the matrix of the nail is formed only by the floor and not also by the roof of the fold up to the anterior border of the lunula. The nail grows continuously from behind forward, and it is formed in layers by separation of the matrix. These layers are parallel with the surface of the matrix, though not with that of the nail. They pass obliquely from above and behind, downward and forward, through the thickness of the nail-structure. The nail is of uniform thickness from the anterior border of the lunula to the free margin. It. there- fore, no longer grows in thickness in this area, ex- cept by the deposition of new cornified layers of cells from the mucous layer on the under surface of the nail. In the course of a year, the fingers yield about 2 grams, the hands and feet, 3.43 grams of nail-substance — in the summer relatively more than in the winter. In the development oi the nail, Unna observed the following stages: (i) Between the second and the eighth month of fetal life, the situation of the nail is occupied by a partial increase of the cornification of the epidermis on the dorsal aspect of the terminal phalanx — the eponychium. As the remains of this, there persists throughout the whole of life the normally formed, epidermal, horny layer that separates the subsequently de- veloped, "definitive nail from the roof of the fold. (2) The definitive nail develops in the fourth month beneath the eponychium. The base of the nail is situated, at first, at the extremity of the terminal phalanx, and subsequently moves fur- ther toward the dorsum. In the seventh month, the actual thin nail, itself still covered with eponychium, covers the entire extent of the nail- bed, and in the eighth month it penetrates the fold wholly. (3) When, subsequently, the eponychium is exfoliated, the nail is disclosed. Afterbirth, the papillae develop upon the nail-bed, and, at the same time, the matrix extends to the most posterior portion of the fold. f r/ ■'■^ Fig. iSi. — Transverse Section of a Hair below the Neck of the Hair-follicle: a, e.xternal sheath of the hair-follicle, with (b) blood-\essels in transverse section; c, internal sheath of the hair- follicle; d, vitreous layer of a hair- follicle; e, external, g, internal root- sheath; /, external layer (Henle's sheath); g, inner layer of the latter (Huxley's sheath); h, cuticula; I, hair. THE NAILS ANM) TllH HAIR. 529 The Hair.— With the exception of tlie pn\m of the hatul, the sole of tlie foot, the dorsal aspect of the third ])halan^es of the tiny;ers and toes, the external surface of the eyelids, the glans penis, the inner surface of the prepuce, a portion of the labia, and the lips, the skin of the entire body is covered with in part large and in part small hairs (lanugo). The hair is embedded by means of its root in a depression in the skin — hair-follicle (Fig. 17S, I) — which jiasses obliquely through the thickness of the skin, at times down into the subcutaneous connective tissue. In the hair- follicle the following parts are distinguished: (i) The external fibrous layer (Fig. 17S, I, and Fig. 181, (/), constituted of nucleated connective-tissue bun- dles pursuing principally a longitudinal course, and in which the vessels and nerves are distributed. (2) The inner iibrous layer (Fig. 178, 2, and Fig. 181, c) , which contains connective-tissue fibers pursuing especially a transverse course. Toward the orifice of the hair- follicles, this layer passes over into the portion of the cutis vera forming the papilLne. At the bottom of the hair-follicle there is formed from the inner tibrotis sheath the bulbous, vascular hair-papilla — compara- ble to a papilla of the cutis — the matrix of the hair, from which the growth of the hair takes place. (3) The innermost layer of the hair-follicle proper forms, be- sides, a vitreous layer (Fig. 178, 3, and Fig. 181, d). It terminates at the neck of the hair-papilla; above, its prolongation passes to the junction between the cutis vera and the epidermis. In addition to these layers, the hair-follicle has an epithelial lining, which must be looked upon as related to the epidermis. Thus, the external root-sheath (Fig. 178, 4, and Fig. 181, r), consisting of several layers of soft cells of fibrillar appearance, separated by spaces, and lying in contact with the vitreous layer, appears as a direct continuation of the Malpighian mucous layer, and its outermost layer exhibits cells stretched laterally. At the bottom of the hair-follicle it becomes narrower, and on fully developed hairs it is delimited from the root of the hair itself. The horny layer of the epidermis, passing down into the hair-follicle to the orifice of the sebaceous glands, retains the properties that it possesses upon the external skin. Below the orifice, however, its con- tinuation forms the so-called internal root-sheath. This consists (i) of the outer single layer (Fig. 178, 5, and Fig. 181, /) of longitudinal, flat, homogeneous, nucleated cells (Fig. 178, magnified at i)— Henle's layer — ^lying next to the outer root-sheath. Internal to this, there lies (2) the layer of Huxley (Fig. 178, 6, and Fig. 181, g), constituted of nucleated, rather longitudinal, polygonal cells (Fig. 178, x) ; and, finally (3) the cuticula of the inner root-sheath, a layer formed of cells in a manner analogous to the superficial covering of the hair, separates the inner root-sheath from the hair itself. To\vard the hair-bulb, this triple layer becomes ill deflned, its cells mingling with those of the hair-bulb, without distinct limitation. All hair-bulbs are provided with nerve-cells and nerve-fibers, the latter having a bifid termination. The arrecior pili muscle (Fig. 178, A) is a flat, expanded layer of unstriped muscle-fibers passing from the outer fibrous layer of the bottom of the hair- follicle to the upper layer of the true skin, and always subtending the obtuse angle formed by the obliquely directed hair-follicle with the surface of the skin. Therefore, its contraction must cause the hair to become erect (goose-flesh). As a sebaceous follicle is usually present in the angle mentioned, the contraction may, by pressure, cause evacuation of the secretion of the gland. In addition, the muscle exerts a compressing effect upon the vessels of the papillary body. Goose-flesh never occurs upon the ear, the hand, or the foot. Occasionally it is only unilateral or confined to circumscribed areas. The pilomotor nerves are described on p. 719. The arrectores pilorum receive their nerves (pilomotor nerves) from branches that pass from the spinal cord and thence into the sympathetic. The irritation of certain ganglia of the sympathetic has caused erection of the hair in definite circumscribed areas of the skin in the ape. The muscles are stimulated by reflex influences, which either extend over the entire body or remain strictly unilateral or local. The hair, which remains firmly attached to the surface of the' hair-papilla by means of its swollen, lowermost portion, the head of the hair, consists of three parts: (i) The medullary substance (Fig. 178, I, i), which is wanting in the lanugo and in the hair of early childhood, consists of a central row of cells, from two to eight in number, lying side by side (H, c). (2) Surrounding this is the thicker cortical layer (h), 'which cons'ists of long, rigid, cornified hair-fiber cells (H, f, f), containing the pigment-granules of the hair. Nevertheless, the hair- fibers at times possess, besides, a diffuse tint. These fibers consist of minute longitudinal horn-fibrils, and exhibit a longitudinal nucleus when boiled with 34 530 THE KAILS AND THE HAIR. caustic alkalies. (3) Upon the surface of the hair is the cuticula (k;, consisting of laminated and non-nucleated scales arranged like the shingles on a roof (H, e). The graying of the hair in late life is dependent upon a deficiency in pigment- formation in the cortical structure. The silvery luster of white hair is further increased by the development of numerous air-bubbles, in large number in the medulla, but also in small number in the cortex, which reflect the light. Occa- sionally pigment develops in the growing hair, at times not, so that, accordingly, it appears discolored in places and not so in others. Sudden graying of the hair, of which well-authenticated records exist, and which has also been oVjserved upon one side of the body, was found by Landois in the case of a man who during an attack of delirium tremens was harassed by frightful hallucinations and became gray during a single night, to be de- pendent upon the presence of many air-bub- bles throughout the entire medulla of the blond hair, and in smaller numbers, also, in the cortical structure, while the pigment was preserved. These air- bubbles imparted an exquisite gray luster to the hair. In rare cases, intermittent graying of the hair of the scalp has been observed; so that the hair ex- hibited alternately light and dark curls at in- tervals of about I mm. In such a case, Lan- dois found the bright areas to be due to an abundant development of small air-bubbles in the medullary canal and the surrounding corti- cal area, v/hile the pigment was well preserved. As to the development of (he hair, KoUiker has discovered that, first, about the twelfth or thirteenth week, depressions like the finger of a glove take place from the epidermis into the corium. They are bounded externally by a vitreous membrane, and internally are occu- pied by soft homogeneous cells of the Malpig- hian mucous network. As these depressions subsequently enlarge downward and acquire a flask-like shape, the cells, arranged axially, ac- quire a rather longitudinal form and constitute a conical body, rising from the bottom of the recess. On this body there can be recognized an inner, darker portion, the primitive hair; and a thin, light, overlying cover, the inner root-sheath. The outermost cells, in contact with the wall of the fold, become the external root-sheath. Even before this, the papilla grows from below toward the hair-root; while, at the same time, the fibrous layers of the hair- follicle develop externally. Later on, the apex of the hair grows toward the homy layer of the epidermis. Here the apex penetrates the inner root-sheath, which is reflected upon the constantly growing hair like a sleeve. In the nineteenth week the hairs appear upon the forehead and the brow; between the twenty- third and the twenty-fifth week the lanugo- hair appears free, having a characteristic direction or grain on all parts of the body, just as is the case in animals. According to Kolliker, children are bom only with lanugo-hair. Of the physical properties of the hair, its great elasticity (tension, 0.35 of its length), marked cohesion (traction of from ij to 3 ounces), great resistance to putrefaction, as well as its high hygroscopic power, should be pointed out. The last property is possessed, also, by the epidermal cells, as indicated by the pains of clavi and cicatrices in damp weather. Fig. 182.— Ix)ngitudiiial Section through a Hair-folhcle, with the Hair in Process of Change (after v. Ebner): a, external and middle hair-follicle sheaths; b, \itreous layer; c, hair-papilla: with vascular loop; d, external, e, internal root-sheath (dlflfer- entiated into Henle's and Huxlej-'s layer); /, cuticula of the inner root-sneath; g, cuticula of the hair; h. young, non-medul- lated hair; i, conical tip of the new hair; /. hair polyp of the exfoliated hair with, k, the remains of the exfoliated external root -sheath. THE GLANDS OF THE SKIN. 53I The groivth of the hair takes place by the constant formation by cellular division of new cells, at first soft, upon the surface of the papilla, which represents the matrix of the hair. These cells are situated upon the lower surface of the hair-bulb, acquire the shape characteristic of the dilieront portions of the hair to wliich they become attached, and eventually undcrc;o t-ornitication. Thus, every newly formed layer raises the hair to a higher level out of the follicle. Human beings, between the eighteenth and twenty-sixth year, produce daily 0.20 gram of hair-tissue — corresponding to a loss of nitrogen represented by 0.0615 gram of urea — and even more in summer; and when frequently cut, according to Beneke, 14.6 grams of hair-tissue from the scalp annually. lodin or bromin, ingested into the body, passes into the tissue of the hair. As to changes in the hair, the statements made are by no means unanimous. According to one view, after the hair has attained its typical length, the formative process upon the surface of the hair-papilla is uninterrupted. The hair-bulb rises from the papilla, becomes cornified, remains generally free from pigment, and is finally raised more and more from the surface of the papilla, while its bulbous lower extremity becomes tibrillated like a broom (Fig. 182). The lower portion of the hair-follicle, thus made empty, diminishes in size; and upon the old papilla a new hair is formed through resumption of the formative processes, while the old soon becomes detached and falls out. In opposition to this view, Steinlein, Stieda, and others, contend that the papilla of the old hair is destroyed, while a new one forms in the hair-follicle, from whose surface the formation of the new hair takes place. Finally, KoUiker and Waldeyer believe both that new hair forms upon the old papilla and that its formation may take place upon a new papilla. The statement that hairs may be newly formed in adults, as in the fetus, is denied by v. Ebner. THE GLANDS OF THE SKIN. The sebaceous glands (Fig. 178, I, T) are simple acinous glands that in the case of large hairs empty laterally by from one to three openings into the hair- follicle, while in the case of small hairs the follicle projects free through the ex- cretory duct of the gland (Fig. 183). The glands upon the labia minora, the glans penis, the prepuce (Tyson's glands), and those upon the red surface of the lips bear no relation to hair-follicles. The largest are present upon the nose and the labia; they are entirely wanting upon the palm of the hand and the sole of the foot. The glands contain polyhedral or circularly flat, nucleated, secre- tory cells (Fig. 178, t), through whose proliferation several layers of epithelium result, the elements of which undergo fatty degeneration as they advance toward the lumen of the gland, where they are broken up into fatty detritus. The membrane that gives form to the gland- vesicle is a structureless vitreous skin. The sudoriferous glands (Fig. 178, I, K), also designated sweat-glands, each consist of a long, intestine-like, diverticular tube, whose extremity is rolled into a convoluted mass in the subcutaneous connective tissue; while the somewhat smaller excretory extremity passes through the corium and the epidermis in a spiral manner^n the illustration it is shown in abbreviated form. The cells of the sweat-glands are more compact, and are provided with intercellular and intra- cellular secretory passages and a rod-shaped central body. The glands are numerous and large on the palm of the hand, the plantar surface of the foot, in the axilla, the groin, the forehead, and about the nipple; scanty on the dorsum of the trunk; and are wanting on the glans penis, the prepuce, and the margin of the lips. Modifications are seen in the glands about the anus, the wax-glands of the ears (ceraminous glands), and the glands of Moll at the margin of the lids (which empty into the hair-follicles of the eyelashes) . The glandular tube is lined within the convolution, in the smaller part of the tube by a single layer of nucleated pavement-epithelium, and in the larger part by cylindrical epithelial cells (Fig. 178, S) without membrane, and in part con- taining fatty granules. The membrana propria is structureless and surrounded by delicate connective-tissue fibrils. Unstriated muscular fibers pass in a longi- tudinal direction on the larger glands (Fig. 178, S, a). The excretory duct (sweat-canal) contains no muscular fibers and is lined by a laminated epithelium of flat cells, whose surface possesses a thick, cuticular border. Within the epider- mis, the canal pursues an intercellular course, without an independent mem- brane, between the epidermal cells. A network of capillaries surrounds the con- volution. Before the vessels become capillary, the arteries form an intricate net- 532 THE SKIN AS AN EXTERNAL COVERING. work surrounding the convolution. This hears a remarkahle re emblance to the network forming the glomerulus in the Malpighian capsule of the kidney. Finally, a plexus of nerves passes to the glands. The total number of sudoriferous glands may be about two and one-half millions, representing a secretor}^ superficies of approximately 1080 square meters. With respect to their function, it should be borne in mind that they secrete sweat. Nevertheless, an oily fat is admixed with their secretion, possibly from special cells, and this may predominate in the secretion in animals, as in the hoof-glands of the frog of a horse's foot, the glands on the sole of the dog's foot, and those of birds' feet. Meissner attributes only a secretion of fat to the convoluted glands, and Unna also believes that the sweat is produced from the intercellular spaces of the prickle-cells, which communicate with the penetrating sweat- ducts. Tubular and reticular lymphatics without valves (Fig. 178,1, v) are present in the cutis, in part with blind terminations in the papillae. Neumann observed them arranged in the form of a network about the hair-follicles and their glands. A coarser network of larger lymph- trunks is found in the subcutaneous tissue. The blood-vessels appear principally in two layers; namely, in a superficial layer, from which the loops for the cutaneous papilla; arise; and a deep subcutaneous layer. Both vascular areas anastomose by means of pro- cesses. In addition, the glands of the skin are surrounded by a network of vessels. THE SKIN AS AN EXTERNAL COVERING. It is the function of the subcutaneous fatty tissue to fill the depressions be- tween the different parts of the body, as well as to round off projecting portions, so that the rounded fulness of the body- form, agreeable to the eye, results. The fatty tissue acting as a soft cushion, also affords protection from excessive pres- sure, as on the sole of the foot, in the palm of the hand, on the buttocks; and it encloses various more important parts that may be readily injured, as, for in- stance, the vessels and nerves in the axilla, the inguinal fold, and the popliteal space. As a poor con- ductor of heat, the subcutaneous fat shields the body against ex- cessive loss of heat; the cutis vera and the epidermis exert a similar influence The firm, elastic, readily movable cutis is capable of afford- ing protection against external mechanical injuries, and in this it is aided by the epidermis, whose dry, impervious, horny tissue, without nerves and vessels, is especially adapted to afford protection against poisons in solution; and is capable of offering considerable resistance even to thermic and chemical influences. A thin layer of sebum pro- tects the free surface of the epidermis from maceration by fluids and from the destructive action of the air. The epidermal layer is, further, important in the fluid-economy of the body. It exerts pressure upon the cutaneous capillaries, and thus affords protection against excessive loss Fig. 183. — Sebaceous Gland with a Lanugo- hair: a. glandular epithelium; b, rete Malpighii. continued into the glandular epithelium; <-, fat-containing cells and free fat as glandular contents; d, acini; e, root sheath with the hair. CUTANEOUS RESPIRATION'. CUTANEOUS SECRETION*: 533 of fluid from the vessels of the skin. Portions of skin deprived of epi- dermis, therefore, appear reddened, and exude droplets of moisture. Large weeping areas of skin are capable of impairing considerably the nutritive state of the body through loss of alljumin. The epidermis and the epidermoidal structures are, further, when dry, poor conductors of electricity. The passage of a strong current diminishes this resistance to one-thirtieth, in consequence of cataphoric infiltration. Finally, it may be stated that the presence of the uninjured epidermis yjrotects adjacent parts against adhesion. As the epidermis is but slightly extensible, it is drawn tensely over the folds and papillae of the corium, which are obliterated on stretching the skin. Even the papillae disappear in this way, if the tension is considerable. The hairs serve in various situations as tactile organs — cye-lashes, lanugo- hair of the face; and upon the head, as a poor conductor of heat, they regulate the taking up and the giving off of heat and afford protection against direct radia- tion from the sun. CUTANEOUS RESPIRATION. CUTANEOUS SECRETION. SEBUM. SWEAT. PIGMENT-FORMATION. The secretory activity of the external integument, whose extent ex- ceeds more than one and a half square meters, comprises (i) the respi- ratory excretion; (2) the secretion of the cutaneous fat; and (3) the secretion of sweat. Cutaneous respiration has already been discussed (p. 241). Suppression of the activity of the skin by varnishing is followed, in warm- blooded animals, at first by no reduction in the total gaseous interchange. Proba- bly increased respiratory' activity on the part of the lungs compensates for the loss of the respiratory activity of the skin. In certain mammals, especially in rabbits, death results from varnishing of the skin, probably in consequence of excessive loss of heat. Strong animals die later than weak; horses only in the course of several days, with trembling and emaciation. The greater the area of skin that is not varnished, the later does death take place. Rabbits die after one-eighth of the surface of their body has been varnished ; and after total covering of the skin the temperature at once declines, to as low as 19°. Pulse and respira- tion generally become less frequent; but with circumscribed varnishing, increased respiratory frequency and increased excretion of urea have been observed. Swine, dogs, and horses are said to exhibit only transitory depression of temperature and languor after one-half of the surface of the body has been varnished, though life is preserved. Varnishing of the skin is not injurious to human beings. The sebum of the skin. The fat secreted by the sebaceous glands is fluid when discharged, but stagnating within the excretory duct of the gland it is transformed into a white, tallowy mass, which, principally on the alae of the nose, can be expressed in sausage-shaped comedones. Its function is to keep the epidermis and the hair pliable and to pro- tect the skin against excessive desiccation. Microscopically, the secre- tion contains innumerable fat-globules, a few gland-cells filled with fat and rendered visible on addition of sodium hydrate, and in almost all human beings microscopic mite-like animals— demodex folliculorum. Chemical examination demonstrates the presence principally of fats, particu- larly olein (fluid) and palmitin (solid), together with fatty soaps, and some choles- terin; in addition, a small amount of albumin and unknown extractives. Among the inorganic constituents, the insoluble earthv phosphates preponderate; while the alkaline chlorids and phosphates are subordinate. There is some doubt as to the occurrence of sodium and ammonium phosphate and of ammonium chlorid. 534 CUTANEOUS RESPIRATION. CUTANEOUS SECRETION. The vernix caseosa, which covers the skin of the new-born, is a greasy mixture of cutaneous fat and macerated epidermis. It contains 35 per cent, of water and 14 per cent, of ethereal extracts, together with traces of albumin, chlorin, calcium, magnesium, and phosphoric acid. Examination for fats disclosed the presence of cholesterin, isocholesterin, oleic and palmitic acids (salts of fatty acids) , together with glycerin. The preputial smegma (52.8 per cent, fat) is a similar product, in which an ammonium-soap occurs. Ear-wax is a mixture of the secre- tion of the ceruminous glands, which resemble the sudoriferous glands, and of the glands of the hair-follicles of the auditory canal. It contains, in addition to the constituents of the cutaneous fat, a brown pigment, soluble in alcohol and fat; a bitter yellow extractive; albumin; lecithin; cholesterin; potassium-soaps; and a special fat. The secretion of the Meibomian glands is cutaneous fat. The production of the fatty coating necessary for the oiling of the epidermis takes place, together with the formation of keratin, in part within the epidermis itself. The presence of cholcsterin-fats in this situation has also been demonstrated in the layer of beginning comification. The sweat is secreted by the convoluted glands, the nuclei of the secretory cells acquiring a more nearly circular outline, and the cells, in the horse, becoming granular. So long as the secretion- is confined with- in narrow limits, the water secreted, together with the volatile constitu- ents, evaporates at once from the surface of the skin. As soon, however, as the secretion increases or evaporation is inhibited, the sweat appears in pearly drops at the orifices of the sweat-glands. The former has been designated insensible, the latter sensible perspiration. The insensible perspiration varies widely. Generally, the right side of the body perspires more freely than the left. The palm of the hand sweats in greatest measure. Then, in order, follow the sole of the foot, the cheek, the breast, the thigh, and the forearm. Sweating increases slowly from the morning onward, in greater degree in the afternoon, and declines after the evening meal; then, increasing, it reaches its maximum before midnight. The presence of a large amount of moisture in the surrounding air diminishes the perspiration, as do also copious sweating previously and increased diuresis. Children have a relatively greater insensible perspiration. Ingestion of water increases, and withholding of water diminishes, the sweat; alcohol also diminishes it. The smallest measure of dissipation of watery vapor takes place at 15° C, while both above and below this temperature-level the dissipation increases. The ordinary temperature be- neath the clothing is about 32° C. At this temperature the insensible perspiration equals 1500 grams of water. When the temperature of the surrounding atmos- phere is 23° C. and above, sweating begins. Generous nutrition, warm clothing, and work cause greater excretion of water. Pathological. — The insensible perspiration is increased in the presence of dis- eases of the skin, principally the acute erythemata. It is diminished in cases of scarlet fever, especially in association with uremia. Sweat can be collected in largest amount from human beings by exposure in the steam-bath at a high temperature in a metallic tub in which the subject lies and into which the secretion of the skin flows. In this way Favre collected 2560 grams of sweat in one and a half hours. It is convenient, also, to obtain thus the partial secretion of sweat from the arm, which is placed in a glass cylinder hermetically sealed by rubber bandages about the arm. In animals, sweating takes place in the horse, less in cattle, on the palm and the sole of the foot of the ape, the cat, the hedgehog. Swine sweat (?) on the snout, cattle about the mouth (?), while goats, rabbits, rats, mice, and dogs do not sweat at all. Microscopically, sweat contains epidermal scales and fatty granules from the glands of the skin accidentally present. The sweat is colorless and slightly turbid, with a specific gravity of 1005. It has a salty taste and a characteristic odor in different portions of the body, due to volatile fatty acids. The moist epidermis, including the hair and the nails, has an acid reaction, while the cutis has an alkaline reaction. The sweat secreted CUTANEOUS RESPIRATION. CUTANEOUS SECRETION. 535 during rest has an acid reaction, while if the secretion is increased, the acidity diminishes and the reaction may even become alkaHne. The sweat is composed of a glandular secretion having an alkaline reaction and an acid epidermal secretion. The reaction will vary in accordance with the preponderance of the one or the other of these constituents. The constituents of the sweat: — Water, together with volatile sub- stances, and it increases after copious drinking, 991 parts in 1000. E. Harnack found the solids on the average 8.5 in the thousand, includ- ing organic matters, 2 in the thousand, and inorganic matters, 6.5 in the thousand. Among the organic substances there should be mentioned some neutral fats, palmitin, stearin, found also in the sweat of the palm of the hand, which contains no sebaceous glands; in addition, cholesterin, volatile fatty acids, principally formic acid, together with acetic, bu- tyric, proprionic, caproic, and capric acids, probably varying qualitatively and quantitatively in different portions of the body. They are present in largest amount in the acid sweat first secreted. Further, there are traces of sulphocyanid-combinations, of albumin (resembling casein), considerable urea, more than o.i per cent., and also ammonium-salts as decomposition-products of the latter in the air. Also sulphuric acid, in conjugation with skatol and phenol, and oxy acids were found by Kast in the sweat, uric acid by Tichborne. In the uremic state — anuria attending cholera — urea is even found upon the skin in crystalline form. Marked increase in the secretion of sweat in healthy persons and in uremic patients diminishes the amount of urea in the urine. The reddish-yellow pigment that alcohol extracts from the residue of sweat and that is colored green by oxalic acid, is of unknown composition. Among the inorganic substances, those that are readily soluble pre- ponderate over those that are soluble with difficulty. There have been found sodium chlorid, 0.2; potassium chlorid, 0.02; sulphates, o.oi in 1000, together with traces of earthy phosphates and sodium phosphate. Of gases, the sweat contains carbon dioxid absorbed together with some nitrogen. Of ingested substances, the following appear again in the sweat: readily, benzoic acid, according to H. Meissner, also hippuric acid; cinnamic, tartaric, succinic acids; with greater difficulty, quinin, potassium iodid, mercuric chlo- rid, arsenous and arsenical acids, potassium and sodium arsenate. After the ingestion of iron arsenite, iron is found in the urine and arsenous acid in the sweat. Mercuric iodid is found transformed into chlorid, the iodin passing over into the saliva. When ingested, sweat has toxic effects. Pigment-forynation takes place in the form of agranular deposition, principally in the deeper, and less in the upper layers of the Malpighian network. It thus occurs particularly in the anal fold, on the scrotum, and the nipple; as well as universally in the colored races. The horny layer of the epidermis contains a diffuse yellowish-white pigment , which becomes darker in old age. This pigment-formation is supposed, like the process of comification, to depend upon a chemical process, in con- sequence of which reduction takes place. This process is increased by light. In addition, the prickle-layer contains granular pigment. The dark discoloration of the epidermis can be removed and the process of comification can be prevented by means of free oxygen. Among pathological pigment-formations is that which occurs in liver-spots> freckles, and in conjunction with Addison's disease. 536 IXFLUEXCES AFFECTIXG THE SECRETIOX OF SWEAT. INFLUENCES AFFECTING THE SECRETION OF SWEAT. The secretion of the skin, which on the average equals about -^j of the weight of the body, or twice the ehmination through the lungs, may be increased or diminished as a result of various influences. The tendency to sweating varies greatly in different individuals. Among the influences affecting the secretion of sweat the following are known : i . Elevation of the surrounding temperature causes marked redness of the skin and profuse secretion of sweat. Cold and a temperature of the skin above 50° C. suppress the secretion. 2. The presence of an increased amount of water in the blood, principally after the ingestion of warm fluid in large amount, increases the sweat. 3. Marked activity on the part of the heart and the vessels, in consequence of which the blood-pressure in the capillaries of the skin is increased, has a similar effect. In this category belongs, also, the increased sweating in consequence of violent muscular activity. Under such circumstances the excretion of nitro- gen through the sweat is increased. 4. Certain agents — hydrotics — increase sweating, such as pilocarpin, physostigma, strychnin, picro- toxin, muscarin, nicotin, camphor, and ammonium-combinations. Others, such as atropin and morphin in large doses, diminish the sweat. 5. The antagonism that exists between the secretion of sweat and the secretion of urine and the intestinal discharges, probably in consequence principally of mechanical influences, is especially note- worthy in so far as abundant micturition, as, for instance, in cases of diabetes, and thin stools are associated with dryness of the skin. If the amount of sweat is increased, the proportion of salts, urea and albumin present increases; while the remaining organic substances diminish. The more saturated the air with watery vapor, the more readily does the secretion appear in drops upon the surface; while in dry air in active motion the secretion appears as fluid later in conse- quence of the rapid evaporation. NERVOUS CONTROL AFFECTING THE SECRETION OF SWEAT. As in the secretion of saliva, vascular nerves are principally active in the secretion of sweat, in addition to the true secretory ner^'es; and most frequently the vasodilators, as indicated by the sweating when the skin is reddened. The observation of sweating when the skin is pale (the sweating of fear and of death) shows, however, that also in the presence of vasoconstriction, the sweat-fibers may at the same time be active. Under certain conditions an increase in the amount of blood present appears alone to be sufficient for the occurrence of sweating. In favor of this view is the observation of Dupuy, who noted unilateral sweating of the neck in a horse after division of the cervical sympathetic; and in opposition to this view is the statement of Xitzelnadel, who observed diminution of sweating in human beings after percutaneous galvanization of the cervical sympathetic. Independently of the circulation, sweat -nerves of independent activ- ity control the secretion from the surface of the body. Irritation of the appropriate nerve-trunk still causes transitory secretion of sweat even if the extremity has been previously amputated ; and therefore the circula- tion no longer exists. In addition, the secretion of sweat may take place under higher pressure than that of the blood. In the healthy body, pro- NERVOUS CONTROL AFFECTIXG THE SECRETION OF SWEAT. 537 fuse secretion of sweat, it is true, appears usually to be associated with vascular dilatation, like the secretion of saliva after irritation of the facial nerve. Indeed, the sudoriferous and the vascular nerves appear to pursue almost identical paths. For the hind extremity, in the cat, these fibers are contained in the sciatic nerve. Luchsinger was able to excite constantly renewed secretion of sweat for half an hour by irritation of the peripheral stump, if the paw was constantly kept dry. This nervous activity is destroyed by atropin. If a young cat, whose sciatic nerve on one side has been divided, is placed in a room filled with hot air, the three intact members soon sweat, but not that with the divided nerve, not even when excessive hyperemia of the member is induced by ligation of the veins. The sweat-fibers pass centripetally from the sciatic nerve, in the abdominal sym- pathetic, in order to reach the upper lumbar and lower dorsal cord (twelfth dorsal and first, second, and third lumbar roots in the cat), through the communicating branches of the sympathetic and through the anterior roots. The center for the secretion of sweat in the hind extremities is situated in the ganglia of the anterior horns in the lower dorsal and upper lumbar portions of the spinal cord. According to Langley, non-medullated sweat-fibers pass in the cat to the nerves from the eleventh dorsal to the fifth lumbar, and are derived from the sixth and seventh lumbar and the first and second sacral ganglia of the sympathetic. The origin and course of the vasomotors are, on the whole, the same. This spinal center may be irritated directly (i) through marked venosity of the blood; therefore through dyspneic stimulation. In this category belongs probably also the sweat of the death-agony. (2) Through overheated blood (45° C.) passing through the center. (3) By certain poisons (see p. 536). Reflex stimulation of this center is effected, though wath varying result, through irritation of the crural or peroneal nerve of the same side, as well as of the sciatic nerve of the op- posite side. For the fore-paws, in the cat, the sweat-fibers pass in the ulnar and median nerves. These pass from the dorsal roots between the fourth and the tenth to the dorsal division of the sympathetic, and then pass downward through the stellate ganglion, and thence into the nerves of the anterior limb. An analogous center for the anterior extremities is situated in the lower half of the cervical cord. Irritation of the central stump of the brachial plexus causes reflex sw^eating of the paw of the opposite side. Under such circumstances, the hind paws also sweat at the same time. Pathological. ^Degeneration of the motor ganglia of the anterior horns of the spinal cord induces loss of the secretion of sweat, together with paralysis of the striated muscles of the trunk. Perspiration is increased in enfeebled as well as in edematous extremities. Nephritic patients exhibit great variations in the amount of water given off by the skin. Dieft'enbach observed that sweating reappeared in transplanted bits of skin only after the return of sensitivity. The sweat-fibers for the head (man, horse; snout in swine) are derived from the upper dorsal sympathetic, pass through the stellate ganglion and ascend in the cervical sympathetic. The observation is probably appropriate here that in human beings percutaneous galvanization of the cer\,-ical sympathetic causes sweating on the same side of the face and the arm, as well as the pathological observation that in association with unilateral sweating of the head, neck, and upper extremity, the corresponding pupil is dilated and the skin is pale. In the cephalic portion of the sympathetic the sweat-fibers enter the branches of the trigeminus, and this fact explains the circumstance that irritation of the infra- orbital nerve excites the secretion of sweat. Some fibers, however, arise directly from the trigeminal roots and the facial nerv^e. Undoubtedly, the cerebrum must also exert a direct influence either upon the vasomotor nerves or upon the sweat-fibers, as is shown b}^ the sweating that attends emotional disturbances, fright, etc. 538 PHYSIOLOGICAL CARE OF THE SKIX. An observation of Adamkiewicz and Senator tends to support this view. They noted that in a human being with an abscess in the motor area of the cerebral cortex for the arm, convulsions and sweating occurred in this member. According to Adamkiewicz, all of the four paws of the cat sweat on irritation of the medulla oblongata, in which the dominating center for the secretion of sweat appears to be situated, even three-quarters of an hour after death. Nerve-fibers that pass to the unstriated muscular fibers of the sudorif- erous glands, and are wanting in the smaller glands, must have an influ- ence upon the discharge of the secretion. Pilocarpin and other diaphoretics, when injected subcutaneouslj', even after division of the nerves, cause sweating first at the site of injection. Atropin, in the same way, causes first local suppression of sweat-secretion. If the sweat- nerves are divided, in the cat, the irritability of the fibers (sciatic) to electrical stimulation is lost in the course of four days. In cats operated on, delayed sweating after injection of pilocarpin occurs during the course of three days, and this may be prolonged, after the lapse of six daj^s, even to a delay of ten min- utes. At a later period, the sweating may remain entirely in abeyance. The familiar phenomenon of the dr\- skin of paralyzed members is in accord with this observation. If in man, a motor nerve, such as the tibial, median, or facial, be irritated, sweat appears in the distribution of the active musculature and in the corre- sponding distribution on the unirritated half of the bod}-; and both when the cir- culation is free, as well as when it is arrested. On sensory and thermic irritation of the skin, there likewise occurs reflex sweating always upon both sides, inde- pendently of the circulation. The seat of the sweating is independent of the site of cutaneous irritation. In the case of the author himself, cold sweat appeared immediately upon the forehead as soon as the mucous membrane of the mouth was irritated bv strong vinegar. PHYSIOLOGICAL CARE OF THE SKIN. PATHOLOGICAL ABNORMALITIES IN THE SECRETION OF SWEAT AND SEBUM. In order to maintain the normal secretion of the skin, the care of this organ by means of frequent ablution and baths, soap being used to remove the fattv accumulation upon the skin, is of the greatest significance, as in this way the pores are kept open. By friction of the epidermis, baths aid metabolism., by an action upon the cutaneous vessels influence the circulation and the heat-economv of the body, and have a stimulating eftect upon the nervous system. The estab- lishment of public bath-houses must be considered among the most beneficent measures for the preservation of the public health. Diminution in the secretion of sweat, anidrosis, occurs in cases of diabetes and carcinomatous cachexia; further, together with other nutritive disorders of the skin, in connection with certain nervous diseases, as, for instance, paralytic de- mentia. It has been observed in circumscribed areas of the skin as one of the phenomena of certain trophoneuroses; as, for instance, unilateral atrophy of the face, and in parah'zed parts. In some of these cases there may be paralj'^sis of the nerves in question, or of their spinal centers. Increase in the secretion of sweat, hyperidrosis, occurs in part in readily excit- able persons, in consequence of irritation of the nerves in question. In this cate- gor\- belongs the sweating that attends debilitated states, and that occurs also in hysterical persons, principally upon the head and the hands; and the so-called epilep- toid sweats that occur paroxysmally. Unilateral sweating, principally of the head, long known to earlier physicians, is especially noteworthy. This has been ob- served in conjunction with other nervous disorders, in part among the svmptoms of irritation of the cervical sympathetic — dilatation of the pupils, exophthalmos. Landois has, however, observed unilateral sweating without other evidence of sympathetic disorder, probably as a manifestation of irritation of the true sweat- fibers. Qualitative alterations in the secretion of sweat, paridrosis. In this cate- ABSORPTION THROUGH THE SKIN. 539 gory belong the rare cases of blood-sweat iui^, Itciiiattdrosis, which may also be uni- lateral, and in which, at times, the bloody discharge from the pores of tlie skin appears to take place vicariously for absent menstruation. More commonly, how- ever, the condition has been one of the symptoms of a profound nervous disorder, especially convulsive seizures. Blood-corpuscles, rarely blood-crystals, have been found in the escaping drops of red sweat. Yellow fever also is, at times, attended with bloody sweats. Biliary pigment has been found in the sweat of jaundiced persons; a bluish-black discoloration, further a blue color from indigo, from pyo- cyanin (the rare blue pigment of pus), produced by the bacillus pyocyaneus, or from ferric phosphate, are among the rarest exceptions. Such colored sweating is designated chrontidrosis. Between the epidermal scales and upon the hair there live numerous micro- organisms, which, however, must be designated as innocuous: Two varieties of saccharomyces; the leptothrix epidermidis and various bacteria on surfaces the seat of intertrigo, namely, five varieties of micrococci; and between the toes, the bacterium graveolens and bacillus saprogencs, which generate the odor of the sweat of the foot. Yellow, blue, and red sweat are likewise caused by bacteria, the last b}' the micrococcus ha^matodes. Red sweat and black sweat may be caused also by a variety of torula. Within the lesions of acne and in comedones, there vegetates a thick bacillus, which Hodara considers as the cause for the formation of the pustule. Grape-sugar has been found in the sweat in cases of diabetes; rarely uric acid, in individuals with calculi; cystin, in cases of cystinuria. In the fetid sweat of the feet, leucin, tyrosin, valerianic acid, and ammonia are present. This con- dition can be corrected only by the most systematic and scrupulous cleanliness. To the foot-baths, anti-fermentative and bactericidal substances should be added, such as salicylic acid or potassium permanganate. Odorous secretion of sweat is designated as osmidrosis, fetid sweating as bromidrosis. In the sweating stage of intermittent fever, considerable calcium butyrate has been found; in cases of puerperal fever, lactic acid. The viscid sweat of acute articular rheumatism is said to contain a greater amount of albumin, as does also the sweat attending enforced diaphoresis. With respect to abnormalities in the secretion of the cutaneous sebum, there should be mentioned the pathological increase in secretion — seborrhea — which occurs either locally or disseminated over the entire skin. In cases of premature baldness, there is increased production of sebum on the scalp. Diminished secre- tion of sebum — astcatosis of the skin — causes the skin to become brittle and rough, in part locally and in part extensively. Often, as upon the bald head in the aged, the sebaceous glands undergo atrophy. If the excretory ducts of the seba- ceous glands become obstructed, the sebum accumvilates, in greater or lesser amount. Not rarely, the excretory ducts are occluded by particles of dirt, gran- ules of ultramarine derived from washing blue, and vegetable fibers from the clothing. By pressure, the fatty, worm-like comedo is discharged. ABSORPTION THROUGH THE SKIN. GALVANIC CONDUC- TIVITY. After prolonged exposure to v^^ater, the epidermis becomes moist and swollen. On the other hand, the skin is incapable of absorbing sub- stances, either salts or vegetable poisons, from watery solutions, such as baths. This inability is due to the fat normally present in the epi- dermis and the pores of the skin. If, therefore, substances dissolved in such fluids as dissolve and extract the cutaneous sebum, as al- cohol, ether, and particularly chloroform, are applied to the skin, they may be absorbed in small amounts — in larger measure in rabbits. Volatile substances, such as carbolic acid, that exert a corrosive effect upon the epidermis, are capable of absorption through the injured areas. Absorption does not take place from ointments applied simply to the skin. In the case of persistent vigorous inunction, there occurs, at times, a forcible introduction into the pores of the skin, not rarely in association with mechanical lesions in the continuity of the layers of epidermis. 540 COMPARATIVE. HISTORICAL. Under such circumstances, absorption, as of potassium iodid, may take place from ointments. Thus, v. Voit observed globules of mercury be- tv^een the layers of epidermis and even in the corium of an executed in- dividual, to whom, while still warm, he had given vigorous inunctions. In courses of treatment with inunctions of mercurial ointment, globules of mercury penetrate, on rubbing, also into the hair-follicles and excretory ducts of the glands, where under the influence of the glandular secretion they may be transformed into a combination susceptible of absorption. In addition, mercury, in the form of vapor, reaches the respiratory mucous membrane, where, likewise, it is transformed into an absorbable combination. The inflamed skin, especially, however, when covered with fissured or injured epidermis, absorbs rapidly, like a wound-surface. As all substances that irritate the skin sever the continuity of the latter when the effect is long continued, it can readily be understood that they are eventually absorbed from the wounded areas. As the skin, under normal conditions, absorbs oxygen from the atmosphere, it may also absorb gases, such as hydrocyanic acid, hydro- gen sulphid, carbon monoxid, carbon dioxid, vapors of ether and chloro- form. From a bath that contains absorbed hydrogen sulphid, this gas is absorbed; conversely, carbon dioxid is given off to the bath- water. In frogs, active absorption of watery solutions takes place through the skin, the epidermal cells undergoing enlargement and exhibiting motor phenomena. These phenomena may also be induced artificially by electric stimulation. The frog also absorbs much water through the skin even when the circulation is elimi- nated and the central nervous system is destroyed; though more, however, when the circulation is maintained. The skin of the frog exhibits, in the process of absorption, a vital cellular activity, in consequence of which penetration takes place from without inward. "^he transfer of watery solutions through the skin by means of the constant galvanic current, cataphoric action, is a matter of especial interest. Both elec- trodes are impregnated with a watery solution of the substance in question, and the direction of the current is altered from time to time. Thus, H. Munk was able to introduce through the skin of rabbits within several minutes strychnin, from the effects of which they died. In man, the introduction of quinin and po- tassium iodid into the body was thus effected, these svibstances being subsequently demonstrated in the urine. In the introduction, the compound bodies are (always?) decomposed by the current; thus, for instance, the positive pole of the current introduces the calcium of calcium chlorid; the negative, only chlorin. COMPARATIVE. HISTORICAL. In all vertebrates, the skin consists of corium and epidermis. In reptiles, the cornification of the epidermis occurs in large plates (scales of the snake, shell of the tortoise). Among mammals, the armadillo exhibits a similar forma- tion. In addition to hair and nails, there occur in animals, as epidermoidal struc- tures, prickles, bristles, feathers, claws, hoofs, horns (the antlers of the deer are bony formations arising from the frontal bone) , spurs (cock) , the horny covering of the beak of turtles and of birds, and the horn of the rhinoceros. The scales of fish, on the other hand, consist of ossified portions of skin. Some fish possess considerable portions of bone upon the skin. The skin is provided with a large variety of glands. In the amphibia, they secrete either mucus alone or poisonous substances. Serpents and tortoises possess no cutaneous glands at all. In lizards, the thigh-glands extend from the anus to the popliteal spaces. In crocodiles the glands open beneath the margin of the cutaneous osseous scales. Birds have no cutaneous glands. The coccygeal gland, situated above the coccygeal vertebra, furnishes a secretion for lubricating the feathers. The civet-glands at the anus of the civet-cat, the preputial glands on the musk-bag of the musk-deer, the inguinal glands of the hare, the pedal glands of ruminants are peculiarly developed sebaceous glands. The strongly odorous castoreum is the secretion of the prepuce in both sexes of the beaver. COMPARATIVE. HISTORICAL. 541 In molluscs, the skin, consisting of epidermis and cerium, is intimately united with the imderlying muscles to form the musculo-cutaneous tube of the body. Cephalopods have, in their skin, the so-called chromatophores; that is, round cells tilled with granular pigment, at the periphery of which muscular fibers are attached in a radiate manner, so that their contraction must increase the colored surface. Through the play of these muscles there result the color-variations observed in cuttle-fish. Chromatophores are present, also, in other classes of animals, such as amphibia (frog) and fish (pike). In these animals, they appear as connective-tissue cells, within which pigment-granules either collect toward the center or swarm toward the periphery, while the processes of the cells them- selves do not change their place. Every cell is provided with numerous nerve- endings, which surround the pigment-mass in the form of garlands, with free terminal radiations. Special glands furnish the material for the formation of the scales of the snails. In all invertebrates, the development of the scales takes place from a portion of the surface of the body of the animal that has been desig- nated the mantle. In articulates, the entire surface of the body is covered by a more or less solid shield, which is to be considered as a cuticular structure consisting of chitin, which is separated from the underlying matrix. It extends for some distance into the digestive tube and the trachea. In the formation of the skin it is thrown off and replaces itself anew from the matrix. This shield, which affords protection to the body, serves, at the same time, for the attachment of the muscles. It thus becomes a passive motor organ comparable to the skeleton of the vertebrates. The echinoderms exhibit deposits of lime in their skin, in consequence of which they often acquire a cutaneous skeleton. The deposits of lime are either united to form large immovable plates, as in the scale of the sea-urchin, or united together in segments, as in the arms of the star-fish. In holothurians alone, the significance of calcification with respect to the cutaneous skeleton is of subordinate importance. In them, only isolated plates of lime have remained in various forms. In worms, the skin forms with the underlying muscles the musculo- cutaneous tube. The epidermis is. in some, provided with cilia; in others (tape- worms) it is traversed by pores; w'hile in still others it is without any appendage. The booklets on the head of teniEe, the rod-shaped motor bristles on the body of earth-worms, are cuticular formations. Cutaneous glands are present in the more highly developed worms, such as the leech. The integument of coelentrates (zoophytes) is characterized by the forerunners of disseminated nettle-cells; that is. cells provided with whip-like processes, w^hich contain a corrosive fluid and serve as organs of capture. Cilia are present in many; in some a tubular, external, chitin-like skeleton is formed. The integument of sponges is suggestive of that of zoophytes. Infusoria possess numerous cilia, which in part are even subject to voluntary stimulation. Rhizopods are wholly unpro- vided with a true skin. Nevertheless under these circumstances the formation of silicious (radiolaria) or calcareous structures (monothalamia and polythalamia) is noteworthy. Historical: Hippocrates (bom 460 B. C.) and Theophrastus (bom 371 B. C.) distinguished perspiration from sweat. According to the latter the secretion of sweat stands in a certain antagonistic relation to the secretion of urine and to the amount of water in the feces. Individuals suffering from fright were believed to sweat more freely from the feet. Father Augustinus stated that he knew an individual who was able to sweat voluntarily. According to Cassius Felix (97 A. D.) the skin absorbs water in the bath. He made investigations into the evaporation from the skin. Sanctorius (16 14) measured more accurately the insensible perspiration and the loss of weight on the part of a fasting individual. The hair-follicle and the root of the hair are mentioned in the Talmud. Alberti (1581) recognized the hair-bulb. Donatus (1588) made the first report of sudden graying of the hair. Riolan (1626) discovered the cutaneous pigment of the negro in the epidermis. De Heyde (1684) and Leeuwenhoeck described the ciliated movement on the beard of mussels (1694). PHYSIOLOGY OF THE MOTOR APPARATUS. STRUCTURE AND ARRANGEMENT OF THE MUSCLES. The striated (voluntaryj muscles are covered on their outer surface by a connective-tissue sheath, the external periniysiunt. From this sheath septa extend into the interior of the muscle, the internal perimysium, carrying vessels and nerves, and dividing the muscle into bundles of fibers, which are sometimes finer (eye muscles) and sometimes coarser (gluteals). Each compartment thus formed contains a number of muscle-fibers lying close together. Each muscle-fiber is surrounded by a rich meshwork of blood-capillaries, with neighboring lymphatics; it also has a nerve-fiber leading to it. These structures are held on the surface of the muscle-fiber by means of an extremely delicate connective tissue with a scarcely recognizable fibrillar structure, representing to a certain extent a perimysium for each separate fiber. The individual muscle-fibers or primitive muscular bundles may be isolated by means of a 35 per cent, solution of potassium hydroxid, or of nitric acid containing an excess of potassium chlorate. They are from 10 to 100 u in diameter, and are of limited length, in man from 5.3 to 9.8 cm. Within short muscles (the sta- pedius among others and the small muscles of the frog) the fibers, therefore, traverse the entire length of the muscle; within longer muscles, however, each fiber tapers to a point and is attached obliquely by cement-substance to the succeeding, similarly pointed fiber. Each muscular spindle is completely en- closed in a structureless, transparent sheath, the sarcolemma (Fig. 184, i, S). The muscle-fiber exhibits at intervals of from 2 to 2.8 ,« a transverse striation due to alternate light and dark layers (i, Q). As a result of the action of hydro- chloric acid (i : 1000) or of the gastric juice, or after freezing, the fiber not rarely undergoes a solution of continuity in the region of the light bands, so that it breaks up into plates or discs (5) resembling an overthrown pile of coins, the discs always corresponding to the dark parts of the fiber. In addition to the transverse striation, a longitudinal striation may be observed in the fiber. This is due to the fact that the muscle-fiber is made up of numerous, fine, contractile threads (from i to 1.7 ," in diameter), the primitive fibrils (Fig. 184, i, F), lying side by side. Each separate fibril is striated transversely, and all are bound together by a small amount of a fluid, finely granular, cement-substance (RoUet's sarcoplasm) , in such manner that the transverse striations of all fibrils are situated at the same level. The sarcoplasm embeds all of the fibrils uniformly, and occurs also in a thin layer between the sarcolemma and the muscle-substance; it contains minute interstitial granules (fat and lecithin). The fibrils are prismatically flat- tened against one another; hence, a cross-section of a fresh frozen muscle exhibits a design consisting of polygonal figures — Cohnheim's fields (2). The study of an isolated fibril under high magnification shows it to be a columnar structure, made up of numerous parts superposed in layers. These sections, which may be termed muscular elements, exhibit individually a com- plicated structure. Each muscular element (4) is a prismatic body, from 2 to 2.8 " in height, with plane terminal surfaces. The entire middle layer is occupied by the darker and more highly refractive, true contractile substance, the trans- verse disc (Bowman's sarcous elements, Kuhne's muscle-prisms). This is doubly refractive (anisotropic) and contains a bright layer, the median disc (4 c), which can be recognized as a bright line bisecting the dark field. On the upper and lower surfaces of the darker, contractile substance is a layer of light, singly refractive (isotropic) substance (4 d). Where this lighter disc comes in contact with that of the adjacent element, a dividing band can be recognized, the terminal or intermediate disc (4 a) , which appears as a dark line. 542 STRUCTURE AND ARRANGEMENT OF THE MUSCLES. 543 In the muscles of arthropods there hes within the isotropic layer, at a short distance from the terminal disc, still another narrow layer of doubly refractive substance, the accessory disc, which contains chromatin. Every muscle-liber is closed off toward its extremity by a layer of singly refractive substance. When the tube of the microscope is lowered, the doubly refractive discs appear dark, the singly refractive, light; when the tube is raised, the conditions are reversed. The iibrils arc readily obtained singly from the muscles of insects; in mamma- lian muscles they may be isolated after the action of dilute alcohol or Muller's fluid, especially at the torn ends of the fibers (Fig. 184, 3). Fig. 184. — Histology of Muscular Tissue: i. Diagrammatic representation of the parts of a striated muscle- fiber: S, sarcolemma; Q, transverse striation; F, fibrils, further on giving rise to longitudinal striation; K, nuclei of the muscle-fiber; N, motor nerve leading to the fiber, vpith the axis-cylinder a, which passes over into the motor end-plate, seen in profile, the latter lying upon a nucleated, protoplasmic layer e. 2, Part of a cross-section of a striated muscle-fiber with Cohnheim's fields c; K, a muscle-nucleus in contact with the sarcolemma. 3, Isolated fibrils from a striated muscle-fiber. 4, Part of a fibril from an insect's muscle, highly magnified: a, Krause-Amici line limiting the muscular elements; b, the dark, doubly refrac- tive substance; c, Hensen's fine; d, the singly refractive substance, s, Striated muscle-fiber breaking up into discs. 6, Striated muscle-fiber from the heart of the frog. 7, Structure of a striated muscle-fiber from a three-months' human embryo. 8, Reticulated muscle-fibers of the heart, o, Cross-section of the heart-muscle: c, capillaries; b, connective-tissue corpuscles. 10, Unstriated muscle-fibers. 11, Unstriated muscle-fibers in cross-section. 12, Striated muscle-fibers with the related tendon S (detached). In all fibers there are encountered several nuclei, from 9 to 13 ,looded animals. It is precipitated from its solutions by saturation with sodium chlorid or inagnesium sulphate. When dissolved in a 10 per cent, solution of sodium chlorid, it is coagulated by heat. It is dissolved by 2 per cent, hydrochloric acid, with the formation of acid-albumin (syntonin), and by alkalies or alkaline carbonates, with the formation of alkali- albuminate. Like tibrin, myosin actively decomposes hydrogen dioxid. A. Danilewsky has succeeded in reconverting syntonin in part into myosin. Myosin is not present in unstriated muscles. Muscle-serum contains further small amounts of myoalbumin {Q^^^^- Hjy^NaoSO;,,,), which is coagulable at 73° C, but is not precipitated by sat- uration of the serum with magnesium sulphate ; also niyoglobidin, which is precipitated by this last procedure, and is coagulable at 63° C; and a little nucleoalbumin. Halliburton distinguishes the following proteids in muscle: (i) Paramyosino- gen, or musculin, a globulin-like body, forming 20 per cent, of the total proteids. and coagulating at 47° C. (2) Myosinogcn, forming 77 per cent, of the total proteids, coagulating at 55°. Both of these bodies are coagulable spontaneously, forming myosin. (3) According to v. Fiirth myosinogen gives rise to myogen- tibrin, which is soluble, is coagulable at 35°, and, like paramyosinogen, is readily transfonned into a librin-like modification that is dissolved with difficulty. Cer- tain salts or organic substances (caft'ein, veratrin) accelerate this process, while it is inhibited by blood-serum, and also by egg-albumin. (4) Myoalbumin, which is similar to serum-albumin. The coloring-matter of muscle {myohcmatin) appears to be different from hemoglobin. The absorption-bands are situated somewhat nearer to the red end of the spectrum. According to Levy, myohematin is identical with hemochromogen. There is an oxidized and a reduced myohematin (by am- monium sulphid). The muscle-nuclei yield some nuclein. The sarcolemma con- tains a substance resembling keratin. Several ferments are present in traces: pepsin, diastatic, lactic-acid (?), glycolytic, and coagulating (fibrin-) ferments. Proteic acid is a proteid substance in the flesh of fish. The other chemical constituents of muscle have already been mentioned in the consideration of meat (p. 423). It will suffice to add a little more here, (i) In addition to volatile fatty acids (formic, acetic, and butyric acids), two isomeric lactic acids are found in muscle having an acid reaction: (a) Ethylidene-lactic acid in the modification of dextrorotatory paralactic or sarcolactic acid. (6) Ethylene- lactic acid in small amount, which Maly also observed develop as an occasional fermentation-product of carbohydrates (glycogen, etc.). The formation of lactic acid during the rigidity of death is discussed on p. 552. Acid potassium phosphate also contributes to the acid reaction. (2) Glycogen is found to the amount of I per cent, after an abundant meat-diet, and of 0.5 per cent, during fasting. During digestion it is stored up in the muscles, as well as in the liver, but it dis- appears in the state of hunger. It is formed in the muscles themselves, probably from albuminates. (3) Dextrose, 0.02 per cent. (4) Of gases, there are present carbon dioxid (from 15 to iS vol. per cent., partly absorbed, partly in chernical combination, the latter probably being formed as a result of decomposition), some absorbed nitrogen; but no oxygen, although muscle continually absorbs oxygen from the blood. The muscles contain a substance that yields carbon dioxid on decomposition; exercise consumes this substance, so that muscles that are greatly fatigued are capable of generating less carbon dioxid. METABOLISM IN MUSCLE. THE SOURCE OF MUSCULAR ENERGY. The resting muscle continuously abstracts oxygen from, and returns carbon dioxid to, the capillary blood passing through it. Nevertheless, the muscle excretes less carbon dioxid than corresponds to the amount of oxygen it absorbs. Excised muscles deprived of blood exhibit an analogous but diminished interchange of gases. Further, as such muscles 5SO THE SOURCE OF MUSCULAR ENERGY. retain their irritability longer in oxygen or in air than in indifferent gases free from oxygen, it is to be assumed that this gaseous interchange is a vital phenomenon connected with normal metabolism, and to which the functional activity of the muscle is due. The excised, resting, surviving muscle gives off carbon dioxid, which in part has been present in the muscle preformed, and in part is subsequently generated by processes of decomposition that accompany the development of rigidity. A small part of this carbon dioxid arises only when oxygen is supplied. Bacterial putrefaction of the muscles causes marked excretion of carbon dioxid. In active muscle the blood-vessels are always dilated, and the amount of blood passing through them is increased three or four times, a cir- cumstance that obviously indicates increased metabolic activity. Ac- cordingly, active is distinguished from passive muscle by a series of chemical changes : 1. The contents of living passive muscle have an alkaline, or, more correctly, a neutral reaction, changing red litmus to blue, but acid to turmeric paper. The reaction becomes acid in active muscle (not of the unstriated variety), and, indeed, the degree of acidity increases, to a certain limit, in proportion to the amount of work performed. The acidity is due to phosphoric acid resulting from the decomposition of lecithin and nuclein. The earlier view, that the acidity is due to the development of lactic acid produced from glycogen, has not been substantiated. Pfluger and Warren, and also Astaschewsky and Heffter, even found the quantity of lactic acid in active muscles diminished, as compared with passive muscles. Other investigators, how- ever, still adhere to the theory of lactic-acid formation, especially if there is a deficiency of oxygen during the work. 2. The active muscle excretes considerably more carbon dioxid than the resting muscle: (a) Active muscular exertion in man or animals increases considerably the excretion of carbon dioxid from the body, (b) Venous blood flowing from the tetanized muscles of an extremity contains an increased quantity of carbon dioxid; and, indeed, under these conditions more carbon dioxid is excreted than corresponds to the amount of oxygen simultaneously absorbed, (c) Also, excised, con- tracted muscles excrete an increased amount of carbon dioxid. 3. Active muscle consumes a greater amount of oxygen : (a) During work the entire body takes up much more oxygen, even four or five times as much, (b) Venous blood flowing from the active muscles of an extremity contains a diminished amount of oxygen. Nevertheless, the increase in the consumption of oxygen by an active muscle is not so great as the increase in the excretion of carbon dioxid. The increase in the interchange of gases continues in the period of rest immediately following the activity. The consumption of oxygen can also be demonstrated volumetrically in excised muscles deprived of blood. It is true, oxygen is not absolutely necessary for muscular activity of short duration, as the excised muscle is capable of contracting for some time in a vacuum or in a gaseous mixture free from oxygen, and no free oxygen can be obtained from its tissue. The muscle must, therefore, contain a supply of oxygen in chemical combination, which is consumed during activity. Frogs' muscles ab- stract the oxygen from easily reducible substances; thus, they may de- colorize a solution of indigo. Muscles that have rested act less energet- ically than those that have been active. THE SOURCE OF MUSCULAK ENERGY. 55I 4. An active muscle contains less extractives soluble in water, but, on the other hand, more of those solu])le in alcohol. It also contains less of the substances that form carbon dioxid, less fatty acids, kreatin, krea- tinin, and sarcophos]")horic acid. 5. During contraction the amount of water in muscular tissue is in- creased, while that in the blood is corres])ondingly diminished. The solid matters of the blood are increased, while those of the lymph (al- bumin) are diminished. 6. The question as to the extent to which the proteids of muscular substance generate the kinetic energy of muscular activity, by the trans- formation of their chemical potential energy, has been answered by Pfliiger with the statement that albumin, if given in sufficiently large amounts, may be the exclusive source of muscular force. This albumin represents a special variety, and is thought to be formed syn- thetically from ordinary living albumin by the absorption of alcohol-radicals, which may be withdrawn either from another protcid, or from fat and sugar if there is a deficiency of proteids. The living albumin is transformed into a readily decomposable, living protcid, which contains a greater amount of carbon, and represents the immediate source of muscular energy. If a lean dog, fed only with lean meat and in a state of metabolic equilibrium during muscular rest, is subjected to a period of several days' work, it must receive a definite excess of lean meat in order to maintain its bodily weight. During the period of activity, the animal, therefore, decomposes more proteid, in accordance with the extent of the activity, and the metabolic equilibrium is thus maintained. Undoubtedly the work performed is accomplished at the expense of an increased consumption of proteids. If the dog does not receive an increased quantity of proteids on beginning to work, it loses in bodily weight. Even though sufficient quantities of fat and carbohydrates, in addition to the proteid, be administered to the active dog, there will still be an increased con- sumption of proteids during work. As on administration of a sufficient amount of proteid the muscular work is performed with the aid of this alone, and as in the decomposition of this proteid neither fat nor carbohydrate results, the fat and carbohydrate cannot be the true source of muscular force (Pfliiger). The carbon dioxid resulting from the decomposition of proteid leaves the body quickly through the pulmonary respiration; while the nitrogenous products of decomposition are excreted slowly, even for as long as two days after the com- pletion of the work. One and the same readily decomposable proteid is thus oxidized slowly and continuously in the muscular tissue, with the generation of heat, while under the influence of innervation it is consumed rapidly and in larger amount, and is then the source not only of heat, but also of kinetic energy. Pfliiger estimated that in his experimental dog one gram of nitrogen in the proteid, decomposed within the body, produced 7456 kilogrammeters of work. Of the total supply of energy contained in the proteid (measured by means of the calorimeter in calories), the dog converted 48.7 per cent, into kinetic energy, the remainder being transformed into heat. This 48.7 per cent, represents the mechanical equivalent of the proteid. At an earlier period Fick and Wislicenus, as well as v. Voit and v. Pettenkofer, had reached the conclusion as a result of their experiments that the daily excretion of nitrogen is not increased to any considerable extent by forced work, whereas the consumption of oxygen and the excretion of carbon dioxid are increased, provided that the body' has at its disposal sufficient material containing carbon, such as glycogen and fat, in its tissues or in the food. Hence, the proteid cannot be the source of muscular energy. Increased elimination of nitrogen takes place only when the activity gives rise to dyspnea, for deficiency in oxygen causes decomposition of albuminates. Also the increased excretion of sulphuric acid resulting from work is indicative of 55 2 MUSCULAR RIGIDITY. a more active decomposition of albuminates. The excretion of sulphur is increased by muscular exertion, and indeed the non-oxidized sulphur is at first excreted more rapidly than the oxidized. The excretion of phosphoric acid also is in- creased. 7. In the muscles of animals the amount of glycogen (0.43 per cent.) has been observed to diminish as a result of activity, and even to dis- appear completely in consequence of strychnin-convulsions. The same observation has been made with respect to the glycogen of the liver. Luchsinger maintains that muscles can still contract when completely free from glycogen; so that the latter cannot be the source of muscular energy. Also, the sugar of the blood undergoes a decrease in the muscles as a result of activity. There is a difference of opinion as to whether the muscle-glycogen is carried by the circulation from the liver into the muscles, or whether it is produced in the muscular tissue itself as the result of an as yet unknown decomposition of the albuminates. Kiilz observed an increase in the amount of glycogen in the muscles of frogs that had been deprived of their livers after subcutaneous injections of sugar. Likewise, the muscles retained their glycogen for a much longer time than the liver during the state of hunger. These facts indicate the formation of glycogen in the muscular substance itself. In any event, the normal circulation is a requisite for the production of glycogen in muscle, for this diminishes after liga- ture of all of the vessels. Surviving muscle converts glj'^cogen into sugar. Some investigators, however, assume also that not only proteid but, in part, also fat and carbohydrate may be the source of muscular energy in the body. MUSCULAR RIGIDITY (CADAVERIC RIGIDITY, RIGOR MORTIS). Excised muscles, striated as well as unstriated, and also the muscles of the intact body some time after death, pass into a state of rigidity, described more fully later on, that is designated muscular rigor. If the muscles of the dead body become involved, the entire cadaver be- comes completely stiff (cadaveric rigidity). The cause of this phenome- non resides in a spontaneous coagulation of the myosin within the muscle- fibers, with the development of a small amount of acid. During this process of coagulation, heat is liberated owing to the transition of the fluid myosin into the solid condition, and, also, owing to the thickening of the tissue that takes place at the same time. Myosin, dissolved in a 5 per cent, solution of magnesium sulphate diluted with water, separates after a time in the form of solid Hakes, with the development of an acid reaction. Warming hastens this process. The rigid muscle exhibits the following properties: It is shortened, thickened, and somewhat denser; stiff, firm and solid; turbid and opaque, in consequence of the coagulation of the myosin; incompletely elastic, less extensible, and less readily torn. It is completely unresponsive to stimuli, and its electrical potential has disappeared. The amount of glycogen present is diminished. Striated muscle has an acid reaction, on account of increased formation of the two varieties of lactic acid (un- striated has not), and it develops free carbon dioxid. If incisions be made into rigid muscles, a fluid exudes spontaneously, the muscle- serum. The view was formerly held that during rigidity, partial or complete trans- formation of the glycogen occurred, first into sugar and then into lactic acid. This view, however, has been contested by Bohm. who asserted that during MUSCULAR RIGIDITY. 553 digestion a transitory accumulation of large amounts of glycogen takes place in the muscles, as in the liver; so that approximately as much can be found in the former as in the latter. Rigidity causes no diminution of glycogen, provided putrefaction is prevented: hence, the lactic acid of rigid muscles cannot arise from glycogen, but prolmbly from decomjiosition of albuminates.' Hetfter main- tains that lactic acid is not formed at all during postmortem rigidity. The amount of acid does not vary, whether the rigidity develops slowly or rapidly. With the onset of acidihcation, the rigidity becomes more marked, on account of the coagulation of the alkali-albumin in the muscle. The less carbon dioxid there is generated by the rigid muscle the more it had already given off previously during activity. Fibrin-ferment is present in muscle in a state of cadaveric rigidity. It is in general a product of protoplasm, and is never wanting where the latter is present. There is thus an analogy between coagulation of blood and muscular rigidity. Two Stages of rigidity are to be distinguished: In the first stage the muscle is already somewhat stiff, but still excitable; the myosin in this stage acquires a gelatinous consistency. Restitution is still possible from this stage. In the second stage the rigidity is fully developed in all of the characteristics mentioned. Rigidity appears in man in from ten minutes to seven hours; the duration is likewise varialDle, from one to six days. After its disappearance, the muscles again become soft, owing to the onset of further decomposition and an alkaline reaction; the rigidity yields. The onset of rigidity is always preceded by a dis- appearance of nervous activity. Therefore, the muscles of the head and the neck are first affected, and then the others in a descending order. Likewise those muscles that usually degenerate earliestjare the first to become rigid; for example, in the frog the flexors before the extensors. Rigidity disappears earliest also in those muscles that first became rigid. Great muscular activity before death, for example during the convulsions of tetanus, cholera, strychnin-poisoning, or opium- poisoning, causes rapid and intense rigidity. Therefore, the heart becomes strongly rigid and with relative rapidity. White muscles become rigid later than red muscles. Wild animals, hunted to death, may become rigid in a few minutes. Usually the rigidity lasts the longer the later it sets in. Rigidity never occurs in the fetus before the seventh month. Frogs' muscles cooled to 0° C. become rigid only after from four to seven daj^s. Stenson's Experiment. — The influence of the amount of blood in the muscles upon the onset of rigidity is especially worthy of notice. Ligation of the muscular arteries in warm-blooded animals causes first increased irritability of the muscular tissue, lasting a few minutes, then rapid diminution in the irritability, followed by the onset of both stages of rigor in succession. If the arteries of the muscles were ligated, Stannius observed that the irritability of the motor nerves disap- peared in the course of an hour, that of the muscular tissue itself in from four to five hours; then rigidity sets in. Pathological. — Thrombotic occlusion of the muscular vessels will also cause rigidity. Excessively tight bandaging may give rise to true rigidity in man by cutting off the circulation. The muscles become paralyzed and stiff, and later break up into flakes, and the contents of the fibers are subsequently absorbed. The circu- latory disturbances, arising in muscles under the influence of cold, also cause paralyses that are often designated rheumatic. Also in cases of trichinosis the affected muscle-fibers are the seat of rigidity, and the stiffness in the muscles is thus explained. The contractures occurring in cases of cholera should probably be included in the class of muscular contractions resulting from circulatory dis- turbances, the inspissated blood giving rise to stagnation; as should also certain contractions occurring in the presence of atheroma and in the agonal period. The sensor}^ nerves in completely anemic extremities retain their irritability for from five to ten hours. If the circulation be restored in the first stage of rigidity, the muscle soon recovers. If, however, the second stage has set in, restittition is impossible. In cold-blooded animals rigidity does not set in for several days after ligature of the vessels. Brown-Sequard, by the injection of fresh blood containing oxygen, succeeded in restoring softness and irritability to a human cadaver in the first stage of rigidity even four hours after death. Heubel obtained the same result with the frog's heart as long as fourteen and one-half hours after death. On pass- 554 MUSCULAR RIGIDITY. ing blood containing oxygen through excised muscles, C. Ludwig and Al. Schmidt found that the onset of rigidity was retarded for a long time; this did not occur, however, with blood deprived of oxygen. After considerable loss of blood, rigidity sets in relatively early. If an artihcial circulation be kept up in the dead muscles of a frog by means of feebly alkaline fluids, rigidity does not occur. Previous section or paralysis of the motor nerves results in delayed onset of rigidity in the relaxed muscles. The reason is found in the greater abundance of blood in these muscles, in consequence of associated paralysis of the vasomotors, the alkaline blood remaining in the muscles even after death, while the arteries in other parts of the body become empty. This view is supported by the fact that rigidity appears much later in fish whose medulla oblongata is suddenly destroyed than in those that die slowly. According to Ewald and Willgerodt the labyrinths of the car, as organs controlling tone, likewise have an influence on the course of rigidit}^ Freezing and thawing cause rigidity to set in more rapidly, and it is favored likewise by mechanical injury. Continuous passive movements may retard the onset of rigidity, but on their cessation their rigidity sets in all the more rapidly. Rigidity that has already developed may be overcome by forced movements, taut it may set in again. Rigidity may be induced artificially: 1. By heat (heat-rigor) , which causes coagulation of the myosin in cold-blooded animals at 40°, in mammals at from 45° to 47° C, and in birds at about 53° C. Under such circumstances there is marked excretion of carbon dioxid, btit less after previous tetanization. Protoplasm, for example of the ama?ba, is similarly subject to heat-rigor. The degree of heat required to bring about rigidity is the higher the longer the muscles have been excised. If the muscles of a frog in a state of cadaveric rigidity be heated, the remaining proteids undergo coagulation successively, and the inuscle becomes still more rigid as a result of these coagulative processes. 2. Saturation with water induces water-rigor, with the development of an acid reaction, in consequence of the coagulation of the globulin-substances, the excretion of carbon dioxid not being increased. If the thigh of a frog be ligated, and the muscles, deprived of their skin, be immersed in warm water, they will become rigid. On loosening the ligature a slight degree of rigidity may disappear through restoration of the circulation. On the other hand, a more marked degree of rigidity can be removed only by placing the leg in a 10 per cent, soltition of sodium chlorid, which will dissolve the myosin- coagulum. 3. Acids, even weak acids such as cai^bon dioxid, induce rapid acid-rigor. This is probably different from normal rigidity, as the muscle does not develop free carbon dioxid. Injection of from o.i to 0.2 per cent, solutions of lactic or hydrochloric acid into the vessels of frogs' muscles causes immediate rigidity, which can be overcome by 0.5 per cent, acid, and also by a neutralizing solution of sodium bicarbonate, or 13 per cent, solution of ammonium chlorid. The acids enter into combination with the myosin. 4. Among poisons and other stibstances, the following promote rigidity: Caffein, quinin, digitalin, veratrin, hydrocyanic acid, also oils of mustard, fennel, and anise, and, when placed in direct contact with the muscles, potassium sulpho- cyanid, ammonia, metallic salts, alcohol, ether, chloroform. Chloroform, acetic acid, and heat induce rigidity with shortening; ammonia, on the other hand, rigidity without shortening. The position of the entire body during rigidity is usually that which it occupied at death. The position of the limbs corresponds to the resultant of the various degrees of muscle-tension. If the limbs occupied another position before death, they are frequently seen to move during the onset of rigidity. The arms and fingers especially are readily flexed. If the rigidity develops with especial firmness and rapidity in certain groups of muscles, an unusual position may be assumed, for example the fencing attitude of cholera-cadavers. If the rigidity occtirs rap- idly, the body at times remains in the same position that it occupied at the moment of death, for example on the battle-field. Under such circixmstances, however, the contracted muscle never passes immediately into a condition of rigidity, a period of relaxation intervening, even though short. Muscles scalded by immersion in boiling water do not become rigid; neither do they become acid, nor evolve free carbon dioxid. Muscles coagulated by concentrated alcohol or by immersion in concentrated solutions of sodium chlorid, potassium nitrate, sodium and magnesium sulphate, do not yield an acid reaction. IRRITABILITY AND STIMULATION OF THE MUSCLE. 555 Attention has repeatedly been directed to the analogies between muscle in active contraction and in the state of rigidity- The form of the contracted and of the rigid muscle is shortened and thickened; both are denser, of changed elas- ticity, and evolve heat; the contents of the contracted as of the rigid muscle are negative electrically as compared with resting or non-rigid contents; both evolve free carbon dioxid and the reinaining acid from the same source. A contraction may, therefore, be regarded as a temporary rigidity, disappearing physiologically, just as earlier investigators, and recently Bernstein, designated rigidity as being, to a certain extent, the final vital act of the muscles. A muscle in process of becoming rigid will lift a weight, like a living, con- tracting muscle. The height to which the weight is lifted by a rigid muscle is greater in the case of small weights and less for heavy ones than if the living muscle be stimulated to a maximum degree. If a muscle, in which heat-rigor has been induced, be at first prevented from contracting, and if later (for example after ten minutes) it be set free, its elastic energy will cause it to contract, and it must lose heat at the same time. The disappearance of cadaveric rigidity takes place at first as a result of increased formation of acid in the muscle, by which the myosin is redissolved. Subsequently, with the development of microorganisms putrefaction sets in, with the associated evolution of ammonia, hydrogen sulphid, nitrogen, and carbon dioxid. The loss of irritability in the muscles that precedes the onset of rigidity occurs in the foUow-ing order in man (beheaded ci-iminal) : Left ventricle, stomach, intes- tine (fifty-five minutes), urinary bladder; right ventricle (sixty minutes); iris (one hundred and five minutes) ; muscles of the face and the tongue (one hundred and eighty minutes) ; the extensors of the extremities about one hour before the flexors ; the muscles of the trunk (from five to six hours) . The esophagus remains irritable for a lona: time. IRRITABILITY, STIMULATION, AND DEATH OF THE MUSCLE. By the irritability of a muscle is understood its ability to contract in response to stimuli applied directly to it (not to its nerves). Stimu- lation is the state of functional activity in which a muscle is placed by stimuli. At the moment of activity the stimulation causes the chemical potential energy of the muscle to be converted into work and heat; stimuli thus act as liberating forces. The mean temperature of the body is most favorable for the manifestation of irritability. Each muscle appears to possess a special degree of irritability peculiar to it- self, as do likewise the nerves. So long as the current of blood in the muscle is uninterrupted, stimu- lation first causes an increase in its functional activity, partly because the circulation becomes more active in association with dilatation of the vessels; later, however, the functional activity diminishes. This diminution in functional activity is a sign of fatigue. If the same stimu- lation be continued, the muscular activity will exhibit a periodic variation, in such manner that after a series of weaker contractions stronger ones will again set in, followed in turn by weaker, and so on. This phenomenon depends upon periodically recurring improvement in the nutrition of the muscle, as a result of analogous variations in its circulation. In excised muscles also, especially if the large nerve-trunks have al- ready undergone degeneration, the irritability is at first somewhat in- creased after each stimulation, so that with a uniform series of stimuli the contractions at first exhibit an increase in extent. Thus, it may happen that, while the first weak stimulus is still ineffectual, the second will give rise to a contraction. The unstriated muscles exhibit, under certain conditions, automatic and rhythmic movements without the intervention of nerves. 5S6 IRRITABILITY AND STIMULATION OF THE MUSCLE. Frogs' muscles that have been cooled, or those in which desiccation has begun, exhibit an excessively increased irritability, especially to mechanical stimuli. This fact may explain the remarkable muscular movements that often take place in cholera-cadavers. Cooled muscles from the frog or the tortoise may preserve their irritability for as long as ten days, but the muscles of warm- blooded animals often degenerate in from one and one-half to twg and one-half hours. The irritability of the heart-muscle is considered on p. ii8. Curarized, isolatedfrogs' muscles exhibit the least amplitude of contraction at o°, the greatest at 30°; if heated beyond the latter temperature, the contraction gradually dimin- ishes, until the point is reached where rigor sets in. The duration of contraction and the latent period are also shortest at 30°. Since the time of Alb. v. Haller (1743) it has been thought necessary to attribute to muscle a peculiar irritability (even without the intermediation of the motor nerve) . In more recent times attempts have been made to adduce further support in favor of this specilic muscular irritability: (i) There are chemical irritants that induce no movement when applied to the motor nerves, but cause contraction when applied directly to the muscle; for example ammonia, lime- water, carbolic acid. (2) The extremities of the sartorius muscle of the frog, in which no nerve-endings can be demonstrated by means of the microscope, never- theless react to direct stimulation by contractions. (3) Curare paralyzes the motor nerves, while the muscle itself remains irritable. The action of cold, or the arrest of the circulation in the muscle of an animal, will likewise abolish the irritability of the nerve, but not of the muscle at the same time. In general, the directly stimulated muscle will still contract for some time after its motor nerve has degenerated. (4) After section of the nerves, the muscles still remain irritable, even though the nerves have undergone total fatty degeneration. (5) At times electrical stimuli act only upon the nerves, and not upon the muscles them- selves. In lower animals (hydra, medusa) unicellular structures, neuro-muscular cells, have been found in which nervous and muscular tissue are represented in one and the same cellular structure. With regard to the stimuli that act upon the muscles, the following are to be noted: 1. The normal stimulus under ordinary circumstances acts upon the muscle by way of its nerve, as in voluntar\' movement, the automatic motor impulse, reflex excitation. Its nature is unknown. The irritation of a muscle through the intermediation of its nerve is designated indirect stimulation. Pseudomotor effects are considered on p. 559. 2 . Chemical Stimuli. — ^All chemical agents that alter the chemical constitution of musciilar tissue with sufficient rapidity act as muscle-stimuli. According to Kiihne, the mineral acids (o.i per cent hydrochloric acid), acetic and oxalic acids, the salts of iron, zinc, copper, silver, and "lead, bile, all act as stimuli to the muscle in dilute solution, and only on the nerves in much stronger solutions. Lactic acid and glycerin, when concentrated, excite only the nerve (?) ; when dilute, only the muscle. The neutral alkaline salts act equally on muscle and nerve. Alcohol and ether both act feebly. Water, especially if injected into the muscular vessels, causes fibrillary contractions. Solutions of sodium chlorid, from 0.6 to 0.9 per cent., or normal solutions of other sodium-salts, act indifferentlv toward the muscular substance, even after the latter is exposed to their influence for days; this is especially true after the addition of a trace of calcium chlorid or calcium phosphate. A 6 per cent, solution of sodium chlorid causes the sartorius, when deprived of its nerve, to contract much more strongly than when its nerve is preserved, and especially in its active, thick fibers. Acids, potassium-salts, and meat-extract diminish the irritabilitj^ of the muscle, while other muscle-stimuli, such as alcohol, sodium-salts, some metallic salts, in small doses increase the irritability. Gases and vapors also have a stimulating influence on the muscles, either exciting simple contractions or immediately causing contracture. Pro- tracted exposure to the gases causes rigidity. Only the vapor of carbon disulphid has an irritating effect on the nerves, while most vapors (for example, of hydro- chloric acid) destroy without causing excitation. In comparative observations on the influence of chemically related substances, only chemically equal quantities, for example normal solutions^ should be employed. Thus, among the halogens, sodium iodid, with its high molecular weight, has the strongest effect; while sodium chlorid, with its low molecular weight, has the feeblest effect. The combinations of the metals act in like manner; also the salts of the alkaline earths. Those with the highest molecular weight cause the IRRITABILITY AXl) STIMULATION OF THE MUSCLE. 557 greatest excitation and the least injury. The following substances cause injury in the order of their sequence, arranged from those with stronger to those with weaker cllects: ammonia, potassium, sodium, hydrochloric acid, nitric acid, sulphuric acid, phosphoric acid (in accordance with their avidity) ; the fatty acids with larger molecules as compared with those with smaller; the higher alcohols as compared with the lower. In making experiments upon the chemical irritation of muscles, it is inad- visable to immerse the transverse section of the muscle in the solution. The substance in solution should rather be applied to a limited area on the uninjured surface of the muscle. The stimulation will then be manifested in a few seconds by contraction or fibrillary motion of the superticial muscular layers. If the sartorius of a curarized frog be immersed in a solution of 5 grams of sodium chlorid, 2 grams of alkaline sodium phosphate, and 0.5 gram of sodium carbonate in i liter of water at 10° C, the muscle will be thrown into rhythmic contractions, which may persist even for days. These contractions suggest, to a certain degree, the rhythmic action of the heart (Biedermann). The following act as chemical irritants upon unstriated muscles: ergot, aloes, colocynth, the alkalies; atropin and nicotin paralyze the nervous elements in such muscles, as does also ether; chloroform also destroys the muscle-fibers them- selves. Carbon dioxid in small amounts acts as an irritant to the nerves, in larger amounts as a paralyzant, and in still larger amounts it irritates and finally paralyzes the muscle-tibers themselves. 3. Thermal Stimuli. — If a frog's muscle be rapidly heated, a gradually in- creasing contraction begins at about 28° C, becomes more pronovmced at 30° C, and attains its maximum at 45° C; following this, further heating rapidly leads to heat-rigor. Local cooling of the muscle increases its irritability for all kinds of stimuli. Frog's muscle cooled to 0° is exceedingly responsive to me- chanical irritation, and it may be stimulated by degrees of cold below 0°, until freezing takes place. Heat has a relaxing effect on unstriated muscle (frog), while cold has a moderately stimulating effect. Variations in temperature, how- ever, also affect the nerves of these muscles, each fluctuation causing reflex con- traction, which does not occur if the nerves are paralyzed. CI. Bernard made the remarkable observation that the muscles of artificially cooled animals retain their irritability for many hours after death. Heat causes rapid disappearance, with temporary increase of the irritability. 4. Mechanical stimuli of all kinds cause a contraction at each separate, sudden blow; and tetanus if repeated. Strong, local stimuli induce an elevated contrac- tion of considerable duration at the point of application. Moderate stretching of a muscle increases its irritability. Mechanical stimulation of a muscle poisoned with veratrin causes a heaving movement of its fibers, which may persist for as long as one minute. 5. Electrical stimuli are discussed in conjunction with nerve-stimuli (p. 631). Curare, the arrow-poison of the South American Indians, is the dried juice of the root of Strychnos Crevauxi. When introduced into the blood or injected subcutaneously, it first causes paralysis of the intramuscular termination of the motor nerves, the muscles themselves retaining their irritability, while the sensory nerves and those of the central organs and the viscera (heart, intestine, and ves- sels) remain for a time unaffected. In warm-blooded animals the paralysis of the respiratory muscles naturally causes early asphyxia, which is unattended with convulsions. Frogs, whose skin is their most important respiratory organ, on receiving a suitable dose, may recover completely, after remaining motionless for days, during which the poison is eliminated through the urine. Larger doses paralyze also the cardiac inhibitory and vasomotor nerves. In electrical fish paralysis of the nerve transmitting the electrical shock occurs. In frogs the lymph-hearts also are paralyzed. If the doses that are fatal when administered subcutaneously be given by mouth, poisoning does not result, because the poison is eliminated by the kidneys at the same rate that it is absorbed by the gastric mucous membrane. For the same reason the flesh of an animal killed by a poisoned arrow is harm- less. If, however, the ureters be ligated, the poison accumulates in the blood, and intoxication results. Large doses, however, will kill uninjured animals also by way of the intestinal tract. Atropin appears to be a specific poison for unstriated muscle-fibers, although different muscles are variously affected by it. The irritability of the muscles after lesions of the nerves deserves especial attention. After three or four days the irritability of the paralyzed muscle is diminished for direct or indirect (nerve) stimuli. There then follows a stage in 558 CHANGE OF SHAPE IN ACTIVE MUSCLE. which a constant current has an abnormally excessive effect, while induced cur- rents are almost or completely without effect; irritability to direct, mechanical stimuli is also increased. This increased irritability is observed at about the seventh week. It then diminishes gradually, until 'it completely disappears at about the sixth or seventh month. Beginniiig with the second vieek, the muscle begins to undergo progressive fatty degeneration, to the point of complete atrophy. In experiments on animals Schmulewitsch found, immediately after section of the sciatic nerve, that irritability was increased in the muscles innervated by it. After death the muscles degenerate (excised muscles more rapidly), and the earlier if they have been exhausted and exposed to stimuli of considerable intensity. Thick muscles survive longer (in their inte- rior) than thin muscles. It would appear that there is a definite stage of early or late death for each individual muscle; for example, the extensors in man degenerate earlier than the flexors. The muscles of the frog degenerate in twenty-four hours at summer tem- perature, in the course of two or three daj^s at moderate temperature, and only after about twelve days at o°. The muscles of warm-blooded animals degenerate on an average in the course of from one-sixth to twelve hours. The degeneration of the heart is considered on p. 113. CHANGE OF SHAPE IN ACTIVE MUSCLE. Macroscopic Phenomena. — i. Active muscle becomes shorter and at the same time increases in thickness. The degree of shortening, which in exceedingly irritable frogs mav amount to as much as from 65 to 85 per cent, (on an average 72 per cent.) of the entire length of the muscle, depends upon various factors: (a) To a certain degree an increase in the strength of the stimuhis gives rise to a greater amount of shortening. (6) "With increasing exhaustion after continuous, vigorous activity, the same strength of stimulus causes less shortening, (c) Elevation of temperature up to 30° C. causes stronger contractions in the frog's muscles. If the temperature be further elevated the degree of shortening is again diminished. 2. The contracting muscle is somewhat diminished in volume. Con- sequently, the specific gravity of contracting muscle is somewhat in- creased, the ratio to that of non-contracting muscle (in the marmot) being as 1062 : 1061. The diminution in volume amounts to only y^^. Method. — Swammerdam placed a frog's muscle in a glass tube containing air and drawn out into a thin tubule containing a small drop of fluid. The nerve was conducted to the exterior through a small lateral opening. Mechanical stimulation of the exposed nerve caused contraction of the muscle and descent of the small drop. In an analogous manner Ermann placed irritable fragments of an eel in a similar tube, filled with an indifferent fluid. The fluid rises to a certain level in a thin tubule communicating with the glass container. When the muscu- lature of the eel was made to contract, the fluid sank. Landois demonstrated the diminution in volume of contracted muscle by means of the manometric flame. The cylindrical glass vessel containing the muscle receives two electrodes passing through its walls in an air-tight manner. It communicates at one point with a gas-supply pipe, and at another point it gives off a thin tubule, at the extremity of which a small flame is ignited at low gas-pressure. The muscular contraction following each electrical stimulus causes a reduction in the size of the flame. If a pulsating heart, naturally containing no air, be placed in the gas- chamber, each pulsation will be attended with a reduction in the size of the flame. 3. Under normal conditions, all stimuli applied to the muscle, as well as to the motor nerve, will cause contraction in all of its fibers. The muscle thus conducts to all of its fibers the impulses communicated to it. Deviations from this rule are observed, however, in two direc- tions: (a) When the muscle is greatly exhausted, or when it is about CHANGE OF SHAPE I\ ACTIVE MUSCLE. 559 to deg;enerate, a violent mechanical, and also a chemical or electrical stimulus, applied to a circumscribed portion of the muscle will cause contraction in this portion alone; so that an elevated thickening of the fibers (Schiff's idiomiiscular contraction) is observed at this point. The same phenomenon may be induced in the muscles of a healthy person, and especially in weakened and poorly nourished individuals, if the fibers be struck with a blunt edge at right angles to their course, (b) Under certain conditions, as yet not fully known, the muscles will be seen to exhibit so-called fibrillary contractions , that is the various bundles of fibers in the muscle are from time to time traversed by short contractions. Such a condition is observed in the tongue-muscles of the dog after section of the hypoglossal nerve, and in the face-muscles after section of the facial nerve. According to Bleuler and Lehmann, section of the hypoglossal nerve in the rabbit is followed in the course of from sixty to eighty hours by fibrillar con- tractions that persist for inonths, even when stimulation of the healed nerve above the point of union again excites movements in the corresponding half of the tongue. Stimu- . lation of the lingual nerve increases the fibrillar ' contractions. This nerve contains vasodilator h ■ fibers from the chorda tympani. Schiff believes f 1 that the cause of the contractions resides in the c increased blood-supply to the tongue. Sigm. ^ Mayer also observed contractions in the facial ^ muscles in rabbits, after restoration of the cir- ^ culation in the carotids and subclavians, pre- □ ,, viously compressed. Section of the motor nerves 5 i in the face does not abolish the phenomenon, ^ while repeated compression of the arteries does Fig. 191.— The Microscopic Phenomena so. The cause of the contractions resides, ac- of Muscular Contraction in the Indi- cordingly, in the musculature itself. This motor F^"''iL^If"^^°'' °^ "''' ^'''"'' ^ ■^""'' , ^ -' ' . 1 . , , T h-ngelmarm). phenomenon is designated pseuaomotor. it may be compared to the paralytic secretion of the salivary glands. Similar phenomena have been observed also in man under pathological conditions, but at times fibrillar contractions may be observed even in the absence of other evidence of pathological disturbances. Microscopic Phenomena. — i. The separate fibrils of the muscle exhibit the same phenomena as does the entire muscle, in that they be- come shorter and thicker. 2. The observation of the individual muscle- elements is attended with especial difficulties. In the first place, it is certain that during contraction they become collectively shorter and thicker, so that the transverse striations appear to be pushed more closely together. 3. Opinions are not fully in accord as to the behavior of the constituent parts of each muscle-element during contraction. Fig. 191,1 represents, according to Engelmann, on the left a muscular element at rest; from c to d extends the doubly refractive, contractile substance, in the middle of which the median disc a b is situated; h and g are the terminal discs. In addition, there is in each singly refractive light layer an accessory disc, f and e, which is doubly refractive in but slight degree, and occurs only in the muscles of insects. Fig. i shows on the right the same element in polarized light, the middle portion of the element, so far as the actual contractile substance extends, appearing light on account of the double refraction; while the remainder of the muscle-element appears black on account of the single refraction. Fig. 191, 2 represents the transition-stage, and 3, the actual contractile stage of the muscle- element, both on the left as viewed in ordinary light, and on the right in polarized light. According to Engelmann, during contraction (3) the singly refractive layer becomes on the whole more highly refractive, and the doubly re- 560 THE TIME RELATIONS OF MUSCULAR COXTRACTIOX. fractive layer less so. As a result, the fiber may with a certain degree of shortening (2) appear homogeneous and only faintly striated when observed in ordinary light, the homogeneous or transitional stage CSlev- kel's stage of dissolution). If the shortening be more 'pronounced (3), distinct dark striae again appear, corresponding to the singly refractive discs. At every stage of shortening, including, therefore, the transition- stage, the singly and doubly refractive layers may be demonstrated, by means of the polarizing apparatus, as sharply defined, regularly alternat- ing layers (in i, 2, 3, to the right). They do not exchange places in the muscle-compartment during contraction. The height of both layers is diminished during contraction, that of the singly refractive much more rapidly than that of the doubly refractive layer. The total volume of each element is not apprecialjly changed during contraction. There- fore, the doubly refractive layers increase in volume at the expense of the singly refractive layers. Hence it follows that during contraction fluid passes from the singly into the doubly refractive layer; the former shrinks, the latter swells. Method. — The phenomena described can be best observed by instantaneously coagulating the living muscle-fibrils of insects in the various stages of rest or contraction by suddenly applying alcohol or dilute perosmic acid to the muscles, and thus fixing the different stages. The movement itself may be followed under the microscope, either by stimulating the thin, outspread muscle electrically, or, still better, by observing the independent muscular contractions in the trans- parent parts of an insect, for example in the head of the gnat's larva. A thin, extended muscle, for example the sartorius of the frog, yields a double spectrum (like a Xobert's glass screen), if light be allowed to pass through a narrow slit, held closely in front of the fibers and at right angles to them. If the muscle be made to contract, for example by mechanical stimulation, the spectrum broadens, an evidence that the intervals between the transverse striae become smaller. At the same time the transparency of the muscle becomes greater than during rest. THE TIME-RELATIONS OF MUSCULAR CONTRACTION. MYOGRAPHY. SIMPLE CONTRACTION. TETANUS. ISOTONY. ISOMETRY. Isotonic muscular activity is the term applied to the contraction in which the tension of the muscle remains the same, while the fibers be- come shorter. Method. — The time-relations of the contraction in the isotonic muscular act may be shown by v. Helmholtz's myograph (Fig. 192). The suspended muscle (M), fastened at its upper extremity (K), is attached by its lower extremity to a lever constructed like a balance, which can be weighted by means of the weights (W) as desired, and is raised by the shortening of the muscle. From the free extremity of the arm of the lever is suspended b}' means of a hinge-joint a style (F), which records the movement of the lower extremity of the muscle on the smoked surface of a cylinder made by means of clocku'ork to rotate at a uniform speed in front of the style. In this way the contracting muscle itself records its contraction-ciirve, in which the abscissas represent the units of time calculated from the known rapidity of rotation of the cylinder, and the ordinates represent the degree of shortening at any particular moment. Fick improved the myograph materially by making the writing lever ex- ceedingly light, and applying the weight close to the rotation-axis of the balance. In this way the swinging movement accompanying the muscular contraction is reduced to a minimvun, as is also the change in tension brought about by such movements. The surface intended for the reception of the myogram must be moved rapidly, as the process of movement takes place rapidly. Therefore, either a plate fastened ISOTONIC MUSCULAR CONTRACTION. 561 to the rod of a pendulum (Pick's pendukim-myoRraph), or a surface set in motion by gravity (Jendrassik's gravity-myograj)h) or by means of a spring (Du Bois« Reymond) or a rotating convex surface (Rosenthal's rotating myograph), may be employed. Under the myogram a time-curve is traced by means of a vibrating tuning-fork. The apparatus is, in addition, provided with an arrangement for indicating in the tracing the moment of stimulation. The curve may be traced advantageously on the vibrating plate of a tuning- fork (Fig. i()4, I). The time-units are thus registered in all parts of the curve, each complete vibration being equal to 0.01613 second. The moment of stimula- tion coincides with the beginning of the vibration of the fork, which is at first moved to one side for a time, without vibrating. This is accomplished by re- leasing a clamp, which at the same time opens a galvanic circuit, and sends an induction (opening) shock of the secondary coil through the muscle. The tuning- fork can also be set in vibration by a blow on one of its prongs. If under such circumstances the nerve is so placed upon the fork as to be struck by the blow, the latter acts at the same tiine as a mechanical nerve-stimulus. The balance, together with the imposed weights, is jerked upward at the commencement of the contraction. As a result the curve is distorted, because the muscle is no longer weighted after the moment of occurrence of the jerk. For this reason the muscle has been made to draw up an elastic spring. In this way, however, a stronger pull must be made on the muscle as the spring is raised higher and higher. To avoid this Griitzner constructed a spring that exerts a steadily diminishing tension on the apparatus as the muscle pro- gressively contracts. If it be desired to record onh?^ the extent (height) of the contrac- tion, the tracing is made on a stationary surface, which is dis- placed slightly after each move- ment (Pfliiger's myograph). Muscular contractions may also be recorded in the case of man. It is best to transfer the increase in thickness attending contraction either to a lever or to a drum covered with rubber, for example that of Brondgeest's pansphygmograph (p. loi). Fig. IQ2. — Diagrammatic Representation of v. Helmholtz's Myograph: M, the muscle, fastened at K; F, the writing- style, suspended from the arm of the lever that is to be raised; P, a counterweight for maintaining equilibrium; W, scale-pan for weighting the muscle as desired; S S, posts supporting the balancing lever. If a single stimulus of momentary duration be ap- plied to a freely movable mus- cle, the latter executes a simple contraction , that is it shortens rapidly and also returns quickly to the relaxed condition. Under such circum- stances the internal tension of the muscle reinains the same during the course of the entire contraction, and for this reason the resulting curve is designated an isotonic 'myogram. The follovi^ing details can be noted in an isotonic contractioii-curve described by a muscle that has to lift only the light writing lever, and is not overweighted by any other attached weights: i. The stage of latent stimulation (Fig. 193, a b), which arises from the fact that the con- traction of the muscle does not begin at the moment of stimulation, but always somewhat later. If the momentary stimulus, for example an induction-shock, be applied directly to the entire muscle, the latent period is about 0.0 1 second. In man the stage of latent stimulation varies from 0.004 to 0.0 1 second. 36 562 ISOTONIC CONTRACTION CURVE. If provision is made in the experiment for the muscle to contract immediately, so that no time is lost between the act of the relaxed muscle becoming tense and the commencement of the contraction, the latent stage may fall below 0.004 second. For the excised frog's muscle, Bernstein and Engelmann found the shortest period to be 0.0048 second. If the animal's muscle remains attached to the body, protected as well as possible from external injuries and supplied with circu- lating blood, then the latent stimulation may be shortened to 0.0033 second, and even to 0.0025 second. Influences Affecting the Duration of the Latent Period. — The latent period is diminished by increase in the strength of the stimulus and by heat, and increased by fatigue, cooling, and increase in the weight. The latent period of an opening contraction is also longer (even 0.04 second) than that of a closing contraction. Before the muscle contracts as a whole, individual muscle-elements within it must already have undergone contraction. It is, therefore, assumed that the latent period of the individual muscle-elements is shorter than that of the entire muscle. The latent period is shorter after direct muscle-stimulation than after indirect stimulation through the nerve, as the transference of the stimulus through the motor end-organ requires some time. The transmission of the nerve-stimulus is considered on p. 667. 2. From the beginning of the contraction to the height of the short- ening (b d), the muscle contracts at first somewhat slowly, then more rapidly, and finally toward the end of the shortening more slowly again; so that the ascending limb of the curve has the form of an J , This is termed the stage of increasing energy; it lasts about 0.03 or 0.04 second. Fig. 193. — Myogram of an Isotonic Contraction. Its duration is the shorter the smaller the contraction (weaker stimulus), the smaller the weight to be raised, and the less fatigued the muscle. 3. After the height of contraction has been reached, the muscle again becomes extended, at first slowly, then more rapidly, and finally more slowly again; so that the descending limb has the form of an inverted I . This is the stage of diminishing energy (d e) ; it is usually of shorter duration than that of increasing energy. 4. After the descending limb of the curve has been recorded, there fol- low several after-vibrations (from e to f), due to the elasticity of th^ muscle, and disappearing gradually. These constitute the stage of elastic after -vibrations. The latter are, however, regarded as factitious, and due to the after-vibrations of Helmholtz's apparatus. If the stimulus is applied to the motor nerve instead of the muscle, the contraction is the greater and lasts the longer the nearer to the spinal cord the nerve is stimulated. It has, until now, been assumed that the muscle is w^eighted only with the light writing lever that it has to raise in recording the curve. If, however, it be after-loaded, that is if additional weights be hung on the lever that, sup- ported during rest, must be lifted during contraction, then the commencement of the contraction is delayed as the after-loading is increased. This is due to the ACTION OF POISONS ON MUSCLE. 563 fact that the muscle, from the moment of stimulation on, must first accumulate so much contractile force as is necessary to raise the weight. The greater the weight the longer is the period of time that must elapse before the act of lifting begins. Finally, a degree of after-loading is reached at which it is no longer possible to raise the weight. This indicates the limit to which the lever-force may operate. If a muscle, during contraction, be subjected to a temporary increase in tension, it will be found that a short, quick, and considerable increase in tension immediately diminishes the contraction; while a more prolonged and slow increase somewhat later increases the contraction. The temperature of the muscle also has some influence. The duration of the contractile force diminishes with increasing temperature, increasing with increase in weighting. The rapidity with which the contractile force develops increases with increasing temperature, diminishing with increased weighting. The height to which an unweighted muscle may lift a weight increases with its temperature. A frog's muscle, supplied with circulating blood, exhibits the greatest contraction in response to stimuli at 0° C. As the temperature rises, the extent of contraction diminishes progressively. If the muscle becomes fatigued as a result of repeated stimulation, the stage of latent stimulation becomes longer and the curve remains lower, because the contraction of the muscle is less; while the abscissa becomes longer, because the muscle contracts more slowly (Fig. 194, I). Cooling of a muscle has like effects. Also the muscles of the new-bom behave in a similar manner. The con- traction-curve has a flat apex, and is considerably prolonged, especially in the descending limb. If the nerve of the muscle is stimulated by the closing or opening of a constant current, the muscular contraction corresponds exactly to that already described. If, however, the current is applied directly to the muscle itself, and is closed and opened, a certain degree of persistent contraction, though often but slight, takes place during the period of closure, so that the curve assumes the form shown in Fig. 194, IV, in which the current was closed at S and opened at O. According to Cash and Kronecker, the individual muscles have a special form of contraction-curve. Thus, the omohyoid of the tortoise contracts more rapidly than the pectoral. The flexors of the frog contract more quickly than the extensors. The muscles of tortoises, the adductors of mussels, the muscles of the bat, and the heart contract slowly. The muscles of flying insects contract with great rapidity, those of the fly 350 times, and of the bee 400 times in a second. There are, however, slowly contracting muscles among beetles also, for example in the water-beetle, hydrophilus. White muscle-fibers are more irritable , have a shorter latent period, and are more readily fatigued than red fibers; their contraction -period is shorter. They are therefore more active, and the contraction-wave is propagated more rapidly in them. They also produce more acid and heat during their activity. The red fibers execute protracted, continuous movements; hence, moderate, physiological tetanus. They intermediate the adjustment of the muscular force to the resistance to be overcome. Red fibers, or those rich in protoplasm, are further present, especially in the continuously active muscles— respiratory, masticatory, ocular, and cardiac. The white fibers execute the rapid, single movements. Muscles that contain principally white fibers have a greater lifting capacity and a more marked absolute power in the single contraction, but they are inferior to the red muscles in tetanic contraction. The contraction-curves of a mixed muscle con- taining white and red fibers may exhibit two elevations in the ascending limb, the first being due to the contraction of the active white fibers, and the second to that of the more sluggish red fibers. These are observed especially after the action of veratrin on the muscle-substance. The nerves supplying the white and red muscles also exhibit differences in their irritability. Action of Poisons. — Small doses of curare, as well as quinin and cocain, in- crease the size of the contractions induced by stimulation of the nerve; larger doses reduce the size to the point of complete paralysis. Suitable, small doses of veratrin likewise increase the size of the contractions, while the stage of re- laxation is conspicuously lengthened. Acids accelerate the relaxation. Veratrin, antiarin, and digitalin in large doses induce such changes in the muscle-substance that the contractions become greatly prolonged and similar to a continuous, tetanic contraction. In muscles poisoned with veratrin or strychnin , the latent stage of contraction is at first shortened, but later lengthened. The gastrocnemius of a frog will contract more rapidly if supplied with circulating blood containing sodium bicarbonate. Kunkel believes that the essential factor in the action of 564 THE DURATION OF A MUSCLE CONTRACTION. the muscle-poisons consists in their control of the imbibition of water by the muscle-substance. As the muscular contraction depends on imbibition, the form of contraction of the poisoned muscle will be influenced by the state of imbibition produced in it by the poison. The contraction-curves of unstriated muscles are similar to those of striated muscles, but the contraction takes place, after a latent period of as much as several seconds, visibly later and more slowly. The contraction in a preparation of a frog's stomach lasts 600 times as long as that of a striated muscle, and the latent stage amounts to 1.5 seconds. The curve ascends more steeply than it descends, and its apex is flattened. Warming increases the height of the curve, and shortens the latent period and the duration of contraction; above 39° C, however, the conditions are reversed. A muscle contracted as a result of stimulation returns to its original length only if a sufficient extending force is applied to it, as by weights suspended from it. Otherwise it will remain somewhat shortened for a considerable time, the resulting condition being designated contracture or contraction-remainder. This is especially well marked in muscles that have been previously subjected to strong, direct stimulation, or are greatly fatigued, or more strongly acid, or approaching \AAV\ A'v^ArvVv Fig. 104. — I, Contraction of a fatigued calf-muscle from the frog, recorded on a vibrating plate attached to a tuning- fork. Each dentation represents 0.01613 second; a b, latent irritation; b c, stage of increasing energy; c d, stage of diminishing energy. II, The most rapid writing movement of the right hand, recorded on the vibrating plate of a tuning-fork. Ill, The most rapid tetanic tremor-movement of the right forearm, recorded on the same plate. IV, Myographic curve on closing and opening a current applied to the muscle itself (after Wundt). a condition of rigor, or have been obtained from animals poisoned with veratrin. The phenomenon of contracture is also observed in man. In man, single twitching movements of the muscles may be executed with great rapidity. The determination of the time-relations of such movements may be made most simple by recording the movement in question upon the vibrating plate of the tuning-fork. Fig. 194, II, represents the most rapid movement that Landois could execute voluntarily with the right hand in writing the letters n n in succession. Each ascending and descending part of the movement comprises 3.5 vibrations (i = 0.01613 second) = 0.0564 second. In III the right arm was made to vibrate laterally to and fro oh the tuning-fork plate in tetanic tremor; here the to-and-fro movement comprised from 2 to 2.5 vibrations — from 0.0323 to 0.0403 second. V. Kries found that a simple muscular contraction excited by an induction- shock lasts longer than a single, momentary, voluntary movement. The direct registration of the muscular thickening during a single voluntary contraction shows that the contraction within the muscle lasts longer than the movement developed in the passive motor organ itself. This shorter duration of the resulting movement, which at first appears paradoxical, is due to the fact that, shortly after the primary voluntary muscular contraction, a contraction of antagonists takes place, and as a result a part of the intended movement is cut off. Even with the most rapid voluntary movements in man, v. Kries found that about THE lil FECT OF TWO SUCCESSIVE STIMULI. 56$ four impulses in the muscle were effective, so that they really represented short tetanic contract ii)ns. Pathological. — In the presence of secondary degeneration of the spinal cord following apojilexy, of atrophic muscles associated with ankylosed extremities, of muscular atrophy, of progressive ataxia, and of paralysis agitans of long standing, the latent period is increased. On the other hand, it is diminished in the presence of the contractures attending senile chorea and spastic tabes. The entire curve appears to be lengthened in cases of icterus and diabetes. In cases of cerebral hemiplegia in the stage of contracture the muscular contraction resembles the vcratrin-curvc, as it does likewise in cases of spastic spinal ]iaralysis and amyo- tro]iliic lateral sclerosis. In cases of pseudohypertrophy of the muscles, the as- cending limb is short and the descending limV) greatly lengthened. In the presence of muscular atrophy following cerebral hemiplegia and tabes, the height of the curve is reduced, ascent and descent take place gradually, and the contraction of the atrophic muscle resembles that of a fatigued muscle. In cases of chorea the curve is short. The reaction of degeneration is described on p. 669. According to Goldschcider contraction takes place sluggishly also in conjunction with affec- tions of the nerves, without any change in the irritability of the muscles them- selves. In rare cases the observation has been made in man that spontaneous motor stimuli give rise to prolonged muscular contractions, followed by after- contractions (Thomsen's disease). The muscle-fibers of such patients are broad, the nuclei increased in number, and the iibrils hypertrophied; it has been sug- gested that the white fibers are wanting. Fr. Schultze and others have observed a peculiar muscular undulation. If two momentary shocks be applied successively to tlie muscle in such a way that each would alone have induced a maximal contraction, that is the greatest possible contraction, the effect will vary in accordance w'ith the time that elapses between the two shocks. If the second shock be applied after the muscle has already become relaxed from the contrac- tion of the first stimulus, then a second maximal contraction simply results. If, however, the muscle is still in a phase of contraction or re- laxation from the influence of the first stimulus, the second shock gives rise to a new maximal contraction from the phase of contraction existing at that time. If, finally, the second shock follows so quickly upon the first that both occur during the period of latent stimulation, only one maximal contraction results. If both stimuli are only of moderate strength, not sufficient to induce maximal contraction, a summation of the effects of both takes place. At whatever stage of contraction the muscle may be as a result of the first stimulus (Fig. 195, /, b), the second shock will have an effect (b c) as if the phase of contraction brought about by the first shock were the natural passive form of the muscle. Thus, under favorable conditions, the contraction may be even twice as large as that induced by the first stimulus alone. The most favorable condition is the application of the second stimulus ^V second after the first. The effects of both are also produced if the second shock is applied within the period of latent stimu- lation. The second contraction of a summated contraction reaches its height in a shorter period of time than the first contraction alone would have done. The time for b c (Fig. 195, /) is, thus, shorter than that for a b. If a series of shocks be applied to the muscle in rather rapid succession, the muscle will have no time to relax in the intervals. It, therefore, in accordance with the rapidity with which the stimuli follow one another, remains in a state of continuous, shock-like, tremulous contraction that is designated tetanus. The condition of tetanus, or rigid spasm, is, thus, not a state of continuous, uniform contraction, but a discontinuous 566 TETANUS. form of movement, resulting from accumulated contractions. If the stimuli succeed one another with only moderate rapidity, the separate shocks may still be recorded in the curve (//). If, however, the stimuli are applied in more rapid succession, the curve has an uninterrupted ap- pearance {III). As a single contraction takes place more slowly during fatigue, it is obvious that a fatigued muscle will be more readily thrown into tetanus by a smaller number of single stimuli than a fresh muscle. All movements of considerable duration excited in the human body are thus to be regarded as tetanic, for they are constituted of a series of single contractions in rapid succession. Accordingly, every movement, however steady, will on close observation be found to exhibit intermittent vibration, which reaches its climax in tremor and becomes so conspicuous in cases of paralysis agitans. The number of single impulses sent to the muscles of the body in the execution of voluntary movements varies considerably — when the contractions are slow from 8 to 14 in a second, when the contractions are rapid from 18 to 20, the average being 12.5 in a second. Fig. 196, I, represents a myogram of the left flexor brevis pollicis and the abductor poUicis during a continuous contraction of moderate intensity, recorded on the vibrating plate of a tuning-fork. The wave-like eleva- tions indicate the separate impulses, each dentation being equal to 0.01613 second. II represents a similarly recorded curve made by the extensor digiti tertii. Fig. 195. — /, Two successive submaximal contractions. //, A series of contractions induced by 12 induction- shocks in a second. /// Marked tetanus induced by rapid shocks. By the summation of single stimuli, the muscle voluntarily excited slowly to contraction is gradually brought to the desired degree of shortening. It is cus- tomary to effect an exact adjustment of the extent of movement by the develop- ment of resistances through antagonistic muscles, as observations on lean, mus- cular persons show. The tetanic contraction that occurs under normal conditions in the intact body has also been shown to be composed of single, successive contractions, as secondary tetanus may result from it; the latter may be induced also from a muscle in a state of strychnin-tetanus. If a muscle be connected with a telephone whose wires are attached to two pins, one of which is inserted into the tendon and the other into the tissue of the muscle, a sound will be heard when the muscle is thrown into tetanus, indi- cating that periodic motor processes, that is, successive contractions, are taking place in the muscle. The sound is most distinct when the tetanizing Neef's hammer vibrates about fifty times a second. The rapidity with which the successive stimuli must follow one another in order to induce tetanic contraction varies for the different muscles of the body, as well as for those of different»animals. In the case of the muscles of the frog 15 successive shocks in a second are required on an average to induce tetanus (in the hyoglossus muscle only 10, in the gastrocnemius 27 shocks). If the shocks are feeble, more than 20 in a second are required. The muscles of the tortoise are thrown into a state of tetanus by only 2 or 3 shocks in a second; the red muscles of the rabbit by 10, the white TETANUS. 567 muscles by more than 30, human muscles by from 8 to 12. the sluggish abductor minimi digiti of man by 6 shocks in a second. The muscles of birds are not thrown into a state of tetanus even by 70 shocks, and the muscles of insects not even by from 350 to 400 in a second. In the muscles of the crab's claw, rhythmic contractions or rhythmically interrupted tetanus (in the astacus and hydrophilus) are observed as a result of tetanic stimulation. O. Soltmann found that the white muscles of new-bom rabbits are tetanized by 16 shocks in a second, and that the tetanus thus induced resembles that of fatigued adult muscles. This fact explains the readiness with which tetanus occurs in the new-bom. Curarized muscles are at times thrown into a state of tetanic contraction by a momentary stimulus. The extent of shortening in a muscle in a state of tetanic contraction is, within certain limits, dependent upon the strength of the individual stimuli, and also upon their frequency. The steepness of the tetanus-curve increases with increase in the strength of the stimtili rather than with increase in the frequency of the individual stimuli. With feeble stimuli the muscle exhibits greater con- tinuity in its contraction; intensification of the stimuli then causes a greater discontinuity in the curve (tendency to clonic spasm) ; and if the intensity of the stimuli be still further increased the curve becomes again more nearly con- tinuous. The contracture that may remain after tetanus is the more marked the stronger and longer the stimulation and the weaker the muscle. The height of the contraction and that of tetanus are the same for an unweighted muscle. Only in the case of the weighted muscle is the height of the single contraction less Fig. 196. — I, Fluctuations during a continuous contraction of the fle.xor brevis pollicis and the abductor pollicis. II, of the extensor digiti tertii. than that of the tetanic contraction. At times a stimulus applied immediately after tetanus has a greater effect than one applied before tetanus. The tetanized muscle cannot maintain the same degree of contraction in- definitely if the succession of shocks remains the same. On the contrary, it will lengthen somewhat as fatigue sets in, at first rapidly, but later more slowly. If the tetanizing stimulus is withdrawn, the muscle does not immediately regain its natural length, but a certain contraction-remainder persists for some time, especially after long-continued induction-shocks. Muscle may also enter into a state of permanent contraction, which has not been definitely determined to be due to fusion of single contractions; for example the transient contraction induced by certain chemical agents (such as ammonia and others), the elevations attending idiomuscular contraction, and that induced by the passage of a constant current. If rapid, weak induction-shocks (more than 224 and 360, even as many as 5000 in a second for frogs' muscles) be applied to the muscle or its motor nerve, the tetanus may cease after the initial contraction. This occurs with the least frequency of stimulation when the nerve is cooled; the higher the temperature of the nerve the greater the frequency of stimulation that may still be effective in inducing a long-continued tetanus. This initial contraction is a short tetanus; increase in the strength of the current renders the tetanus continuous. On the other hand, Kronecker and Stirling, however, observed tetanus occur with more than 24,000 shocks in a second. According to these investigators, the upper limit of frequency for the muscle that will still cause tetanus appears to lie near the limit at which fluctua- tions in the current can no longer be appreciated, even with other rheoscopes. 568 ISOMETRIC MUSCULAR CONTRACTION. Isometric Muscular Activity. — While the experiments discussed in the foregoing are concerned with the determination of the changes in the length of a muscle on stimulation and the movement of a weight sup- ported by it, Fick has investigated the changes that take place in the tension of a muscle under the influence of stimuli, when its length is kept constant. Fick designates this process the isometric muscular act. The following apparatus will serve to demonstrate the isometric muscular act (Fig. 197): The angular frame R is provided at its base with a long writing- lever S (abbreviated in the illustration), which is movable at the hinge-joint p. The muscle M, suspended from above, is connected with the writing-lever near its point of attachment. A strong spiral spring F is connected with the other arm of the writing-lever, and during the activity of the muscle, permits only the slightest degree of shortening to take place. This, however, is sufficiently magnified by the great length of the lever. A momentary electric stimulus is applied to the muscle by means of two elec- trodes (r r), and the writing-lever records the isometric curve. The isometric contraction-curve is, on the whole, similar to the isotonic curve, as a comparison of the curves in Fig. 197 will show. Nevertheless, the following differ- ences exist: (i) The contracting muscle attains its maximum tension in the isome- tric muscular act more rapidly than it attains its maximum shortening in the iso- tonic act. (2) The contracting muscle in the isometric act maintains the degree of highest tension somewhat longer, while in the isotonic act it recedes more rapidly from the highest degree of shortening. In the isometric muscular act in man, voluntary excitation gives rise to a higher degree of tension than electric stimulation. In the frog, the tension of the muscle in a state of tetanus is about twice as great as it is in a maximal con- traction; in human muscle it may be even ten times as great. During extension of the tetanized muscle, as during its contraction, equal degrees of tension cor- respond to smaller lengths. In the case of unstriated muscles, the entire curve is much shorter in the isometric act than during the isotonic act, and its form is almost svminetrical. Fig. 197. — Isometric Muscular Act. RAPIDITY OF PROPAGATION OF MUSCULAR CONTRACTION. If a muscle of considerable length is stimulated at one extremity a contraction occurs at that point, and rapidly traverses in a wave-like manner the entire length of the muscle to its other extremity. The excitation is therefore communicated to each successive part of the muscle by virtue of a special conductive capacity on the part of the muscle to enter into a state of contraction. In the frog the wave of contraction has an average velocity of from 3 or 4 to 6 meters in a second, in the rabbit of from 4 to 5 meters, in the lobster of only i meter, in MUSCULAR WORK. 569 unstriated muscles and in the heart of only from lo to 15 millimeters. These figures, however, apply only to excised muscles, for in the striated muscles of living human beings the rapidity of propagation is much greater, namely from 10 to 13 meters. Method. — For the demonstration of this motor phenomenon, Aeby placed a writinj:;-lever transversely across the origin of a muscle of considerable length and another across its insertion. Both were raised by the thickening resultnig from the contraction of the respective parts of the muscle, and the movements were recorded one above the other on the drum of a kymograph. If one ex- tremity of the muscle is now stimulated, the contraction-wave that rapidly traverses the muscle lifts first the proximal and then the distal lever. As the velocity with which the drum revolves is known, the rapidity with which the contraction- wave is propagated through the portion of muscle under examination can readily be calculated from the distance between the elevations of the two levers. The time corresponding to the length of the abscissa of the curve in- scribed by each recording lever is equal to the duration of the contraction in that part of the muscle; according to Bernstein this is from 0.053 to 0.098 second. By multiplying this value by the ascertained rapidity of propagation of the contraction-wave through the muscle, the wave- length of the contraction-wave is obtained; this equals from 206 to 380 millimeters. The rapidity and the height of the contraction-wave are diminished by cold, fatigue, gradual degeneration, and some poisons. On the other hand, the strength of the stimulus and the extent to which the muscle may be weighted have no influence on the rapidity of the wave. In ex- cised muscle the wave diminishes in size during its course through the muscle, but not in the muscles of a living human being or animal. The contraction-wave never passes from one fiber to an adjacent fiber; neither does it leap over an interposed tendon or a transverse tendinous septum. If a muscle of considerable length be stimulated locally at its middle, a contraction-w^ave is propagated from the point of stimulation toward both extremities, and in other respects possesses the properties pre- viously described. If two or more points in the muscle are stimulated at the same time, the wave-movement sets out from each, and one may even pass over another. If a stimulus be applied to the motor nerve of a muscle, it will be conducted to each muscle-fiber, whose contraction-wave must develop at the motor end-plate and be propagated thence in both directions along the fiber, which is only from 5 to 9 centimeters in length. In accord- ance with the obvious inequality in the length of the motor fibers from the nerve-trunk to the end-plates, the contraction will not commence at absolutely the same moment in all of the muscle-fibers, as the conduction through the inotor nerves likewise occupies a certain amount of time. The difference, however, is so small that the muscle, stimulated through its nerve, appears to contract simultaneously as a whole. An absolutely simultaneous, momentary contraction of all of the fibers of a muscle can occur only if all are stimulated at the same time. MUSCULAR WORK. The muscles are most perfect inachines not only because they utilize most completely the substances consumed in their activity, but be- 57° MUSCULAR WORK. cause they are distinguished from all machines of human construction by the fact that, as a result of repeated exercise, they become stronger, better developed, and capable of increased activity. According to the usual method of estimation, the amount of work performed by a muscle is equal to the product of the weight lifted (P) and the height to which it is lifted (s); hence, A = s P. From this it follows, first, that if the muscle is not at all weighted, therefore, if P equals o, then A must equal o; that is, no work is performed if there is no weight- ing. Further, if the muscle is burdened with an excessively heavy weight so that it is no longer able to contract, therefore, s equals o, then, likewise, no work is performed. Between these two extremes the active muscle is able to execute work. Strictly speaking, the contracting muscle lifts, in addition to the suspended weight P, half of its own weight p, which should be added to P as i p; hence, A=(P + ip)S. With the strongest possible stimulation, or maximal stimulus, that is, a strength of stimulus that causes the maximum degree of contraction in the unweighted muscle, the work performed increases progressively with each contraction as the weight increases to a certain maximum. If, as the weight is increased, the muscle can raise it to a gradually dimin- ishing height, the amount of work diminishes progressively; and, finally, as already noted, it becomes o, when no elevation is effected. The following table will illustrate the work performed by a frog's muscle, according to Edward Weber: eight Lifted, Height in MiUi- Amount of Work Performed in Grams. meters. in Gram-millimeters. 5 27.6 138 IS 251 376 25 11-45 286 30 6.3 189 If the weight be increased at any given moment during the contraction of the muscle, more work can be performed, but only if the stimulus applied does not fall below a certain minimum. The duration of the contraction is longer. If a muscle has contracted as much as possible for the purpose of lifting a heavy weight, it can be made to perform still more work by gradually diminishing the weight. It contracts still further and performs additional new work by raising the diminished weight. If the amount of work performed by the muscle be diminished by raising the weight before the contraction to a part of the height to which it would have been lifted by the muscle stimulated to the maximum, then the muscle will raise the weight to a still higher level. The investigations concerning muscular work yield the following results : 1. The muscle is capable of lifting a greater weight the larger its transverse section, that is the more fibers it contains arranged side by side. 2. The muscle is capable of lifting a weight the higher the longer it is, that is the more muscle-fibers it contains arranged in succession. 3. The muscle is capable of lifting the greatest weight at the com- mencement of contraction; as the contraction progresses, it is capable of lifting only a progressively smaller weight, and near the maximum con- traction only a relatively light weight. 4. By the term absolute muscular energy is meant, according to Ed. Weber, the weight that the muscle stimulated to the maximum is no MUSCULAR WORK. 57I longer capable of raising while in its natural passive form, without being stretched by the weight at the moment of stimulation. In order to obtain a standard for the comparison of the absolute muscular energy in different muscles and also in different animals, an estimation is made of the absolute muscular force for one square centimeter of cross-section. The mean cross-section of a muscle is determined by dividing its volume by its length. The volume is equal to the absolute weight of the muscle in question divided by the specific gravity of muscle-substance (1058). Thus, the absolute muscular energy for one square centimeter of a frog's muscle is from 2.8 to 3 kilos; for one square centimeter of human muscle from 7 to 8 or even from 9 to 10 kilos. Analogous figures for crustaceans are from 1.8 to 3.2; for beetles from 3.4 to 6.9; for mussels from 4.5 to 12.4 kilos. The transverse section of the muscles tested in man is estimated from cadavers having the same constitution and muscular development as the person under observation. In conformity with proposition 3 it is evident that a muscle during contraction will develop the greater absolute muscular energy the more it is extended before contraction. 5. If a muscle in a state of tetanic contraction maintains a weight in an elevated position, it performs no work during the time, but only in the act of elevation. Nevertheless, the muscle in the state of tetanus requires continued stimuli, and it exhibits metabolic changes and fatigue. The transformation of its potential energy is applied to the generation of heat. When the maximal stimulus is applied, a muscle is not capable of lifting as heavy a weight at one contraction as when tetanic stimulation is applied. During tetanic stimulation, moreover, the muscle develops the greater energy (even as much as twice the ordinary) the more frequent the stimulation, as has been ob- served with increasing frequency up to 100 stimuli in a second. If only moderate stimuli that do not excite the maximal contraction are applied to the muscle two possibilities present themselves. If the feeble stimulus remains constant, while the weight changes, the amount of work performed follows the same law that is operative during maxi- mal stimulation. If the weight remains the same, while the strength of the stimulus varies, then, according to Fick, the height to which the weight is raised varies in direct proportion to the strength of the stimulus. The stimulus that sets a muscle into activity must, naturally, attain a certain strength before it becomes effective — liniinal intensity of the stimulus. This is independent of the weight attached to the muscle. With a minimal stimtilus a small weight is raised to a higher level than a large one; but as the stimtdus is increased, the contractions increase in greater proportion with a heavy weight. A contracting muscle is capable of performing considerably more work if the weight to be lifted is attached to an inert mass that acts like a fly-wheel, or if the weight is swung to a considerable height. Starke was able almost to quadruple the work corresponding to a maxi- mal contraction by a proper selection of materials for this purpose. Also the production of heat is increased under such conditions, although in much less degree, and it is much more quickly diminished on fatigue. If the resistance applied to prevent the movement of a limb whose muscles, strained to the utmost degree, be suddenly removed, the limb will, with the greatest energy and rapidity, assume the position brought about by the muscles. Such springing movements are observed especially in grasshoppers, leaping beetles, and cheese-mites. Under special conditions a muscle may perform considerable work through its increase in thickness. In the intact body the vessels of a muscle dilate during muscular contraction, 572 THE ELASTICITY OF PASSIVE AND ACTIVE MUSCLE. SO that the amount of blood circulating thrdugh it is increased. Evidently the vasodilator nerve-fibers contained in the same nerve-trunks as the motor nerves are stimulated at the same time as the latter. In estimating the absolute muscular energy of single rmiscles or groups of muscles in man, close attention should always he paid to the physical relations, for example leverage, effects, direction of the traction, degree of shortening, and the like. The absolute energy of certain groups of muscles may practically be measured readily by means of the dynamometer. This is constructed in part on the principle of the spring-scales, upon which the pressure or pull of the muscles in question is allowed to act. Quetelet has determined statistically the strength of certain groups of muscles. The pressure of both hands in man equals 70 kilos. The pull amounts to double this weight. The strength of the hands of a woman is about one-third less. Further, a man can carry more than twice his own weight, a woman only half her weight; boys are able to carry about one-third more than girls. In estimating the work done by man, not only the amount of work he is able to perform in any one moment should be taken into consideration, but also the number of times in succession he can perform this work. In accordance with practical experience, the mean value of the daily work performed by a man during eight hours' activity has been estimated at from 6.3 to 10 (at most from 10.5 to 11) kilogrammeters in a second, hence a daily usefulness of 288,000 (in round numbers 300,000) kilogrammeters. The work performed by a horse in a second is assumed to be 75 kilogrammeters — horse-power or dynamic horse. This average performance of work may, it is true, be temporarily increased, but the organism then requires a prolonged rest after the work is done, so as not to suffer in health as a result of the overexertion. The amount of work performed in walking and in bicycling is discussed on p. 595. Some substances, when introduced into the body, impair and eventually abolish muscular activity; for example mercury, digitalin, helleborin, potassium- salts, apomorphin, and others. Others have been shown to increase the functional activity of muscular tissue; for example caffein. theobromin, veratrin, muscarin in small doses, glycogen, kreatin, and hypoxanthin; extract of meat likewise causes rapid recovery of the muscles after fatigue. Unstriated muscles are capable of performing a great amount of work, for example the uterus during labor, the craw of granivorous animals. The longitudinal musculature of the earth-worm is capable of raising more than 15 kilos, the frog's intestine of overcoming the pres- sure of a column of water of i^ meters. THE ELASTICITY OF PASSIVE AND ACTIVE MUSCLE. MYOTONOMETRY. Preliminary Physical Considerations. — Every elastic body has its natural form, that is the outer form that it possesses when no external force (traction or pressure) operates upon it. Thus, the passive muscle also possesses a natural form, when no traction or pressure is exerted upon it. If traction in a longitudinal direction be made on a muscle its connected parts must be somewhat separated from one another, and the natural form will be stretched under the influence of the elastic energy. If the extending force be removed, the elastic body will return to its natural form. A body is said to be completely elastic if it returns entirely to its natural form after the tension ceases. By amount of elasticity (modulus) is meant the weight, expressed in kilograms, by which an elastic body having a cross-section of one square millimeter would be stretched the equivalent of its own length, provided it did not previously rupture, as, naturally, often it does. For passive muscle this equals 0.2734, for bone 2294, for tendon 1.6693, for nerves 1.0905, for the coats of the arteries 0.0726. The amount of elasticity of passive muscle is, thus, small, as the latter yields readily to tractile force; hence its elasticity is not great. The coefficient of elasticity is that fraction of the length of an elastic body to which it is stretched by the unit of weight applied to it. This is large for muscle at rest. When the traction reaches a certain degree the elastic body finally ruptures. The carrying capacity of muscular tissue. THE ELASTICITY OF PASSIVE AND ACTIVE MUSCLE. 573 just short of the point of rupture, varies for youth, middle and advanced age approximately in the proportions 7 13 : 2. In the case of unorganized elastic bodies the amount of extension is always directly proportional to the extending weight. In that of organized Vjodies, therefore also of muscle, this is not the case, however, as with continued increase in weight in equal amount they are extended less and less in the further course of observation than at first. At the same time, they may for days or even weeks gradually imdergo a still further increase in length after the primary extension, corresponding to the svispended weight, has been attained, if the same weight be continued. This is designated elastic after-effect. The elasticity of passive muscle is small but complete, and is com- parable to that of India rubber. The muscle can be greatly elongated by means of small weights. With the uniform addition of further units of weight, uniform extension, however, no longer takes place, but a slighter increase in length corresponds with equal increments of weight the greater the load. This phenomenon may also be expressed as follows : the amount of elasticity of passive muscle increases with its increased extension. Method. — For the purpose of studying elasticity, the muscle is suspended free from a support provided with a scale, and the lower extremity is loaded successively with different weights placed in a small attached weighing-pan. The resulting elongation is measured in each instance. To construct a curve of elonga- tion, the units of weight added successively are taken as abscissas, and the lengths corresponding to each load as ordinates. The following is an example from the hyoglossus of the frog: Weight in Muscle-length in Elongation in Elongation in Grams. Millimeters. Millimeters. Percentages. 0-3 24.9 — — 1-3 30.0 51 20 ^■S 52 -i 2-3 7 3-3 33-4 I.I 3 4-3 34-2 0.8 2 5-3 34.6 0.4 I The curve of elongation is not a straight line, as in the case of unorganized bodies, but it resembles a hyperbola in form. The stretched muscle has a some- what diminished volume, as have the contracted and the rigid muscle. Muscles permitted to retain their connections in the living animal with their vessels and nerves are more extensible than excised muscles. Perfectly fresh muscles elongate at first proportionately to the weight if the increase in the latter be uniform and be kept within narrow limits, therefore like unor- ganized bodies. If the weights be heavy the observations are not made without consideration of the elastic after-effect. Dead, and especially rigid, muscle possesses a greater elasticity than fresh, living muscle; that is a greater weight is required to stretch the former than is needed to stretch the latter to the same length. On the other hand, the elas- ticity of dead muscle is less complete; that is, after being stretched, it regains its natural form only within narrow limits. In contradistinction from the elastic after-extension of muscle when weighted, after the tension has become constant, Blix recognizes an after-contraction of muscle, which comes into play after removal of the weight. Further, he dis- tinguishes an after-relaxation in mviscle that has been stretched, its tension in- creasing with the increase in length, but diininishing when the length has become constant; and, finally, an after-tension in a previously stretched muscle, whose length is diminished, the previously low tension again increasing, when the length has become constant. In the intact body the muscles are already stretched to a slight extent, as indicated by the moderate retraction that usually takes place when the muscular insertion is detached. This slight degree of extension is of importance with the occurrence of contraction; as otherwise the muscle would first have to contract, without immediately entering into activity, before it could exert traction upon the bones. The elasticity of the muscles becomes evident on the contractions of 574 THE ELASTICITY OF PASSIVE AND ACTIVE MUSCLE. its antagonists. The position of a passive limb depends upon the resultant of the elastic traction of the various muscle-groups. The elasticity of active muscle is diminished as compared M^ith that of passive muscle; that is it is lengthened by the same v^eight to a greater extent than is resting muscle. For this reason active muscle is softer, as can be demonstrated in an excised, contracted muscle. The appar- ently increased hardness of tense, contracted muscles is due only to their tension. When an active muscle becomes fatigued, its elasticity is still further diminished. During the latent period, in vi^hich the develop- ment of electrical phenomena and of heat points to metabolic activity in the muscle, no change in elasticity has as yet been demonstrated. Method. — Ed. Weber made observations in the following manner. The hyo- glossus muscle of the frog was suspended vertically, and its length was measured in the passive state. The muscle was then tetanized by induction-shocks and again measured. Progressively increasing weights were then attached to it, in succession, and the amount of stretching of the passive and then the length Fig. 198. — Bli.x's Elasticity Recorder. of the tetanized muscle (supporting the same weight) ascertained. The extent to which the active, weighted muscle contracted from the passive, weighted condition is termed the height of the lift. This becomes steadily less as the weight increases, until finally the heavily weighted, tetanized muscle can no longer con- tract; that is the height of the lift is zero. Indeed, if the weight be exceedingly heavy it may happen that the muscle, when stimulated, not only can contract no further, but it may even elongate. According to Wundt, however, the elas- ticity of the muscle does not change under such conditions. In these observations the length of the active, weighted muscle is equal to the length of the equally weighted, passive muscle, minus the height of the lift. Tracings of the length-curves recorded by passive or contracting muscle stretched by weights can be conveniently made by means of the apparatus of Blix, as shown in Fig. 198. The rectangular piece (A B C) is movable hori- zontally between two strips (R R). To the vertical portion of the former is attached the freely suspended muscle (m), which is connected with the writing- lever (S S), the latter being attached to the horizontal portion near C by means of a hinge-joint. The writing-lever is provided with a small movable rod (d d) , from which a weight is suspended. When the rectangular piece (A B C) is moved in the direction of the arrow, the weighted rod (d d) more closely ap- proaches the muscle, which thus becomes constantly more and more heavily weighted. With the muscle at rest (m) the curve o a b c e is first recorded by means of the displacement described. Then a similar curve is recorded while the muscle THE ELASTICITY OF PASSIVE AND ACTIVE MUSCLE. 575 is tetanized (M) by electrical stimulation; and the curve h i k is thus traced. With the aid of the apparatus both the extension-curve with increasing weight and the contraction-curve with diminishing weight can be recorded. Both curves are necessarily analogous, except that their form is reversed. The elasticity of muscle may also be measured by its rate of oscillation when twisted about its longitudinal axis. Kaiser found that the elasticity of active muscle depends upon its length at the time. It is least when the muscle has the same length in the active as in the passive state. If shortening occurs in a muscle stretched by a weight, its elasticity is diminished, and this reaches its minimum when the muscle becomes of the same length as the passive, unweighted muscle. If the active muscle contracts still further, its elasticity increases. Under the intiuence of certain poisons the elasticity of the muscles is altered as a result of changes in the condition of the contractile substance. Potassium causes shortening of the muscle, with simultaneous increase in its elasticity. Digitalin causes elongation of the muscle, together with increased elasticity. Physostigmin also increases the elasticity, while veratrin diminishes it and inter- feres with its completeness. Tannic acid renders the muscles less extensible, but more elastic. Ligation of the vessels causes first a diminution, and later an increase in the elasticity. Separation oj the nerves from the muscle results in a diminution of the elasticity. The influence of temperature on the extensibility is as follows: As the temperature increases — from 0° to 30° — the muscle elongates, as its extensibility increases. The increase in length is proportional to the load. At 34° contraction occurs as a result of the thermal stimulation; above 47° the muscle-proteid coagulates. Unstriated muscles possess an exceedingly small amount of elasticity; at the same time the elastic after-effect lasts much longer, and immediately follows the primary stretching. Fibrous connective tissue possesses the greatest elasticity, elastic tissue less, and unstriated muscular tissue the least. The elasticity of a complex organ, made up of these tissues, depends, accordingly, upon the relative abundance of these elements. As a result of his experiments Edward Weber has reached the following con- clusions as to the nature of the contractile energy of muscle. He assumes the existence of two states in muscular tissue — the passive and the active. Each of these is characterized by a special natural form. The passive muscle possesses the longer, thinner form; the active muscle the shorter, thicker form. Both the active and the passive muscle tend to maintain their respective form. If, now, the passive muscle be thrown into activity, the passive form suddenly changes into the active form, by virtite of its elastic energy. It is this latter that is capable of performing the work of the muscle. Schwann has already alluded to the simi- larity between the energy of an active muscle and that of a long, elastic, tense spiral spring. Both are able to lift the greatest weight only from the form in which they are most stretched. The greater the shortening they have already undergone, the smaller is the weight that they are further able to raise. Observations on elasticity can also be made on the muscles of living human beings. Under such circumstances, however, not alone the simple physical law of elongation is to be taken into consideration, for the elongation at the same time causes in the muscle changes in its irritability and in the blood-supply, as well as direct or reflex stimuli, all of which must necessarily modify its extensi- bility. If the extremity of the foot in man be raised vertically by means of a cord passing over a pulley and having weights attached to it, the muscles of the calf will be stretched. Mosso and Benedicenti found that, as the weight increased, the muscles became longer at the same or at an increasing rate, if the weight were continuous and increasing. If, however, the mixscle is completely released, before the new, heavier weight is applied, then the length of the stretched muscle diminishes as the weight is increased. Further, the curve of elongation exhibits individual dift'erences; it exhibits fluctuations in association with the respiratory curves; it may exhibit after-extensions and after-contractions; it changes with frequent repetition, with heat and cold. Strong, sudden stretching, and previous voluntary contraction and fatigue likewise have an effect. Investi- gations of this sort are designated myotonofnetry. 576 HEAT-PRODUCTIOX IX ACTIVE MUSCLE. HEAT-PRODUCTION IN ACTIVE MUSCLE. Method. — The increased temperature of a mviscle during contraction may be determined either by means of deUcate thermometers introduced between the muscles, or thermo-eiectrically. The passive muscle on the opposite side of the body, or the blood within a vein, will serve for purposes of comparison. As the resistance to conduction in metals (platinum wire, lead strips) is increased by heat, the observation ma}- also be made in this way. After Bunzen, in 1805, had observed the development of heat during muscular activity, v. Helmholtz demonstrated in 1848 that also ex- cised frogs' muscles, tetanized for two or three minutes, exhibit a rise in temperature of from 0.14° to 0.18° C. R. Heidenhain even succeeded bv thermo-electrical means in demonstrating an increase in temperature of'from 0.001° to 0.005° C. for each individual contraction. A similar condition exists in the beating heart, whose temperature rises with each systole. The production of heat in the muscle exhibits a latent stage, which is, however, of shorter duration than the latent period of move- ment. A contraction of a frog's muscle, weighing one gram, will produce an amount of heat equal to about three microcalories, which will raise the temperature of three milligrams of water from 0° to 1° C. The following facts have been ascertained concerning heat-produc- tion : T. It hears a relation to tJie amount oj work performed, (a) If the muscle during contraction carries a weight that during rest extends it again, it performs no work that is communicated externally. All of the transformed, chemical, potential energy is, therefore, converted into heat during this movement. Under these conditions the genera- tion of heat corresponds with the activity; that is it increases at first with the weight and the height of the lift to the maximum point, and then, as the weight is further increased, the generation of heat diminishes. The heat -maximum, however, is attained with a smaller weight than the maximum of w^ork. {h) If the muscle at the height of its contraction is relieved of its weight, then it will have performed some active work communicated externally. Under such circumstances the amount of heat generated is less than in the previous case ; and, indeed, the amount of work performed and the lesser amount of heat evolved, are the same in accordance with the law of the conservation of energy. (c) If the same amount of work is performed in the one case by many small contractions, and in the other by fewer but larger contractions, the amount of heat generated is greater in the latter instance. This fact indicates that large contractions are attended with a relatively greater metabolism than smaller ones, and experience is in accordance with it. Thus, the ascent of a tower by steps with a high tread causes much more fatigue (that is requires more metabolism) than ascent by steps with a low tread. {d) If a weighted muscle executes single contractions in succession, by means of which it performs work, the amount of heat thus generated is greater than if it carries the weight constantly in tetanic contraction. The transition of the muscle into the shortened form thus develops a greater amount of heat than the maintenance of that form. Also sum- IlKAT-PROnUCTION IN ACTIVE MUSCLE. 577 mated contractions are, accordingly, attended with the generation of a smaller amount of heat than corresponds to that develo])ed by two single successive contractions. As the stimulus becomes stronger, heat-production increases, in the case of isometric contractions jiroportionately to the degree of tension; that of isotonic contractions at tirst more rapidly than the height of the lift, but with strong stimuli ])roportionately to the latter. Even if the height of the lift, the strength of the stimulus, and the tension of the contracting muscle remain the same during successive contractions, the muscle nevertheless generates more heat during the first than during the following contractions. The amount of heat generated also depends upon the character of the stimulus employed; thus, a muscle tetanized by slow shocks generates more heat than one contracted by rapid shocks. 2. 'J he development of heat depends upon the tension of the muscle; it increases with increase in tension. If the muscle be prevented from con- tracting by fixation of its extremities, the maximum of heat -production takes place during stimulation, and the more quickly the more rapidly the stimuli succeed one another. Such a condition arises during tetanus, in which the violently contracted muscles mutually oppose each other. Therefore, a marked development of heat has been observed in con- nection with this disease. Dogs thrown into a state of continuous tetanus by electrical stimulation or by the induction of spasm die in consequence of elevation of their bodily temperature to a fatal height (44° or 45° C). This large production of heat is attended with a con- siderable degree of acidity and the formation of alcoholic extractives in the muscular tissue. In the case of isometric tetanus the metabolism and heat-produetion increase more rapidly than the tension as the stimulus becomes stronger. The continuous maintenance of tension in the muscle on the one hand, as well as the contraction of the muscle with a small amount of work without considerable tension, never- theless requires only relatively little metabolism for the generation of heat, as compared with the work, which is essentially proportional to the consumption of combustible material. If the stimulated muscle be so fixed that it cannot con- tract, and if it then by releasing its lower extremity be permitted to contract and lift a weight, an additional amount of chemical potential energy will be trans- formed for the performance of this latter task. 3. Heat -production diminishes as fatigue increases, and it again in- creases during recovery. The muscle becomes fatigued earlier in its production of heat than in its performance of work. 4. In a muscle normally supplied with circulating blood the produc- tion of heat, and also the mechanical performance of work, takes place much more energetically than in a muscle whose circulation is inter- rupted. Recovery following fatigue also takes place under such con- ditions more rapidly and completely. The total amount of work and heat in a muscle must alwa^^s be equivalent to the transformation of a corresponding amount of chemical potential energy. Of this the portion that is transformed into work will be the larger the greater the force that is opposed as a result of the contraction of the muscle. In the latter event this equals about one-fourth of the transformed potential energy. If the resistance be less, the work perfonned is a smaller fraction of the transformed potential energy'. At a high temperature, therefore probably in the febrile state, muscle exhibits greater inetabolism for the generation of increased amounts of heat, without increase in the work performed. In man, the production of heat in muscles made to contract by electrical stimulation can be appreciated through the skin. It was observed by Landois also when voluntan,^ movements were executed. Venous blood flowing from a contracting muscle acquires a higher temperature than the arterial blood — by as much as 0.6° C. — as a result of energetic action. 37 578 THE MUSCLE-MURMUR. The Statement made by some that a rise in temperature, amounting to about ^V° C, occurs also in a nc'rve in action is denied by others; but an increase in temperature does occur in a nerve in process of degeneration. 5. As the muscle is an elastic body, thermal phenomena will occur in it as a result of purely physical influences, as in inanimate, elastic bodies, such as India rubber! Thus, heat is set free on stretching living or dead -muscle; and, conversely, the temperature of the muscle falls on elastic -shortening. THE MUSCLE-MURMUR. If a contracted muscle be at the same time maintained in a state of tension by the application of resistance to it, a sound or murmur will be audible, arising from intermittent variations in tension within the muscle. Method. — For purposes of observation, auscultation is practised either by means of the ear applied directly, or with the aid of a stethoscope, over a tetani- -cally contracted muscle in another person. Some individuals are able to appre- ciate the murmurs of their own muscles of mastication on closing the external .auditory canals, and pressing the jaws forcibly together. If one external auditory canal be closed, and into the other there be inserted a small rod from the end of which is suspended a tetanized, weighted frog's muscle, the sound of this isolated muscle can be readily heard. If the contracting muscle is attached to an elastic spring, whose rate of vibra- tion can be varied, and if the rate of vibration is determined that must be im- parted to the spring in order that it shall be energetically set into vibration by the sounding muscle, the rate of vibration of the muscle-sound can be readily deter- mined for each case after a few trials. A writing-style may be fastened to the tip of the vibrating spring, and record the vibrations upon a smoked surface. A muscle, thrown into contraction by the will, vibrates from 19.5 to 20 times a second. The deep tone corresponding to such a small number of vibra- tions is, however, not audible, but the first overtone, corresponding to twice this nurnber, is heard. The sound has the same rate of vibration when the muscle is contracted in animals, by stimulation of the spinal cord, and also when the motor nerve of a muscle is irritated by chemical means. If, however, the motor center in the cerebral cortex be stimulated, the contracting muscle will generate a tone that is the higher the stronger the stimulus. If a tetanizing indticed current be applied to the muscle (also in man), the rate of vibration of the muscular sound corresponds exactly with the rate of vibration of the spring-hammer in the induction-apparatus. The sound can, therefore, be raised or lowered by changing the tension of the spring. Loven found that the muscle-sound is relatively the strongest when the ■weakest cttrrent is employed that will induce tetanus. The sound will then have the vibration-rate of the next lower octave. As the current is increased in strength, the muscle-sound disappears, and with a strong current it reappears with the same rate of vibration as that of the interrupter of the induction-apparatus. If the induction-shocks are sent through the nerve, the sound is not so loud, but otherwise it is of the same vibratory duration. By means of rapid induction- shocks sounds have been produced up to 704 and 1000 vibrations in a second. The first sound of the heart is in part a muscle-sound. Landois, in 1873, first reported the observation that the rumbling murmurs emitted by many fish (Cottus, sea-scorpion) are due to the loud sounds generated by the spasmodically contracted muscles of the shoulder-girdle, and still fur- ther intensified by the resonance of their large oropharyngeal cavity sur- rounded by a firm bony framework. He fotmd at that time that even a single induction-shock that excited the muscles was able to generate the muscle-sound. Herroun, Yeo, and Mac William also noted a like condition in the contracting mus- cles of man. It must, accordingly, be considered as doubtftd whether the muscle- sound can be regarded as evidence that tetanus is made up of a series of fluctua- tions in the density of the muscle. According to Bernstein, the sound heard during contraction occurs in the latent period. Hence, the cause of the muscle-sound is not to be sought in a displacement of the mass of the muscle. FATIGUE OF MUSCLE. 579 which is stationary during the hitent stage, but in molecular processes that are responsible also for the process of negative variation in the current. FATIGUE OF MUSCLE. The term fatigue is applied to tliat condition of diminished functional capacity in which the muscle is ]jlaced as a result of ])rolonged activity. This condition is recognized during life by a peculiar sensory perception localized in the muscles. In the intact body the fatigued muscle is capable of recovery, as is also the excised muscle to a slight degree. A muscle is more readily fatigued than its motor nerve. The cause of fatigue is the accumulation in the muscular tissue of the products of metabolism, fatig^ie -bodies, that are formed as a result of mus- cular activity. Among these products are : phosphoric acid, free or com- bined in acid salts; acid potassium phosphate; glycerin-phosphoric acid ( ?) ; and carbon dioxid. The accuracy of the foregoing explanation is indicated by the fact that the fatigued muscle becomes again more capa- ble of activity if the substances named are washed away by the passage of a normal solution (0.6 per cent.) of sodium chlorid or of a weak solu- tion of sodium carbonate through the blood-vessels of the muscle. The consumption of oxygen on the part of the active muscle also promotes fatigue; for the passage of arterial (but not venous) blood through the vessels removes the fatigue by replacing substances that have been con- sumed by the muscle. Conversely, a muscle that is capable of activity may be rapidly fatigued by the injection of dilute phosphoric acid, acid potassium phosphate, or dissolved meat-extract into its vessels. An animal may be fatigued also by the transfusion of blood from a com- pletely fatigued animal. A muscle fatigued by work absorbs less oxy- gen while in this condition, and it also generates only a small additional amount of acid and of carbon dioxid. The activity that gave rise to fatigue has thus induced considerable metabolic activity in the muscle. The fatigued muscle requires a stronger stimulus than the fresh muscle in order to perform the same amount of work, that is, to lift a weight the same distance. The fatigued muscle is no longer able to raise heavy weights; its absolute .muscular energy is therefore diminished. If the muscle is loaded with the same weight throughout the experiment, and if the stimulus is a maximal one (strong induced opening shock), then, from one contraction to the other, the height of the lift steadily diminishes by a constant fraction of the shortening. The fatigue-trac- ing is, thus, a straight line. The more rapidly the contractions follow one another, the more marked is this diminution in the height of the lift, and conversely. The excised muscle becomes fatigued to the point of exhaustion after a certain number of contractions. Under such circumstances it is a matter of indifference whether the stimuli follow one another in rapid or in slow succession. Analogous conditions are also observed in connection with submaximal stimuli. The fatigued muscle requires, further, a longer period of time for its contraction, which, therefore, takes place more sluggishly. Finally, the period of latent stimulation is also lengthened in a state of fatigue. The fatigued muscle is said to be more extensible. If the muscle is loaded with a weight so heavy that it cannot be lifted at all when contraction takes place, the muscle, nevertheless, be- comes fatigued, and, indeed, in a still higher degree than if it were able 580 FATIGUE OF MUSCLE. to lift the weight. The metabohsm and the formation of acid are, thus, greater in a stimulated muscle maintained in an extended position than in one that contracts when stimulated. If a muscle loaded with no weight is made to contract by stimulation, it becomes fatigued but •gradually. If the muscle is weighted only during the contraction, but not during the extension, it tires more slowly than if it were continuously weighted; as it does also if it is required to lift its weight only in the course of its contraction, instead of raising it at once at the beginning of the contraction. The suspension of weights from a muscle that is con- tinually at rest does not cause fatigue. If the arteries of a warm-blooded animal are ligated, complete fatigue will result after from 120 to 240 contractions, in from two to four minutes, on irritation of the nerve. Direct irritation of the muscle, however, will still be able to excite an additional series of contractions. The fatigue-tracings in both cases are straight lines. If the circulation in the muscles of a warm-blooded animal be unmterrupted, the contractions first increase in height, and then diminish, to pursue a straight line on stimulation of the nerve. Accordingly, it is found in persons that have used their muscles to the point of fatigue that the muscles and their nerves respond more actively to galvanic and faradic stimulation in the beginning, but to a steadily diminishing degree in the ftirther course of the work. Novi has demonstrated with greater detail the course of the contraction to the point of fatigue. According to him, the isolated muscle stimulated to the point of fatigue exhibits several phases in its action. The first phase exhibits a period in which the contractions occur rapidly and increase in size — an indication that the repetition of the stimulus causes an increase in the irritability of the muscle. In the second phase, of longer duration, the rapidity of the contractions is maintained, but their height diminishes — a sign that the irritability of the muscle is now decreasing. The third phase, again shorter, embraces contractions of slower course, the height remaining unchanged. In a fourth phase the con- tractions become still slower, but again increase in height. Finally the fifth phase exhibits uniform diminution in the height of the contractions and increase in their duration, until exhaustion occurs. Only this last phase corresponds to Kronecker's law. According to v. Kries a fatigued muscle tetanized in maximum degree behaves like a fresh muscle tetanized in submaximum degree. Both exhibit an incom- plete transition from the passive to the active state. Recovery from the condition of fatigue may be brought about by the passage of a constant galvanic current through the entire length of the muscle, likewise by the injection of fresh arterial blood into its vessels, or of small doses of veratrin. Relatively small amounts of sugar (30 grams) increase the muscttlar energy. Cocoa, coffee, tea, and other substances exert a stimulating influence on muscular activity. Among the poisons, curare and the putrefaction-toxins (ptomains) cause the fatigue-curve to pursue an irregular course. A. Mosso and Maggiora made observations on living persons, by having a weight lifted by the flexors of the middle finger, with the arm in a fixed position. Mosso found that the muscle tires sooner when stimulated directly than when excited indirectly through its nerve. Only for medium weights is the fatigue-tracing a straight line; for smaller weights "it is S-shaped, and for larger ones hyperbolic. If a tetanizing, electrical stimulus be continued until the muscular power is ex- hausted, there will still be left in the muscle a residue of energy that can be utilized by the will; and, conversely, a muscle finally exhausted by voluntary contractions can still perform some work when impelled by an electrical stimulus. If both forms of excitation be employed in immediate succession, they will exhaust the muscle completely. Mental exertion diminishes the muscular energy in a marked degree, as do likewise hunger and high temperature, especially in conjunction %yith marked humidity and diminution of atmospheric pressure; also local artificial elevation or diminution of the muscle-temperature. The strongest muscular con- MECHANISM OF THE BOXES AXD THEIR ATTACHMEXTS. 581 traction induced by the will cannot be further increased by strong electrical stimulation of the motor nerve. On the other hand, if the motor nerve be stimu- lated so that a less powerful contraction results, the will is unable to strengthen this contraction. The work performed by a muscle already fatigued is much more exhausting than a greater amount of work performed when it has been rested. Anemia gives rise to symptoms similar to those of fatigue, up to the point of inability to contract; while an abundant supply of blood rapidly refreshes the muscle. Fatigue of the legs, as after marching, hastens fatigue in the arms. Long- continued watching and fasting favor fatigue. Massage exerts a favorable in- fluence on fatigued muscles. If a muscle be completely exhausted by voluntary movement, and if, never- theless, the will be allowed to act as if to excite a contraction, the muscle will actually begin to contract again after a period of rest, until it becomes again exhausted, and so on. Mosso and Brandis assvime that involvement of the central nervous system, including the psychic centers, is, in part, to be taken into account in connection with fatigue in man. If a sensory stimulus be applied at the com- mencement of a voluntary contraction, the movement will be intensified and accelerated. Pathological. — In rare cases a morbid increase in the liability to muscular fatigue (mvasthenia) has been observed without muscular atrophy or sensory or reflex disturbances. MECHANISM OF THE BONES AND THEIR ATTACHMENTS. The bones exhibit in their spongA* structure an internal architecture, consisting of lamellcB arranged for pressure and traction exactly in accordance with those lines that would be constructed by graphic statics in the representation of the forces in weighted beams of the same form. This architecture is, therefore, so completely adapted to the function of bone that it combines the greatest capa- bility as a supporting apparatus with the least expenditure of material. The joints are covered with a layer of cartilage, which moderates, by means of its elasticity, the concussions communicated to the bones. The surface of the articular cartilage is smooth, and thus permits the articular extremities to move freely upon each other. At the outer boundary of the cartilage arises the capsule of the joint, which encloses the cartilaginous extremities like a sac. The inner surface of the capsule is lined by synovial membrane, which secretes the viscid, slippery synovial fluid, and this facilitates considerably the free movement of the surfaces. The outer surface of the capsule of the joint is covered with numer- ous fibrous bands, which act partly as fortifying and partly as restraining liga- ments. The bony processes also are included among the restraining contrivances, for example the coronoid process of the ulna, which permits the forearm to be flexed only to an acute angle; also the olecranon, which prevents hyperextension at the elbow-joint. The continuous apposition of the articular surfaces is made possible (i) by the adhesion of the smooth cartilaginous surfaces, covered with synovial fluid and sliding on each other; (2) by the external capsular ligament; and (3) by the elastic tension and the contraction of the muscles. The articular cavities must be regarded as cleft spaces, bounded by free con- nective-tissue surfaces, and unprovided with endothelium. The articular carti- lage and also the adjacent connective tissue are bare. The intima of the synovial membrane does not consist of endothelium, but of protoplasmic cells provided with processes, together with a fibrous interstitial substance. It is almost every- where separated from the articular cavity by a thin layer of fibrillar tissue. The synovial membrane is composed of delicate bundles of connective tissue intermixed \vith elastic fibers; it is provided on its inner surface in part with folds containing fatty tissue and in part with villi containing blood-vessels. The internal articular ligaments or cartilages are not lined by synovial membrane. The points of attachment of the synovial membrane to the bones are termed insertion-zones. The colorless, stringy, synovial fluid has an alkaline reaction and the compo- sition of transudates. In addition, it contains a substance resembling mucin, as well as albumin and traces of globulin, lecithin, cholesterin, fat, soaps, lutein, and also salts. Excessive movement diminishes its amoiint and increases its density and also the amount of mucin, but diminishes the amount of salts. With regard to the mode of movement, joints may be divided into the fol- lowing classes: 582 MECHANISM OF THE BONES AND THEIR ATTACHMENTS. 1. Joints with a Rotatory Movement about One Axis. — (a) The hinge-joint or ginglymus. The one articular surface represents a section of a cyHnder or cone, about one axis of which the other surface, with a corresponding concavity, moves on flexion or extension at the joint. Examples: the joints of the fingers and the toes. Strong lateral supporting ligaments are always present, to prevent lateral flexion of the joint. The screw-hinge joint is a modification of the hinge-joint. The humero-ulnar articulation belongs to this class. Strictly speaking, simple fiexion and extension do not take place at the elbow-joint; but the ulna is rotated on the trochlea of the humerus like a nut on a bolt; on the right humerus the screw is wound to the right, and on the left humerus to the left. The ankle-joint also belongs to this class; the nut is the articular surface of the tibia; the right joint resembles a left-handed screw, the left joint the reverse. (6) The pivot- joint (rotatio), with a cylindrical articular surface; for example, the articulation between the atlas and the odontoid process of the axis, which represents the axis of rotation. The axis of rotation of the articulation at the elbow-joint for pronation and supination extends from the middle of the cotyloid cavity on the head of the radius to the styloid process of the ulna. Accessory joints for this pivot- joint are, above, the articulation between the articular cir- cumference of the head of the radius and the lesser sigmoid cavity of the ulna; and, below, the articulation between the head of the ulna and the sigmoid cavity of the radius. 2. Joints with a Rotatory Alovenient about Two Axes. — (a) The joints exhibit in the two axes, which intersect at right angles, a curvature that is different in degree, but the same in direction: for example, the atlanto-occipital articulation, or the wrist-joint, in which both flexion and extension, as well as lateral inclination, are possible. (6) The joints have a surface of curvature that pursues a different direction in the two axes, which intersect at right angles. To this class belongs the saddle-joint, the surface of which is concave in the direction of the one axis, and convex in that of the other; for example, the articulation between the tra- pezium and the metacarpal bone of the thumb. The principal movements here are (i) flexion and extension, and (2) abduction and adduction. Further, move- ment is possible to a limited degree in all other directions, and a cone-shaped space can be circumscribed by the thumb. In this manner the saddle- joint re- sembles a limited arthrodial joint. 3. Joints with a Movement on a Spiral Articular Surface (Spiral Joints). — To this class belongs above all the knee-joint. The condyles of the femur, curved from before backward, exhibit, on sagittal section of their articular surface, a spiral the center of which lies toward the posterior portion of the condyle, and whose radius vector increases from behind downward and forward. The joint permits, first of all, extension and flexion. The strong lateral ligaments on both sides arise from the condyles of the femur, at a point corresponding to the center of the spiral, and are inserted on the head of the fibula and the internal condyle of the tibia respectively. When the knee-joint is strongly flexed, the lateral liga- ments are relaxed; they become tense as extension increases, and in complete extension they form tense bands, which ensure lateral fixation of the knee-joint. In accordance with the spiral form of the articular surface, fiexion and extension do not occur about one axis, but the axis constantly shifts with the points of contact; the axis traverses a path that likewise is spiral. The greatest fiexion and extension cover about 145°. The anterior crucial ligament is made more tense during extension, and acts as a check-ligament for excessive extension; the posterior crucial ligament is made more tense during flexion, and is a check- ligament for excessive fiexion. The movements of extension and flexion at the knee are, however, rendered more complex by the screw-like movement of the joint, with the result that the leg deviates outward during extreme extension. Accordingly, the thigh must be rotated outward during fiexion, if the leg is fixed. Pronation and supination further are observed in the knee-joint, amounting to 41° in extreme flexion, but being entirely absent in extreme extension. They are due to rotation of the external condyle of the tibia about the internal condyle. In all positions of flexion the crucial ligaments exhibit a fairly uniform degree of tension, as a result of which the articular extremities are held in apposition. It is owing to their arrangement that with increase in the tension of the anterior ligament during extension the condyles of the femttr must roll more on the anterior portion of the articular surface of the tibia; while with increase in the tension of the posterior ligament during flexion they must roll more on the posterior FUNCTION OF THE MUSCLES IN THE BODY. 583 portion. Braune and Fischer found in the course of their investigations that flexion at the knee-joint is attended with rotation of the tibia. The transition from a position of extension to one of flexion of 20° is attended with an internal rotation of 6°. From this point further flexion is attended with an external rotation, which amovmts to 6° at a flexion of 90°. 4. Yoints with Rotation about One Fixed Point. — These are the freely movable ball-and-socket joints (arthrodia). Movement is'possible about innumerable axes, all of which intersect at the point of rotation. The one articular surface has an approximately spherical shape, while the other has that of a hollow sphere. The shoulder-joint and the hip-joint are types of this articulation. Instead of the numerous axes, about which movement is possible, three may be substituted, intersecting at right angles in space. Therefore, these joints have also been designated tri-axial. The movements possible are: (i) pendulum-like movements in any desired plane; (2) rotation about the longitudinal axis of the extremity; (3) movements circumscribing the surface of a cone, the apex of which corre- sponds to the center of rotation of the joint, and whose surface is circumscribed by the extremity itself. Limited arthrodial joints are ball-and-socket joints with a more limited range of movement, and in which, moreover, rotation about the longitudinal axis is wanting; for example, the metacarpo-phalangeal joints. 5. Rigid joints {am phiarthrosis) are characterized by the fact that movement is possible in all directions, but is limited in extent, owing to short and tmyielding external articular ligaments. The articular surfaces are usually of the same size, and are almost flat. Examples are afforded by the articulations of the carpal and tarsal bones with one another. With regard to the mechanical origin of the articular forms of two bones movable upon each other, it is to be noted that the articular extremity to which the muscles are inserted near the joint becomes the acetabulum; while that ex- tremity to which the muscles are inserted at a greater distance becomes the head. Symphyses, synchondroses, and syndesinoses represent the junction of bones without the formation of an articular cavity. They are movable in all directions, but only to an extremely limited extent. Physiologically, they are thus closely related to the amphiarthroses. Sutures unite bones without permitting any yielding. The physiological significance of sutures resides in the fact that the bones may grow at their mar- gins, so that distention of the cavity enclosed by the bones is possible. ARRANGEMENT AND FUNCTION OF THE MUSCLES IN THE BODY. The muscles form 45 per cent, of the total mass of the body. The musculature on the right side of the body is heavier than that on the left. If the muscles are considered with regard to their function from the mechanical standpoint, the following categories may be distin- gidshed : A. Muscles without Definite Origin and Insertion, T. The hollow muscles, enclosing spherical, oval, or irregular cavities, such as the urinary bladder, the seminal vesicle, the gall-bladder, the uterus, the heart; or forming the walls of more or less cylindrical canals, such as the intestinal tract, the muscular ducts of glands, the ureters, the oviducts, the vasa deferentia, the blood-vessels, and the lymphatics. Under such circumstances the muscle-fibers frequently are arranged in several layers, for example in longitudinal, circular, and oblique direc- tions. During activity all of the layers contract to effect diminution in the size of the enclosed cavity. It is inadmissible to ascribe different individual mechanical effects to the various layers, for example to main- tain that the circular fibers of the intestine narrow the tube, while the longitudinal fibers dilate it. Both sets of fibers rather act together in diminishing the enclosed cavity, namely by narrowing and shortening it. If, however, the wall of a hollow organ is pushed or folded inward either 584 FUXCTIOX OF THE MUSCLES IX THE BODY. by pressure from without or by partial contraction of a number of circu- lar fibers, muscle-fibers that pass through the valley of the excavation to the surrounding borders may obliterate the depression by partial contraction, thus partially dilating the enclosed cavity, and converting the concave aspect of the depression into a smaller, plane one. The various layers are innervated from the same motor source, a fact that likewise supports the view of their homologous action. 2. The sphincters encircle an opening or a short canal, which is either narrowed or firmly closed by their action; for example the iris, orbicu- laris palpebrarum, orbicularis oris, sphincter pylori, sphincter ani, sphincter vulvae, sphincter urethrse. B. Muscles with Definite Origin and Insertion. 1. The origin is completely fixed when the muscle is in action. The course of the muscle-fibers to their insertion is such that during con- traction the insertion approaches the origin in a straight line; for ex- ample the attollens, attrahens, and retrahens auriculas, and the rhom- boids. In the case of some of these muscles, the insertion is lost in soft structures, which then follow the line of traction; for example the azygos uvulae, the elevator of the soft palate, most of the facial muscles arising from the bones and inserting into the skin, the styloglossus, stylophar- yngeus, and others. 2. I^oth Origin and Insertion are Movable. — Under such circum- stances the movements of both points are inversely as the resistances that have to be overcome by the movement. In this connection it should be borne in mind that these resistances can often be voluntarily increased either at the origin or at the insertion. Thus, for example, the stemo-cleido-mastoid may act either as a depressor of the head, or, if the head be fixed, as an elevator of the chest; the pectoralis minor may act either as an adductor and depressor of the shoulder or, if the shoulder be fixed, as an elevator of the third, fourth, and fifth ribs. 3. Some muscles with a fixed origin undergo a deviation from the straight line in the further course of their fibers or their tendons. This may be merely a slight curving, as in the occipito-frontal or the elevator of the upper eyelid; or it may be an angular deflection of the tendon around a firm prominence, so that the muscular traction is made in an entirely different direction, namely as if the muscle acted from this pro- cess directly on its insertion. Examples of the latter are the superior oblique muscle of the eyeball, the tensor tympani, tensor veli palatini, obturator internus. 4. Many muscles of the extremities act upon the long bones as upon levers: (c7j The muscle may act upon a lever with a single arm, the insertion of the muscle and the weight being situated upon the same side of the point of support, or fulcrum, for example the biceps, the deltoid. The point of application of the force, under such circumstances, is often situated close to the fulcrum. By this means, the rapidity of the move- ment during contraction of the muscle is greatly increased at the ex- tremity of the arm of the lever; for example, in throwing, the hand may move at a rate exceeding 22 meters a second; but force is lost. This arrangement, however, has the advantage that with lesser contraction of the muscle its force is diminished less than it would be if the contrac- tion were more marked, (b) The muscles may act upon the bones as upon levers with two arms, the point of application of the force (muscu- lar insertion) being situated upon the other side of the fulcrum than the FUNCTION' OF THE MUSCLES IN THE BODY. 585 point of application of the weight; for example the triceps, the muscles of the calf. In both instances the muscular force necessary to overcome a given resistance is calculated according to the laws of the lever. Equi- libriitm will be established when the static factors — that is the product of the force in its vertical distance from the fulcrum — are equal; or when the force and the weight are inversely proportional to their ver- tical distances from the fulcrum. In determining the amount of muscular force and the weight, especial attention should be given to the direction in which these act on the arms of the lever. Thus, it often happens that the direction that was perpen- dicular to the arm of the lever in a certain position may act obliquely U])on it during movement. The static factor of a force or weight acting obliquely on the arm of the lever is obtained by multiplying the force by the perpendicular dropped from the fulcrum upon the line of direction in which the force is acting. I. 111. AA' minastics are employed to strengthen systematically the muscles in persons suffering from weakness of certain muscles or muscle- groups, and in consequence not infrequently exhibiting deformities in the position of the skeleton. The movements of these muscles are practised especially, being opposed by suitable resistance, which should be overcome by the subject, or be opposed by him without overcoming them. 588 GYMNASTIC EXERCISES AND THERAPEUTIC GYMNASTICS. Kneading, pressing, and stroking the muscles (massage) also promote the circulation of blood through them. These procedures may, therefore, be applied with advantage to muscles that are so enfeebled by disease that independent, systematic training by exercises or gjTnnastics can no longer be successfully pur- sued. Derangement of nonnal movements may occur in the apparatus concerned in passive movements, namely the bones, joints, ligaments, and aponeuroses, or in apparatus concerned in active movements, namely the muscles with their ten- dons and motor nerves. Fractures, caries, and necrosis, and also inflammatory processes, which render movements of the bones painful, impair such movements or even render them wholly impossible. A similar result is caused by dislocations or inflammations of the joints, relaxation of the articular ligaments, or firm adhesions between the articular surfaces (ankylosis) or between the ligainents and soft parts surrounding the joint. Deviations from the normal function may further be caused by abnormal curvatures of the bones^ enlargements (hyperostosis), or outgrowths (exostosis). Among the abnormal positions of the skeletal parts that occtir frequently are to be included curvature of the spinal column laterally (scoliosis) , backward (kypho- sis) , or forward (lordosis) . These also give rise to disturbances of the respiratory movements. In the lower extremities, which have to bear the weight of the body, genu valgum (knock-knee) develops, especially in flabby, tall, young persons engaged in trades requiring much standing. The opposite curvature of the legs, genu varum (bowlegs), is usually the result of rachitic disease. Flat-foot (pes valgus) is due to depression of the arch of the foot, which then no longer rests upon its three normal points of support. This condition is often due to the same causes as genu valgum. The ligaments of the small tarsal joints are stretched, and the longitudinal axis of the foot is usually directed outward in marked degree. The inner border of the foot is brought closer to the ground. Pains in the foot and the malleoli render walking and standing difficult. Club-foot (pes varus) is the condition in which the inner border of the foot is raised, and the point of the foot is turned upward and inward; it is caused by a fetal arrest of develop- ment. All children are born with a slight degree of this position. Pointed toe (pes equinus) is the condition in which the point of the foot touches the ground; pes calcaneus, that in which the heel touches the ground. Both are usually de- pendent upon contracture of the muscles causing these positions, or upon paralysis of their antagonists. Persistent absence of earthy salts from the food results in a deficiency of these in the skeleton; the bones become thin, transparent, and even flexible. Rickets in children and the identical lameness in young domestic animals are caused by the fact that the calcium-salts of the food cannot be absorbed, on account of persistent disturbances of digestion. Analogous disturbances of the motor functions develop if the fully developed bones subsequently lose their calcium-salts to the extent of one-third or one-half (halisteresis) , and thus become brittle and soft — -osteomalacia. A certain minor degree of fragility of the bones and halisteresis occurs in old age. With regard to pathological alterations in the muscles, it should first be pointed out that the normal nutrition of muscular tissue can only take place if a sufficient supply of sodium chlorid and of potassium-salts is provided in the food, as these are integral constituents of muscular tissue. Otherwise, the muscles atrophy, and their reconstruction is prevented. Under such conditions, further, the central nervous system and the digestive apparatus also suffer, and the animals perish. The extent to which the muscles suffer in a state of inanition is described on page 440. Muscles and bones that for any reason are thrown out of function also undergo atrophy. In the atrophic muscles associated with ankylosis there is often found an enormous proliferation of the muscle-corpuscles, occurring as an "atrophic proliferation" at the expense of the contractile stibstance. A certain degree of muscular atrophy takes place normally in old age. The great reduction (from 1000 to 350 grams) in the muscular structure of the uterus after parturition is especially noteworthy. This is due in part to the diminished vascularization of the organ. In cases of lead-poisoning the extensors and interossei especially undergo atrophy. Atrophy and degeneration of the muscles give rise to secondary shortening and thinning of the bones to which they are attached. Section and paralysis of the motor nerves cause inactivity and finally de- generation of the muscles. Inflammation, softening, and sclerosis of the ganglion- STANDIN'G. 589 cells in the anterior horns or in ihc motor nuclei of the medulla ol)lonj;ata also give rise to atro])hy of the muscles connected with them. Spinal paralysis and acute bulbar palsy (paralysis of the medulla oblongata) thus have an acute onset, while progressive muscular atrophy and progressive bulbar paralysis pursue a chronic course. Under these conditions the muscles and their nerves become thin and wasted. The muscles exhibit many nuclei, their contractile substance is partly in a state of fatty degeneration, and later disappears altogether. The intramuscular connective tissue is increased, often also the interstitial fat. Ac- cording to Charcot, the central nerve-cells are also the trophic centers for the nerves arising from them and for the related muscles. According to Friedreich, however, j^rogressivc muscular atrophy is a primary disease of the muscles, a primary interstitial myositis resulting in atrophy and degeneration, the central nervous system becoming involved in the degenerative processes only secondarily; just as after amputation of an extremity corresponding parts of the spinal cord degenerate secondarily. Finally, mention should be made of pseudo-hypertrophy or lipomatous mus- cular atrophy, in which the muscle-libers are completely atrophied, in association with an abundant development of fat between the fibers, without, however, degeneration of the nerves or the spinal cord. The muscular substance may also undergo amyloid degeneration, the amyloid substance penetrating and infiltrating the tissue. At times atrophic muscles exhibit a deep brownish-red color, probably due to alteration of the muscle-pigment. Muscles constantly compelled to per- form a large amount of work, such as the heart-muscle, the bladder, the intestine, undergo hypertrophy. If the mechanism of the skeleton becomes altered, for example as a result of rigidity of a number of joints, the muscles adapt them- selves more or less completely to the altered mechanical conditions by changes in their growth, expenditure of energy, and manner of movement. SPECIAL MOVEMENTS. STANDING. Standing is the vertical position of equilibrium of the body, secured by muscular action, in which the line of gravitation — that is a perpen- dicular dropped from the center of gravity of the body — strikes the ground within the supporting area of the soles of both feet. Of the various posi- tions, that of "standing erect" will be analyzed here. In this position, muscular activity is exercised in two directions : ( i ) to fix the articulated body into an inflexible column (to "stiffen"); and (2) in case of a variation of the equilibrium to neutralize the disturbance by suitable muscular contractions. The following muscular activities are observed in standing: I. Fixation of the head on the vertebral column. The occiput may move in various directions on the atlas, whose two concave articular surfaces converge anteriorly. The act of nodding is the most readily performed. As the center of gravity of the head lies in front of the supporting points on the atlas, relaxation of the muscles, as in sleep or in death, causes the chin to fall upon the chest. The strong muscles of the neck, which pull from the spinal column upon the occiput, fix the head on the vertebral column. In addition to the nodding movement directlv forward, a similar movement is also possible obliquely forward and to the side'. Rotation of the head in the articulations of the atlas is possible only to an inappreciable extent around the sagittal axis, likewise around the vertical axis, the latter occurring only w^hen the head is flexed. No special muscular activity is necessary to prevent these movements in standing. When the head is rotated to the side, the contralateral vertebral artery is compressed in the vertebral sulcus, while that on the same side is enabled to carry more blood. The chief rotatory movement of the head occurs about the vertical axis of 59© STAXDING. the odontoid process of the axis. The articular surfaces on the pedicles of the first and second vertebrse are convex toward each other in the middle, becoming somewhat lower anteriorly and posteriorly. The head is, therefore, highest in the erect position; if it is rotated on the odontoid process, it undergoes a slight spiral movement downward. In this way distortion of the medulla is avoided when the head is strongly rotated. In standing, no muscular action is required to fix these vertebrae, as rotation cannot occur when the muscles of the neck and the flexors and extensors of the head are at rest. 2. The vertebral column requires fixation by muscles in those sec- tions where its mobility is the greatest ; these are the cervical and lumbar regions. Here fixation is secured by the numerous and strong muscles of the cervical vertebrae, especially those of the neck, and the lumbar mus- cles, especially the strong origins of the extensor dorsi communis, sup- ported by the quadratus lumborum. The least movable vertebrae are those from the third to the sixth dorsal; the sacrum is completely immovable. For a definite length of the column the mo- bility depends upon the following factors: (a) The number and the thickness of the elastic intervertebral discs. These are most numerous in the cervical region, and are thickest in the lumbar region and relatively also in the lower cervical region. They peimit movement in every direction. The intervertebral discs together form one-fourth the entire length of the spinal column. They are com- pressed somewhat by the weight of the body; hence, the body is longest in the morning and after rectimbency of some duration. The smaller circumference of the bodies of the cervical vertebrae must be more favorable for their movement on the discs than is the greater size of the lower vertebrae. (6) The position of the processes also materially influences the mobility. The greatly depressed spines of the dorsal vertebras prevent hyperextension. The articular processes of the cervical vertebrae are so situated that their surfaces are directed obliquely from before and above backward and downward. By this means relatively free movement is rendered possible in rotation, lateral inclination, and flexion. In the dorsal region the articular surfaces of the superior articular processes are directed vertically and directly forward, while those of the inferior articular processes are directed directly backward; in the lumbar region the corresponding position is almost vertical and sagittal. In the act of bending backward as far as possible, the most movable points of the spinal column are the lower cervical vertebrae, from the eleventh dorsal to the second lumbar vertebra, and the two lower lumbar vertebrae. 3. The center of gravity of the part of the body thus stiffened (the head and the trunk with the arms) is situated on the anterior border of the inferior surface of the eleventh dorsal vertebra. The perpendicular line dropped from the center of gravity passes behind a line joining both hip-joints. Hence, the trunk would fall backward at the hip-joints; but this is prevented by the ilio-femoral ligament, 14 mm. thick, stretched between the anterior inferior spine and the anterior intertrochanteric line, and also by the anterior tense layer of the fascia lata. As ligaments alone are never able to withstand continuous traction, they are mate- rially supported by the ilio-psoas muscle, which is inserted on the lesser trochanter, and also in part by the rectus femoris, whose origin extends upward over the acetabulum to the anterior inferior spine. A lateral movement of the hip-joint, in which one thigh would be abducted and the other adducted, is prevented especially by the large mass of the gluteal muscles, which fix the thigh on the pelvis posteriorly and lat- erally. When the thigh is extended, the ilio-femoral ligament also is able to prevent adduction, aided by the tense fascia lata. 4. The part of the body that has thus far been made rigid, including the head and the trunk, with the arms and the thighs, and whose center of gravity is situated somewhat lower and only to such a slight degree further STANDING. 591 forward that the Hne of gravity passes through the line connecting the posterior Ijorders of the knee-joints, must now be fixed at the knee- joints. Falhng backward is prevented by the strength of the quad- riceps femoris, supported by the tension of the fascia lata. Indirectly, the ilio-femoral ligament is believed also to aid in preventing falling backward, because in this act the thigh must be rotated outward, and this is prevented by the tension of the ligament named in the upright posi- tion. Lateral flexion at the knee-joint is impossible on account of the arrangement of the hinge-joint, strengthened by the strong lateral liga- ments of the knee. Rotation at the knee-joint is impossible in the ex- tended position. 5. The center of gravity of the entire body is situated 4.5 cm. in a vertical line below the promontory of the sacrum. A perpendicular dropped from this point strikes the ground a little in front of the line connecting both ankle-joints. The body would, therefore, fall forward at the latter joints. This is prevented by the muscles of the calf, aided by the muscles of the deep layer, namely the tibialis posticus, the flexors of the toes, and the peroneus longus and brevis. The following additional factors have also been considered worthy of mention : (a) As the longitudinal axes of the feet form an angle of 50° at the heels, falling forward can take place only if the feet have taken a position more nearly parallel to their longitudinal axes, (b) Falling forward is opposed also by the form of the articular surfaces of the foot, as under such circumstances the anterior, broader part of the astragalus would have to be pressed between the two condyles. This last factor is actually of little importance, as falling forward does not require such a marked change of position as would be necessary to bring this mechanism into play. 6: The tarsal and metatarsal bones, united by tense ligaments, form the arch of the foot. This touches the ground at three points, the tuber- osity of the OS calcis, the head of the first metatarsal, and the head of the fifth metatarsal bone. Between the last two points, however, the heads of the other metatarsal bones also form points of support. The weight of the body falls upon the highest point of the arch, the head of the as- tragalus. The arch of the foot is maintained only by ligaments. The toes are able materially to aid in balancing the body by means of their muscle-play. Standing erect causes more fatigue th-an walking. Braune and Fischer have recently distinguished the following varieties of station, for which, in contradistinction from the foregoing older exposition, a different form of muscular activity is required, (i) The "normal position" is characterized by the fact that the line of gravity passes downward through the lines connecting the central points of both hip-joints, knee-joints, and ankle- joints, and passes upward through the centers of gravity of the trunk and the head. Accordingly, the body need only be stiffened; no muscular activity at all is required to prevent falling forward or backward. (2) In the "comfortable position" the line of gravity strikes the ground in front of the line connecting the centers of both ankle-joints at a point corresponding approximately to the anterior border of the ankle-joint. Hence, muscular action is necessary to prevent falling forward at the ankle-joints. (3) In the "military position" the line of gravity falls in front of the knee-joints and ankle-joints, striking the ground at a point corresponding approximately to the middle of the sole. Hence, falling forward must be prevented at both joints, and this induces great fatigue on account of the considerable and continuous muscular exertion. The position of the center of gravity in the living person is determined as follows: The body is placed on a narrow board the length of the body. A balanc- ing edge is placed beneath the board, and first the upper and lower halves are balanced, then the right and left halves. Finally, the body is balanced when standing upright on a small board. The center of gravity is situated at the 592 SITTING, WALKI.VG, RUXXIXG, JUMPING. intersection of the three planes, passing in each instance at right angles to and along the balaning edge. The center of gravity of individual parts of the body may be determined in a similar manner on sections of a frozen cadaver. Pathological. — The security of firm station is recognized from the swaying of the body, which may be easily registered with the aid of a small rod placed verti- cally on the top of the head, the swaying being recorded by means of a pen or a brush on a stuiace stretched horizontally above the head. Disturbances of sensation, such as occurs in tabes and the like, cause marked swaying; as do also muscular weakness, tremor, fatigue, coldness of the feet, the action of an- esthetics on the soles of the feet. SITTING. Sitting is the position of equilibrium in which the body is supported on the tuberosities of the ischia, on which a to-and-fro rocking movement can take place, as upon the rockers of a rocking-horse. The head and the trunk together are made rigid so as to form an immovable column, as in standing. The essential purpose of sitting is to place the lower ex- tremities out of service from time to time, in order that their muscles may recover from fatigue. The following varieties of the sitting posture have been distinguished: i. The forivard sitting posture, in which the line of gravity passes in front of the tuberosities. In this position the body is supported either against a firm object, for example by means of the arms on a table, or on the upper surface of the thigh, which is either held horizontally or is flexed to an acute angle at the hip by a support placed under the feet. 2. The backzi'ard sitting posture is characterized by the passage of the line of gravity behind the tuberosi- ties. Falling backward is prevented under such circumstances by the back of a chair (if the latter extends upward as far as the head the neck- muscles also may undergo relaxation during rest J, or by the counter- weight of the legs, kept extended by muscular action. In the latter event the sacrum may ser\^e as a further point of support, while the trunk is fixed on the thigh by the ilio-psoas and the rectus femoris, and the leg is kept extended by the extensor quadriceps. Usually the center of gravity is so situated that the heels form additional points of support. This latter sitting posture is naturally not adapted for resting the mus- cles of the lower extremities. 3. In the median sitting posture (sitting erect) the line of gravity passes between the tuberosities. The muscles of the lower extremities are relaxed ; the rigid trunk requires only slight muscular action to balance it, falling backward being prevented by the ilio-psoas and the rectus femoris, and falling forward by the lumbar portion of the strong dorsal muscles. Usually, the balancing of the head is sufficient to maintain eqtiilibrium. WALKING, RUNNING, JUMPING. By walking is understood horizontal progression effected with the least possible muscular exertion by alternate activity of the two legs. Method. — ^The brothers William and Edward Weber, in 1836, anah'zed the various positions of the body during the movements of walking, running, and jumping, and recorded these positions in continuous series, which thus represent a true picture of all the successive phases of locomotion. Mare}-, in 1S72, deter- mined the time-relations attending change of position by connecting the motor organs in man and animals with apparatus that registered by means of air-trans- ference. He also further developed Weber's original idea, and has recorded the various phases of movement in walking, running, and jumping, and in moving animals by means of complete series of instantaneous photographs taken by a camera working on the principle of the revolver. The duration of exposure in WALKING, RUNNING, JUMPING. 593 each instantaneous photograph equals ,„Vr, "f a second. When placed in a stroboscope, these series reproduce the natural movements; and by projection with the aid of a kinematograph they may also be shown as "moving pictures." Figs. 20 1, 202, and 20,^ represent such series of instantaneous photographs ob- tained in the manner described. Braunc and O. Fischer, between 1S95 and 1899, introduced a new method of recording the motor process in walking by means of bilateral chronophotographic exposures on an extensive coordinating system. In the act of walking the legs are alternatively active. While one, the "supporting" or "active" leg, carries the body, the other, the "hang- ing," "swinging," or "passive" leg, is inactive. Thus, each leg in regu- lar alternation goes through an active and a passive phase. The motion of walking may be divided into the following acts: First Act (Fig. 200, 2). — The active leg is vertical, slightly flexed at the knee, and supports alone the center of gravity of the body. The passive leg is fully extended, and touches the ground only with the tip of the great toe {z). This position of the legs corresponds to a right-angle triangle, in which the active leg and the ground form the two sides (catheti), and the passive leg the hypothenuse. Fig. 200. — Phases of the Movement of Walking. The thick lines represent the active, the thin lines the passive leg: A, hip-joint; k a, knee-joint; / b, ankle-joint; c d, heel; m e, ball of the metatarsophalangeal joint; z g, tip of the great toe. Second Act. — To advance the trunk, the active leg tilts from its ver- tical position (cathetus) into an oblique position (3) inclined forward (hypothenuse). In order that the trunk may remain at the same height, it is necessary for the active leg to be lengthened. This is accomplished first by complete extension of the knee (3, 4, 5), then by elevation of the heel from the ground (4, 5), so that the foot rests on the ball formed by the heads of the metatarsal bone, and finally by elevation of the foot on the joint of the great toe (2, thin line). As both sections of the foot are successively raised from the ground, like the links of a measuring chain that is lifted from the ground ("unwound"), the elevation of the foot from the ground has also been termed "unwinding" of the foot. During the extension and forward inclination of the active leg the tips of the toes of the passive leg have been compelled to leave the ground (3). While this leg now becomes slightly flexed at the knee for the pur- pose of shortening, it executes at the same time a "pendulum-like" movement (4, 5), by means of which its foot is moved just as far in front of the active foot as it was previously behind the latter. W^hen it attains this position, the foot is placed flat upon the ground 38 594 WALKING, RUNNING, JUMPING. (r, 2, thick line). The center of gravity is transferred to this, the hence- forth active leg, which at the same time assumes a vertical position, somewhat flexed at the knee. The first act is now begun again. In walking, the trunk also exhibits some characteristic secondary movements: (i) It inclines each time toward the active leg, as a result of traction of the glu- teal muscles and the tensor vaginae femoris, with the object of transferring the center of gravity. In heavy, short persons with broad pelves this produces the "waddling" gait. (2) In order to overcome the resistance of the air, especially 4 5 6 1 2 =i 1 n ni TV V VI 4 5 6 1 2, 3 J n mwv Yi * 3 Ad mi 1 '^ '^ ^4d -a ^ ^ ^ '^ ^ r^ ¥4 Xi' 1 , 1 1 -| 0 O.50 1 1.5U 2 ■2.50 ci Met^r- . Fig. 201. — Slow Walking, Photographed in Instantaneous Pictures (after Marey). Only the side direct toward the observer is represented. From the vertical position of the right active leg (/) the entire phase of the movement of this leg follows in six pictures (from I to IV); after VI the vertical position is again reached. The Arabic numerals denote the simultaneous corresponding positions of the left leg, thus i = /, 2 = //, etc., so that, for example, during position 71' of the right leg the left leg at the same time has the position 1. Fig. 202. — Instantaneous Photographs of a Runner (after Marey). Ten pictures in a second; the base line repre- sents the distance traversed in meters. in rapid walking, the trunk is balanced at a forward inclination. (3) During the " pendulum "-motion the trunk rotates slightly about the head of the active femur. This rotation is compensated, especially in rapid walking, by the arm on the same side as the oscillating leg swinging in the opposite direction; while that on the other side at the same time swings in the same direction as the oscil- lating leg. O. Fischer has accurately determined the movement of the center of gravity of the body.' The external forces to be considered are the weight, the resistance of the groimd, the friction on the latter, and the resistance of the air. The time-relations of walking are influenced by the following conditions: (i) The duration of the step. As the rapidity of the pendulum-motion depends upon WALKING, RUNNING, JUMPING. 595 the lenjjth of the leg, it is evident that each individual, in accordance with the length of his leg, has a certain natural time of oscillation, which especially in- fluences his accustomed rate of walking. In addition, however, the duration of the step depends upon the length of time during which both feet touch the ground simultaneously. Naturally, this can be increased voluntarily. With a "rapid pace" the period of time is zero; that is, at the same moment that the active leg is placed on the ground the passive leg is raised. (2) The length (or stretch) of the step, which amotmts to six or seven decimeters on the average, must be the greater, the more the length of the hypothenuse of the passive leg exceeds the cathetus of the active leg. Hence, in the longest steps the active leg is markedly shortened by flexion at the knee, so that the trunk is carried at a lower level. Similarly, long legs are especially able to make greater steps. According to Marey, Carlet, and H. Vierordt the pendulum-movement of the passive leg cannot be regarded as a true pendulum-oscillation, because it possesses a more nearly uniform rapidity, owing to muscular action. During the pendulum- movement of the whole limb, the leg oscillates independently at the knee-joint, as is especially evident in women. According to Ed. and Wm. Weber the head of the femur of the passive leg is held in the acetabulimi chiefly by air-pressure, so that no muscular activity is necessar\- to earn,' the whole extremity. If all the muscles and the joint-capsule be divided, the head still remains attached to the acetabulum. By pulling on the thigh the borders of the cartilaginous rim of the acetabulum are closely applied in a valve-like manner to the margin Fig. 203. — Instantaneous Photographs of a High Jump (after Marey). The pictures partly overlap as soon as the velocity of the forward movement diminishes on the descent after the jump. In the upper, left-hand corner is a dial, the white radius of which has moved forward one division in one-twelfth of a second. The base line represents the distance traversed, in meters. of the cartilage on the head of the femur. According to the statements of the brothers Weber, the thigh is released from the acetabulum as soon as air is allowed to penetrate the articular cavity by perforating the bottom of the socket. The brothers Weber showed that in walking on level ground an appreciable amount of mechanical work is performed, as the weight of the body must be lifted several centimeters with every step. Marey and Demerj^ estimated that the work performed by a person weighing 64 kilos, when walking slowly, is equal to six kilogrammeters in a second; when running rapidly, it amounts to 56 kilo- grammeters. The performance consists in raising the whole body and extremities, in imparting rapidity of motion to them, and in maintaining the center of gravity. According to Rziha the work performed in each second in walking slowly is 3.5 kilogrammeters, in walking at a medium gait 5.46, in walking rapidly 7.87, in a short run 21.87, in ^ brisk run 42.87, and in a fast run 87. 50 kilogrammeters. A bicycle-rider going at the rate of two meters in a second, performs 1.12 kilogrammeters, at a four-meter pace 4.51 kilogrammeters, at a five-meter pace 7.05, and at a six-meter pace 10.15 kilogrammeters. The normal capability of 596 COMPARATIVE STUDY OF MOTION. a bicycle-rider is three and one-half minutes for each kilometer, or a rate of 4.73 meters a second, with a daily capability of from 90 to 100 kilometers. The normal capability of a workman is in this connection assumed by comparison to be 6.3 kilogrammeters a second. A bicycle-rider, going at an average rate, traverses the same distance in half the time and with half the expenditure of energy that a pedestrian requires. "With the same metabolic consumption of muscular tissue, the exertion and the degree of fatigue are greater in Avalking than in cycling. In long-continued cycling, likewise in long marches, there is an increase in the consumption of energy^ for the successive units of distance covered; at a moderate pace this increase amounts to about 20 per cent. The pressure on the ground in walking is distributed in the following manner: The supporting leg alwaj-s presses more firmly on the ground than the other; the longer the step the stronger the pressure. The heel attains the maximum pressure more rapidly than the point of the foot. The length of the step varies not inconsiderably even when a voluntary attempt is made to have the steps of equal length ; as do also the degree of spread- ing of the legs and the duration of the various phases of walking. Running (Fig. 202) differs from rapid walking in the fact that a mo- ment exists in which both legs are off the ground, so that the body hovers in the air. The active leg, in being forcibly extended from a more flexed position, must each time give the body the necessary impetus. In jnmping (Fig. 203) the body is suddenl}' raised by the most rapid and powerful contraction possible of the muscles in the lower extremi- ties, care being taken at the same time to maintain the equilibrium by appropriate muscular action. Pathological. — Variations in the walking movements depend primarily upon diseases of the bones, joints, ligaments, muscles, and tendons. Then the motor nerves must be taken into consideration, irritation and paralysis of which give rise to disturbances of the normal movements. The extent to which the sensory nerves and the reflex apparatus in the spinal cord influence the gait is pointed out on pages 716 and 72 S. H. Vierordt Jias applied the graphic method to the analysis of pathological varieties of gait. Among these are, for example, the spastic, the oscillating or zig-zag gait, the gait of tabes and that of paralysis agitans. Abasia and astasia are the terms applied by Blocq in 188S to the inability to walk and stand, arising from cerebral affections (hysteria, hypochondria, violent emotions, imperative conceptions, vertigo), while all other :novements, even those of the legs, can be executed with full force and coordination. COMPARATIVE STUDY OF MOTION. The absolute muscular energy in animals is not, generally speaking, appreciably different from that of man. The greater exhibitions of force encountered in the animal kingdom arise from the thickness and number of the muscles, as well as from difterences in the arrangement of their leverage or in the means for the transference of force. Thus, for example, insects are capable of exerting a great amount of force; some of them being able to drag 67 times their own weight, while a horse can scarcely drag its own weight. While further, for example, a man, by pressure on a dynamometer with one hand, overcomes a weight equal to 0.70 time his own body -weight, a dog by lifting his lower jaw can overcome a weight &.t, times that of his body; a crab by closing its claw overcomes 28.5 times its weight ; a mussel in closing its shell, 3S2 times its body-weight. Standing is made easier in quadrupeds by reason of the much greater sup- porting surface ; the springing animals assume, besides, more of a sitting position, and often use the tail as an additional support (kangaroo, squirrel). Birds possess a mechanical arrangement by means of which, in perching, their toes are flexed; in this way they are able to retain their grasp on twigs when asleep. In the stork and the crane, prolonged standing on one leg is made easy b)- the fact that no muscular action is required to render the leg rigid; fixation is secured by a process of the tibia fitting into a depression on the artictilar surface of the femur. In walking, a gait can be distinguished in quadrupeds; the four feet are moved COMPARATIVE STUDY OF MOTION. 597 at different times, and always diagonallj' one after the other; for example, in the horse, ri.s^ht fore, left hind; left fore, rij^ht hind. In trotting there is an accelera- tion of this gait, so that the legs are moved together diagonally at two different times, while the body is at the same time raised higher. In the interval between both hoof-beats the body is in the air half the time in ordinary trotting, longer in an extended trot. The gallop: When a (right) galloping horse moves horizontally through the air, the left hind foot comes down first. Shortly afterward the left fore foot and the right hind foot come down simultaneously; the right fore foot has not yet reached the ground, and is directed far forward. Up to this point the body has maintained its horizontal position. When, however, a few moments later, the left hind foot leaves the ground, it is at a higher level than the fore foot; at the same time, the right fore foot is also brought down and placed far forward; the right hind leg and the left fore leg are in extreme exten- sion. At the next moment these liinbs also leave the ground, and the hind foot acquires such an ascendency over the fore foot that it comes to be situated much higher than the latter. The body, therefore, is thrown forward and dowmward until the right fore leg, which alone still touches the ground, contracts actively, and pushes the body forcibly from the ground. When this has occurred, the horse again soars in air with the body directed horizontally. In galloping the longitudinal axis of the horse's body is placed obliquely to the direction of the movement, forming an acute angle. In an extended gallop (carriere), which is really a continuous jumping motion, the right hind leg and the left fore leg, for example, do not reach the ground simultaneously, the former striking first. The rapidity of this movement in the horse is 82^ feet a second. Most beasts of prey, hares, etc.. employ only the carriere for rapid movements. The amble is a modification of the gait that is peculiar to many animals, for example the camel, the giraffe, the elephant. It occurs also in dogs and in horses, but it is not a favorite gait with the latter. It consists in advancing both feet on the same side simultaneously or almost so. Marcy fastened compressible ampullae under the hoofs of the horse, connecting them with registering apparatus; and thus accurately recorded the time-relations of the various gaits. Aluybridge, in 1872, was the first to obtain series of instanta- neous photographs of running horses, which Schmidt-Mulheim placed together in the stroboscope. In snakes the progression of the body is secured by elevation and depression of the ribs in a manner resembling rowing. Swimming is an acquired art on the part of man. The specific gravity of the whole body is, on an average, somewhat higher than that of river-water, though somewhat lower than that of sea-water. In the quiet dorsal decubitus, with only the inouth and the nose above the surface of the water, sinking can be prevented b}' slight downward pressing movements of the hands ; sometimes no movement at all may be necessary. In this position progression may be accom- plished by simple extension and adduction of the legs. The movement may be accelerated by oar-like strokes with the arms. Swimming on the abdomen is more difficult, because the head, being held above water, increases the specific weight of the body. The body is advanced and held above water by movements divided into the following three phases: First phase, horizontal rowing movement of the extended arms from before backward to the horizontal position (forward movement) ; second phase, downward pressure of the arms toward the depth, w4th subsequent adduction of the elbows to the body (elevation of the body), together with a drawing up of the extended legs; third phase, forw-ard thrust of the arms, in contact with each other, and at the same time extension and ad- duction of the legs obliquely backward and toward the depth, as a result of which both elevation of the body and forward progression are effected. Unduly rapid movements are exhausting and defeat their own purpose. Special attention should be paid to suitable respiratory inovements. Man}^ land mammals, whose bodies are specifically lighter than water, move through it with a walking motion, especially of the hind legs; at the same time the feet, being directed downward, assure the normal position of the body, as they are specifically the heaviest parts of the body. Those mammals that live much in the water, as well as reptiles and amphibia, possess webbed feet and a propelling tail partly resembling that of fish. Whales resemble fish in the external appearance of their bodies. Fish primarily make use of their tail as a motor organ, which is moved by 598 COMPARATIVE STUDY OF MOTION. the powerful lateral muscles. Usually the caudal fin is bent in two opposite directions above and below; in slight movements it is bent only in one direction. By sudden extension of the tail, the fish exerts a pressure against the water, and thrusts itself foru-ard. Many fish, such as the salmon, can thus hurl them- selves up out of the water. The dorsal and anal fins maintain the vertical posi- tion. The pectoral and abdominal fins, corresponding to the extremities, effect the smaller movements, especially upward and downward; during sleep the ab- dominal fins are spread out. Most fish possess a swimming-bladder. This is wanting, however, in many cartilaginei (cyclostomi), or is rudimentary, as in the shark. It either opens into the alimentan,- tract through the air-passage, or the latter is only a temporan.- structure that is later obliterated. The swimming- bladder is. in part, to be regarded as a respirator}- organ with aft'erent and efferent vessels, while in part it ser\-es for hydrostatic purposes. In the dipnoi the bladder is transformed into a lung. The body of swimming birds has a much lighter specific gravity than has water, while their feathers are lubricated by the coccygeal glands. They propel themselves forward with their webbed feet. Flying, in mammals, is confined to the bat and its allied species. The bones of the upper extremities, including the phalanges, are greatly lengthened. Be- tween the latter, as well as the hind limbs (except the feet), is stretched a thin membrane, which also partially includes the tail. The flying movement of this membrane is effected by the powerful pectoral muscles, which arise in part from a ridge-like elevation of the sternum and the strong clavicles. The so-called flying lemurs, squirrels, and opossums have merely a duplication of the skin, stretched laterally between the larger bones of the extremities, and ser^nng as a parachute in jumping. Man is unable to imitate flying movements successfully, for even though he were able to construct artificial wings, he would still lack the strength of the pectoral muscles that is necessan,- to effect elevation of the bod\-. In birds the body specifically is exceedinghv' light. Large air-sacs extend from the lungs into the thoracic and abdominal cavities; even the bones are connected with the Itmgs by special canals, so that all the spaces in the bones of the cranium, spinal column, 'bill, and extremities are filled with air instead of marrow. The upper extremities, transformed into wings, are supported by the powerful coracoid bone and the clavicles (furcula), the latter being fused in the middle. The wings are operated by the powerful pectoral muscles, which arise from the large crest of the stemtmi. In flying upward the wings are half closed, and are moved with the anterior border directed obliquely forward and upward. The plane of the wings, without offering resistance to the air, follows in the same direction as the edge of the wings. Then the latter are spread out in a large arc downward and backward. with their surfaces pressed do^Tiward. While the under surfaces of the wings press against the air from above and forward, downward and backward, the bird moves fon\"ard and upward. Birds can rise only against the wind, partly because the wind striking horizontally against their backs would press them down, and partly because it would disarrange their feathers. By means of a revolving photo- graphic camera, arranged in an apparatus resembling a musket, Marey obtained complete series of pictures of flj'ing birds at which he directed the apparatus. Among invertebrates, all insects possess six legs. In addition some of them (butterflies, bees) have two pairs of wings on the second and third thoracic segments. In beetles and earwigs the first pair is merely a covering; in the strepsiptera it is entirely rudimentary. Conversely, in the flies the second pair of wings is reduced to small swinging bulbs. Lice, fleas, and bedbugs have no wings at all. All spiders have eight legs, the moths having six in their youth. In the centipedes the first three body-rings carr>- each one pair of legs, while all the rest have either one or two pairs. The crustaceans also possess numerous feet, as a rule, some of them tmdergoing peculiar transformations, for example in the river-crawfish into mandibles, claws, ambulatory- feet, abdominal swimming feet and fin-foot. In the arthropods all of the muscles are inserted on the inner surface of the chitinous covering. The muscles themselves are highly developed and capable of a great amoimt of energy' and rapidity of movement Molluscs lack internal supporting organs, while external ones (shells) of simpler construction are present. The muscles, which are partly striated, form a musculo- cutaneous tube about the body that causes the changes in the form of the body. In mussels the strong single or double sphincter-muscle of the shells is noteworthy. In the pecten (scallops) this muscle effects a springing movement in the water VOICE AND SPEECH. 599 by rapidly bringing the shells together. The molluscs provided with shells possess strong retractors. In the worms likewise the integument forms with the muscles a musculo- cutaneous tube. The imstriated muscle-fibers pass either longitudinally only (round-worms), or longitudinally and transversely (scratching worms), or finally longitudinally, transversely and vertically through the body (flat-worms). Some worms possess muscular suckers, and others one or two pairs of motile stump- like feet, in round-worms the epidermal cells, and in some bri.stle-worms the intestinal epithelium , pass directly over into muscle-cells, both together being called "epithelio-muscular cells." In the cchinoderms also the muscles are united with the integument; in the holothurians there is an external, continuous layer of circular libers, beneath which is a longitudinal musculature, arranged in live separate bands. In the star-fish and the hair-stars special mvisclcs move the limbs of the radiating parts of the body. The sea-urchin, surrounded by a firm lime-capsule, has special muscles that move its spines, and by means of which it is capable of locomotion. The ambulacral feet also aid in locomotion. In the celenterates the muscle-fibers arc transformed sections of epithelial cells. Hence, there are present "epithelio-muscular cells," which are striated in the medusa, and unstriated in the anemone and hydroid polyp. The free epithelial part may be provided with cilia. In the medusa these elements lie partly on the umbrella and partly on the tentacles. Among the polyps, the actinia have a strong muscular base, and, in addition, longitudinal and circular fibers on the body and on the tentacles. In some polyps muscles also accompany the gastro- vascular apparatus. Among the protozoa, striated muscle-fibers have been found in some infusoria, for example in the pedicle of the vorticella; while, in addition, the movements are executed by the movable protoplasm of the body, or by voluntarily motile cilia. VOICE AND SPEECH. SCOPE OF THE VOICE. PRELIMINARY PHYSICAL CONSIDERATIONS CONCERNING THE PRODUCTION OF SOUND IN REED-APPARATUS. The current of expired air, and under certain circumstances also that of inspired air, can be employed to throw the tense true vocal bands of the larynx into regular vibration, as a result of which a sound is pro- duced. This is termed the human voice. The true vocal bands of the larynx are elastic, "membranous reeds." By "reeds" are meant elastic plates that almost completely fill the space (frame) in which they are spread out, leaving, however, a small space for their movement. If air be blown against the reeds from a tube below them (air-tube), they will yield at the moment that the tension of the air overcomes the elastic tension of the reeds. In this way a considerable quantity of air suddenly escapes, its tension rapidly diminishes, and the reeds return to their former position, to repeat again the movement described. From the foregoing it results that — 1. During the vibration of the reeds, alternate condensation and rarefaction of the air must take place. It is chiefly this that (as in the siren) produces the sound, not so much the reeds themselves. 2. The "air-tube," which conducts the air to the membranous reeds, consists in the human voice-apparatus of the lower section of the larjmx, the trachea, and, below, the entire bronchial tree. The bellows is the thorax, diminished in size during expiration by muscles. 3. The air-passage above the reeds is called a "reinforcing tube," and consists of the upper section of the larynx, the pharynx, and also the oral and nasal cavities, which are arranged in two stories one above the other, and can be closed alternately. The pitch of the tone depends upon the following factors: (a) The length of the elastic plates. The pitch is inversely proportional to the length of the elastic plates; that is the fewer the units of length that enter into the elastic plates the more numerous will be the units of time (vibrations) entering into the tone produced. For this reason the pitch of the shorter vocal bands in children and in women is higher than that in adults and in men. (b) The pitch of the tone is, further, directly proportional to the square root 600 ARRAXGEMEXT OF THE LARYXX. of the elasticity of the elastic plates. In the case of membranous reeds, and also in that of silk, it is directly proportional to the square root of the extending weight, which in the lar}-nx corresponds to the force of the tensor muscles. (c) In the case of membranous reeds a more powerful blast not only strengthens the tone by increasing the amplitude of vibration, but it also raises the pitch of the tone, because the greater amplitude of vibration increases the mean tension of the elastic membrane. Among physical influences the following further are to be noted: ((i) The reinforcing tube, which is exceedingly variable in form, also resounds when the larjmx is intonated ; its primary tone is mingled with the sound of the elastic reeds, and, thus, it is able to reinforce certain overtones of the latter. This subject will be discussed in greater detail in the section on voice-formation. The individual characteristics of the voice depend essentially upon the form of the reinforcing tube. In reed-instruments the pitch of the tones can undoubtedly be influenced by var\'ing lengths of the reinforcing tube; but this is not taken into consideration in the case of the lar^-nx. (c) During intonation of the reeds the strongest resonance takes place in the air-tube, as the latter contains compressed air. This causes the vocal resonance that is heard when the ear is applied to the chest-wall. Strong intonation may even cause an accompanying vibration of the thoracic wall. In weak individuals, and in cases of falsetto voice, the vocal resonance is exceedingly slight. (/) Narrowing or widening of the glottis has no eft'ect on the pitch of the tone; but with the glottis wide open, disproportionately more air must pass through it, thus materially increasing the work of the thorax. ARRANGEMENT OF THE LARYNX. Cartilages and Ligaments of the Larynx. — The fundamental framework of the larynx is formed by the cricoid cartilage, which is shaped like a seal-ring. The inferior comu of the thyroid cartilage articulates with the cricoid in its postero- lateral region. This joint allows the plate of the thyroid cartilage to tilt fon\-ard, the inclination occurring as a rotaton,- movement about a horizontal axis connecting the two joints, the upper border of the cartilage moving forward and downward. The joints also permit a slight shifting of the thyroid cartilage on the cricoid upward and downward, forward and backward. The triangular, pyramidal ar>^tenoid cartilages articulate on the upper border of the plate of the cricoid cartilage to one side of the median line, forming approximately a saddle-shaped joint with oval articular surfaces. The latter permit a double movement on the part of the ar\-tenoids, namely rotation on their base about their vertical, some- what oblique, longitudinal axis, by which the vocal process directed for^'ard is rotated outward and upward, and the muscular process directed outward and overlapping the border of the cricoid cartilage posteriorly is rotated inward and downward, or conversely. In addition, the ar\-tenoid cartilages may be displaced somewhat inward or outward on their bases. The true vocal bands, or vocal ligaments, are composed principally of elastic fibers. They arise close together from about the middle of the internal angle of the thyroid cartilage, and are inserted on the vocal processes of the arj-tenoid cartilages directed fonvard. The "ventricles of Morgagni" allow free play for the vibrations of the bands, and separate them from the upper "false" bands, or ventricular ligaments, which are covered by a fold of mucous membrane. The latter take no part in phonation. Numerous mucous glands of the mucous mem- brane keep the vocal bands moist. In accordance with the functions of the lar^-ngeal cartilages in connection with the voice-apparatus, C. Ludwig has called the cricoid the " foundation -carti- lage," the thyroid the "tension-cartilage," and the an^-tenoids the "position- cartilages." Owing to the oblique downward inclination of their under surfaces the vocal bands readily come together when the glottis is narrowed during inspiration (for example in sobbing) ; and if the glottis is already closed, inspiration makes this closure still firmer. The false vocal bands exhibit the opposite relation, for when in mutual contact they are readily separated during inspiration; while during expiration they readily close, owing to the inflation of the ventricles of Morgagni. Action of the Laryngeal Muscles. — Dilatation of the glottis is effected by the posterior crico-arytenoid muscles. In drawing the muscular ARRANGEMENT OF THE LARYNX. 60 1 processes of the arytenoid cartilages backward, downward, and toward the median line (Fig. 208), these muscles cause the correspondmg vocal processes (/, /) to separate and move upward (//, //). A large isosceles triangle is thus formed between the vocal bands, and another between the inner borders of the arytenoid cartilages, having their bases in con- tact, so that the aperture assumes a rhomboidal form. Patholoeical.— Paralysis of these muscles may cause intense inspiratory dyspnea, on account of the failure of the glottis to dilate The voice remains uhchan^-cd In a freshly excised larynx the dilators first lose their excitability. X^V—-^ Fig 204. — .•Vnlerior View of the Larynx, with its Liga- ments and Muscular Insertions: O. h, hyoid bone; C. Ih., thyroid cartilage; Corp. Irit., corpus triU- ceum; C. c, cricoid cartilage; C. tr., tracheal cartilages; Lig. thyr.-hyoid. med., median thyro- hyoid ligament; Lig. th.-h. lat., lateral thyro-hyoid Ugaraent; Lig. cric.-thyr. med.. median crico-thy- roid ligament; Lig. eric, track., crico-tracheal liga- ment; M. st.-h., sterno-hyoid muscle; M. th.- hyoid, thyro-hvoid muscle; M. st.-lh., sterno-thy- roid muscle; J/. cr.-lh., crico-thyroid muscle. Fig. 205.— Posterior View of the Larynx, after Re- moval of the Muscles: E. epiglottis with the cush- ion (IV); Z..ar.-e/'.,arv-epiglottic ligament; M.m., mucous membrane; C. W., cartilage of Wnsberg; C. S., cartilages of Santorini; C. aryl., arytenoid cartilages; C. c, cricoid cartilage; P. m., mus- cular process of the arytenoid cartilage; L. cr. ar., crico-arvtenoid ligament; C. s, superior cornu, C. i., inferior cornu of the thyroid cartilage; L. ce.- cr. p. »., postero-inferior kerato-cricoid Ugament; C. tr., tracheal cartilages; P. m. tr., membranous portion of the trachea. Also in the presence of organic disease in the distribution of the recurrent nerve, the branch to the posterior crico-arytenoid muscle is the first to be paralyzea Likewise, in cooling the exposed recurrent nerve, this branch is always the hrst to fail in its function. The constrictor of the entrance to the larynx is the transverse arytenoid muscle, which connects the two outer borders of the arytenoid carti- lages by transverse fibers throughout their length (Fig. 209). On the posterior surface of this muscle are situated the crossed bundles of the oblique arytenoid muscles (Fig. 206), which have a similar action. Pathological.— Paralysis of these muscles renders the voice feeble and hoarse, as much air escapes between the arytenoid cartilages during phonation. 6o2 ARRANGEMENT OF THE LARYNX. The intimate approximation of the vocal bands is efifected by bringing the vocal processes of the arytenoid cartilages close together. To this end the latter must be rotated inward and downward by a forward and upward movement on the part of the muscular processes affected through the vocal or internal thyro-arytenoid muscles. These muscles, which are applied to the elastic borders of the vocal bands, and in fact are embedded in their substance and whose fibers extend to the outer borders of the arytenoid cartilages, rotate the latter so that their vocal . 206. — Posterior View of the Larynx, with the Muscles: E, epiglottis with the cushion (W); C.-W., cartilages of Wrisberg; C.-S., cartilages of Santorini; Cart. eric, cricoid cartilage; Cornu stip., superior cornu, Cornu inf., inferior cornu of the thyroid cartilage; M. ar. tr., transverse aryte- noid muscle; Mm. ar. obi., oblique arytenoid mus- cles; M. cr. aryt. post., posterior crico-arytenoid muscle; Pars cart., cartilaginous portion of the trachea; Pars memb., membranous portion of the trachea. Fig. 207. — Ner\cs of the Larynx. O. h., hyoid bone; C. th., thyroid cartilage; C. c, cricoid cartilage; Tr., trachea; M. th.-ar., thyro-arytenoid muscle; M. cr. ar. p. posterior cricoarytenoid muscle; M. cr. ar. L, lateral crico-arytenoid muscle; M. cr. th., crico-thyroid muscle; A^. LAR. SUP. V., supe- rior laryngeal branch of the vagus; R. /., internal branch; R. E., external branch; A''. L. R. V., recurrent laryngeal branch of the vagus; R. I. N. L. R., its internal branch; R. E. N. L. R., its ex- ternal branch. processes must move inward. The glottis between the vocal bands is thus narrowed to a slit, while a broad, triangular opening remains be- tween the bases of the arytenoid cartilages (Fig. 210). The lateral crico-arytenoid muscle is inserted into the anterior border of the articular surface of the arytenoid cartilage; hence, it can only draw the cartilage forward. Some investigators, however, believe that it also can effect a rotation of the arytenoid cartilage similar to that of the vocal or internal th3^ro-arytenoid muscle, with the difference that the vocal process are not brought so close together. Pathological. — Paralysis of the muscles effecting approximation of the vocal bands results in loss of voice. ARRANGEMENT OF THE LARYNX. 603 The tension of the vocal bands is effected by the action of muscles in separating their two points of attachment from each other. To this end the thvroiil cartilage is drawn forward and downward chiefly by the crico-thyroid muscles, the angle of this cartilage being at the same time somewhat enlarged. One can readily convince himself of this move- ment bv feeling his own larynx during the emission of high tones. The same muscles also approximate the anterior arch of the cricoid cartilage to the inferior border of the thyroid cartilage; and as a result the posterior plate of the cricoid cartilage undergoes a backward in- clination. At the same time the posterior crico-arytenoid muscles must draw both arytenoid cartilages somewhat backward, and hold them in that position. The tense vocal bands become longer and nar- rower. Fig. 208. — Diagrammatic Horizontal Section through the Larynx: /, I, Position of the arytenoid carti- lages during respiration, in horizontal section; from their anterior angles run the convergent vocal bands to the internal angle of the thyroid cartilage. The arrows indicate the direction of traction of the posterior crico-arytenoid muscles. //, //, Posi- tion of the arytenoid cartilages as a result of the action of these muscles. Fig. 200. — Diagrammatic Horizontal Section through the Larynx, to Illustrate the Action of the Aryte- noid Muscle: /, /, Position of the arytenoid carti- lages during quiet respiration. The arrows indi- cate the direction of traction of the muscle. //, //, Positions of the arytenoid cartilages produced by the action of this muscle. The tension of the vocal bands is aided by the genio-hyoid and hyo-thyroid muscles, which together draw the hyoid bone, and thus indirectly the thyroid cartilage, upward and forward in the direction of the chin. According to Harless, Schech, Kiesselbach, Hooper, and others, the crico-thyroid muscle effects elevation of the arch of the cricoid cartilage toward the thyroid cartilage. In this way the plate of the cricoid cartilage is directed backward and downward, thus causing increased tension of the vocal bands. Pathological. — Paralysis of the crico-thyroid muscles renders the voice harsh and deeper, on account of insufficient tension of the vocal bands. The tension thus induced is of itself by no means sufficient for pho- nation, for on the one hand the triangular aperture of the glottis between the arytenoid cartilages that would result from the isolated action of the internal thyro-arytenoid muscles must be closed. This is brought about by the transverse and oblique posterior arytenoid muscles. Then the vocal bands themselves, which, with the action of the crico-thyroid and posterior crico-arytenoid muscles, retain their concave border, so 6o4 ARRANGEMENT OF THE LARYNX. that the glottis between them appears as a space having the form of a myrtle leaf, must be fully stretched, so that the glottis assumes the shape of a linear slit (Fig. 214). This compensation likewise is brought about by the internal thyro-arytenoid muscle. It is this muscle, moreover, that effects those delicate gradations of tension in the vocal band itself that are necessary for the production of tones of slightly different pitch. It is especially adapted for this purpose, as it comes close to the edge of the vocal band and is firmly inserted into the elastic tissue of the latter. The contracting muscle in addition gives to the vibrating vocal band the resistance necessary for its vibrations. As some of the fibers of the vocal muscle terminate in the elastic tissue of the vocal band itself, they may impart increased tension to individual segments of the vocal band, as a result of which modifications in tone- formation are possible. It must, therefore, be assumed that the coarser variations in tension are caused by separation of the thyroid cartilage from the arytenoid cartilages, while the finer gradations of tension are induced by the vocal muscle. The usefulness of the elastic tissue in the vocal bands does not consist so much in its ex- tensibility, as in its property of shortening without forming folds or creases. Pathological. — When these muscles are paralyzed the voice can be produced only by powerful blasts, as much air escapes through the glottis. At the same time the tones are deep and impure. Uni- lateral paralysis results in flapping of the corresponding vocal band. Relaxation of the vocal bands occurs spontaneously when the stretching forces cease to act, the thyroid car- tilage drawn forward and the arytenoid cartilages fixed pos- teriorly returning to the posi- tion of rest in consequence of the elasticity that is peculiar to their arrangement. Relaxation of the vocal bands may result also from the action of the thyro-arytenoid and lateral crico-arytenoid muscles. From the foregoing it follows that tension of the vocal bands and narrowing of the glottis are necessary for phonation. The epiglottis, which becomes more erect with high tones and falls with low ones, has an influence on the timbre (clear or muffled) of the voice, but has no effect on the pitch. The mucous membrane of the lar}'nx, as well as the submucosa, is rich in delicate, elastic networks of fibers. The submucosa is loose and yielding in the region of the entrance to the larynx and the ventricles of Morgagni, a fact that explains the enormous swelling that often occurs in connection with so-called edema of the glottis. A clear, even, limiting layer lies beneath the epithelium. The epithelium is stratified, cylindrical, and ciliated, interspersed with goblet-cells, except on the true vocal bands and the upper surface of the epiglottis, where a stratified, squamous epithelium covers the mucous membrane, which in this situa- FiG. 210. — Diagrammatic Horizontal Section through the Larynx, to Illustrate the Action of the Internal Th>To- ar}tenoid Muscles in Narrowing the Glottis: //, //, Po- sition of the arytenoid cartilages during quiet respiration. The arrows indicate the direction of traction of the mus- cles. /, /, Position of the ar>tenoid cartilages brought about by action of these mtiscles. ARRANGEMENT OK THE LARYNX. 605 tion bears papillae. Racemose mucous glands are present in groups on the carti- lages of Wrisberg, the cushion of the epiglottis, and in the ventricles of Morgagni; and are scattered in the other situations, especially on the posterior wall of the larynx. The blood-vessels form a dense, capillary network under the limiting layer of the mucous membrane; beneath this are two more layers of vascular net- works. The lymphatics form a superficial , narrower network beneath the blood- capillaries, and a deeper, coarser network. The medullated nerves, which have Fig. 211. — A, Vertical section through the head and neck as far as the first dorsal vertebra: a sliows the position of the laryngoscope in order to see the posterior part of the glottis, the arytenoid cartilages, the upper surface of the posterior laryngeal wall, etc.; b shows the position of the laryngoscope in order to obtain a \-iew of the anterior angle of the glottis. B, Large (6) and small (a) laryngeal mirrors. ganglia on their branches, are numerous in the mucous membrane; their termina- tions are unknown. The cartilage is hyaline in the thyroid, the cricoid, and almost in the entire arytenoid cartilage, with a tendency to ossification. Fibro- cartilage is found toward the apex and the vocal process of the arytenoid cartilage, and also in all the remaining laryngeal cartilages. The larynx grows tmtil about ^he sixth year, then rests, but rapidly increases . in size again at puberty. 6o6 EXAMINATION OF THE LARYNX. EXAMINATION OF THE LARYNX. LARYNGOSCOPY. EXAMINATION OF THE EXCISED LARYNX. After Bozzini, in 1807, had given the first impulse toward illuminating and examining the internal cavities of the body by means of the mirror, and Babington, in 1829, had viewed the glottis in this way, the singing-teacher, Manuel Garcia, in 1854, made investigations, by means of the laryngoscopic mirror, on himself and other singers, concerning the movements of the vocal bands during respiration and phonation. Tiirck and Czermak rendered the greatest service in the applica- FiG. 212. — Method of Making a Laryngoscopic Examination. tion of the laryngoscope to medical purposes, the latter being the first to use artificial Hght for illumination. Rhinoscopy was first attempted by Baumes in 1838, and was systematically developed by Czermak. The laryngoscope consists of a small mirror, attached to a handle at an angle (Fig. 211, B), the instrument being introduced with the mouth wide open and the tongue drawn out (Fig. 211, A). The position of the mirror must be changed in accordance with the region to be reflected; and it may at times even be necessary to ele- vate the soft palate by means of the mirror (6). The mirror receives the picture of the larynx in the direction of the dotted line, and reflects it at the same angle through the oral cavity to the eye of the observer, which has taken its position in the line of the reflected rays. The illumination of the larynx is ac- complished by collecting either sunlight or light from an artificial source in a concave mirror, and permitting the concentrated bun- dle of rays to fall on the laryngoscopic mirror held in the throat. The latter reflects the light against the larynx, which is thus illumi- nated. The obeerver looks in the same direc- tion as the rays of light, either under the edge of the illuminating mirror, or through a cen- tral perforation in the latter. The laryngoscope received an important improvement at the hands of Oertel, who showed how the movements of the vocal bands could be followed directly with the eye by means of rapidly intermittent illumination through the disc of a stroboscope (laryngo-stroboscope) . By replacing the eye by a photographic camera, Ssimanowsky was able to photograph the movements of the vocal bands in an artificial larynx. Fig. ai3- -The Laryngoscopic Image During Respiration. EXAMINATION OF THE LARYNX. 607 V. Ziemssen showed that long, thin electrodes could be introduced as far as the larj-^nx under the guidance of the laryngoscope, and that the vocal bands could be stimulated to activity by irritation of the muscles. Rossbach succeeded in stimulating the muscles and nerves of the larynx externally through the skin. Fig. 214. — Image of the Larynx when a Sound is Begun. Fig. 215. -View of the Trachea as far as the Bifurca- tion. In this way physiological information may be gained, or therapeutic applications may be made to the parts. Autolaryngoscopy was first employed by Garcia, and then by Czermak espe- cially for the study of the movements of the larynx. If one introduce an illumi- nated laryngoscopic mirror into his own throat, while placing the mouth opposite a plane mirror, he may easily see the picture of his own lar>-nx re- r-jj] fleeted in the latter. ^Ml The laryngoscopic picture (Fig. 213) exhibits the follow- ing details: L, the root of the tongue, from the middle of which the glosso-epiglottic ligament passes downward ; on each side of the latter are the so-called valleculae {V V). The epiglottis {E) appears as an arch, shaped like the upper lip; beneath it in quiet res- piration is seen the lancet- shaped chink of the glottis {R), and on either side the bright, yellowish vocal liga- ment {L.V.). This vocal band is from 6 to 8 mm. long in chil- dren, from 10 to 15 mm. long in women when relaxed, and from 1 5 to 20 mm. when tense. In men it measures from 15 to 20 mm. and from 20 to 25 mm. respectively. The whole chink of the glottis is 23 mm. long in men and 17 mm. in 27.5 and 20 mm. respectively. The width of the vocal bands varies from 2 to 5 millimeters. Ex- ternal to the vocal band is the entrance (rima vestibuli) tO the sinus of ^Morgagni (S. M.), represented by a dark band. Still further outward, and on a higher plane, may be seen the fold of mucous membrane (plica Fig. 216.— Position of the Laryngeal Mirror in the Practice of Rhinoscopy. women; when the vocal bands are tense 6o8 EXAMIXATIOX OF THE LARYN'X. ventricvdaris) covering the false vocal band or the ventricular ligament (L. V. s.). On the lower, lip-shaped border of the entrance to the larynx may be distinguished the posterior lower notch of the ostium phar\-n- geum lar\-ngis (above P.); and on either side of this the apices of the car- tilages of Santorini (5. S.) are visible, resting on the apices of the an.'ten- oid cartilages; immediately behind is the adjacent pharyngeal wall (P.). In the ary-epiglottic ligaments (IF. IT.) are the cuneiform cartilages of Wrisberg, and finally, external to these, may be recognized the depres- sions of the sinus piriformes (S. p.). Special attention should be given to the condition of the glottis and the vocal bands during respiration and phonation. During quiet respira- tion the chink of the glottis (Fig. 213) appears as a lancet-shaped slit, which is wider during life than in the cadaver. If deep respirations are taken, the chink widens considerably (Fig. 215), and if the mirror is favorably placed, it may be possible to see the rings of the trachea, and even the bifurcation. When the voice is produced, the glottis closes each time to a narrow slit (Fig. 214). Appendix. — Rhinoscopy. — -The nasal cavity has important relations to speech and to respiration. By the introduction of a mirror bent at an angle, with the reflecting surface directed upward, it is pos- sible gradually to survey a field such as is reproduced in Fig. 217. In the middle appears the nasal septum (S. H. ) , on either side the longitudinally oval choanae (Ch.), and further below the soft palate (P. in.) with the pendant uvula (U.). On the borders of the choanal openings may be recognized the posterior portions of the inferior (C. i.), middle (C. jn.) and superior (C. s.) turbinated bones, with the corre- sponding nasal meatus beneath each one. Least distinct are the upper turbinated bone and the lower meatus. At the uppermost part a strip of the roof of the pharj-nx (O. R.) may yet be seen, with the more or less developed phar\-ngeal tonsil. This latter structure is composed of lymphatic glandular tissue, and extends in an arch- like manner over the roof of the pharvrnx between the openings of the two Eustachian tubes {T. T.). External to the mouth of the Eustachian tube on each side is the so-called tubal eminence (IF.), and still more external the fossa of Rosenmuller (R.). For the study of the lan,-nx experimentation on the excised lar\-nx is further of importance, as carried out by Ferrein in 1741 and especially by Johannes Muller in 1S39. The latter conducted the air into an excised human lar\-nx through a tracheal tube the air-tension of which was measured by a communicating mercTorial manometer. The bases of the arytenoid cartilages were held in a fixed position against each other by means of a suture: while a cord passing over a ptdlev and carr\'ing weights drew the thjToid cartilage forward. By increasing the tension the' tones could be raised about 2^ octaves. When the tension re- mained the same, stronger blasts of air raised the tone to the fifth. The tone was not lowered bv placing tubes over the lar\-nx to increase its length, but these measures modified the timbre and increased the resonance of the note. Landois employed the fresh, living, excised lar\-nx from the dog or the sheep; the muscles being stimulated by various pairs of electrodes, while a bellows supphed the air through a tracheal tube. In this way the most reliable information con- cerning the action of the various muscles can be obtained. The Rontgen rays have recently been applied with success to the study of the position of the larjiigeal cartilages and the hj-oid bone, and also of the soft palate. Fig. 217. — The Rhinoscopic Image. This illustra- tion is more or less diagrammatic, in so far as a repeated shifting of the mirror is necessary- in order to obtain the entire image as is given here. THE SOUNDS OF TIIK VOCAL APPARATUS. 609 CONDITIONS INFLUENCING THE SOUNDS OF THE VOCAL APPARATUS. The pitch of the voice-tone de])ends upon the following factors: 1. The tension of the vocal bands; hence upon the degree of contrac- tion of the crico-thyroid and posterior crico-arytenoid muscles, with the assistance of the vocal or internal thyro-arytenoid muscles. 2. The length of the vocal bands. In this connection it should be noted: (a) That children and women, with shorter vocal bands, pro- duce higher tones. The voices of women are about one octave higher than those of men. (6) If the arytenoid cartilages are pressed tightly together bv the action of the transverse and oblique posterior arytenoid muscles, so that only the vocal bands themselves can vibrate, while the intercartilaginous parts between the vocal processes cannot, then the tone will be higher. To produce deeper tones, the vocal bands, and also the margins of the arytenoid cartilages, must vibrate. At the same time the space above the exit of the larynx enlarges, so that the throat becomes more prominent, (c) Each individual has a certain medium pitch of voice, which corresponds to the least possible muscular tension within the larynx. 3. The strength of the blast. That the strength of the blast is able to raise the pitch of the tone in the human larynx is shown by the fact that the highest tones can be emitted only in a loud voice. With medium tones the air-tension in the trachea amounts to r6o mm., with high tones to 200 mm., with exceedingly high notes to 945 inm., in whispering only to 30 mm. of water measured through a tracheal fistula. In changing the intensity of a tone from loud to soft, or conversely, while maintaining the same note, the muscular action must undergo a change in force. When the note is loud the force diminishes, while it increases as the tone becomes soft. J. Miiller called this process the "compensation of energy in the larynx." The following accessory phenomena have been observed in the production of high notes, but no certain interpretation of them has been given: (a) As the pitch of the note increases, the larynx becomes elevated, partly because the elevating muscles of the lar^'nx are brought into activity, and partly because the intra- tracheal air-pressure lengthens the trachea to such an extent that the larynx is raised up. The uvula also is raised higher and higher, (b) The txpper vocal bands approach each other more and more, without touching or participating in the vibrations, (c) The epiglottis inclines more and more backward over the glottis. In explanation of c and b it is supposed that, in the production of high tones, all of those muscles are active that aid in shortening the vibrating section of the rim of the glottis and in constricting its opening. In this act the edge of the (external) thyro-arytenoid muscle displaces the upper vocal band inward; while the epiglottis is drawn downward b}^ those fibers that pass upward toward it laterally — the thyro-ary-epiglottic muscle. 4. So-called registers can be distinguished in the voice. There is generally the chest-register, the thorax vibrating (pectoral fremitus), and the voice appearing to come from the depths of the chest ; and also the head-register, the voice apparently coming from the throat. The latter, with its soft timbre and lack of resonance in the air-tube, is designated also a falsetto voice or shriek. Oertel observed under such circumstances that the vocal bands vibrated so as to form nodal lines across their width; at times only one nodal line is formed, so that the free border of the vocal band and the basal border vibrate, and are sepa- rated from each other by a nodal line parallel to the edge of the vocal 39 6io RANGE OF THE VOICE. band. In high falsetto notes, as many as three such nodal lines may- arise in succession. The formation of the nodal lines must be occasioned by a partial contraction of the fibers of the internal thyro-arytenoid mus- cle. At the same time the vocal bands mmst be stretched into the thinnest possible plates by the combined action of the crico-thyroid, posterior ary- tenoid, thyro-hyoid, and genio-hyoid muscles. The glottis is elliptical in form, while with the chest-voice it is bounded by the straight lines of the vocal bands. In the latter case more air passes out of the larynx. Oertel found, moreover, that with the falsetto voice the epiglottis assumes a vertical position. The apices of the ar>'tenoid cartilages are inclined somewhat backward ; the entire larj-nx appears longer in its sagittal diameter and narrower in its transverse diameter; the ary-epiglottic folds are stretched tensely, with sharp edges; the entrance to the ventricles of Morgagni is constricted. The vocal bands are longer than in the production of the same tone with the chest-voice; further, they are narrower, and the vocal processes are in contact with each other. The rotation of the ar^-tenoid cartilages necessary for this is brought about solely by the lateral crico-arytenoid muscle, while the thyro-arj'tenoid is to be regarded only as an accessory, aiding muscle. Elevation of the pitch with the falsetto voice is effected exclusively by increasing the tension of the vocal bands. In addition to the characteristic modification in the vibration of the vocal bands already described, still another series of partly transverse and partly longitudinal partial vibrations are superposed upon the former. In the case of the chest-voice a narrower edge of the vocal band vibrates than in that of the falsetto voice ; in the production of the latter there is a feeling of less muscular exertion in the larynx. The uvula is raised horizontally. In the so-called chest-register the entire width of the vocal band vibrates, in the middle register only the inner narrower border. In the chest-voice the overtones in the note are richest and strongest, while in the falsetto voice thej^ are less numerous and feebler. Pathological. — By means of Oertel's laryngo-stroboscope important informa- tion can be obtained concerning variations in the vibrations of the vocal bands, such as unequal amplitude of vibration in the two vocal bands (laryngeal catarrh) , with or without alternating vibrations; the formation of vibration-nodes in one band; the absence of vibrations in one or both bands. In order that the voice may be produced, the following processes are necessary : ( i ) The required amount of air is accumulated in the thorax ; (2) the larynx and its parts are fixed in the appropriate position; (3) then follows the "onset" of the voice, either the closed glottis being forced open by means of an expiratory effort, or some air being per- mitted to pass almost noiselessly through the glottis, and the vocal bands being then thrown into vibration as the blast of air is gradually increased. RANGE OF THE VOICE. The range of the human voice for the chest-register is shown in the accompanymg diagram: -56 Soprano. 1024 171 Alto. 684 r E F G A B c d e f g a b c' d' e' f p-' a' b^ 3 ~ $m --4- zzt— e//(j//e//f //g//^/. b//,g/// 80 Bass. 342 128 Tenor. 512 SPEECH. Till' VOWELS. 6ir The figures indicate the number of vibrations in a second for the corresponding tone. It will be readily seen that the notes from c' to f are common to all voices^ nevertheless, each has a different timbre. The lowest note, which exceptionally is sung by bass singers, is the contra-F with only 42 vibrations; the highest note of the soprano voice is a'" with 1708 vibrations. Hensen devised an especially ingenious method for determining with exactness the pitch of a sung note. The note is emitted against a Konig's capsule, with a gas-llame. Ojipositc this is a tuning-fork, vibrating horizontally, and provided at the extremity of one prong with a inirror, in which the fla:nc is reflected. If the pitch of tlie voice is the same as that of the fork, the ilame appears in the mirror as a single jet; at the octave two jets a])pear, at the twelfth three jets, and at the double octave four. Each individual has his characteristic voice-timbre, which depends upon the configuration of all of the cavities belonging to the vocal organ. The so-called palatal tones arise from the approximation of the soft palate to the posterior pharyngeal wall. In the production of nasal tones the air in the nasal cavities vibrates more forcibly, as access to these cavities must be freer. SPEECH. THE VOWELS. The motor processes concerned in speech are carried out in the reinforcing tube — the pharyngeal, oral, and nasal cavities; they are directed toward the production of tones and noises. If the latter alone are developed, the voice-apparatus being passive, "whispering" results (vox clandestina) ; if, however, the vocal bands vibrate at the same time, "audible speech" results. Whispering itself may be made quite loud, but to bring about this result a strong blast is required; hence it is fatiguing. It can be practised during both inspiration and expira- tion, in contradistinction to audible speech, which sounds transient and indistinct when produced during inspiration. Whispering results from the sound that is generated, when the glottis is moderately nar- rowed, by the passage of the air over the blunt margins of the vocal bands. In the production of audible speech the vocal processes are so placed that the sharp margins of the vocal bands are directed toward the air-current, and are thrown into vibration by it. The soft palate always participates in the production of speech. It is raised with every word, Passavant's transverse ridge being at the same time formed in the pharynx. The palate is raised highest during the utterance of u (00) and i (ee) ; less high with o and e (a) , and least high with a (ah) . During the enuncia- tion of ni and n the palate is stationary; with the explosives it is about as high as with n; and it is lower with the fricatives. With /, ,s-, and especially with the guttural r, it is thrown into a tremulous movement. Speech is made up of vowels and consonants. Vowels. — (Analysis and artificial formation are considered on page 905-) In whispering, a vowel is the sound produced, during either expira- tion or inspiration, by the inflated characteristically shaped oral cavity, the sound having not only a definite pitch, but also a characteristic timbre. The characteristically shaped oral cavity may be designated the "vowel-cavity." 6l2 SPEECH. THE VOWELS. The pitch of the vowels may be determined musically, either by paying close attention to one's own whispered vowels, or in the case of another by blowing by means of a suitable air-tube from the opening of the mouth into its cavity placed in the position peculiar to the vowel in question. It is a remarkable fact that the fundamental tone of the "vowel-cavity" is almost constant for various ages and sexes. The differences in the internal capacity of the mouth can be com- pensated for b}- varying the size of the opening of the mouth. The pitch of the vowel-cavity maj- also be estimated by holding a series of vibrating tuning-forks of var3-ing pitch in front of the mouth. When the one is found that corresponds with the fundamental tone of the vowel-cavity, the note of the tuning-fork will be strengthened considerably by resonance from the oral cavity. Finally, a mem- brane having the same rate of vibration as the vowel-tone may be held in front of the mouth, and the vibrations of the vowel-tone may be transferred to the membrane, the vibrations of the latter being recorded on smoked paper, as in the "phonautograph" of Bonders. Konig found the fundamental tones of the vowel-cavities to be as follows: U (00):= b, 0 = b', A (ah) = b", E (a) = b'", I (ee) = b"". If the vowels be wdiispered in this series, their pitch will at once be heard to increase. Otherwise, these fundamental tones of the mouth in the vowel-positions may vary within certain limits ; hence it is better to speak of the region of a characteristic tone-position. This may be best demonstrated by placing the mouth in the characteristic position and percussing the cheeks. The sound of the vowel w411 then be heard, and its pitch will vary within certain limits in accordance with the position of the mouth. In pronouncing .4 (ah), the mouth has the shape of a funnel dilating anteriorly (Fig. 218, A). The tongue lies on the floor of the mouth; the lips are wide open. The soft palate is raised moderately; being successively more elevated w4th O. E (a), U (00), I (ee). The hyoid bone is in a position of rest when A (ah) is being uttered; but the larynx is somewhat raised, being higher than with U (00), but lower than with I (ee). When a transition is made from A (ah) to I (ee) , the larj-nx and the hyoid bone retain their relative positions, but both ascend. During the transition from A (ah) to U (00), the larj-nx sinks to the lowest possible level. At the same time the hyoid bone moves slightly forward. In pronouncing A (ah) , the space between the lar\-nx, the posterior phar\-ngeal wall, the soft palate and the root of the tongue is only moderately dilated; it becomes larger with E (a) and espe- cially with I (ee) , and is smallest with U (00) . In sounding U (00), the shape of the mouth is that of a capacious flask w4th a short, narrow neck. The entire reinforcing tube is under such conditions longest. Accordingly, the lips are protruded as far as possible, are corrugated, and are brought together so as to form a small opening. The larynx is at its lowest level. The root of the tongue is approximated to the posterior palatine arch. In sounding O, the mouth, as with U (00), resembles a wide-bellied flask with a short neck. The latter, however, is shorter and at the same time more widely open, the lips approaching more closely to the teeth. The larynx is somewhat higher than with U (00). The entire reinforcing tube is, therefore, shorter than with U (00). In sounding / (ee), the mouth has the shape of a flask with a small belly in the posterior part, and a long, narrow neck. The belly has the fundamental tone f , while the neck has that of d"". The reinforcing tube is shortest with I (ee), as the larynx is raised as far as possible, and SPEKCir. THE VOWELS. 613 the mouth is bounded anteriorly by the teeth, the hps being retracted. The oral canal between the hard palate and the back of the tongue is greatlv constricted to a median, narrow channel. Hence, the air can pass through onlv with a clear, whistling sound, and even the vertex of the skull may be set into perceptible vibration; if the ears are stopped up, a shrill sound may be audible in them. It is impossible to pro- nounce I (ee) when the larynx is depressed and also when the lips are protruded, as for U(oo). In pronouncing E (a), which stands next to I (ee), the cavity has likewise the form of a flask with a small belly (fundamental tone f) and a long, narrow neck (fundamental tone b'"). The neck, however, is wider, so that it does not give rise to a whistling sound. The larynx is somewhat lower for E (a) than for I (ee), but higher than for A (ah). Fundamentally, Briicke is right in assuming that there are only three funda- mental vowels, namely / (ee), A (ah), U (00), between which the others, as well as the so-called diphthongs, are interpolated. The hieroglyphic, Indian, old Hebraic, and Gothic writings contain only these three vowels. '^:\' Fig. 218. — Sagittal Section through the Human Larynx in the Vowel-positions A (ah), I (ee) and U (oo) : Z, tongue; />, soft palate; e, epiglottis; g, glottis; /j, hyoid bone; i, thyroid cartilage; 2, 3, cricoid cartilage; 4, arytenoid cartilage. Diphthongs occur during the utterance of a sound, by passing from the position of one vowel into that of another. Distinct diphthongs are sounded only on passing from a vowel with a wider oral opening to one with a narrower opening; if the reverse occurs, the vowels appear separated to the ears. Landois was especially successful in producing the vowels artificially. In the two halves of a head sawn through in a sagittal plane he arranged all of the parts in the positions that they would have to assume in enunciating a certain vowel, and then the entire space from the trachea to the lips was filled with paraffin. Both halves were then welded together. A paraffin cast was thus obtained of the vowel-cavity. The cast was covered with plaster-of- Paris, and then the paraffin was removed by melting. In this way a plaster reproduction of the vowel-cavity was obtained. A vocal apparatus was then introduced into the trachea from below. This apparatus was made of a thin, ivory reed, set in a wide frame, and having its pitch accurately adjusted to the fundamental tone of the plaster cavity. All the vowels, even I (ee), were thus produced with sur- prising success. In addition to the pitch the characteristic timbre, or tone-color, of the vowel is worthy of notice. In this connection the mouth, charac- teristically shaped for the utterance of a vowel, may be compared to a 6l4 SPEECH. THE VOWELS. musical instrument, which not only gives forth its sound in a certain pitch, but also allows it to ring with a characteristic timbre. Thus, the vowel-sound U (oo), when whispered, has, besides its fundamental tone b, a soft, whistHng timbre; I (ee), with its fundamental tone b"", a hissing, whistling timbre; A, with its tone b", an open, blowing timbre. This timbre depends upon the nuinber and the pitch of the overtones peculiar to the vowel- sound, which are considered in the section on analysis of the vowels (auditory apparatus, p. 905). The timbre of the vowels may, further, be modified in a special manner when they are uttered with a "nasal" twang, as is prevalent in the French language. The nasal timbre is produced when the soft palate does iiot close off the nasal cavity, as happens during utterance of the pure vowels, so that the air in the nasal cavity is set into sym- pathetic vibration. When a vowel is spoken with a nasal timbre, the air thus escapes through both the mouth and the nose ; when the vowel is spoken purely, the air escapes only through the mouth. Hence, in the former case, a light held in front of the nostrils will flicker, or a cold glass or metal will be moistened; but not in the latter case. In closure of the nasal cavity the soft palate is raised, in smallest measure when A (ah) is pronounced; then follow O, E (a), U (00), I (ee). High and loud tones require more marked elevation, during which the velum presents a notch in the situation of the elevators of the palate. The opening of the Eusta- chian tube is constricted, but never entirely closed, by the elevation of the palate. In uttering the pure, non-nasal vowels, the nasal cavity is so firmly closed off from the mouth that it can be sprung open only b}'^ an artificial increase in the pressure within the nose of from 30 to 100 mm. of inercury, with the develop- ment of a gurgling rhonchal sound. The nasal twang occurs as a result of resonance in the naso-pharyngeal cavity; at the same time a portion of the cavity of the mouth is excluded by elevation of the dorsum of the tongue and depression of the palate. Especially the vowels a (ah), a (se), 6 (oe), o, e (a), are employed with a nasal accent. The nasal i (ee), however, does not appear to occur in any language. At all events it is hard to form, because in sounding it the oral canal is so narrow that if the nasal cavity be open at the same time the air will escape almost completely through the latter, while the small amount passing through the mouth is hardly sufficient to produce a sound. In pronouncing the vowels it should also be observed whether they are uttered through a previously closed glottis, as is the case in German with all vowels placed at the beginning of words. Thus, the glottis is at first closed, but it is sprung open simultaneously with the intona- tion at the moment of commencing the word. Pronunciation of vowels in this manner was termed by the Greeks spiritus lenis. If, however, the vowel is pronounced after a preliminary breath has passed through the open glottis, and the sound of the vowel follows immediately, then the aspirate vowel results, corresponding to the spiritus asper of the Greeks. If the vowels are pronounced audibly, therefore with a simultaneous sound of the voice, the fundamental tone of the vowel-cavity, with its constant, absolute pitch, strengthens in a characteristic manner the corresponding partial tone present in the sound of the voice. Accord- ingly, the vowels are intonated most purely from a musical point of view when the pitch of the tone is so adjusted as to contain overtones THE CONSONANTS. 615 that correspond harmonically with the fundamental tone of the vowel- cavity when blown upon. THE CONSONANTS. The consonants are noises that are generated at certain parts of the reinforcing tube. They are classified as follows: I. According to their acoustic properties into (r) sounding or liquid consonants, that is those that are audible even without vowels (m, n, I, r, s); (2) mutes, including all the rest, which cannot be distinctly heard without the simultaneous ^pronunciation of a vowel. II. According to the mechan- ism of their formation, as well as the parts of the speech-apparatus by which they are produced. 1. Mutes, stops, checks, or explosives, the air being forced through an existing closure, with the production of more or less noise; or, con- versely, the current of air may be suddenly interrupted, while at the same time the nasal cavity is closed off by elevation of the soft palate. 2. Fricatives or spirants or sibilants , the canal being constricted at one point, so that the air is forced through with a hissing noise, while the nasal cavity is closed off. L and similar consonants are closely related to the fricatives, differ- ing, however, from these in that the narrow passage through which the air is forced is not situated in the middle line, but to either side of the closed middle. The nasal cavity is closed off. 3. Vihratives, which result when air is forced through a narrow part of the canal, so that the margins of the constriction are thrown into vibra- tion. The nasal cavity is closed off. 4. Resonants, also designated nasals or semi-vowels. The nasal cavity is entirely open, but the mouth is tightly closed anteriorly at one point. In accordance with the position of this closure of the mouth, the air in a larger or smaller portion of the oral cavity may be set into sympathetic vibration. In addition to these possible forms of origin of the sounds the points at which they may be produced must be taken into consideration. These points m.a.Y he designoXed articulation-positions . They are: A, between the lips; B, between the tongue and the hard palate; C, between the tongue and the soft palate; D, between both true vocal bands. (A) Consonants of the First Articulation-position. 1. Explosive Labials. — b (bay): the voice is sounded before the soft explosion occurs; p (pay): the voice is sounded only after the much stronger explosion has taken place. 2. Fricative Labials. — /: between the upper incisor teeth and the lower lip (labio-dental) ; it is absent from all true Slavic words ; v (fow) : between the two lips (labial) ; w (vay) : results when the mouth is adjusted as for / (labial, as well as labio-dental), but instead of merely blowing air out, the voice is also sounded. There are really two different forms of w (vay), namely, one corresponding to the labial /, as in Wiirde (pronounced veerde), and the labio-dental, as in Quelle (pronounced kwelle). 3. Vibrative Labials. — The "burring" sound of drivers, not employed in civilized languages. 4. Resonant Labial. — ni is formed when the voice is sounded, and the air in the oral and nasal cavities is thrown into resonance. 6l6 THE COXSOXANTS. (B) Consonants of the Second Articnlaiio)i-position. Method. — In order to determine the extent to which the tongue and the palate are in contact in the formation of consonants in the second and third articu- lation positions, the tongue is sprinkled with a powdered dye. while the mouth is held wide open. When the consonant is formed, the palate receives a colored impres- sion at those points where contact has taken place. Also in the case of the con- sonants, with the exception of m, n, ng, the soft palate is elevated. r. The explosives, which are produced between the tongue and the hard roof of the oral cavity, are the hard 7"-sounds (also dt and //), when enunciated sharply and without the voice; the soft D-sounds when uttered softly with simultaneous intonation of the voice. Vari- ously designated and uttered modifications of these consonants occur in various languages, accordingly as the tip or the back of the tongue, on the one hand, and the teeth or the alveolar process or the hard palate, on the other hand, are employed in their formation. 2. The fricatives embrace the consonants allied to 5, including the sharp s (also written .?5 and sz), which is produced without the sound of the voice, and the soft s, which can be produced only with intonation of the voice. Modifications occur also here, in accordance with the regions between which the aspirate consonant is formed. Thus, to the sharp aspirates belong also the sharp Sch and the hard English Th; to the soft aspirates the soft French J and the soft English Th. The sound L likewise belongs to this class, occurring in manifold modifications in various tongues, for example the soft L of the French. The sound L may also be uttered softly with the voice, or sharply without it. 3. The vibratives of the second articulation -position, or the lingual 7\^-sounds, are usually enunciated with the sound of the voice, although they may also be formed without it. 4. The resonants are the A'-sounds, which likewise may occur in various modifications. (C) Consonants of the Third Articulation-position. 1. The explosives are the /v -sounds, if hard and without the sound of the voice; or the G'-sounds (gay), if the voice is also given. There are various modifications of both; for example, the explosive position of G (gay) and K preceding e (a) and i (ee) is situated farther forward on the palate than that of G (gay) and K before a (ah), o, u (00). 2. The aspirates of these positions are the C/^-sounds, hard and with- out the voice; and J (y), if soft and without the voice. Following a (ah), o, u (00), these consonants are formed farther back on the palate than those that follow e (a) and i (eej. 3. The vibrative is the palatal R, which results from vibration of the uvula. 4. The resonant is the palatal A'. After e (aj and i (ee) the closure is displaced further forward, after a (ah), o, u (00), further back. The nasal N of the French is, however, not a consonant at all, but only the nasal timbre of the vowel that results from the patulousness of the nasal cavity. According to Saenger the participation of the nasal cavities in the production of m, n, and ng consists chiefly in affording a passage for the air expired during phonation. PATHOLOGICAL \AKIATIO.\ IN' AOICE AXI) SPRECH. 617 (1)) ( 'oiisonants oj the h'oitrih Articulation-position. Logically, the glottis itself may further be considered as a fourth articulation-position. r An explosive consonant is not produced by forcing open the glottis, if a vowel has been loudly intonated from a previously closed glottis. If this occurs during whispering, a feel)le, short sound may undoubtedly be heard, arising from the sudden opening of the glottis. As already noted, the Greeks applied the term spiritus lenis to the utterance of vowels from a previously closed glottis. 2. The aspirates of the glottis are represented by the //-sound (hah), which is produced with a moderately wide glottis. The Arabic Hha is emitted with especial sharpness from a still narrower glottis. 3. A glottis-vibrative occurs in the so-called laryngeal R of lower Saxony, and in the Arabic Ain. It can be produced by pronouncing a vowel with the deepest possible voice. This is followed by a distinct; shock-like, resounding vibration of the vocal bands, which represents the laryngeal /\. The sound is represented especially in the low German dialect of Hither Pomerania, for example in Coarl (Carl), Wuort (Wort). 4. A laryngeal resonant cannot be produced. The combination of different consonants is accomplished by the rapid, successive execution of the movements necessary for each one. Com- pound consonants are those that are formed by adjusting the parts of the mouth for two different consonants at the same time, so that a mixed sound is formed from the simultaneous production of both sounds. Ex- amples: Sell, tsch, tz, ts, Ps (