DENTAL DEPARTMENT Gift of Major Nathan C. Pickles HAND-BOOK OF PHYSIOLOGY RLDDO-SPECTRA COMPARED WITH SPECTRUM DP ARGANQ- LAMP 1 Spectrum oF Ardand-lamp with FraunhoFers lines in position. 2 Spectrum aF Dxyhsmndlabin in diluted hlaad. 3 Spectrum oF Reduced nsmo^lobin. 4 Spectrum aF Carbonic oxide Hffimo^lobin. 5 Spectrum oF AcidHaEmatm in etherial solution. 6 Spectrum oF Alkaline Heamatin. 7 Spectrum aF CblnrnFarm extract of acidulated Dx-Bile.* 8 Spectrum oF MethaBmoglobin. 9 Spectrom oF HeamDchrornDgBn. 10 Spectrum aF Hsmatoporphyrin. Most of the above Specfm have been drawn from observations byMTWLepraffc F.C.S. KIRKES' HANDBOOK OF PHYSIOLOGY Revised and Rewritten by CHARLES WILSON GREENE, A.M., Ph.D Professor of Physiology and Pharmacology University of Missouri Strtfo Bmerican tRevtston WITH FIVE HUNDRED AND SEVEN ILLUSTRATIONS, INCLUDING MANY IN COLORS NEW YORK WILLIAM WOOD AND COMPANY MDCCCCVII Copyright, 1907 By WILLIAM WOOD AND COMPANY PREFATORY NOTE THE general organization of the Handbook has been retained in the present revision, but the anatomical discussions have been very greatly reduced. The text has been largely rewritten throughout, and many new illustrations of physiological experiments have been intro- duced. An entirely new feature is the introduction, at the end of the chapters, of directions for laboratory work. It is hoped that this will greatly increase the utility of the book both to the teacher and to the student. Acknowledgment is given my colleagues, Dr. C. M. Jack- son for reading the manuscript on the Nervous System, and Miss Caroline McGill for similar criticism of the chapter on the Elementary Structure of the Tissues. CHAS. W. GREENE. COLUMBIA, MISSOURI, October 1, 1907. CONTENTS PAGE CHAPTER I — THE PHENOMENA OF LIFE; Properties of Protoplasm, i Structure of Protoplasm, .... . . CHAPTER II — CELL DIFFERENTIATION AND THE STRUCTURE OF THE ELEMENTARY TISSUES; The Structure of the Cell, The Structure of the Elementary Tissues. I. The Epithelial Tissues. II. The Con- nective Tissues. III. Muscular Tissue. IV. Nervous Tissue, . 17 CHAPTER III— THE CHEMICAL COMPOSITION OF THE BODY; The Nitrogenous Bodies, Classes of Proteids, Oils and Fats, Carbohy- drates, Inorganic Principles, Laboratory Experiments, . . .78 CHAPTER IV— THE BLOOD; Quantity of the Blood, Coagulation of the Blood, Morphology of the Blood, Chemical Composition of the Blood, Globulocidal and Other Properties of Serum, The Character and Composition of Lymph, Laboratory Experiments, .... 101 CHAPTER V — THE CIRCULATION OF THE BLOOD; Anatomical Con- siderations, The Action of the Heart, The Regulative Influence of the Central Nervous System, The Circulation through the Blood- Ves- sels, The Pulse, The Peripheral Regulation of the Flow of Blood, Vaso-constrictor and Vaso-dilator Nerves for Individual Organs, Laboratory Experiments, . .141 CHAPTER VI— RESPIRATION; The Respiratory Apparatus, The Move- ments of the Respiratory Mechanism, Respiratory Changes in the Air Breathed, The Respiratory Changes in the Blood, The Nervous Regulation of the Respiratory Apparatus, The Effect of Respira- tion on the Circulation, Laboratory Experiments in Respiration, . 243 CHAPTER VII— SECRETION IN GENERAL; Organs and Tissues of Secre- tion, Secreting Glands, The Process of Secretion. Influence of the Nervous System on Secretion, . . . . . . . . 291 v vi CONTENTS PAGE CHAPTER VIII — Fooi> AND DIGESTION; Food and Food Principles, The Process of Digestion, Digestion in the Mouth, Deglutition, Ner- vous Mechanism of Deglutition, Digestion in the Stomach, Move- ments of the Stomach, Digestion in the Intestines, Movements of the Intestines, Laboratory Experiments in Digestion, Saliva and Sali- vary Digestion, Gastric Juice and Gastric Digestion, Pancreatic Juice and Pancreatic Digestion, . -297 CHAPTER IX — ABSORPTION; Absorption in the Stomach, Absorption in the Intestines, Absorption from the Skin, the Lungs, etc., . . .361 CHAPTER X— EXCRETION; Structure and Function of the Kidneys, General Structure, The Urine, The Method of Excretion of Urine, The Discharge of the Urine, The Structure and Excretory Func- tions of the Skin, Laboratory Experiments in Excretion, . . -371 CHAPTER XI — METABOLISM, NUTRITION, AND DIET; Metabolism of Proteids, The Metabolism of Fats, The Metabolism of Carbohy- drates, Requisites of a Normal Diet, The Influence of the Ductless Glands on Metabolism, ......... 405 CHAPTER XII — ANIMAL HEAT; Heat-producing Organs, Variation in the Loss of Heat, Variation in the Production of Heat, Influence of the Nervous System on Heat Production, 433 CHAPTER XIII— MUSCLE-NERVE PHYSIOLOGY; Chemical Composi- tion of Muscle, The Properties of Living Muscle, Single Muscle Con- tractions, Conditions which Affect the Irritability of the Muscle and the Character of the Contraction, Tetanic and Voluntary Muscular Contractions, The Type of Contraction in Involuntary Muscle and in Cilia, The Function of Nerve Fiber, Some Special Coordinated Motor Activities, Locomotion, The Production of the Voice, Laboratory Experiments on Muscle and Nerves, . . 440 CHAPTER XIV— THE NERVOUS SYSTEM; I. Function of the Nerve Cell. II. The Structure and Function of the Spinal Cord, The Ar- rangement of Nerve Cells in the Spinal Cord, Columns and Tracts in the White Matter of the Spinal Cord, The Reflex Arc and Reflex Action, Spinal Reflexes in Man and Mammals. III. The Brain Stem, The Medulla Oblongata or Bulb, The Pons Varolii, The Mid- brain, The Optic Thalami, The Cranial Nerves. IV. The Cere- bellum. V. The Cerebrum, Structure of the Cerebral Cortex, Gen- eral Functions of the Cerebrum, Localization of the Motor Function of the Cerebral Cortex, Localization of Sensory Function in the Cere- bral Cortex, Association Centers of the Cerebral Cortex, The Physiol- ogy of Sleep. VI. The Sympathetic System, . .... 503 CONTENTS Vll PAGE CHAPTER XV— THE SENSES; I. The Senses of Touch, Pain, Tem- perature, and the Muscle Sense. II. Taste and Smell, The Sense of Taste, The Sense of Smell. III. Hearing and Equilibration, The Anatomy of the Ear, The Physiology of Hearing, The Sense of Equi- librium. IV. The Sense of Sight, The Eye, The Optical Apparatus, Accommodation, Defects in the Optical Apparatus, Visual Sensa- tions from Excitation of the Retina, Color Sensations, Binocular Vision, Visual Judgments, Laboratory Directions for Experiments on the Sense Organs, ......... 595 CHAPTER XVI— THE REPRODUCTIVE ORGANS; The Reproductive Organs of the Male, The Reproductive Organs of the Female, Ovu- lation and Menstruation, Menstrual Life, 679 CHAPTER XVII— DEVELOPMENT; Changes which Occur in the Ovum Prior to Impregnation, Changes Following Impregnation, Circula- tion of Blood in the Fetus, Parturition, Lactation, . , . .691 INDEX, 701 FAHRENHEIT and CENTIGRADE SCALES. MEASUR FRENCH IN: LENGTH. 1 metre 1 10 decimetres I = 39.37 English 100 centimetres f inches. EMENTS. CO ENGLISH. A grain equals about 1.16 gram., a Troy oz. about 31 gram., a Ib. Avoirdupois about £$ Kilogrm., and 1 cwt. about 50 Kilogrms. F. 500° 401 392 383 374 356 347 338 329 320 311 302 • 284 275 266 248 239 230 212 203 194 176 167 140 122 113 105 104 100 C. 260° 205 200 195 1,000 millimetres J (or 1 yd. and 3^ in.) CAPACITY. 1,000 cubic decimetres ) = 1 cubic 1,000,000 cubic centimetres f metre. 190 180 175 170 1 decimetre ) 10 centimetres V = 3.937 inches 100 millimetres ) (or nearly 4 inches.) 1 cubic decimetre j 365 160 155 150 140 185 130 120 115 110 100 95 90 80 75 60 50 45 40.54 40 37.8 1 centimetre ) = .3937 or about 10 millimetres j (nearly g inch.) 1 millimetre = nearly fa inch. OR, ONE METRE = 39.37079 inches. (It is the ten-millionth part of a quarter of the meridian of the earth.) 1 Decimetre = 4 in. 1 Centimetre = A in. 1 Millimetre = «ft in. D6cametre = b2.80 feet. Hectometre — 109.36 yds. Kilometre = 0.62 miles. One inch = 2.539 Centimetres. One foot = 3.047 Decimetres. or V = 1 litre. 1,000 cubic centimetres \ OR ONE LITRE = 1 pt. 15 oz. 1 dr. 40. (For simplicity, Litre is used to signify 1 cubic decimetre, a little less than 1 English quart.) Decilitre (100 c.c.) = 3^ oz. Centilitre (10 c.c.) = 2f dr. Millilitre (1 c.c.) = 17 m. Decalitre ' = 24 gal. Hectolitre = 22 gals. Kilolitre (cubic metre) = 27J^ bushels. A cubic inch = 16.38 c.c. ; a cubic foot = 28.315 cubic dec., and a gallon = 4.54 litres. One mile = 1.60 Kilometre. The cubic centimetre (15.432 grains— 1 gramme) is a standard at 4° C., the grain at 16°. 66 C. CONVERSION SCALE. To convert GRAMMES to OUNCES avoir- dupois, multiply by 20 and divide by 567. To convert KILOGRAMMES to POUNDS, multiply by 1,000 and divide by 454. To convert LITRES to GALLONS, mul- tiply by 22 and divide by 100. To convert LITRES to PINTS, multiply by 88 and divide by 50. To convert MILLIMETRES to INCHES, multiply by 10 and divide by 254. To convert METRES to YARDS, multi- ply by 70 and divide by 64. 98.5 95 86 77 68 50 41 32 23 14 + 5 - 4 -13 -22 -40 -76 36.9 qe 30 25 20 10 5 0 - 5 -10 WEIGHT. (One gramme is the weight of a cubic centimetre of water at 4° C. at Paris). 1 gramme "j 10 decigrammes I = 15.432349 grs. 100 centigrammes j (or nearly 15^). 1,000 milligrammes j SURFACE MEASURE. 1 square metre = about 1550 sq. inches. Or 10.000 sq. centimetres, or 10.75 sq. ft. 1 sq. inch — about 6 4 sq. centimetres. 1 sq. foot - " 930 " - 20 -25 -30 -40 -60 1 d6cigramme ) 10 centigrammes V = rather more 100 milligrammes ) than 1J^ grain. 1 centigramme ) — rather more 1 deg F — 54°C 10 decigrammes f than 5% grain. ENERGY MEASURE. 1 kilogrammetre=about7.24ft. pounds. 1 foot pound = " .1381 kgm. 1 foot ton = " 810 kgm. 1.8 " = 1°C. 3.6 " = 2°0. 4.5 " -.= 2.5°C. 5.4 " = 3°C. 1 milligramme = rather more than 5&y grain. OR To convert de- grees F. into de- grees C., subtract 32, and multiply byi- 1 Decigramme — 2 dr. 34 gr. 1 Hectogrm. = 3^ oz. (Avoir.) 1 Kilogrm. = 2 Ib. 3 oz. 2 dr. (Avoir.) HEAT EQUIVALENT. 1 kilocalorie = 424 kilogrammetres. ENGLISH : Apothecaries Weight. 7000 grains = 1 Ib. Or 437.5 grains = 1 oz. MEASURES. Avoirdupois Weight. 16 drams = 1 oz. 16 oz. = 1 Ib. 28 Ibs. =-• 1 quarter. 4 quarters = 1 cwt. 20 cwt. = 1 ton. To convert de- grees C. into de- grees F., multiply by f , and add 32°. Measure of 1 decimetre, or 10 centimetres, or 100 millimetres. 1234 567 The micron (symbol, M.) is the unit of microscopic measurement 8 9 Ifl mm. = nfov inch. HANDBOOK OF PHYSIOLOGY CHAPTER I THE PHENOMENA OF LIFE PHYSIOLOGY is the science which treats of the various processes or changes which take place in the organs and tissues of the body during life. These processes, however, must not be considered as by any means peculiar to the human organism, since, putting aside the properties which serve to distinguish man from other animals, the changes which go on in the tissues of man go on in much the same way in the tissues of all other animals as long as they live. Furthermore it is found that similar changes proceed in all living vegetable tissues; they indeed constitute what are called vital phenomena, and are those properties which mark out living from non-living material. The lowest types of life, whether animal or vegetable, are found to consist of minute masses of a jelly-like substance, which is generally known under the name of protoplasm. Each such living mass is called a cell, so that these minute elementary organisms are designated unicellular. Not only is it true that the lowest types of life are made up of cells, but it has also been shown that the tissues of which the most complex organisms are composed consist of cells. The phenomena of life are exhibited in cells, whether existing alone or de- veloped into 'he organs and tissues of animals and plants. It must be at once evident that a correct knowledge of the nature and activities of the cell forms the very foundation of physiology; cells being, in fact, physiological no less than morphological units. The prime importance of the cell as an element of structure was first established by the researches of the botanist Schleiden, and his conclusions, drawn from the study of vegetable histology, were at once extended by Theo- dor Schwann to the animal kingdom. The earlier observers defined a cell as a more or less spherical body limited by a membrane, and containing a smaller body termed a nucleus, which in its turn incloses one or more still smaller bodies or nudeoli. Such a" definition applied admirably to most veg- etable cells, but the more extended investigation of animal tissues soon showed that in many cases no limiting membrane or cell-wall could be demonstrated. The presence or absence of a cell-wall, therefore, was then regarded as quite a secondary matter, while at the same time the cell-substance came 1 1 THE PHENOMENA OF LIFE — ... Space contain- ing liquid. Protoplasm. Nucleus. Cell wall. FIG. i.— Vegetable Cells. gradually to be recognized as of primary importance. Many of the lower forms of animal life, the Rhizopoda, were found to consist almost entirely of matter very similar in appearance and chemical composition to the cell- substance of higher forms; and this from its chemical resemblance to flesh was termed Sarcode by Dujardin. When recognized in vegetable cells it was called Protoplasm by Mulder, while Remak applied the same name to the substance of animal cells. As the presumed formative matter in animal tissues it was termed Blastema, and in the be- lief that, wherever found, it alone of all sub- stances has to do with generation and nutrition, Beale has named it Germinal matter or Bio- plasm. Of these terms the one most in use at the present day, as we have already said, is protoplasm, and inasmuch as all life, both in the animal and vegetable kingdoms, is associated with protoplasm, we are justified in describing it, with Huxley, as the "physical basis of life," or simply "living matter." Properties of Protoplasm. Protoplasm is a semi-fluid substance, which absorbs but does not mix with water. It is transparent and generally colorless, with refractive index higher than that of water but lower than that of oil. It is neutral or weakly alkaline in reaction, but may under special circumstances be acid, as, for example, after activity. It undergoes heat-coagulation at a temperature of about 54.5° C. (130° F.), and hence no organism can live when its own temperature is raised above that point. It is also coagulated and therefore killed by alcohol, by solutions of many of the metallic salts, by strong acids and alkalies, and by many other chemical substances. Under the microscope it is seen almost universally to be granular, the granules consisting of different mibstanre<; albii- FIG. 2. — Semidiagrammatic Representation of a Human .CS, 1DU Ovum, showing the parts of an animal cell. (Cadia.) minous, fatty, or carbohydrate matter. The granules are not equally distributed throughout the whole cell-mass, as they are sometimes absent from the outer part or layer, and very numerous in the interior. In addition to granules, protoplasm generally exhibits spaces or vacuoles, usually globular in shape, except- ing during movement, when they may be irregular, and filled with a watery ger- minal vesicle. L Nucleolus or ger- minal spot. Space left by re- traction of yolk. ... Vitellus or yolk. Vitelline mem- brane. CHARACTERISTICS OF PROTOPLASM 3 fluid. These vacuoles are more numerous and pronounced in vegetable than in animal cells. Gas bubbles also sometimes exist in cells. It is impossible to make any definite statement as to the exact chemical composition of living protoplasm, since the methods of chemical analysis necessarily imply the death of the cell; it is, however, stated that protoplasm contains 75 to 85 per cent of water, and of the 15 to 25 per cent of solids the most important part belongs to the class of substances called proteids or al- bumins. Proteids contain the chemical elements carbon, hydrogen, nitrogen, oxygen, sulphur, and phosphorus, the last two in very small quantities only. A proteid-like substance, nuclein, found in the nuclei of cells, contains phos- phorus in greater abundance. In the cell nucleus a compound of nuclein with proteid, called nucleoproteid, forms the most abundant proteid sub- stance. Other bodies are frequently found associated with the proteids, such FIG. 3. — Phases of Ameboid Movement. as glycogen, starch, cellulose, which contain the elements carbon, hydrogen, and oxygen, the last two in the proportion to form water, and hence are termed carbohydrates; fatty bodies, containing carbon, hydrogen, and oxygen, but not in proportion to form water; lecithin, a complicated fatty body containing phosphorus; cholesterin, a monatomic alcohol; chlorophyll, the coloring matter of plants; inorganic salts, particularly the chlorides and phosphates of calcium, sodium, and potassium; ferments, and other substances. The Physiological Characteristics of Protoplasm. The properties of protoplasm may be well studied in the microscopic animal called the ameba, a unicellular organism found chiefly in fresh water. These properties may be conveniently studied under the following heads: — The Power of Spontaneous Movement. When an ameba is observed with a high power of the microscope, it is found to consist of an irregular mass of protoplasm containing one or more nuclei, the protoplasm itself being more or less granular and vacuolated. If watched for a minute or two, an irregular projection is seen to be gradually thrust out from the main body; other masses are then protruded until gradually the whole protoplasmic sub- stance is, as it were, drawn over to a new position, and when this is repeated several times we have locomotion in a definite direction, together with a con- tinual change of form. These movements, figure 3, when observed in other cells, such as the colorless blood-corpuscles of higher animals, in the branched corneal cells of the frog and elsewhere, are termed ameboid. 4 THE PHENOMENA OF LIFE The remarkable movement of pigment granules observed in the branched pigment cells of the frog's skin by Lister are also probably due to ameboid movement. These granules are seen at one time distributed uniformly through the body and branched processes of the cell, while at another time they collect in the central mass leaving the branches quite colorless. This movement within the pigment cells might also be considered an ex- ample of the so-called streaming movement not infrequently seen in certain of the protozoa, in which the mass of protoplasm extends long and fine pro- cesses, themselves very little movable, but upon the surface of which freely moving or streaming granules are seen. A gliding movement has also been noticed in certain animal cells; the motile part of the cell being composed of protoplasm bounding a central and more compact mass. By means of the free movement of this layer, the cell may be observed to move along. In vegetable cells the protoplasmic movement can be well seen in the hairs of the stinging-nettle and Tradescantia and in the cells of Vallisneria and Chara; it is marked by the movement of the granules nearly always embedded in it. For example, if part of a hair of Tradescantia, figure 5, be viewed under a high magnifying power, streams of protoplasm containing crowds of FIG. 4. — Changes of Form of a White Corpuscle, Sketched at Brief Intervals, show also the ingestion of two small granules. (Schafer.) The figures granules hurrying along, like the foot-passengers in a busy street, are seen flow- ing steadily in definite directions, some coursing round the film which lines the interior of the cell-wall, and others flowing toward or away from the irregu- lar mass in the center of the cell-cavity. Many of these streams of protoplasm run together into larger ones and are lost in the central mass, and thus ceaseless variations of form are produced. The movement of the protoplasmic granule? to or from the periphery is sometimes called vegetable circulation, whereas the movement of the protoplasm round the interior of the cell is called rotation. The first account of the movement of protoplasm was given by Rosel in I755> as occurring in a small Proteus, probably a large fresh-water ameba. His description was followed twenty years later by Corti's demonstration of the rotation of the cell sap in characeae, and in the earlier part of the century CHARACTERISTICS OF PROTOPLASM 5 by Meyer in Vallisneria, 1827; Robert Brown, 1831, in "Staminal Hairs of Tradescantia." Then came Dujardin's description of the granular streaming in the pseudopodia of Rhizopods and movements in other cells of animal protoplasm (Planarian eggs, von Siebold, 1841; colorless blood-corpuscles, Wharton Jones, 1846). The Power of Response to Stimuli, or Irritability. Although the movements of the ameba have been described above as spontaneous, yet they may be in- creased under the action of external agencies which excite them and are there- fore called stimuli, and if the movement has ceased for the time, as is the case if the temperature is lowered beyond a certain point, movement may be set up by raising the temperature. Contact with foreign bodies, gentle pressure, cer- FIG. 5. — Cell of Tradescantia Drawn at Successive Intervals of two Minutes. — The cell- contents consist of a central mass connected by many irregular processes to a peripheral film, the whole forming a vacuolated mass of protoplasm, which is continually changing its shape. (Schofield.) tain salts, and electricity produce or increase the movement in the ameba. The protoplasm is, therefore, sensitive or irritable to stimuli, and shows its irri- tability by movement or contraction of its mass. The effects of some of these stimuli may be thus further detailed: — a. Changes of Temperature. Moderate heat acts as a stimulant; the move- ment stops below o° C. (32° F. ), and above 40° C. (104° F.); between these two points the movements increase in activity; the optimum temperature is about 37° to 38° C. Exposure to a temperature even below o° C. stops the movement of protoplasm, but does not prevent its reappearance if the tem- perature is raised; on the other hand, prolonged exposure to a temperature of over 40° C. kills the protoplasm and causes it to enter into a condition of coagulation or heat rigor. b. Mechanical Stimuli. When gently squeezed between a cover and object-glass under proper conditions, a colorless blood-corpuscle contracts and ceases its ameboid movement. c. Nerve Influence. By stimulation of the nerves of the frog's cornea, contraction of certain of its branched cells has been produced. d. Chemical Stimuli. Water generally stops ameboid movement, and by imbibition causes great swelling and finally bursting of the cells. In some cases, however (myxomycetes), protoplasm can be almost entirely dried up, but remains capable of renewing its movements when again moistened. THE PHENOMENA OF LIFE Dilute salt-solution and many dilute acids and alkalies stimulate the move- ments temporarily. Strong acids or alkalies permanently stop the movements; ether, chloroform, veratrium, and quinine also stop it for a time. Movement is suspended in an atmosphere of hydrogen or carbonic acid and resumed on the admission of air or oxygen, but complete withdrawal of oxygen will after a time kill the protoplasm. e. Electrical. Weak currents stimulate movement, while strong currents cause the cells to assume a spherical form and to become motionless. The Power of Digestion, Respiration, and Nutrition. This consists in the power which is possessed by the ameba and similar animal cells of taking in food, modifying it, building up tissue by assimilating it, and rejecting what is not assimilated. These various processes are effected in some one-celled ani- mals by the protoplasm simply flowing around and enclosing within itself minute organisms such as diatoms and the like. From these it extracts what it requires, and then rejects or excretes the remainder, which has never formed part of the body. This latter proceeding is done by the cell withdrawing itself from the material to be excreted. The assimilation constantly taking place in the body of the ameba is for the pur- pose of replacing waste of its tissue consequent upon manifestation of energy. The respiratory process of absorbing oxygen goes on at the same time. The processes which take place in cells, both animal and vegetable, are summed up under the term metabolism (from peTafioty, change). The changes which go on are of two kinds, viz., assimilation, or building up, and disassimilation, or breaking down ; they may be also called, using the nomenclature of Gas- kell, anabolism or constructive metabolism, and catabolism or destructive metabolism. In the direction of anabolism two processes occur, viz., the building up of materials which it takes in, and secondly, the building up of its own substance by those or other materials. As we shall see in a subsequent paragraph, the process of anabolism differs to some ex- tent in vegetable and animal cells. The catab- olism of the cell consists in chemical changes which occur in the cell- substance itself, or in substances in contact with it. The destructive metabolism of a cell is increased by its activity, but goes on also during quiescence. It is probably of the nature of oxidation, and re- sults in the evolution of carbon dioxide and water on the one hand, and in the FIG. 6. — Cells from the Staminal Hairs of Tradescantia. A, Fresh in water; B, the same cell after slight electrical stimulation; a, b, region stimulation; c, d, clumps and knobs of contracted proto- plasm. (KUhne.) CHARACTERISTICS OF PROTOPLASM 7 formation of various more complex chemical substances on the other, some of which may be stored up in the cell for future use, and are called secretions, and others, like carbon dioxide, for example, and bodies containing nitrogen, are eliminated as excretions. The Power of Growth. In protoplasm it is seen that the two processes of waste and repair go on side by side, and so long as they are equal the size of the animal remains stationary. If, however, the building up exceed the waste, then the animal grows; if the waste exceed the repair, the animal FIG. 7. — Diagram of an Ovum (a) Undergoing Segmentation. In (6) it has divided into two. in (c) into four; and in (d) the process has ended in the production of the so-called "mulberry mass." (Frey.) decays; and if decay go on beyond a certain point, life becomes impossible, and the animal dies. The power of increasing in size, although essential to our idea of life, is not, it must be recollected, confined to living beings. A crystal of common salt, for example, if placed under appropriate conditions for obtaining fresh mate- rial, will increase in size in a fashion as definitely characteristic and as easily to be foretold as that of a living creature; but the growth of a crystal takes place merely by additions to its outside; the new matter is laid on particle by particle, and layer by layer, and, when once laid on, it remains unchanged. In a living structure, where growth occurs, it is by addition of new matter, not to the surface only, but throughout every part of the mass, and this matter be- comes an intimate part of the living substance. The Power of Reproduction. The ameba, to return to our former illus- tration, when the growth of its protoplasm has reached a certain point, mani- fests the power of reproduction, by splitting up into (or in some other way pro- ducing) two or more parts, each of which is capable of independent existence. The new amebae manifest the same properties as the parent, perform the same functions, grow and reproduce in their turn. This cycle of life is being con- tinually passed through. In more complicated structures than the ameba, the life of individual protoplasmic cells is probably very short in comparison with that of the organ- ism they compose ; and their constant decay and death necessitate constant re- production. The mode in which this takes place has long been the subject of controversy. It is now very generally believed that every cell is descended from some pre-existing mother cell. This derivation of cells from cells takes place by gemmation, which essentially consists in the budding off and separation of a portion of the parent cell; or by fission or division. 8 THE PHENOMENA OF LIFE The exact manner of the division of cells is a matter of some difficulty, and will not be described until the subject of the structure of protoplasmic cells has been considered. STRUCTURE OF PROTOPLASM. Elemental Structure. Protoplasm was formerly thought to be homogeneous. It is now generally found to consist of the elemental divisions called cells. Each cell, from a morphological point of vi consists of dif- ferentiated parts, the most constant of which are the cell nucleus and the cell cytoplasm. The cytoplasm is differentiated further into two substances, spongioplasm and hyaloplasm. The spongioplasm or reticulum forms a fine network, increases in relative amount as the cell grows older, and has an affinity for staining reagents. The hyaloplasm is less refractile, elastic, or extensile, and has little or no affinity for stains; it predominates in young cells Cell membrane — Cell reticulum .... Membrane of nucleus. Achromatic substance of nucleus. Chromatic substance of nucleus. PlO. 8. — Cell with its Ketiailum Disposal K;u!i;illv; fn.ni Mir intrst.innl epithelium of n worm. (Carnoy.) is thought to be fluid, and fills the interspaces of the reticulum. The nodal points of the reticulum, with the granular microsomes, found in the proto- plasm, cause the granular appearance. The arrangement of the reticulum varies considerably in different cells, and even in different parts of the same cell. Sometimes, for example, figure 8, the. meshwork has an elongated radial arrangement from the nucleus; at others, the meshwork is more evenly disposed, as in figure 9. At the junctions of the fibrils there are usually slight enlargements or nodes. In some cells, particularly in plants, but also in some animal cells, there is a tendency toward a formation of a firmer external envelope, constituting in vegetable cells a membrane distinct from the more central and more fluid part of the protoplasm. In such cases the reticulum at the periphery of the cell is made up of very fine meshes. The membrane when formed is usually pierced with pores by which fluid may pass in, or through which protrusion of the protoplasmic filaments forming the cell's connection with other cells surround- ing it may take place. STRUCTURE OF PROTOPLASM 9 Tl is an exceedingly interesting question whether in cells the one part of the protoplasm ran exist \vithout the other. Schafer summarizes the matter thus: "There are cells, anil unirellular organisms both animal and vegetable, in which no reticular structure can be made out, and these may be formed of hyaloplasm alone. In that ease, this must be looked upon as the essential part of protoplasm. So far as ameboid phenomena are concerned it is cer- tainly so; but whether the chemical changes which occur in many cells are effected by this or by spongioplasm is another matter." The Cell Nucleus. All cells at some period of their existence pos- sess nuclei. The origin of a nucleus in a cell is the first trace of the differentia- tion of protoplasm. The existence of nuclei was first pointed out in the l-'ii; o. — A: The IVI.M -U-ss \M,\\\ Corpuscle, Showing the Intracellular Network, and two nuclei with intranuclear network. B; Colored blood-corpuscle of newt showing the intracellular m-t \\ork ot fibrils. Also oval nucleus composed of limiting membrane and fine intranuclear net- \\IM-W ot fibrils. X 800. (Klein and Noble Smith.) Near iS^; by Robert Brown, who observed them in vegetable cells. They are either small transparent vesicular bodies containing one or more smaller parti- cles called nucleoli, always when in the resting condition bounded by a well- defined envelope. In their relation to the life of the cell they are certainly hardly second in importance to the cytoplasm itself, and thus Beale is fully justified in comprising both under the term "germinal matter." They con- trol the nutrition of the cell, and probably initiate the process of subdivision. If a cell be mechanically divided, that portion not containing the nucleus dies. Uistologists have long recognized certain important characters of nuclei. One is their power of resisting the action of various acids and alkalies, particu- larly acetic acid, by which theiroutlines are more clearly defined, and they are rendered more easily visible. Another is their quality of staining in solu- tions of carmine, hematoxylin, etc. This indicates some chemical difference between the c\ toplasm of the cells and their nuclei, as the former is destroyed by these reagents. Nuclei are most commonly oval or round, and do not necessarily conform to the diverse shapes of the cells; they are altogether less variable elements than cells, even in regard to size, of which fact one may see a good example in the uniformity of the nuclei in cells so multiform as those of epithelium. But sometimes nuclei occupy almost the whole of the cell, as in the lymph corpuscles 10 THE PHENOMENA OF LIFE of lymphatic glands, and in some small nerve cells. Their position in the cell is very variable. -In many cells, especially where active growth is progressing, two or more nuclei are present. Cell Division and Growth. The division of a cell is preceded by division of its nucleus, which may be either direct or indirect. Direct or simple division, amitosis or akinesis, see figure 10, occurs without any change in the arrangement of the intranuclear network. A constriction develops at the cen- ter of the nucleus, possibly preceded by division of the nucleoli, and gradually divides it into two equal daughter nuclei. A similar constriction of the pro- toplasm of the cell occurs between the daughter nuclei and divides it into two parts. Indirect division, mitosis, or karyokinesis is the usual method, and consists of a series of changes in the arrangement of the intranuclear network, resulting a FIG. 10. — Akinesis, Amitosis, or Direct Cell Division. A, Constriction of nucleus; B, division of nucleus and constriction of cell body; C, daughter nuclei still connected by a thread, division being delayed; D, division of cell body nearly complete. (After Arnold.) in the exact division of the chromatic fibers into two parts, which form the chromoplasm of the daughter nuclei. The changes follow a closely similar course in both plant and animal cells. Differences between Animals and Plants. Having considered at some length the vital properties of protoplasm, as shown in cells of animal as well as of vegetable organisms, we are now in a position to discuss the ques- tion of the differences between plants and animals. It might at the outset of our inquiry have seemed an unnecessary thing to recount the distinctions which exist between an animal and a vegetable as they are in many cases so obvious, but, however great the differences may be between the higher animals and plants, in the lowest of them the distinctions are much less plain. In the first place, it is important to lay stress upon the differences between vegetable and animal cells, first as regards their structures and next as re- gards their functions. DIFFERENCES BETWEEN ANIMALS AND PLANTS 11 It has been already mentioned that in animal cells an envelope or cell-wall is by no means always present. In adult vegetable cells, on the other hand, a well-defined wall is highly characteristic; this is composed of cellulose, is non- nitrogenous, and thus differs chemically as well as structurally from the contained protoplasmic mass. Moreover, in vegetable cells, figure 12, B, the FIG. ii. — Karyokinesis, Mitosis, or Indirect Cell Division (diagrammatic). A, Cell with rest- ing nucleus; B, wreath, daughter centrosomes and early stage of achromatic spindle; C, chromo- somes; D, monaster stage, achromatic spindle in long axis of nucleus, chromosomes dividing; E, chromosomes moving toward centrosomes; F, diaster stage, chromosomes at poles of nucleus, commencing constriction of cell body; G, daughter nuclei beginning return to resting state; H, daughter nuclei showing monaster and wreath; 7, complete division of cell body into daughter cells whose nuclei have returned to the resting state. (After Bohm and von Davidoff .) protoplasmic contents of the cell fall into two subdivisions: i, a continuous film which lines the interior of the cellulose wall; and, 2, a reticulate mass con- taining the nucleus and occupying the cell-cavity. The interstices are filled with fluid. In young vegetable cells such a distinction does not exist; a FIG. 12.— A. Young Vegetable Cells.Showing Cell-Cavity Entirely Filled with Granular Pro- toplasm Enclosing a Large Oval Nucleus, with one or more Nucleoli. B. Older cells from same plant, showing distinct cellulose- wall and vacuolati.on o f protoplasm. finely granular protoplasm occupies the whole cell-cavity, figure 12, A. As regards the respective functions of animal and vegetable cells, one of the most important differences consists in the power which vegetable cells possess of being able to build up new complicated nitrogenous and non-nitrogenous 12 THE PHENOMENA OF LIFE bodies out of very simple chemical substances obtained from the air and from the soil. They obtain from the air oxygen, carbon dioxide, and water, as well as traces of ammonia gas; and from the soil they obtain water, ammonium salts, nitrates, sulphates, and phosphates in combination with such bases as potassium, calcium, magnesium, sodium, iron, and others. The majority of plants are able to work up these elementary compounds into other and more complicated bodies. This they are able to do in consequence of their contain- ing a certain coloring matter called chlorophyll, the presence of which is the cause of the green hue of plants. In all plants which contain chlorophyll two processes are constantly going on when they are exposed to light: one, which is called true respiration and is a process common to animal and vegetable cells alike, consists in the taking of the oxygen from the atmosphere and the giving out of carbon dioxide; the other, which is peculiar apparently to bodies containing chlorophyll, consists in the taking in of carbon dioxide and the giving out of oxygen. It seems that the chlorophyll is capable of decomposing the carbon dioxide gas and of fixing the carbon in the structures in the form of new compounds, one of the most rapidly formed of which is starch. Vegetable protoplasm by the aid of its chlorophyll is able to build up a large number of bodies besides starch, the most interesting and important being proteid or albumin. It appears to be a fact that the power which bodies pos- sess of being able to synthesize is to a large extent dependent upon the chloro- phyll they contain. Thus the power is present to a marked extent only in the plants in which chlorophyll is found, and is absent in those which do not possess it. It is probably present only in slight degree as one of the proper- ties of animal protoplasm. It must be recollected, however, that chlorophyll without the aid of the light of the sun can do nothing in the way of building up substances, and a plant containing chlorophyll when placed in the dark, while it continues to live, and that is not as a rule long, acts as though it did not contain any of that sub- stance. It is an interesting fact that certain of the bacteria have the chlorophyll replaced by a similar pigment which is able to decompose carbon dioxide gas. Animal cells do not possess the power of building up or synthesizing from simple materials; their activity is chiefly exercised in the opposite direction, viz., they have brought to them as food the complicated compounds produced by the vegetable kingdom. With these foods they are able to perform their complex functions, setting free energy in the direction of heat, motion, and electricity, and at the same time eliminating such bodies as carbon dioxide and water, and producing other bodies, many of which contain nitrogen, but are derived from decomposition. With reference to the substance chlorophyll it is necessary to say a few words. It has been noted that the synthetical operations of vegetable cells are peculiarly associated with the possession of chlorophyll and that these opera- tions are dependent upon the light of the sun. It has been further shown that DIFFERENCES BETWEEN ANIMALS AND PLANTS 13 a solution of chlorophyll has a definite absorption spectrum when examined with the spectroscope, and that it is particularly those parts of the solar spec- trum corresponding to these absorption bands which are chiefly active in the decomposition of carbon dioxide. In the synthetical processes of the plant then, by aid of its chlorophyll, the radiant energy of the sun's rays becomes stored up or rendered potential in the chemical products formed. The poten- tial energy is set free, or is again made kinetic, when these products simply by combustion produce heat, or when they are taken into the animal organism and used as food and to produce heat and motion. The influence of light is not an absolute essential to animal life; indeed, it is said not to increase the metabolism of animal tissue to any great extent, and the animal cell does not receive its energy directly from the sun's light, nor yet to any extent from the sun's heat, but from the potential energy of the food stuffs. But it must be always kept in mind that anabolism is not peculiar to vegetable, or katabolism to animal cells; both processes go on in each. Some of the lowest forms of vegetable life, e.g., the bacteria, will live only in a highly albuminous medium, and in fact seem to require for their growth elements of food stuffs which are essential to animal life. In their metabolism, too, they very closely approximate animal cells, not only requiring an atmos- phere of oxygen, but giving out carbon dioxide freely, and secreting and excret- ing many very complicated nitrogenous bodies, as well as forming proteid, carbohydrates, and fat, requiring heat but not light for the due performance of their functions. Certain bacteria grow only in the absence of oxygen. There is, commonly, a difference in general chemical composition between vegetables and animals, even in their lowest forms; for associated with the protoplasm of the former is a considerable amount of cellulose, a substance closely allied to starch and containing carbon, hydrogen, and oxygen only. The presence of cellulose in animals is much rarer than in vegetables, but there are many animals in which traces of it may be discovered, and some in which it is found in considerable quantity. The presence of starch in vegetable cells is very characteristic, though, as we have seen above, it is not distinctive, and a substance, glycogen, similar in composition to starch, is very common in the organs and tissues of animals. Inherent power of movement is a quality which we so commonly consider an essential indication of animal nature that it is difficult at first to conceive of its existence in any other. The capability of simple motion is now known, however, to exist in so many vegetable forms that it can no longer be held as an essential distinction between them and animals, and ceases to be a mark by which the one can be distinguished from the other. Thus the zoospores of many of the Cryptogams exhibit ciliary or ameboid movements of a like kind to those seen in amebae; and even among the higher orders of plants, many, e.g., Dioncza muscipula ( Venus Js fly-trap), and Mimosa sensitive, (Sensi- tive plant) exhibit such motion, either at regular times or on the applica- 14 THE PHENOMENA OF LIFE tion of external irritation, as might lead one, were this fact taken by itself, to regard them as sentient beings. Inherent power of movement, then, al- though especially characteristic of animal nature, is, when taken by itself, no proof of it. Cell Differentiation and the Functions of Organized Cells. As we proceed upward in the scale of life from the unicellular organisms, we find another phenomenon exhibited in the life history of the higher forms, namely, that of development. The one-celled ameba comes into being derived from a previous ameba; it manifests the properties and performs the functions of its life which have been already enumerated. In the higher organisms it is different. Each, indeed, begins as a single cell, but the cells which result from division and subdivision do not form so many independent organisms, but adhere in one differentiated community which ultimately forms the complex but co-ordinated whole, in man the human body. Thus, from the ovum, or germ cell which forms the starting-point of ani- mal life, in a comparatively short time there is formed a complete membrane of cells, polyhedral in shape from mutual pressure, called the Blastoderm; and FIG. 13. — Transverse Section through Embryo Chick (26 hours), a, Epiblast; b, mespblast; c, hypoblast; d, central portion of mesoblast, which is here fused with epiblast; e, primitive groove; /, dorsal ridge. (Klein.) this speedily differentiates into two and then into three layers, chiefly from the rapid proliferation of the cells of the first single layer. These layers, figure 13, are called the Epiblast, the Mesoblast, and the Hypoblast. In the further development of the animal it is found that from each of these layers is produced a very definite part of the completed body. For example, from the cells of the epiblast are derived, among other structures, the skin and the central nervous system; from the mesoblast the muscles and connective tissue of the body, and from the hypoblast the epithelium of the alimentary canal, some of the chief glands, and so on. It is obvious that the tissues and organs so derived will exhibit in a varying degree the primary properties of protoplasm. The muscles, for example, derived chiefly from certain cells of the mesoblast are particularly contractile and respond to stimuli readily, while the cells of the liver, although possibly contractile to a certain extent, have to do chiefly with the processes of nutrition. SOURCES AND UTILIZATION OF PHYSIOLOGICAL MATERIAL 15 As the cells of the embryo increase in number in development there is a corresponding differentiation of function among the groups of cells. The various functions which the original cell may be supposed to discharge, and the various properties it may be supposed to possess, become divided among groups of cells in which the work of each group is specialized. As a result of this division of labor the functions and properties are developed and made more perfect, with a view to the more economic and effective accomplishment of the activities of the body as a whole. In studying the functions of the human body it is necessary first of all to know of what it is composed, of what tissues and organs it is made up; this can of course be ascertained only by the dissection of the dead body, and thus it comes that Anatomy, the science which treats of the structure of organized bodies, is closely associated with physiology, which treats of the function of the same structures. So close, indeed, is the association that Histology, which is especially concerned with the minute or microscopic structure of the tissues and organs of the body, and which is strictly speaking a department of anatomy, is often included in works on physiology. There is much to be said in favor of such an arrangement, since it is impossible to consider the changes which take place in any tissue during life, apart from the knowledge of the structure of the tissues themselves. There is indeed an almost insep- arable relation between the structure and the function of the differentiated animal body in which the one is made the means to a knowledge of the other as an end, and vice versa, according to the aims and purposes of the student. An equally important essential to the right comprehension of the changes which take place in the living organism is a knowledge of the chemical com- position of the body. Here, however, we can deal directly only with the composition of the dead body, and it is well at once to admit that there may be many chemical differences between living and non-living tissues; but as it is impossible to ascertain the exact chemical composition of the living tissues, the next best thing which can be done is to find out as much as possible about the composition of the same tissues after they are dead. This is the assistance which the science of Chemistry can afford to the physiologist. Having mastered the structure and composition of the body, we are brought face to face with physiology proper, and have to investigate the vital changes which go on in the tissues, the various actions taking place as long as the or- ganism is at work. The subject includes not only the observation of the mani- fest processes which are continually taking place in the healthy body, but the conditions under which these are brought about, the laws which govern them and their effects. Sources and Utilization of Physiological Material. It may be well to mention as a preliminary that the physiological information which we have at our disposal has been derived from many sources, the chief of which are as follows: From actual observation of the various phenomena occurring in 16 THE PHENOMENA OF LIFE the human body from day to day, and from hour to hour, as, for example, the estimation of the amount and composition of the ingesta and egesta, the res- piration, the beat of the heart, and the like; from observations upon other animals, the bodies of which we are taught by comparative anatomy approxi- mate the human body in structure and may be supposed to be similar in function; from observations of the changes produced by experiment upon the various processes in such animals, or in the organs and tissues of animals; from ob- servations of the changes in the working of the human body produced by dis- eases; from observations upon the gradual changes which take place in the functions of organs when watched in the embryo from their earliest beginnings to their completed development. The physiologist, in order to utilize the sources of material, must be familiar with the gross structure of the animals or parts of animals which he proposes to use in experimental procedure. So simple a matter as the determination of arterial blood pressure involves familiarity with extensive anatomical structure. Experimental procedure must also draw on the field of microscopic structure or histology, and many of the most instructive bodies of physiological knowledge have come directly from the utilization of the facts of comparative anatomy and of biology. The problems in animal nutrition which are under such ex- tensive investigation at the present time require for their solution not only the use of the most complex methods of chemistry, both analytical and synthet- ical, but also the principles and methods of physics. Indeed, since the work of Helmholz, the interpretation of physiological phenomena by means of physi- cal laws and methods has contributed more than any other means toward the prominent scientific position of physiology at the present time. In a word, physiology must utilize the facts of anatomy, histology, biology, physics, and chemistry to interpret the phenomena of life. CHAPTER II CELL DIFFERENTIATION AND THE STRUCTURE OF THE ELEMENTARY TISSUES A CAREFUL examination of the human body shows that the functional unit for the various and complicated life phenomena is the microscopical structure, the cell. The cell, alone or in combination, is capable of all the activities manifested by the living body. As a basis for brief review of the elementary structures of the body we shall first discuss the structure and development of the cell. THE STRUCTURE OF THE CELL. The typical tissue cell is a spherical or ovoid mass of protoplasm. Its structure is quite complex, but the most general differentiation is into the cell mass or cytoplasm, and its contained nucleus. The cytoplasm is sometimes bounded by a definite cell membrane, but in differentiated animal tissues this membrane is usually not present. The Cell Body. The cell body or cytoplasm is a complex semi- fluid mass, the detailed structure of which has presented problems of many difficulties. It is usually described as having a framework of spongioplasm or formed elements, and a homogeneous hyaloplasm. In some cells there are formed materials resulting from the cellular activity called metaplasm, figure 14. These structural features are made more evident by their affinity for certain staining reagents. The spongioplasm or reticulum varies greatly in different types of cells, and even in different parts of the same cell. It has considerable affinity for stains which exhibit a fine network, the reticulum. It increases in amount in older cells and also in constancy in the type of arrangement. The hyaloplasm is more fluid, less refractile, and stains with great difficulty. It fills the interspaces of the spongioplasm. In this material may be embedded such substances as the metaplasts mentioned above. Structure of the Nucleus. The nucleus when in a condition of rest is bounded by a distinct membrane, the nuclear membrane, possibly derived from the spongioplasm of the cell, which encloses the nuclear contents, nucleo- plasm or karyoplasm. The membrane consists of an inner, or chromatic, and of an outer, or achromatic layer , so called from their reaction to stains. The nucleoplasm is made up of a reticular network, or chromoplasm, whose inter- spaces are filled by the karyolymph, or nuclear matrix, a homogeneous sub- 2 17 18 CELL DIFFERENTIATION AND THE ELEMENTARY TISSUES stance which is rich in proteids, has but slight affinity for stains, and is supposed to be fluid. The network is composed of linin or achromatin, a transparent unstainable framework; and of chromatin, which stains deeply. It is supported by the linin, and occurs sometimes in the form of granules, but usually as irregular anastomosing threads, both thicker primary fibers and thinner connecting branches. The threads often form thickened nodes, karyosomes or false nucleoli, at their points of intersection. It is now quite generally believed that Cell membrane. Metaplasm gran- < ules. Karyosome or net- knob. Hyaloplasm. Spongioplasm. Linin network. Nucleoplasm. Attraction sphere. Centrosome. , Plastids. .-•"- Chromatin network Nuclear membrane. Nucleolus. Vacuole. FIG. 14. — Diagram of a Typical Cell. (Bailey.) the chromatin occurs as short, rodlike, and highly refractive masses, which are embedded in the linin in a regular series. The nucleoli, or plasmosomes, are spherical bodies which stain deeply, and may either lie free in the nuclear matrix or be attached to the threads of the net- work. The Centrosome and Attraction Sphere. In addition to the nucleus, a minute spherical body called the centrosome is believed to be constantly present in animal cells, though sometimes too small to be demonstrated. The centrosome is smaller than the nucleus, close to which it lies, and exerts a peculiar attraction for the protoplasmic filaments and granules in its vicinity, so that it is surrounded by a zone of fine radiating fibrils, forming the attraction sphere or archoplasm. Some authorities assert that the centrosome lies within the nucleus in the resting state, and passes into the cell proper only in the earlier stages of cell division. The attraction sphere is most distinctly seen in cells about to divide. It plays an important role in nuclear division, but it is doubted if it gives the initial impulse to the process. Cell Multiplication. Cells increase in number by a process known as cell division, of which the first act is nuclear division. In fact the nucleus is the center of control of the cell-mass in the process of division. Cell multi- CELL MULTIPLICATION 19 plication takes place by two recognized methods, direct (amitosis), in which there is little disturbance of the nuclear network, and indirect (mitosis), in which there is a complex series of nuclear network changes. These mitotic changes result in the division of the chromatin fila- ments into the two new parts which form the chromo- plasm of the daughter nuclei. The process may be divided into the following stages:— Prophase. The resting nucleus becomes somewhat enlarged, and the centrosome (according to those who regard it as lying normally within the nucleus) migrates into the cell protoplasm. The centrosome then divides into two daughter centrosomes which lie near the nucleus but are separated by a considerable interval. Each is surrounded by the radiating fibrils of the attraction sphere, and some of these fibrils pass continuously from one centrosome to the other, forming the achromatic spindle. At the same time the intranuclear network be- comes converted into a fine convoluted coil (spirem or skein) which may be either continuous or else broken up into several threads. The thread or threads then shorten and become thicker, while the convolutions, which have become less numerous, arrange themselves in a series of con- necting loops, forming the wreath. The nuclear membrane and the nucleolus disappear, the latter passing at times into the cell protoplasm and disintegrat- ing. The wreath then breaks up into V-shaped segments, the chromosomes, of which each species of animal has a constant and characteristic number. This varies in the different animals, but is sixteen in man. The two centrosomes migrate to the poles of the nucleus, while the achro- matic spindle which connects them occupies the long axis of the nucleus. The FIG. 15 — Leucocyte of Salamander Larva, Showing Attraction Sphere. (After Flem- ming.) FIG. 1 6. — Early Stages of Karyokinesis. A. The thicker primary fibers remain and the achro- matic spindle appears. B. The thick fibers split into two and the achromatic spindle becomes longitudinal. (Waldeyer.) chromosomes, becoming much shorter and thicker, gather around the spindle in its equatorial plane, with their angles directed toward the center, forming the aster or monaster. Metaphase. The actual division of the nucleus is begun at this time by the splitting of each chromosome longitudinally into halves which lie at first close CELL DIFFERENTIATION AND THE ELEMENTARY TISSUES together so that each seems doubled. Soon afterward the fibrils of the achro- matic spindle begin to contract, and thus separate the halves of the chromosomes in such a way that one-half of each is turned toward one pole, and the other half toward the other. As this continues, the two groups, which are equal in central _.. particle, Polar r*u&*0en, (Cyt«*t*r) afav&tlon, sphere* dear area of nucleus- cen&vtZ «• jUxrUdo FIG. 17. — Monaster Stage of Karyokinesis. (Rabl.) size, draw away from each other and from the equator, each group being formed of daughter chromosomes. Anaphase. The two groups (daughter chromosomes) now gradually ap- proach their respective poles, or centrosomes, and the equator becomes free. On reaching the pole, each group gathers in a form which is similar in arrange- ment to the monaster and is known as the diaster. During this time the cell body becomes slightly constricted by a circular groove at its equatorial plane. Telophase. Soon afterward the fibrils of the chromatic spindle which connect the two groups begin to grow dim and finally disappear. The daugh- FIG. 18. — Stages of Karyokinesis. (Rabl.) A. Commencing separation of the split chromo- somes. B. The separation further advanced. C. The separated chromosomes passing along the fibers of the achromatic spindle. ter chromosomes assume the form of threads twisted in a coil and develop each a nuclear membrane and a nucleolus, forming a daughter nucleus. The nuclei enlarge and the nuclear threads assume the appearance of the resting state of the nucleus. Meanwhile, the constriction about the body of the cell has become deeper and deeper until the protoplasm is divided into two equal parts, or daughter cells, each with its daughter nucleus, and the process of karyokinesis is completed. MODES OF CELL CONNECTION 21 The Cell Types. All of the elementary tissues consist of cells and of their altered equivalents. It will be as well therefore to indicate some of the differences between the cells of the body. They are named in various ways, according to their shape, origin, and junctions. From their shape, cells are described as spherical or spheroidal, which is the typical shape of the free cell; this may be altered to polyhedral when the pres- sure on a mass of cells in all directions is nearly the same; of this the primitive segmentation cells afford an example. The discoid form is seen in blood- corpuscles, and the scale-like form in superficial epithelial cells. Some cells have a jagged outline and are then called prickle cells. Cells of cylindrical, conical, or prismatic form occur in various places in the body. Such cells may taper at one or both ends into fine processes, in the former case being caudate, in the latter fusiform. They may be greatly elongated so as to become fibers. ...-. Remains of spindle. Line of division •-•-^^?T7>rr-'-"'r^^VA ""** Lighter substance of cells. """ of nucleus- Antipole of ^^^^^mWl ______ Cell protoplasm. nucleus. MllllWwmJfcl^J/Jlllf ---- Hilus. FIG. 19. — Final Stages of Karyokinesis. In the lower figure the changes are still more ad- vanced than in the upper. (Waldeyer.) Cells with hair-like processes, or cilia, projecting from their free surfaces, are a special variety. The cilia vary greatly in size, and may even exceed in length the cell itself. Finally, cells may be branched or stellate with long outstanding processes. From their function cells are called secreting, protective, sensitive, contractile, and the like. From their origin cells are called epiblastic and mesoblastic and hypoblastic (ectodermic, mesodermic, and endodermic). Modes of Cell Connection. Cells are connected together to form tissues in various ways. They are connected by means of a cementing intercellular substance. This is probably always present as a transparent, colorless, viscid, albuminous substance, even between the closely apposed cells of epithelium; while in the case of cartilage it forms the main bulk of the tissue, and the cells only appear as embedded in, not as cemented together by, the intercellular substance. This intercellular substance may be either homogeneous or fibrillated. In many cases, e.g., the cornea, it can be shown to contain a number of irregular branched cavities, which communicate with each other, and in which branched 22 CELL DIFFERENTIATION AND THE ELEMENTARY TISSUES cells lie. Nutritive fluids can find their way through these branching spaces into the very remotest parts of a non-vascular tissue. The basement mem- brane (membrana propria) must be mentioned as a special variety of intercellu- lar substance which is found at the base of the epithelial cells in most mucous membranes, and especially as an investing tunic of gland follicles which deter- mines their shape. Cells are connected by anastomosis of their processes. This is the usual way in which stellate cells, e.g., of the cornea, are united. The individuality of each cell is thus to a great extent lost by its connection with its neighbors to form a reticulum. As an example of a network so produced we may cite the anastomosing cells of the reticular tissue of lymphatic glands. Derived Elements. Besides the cell, which may be termed the primary tissue element, there are materials which may be termed secondary or derived elements or formed materials. Examples of this type of structure are found in the matrix of cartilage, the fibers of connective tissue, bone, etc. Decay and Death of Cells. There are two chief ways in which the comparatively brief existence of cells is brought to an end, by mechanical abra- sion and by chemical transformation. The various epithelia furnish abundant examples of mechanical abrasion. As it approaches the free surface, the cell becomes more and more flattened and scaly in form and more horny in consistency, till at length it is simply rubbed off as in the epidermis. Hence we find free epithelial cells in the mucus of the mouth, intestine, and in the genito-urinary tract. In the case of chemical transformation the cell-contents undergo a degener- ation which, though it may sometimes be pathological, is very often a normal process. Thus we have cells by fatty metamorphosis producing oil-globules in the secretion of milk, fatty degeneration of the muscular fibers of the uterus after the birth of the fetus. Calcareous degeneration is common in the cells of many cartilages. THE STRUCTURE OF THE ELEMENTARY TISSUES. There are certain elementary structures formed in the process of differentia- tion which alone or when combined in varying proportions form the whole of the organs and tissues of the body. These elementary tissues are: The Epithelial, The Connective, The Muscular, and The Nervous Tissues. To these four some would add a fifth, looking upon the Blood and Lymph, con- taining, as they do, formed elements in a fluid menstruum, as a distinct tissue. I. THE EPITHELIAL TISSUES. Epithelium is a tissue composed almost wholly of cells, with a very small amount of intercellular substance which glues the cells together. In general it includes all those cellular membranes which cover either an external or CLASSIFICATION OF EPITHELIA 23 an internal free surface, together with the cellular portions of the glands which are connected with, or developed from, these free surfaces. Epithelium clothes (i) the whole exterior surface of the body, forming the epidermis with its appendages ; becoming continuous at the chief orifices of the body — nose, mouth, anus, and urethra — with (2) the epithelium which lines the whole length of the respiratory, alimentary, and genito-urinary tracts, together with the ducts and secretory cells of their various glands. Epithelium also lines the cavities of (3) the brain and the central canal of the spinal cord, (4) the serous and synovial membranes, and (5) the interior of blood-vessels and lymphatics. Epithelial cells vary in size and shape, pressure being the main factor in this variation. The protoplasm may be granular, reticular, or fibrillar in appear- ance. The nucleus is spherical or oval, usually there is only one, but there may be two or more, present. Epithelial tissues are non-vascular, that is to say, do not contain blood- vessels, but in some varieties minute channels exist between the cells of certain layers. Nerve fibers are supplied to the cells of many epithelia. CLASSIFICATION OF EPITHELIA. As to form and arrangement of cells. I. Epithelia in the form of membranes (covering surfaces). 1. Simple epithelium. Cells only one layer in thickness. (1) Squamous or pavement. Cells flattened. (a) Non-ciliated. Alveoli of lungs, also includes endothelium, lining the blood-vessels, and mesothelium, lining the large serous spaces. (b) Ciliated. The peritoneum of some forms at breeding season. (2) Cubical epithelia. Cells with the three dimensions approxi- mately equal, mainly glandular. (a) Non-ciliated. The usual type. It is found lining both ducts and secretory portions of most glands, the pigmented layer of the retina, etc. (b) Ciliated. Not common. Lining of some of the smaller bronchial tubes. (3) Columnar. Cells may be cylindrical, conical, or goblet shaped. (a) Non-ciliated. Intestinal. (b) Ciliated. Fallopian tube and uterus. (c) Pseudo-stratified. Smaller bronchi, nasal duct, etc. 2. Stratified epithelia. Cells more than one layer in thickness, (i) Squamous. Surface cells flattened. (a) Non-ciliated. Skin, mouth, vagina, etc. (b) Ciliated. Pharynx of embryo. 24 CELL DIFFERENTIATION AND THE ELEMENTARY TISSUES (2) Columnar. Surface cells columnar. (a) Non-ciliated. Portions of male urethra. (b) Ciliated. Trachea, bronchi, etc. II. Epithelia not in the form of membranes, but in solid masses or cords, usually glandular, (i) Cells spheroidal, ova. (.2) Cells polyhedral, liver, suprarenal, etc. Epithelia, classified mainly as to function. I. Protective. Skin, mouth, alimentary canal. 1. Cornified. Skin, nails, hair. 2. Cuticular border. Columnar cells of intestine. II. Glandular. 1. Secretory. Cells of salivary glands, pancreas, etc. 2. Execretory. Cells of kidney. 3. Absorptive. Cells of alimentary canal. III. Sensory Epithelium. Cells of olfactory membrane, organ of Corti, taste buds, etc. IV. Reproductive. Sex cells. V. Pigmented. Pigmented layer of retina. VI. Ciliated. Trachea, uterus, Fallopian tube, etc. Only a few of the more important of the above-mentioned types of epithe- lium will be described here. Simple Epithelium. Simple Squamous. This form of epithelium is found arranged in a single layer of flattened cells, for example, the lining of the alveoli of the lungs and of the descending arm of Henle's loop of the kidney tubule. Aside from endothelium as mesothelium it has very limited dis- tribution in man. Endothelium and mesothelium are typical simple squamous FIG. 20. — The Endothelium of a Small Blood-vessel. Silver-nitrate stain. X 35°. epithelia. They consist of much flattened cells with clear or slightly granular protoplasm and oval bulging nuclei, the edges of the cells are peculiarly wavy or serrated. The presence of endothelium in any locality may be demonstrated by stain- ing with silver nitrate, which brings into view the intercellular cement sub- SIMPLE EPITHELIUM 25 stance. When a small portion of a perfectly fresh serous membrane, for example, figure 20, is immersed for a few minutes in a solution of silver nitrate, and exposed to the action of light, the silver is precipitated in the in- FIG. 21. — Abdominal Surface of Central Tendon of the Diaphragm of Rabbit, showing the general polygonal shape of the endothelial cells; each cell is nucleated. (Klein.) X 300. tercellular cement substance, and the endothelial cells are thus mapped out by fine, dark, and generally sinuous lines of extreme delicacy. Endothelial cells in certain situations may be ciliated, e.g., those of the mesentery of the frog, especially during the breeding season. On those portions of the peritoneum and other serous membranes in which lymphatics abound, apertures, figure 22, are found surrounded by small, more or less cubical, cells. These apertures are called stomata. They are particularly well seen in the anterior wall of the great lymph sac of the frog, FIG. 22.— Peritoneal Surface of a Portion ot the Septum of the great Lymph-Sac of Frog. The stomata, some of which are open, some collapsed, are surrounded by endothelial cells. (Klein.) Xi6o. figure 22, and in the omentum of the rabbit. These are really the open mouths of lymphatic vessels or spaces, and through them lymph-corpuscles and the serous fluid from the serous cavity pass into the lymphatic system. Simple N on-Ciliated Columnar Epithelium, figure 23, lines, a, the mucous membrane of the stomach and intestines as a single layer, from the cardiac 26 CELL DIFFERENTIATION AND THE ELEMENTARY TISSUES orifice of the stomach to the anus, and 6, wholly or in part all the ducts of the glands opening on its free surface, and c, many gland-ducts in other regions of the body, e.g., mammary, salivary, etc. The intracellular and intranuclear networks are well developed, and in some cases the spongioplasm is arranged FIG. 23. — Simple Columnar Ephithelial Cells from the Human Intestinal Mucous Membrane. a, Mucous (goblet) cell; b, basement membrane; c, cuticle; d, leucocyte nucleus; e, germinating cell. (Bailey.) in rods or longitudinal striae at one part of the cell, as in the cells of the ducts of salivary glands. The protoplasm of columnar cells may be vacuolated and may also contain fat or other substances seen in the form of granules. Certain columnar cells transform a large part of their protoplasm into mucin, goblet cells, figure 24, which is discharged by the open mouth of the goblet, leav- FIG. 24. FIG. 25. FIG. 24. — Goblet Cells. (Klein.) FIG. 25. — Cross- section of a Villus of the Intestine, e. Columnar epithelium with striated border; g, goblet cell, with its mucus partly extruded; /, lymph-corpuscles between the epithelial cells; b, basement membrane; c, sections of blood -capillaries; m, section of plain muscle fibers; c.l, central lacteal. (Schafer.) ing only a nucleus surrounded by the remains of the protoplasm in its narrow stem. This transformation is a normal process which is continually going on during life, the cells themselves being supposed to regenerate into their original shape. STRATIFIED EPITHELIUM 27 Stratified Epithelium. The term stratified epithelium is employed to describe the type found in the skin or its derivatives in which the cells forming the epithelium are arranged in a considerable number of superim- posed layers. The shape and size of the cells of the different layers, as well as the number of layers, vary in different situations. Thus the superficial cells may be either squamous or columnar in shape and the deeper cells range from polygonal to columnar in form. Stratified Squamous. The intermediate cells are polygonal in shape and approach more to the flat variety the nearer they are to the surface, and to the FIG. 26. — Squamous Epithelium Scales from the Inside of the Mouth. X 260. (Henle.) columnar as they approach the lowest layer. In many of the deeper layers of epithelium in the mouth and skin, the outline of the cells is very irregular, in consequence of processes passing from cell to cell across these intervals. Such cells, figure 28, are termed " prickle " cells. These " prickles " are the in- tercellular bridges which run across from cell to cell, the interstices being filled by the transparent intercellular lymph. When this increases in quantity FIG. 27.— Vertical Section of the Stratified Epithelium Covering the Front of the Cornea. Highly magnified. (Schafer.) c, Lowermost columnar cells; p, polygonal cells above these; ft, flat- tened cells near the surface. The intercellular channels, bridged by minute cell processes, are well seen. in inflammation the cells are pushed further apart, and the connecting fibrils or " prickles" are elongated and more clearly visible. The columnar cells of the deepest layer are distinctly nucleated; they multiply rapidly by division; and as new cells are formed beneath, they press the older cells forward, to be in turn pressed forward themselves toward the sur- face, gradually altering in shape and chemical composition until they die and are cast off from the surface. 28 CELL DIFFERENTIATION AND THE ELEMENTARY TISSUES Stratified squamous epithelium is found in the following situations: i. Forming the epidermis, covering the whole of the external surface of the body; 2. Covering the mucous membrane of the nose, tongue, mouth, pharynx, and esophagus; 3. As the con junctival epithelium, covering the cornea 54. Lining the vagina and the vaginal part of the cervix uteri. Stratified Columnar Epithelium. In this type of epithelium, the surface cells alone are columnar, the deeper cells being irregular in shape From FIG. 28. — Epithelial Cells from the Stratum Spinosum of the Human Epidermis, Showing "Intercellular Bridges." X 700. (Szymonowicz.) the surface cells long processes extend down among the underlying cells. This type of epithelium is usually ciliated, as in the trachea, bronchi, etc., but may be non-ciliated, as in portions of the human male urethra. Transitional Epithelium. This is a stratified epithelium consisting of only three or four layers of cells. The superficial cells are large and flat, often M FIG. 29. — Stratified Columnar Ciliated Epithelium from the Human Trachea. A mucous (goblet) cell also is present. containing two nuclei. The under surfaces of these cells are hollowed out, and into these depressions fit the large ends of the pyriform cells which form the next layer. Beneath the layer of pyriform cells are from one to four layers of polyhedral cells. This type of epithelium occurs in the bladder, ureter, and pelvis of the kidney. STRATIFIED EPITHELIUM Specialized Epithelium. Glandular Epithelium forms the active secreting agent in the glands; the cells are usually spheroidal, but may be polyhedral from mutual pressure, or even columnar; their protoplasm is generally oc- cupied by the materials which the gland secretes. Examples of glandular FIG. 30. — Transitional Epithelium from the Human Bladder. (Bailey.) epithelium are to be found in the liver, figure 31, in the secreting tubes of the kidney, and in the salivary, figure 32, and gastric glands. Ciliated epithelium consists of cells which are generally cylindrical in form, figures 29, 30, but may be spheroidal or even squamous. This form of epithelium lines: a. The mucous membrane of the respiratory tract beginning just beyond the nasal aperture, and completely covers the nasal passages, except the upper part to which the olfactory nerve is distributed, FIG. 31 FIG. 32. FIG. 3 1 .—A Small Piece of the Liver of the Horse. (Cadiat.) FIG. 32. — Glandular Epithelium. Small lobule of a mucous gland of the tongue, showing nucleated glandular cells. X 200. (V. D. Harris.) and also the sinuses and ducts in connection with it and the lachrymal sac, the upper surface of the soft palate and the naso-pharynx, the Eustachian tube and tympanum, the larynx, except over the vocal cords, to the finest sub- divisions of the bronchi. In part of this tract, however, the epithelium is in several layers, of which only the most superficial is ciliated, so that it should 30 CELL DIFFERENTIATION AND THE ELEMENTARY TISSUES more accurately be termed transitional, page 28, or stratified, b. Some portions of the generative apparatus in the male, viz., lining the "vasa efferentia" of the testicle, and their prolongations as far as the lower end of the epididymis, and much of the vas deferens; in the female, c, commencing about the middle FIG. 33. — Specialized Pigmented Epithelial Cells of Retina. of the neck of the uterus, and extending throughout the uterus and Fallopian tubes to their fimbriated extremities, and even for a short distance on the per- itoneal surface of the latter, d. The ventricles of the brain and the central canal of the spinal cord are clothed with ciliated epithelium in the child, but in the adult this epithelium is limited to the central canal of the cord. FIG. 34- FIG. 35. FIG. 34. — Spheroidal Ciliated Cells from the Mouth of the Frog. X 300 diameters. (Sharpey.) FIG. 35. — Ciliated Epithelium from the Human Trachea, a, Large, fully formed cell, b, shorter cell; c, developing cells with more than one nucleus. (Cadiat.) The cilia themselves are fine rounded or flattened homogeneous processes. According to some observers these processes are connected with longitudinal fibers which pass to the other end of the cell, but which are not connected writh the nucleus. CONNECTIVE TISSUES 31 Functions of Epithelium. According to function, epithelial cells may be classified as: i, protective, e.g., in the skin, mouth, blood-vessels, etc.; 2, protective and mo- tive, ciliated epithelium; 3, secreting, glandular epithelium ; 4, germinal, as epithelium of testicle producing sperma- tozoa; 5, absorbing and secreting, e.g., epithelium of intes- tine; 6, sensory, e.g., olfactory cells, organ of Corti. Epithelium forms a continuous smooth investment over the whole body, being thickened into a hard, horny tissue at the points most exposed to pressure, and develop- ing various appendages, such as hairs and nails. Epi- thelium lines also the sensorial surfaces cf the eye, ear, nose, and mouth, and thus serves as the medium through which all impressions from the external world — touch, smell, taste, sight, hearing — reach the delicate nerve end- ings, whence they are conveyed to the brain. The ciliated epithelium which lines the air-passages serves to promote currents of the air in the bronchial tubes and to propel fluids and minute particles of solid matter out of the body. In the case of the Fallopian tube, the cilia assist the progress of the ovum toward the cavity of the UterUS. FIG. 36. — Ciliated Cell of the Intestine The epithelium of the various glands, and of the of a Moiiusk. (En- ¥ gelmann.) whole intestinal tract, has the power of secretion, i.e., of producing certain materials by processes of metabolism in its protoplasm. Epithelium is likewise concerned in the processes of transudation, diffusion, and absorption. II. THE CONNECTIVE TISSUES. This group of tissues forms the skeleton with its various connections — bones, cartilages, and ligaments — and also affords a supporting framework and investment to the various organs composed of nervous, muscular, and glan- dular tissue. Its chief function is the mechanical one of support, and for this purpose it is so intimately interwoven with nearly all the textures of the body that if all other tissues could be removed, an4 the connective tissues left, we should have a wonderfully exact model of almost every organ and tissue in the body. General Structure of Connective Tissue. The connective tissue is made up of two chief elements, namely, cells and intercellular or formed sub- stance. Cells. The cells are usually of an oval shape, often with branched processes, which are united to form a network. They are most readily 32 CELL DIFFERENTIATION AND THE CONNECTIVE TISSUES observed in the cornea, in which they are arranged, layer above layer, parallel to the free surface. They lie in spaces in the intercellular or ground substance, which form by anastomosis a system of branching canals freely communicating, figure 37. The flattened tendon corpuscles which are arranged in long lines or rows parallel to the fibers belong to this class of cells, figure 39. These branched cells often contain pigment granules, giving them a dark appearance; they form one variety of pigment cell. Pigment cells of this FIG. 37. — Horizontal Preparation of the Cornea of Frog, Stained in Gold Chloride; showing the network of branched corneal corpuscles. The ground substance is completely colorless. X 400. (Klein.) kind are found in the outer layers of the choroid. In many of the lower ani- mals, such as the frog, they are found widely distributed not only in the skin, but also in internal parts, the mesentery, sheaths of blood-vessels, etc. Under the action of light, electricity, and other stimuli, the pigment granules become massed in the body of the cell, leaving the processes quite hyaline; if the stimulus be removed, they will gradually be distributed again throughout the processes. Thus the skin in the frog is sometimes uniformly dusky, and some- times quite light-colored, with isolated dark spots. Intercellular Substance. This is fibrillar, as in the fibrous tissues and in certain varieties of cartilage; or homogeneous, as in typical mucoid tissue. The fibers composing the former are of two kinds, white fibrous and yellow elastic tissue. The chief varieties of connective tissues may be thus classified: White fibrous. Elastic.' Areolar. Gelatinous. THE WHITE FIBROUS TISSUE Adenoid or retiform. Adipose. Neuroglia. Cartilage. 1. Hyaline. 2. White fibrous. 3. Elastic. Bone and dentine. The White Fibrous Tissue. It is found typically in tendon; also in ligaments, in the periosteum and perichondrium, the dura mater, the peri- cardium, the sclerotic coat of the eye, the fibrous sheath of the testicle, in the fasciae and aponeuroses of muscles, and in the sheaths of lymphatic glands. Structure. To the naked eye, tendons and many of the fibrous membranes, when in a fresh state, present an appearance as of watered silk. This is due FIG. 38. FIG. 38. — Mature White Fibrous Tissue of Tendon, Consisting Mainly of Fibers with a Few Scattered Fusiform Cells. (Strieker.) FIG. 39. — Caudal Tendon of Young Rat, Showing the Arrangement, Form, and Structure of the Tendon Cells. X 300. (Klein.) to the arrangement of the fibers in wavy parallel bundles. Under the micro- scope the tissue appears to consist of long, often parallel, bundles of fibers of different sizes. The cells in tendons, figure 39, are arranged in long chains in the ground substance separating the bundles of fibers, and are more or less regu- larly quadrilateral with large round nuclei containing nucleoli, generally placed so as to be contiguous in two cells. Each of these cells consists of a thick body from which processes pass in various directions into, and partially fill up the spaces between, the bundles of fibers. The rows of cells are sep- arated from one another by lines of cement-substance. Yellow Elastic Tissue. Yellow elastic tissue is found chiefly in the ligamentum nuchae of the ox, horse, and other animals; the ligamenta subflava of man; the arteries, constituting the fenestrated coat of Henle; 3 CELL DIFFERENTIATION AND THE ELEMENTARY TISSUES the veins in the lungs and trachea; the stylo-hyoid, thyro-hyoid, and crico- thyroid ligaments; in the true vocal cords; and in areolar tissue. Structure. Elastic tissue occurs in various forms, from a structureless, elastic membrane to a tissue whose chief constituents are bundles of fibers crossing each other at different angles; when seen in bundles elastic fibers are yellowish in color, but individual fibers are not so distinctly colored. The varieties of the tissue may be classified as follows: a. Fine elastic fibrils, which branch and anastomose to form a network. This variety of elastic tissue occurs chiefly in the skin and mucous membranes, in subcutaneous and sub- mucous tissue, in the lungs and true vocal cords. b. Thick fibers, sometimes cylindrical, some- times flattened, which branch, anastomose and form a network: these are seen most typically in the ligamenta subflava and also in the ligamen- tum nuchae of such animals as the ox and horse, in which that ligament is largely developed, figure 40. A certain number of connective-tissue cells are found in the ground substance between the elastic fibers which make up this variety of connective tissue, page 33. Areolar Tissue. This variety of fibrous tissue has a very wide dis- tribution and constitutes the subcutaneous, subserous, ' and submucous tis- sue. It is found in the mucous membranes, in the true skin, and in the outer sheaths of the blood-vessels. It forms sheaths for muscles, nerves, glands, and the internal organs, and, penetrating into their interior, supports and con- nects the finest parts. Structure. To the naked eye it appears, when stretched out, as a fleecy, white, and soft meshwork of fine fibrils, with here and there wider films joining in it, the whole tissue being evidently elastic. The openness of the meshwork varies with the locality from which the specimen is taken. Under the micro- scope it is found to be made up of fine white fibers, which interlace in a most irregular manner, together with a variable number of elastic fibers. On the addition of acetic acid, the white fibers swell up, and become gelatinous in appearance; but as the elastic fibers resist the action of the acid, they may still be seen arranged in various directions, sometimes appearing to pass in a more or less circular or spiral manner round a small gelatinous mass of changed white fiber. The cells of areolar tissues are connective-tissue corpuscles. Gelatinous Tissue. Gelatinous connective tissue forms the chief part of the bodies of such marine animals as the jelly-fish. It is found in FIG. 40. — Elastic Fibers from the Ligamenta Subflava. X 200. (Sharpey.) ADENOID OR LYMPHOID TISSUE 35 many parts of the human embryo. It may be best seen in the " Whartonian jelly" of the umbilical cord and in the enamel organs of developing teeth. FIG. 41- FIG. 42. FIG. 41. — Mucous Connective Tissue from the Umbilical Cord, a, Cells; b, fibrils. FIG. 42. — Part of a Section of a Lymphatic Gland, from which the Corpuscles have been for the most part Removed, showing the Adenoid Reticulum. (Klein and Noble Smith.) Structure. It consists of cells, which in the jelly of the enamel organ are stellate, embedded in a soft jelly-like intercellular substance which forms the bulk of the tissue. Adenoid or Lymphoid Tissue. Distribution. This variety of tissue makes up the stroma of the spleen and lymphatic glands, and is found also FIG. 43. — Portion of Subtnucous Tissue of Gravid Uterus of Sow. a, Branched cells, more or less spindle-shaped ; b, bundles of connective tissue. (Klein.) in the thymus, in the tonsils, and in the follicular glands of the tongue; in Peyer's patches, in the solitary glands of the intestines, and in the mucous membranes generally. Structure. Adenoid or retiform tissue consists of a verv delicate network of 36 CELL DIFFERENTIATION AND THE ELEMENTARY TISSUES minute fibrils, figure 46. The network of fibrils is concealed by being covered with flattened connective-tissue corpuscles, which may be readily dissolved in caustic potash, leaving the network bare. The network consists of white fibers, the interstices of which are filled with lymph-corpuscles. The cement- substance of adenoid tissue is very fluid. Neuroglia. This form of connective tissue found in the nervous system is described on page 77. Development oj Fibrous Tissues. In the embryo the place of the fibrous tissues is at first occupied by a mass of roundish cells, derived chiefly from the mesoderm, but also from ectoderm and from entoderm. These develop either into a network of branched cells or into groups of fusiform cells, figure 43. The cells are embedded in a semifluid albuminous substance derived probably from the cells themselves. Later this formed material is converted into fibrils under the influence of the cells. The process gives rise to fibers arranged in the one case in interlacing networks, areolar tissue, in the other FIG. 44. — Blood- Vessels of Adipose Tissue. A, Minute flattened fat-lobule, in which the vessels only are represented, o, The terminal artery; v, the primitive vein; b, the fat-vesicles of one border of the lobule separately represented. X 100. B, Plan of the arrangement of the capillaries. c, on the exterior of the vesicles; more highly magnified. (Todd and Bowman.) in parallel bundles, white fibrous tissue. In the mature forms of purely fibrous tissue not only the remnants of the cell-substance, but even the nuclei, may disappear. The embryonic tissue, from which elastic fibers are developed, is composed of fusiform cells, and a structureless intercellular substance. The fusiform cells dwindle in size and eventually disappear so completely that in mature elastic tissue hardly a trace of them is to be found: mean- while the elastic fibers steadily increase in size. ADIPOSE TISSUE 37 Adipose Tissue. In almost all regions of the human body a larger or smaller quantity of adipose or fatty tissue is present. Adipose tissue is almost always found seated in areolar tissue, and forms in its meshes little masses of unequal size and irregular shape, to which the term lobules is com- monly applied. Structure. Adipose tissue consists essentially of cells which present dark, sharply denned edges when viewed with transmitted light; each consisting of a structureless and colorless membrane or bag formed of the remains of the original protoplasm of the cell, filled with fat. A nucleus FIG. 45. — A Lobule of Developing Adipose Tissue from an Eight- Months' Fetus, a, Spherical or, from pressure, polyhedral cells with large central nucleus, surrounded by a finely retic- ulated substance staining uniformly with hematoxylin. b, Similar cells with spaces from which the fat has been removed by oil of cloves, c. Sim- ilar cells showing how the nucleus with enclosing protoplasm is being pressed toward periphery, d. Nucleus of endothelium of investing capilla- ries. (McCarthy.) Drawn by Treves. FIG. 46. — Branched Connective- Tissue Corpuscles, Developing into Fat-Cells. (Klein.) is always present in some part or other of the cell protoplasm, but in the ordinary condition of the loaded cell it is not easily or always visible. This membrane and the nucleus can generally be brought into view by extracting the fat with ether and by staining the tissue. The ultimate cells are held together by capillary blood-vessels, figure 44; while the little clusters thus formed are grouped into small masses, and held so, in most cases, by areolar tissue. The oily matter contained in the cells is composed chiefly of the compounds of fatty acids with glycerin, olein, stearin, and palmitin. Development of Adipose Tissue. Fat c'ells are developed from connective- tissue corpuscles. In the infra-orbital connective tissue there are cells ex- hibiting every intermediate gradation between an ordinary branched connec- tive-tissue corpuscle and mature fat cells. Their developmental appearance 38 CELL DIFFERENTIATION AND THE ELEMENTARY TISSUES is as follows: a few small drops of oil make their appearance in the proto- plasm, and by their confluence a larger drop is produced, figure 45. This gradually increases in size at the expense of the original protoplasm of the cell, which becomes correspondingly diminished in quantity till in the mature cell it forms only a thin crescentic film with a nucleus closely pressed against the cell-wall. Under certain circumstances this process may be reversed, A large number of blood-vessels are developed in adipose tissue, which subdivide until each lobule of fat contains a fine meshwork of capillaries ensheathing each individual fat-globule, figure 44. Adipose tissue serves as a storehouse of combustible matter which may be reabsorbed into the blood when occasion requires, and, being used up in the metabolism of the tissues, may help to preserve the heat of the body. That part of the fat which is situated beneath the skin must, by its want of conducting power, assist in preventing undue waste of the heat of the body by escape from the surface. CARTILAGE. All kinds of cartilage are composed of cells embedded in a substance called the matrix. The apparent differences of structure met with in the various kinds of cartilage are more due to differences in the character of the matrix than of the cells. With the exception of the articular variety, FIG. 47. — Hyaline Articular Cartilage (Human). The cell bodies entirely fill the spaces in the matrix. X 340 diams. (Schafer.) cartilage is invested by a thin but tough firm fibrous membrane called the perichondrium. Cartilage exists in three different forms in the human body, viz., hyaline cartilage, yellow elastic cartilage, and white fibro-cartilage. Hyaline Cartilage. This variety of cartilage is met with largely in HYALINE CARTILAGE 39 the human body where it invests the articular ends of bones, and forms the costal cartilages, the nasal cartilages, and those of the larynx with the ex- FIG. 48.— Fresh Cartilage from the Triton. (A. Rollett.) ception of the epiglottis and cornicula laryngis, the cartilages of the trachea and bronchi. Structure. Like other cartilages it is composed of cells embedded in a matrix. The cells are irregular in shape, generally grouped together in patches, figure 47. The patches are of various shapes and sizes and placed at unequal distances apart. They generally appear flattened near the free FIG. 49. — Costal Cartilage from an Adult Dog, showing the Fat-Globules in the Cartilage Cells. (Cadiat.) surface of the mass of cartilage, and more or less perpendicular to the surface in the more deeply seated portions. The intercellular substance of hyaline cartilage, when viewed fresh or after ordinary fixation, appears homogeneous. However, when subjected to special methods, the seemingly homogeneous intercellular substance can 40 CELL DIFFERENTIATION AND THE ELEMENTARY TISSUES be shown to be made up of fibers, comparable with those found in white fibrous tissue, embedded in the homogeneous matrix. In the hyaline cartilage of the ribs the cells are mostly larger than in the articular variety and there is a tendency to the development of fibers FIG. 50.— Yellow Elastic Cartilage of the Ear. Highly magnified. (Hertwig.) in the matrix, figure 49. The costal cartilages also frequently become calcified in old age, as also do some of those of the larynx. In the fetus cartilage is the material of which the bones are first con- structed; the "model" of each bone being laid down, so to speak, in this FIG. 51. — White Fibro- Cartilage. (Cadiat.) substance. In such cases the cartilage is termed temporary. It closely resembles the ordinary hyaline cartilage but the cells are more uniformly distributed throughout the matrix. BONE 41 Elastic and White Fibro-Cartilage. The first variety is found* in the cartilage of the external ear; the latter in portions of the joints, the inter- vertebral cartilages, etc. Structure. Elastic and white fibro-cartilage are composed of cells and a matrix; the latter being made up almost entirely of fibers closely resembling those of fibrous connective tissue. Development of Cartilage. Cartilage is developed out of mesoblast cells with a very small quantity of intercellular substance. The cells multiply by fission within the cell-capsules. BONE. The characteristic of bone is that the matrix is solidified by a deposit of earthy salts, chiefly calcium phosphate, but some magnesium phosphate and calcium carbonate. To the naked eye there appear two plans of structure in different bones, and in different parts of the same bone, namely, the dense or compact, and the spongy or cancellous tissue. In a longitudinal section of a long bone, as the humerus, the articular extremities are found capped on their surface by a thin shell of compact bone, while their interior is made up of the spongy or cancellous tissue. The shajt is formed almost entirely of a thick layer of the compact bone which surrounds a central canal, the medullary cavity, so called from its containing the medulla, or marrow. In the flat bones, the parietal bone or the scapula, a layer of cancellous structure lies between two layers of the compact tissue. In the short and irregular bones, as those of the carpus and tarsus, the cancellous tissue alone fills the interior, while a thin shell of compact bone forms the outside. The Marrow. There are two distinct varieties of marrow — the red and the yellow. FIG. 52. — Cells of the Red Marrow of the Guinea- Pig. highly magnified, a, A large cell, the nucleus of which appears to be partly divided into three by constrictions; b, a cell, the nucleus of which shows an appearance of being constricted into a number of smaller nuclei; c, a so-called giant cell, or myeloplaxe, with many nuclei; d, a smaller myeloplaxe. with three nuclei; e-i, proper cells of the marrow. (Schafer.) 42 CELL DIFFERENTIATION AND THE ELEMENTARY TISSUES Red marrow is that variety which occupies the spaces in the cancellous tissue; it is highly vascular, and thus maintains the nutrition of the spongy bone, the interstices of which it fills. It contains a few fat cells and a large number of marrow cells, many of which are undistinguishable from lymphoid corpuscles, and has for a basis a small amount of fibrous tissue. Among the cells are some nucleated cells containing hemoglobin like the blood- corpuscles. There are also a few large cells with many nuclei, termed giant cells or myeloplaxes, which are probably derived from the ordinary marrow cells, figure 52. Yellow marrow fills the medullary cavity of long bones, and consists chiefly of fat cells with numerous blood-vessels. Many of its cells are in every respect similar to lymphoid corpuscles. From these marrow cells, especially those of the red marrow, the red blood-corpuscles are derived. The Periosteum and Nutrient Blood-Vessels. The surfaces of bones, except the part covered with articular cartilage, are clothed by a FIG. 53. — Transverse Section of Compact Bone (of humerus). Three of the Haver sum canals are seen, with their concentric rings; also the lacuna, with the canaliculi extending from them across the direction of the lamella. The Haversian apertures were filled with debris in grinding down the section, and therefore appear black in the figure, which represents the object as viewed with transmitted light. The Haversian systems are so closely packed in this section, that scarcely any inteni'isal lamellae are visible. 'X 150. (Sharpey.) tough, fibrous membrane, the periosteum, which is closely attached to the surface of the bone. Blood-vessels are distributed in this membrane, and minute branches from these periosteal vessels enter the Haversian canals MICROSCOPIC STRUCTURE OF BONE 43 to supply blood to the solid part of the bone. The long bones are supplied also by a proper nutrient artery which, entering at some part of the shaft so as to reach the medullary canal, breaks up into branches for the supply of the marrow, from which again small vessels are distributed to the interior of the bone. Other small nutrient vessels pierce the articular extremities for the supply of the cancellous tissue. Microscopic Structure of Bone. Notwithstanding the differences of arrangement just mentioned, the structure of all compact bone substance is found under the microscope to be essentially the same. Examined with a rather high power its substance is found to contain a multitude of small irregular spaces, approximately fusiform in shape, called lacuna, with very minute canals or canaliculi, as they are termed, leading Fio. 54. — Longitudinal Section from the Human Ulna, Showing Haversian Canals, Lacunae, and Canaliculi. (Rollett.) from them, and anastomosing with similar prolongations from other lacunae, figure 53. In very thin layers of bone, no other canals than these may be visi- ble; but on making a transverse section of the compact tissue of a long bone, as the humerus or ulna, the arrangement shown in figure 53 can be seen. The bone seems mapped out into small circular districts, at or about the center of each of which is a hole, around which are concentric layers, the lamella, the lacuna and canaliculi following the same concentric distribution around the center, with which indeed they communicate. On making a longitudinal section, the central holes are shown to be simply the cut extremities of small canals which run lengthwise through the bone, anastomosing with each other by lateral branches, figure 54, and 44 CELL, DIFFERENTIATION AND THE ELEMENTARY TISSUES are called Haversian Canals, after the name of the physician, Clopton Havers, who first accurately described them. The Haversian Canals. The average diameter of the Haversian canals is 50 p.. They contain blood-vessels, and by means of them blood is con- veyed to even the densest parts of the bone; the minute canaliculi and lacunae absorbing nutrient matter from the Haversian blood-vessels and conveying it still more intimately to the very substance of the bone which they traverse. The blood-vessels enter the Haversian canals both from without from the periosteum, and from within from the medullary cavity or from the can- cellous tissue. The arteries and veins usually occupy separate canals. The lacuna are occupied by branched cells, the bone-cells or bone-corpus- cles, figure 55, which very closely resemble the ordinary branched connective- tissue corpuscles. The processes of the bone-cells extend into the canaliculi. Each cell controls the nutrition of the bone immediately surrounding it. Each lacunar corpuscle communicates with the others in its surrounding FIG. 55. — Bone-Corpuscles with their Processes as Seen in a thin Section of Human Bone. (Rollett.) district, and with the blood-vessels of the Haversian canals by means of the ramifications just described. It will be seen from the above description that bone bears a very close structural resemblance to what may be termed typical connective tissue. The bone corpuscles with their processes occupying the lacunae and canalic- uli correspond exactly to the cornea-corpuscles lying in the branched spaces. The Lamella of Compact Bone. In the shaft of a long bone three distinct sets of lamellae can be clearly recognized: General or fundamental lamellae, which are just beneath the periosteum and parallel with it, and around the medullary cavity; Special or Haversian lamellae, which are concentrically arranged around the Haversian canals to the number of six to eighteen around each ; Interstitial lamellae, which connect the systems of Haversian lamellae, DEVELOPMENT OF BONE 45 filling the spaces between them, and consequently attaining their greatest development where the Haversian systems are few. The ultimate structure of the lamellae appears to be fibrous. A thin film peeled off the surface of a bone, from which the earthy matter has been removed by acid, is composed of a finely reticular structure, formed apparently of very slender fibers decussating obliquely, but coalescing at the points of intersection, as if here the fibers were fused rather than woven together. FIG. 56. — Lamellae Torn Off from a Decalcified Human Parietal Bone at some Depth from the Surface, a, a, Lamellae, showing reticular fibers; b, b, darker part, where several lamellae are superposed; c, perforating fibers. Apertures through which perforating fibers had passed, are seen especially in the lower part, a, a, ot the figure. (Allen Thomson.) The reticular lamellae are perforated by the perforating fibers of Sharpey, which bolt the neighboring lamellae together, and may be drawn out when the latter are torn asunder, figure 56. These perforating fibers originate from ingrowing processes of the periosteum, and in the adult still retain their connection with it. Development of Bone. From the point of view of their develop- ment, all bones may be subdivided into two classes: Those which are ossified directly in membrane or fibrous tissue, e.g., the bones forming the vault of the skull, parietal, frontal, and a certain portion of the occipital bones; Those whose form, previous to ossification, is laid in down hyaline carti- lage, e.g., humerus, femur, etc. The process of development, pure and simple, may be best studied in bones which are not preceded by cartilage, i.e., membrane-formed. Without a knowledge of ossification in membrane it is difficult to understand the much more complex series of changes through which such a structure as the carti- 46 CELL DIFFERENTIATION AND THE ELEMENTARY TISSUES laginous femur of the fetus passes in its transformation into the bony femur of the adult (ossification in cartilage). Ossification in Membrane. The membrane, afterward forming the periosteum, from which such a bone as the parietal is developed, consists of two layers, an .external fibrous, and an internal cellular or osteogenetic. The external layer consists of ordinary connective tissue, with branched corpuscles here and there between the bundles of fibers. The internal layer consists of a network of fine fibrils with nucleated cells and ground or cement substance between the fibrous bundles. It is more richly supplied with capillaries than the outer layer. The relatively large number of its cellular elements, together with the abundance of blood-vessels, clearly mark it as the portion of the periosteum which is immediately concerned in the for- mation of bone. In such a bone as the parietal there is first an increase in vascularity, followed by the deposition of bony matter in radiating spicula, starting from a center of ossification. These primary bony spicula are osteogenetic fibers, composed of osteogen, in which calcareous granules are deposited. Calcareous granules are deposited also in the interfibrillar matrix. By the junction of the osteogenetic fibers and their resulting bony spicula a meshwork of bone is formed. The osteoblasts, being in part retained within the bone trabeculae thus produced, form bone-corpuscles. Lime salts are deposited in the circumferential part of each osteoblast, and thus a ring of osteoblasts gives rise to a ring of bone with the remaining uncalcified portions of the osteoblasts embedded in it as bone-corpuscles. At the same time the plate increases at the periphery by the extension of the bony spicula and by deposits taking place from the osteogenetic layer of the periosteum. The bulk of the primitive spongy bone is gradually converted into compact bony tissue of the Haversian systems. Ossification in Cartilage. Under this heading, taking the femur as a typical example, we may consider the process by which the solid cartilag- inous rod which represents the bone in the fetus is converted into the hollow cylinder of compact bone with expanded ends formed of cancellous tissue in the adult long bone. The fetal cartilage is sheathed in a membrane termed the perichondrium, which resembles the periosteum described above. Thus, the differences between the fetal perichondrium and the periosteum of the adult are such as usually exist between the embryonic and mature forms of connective tissue. There are several steps in the transformation of the fetal cartilage to the adult bone, due to the fact that there is first an impregnation of the cartilage with lime salts, followed later by the resorption of this entire material with formation of the embryonic spongy bone, which is later replaced by the per- manent bone. The complicated phenomenon takes place in steps or stages as follows: OSSIFICATION IN CARTILAGE 4? Stage of Proliferation and Calcification. The cartilage cells in and near the center of ossification become enlarged, proliferate, and arrange them- selves in rows in the long axis of the fetal cartilage, figure 57. Lime salts are next deposited in fine granules in the hyaline matrix of the cartilage, and this gradually becomes transformed into calcified trabeculae, figure 57. The en- larging cartilage cells become more transparent, and finally disintegrate, the spaces occupied by them forming the primordial marrow cavities. During FIG. 57. — Developing Bone of Femur of the Rabbit. (Schafer, from Klein.) X 35°- a, Cartilage cells; b, cartilage cells enlarged in the region of calcifying matrix; c, d, trabeculae of cal- cifying cartilage covered- with e, osteoblasts; /, osteoclasts eroding the trabeculae; g, h, disappear- ing cartilage cells. The osteoblasts are seen to be depositing layers of bony substance. Loops of blood-vessels extend to the limit of the region in which the bone is forming. this stage the perichondrium has become the periosteum, and is beginning to deposit bone on the outside of the cartilage. Stage of V ascularization of the Cartilage. Processes from the osteo- genetic layer of the periosteum containing blood-vessels break through the bone into the primordial marrow cavities and form the primary marrow, 48 CELL DIFFERENTIATION AND THE ELEMENTARY TISSUES beginning at the centers oj ossification, and spreading chiefly up and down the shaft. Stage of Substitution of Embryonic Spongy Bone for Calcified Cartilage. The cells of the primary marrow arrange themselves as a continuous epi- thelium-like layer on the calcified trabecula? and deposit a layer of bone, \v. FIG. 58. — Transverse Section through the Tibia of a Fetal Kitten, semidiagrammatic. X 60. P, Periosteum. O, Osteogenetic layer of the periosteum, showing the osteoblasts arranged side by side, represented as pear-shaped black dots on the surface of the newly formed bone. B, The peri- osteal bone deposited in successive layers beneath the periosteum and ensheathing E, the spongy endochondral bone; represented as more deeply shaded. Within the trabeculae of endochondral spongy bone are seen the remains of the calcified cartilage trabeculae represented as dark wavy lines. C, The medulla, with V, V, veins. In the lower half of the figure the endochondral spongy bone has been completely absorbed. (Klein and Noble Smith.) and ensheath them. The encased trabeculae are gradually absorbed by the osteoclasts of Kolliker. These stages are precisely similar to what goes on in the growing shaft of a bone which is increasing in length by the advance of the process of ossifi- cation into the intermediary cartilage between the diaphysis and epiphysis. In this case the cartilage cells become flattened and, multiplying by division, OSSIFICATION IN CARTILAGE 49 are grouped into regular columns at right angles to the plane of calcifi- cation while the process of calcification extends into the hyaline matrix between them. The embryonic spongy bone, formed as above described, is simply a tem- porary tissue occupying the place of the fetal rod of cartilage; the preceding stages show the successive changes at the center of the shaft. Periosteal bone is at the same time deposited in successive layers beneath the perios- teum at the circumference of the shaft, exactly as described in the section on ossification in membrane, and thus a casing of periosteal bone is formed around the embryonic endochondral spongy bone. The embryonic spongy FIG. 59. — Transverse Section of Femur of a Human Embryo about Eleven Weeks Old. a, Rudimentary Haversian canal in cross- section; b, in longitudinal section; c, osteoblasts; d, newly formed osseous substance of a lighter color; e, that of greater age; /, lacunae with their cells; g, a cell still united to an osteoblast. (Frey.) bone is absorbed, through the agency of the osteoclasts, until the trabeculae are replaced by one great cavity, the medullary cavity of the shaft. Stage of Formation of Compact Bone. The transformation of spongy periosteal bone into compact bone is effected in a manner exactly similar to that which has been described in connection with ossification in mem- brane, page 46. The irregularities in the walls of the spongy periosteal bone are absorbed by the osteoclasts, while the osteoblasts which line them are developed in concentric layers, each layer in turn becoming ossified till the comparatively large space in the center is reduced to a well-formed Haversian canal, figure 59. When once formed, bony tissue grows to some 4 50 CELL DIFFERENTIATION AND THE ELEMENTARY TISSUES extent inter stitially, as is evidenced by the fact that the lacunae are rather further apart in full-formed than in young bone. It will be seen that the common terms ossification in cartilage and ossifi- cation in membrane are apt to mislead, since they seem to imply two processes radically distinct. The process of ossification, however, is in all cases one and the same, all true bony tissue being formed from membrane, perichon- drium or periosteum; but in the development of such a bone as the femur, lime salts are first of all deposited in the cartilage; this calcined cartilage, however, is gradually and entirely reabsorbed, replaced by bone formed from the periosteum. Thus calcification of the cartilaginous matrix pre- cedes the real formation of bone. We must, therefore, clearly distinguish between calcification and ossification. The former is simply the infiltration of an animal tissue with lime salts, while ossification is the formation of true bone. Growth of Bone. Bones increase in length by the advance of the process of ossification into the cartilage intermediate between the diaphysis and epiphysis. The increise in length indeed is due entirely to growth at the two ends cf the shjjt. Increase in thickness in the shaft of a long bone occurs by the deposition of successive layers beneath the periosteum. If a thin metal plate be inserted beneath the "periosteum of a growing bone it will soon be covered by osseous deposit, but if it be put between the fibrous and osteogenetic layers it will never become enveloped in bone, for all the bone is formed beneath the latter. THE TEETH. During the course of his life, man, in common with most other mammals, is provided with two sets of teeth; the first set, called the temporary or milk- teeth of infancy, are shed and replaced by the second or permanent set. Temporary Teeth. MIDDLE LINE OF JAW. Molars. 2 Canine. I Incisors. 2 Incisors. 2 Canine. I Molars. 2 = IO The figures indicate in months the age at which each tooth appears : LOWER CENTRAL INCISORS. UPPER INCISORS. FIRST MOLAR AND LOWER LATERAL INCISORS. CANINES. SECOND MOLARS. 6 to 9 8 to 12 12 tO 15 18 to 24 24 to 30 THE TEETH 51 Permanent Teeth. MIDDLE LINE OF JAW. Canine. I T -c.^ r1 „•„*» Bicuspids or True Incisors. Canine. Molars. The age at which each permanent tooth is cut is indicated in this table in years: INCISORS. BICUSPIDS OR PRE- FIRST MOLARS. CANINES. SECOND MOLARS. MOLARS OR WISDOMS. Centrals. Laterals. First. Second. 6 7 8 9 10 12 tO 14 12 tO 15 17 to 25 Structure. A tooth is generally described as possessing a crown, neck, and root or r00/s. The crown is the portion which projects beyond the level of the gum. The neck is that constricted portion just below the crown which is embraced by the free edges of the gum, and the root includes all below this. On making longitudinal and transverse sections through its center, figure 61, A, B, a tooth is found to be principally composed of a hard superficial FIG. 60. — Normal Well-formed Jaws, from which the Alveolar Plate has been in great part Removed, so as to expose the Developing Permanent Teeth in their Crypts in the Jaws. (Tomes.) material, dentine or ivory, which is hollowed out into a central cavity which resembles in general shape the outline of the tooth, and is called the pulp- cavity. The tooth pulp is composed of fibrous connective tissue, blood-vessels, nerves, and large numbers of cells of varying shapes, and on the surface in 52 CELL DIFFERENTIATION AND THE ELEMENTARY TISSUES close connection with the dentine a specialized layer of cells called odonto- blasts, which are elongated columnar cells with a large nucleus at the taper- ing ends farthest from the dentine. The cells are all embedded in a mucoid gelatinous matrix. The blood-vessels and nerves enter the pulp through a small opening at the apical extremity of each root. A layer of very hard calcareous matter, the enamel, caps the dentine of the crown; beneath the level of the gum is a layer of true bone, called the cement or crusta petrosa. The enamel and cement are very thin at the neck of the tooth where they come in contact, the cement overlapping the enamel. The enamel becomes thicker toward the crown, and the cement toward the lower end or apex of the root. Dentine or Ivory. — Dentine closely resembles bone in chemical com- position. It contains, however, rather less animal matter. Structure. Dentine is finely channelled by a multitude of delicate tubes, which by their inner ends communicate with the pulp-cavity, and by their FIG. 61. — A. — A Longitudinal Section of a Human Molar Tooth, c, Cement; d, dentine; e, enamel; v, pulp cavity (Owen). B. — Transverse section. The letters indicate the same as in A. outer extremities come into contact with the under part of the enamel and cement, and sometimes even penetrate them for a greater or less distance, figures 63, 64. The matrix in which these tubes lie is composed of " a reti- culum of fine fibers of connective tissue modified by calcification, and, where that process is complete, entirely hidden by the densely deposited lime salts" (Mummery). The tubules of the dentine contain fine prolongations from the tooth- pulp, which give the dentine a certain faint sensitiveness under ordinary circumstances and, without doubt, have to do also with its nutrition. They are probably processes of the dentine-cells or odontoblasts lining the pulp- cavity. The relation of these processes to the tubules in which they lie is ENAMEL, 53 precisely similar to that of the processes of the bone-corpuscles to the canalic- uli of bone. The outer portion of the dentine, underlying the cement and the enamel, figure 63, b, c, contains cells like bone-corpuscles. Dentine — Periosteum of alveolus Cemen Enamel Cement , Lower jaw bone PIG. 62. — Premolar Tooth and Surrounding Bone of Cat. Enamel. The enamel, which is by far the hardest portion of a tooth, is composed chemically of the same elements that enter into the composition of dentine and bone, but the animal matter amounts only to a FIG. 63. — Section of a Portion of the Dentine and Cement from the Middle of the Root of an Incisor Tooth, a, Dental tubuli ramifying and terminating, some of them in the interglobular spaces b and c, which somewhat resemble bone lacunae; d, inner layer of the cement with numerous closely set canaliculi; e, outer layer of cement; /, lacunae; g, canaliculi. X 350. (Kolliker.) about 2 or 3 per cent. It contains a larger proportion of inorganic matter and is harder than any other tissue in the body. 54 CELL DIFFERENTIATION AND THE ELEMENTARY TISSUES Structure. Enamel is composed of fine hexagonal fibers, figures 64, 65. These are set on end vertical to the surface of the dentine, and fit into cor- responding depressions in the same. Like the dentine tubules, they are disposed in wavy and parallel curves. The fibers are thus marked by transverse lines. They are mostly solid, but some of them may contain a very minute canal. FIG. 64. FIG. 64. — Thin Section of the Enamel and a Part of the Dentine, a, Cuticular pellicle of the enamel (Nasmyth's membrane); b, enamel fibers, or columns with fissures between them and cross striae; c, larger cavities in the enamel, communicating with the extremities of some of the dentinal tubuli (d). X 350. (Kolliker.) FIG. 65. — Section of the Upper Jaw of a Fetal Sheep. A. — i, Common enamel germ dipping down into the mucous membrane; 2, palatine process of jaw; 3, rete Malpighi. (Waldeyer.) B. — Section similar to A, but passing through one of the special enamel germs here becoming flask- shaped; c, c', epithelium of mouth; /, neck; /', body of special enamel germ. (Rose.) C. — A later stage; c, outline of epithelium of gum; /, neck of enamel germ; /', enamel organ; p, papilla; 5, dental sac forming; fp, the enamel germ of permanent tooth; m, bone of jaw; v, vessels cut. across. (Kolliker.) Copied from Quain's "Anatomy." The enamel prisms are connected together by a trace of hyaline cement- substance. Development. The first step in the development of the teeth consists in a downward growth, figure 65, A, i, from the deeper layer of stratified ENAMEL 55 epithelium of the mouth, which first becomes thickened in the neighborhood of the maxillae or jaws, now also in the course of formation. This epidermal papilla grows downward into a recess of the imperfectly developed tissue of the embryonic jaw. It forms the primary enamel organ or enamel germ, and its position is indicated by a slight groove in the mucous membrane of the jaw. The next step consists in the elongation and the inclination outward of the deeper part, figure 65, B, /', of the enamel germ, followed by an increased development at certain points corresponding to the situations of the future milk-teeth. The enamel germ becomes divided at its deeper portion, or extended by further growth, into a number of special enamel germs corresponding to each of the milk-teeth, and connected to the com- mon germ by a narrow neck. Each tooth is thus placed in its own special recess in the embryonic jaw, figure 65, c, f '. As these changes proceed, there grows up from the underlying tissue into each enamel germ, figure 65, c, p, a distinct vascular papilla, dental FIG. 66.— Part of Section of Developing Tooth of a Young Rat, showing the Mode of Deposi- tion of the Dentine. Highly magnified, a, Outer layer of fully formed dentine; b, uncalcified matrix with one or two nodules of calcareous matter near the calcified parts; c, odontoblasts send- ing processes into the dentine; d, pulp; e, fusiform or wedge- shape cells found between odonto- blasts; /, stellate cells of pulp in fibrous connective tissue. The section is stained in carmine, which colors the uncalcified matrix but not the calcified part. (E. A. Schafer.) papilla, and upon it the enamel germ becomes molded, and presents the appearance of a cap of two layers of epithelium separated by an interval, figure 65, c, I'. While part of the sub-epithelial tissue is elevated to form the dental papillae, the part which bounds the embryonic teeth forms the dental sacs, figure 65, C, s; and the rudiment of the jaw sends up processes forming partitions between the teeth. The papilla, which is really part of the dental sac, is composed of nucleated cells arranged in a meshwork, in the outer layer of which are the columnar cells called odontoblasts. The odontoblasts form the dentine, while the remainder of the papilla forms the pulp. The method of the formation of the dentine from the odontoblasts is said to be as follows: The cells form elongated orocesses at their outer surfaces which are directly converted into the tubules of dentine, figure 66, c, and into the contained fibrils. 66 CELL DIFFERENTIATION AND THE ELEMENTARY TISSUES Each papilla early takes the shape of the crown of the tooth to which it corresponds, but as the dentine increases in thickness the papilla diminishes until when the tooth is cut only a small amount remains as the pulp. It is supplied by vessels and nerves which enter at the end of the root. The roots are not completely formed at the time of the eruption of the teeth. FIG. 67. — Vertical Transverse Section of the Dental Sac, Pulp, etc., of a Kitten, a, Dental papilla or pulp; b, the cap of dentine formed upon the summit; c, its covering of enamel; d, inner layer of epithelium of the enamel organ; e, gelatinous tissue; /, outer epithelial layer of the enamel organ; g, inner layer, and h, outer layer of dental sac. X 14- (Thiersch.) The enamel cap is formed by the enamel cells, by the deposit of a keratin- like substance, which subsequently undergoes calcification. Other layers are formed in the same manner meanwhile. The temporary or milk-teeth are speedily replaced by the growth of the permanent teeth. The development of the temporary teeth commences about the sixth week of intra-uterine life, after the laying down of the bony structure of the jaws. Their permanent successors begin to form about the sixteenth week of intra-uterine life. III. MUSCULAR TISSUE. There are two chief kinds of muscular tissue, differing both in minute structure as well as in mode of action, viz., (i) the smooth or non-striated, and (2) the striated. SMOOTH OR NON-STRIATED MUSCLE SMOOTH OR NON-STRIATED MUSCLE. 57 Non-striated muscle forms the proper muscular coats of the digestive canal from the middle of the esophagus to the internal sphincter ani; of the ureters and urinary bladder; of the trachea and bronchi; of the ducts of glands; of the gall-bladder; of the vesiculae seminales; of the uterus and Fallopian tubes; of the blood-vessels and lymphatics; and of the iris and some other parts of the eye. This form of tissue also enters largely into the FIG. 68. — Isolated Smooth Muscle Cells from Human Small Intestine. X 400. Rod-shaped nucleus surrounded by area of finely granular protoplasm; longitudinal striations of cytoplasm. composition of the tunica dartos of the scrotum. Unstriped muscular tissue occurs largely also in the true skin generally, being especially abundant in the interspaces between the bases of the papillae, and, when it contracts, the papillae are made unusually prominent, giving rise to the peculiar roughness of the skin termed cutis anserina, or goose flesh. It also occurs in all parts FIG. 69. — Smooth Muscle from Intestine of Pig, Showing Syncytial Structure. a, Pro- toplasmic process connecting two muscle fibers; b, end-to-end union of two muscle fibers, showing the continuity of protoplasm and myofibrils; c, nucleus of muscle fiber; d, granular protoplasm at the end of muscle nucleus; e, coarse myofibril; f, Fine myofibril; g, connective-tissue cell with connective-tissue fibrils surrounding it; h, elastic fiber. (New figure by Caroline McGill.) where hairs occur, in the form of flattened roundish bundles which lie alongside the hair-follicles and sebaceous glands. Structure. Unstriated muscle fibers are elongated, spindle-shaped, mononucleated cells, 7 to 8 p, in diameter by 40 to 200 //, in length, figures 68 and 69. The protoplasm of each cell, the contractile substance, is marked by longitudinal striations representing fibrils which have been described as contractile. The nucleus is an oblong mass placed near the 58 CELL DIFFERENTIATION AND THE ELEMENTARY TISSUES center of the cell. It is covered by a nuclear membrane which encloses a network of anastomosing fibrils. Development. In the pig the smooth muscle of the alimentary canal originates in the syncytium of the mesodermal cells which surround the entoderm. The cells soon begin to grow into the adult spindle-shape form and the fibrils make their appearance. Even in the adult muscle the syncytial connections are retained according to Miss McGill. Striated Muscle. Striated or striped muscle constitutes the whole of the muscular apparatus of the skeleton, of the walls of the abdomen, the limbs, etc.— the whole FIG. 70.— Transverse Section through Muscular Fibers of Human Tongue. The deeply stained nuclei are situated at the inside of the sarcolemma. Each muscle fiber shows Cohnheim s fields, that is, the sarcous elements in transverse section separated by clear (apparently linear) interstitial substance. X 450. (Klein and Noble Smith.) FIG. 71. FIG. 72. FIG. 71. — Muscle Fiber Torn Across; the sarcolemma still connects the two parts of the fiber. (Todd and Bowman.) FIG. 72. — Part of a Striped Muscle Fiber of a Water Beetle prepared with Absolute Alcohol. A, Sarcolemma; B, Krause's membrane. The sarcolemma shows regular bulgings. Above and below Krause's membrane are seen the transparent " lateral discs." The chief massof a muscular compartment is occupied by the contractile disc composed of sarcous elements. The substance ot the individual sarcous elements has collected more at the extremity than in the center; hence this latter is more transparent. The optical effect is that the contractile disc appears to possess a "median disc" (Disc of Hensen). Several nuclei, C and D, are shown, and in them a minute net- work. X 300. (Klein and Noble Smith.) of those muscles which are under the control of the will and hence termed voluntary; also the muscle of the heart. SKELETAL MUSCLE 59 For the sake of description, striated muscular tissue may be divided into two classes, (a) skeletal, which comprises the whole of the striated mus- cles of the body except (b) the heart. Skeletal Muscle. The muscle fibers of the skeletal muscles are usually grouped in small parallel bundles, fasciculi. The fasciculi extend through the muscle, converging to their tendinous insertions. Connective- tissue sheaths, endomysium, surround the fasciculi and support the blood- vessels, while a stronger sheath, the perimysium, encases the entire muscle. FIG. 73. — A, Portion of a Medium-sized Human Muscle Fiber. B, Separated bundles of fibril equally magnified; a, a, larger, and b, b, smaller collections; c, still smaller; d, d, the smallest which could be detached, possibly representing a single series of sarcous element. X 800. (Sharpey.) The unit of muscular structure is the fiber. Each muscle fiber is a long cylinder with fusiform ends. The fibers vary in diameter from 10 to 100 JJL, while the length may reach as much as 40 mm. Each fiber is enclosed in a distinct sheath, the sarcolemma. The sarcolemma is a transparent structure- less sheath of great resistance which surrounds each fiber, figure 71. The substance of the fiber enclosed by the sarcolemma, the contractile substance, contains a number of oval nuclei distributed along the length of the fiber and lying just under or through the sarcolemma. Each nucleus is accompanied by a small mass of granular protoplasm at its poles. The main mass of the fiber is characterized by transverse light and dark bands, figure 73, from which the name striated muscle arises. Longitudinal striation is also apparent under certain modes of treat- ment, figure 81. The muscle fibers can be split longitudinally into fibrils, called sarcostyles, figures 73 and 74, each of which exhibits the characteristic 60 CELL, DIFFERENTIATION AND THE ELEMENTARY TISSUES striation of the whole fiber. Under certain treatment the sarcostyles break transversely into smaller discs by cleavage at the line of Krause's membrane. The sarcostyle is, therefore, composed of a number of smaller elements joined end to end. These are the sarcous elements of Bowman. The sar- FIG. 74. — Diagram of Segment of Muscle Fiber, showing Sarcostyle A, Sarcous element B. Krause's line C, Hensen's line D. cous element has a highly refractive denser middle piece surrounded by a less refractive more fluid material. The polarizing microscope reveals the fact that the middle piece which corresponds in position to the dark trans- FIG. 75. FIG. 76. S'.Ei S.E.. FIG. 75. — Sarcostyles from the Wing-Muscles of a Wasp. A, A', Sarcostyles showing degrees of retraction; B, a sarcostyle extended with the sarcous elements separated into two parts, C, sarcostyles moderately extended (semidiagrammatic). (E. A. Schafer.) FIG. 76. — Diagram of a Sarcomere in a Moderately Extended Condition, B. K, K, Krause's membranes; H, plane of Henson; 5, E, poriferous sarcous element. (E. A. Schafer.) verse band is doubly refractive, isotropic, while the surrounding material, the light band, is singly refractive, anisotropic. HEART MUSCLE (51 In transverse section, figure 70, the area of the muscle substance is mapped out into small polygonal areas by a network of clear lines called Cohnheim's areas. The lines represent the substance between the sarcostyles. This substance probably represents the less differentiated contractile substance, called sarco plasm. In figure 81 the interfibrillar sarcoplasm is indicated by the longitudinal and transverse lines. Heart Muscle. The muscle substance of the heart is composed of mononucleated masses of protoplasm, cardiac muscle cells, in which the substance of the cell presents the transversely striated appearance char- acteristic of the voluntary muscle just described. But the heart muscle is phys- iologically much more like an involuntary muscle. The cells are rather small, two i .jfc.. .11 to four times as long as thick, and the nu- A y | cleus is usually situated near the middle of FIG. 77. FIG. 78. FIG. 77-— A Section of Cardiac Muscle, Diagrammatic. (From E. A. Schafer, after Heiden- hain.) FIG. 78.— Intercellular Continuity of Muscle Fibrils in Cardiac Muscle. (From E. A. Schafer after Przewosky.) the cell, figure 79. There is no sarcolemma; on the other hand, the cells present branched and irregular outlines, but adjacent cells interlock in close-fitting contact. Certain observers have described fibrils as extending across the so-called cell boundary and noted that not all such boundaries enclose nuclei. These observations suggest that cardiac muscle belongs to the group of tissues possessing a syncytium. However, the section of cardiac tissue may very possibly cut many cells without enclosing a nucleus. The continuity of 62 CELL DIFFERENTIATION AND THE ELEMENTARY TISSUES fibrils is an important observation from the physiological point of view; see Circulation Chapter. In certain parts of the heart, the cardiac tissue is not completely differ- entiated and retains in the adult somewhat embryonic characters; for ex- FIG. 79- FIG. 80. FIG. 79. — Muscular Fiber Cells from the Heart. (E. A. Schafer.) FIG. 80. — From a Preparation of the Nerve Termination in the Muscular Fibers of a Snake. a, End plate seea o.ily broad-surfaced: b, end plate seen as narrow surface. (Lingard and Klein.) ample, the bundle of His running in the septum from the auricles to the ventricles and the cells containing Purkinje's fibers lying immediately under the endocardium. Blood and Nerve Supply. The muscles are freely supplied with blood-vessels; the capillaries form a network with oblong meshes around the fibers. Nerves also are supplied freely to muscles; the striated voluntary muscles receiving them from the cerebro-spinal nerves, and the cardiac muscle from both the cerebro-spinal and the sympathetic nerves. In striped muscle the nerves end in motor end-plates. The nerve fibers are medullated; and when a branch passes to a muscle fiber, its primi- tive sheath becomes continuous with the sarcolemma, and the axis-cylinder forms a network of its fibrils on the surface of the muscle fiber. This net- work lies embedded in a flattened granular mass containing nuclei of several kinds; this is the motor end-plate, figures 80 and 81. There is considerable variation in the exact form of the nerve end-plate in the muscle. In batrachia the nerve fiber ends in a brush of branching nerve fibrils which are accompanied here and there by attached oval nuclei. Development. The striated muscle of the voluntary variety is usually developed from the mesoderm. The embryonic cells increase enor- mously in size, the nuclei multiply by fission and distribute themselves be- neath the sarcolemma. There is a differentiation of the cell protoplasm DEVELOPMENT 63 which takes place by the formation of sarcostyles. This begins nearest the surface of the cells and proceeds toward the center of the mass. The sarcolemma is apparently produced from embryonic connective tissue. The cardiac muscle cells are at first spindle-shaped embryonic cells which elongate more and more. In further differentiation their protoplasm FIG. 8 1. FIG. 82. FIG. 81. — Two Striped Muscle Fibers of the Hyoglossus of Frog, a, Nerve end- plate; b, nerve fibers leaving the end-plate; c, nerve-fibers terminating after dividing into branches; d, a nucleus in which two nerve-fibers anastomose. X 600. (Arndt.) FIG. 82. — Developing Striated Muscular Fibers, Showing Different Stages of Development and Different Positions of the Unstriated Protoplasm. A. — Elongated cell with two nuclei; the longi- tudinal striation is beginning to show on the right side. From a fetal sheep. (Wilson Fox.) B. — Developing muscular fiber, showing both longitudinal and transverse striations at the periphery, and a central unstriated cylinder of protoplasm containing several nuclei. From a human fetus near the third month. (Ranvier.) n. Nucleus (there is usually a mass of glycogen near each nucleus); p, central unstriated protoplas-n; s, peripheral striated substance. C. — Developing mus- cular fiber, showing a lateral position of the unstriated protoplasm. From a three-months' human fetus. (Ranvier.) n, Nucleus; p, unstriated protoplasm at one side of the fiber; s, striated sarcous substance with longitudinal and transverse striations. exhibits faint striations which pervade the cell as it grows in the great increase in size. The rhythmic contractions begin long before the striations appear. 64 CELL DIFFERENTIATION AND THE ELEMENTARY TISSUES IV. NERVOUS TISSUE. Nervous tissue has usually been described as being composed of two distinct substances, nerve-fibers and nerve-cells. The modern view of the nature of nerve tissue is, however, that the nerve-cell and the nerve fibers are to be considered together as one unit, called the neurone. The neurone is embedded in and supported by a substance called neuroglia. This neurone consists of a cell body, a number of branching processes termed dendrites, and a long process running out from it, the neuraxone, or axone, which be- comes eventually a nerve fiber. The nerve-cell and the nerve fiber are parts of the same anatomical unit, and the nervous centers are made up of those units, arranged in different ways throughout the nervous system, figure 81, A NERVE FIBERS. While the nerve fiber is really to be considered as a process of the nerve- cell, it is convenient to describe it separately. Nerve fibers are of two kinds, medullated or white fibers, and non-medullated or gray fibers. Medullated Fibers. Each medullated nerve fiber is made up of the following parts: An external sheath, called the primitive sheath, neuri- S.N. FIG. 83. — Diagram Showing the Arrangement of the Neurons or Nerve Units in the Architecture of the Nervous System. (Raymon y Cajkl.) A, Pyramidal neurone of cerebral cortex; B, anterior- horn motor cell of spinal cord ; D, collateral branches of A ; E, medullary neurone with ascending axone: F, spinal-ganglion neurones; G, sensory axones of F\ I, collaterals of F in the cord. MEDULLATED NERVE FIBRES 65 C-- lemma, or nucleated sheath of Schwann; an inter- mediate, known as the medullary or myelin sheath, or white substance of Schwann; and a central thread, the axis-cylinder, or axial fiber. The Primitive Sheath. This is a pellucid mem- brane forming the outer investment of the nerve fiber. The sheath is constricted at intervals of a millimeter or less, the nodes of Ranvier. Each in- ternodal segment bears a single nucleus surrounded by a variable amount of protoplasm. This mem- brane is described as having its origin in the meso- blastic cells, and the nuclei are the indications of the cellular nature of each nodal segment. The Medullary or Myelin Sheath. This is the part to which the peculiar opaque white aspect of medullated nerves is due. The thickness of this layer of a nerve fiber varies considerably. It is a semifluid, fatty substance of high refractive power. It possesses a fine reticulum (Stilling, Klein), in FIG. 84. — Two Nerve Fibers of the Sciatic Nerve. A, Node of Ranvier, B. axis-cylinder; C, sheath of Schwann, with nuclei. X 300. (Klein and Noble Smith.) FIG. 85. — A Node of Ranvier in a Medullated Nerve Fiber, viewed from above. The medul- lary sheath is interrupted, and the primitive sheath thickened. Copied from Axel Key and Retzius. X 750. (Klein and Noble Smith.) FIG. 86. — Gray, Pale, or Gelatinous Nerve Fibers. A, From a branch of the olfactory nerve of the sheep; two dark-bordered or white fibers from the fifth pair are associated with the pale olfactory fibers , B, from the sympathetic nerve. X 450. (Max Schultze.) the meshes of which is embedded the fatty material. It stains well with osmic acid. The Axis-Cylinder. The central thread of a medullated nerve fiber is the axis-cylinder. It is the prolongation of a nerve-cell and extends un- 5 66 CELL DIFFERENTIATION AND THE ELEMENTARY TISSUES interrupted for the full length of the fiber. It consists of a large number of primitive fibrillce, as shown in the cornea, where the axis-cylinders of nerves break up into minute fibrils which form terminal networks. From various considerations, such as its invariable presence and unbroken continuity in all nerves, there can be little doubt that the axis-cylinder is the essential con- FIG. 87. — Transverse Section of a Portion of the Sciatic Nerve of the Rabbit, Hardened in Chromic Acid and Stained with Picro- carmine, to show medullated fibers in end view. X 275. a, Perifascicular connective tissue; b, lamellar sheath; e, axis-cylinder. ducting part of the fiber, the other parts having the subsidiary function of support and possibly of insulation. The size of the nerve fibers varies, figure 87. The largest fibers are found within the trunks and branches of the spinal nerves, in which the majority measure from 14 y. to 19 //. in diameter. In the so-called visceral or autonomic nerves of the brain and spinal cord medullated nerves are found, the diameter of which varies from 1.8 [j. to 3.6 /*. In the hypoglossal nerve they are intermediate in size, and generally measure 7.2 fj. to 10.8 //. Non-medullated Fibers. The fibers of the second kind, figure 86, which are also called fibers of Remak, constitute the principal part of the trunk and branches of the sympathetic nerves, the whole of the olfactory nerve, and are mingled in various proportions in the cerebro-spinal nerves. They differ from the preceding chiefly in not possessing the outer layer of medullary substance; their contents being composed exclusively of the axis- cylinder. The non-medullated nerves are only about one-third to one-half as large as the medullated nerves, they do not exhibit the double contour, and they NERVE TRUNKS 67 are grayer than the medullated nerves. The non-medullated fibers fre- quently branch. It is worthy of note that in the fetus, at an early period of development, all nerve fibers are non-medullated. "S- Ar. FIG. 88. — Transverse Section of the Sciatic Nerve of a Cat, about X 100. It consists of bundles (Funiculi) of nerve fibers ensheathed in a fibrous supporting capsule, epineurium, A; each bundle has a special sheath (not sufficiently marked out from the epneurium in the figure) or perineurium, B, the nerve fibers, N, f; L, lymph spaces; A r, artery; V, vein; F, fat. Somewhat diagrammatic. (V. D. Harris.) Nerve Trunks. Each nerve trunk is composed of a variable num- ber of different-sized bundles, juniculi, of nerve fibers which have a special FIG. 89.— Small Branch of a Motor Nerve of the Frog, near its Termination, Showing Divis- ions of the Fibers; a, into two; b, into three. X 350. (Kolliker.) 68 CELL DIFFERENTIATION AND THE ELEMENTARY TISSUES sheath, perineurium. The funiculi are enclosed in a firm fibrous sheath, epineurium; this sheath also sends in processes of connective tissue which connect the bundles together. In the funiculi between the fibers is a delicate supporting tissue, the endoneurium. There are numerous lymph-spaces both beneath the connective tissue investing individual nerve fibers and also beneath that which surrounds the funiculi. Bundles of fibers run together in the nerve trunk, but they merely lie in approximation to each other, they do not unite. Even when nerves anas- tomose, there is no union of fibers, but only an interchange of fibers between the anastomosing bundles. Although each nerve fiber is thus single through most of its course, yet, as it approaches the region in which it terminates, it may break up into several subdivisions before its final ending. Nerve Collaterals. It has been discovered through the researches of Golgi, and confirmed by the further studies of Cajal and other anatomists, that each individual nerve fiber in the central nervous system gives off in its FIG. 90. — Terminal Ramifications of a Collateral Branch Belonging to a Fiber of the Posterior Column in the Lumbar Cord of an Embryo Calf. course branches which pass out from it at right angles for a short distance, and then may run in various directions. These branches are called collaterals. They end in fine, brush-like terminations known as end-brushes, or in little bulbous swellings which come in close contact with some nerve cell, figure 90. In the nerve-centers, that is, in the brain and spinal cord, the different NERVE COLLATERALS 69 nerve fibers end just as the collaterals do, by splitting up into fine branches which form the end-brushes. Collaterals of the nerve fibers and end-brushes are chiefly found in the nervous centers. The nerve fibers of the peripheral nerves end in the muscles, glands, or special sensory organs, such as the eye and ear, each by its own special type of ending. Here, however, some analogy to the end-brush can also be discovered. As the peripheral nerve fibers approach their terminations, they lose their medullary sheath, and consist then merely of an axis-cylinder and primitive sheath. They may even lose the latter, and only the axis-cylinder be left. Finally, the axis- cylinder breaks up into its elementary fibriHae, to end in various ways to be described later. FIG. 91. FIG. 92. FIG. 91. — Nerve Cell with Short Axis-Cylinder from the Posterior Horn of the Lumbar Cord of an Embryo Calf, measuring 0.55 cm. (After Van Gehuchten.) FIG. 92. — Scheme of Lower Motor Neurone. The cell body, protoplasmic processes, axone, collaterals, and terminal arborizations in muscle are all seen to be parts of a single cell and together constitute the neurone. (Barker.) c, Cytoplasm of cell body containing chromophilic bodies, neuro- fibrils, and perinbrillar substance; n, nucleus; n', nucleolus; d, dendrites; ah, axone hill free from chromophilic bodies; ax, axone; sf, side fibril (collateral); m, medullary sheath; nR, node of Ranvier where side branch is given off; si, neurilemma and incisures of Schmidt; m, striated mus- cle fiber; tel, motor end plate. 70 CELL DIFFERENTIATION AND THE ELEMENTARY TISSUES THE NERVE CELL BODY. The nerve-cell body is the nodal and important part of the neurone, and from it are given off the dendrites and axis-cylinder process or axone. It consists of a mass of protoplasm, of varying shape and size, containing within \\ FIG. 93 . — Large Nerve Cells with Processes, from the Ventral Cornua of the Cord of Man. X 3 50 . On the cell at the right two short processes of the cell body are present, one or the other of which may have been an axis-cylinder process (Deiters). A similar process appears also on the cell at the left. FIG. 94. — Multipolar Nerve Cell of the Cord of an Embryo Calf. it a nucleus and nucleolus. All nerve cells give off one or more processes which branch out in various directions, dividing and subdividing like the THE NERVE CELL BODY 71 branches of a tree, but never anastomosing with each other or with other cells. These branches are what have already been referred to as the dendrites of ' FIG. 05— Ganglion Cells, Showing Neurofibrils. A, Anterior-horn cells of human; B, cell from tnT facial nucleus of rabbit; C, dendrite of anterior-horn cell of human. (Bethe.) FIG. 96.-Cell of the Anerior Horn of the Human Spinal Cord, Stained by Nissl's Method, showing ckromophiles. (After Edmger.) the cell. They were formerly called the protoplasmic processes, figures 91, 93 It is thus seen that the neurone or nerve unit consists of a number of subdivisions, namely, the cell body, with its nucleus and nucleolus, the 72 CELL DIFFERENTIATION AND THE ELEMENTARY TISSUES dendrites or protoplasmic processes, and the axone or axis-cylinder process, which forms what is known as a nerve fiber. The protoplasm of the cells is shown by various dyes to consist of neuro- fibrils, perifibrillar substance, and in most cells chromophilic bodies. Apathy and others have demonstrated that a network of interlacing and anasto- mosing fibrils traverses both the cell body and its branches, figure 95. FIG. 97. — An Isolated Sympathetic Ganglion Cell of Man, Showing Sheath with Nucleated Cell Lining, B. A, Ganglion cell, with nucleus and nucleolus; C, branched process or dendrite, D, unbranched process or axone. (Key and Retzius.) X 75°- The perifibrillar substance is a fluid or semifluid substance in which the fibrils are embedded. By treating nerve-cells with special stains granular bodies of varying size are found embedded in the cytoplasm. These bodies are the chromophilic bodies, figure 96. Ganglion cells are generally enclosed in a transparent membranous capsule similar in appearance to the external nucleated sheath of nerve - fibers; within this capsule is a layer of small flattened cells. Nerve Terminations. Nerve fibers terminate peripherally in four different ways; i, by the ter- minal subdivisions which pass in between epithelial cells, and are known as inter-epithelial arborizations; 2, by motor-plates which lie in the muscles; 3, by special end-organs, connected with the senses of sight, hearing, smell, and taste; and, 4, by various forms of tactile corpuscles. The Inter-epithelial Arborizations. This forms a most common mode of termination of the sensory nerves of the body. The nerve fibers THE INTER-EPITHELIAL ARBORIZATIONS 73 to the surface of the skin or mucous membrane lose their neurilemma and myelin sheath, the bare axis-cylinder divides and subdivides into minute ramifications among the epithelial cells of the skin and mucous membrane. In the various glands of the body this form of termination also prevails. FIG. 98. — Sensory-Nerve Terminations in Stratified Pavement Epithelium. Golgi's rapid method. (After G. Retzius.) The hair-bulbs, the teeth, and the tendons of the body are supplied by this same process of terminal arborization, figures 98, 99. The motor nerves to the muscles end in what are known as muscle-plates, the details of whose structure have been already described. The special sensory end-organs will be described later in the chapter on the Special Senses. A fourth form of termination consists of corpuscles that are more or less encapsulated, and these are known as the corpuscles of Pacini, the tactile FIG. 99. — Sensory-Nerve Termination in the Epithelium of the Mucosa of the Inferior Vocal Cord and in the Ciliated Epithelium of the Subglottic Region of the Larynx of a Cat Four Weeks Old. (After G. Retzius.) Golgi's rapid method, n, Nerve-fibers rising from the connective-tissue layer into the epithelial layer, where they terminate in ramified and free arborizations. corpuscles oj Meissner, the tactile corpuscles of Krause, the tactile menisques, and the corpuscles of Golgi. The Pacinian Corpuscles. These nerve endings, named after their discoverer Pacini, are elongated oval bodies situated on some of the cerebro-spinal and sympathetic nerves. They occur on the cutaneous nerves of the hands and feet, the branches of the large sympathetic plexus about the abdominal aorta, the nerves of the mesentery, and have been observed also in the pancreas, lymphatic glands, and thyroid glands, figure 100. Each corpuscle is attached by a narrow pedicle to the nerve on which it is situated, and is formed of several concentric layers of fine membrane, each. 74 CELL DIFFERENTIATION AND THE ELEMENTARY TISSUES layer being lined by endothelium, figure 100. A single nerve fiber passes through its pedicle, traverses the several concentric layers, enters a central cavity, and terminates in a knob-like enlargement or in a bifurcation. The physiological import of these bodies is still obscure. FIG. 100. FIG. ioi. FIG. ioo. — Pacinian Corpuscle of the Cat's Mesentery. The stalk consists of a nerve fiber, n, with its thick outer sheath. The peripheral capsules of the Pacinian corpuscle are continuous with the outer sheath of the stalk. The intermediary part becomes much narrower near the en- trance of the axis-cylinder into the clear central mass. A hook-shaped termination with the end- bulb, a, is seen in the upper part. (Ranvier.) FIG. ioi. — Summit of a Pacinian Corpuscle of the Human Finger, showing the Endothelial Membranes Lining the Capsules. X 220. (Klein and Noble Smith.) The Tactile Corpuscles of Meissner. They are found in the papillae of the skin of the fingers and toes, or among its epithelium. When simple they are small, slightly flattened transparent bodies composed of nucleated cells enclosed in a capsule. When compound, the capsule contains several small cells. The nerve fiber penetrates the corpuscles, loses its myelin sheath, and divides and subdivides to form a series of arborizations. The terminal arborizations occupy the central part of the corpuscle, and are surrounded by a great number of marginal cells. The touch or tactile corpuscles of Meissner have been regarded at one time as epithelial, at another time as nervous, but they are to-day proved to be mesodermic cells, and differentiated for the special purpose of the sense of touch (Dejerine). The Corpuscles of Krause or End-Bulbs. These exist in great numbers in the conjunctiva, the glans penis, clitoris, lips, skin, and in tendon of man. They resemble the corpuscles of Pacini, but have much fewer concentric layers to the corpuscle, and contain a relatively voluminous central TACTILE MENISQUES 75 mass composed of polyhedral cells. In man these corpuscles are spherical in shape, and receive many nerve fibers which wind through the corpuscles and end in the free extremities, figure 103. FIG. 102. — Tactile Corpuscle of Meissner, Tactile Cell and Free Nerve Ending. (Merkel- Henle.) a, Corpuscle proper, outside of which is seen the connective-tissue capsule; b, fiber end- ing on tactile cell; c, fiber ending freely among the epithelial cells. Tactile Menisques. In different regions of the skin of man, one meets, in the superficial layers and in the Malpighian layers, nerves which, after having lost their myelin sheath, divide and subdivide to form FIG. 103. FIG. 104. FIG. 103. — End-,Bulb ot Krause. a, Medullated nerve fiber; b, capsule of corpuscle. FIG. 104.— A Termination of a Medullated Nerve Fiber in Tendon, lower half with Convoluted Medullated Nerve Fiber. (Golgi.) extremely beautiful arborizations. The branches of these arborizations are the tactile menisques. These menisques, which simulate the form of a leaf, represent a mode of terminal nervous arborization (Ranvier). 76 CELL DIFFERENTIATION AND THE ELEMENTARY TISSUES The Corpuscles of Golgi. These are small terminal plaques placed at the union of tendons and muscles, but belonging more properly to the FIG. 105.— Neuroglia Cells in the Cord of an Adult Frog. (After Cl. Sala.) A, Ependyma cells with their peripheral extremities atrophied and ramified; B, C, D, neuroglia cells in different degrees of emigration and separation from the ependymal canal; their central extremity is atro- phied and much contracted; their peripheral extremity, on the other hand, is greatly extended; the ramifications of the latter, terminating in conical buttons, /, end under the pia mater. FIG. 106. — Different Types of Neuroglia Cells. (After Van Gehuchten.) b, Neuroglia cells of the white substance, and c, of the gray substance of the cord of an embryo calf. THE NEUROGLIA 77 tendon. They are fusiform in shape and are flattened upon the surface of the tendon close to its insertion into the muscular fibers. They are composed of a granular substance, enveloped in several concentric hyaline membranes which contain some nuclei. The nerve fiber passes into this little corpuscle, splitting itself up into fine terminals. The corpuscles of Golgi are believed to be related to the muscular sense, figure 104. THE NEUROGLIA. The neuroglia, while not a nervous tissue, is closely mingled with it and forms an important constituent of the nervous system. It consists of cells giving off a fine network of richly branching fibers. Neuroglia is a form of connective tissue, and it is in its functions strictly comparable to the con- nective tissue which supports the special structures of other organs, like the lungs and kidneys, figure 106. In the adult animal the neuroglia-tissue is composed of cells from which are given off immense numbers of fine processes. These extend out in every direction, and intertwine among the nerve-fibers and nerve-cells, figure 105. The neuroglia cell differs in size and shape very much in different parts of the nervous system in accordance with the arrangement of the nervous structures about it. The cell is composed of granular protoplasm, and lying in it is a large nucleus, within which is a nucleolus. The body of the cell is small in proportion to the nucleus. CHAPTER III THE CHEMICAL COMPOSITION OF THE BODY OF the eighty chemical elements which have been isolated, no less than seventeen combine in varying quantities to form the chemical basis of the animal body. The substances which contribute the largest share are the non-metallic elements, Oxygen, Carbon, Hydrogen, and Nitrogen — oxygen and carbon making up altogether about 85 per cent of the whole. The most abundant of the metallic elements are Calcium, Sodium, and Potassium* These elements do not exist in the animal body in the free state, but are combined into complex chemical compounds. Of course we cannot analyze the living protoplasm and isolate its compounds. The first step in the act of separating the composition products of proto- plasm produces changes which destroy the chemical and physical relations of these products which maintain the state of life. Dead protoplasm, how- ever, yields a number of substances which must be very directly derived from the living protoplasm. On the other hand, certain products can be isolated from the animal body which are evidently not a part of the proto- plasm itself, but products of protoplasmic activity. Some of these, like fat, glycogen, etc., are constructive products, others are disintegration products of protoplasmic activity. A large number of the animal compounds, particularly those of the nitrog- enous group, are characterized by their complexity. Many elements enter into their composition, and many atoms of the same element occur in each molecule. This latter fact no doubt explains the reason of their instability. Of the numerous compounds that have been isolated from the animal body, only a very few of the most important will be discussed in this chapter. * The following table represents the relative proportion of the various elements in the body. (Marshall.) Oxygen 72.0 Carbon 13.5 Hydrogen 9.1 Nitrogen 2.5 Calcium i .3 Phosphorus 1.15 Sulphur 0.1476 Sodium o.i Chlorine 0.085 78 Fluorine 0.08 Potassium 0.026 Iron o.oi Magnesium 0.0012 Silicon 0.0002 (Traces of copper, lead, and alu- minum) THE NITROGENOUS BODIES 79 THE NITROGENOUS BODIES. Nitrogenous bodies take the chief part in forming the solid tissues of the body, and are found also to a considerable extent in the circulating fluids (blood, lymph, chyle), the secretions and excretions. They often contain, in addition to carbon, hydrogen, nitrogen, and oxygen, the elements sulphur and phosphorus; but although the composition of most of them is approxi- mately known, no general rational formula can at present be given for the proteids. Proteids. The nitrogenous substances constitute the most im- portant and complex compounds of the body. According to their chemi- cal composition and reactions they are divided into three main classes, viz., i, simple proteids; 2, compound proteids; and 3, albuminoids. The proteids are the chief of the nitrogenous organic compounds and exist in both plants and animals, one or more of them entering as an essential part into the formation of all living tissue. They exist abundantly in the lymph, chyle, and blood. Very little is known with any certainty about their exact chemical composition. Their formulae are unknown, the chem- ists who have attempted to construct the structural formulae differing very greatly among themselves. In fact the very term proteid is an extremely arbitrary one. It simply means a body which, according to Hoppe-Seylerr contains in its molecule the elements carbon, hydrogen, nitrogen, oxygen, and sulphur, in certain arbitrary but varying amounts, thus — Carbon, from 51.5 to 54.5; Hydrogen, from 6.9 to 7.3; Nitrogen, from 15.2 to 17; Oxy- gen, from 20.9 to 23.5; Sulphur, from 0.3 to 2. Some proteids contain from 0.8 to 4.5 per cent of phosphorus; a small amount of iron is usually associ- ated with proteids, but it is not certain whether or not it is an integral part of the molecule. Chittenden defines a proteid as a substance which con- tains carbon, hydrogen, oxygen, nitrogen, and sulphur, the nitrogen being in a form which serves the physiological needs of the body; and yields, on decomposition, a row of crystalline amido-acids and crystalline nitrogenous bases; nearly all contain 52 per cent of carbon and 16 per cent of nitrogen. Properties of Proteids. Proteids are for the most part amorph- ous and non-crystallizable. Certain of the vegetable proteids have been crystallized, and according to Hofmeister, egg albumin is also capable of crystallization. They possess as a rule no power (or scarcely any) of passing through animal membranes. They are soluble, but undergo alteration in composition in strong acids and alkalies; some are soluble in water, others in neutral saline solutions, some in dilute acids and alkalies, none in alcohol or ether. Their solutions exercise a left-handed rotation on polarized light. The hope that it may be possible in the immediate future to synthesize proteids is not very great, because of the extraordinary variety of compounds obtained by the decomposition of proteids by various chemical methods, 80 THE CHEMICAL COMPOSITION OF THE BODY the compounds differing according to the method employed. In the body it seems clear that living proteid is built up by the food supplied to it, which necessarily contains proteid derived from either a vegetable or an animal source; how this process takes place we are yet unable to say. Recently Taylor has been able to synthesize proteid, protamin, by the reversible action of trypsin on the amido-acids which were previously obtained by the digestion of protamin. The reaction is indicated by the equation: Protein -[- Water +± Amido-acids. Robertson has demonstrated a similar reversible reaction of pepsin on para- nuclein derived from the digestion of casein. These experiments lend a new stimulus to the efforts to build up proteids in the chemical laboratory along the lines of catalytic action of enzymes. In the course of later chapters in this book we shall endeavor to trace the steps of the breaking up of proteid in the body, but we may anticipate by mentioning that it is now generally believed that the chief ultimate prod- ucts of this decomposition are urea, a body the formula of which is CO (NHa)a> carbon dioxide and water, while the intermediate substances or by-products are chiefly ammonia compounds. When proteid material is decomposed by putrefaction, by the action of chemical reagents, acids, alka- lies, or by heat, various bodies are produced, of which amido-acids (acids in which one or more of the hydrogen atoms of the radical of the acid are replaced by amidogen, NH2) and bodies belonging to the aromatic or benzene series predominate. Hence it comes that various theories of the way in which proteids are built up have arisen. The one which has appeared to have received the greatest support is that of Latham. This observer has suggested that proteid may be considered as made up of a series of cyan- alcohols (bodies obtained by the union of any aldehyde with hydrocyanic acid) with a benzene nucleus. Taking ordinary ethyl alcohol, CH3CH2OH, as the type, the aldehyde of which is CH3CHO, the corresponding cyan- alcohol would be CHsCHCNOH. CLASSES OF PROTEIDS. Simple Proteids. Native Albumins. Albumins; serum albumins, egg albumins, lactalbumin. Globulins; serum globulin, myosinogen, cytoglobulin, etc. Derived Albumins. Albuminates; acid and alkali albumins. Coagulated proteids ; heat coagulated and enzyme coagulated proteid. Proteose, Peptones, Polypeptids; all derived as cleavage-products of enzyme action on other proteids. PROTEIDS 81 Histons ; contain 35 to 42 per cent of their nitrogen as basi * nitrogen. Protamins; contain 63 to 88 per cent of their nitrogen as basic nitro- gen. Compound Proteids. Hemoglobin; decomposes into a proteid and a chromogen. Nucleoproteid; decomposes into a proteid and nucleic acid. Glycoproteid ; decomposes into a proteid and a reducing substance, mucin. Albuminoid substances; mucin, keratin, albumoid, collagen, elastin, etc. The Albumins. Of native albumins there are several varieties: egg albumin; serum albumin; lact albumin, etc. When in solution in water it is a transparent, frothy, yellowish fluid, neutral or slightly alkaline in reaction. It gives all of the general proteid reactions. On digestion it yields 8 per cent of argenin, 22.6 per cent of leucin, and 2 per cent of tyrosin. At a temperature not exceeding 40° C. it is dried up into a yellowish, transparent, glassy mass, soluble in water. At a temperature of 70° C. it is coagulated into a new substance, coagulated proteid, which is quite insoluble in water. It is coagulated also by the prolonged action of alcohol; by strong mineral acids, especially by nitric acid; also by tannic acid, or carbolic acid; and by ethers. The coagulum is soluble in caustic soda. With strong nitric acid the albumin is precipitated at the point of contact with the acid in the form of a fine white or yellow ring. Serum Albumin is contained in blood serum, lymph, serous and synovial fluids, and in the tissues generally; it may be prepared from serum after removal of paraglobulin, by a saturation with sodium sulphate. It appears in the urine in the pathological condition known as albuminuria. It gives similar reactions to egg albumin, but differs from it in not being coagulated by ether. It also differs from egg albumin in not being easily precipitated by hydrochloric acid, and in the precipitate being easily soluble in excess of that acid. Serum albumin, either in the coagulated or precipi- tated form, is more soluble in excess of strong acid than egg albumin. Globulins. Globulins are found in egg; in blood, lymph, and other body fluids; and in most protoplasm. The globulins give the general proteid tests; are insoluble in water; are soluble in dilute saline solutions; are soluble in acids and alkalies forming the corresponding derived albumin. Most of them are precipitated from their solutions by saturation with solid sodium chloride, magnesium sulphate, or other neutral salt. They are coagulated, but at different temperatures, on heating. A globulin is obtained from the crystalline lens by rubbing it up with 6 82 THE CHEMICAL COMPOSITION OF THE BODY powdered glass, extracting with dilute saline solution, and by passing through the extract a stream of carbon dioxide. It differs from other globulins in not being precipitated by saturation with sodium chloride. The globulin, myosin, may be prepared from muscle by removing all fat, tendon, etc., and washing repeatedly in water until the washing con- tains no trace of proteids, mincing it, and then treating with 10 per cent solu- tion of sodium chloride, or similar solution of ammonium chloride or magne- sium sulphate. The salt solution will dissolve a large portion into a viscid fluid, which filters with difficulty. If the viscid filtrate be dropped little by little into a large quantity of distilled water, a white flocculent precipitate of myosin will occur. Myosin is soluble in 10 per cent saline solution; it is coagulated at 60° C. into coagulated prcteid; it is soluble without change in very dilute acids; it is precipitated by picric acid, the precipitate being redissolved on boiling; it may give a blue color with ozonic ether and tincture of guaiacum. Serum globulin is contained in plasma and in serum, in serous and syno- vial fluids, and may be precipitated by saturating plasma after removal of fibrinogen, or by saturating serum with solid sodium chloride or magne- sium sulphate. Globulin separates as a bulky flocculent substance which can be removed by filtration. It may also be prepared by diluting blood- serum with ten volumes of water, and passing carbonic-acid gas rapidly through it. The fine precipitate may be collected on a filter, and washed with water containing carbonic-acid gas. It is very soluble in dilute saline solutions, 5 to 8 per cent, from which it is precipitated by carbonic-acid gas or by dilute acids. Its solution is coagulated at 72° C. Dilute acids and alkalies convert it into acid or alkali albumin. Fibrinogen is contained in blood plasma, from which it may be prepared by the addition of sodium chloride to the extent of 13 per cent. It may also be prepared from hydrocele fluid or from other serous transudation by a similar method. Its general reactions are similar to those of paraglobulin. But its solution is coagulated at 55°-56° C. Its characteristic property consists in the facility with which it forms the insoluble proteid fibrin. Edestin is a globulin which is found in many edible vegetables, grain, etc. A solution may be prepared by adding hempseed to a 10 per cent solution of sodium chloride and heating to 50° C. Albuminates. There are two principal substances belonging to this class: a, acid albumin; b, alkali albumin. Acid Albumin. Acid albumin is made by adding small quantities of dilute acid (of which the best is hydrochloric, 0.4 to i per cent) to either egg or serum albumin diluted with five to ten times its bulk of water, and keeping the solution at a temperature not higher than 50° C. for not less than half an hour. It may also be made by dissolving coagulated native albumin in strong acid, or by dissolving any of the globulins in acids. Solid acid COAGULATED PROTEIDS 83 albuminate may be formed by adding strong acid drop by drop to a strong solution of proteid matter (e.g., undiluted egg albumin) until solidifica- tion occurs. It is not coagulated on heating, but on exactly neutralizing the solution a flocculent precipitate is produced; if it is then heated to 70° C. it will co- agulate and cannot then be distinguished from any other form of coagu- lated proteids. This may be shown by adding to the acid albumin solution a little aqueous solution of litmus and then adding, drop by drop, a weak solution of caustic potash from a buret until the red color disappears. The precipitate is the derived albumin. It is soluble in dilute acid, dilute alka- lies, and dilute solutions of alkaline carbonates. The solution of acid albumin gives the proteid tests. The substance itself is coagulated by strong acids, e.g., nitric acid, and by strong alcohol; it is insoluble in distilled water, and in neutral saline solutions; it is precipitated from its solutions by satura- tion with sodium chloride. On boiling in lime-water it is partially coagu- lated, and a further precipitation takes place on addition to the boiled solu- tion of calcium chloride, magnesium sulphate, or sodium chloride. Alkali Albumin. If solutions of native albumin, or coagulated albu- min, or other proteid be treated with dilute or strong fixed alkali, alkali albumin is produced. Solid alkali albumin (Lieberkiihn's jelly) may also be prepared by adding caustic soda or potash, drop by drop, to undiluted egg albumin, until the whole forms a jelly. This jelly is soluble in an excess of the alkali or in dilute alkalies on boiling. A solution of alkali albumin gives the tests corresponding to those of acid albumin. It is not coagulated on heating except after neutralization, as in the case of acid albumin. It is thrown down on neutralizing its solution, except in the presence of alkaline phosphates, in which case the solution must be distinctly acid before a pre- cipitate falls. To differentiate between acid and alkali albumin, the following method may be adopted: Alkali albumin is not precipitated on exact neutralization if sodium phosphate has been previously added. Acid albumin is precipi- tated on exact neutralization, whether or not sodium phosphate has been previously added. Coagulated Proteids. These are formed by the action of heat or of ferments upon other proteids; the temperature necessary to produce coagulation varying in the manner previously indicated. They may also be produced by the prolonged action of alcohol upon proteids; the process is one of dehydration. They are soluble in strong acids or alkalies; slightly so in dilute; are soluble in digestive fluids (gastric and pancreatic), and are insoluble in water or saline solutions (except fibrin). Fibrin is formed by the action of fibrin ferment on fibrinogen and can be obtained as a soft, white, fibrous, and very elastic substance by whipping blood with a bundle of twigs and washing the adhering mass in a stream of 84 THE CHEMICAL COMPOSITION OF THE BODY water unto all the blood-coloring matter is removed. It is soluble to a cer- tain extent in strong sodium-chloride solutions. Proteoses. These are intermediate substances of the digestion of other proteids, the ultimate product of which is peptone or lower cleavage products. They are produced by the action of the gastric and pancreatic juices and also, slowly, by boiling with dilute acids. The term is a general one, the proteose of albumin being albumose, that of globulin being globu- lose, etc. They are divided into primary and secondary groups representing the stages of progression from proteids to peptones, so that there may be a primary and a secondary albumose, etc. As digestion is a process of hydra- tion with cleavage, the successive stages present progressively simpler sub- stances. Each group reacts to fewer reagents than the preceding one; e.g., none of the proteoses can be coagulated by boiling. Nitric acid will precipi- tate the primary proteoses but not the secondary ones. Peptones. Peptone is formed by the action of the digestive fer- ments, pepsin or trypsin, on other proteids, and on gelatin. It is a still simpler form of substance than the proteoses and reacts to still fewer reagents. Peptones will be considered in connection with the physiology of digestion, as will also be the intermediate compounds. Histons. Histons are decomposition products but present well- defined proteid reactions. They are strongly basic and have a large con- tent of hexon bases. Histons are soluble in water; are precipitated by weak ammonia; are soluble in acids; do not coagulate by heat in water solutions unless salts are present. They are not changed by and may be recovered from the salt heat coagulation. They do not contain phosphorus. They give the biuret reaction, but do not give Millon's reaction. Protamin. This substance is of special interest in that it is the simplest of the proteids. It is a cleavage product which exists in nature in fish sperm as a nucleic acid compound. It gives the biuret but not Millon's reaction, is not coagulated by heat. It yields amido-acids as cleavage-prod- ucts. These cleavage-products have been recently resynthesized by Taylor by the action of trypsin. Compound Proteids. The compound proteids are compounds of a simple proteid with some other molecule. According to their chemical composition and characteristics they are divided into several classes, viz.: Chromo proteids. This is a combination of a proteid substance with some form of pigment. For example, hemoglobin is a combination of a globulin with hematin, an iron-containing radicle. Hemoglobin is described more fully in the chapter on the Blood. Nucleo proteids. Nucleoproteids are a combination of a proteid substance with a nucleic acid; they are divided into two groups according to the character of the acid. The true nucleo- proteids contain true nucleic acid; the para-nucleoproteids or pseudo-nucleo- proteids contain para-nucleic acid. Both acids, and therefore both groups, MUCIN 85 contain phosphorus; but the true nucleoproteids yield nuclein (xanthin) bases while the para-nucleoproteids do not. The nucleoproteids are found in the nucleus and protoplasm of every cell. The para-nucleoproteids are found in milk, as caseinogen, and in the yolk of egg, as vitellin. Glyco- proieids. Glycoproteid is a combination of a proteid substance with a carbo- hydrate radicle. Examples are mucin, which is found in mucous secre- tions; and mucoids, which are found in certain tissues, cartilages, etc. Mucin. Mucin is a compound of a globulin with a carbohydrate radicle, and is the characteristic component of mucus; it is contained also in fetal connective tissue, in tendons, and in salivary glands. It can be obtained from mucus by diluting with water, filtering, treating the insoluble portion with weak caustic alkali, and reprecipitating with acetic acid. The mucins derived from different sources probably have different compositions. Mucin has a ropy consistency. It can be coagulated; is insoluble in water, salt-solution, and very dilute muriatic acid; is soluble in alkalies and concentrated sulphuric acid. It gives the proteid reaction with Millon's reagent and with nitric acid. Neither mercuric chloride nor tannic acid gives a precipitate. It does not dialyze. When treated with sulphuric acid and then neutralized with solid potassium hydrate, it will give both the biuret test, denoting the presence of proteid matter, and also Fehling's test, show- ing the presence of a sugar. Nucleins. The substance known as nuclein and found in all cells is really a compound proteid and consists of a series of bodies made up of pro- teid and nucleic.acid in varying proportions; there is almost no limit to the possible variations. At one end of the series is nucleic acid (C30H52N9P3O17, according to Kossel), a body containing the maximum (9 to n per cent) of phosphorus but without any proteid, and found as such only in sper- matozoa; in the middle are the nucleins proper; and at the other end are the nucleoproteids, containing the minimum of phosphorus. As phos- phorus is the characteristic component of nucleic acid, its amount will meas- ure the amount of the acid present in any molecule. The chemical differences in the action of cytoplasm and karyoplasm toward solvents are due also to the proportion of nucleic acid and proteid which they contain. These differences are qualitative and not quantitative. All of the nucleoproteids in the cell body are true ones in that they yield nuclein bases. Caseinogen. Caseinogen, the chief proteid of milk, yields para- nuclein on digestion. It bears the same relation to casein that fibrinogen does to fibrin. When acted on by rennin it splits into two parts of which one, the smaller, is peptone-like in character. The other, and larger part, is known as soluble casein and does not solidify in the absence of calcium salts. As calcium is always present in milk, it there unites with it and forms insoluble calcium casein; strictly speaking, therefore, the curd of milk is 86 THE CHEMICAL COMPOSITION OF THE BODY the calcium compound of soluble casein. Caseinogen may be prepared by adding dilute hydrochloric acid to milk until the mixture is distinctly acid, when a flocculent precipitate of caseinogen will be thrown down and may be separated by nitration. The fat which is carried down with this precipitate may be removed by washing with alcohol and then with ether. Caseinogen may also be prepared by adding to milk an excess of crys- tallized magnesium sulphate or sodium chloride, either of which salts causes it to separate out. Caseinogen gives the biuret ' and Millon's reactions. It is soluble in distilled water, dilute or strong alkalies, and sulphuric acid, but insoluble in sodium chloride and 0.2 per cent of hydrochloric acid. Vitellin. Vitellin is prepared from yolk of egg by washing with ether until all the yellow matter has been removed. The residue is then dissolved in 10 per cent saline solution, filtered, and poured into a large quantity of distilled water. The precipitate which falls is impure vitellin. It gives the same tests as myosin, but is not precipitated on saturation with sodium chloride; it coagulates at about 75° C. Albuminoids. The albuminoids belong to the simple tissues of the body which are derived from the epiblast and are characterized by a lack of any degree of activity, either physiological or chemical. They are nitrogenous bodies derived from proteid matter in the cells, and give crys- talline amido-acids and nitrogenous bases on decomposition, but differ from true proteids in not having their nitrogen in a form fit for the physiological needs of the body. In other words, they are not true nitrogen-supplying foods, though gelatin has a certain indirect value as it protects the body proteids from work in many ways. The albuminoids are soluble in dilute acids or alkalies; they may be distinguished from albumin or globulin by being insoluble in water or salt solution respectively. Typical albuminoids are gelatin, elastin, chondrin, keratin, etc. Gelatin. Gelatin is contained in the form of collagen, its anhy- dride, in bone, ossein, teeth, fibrous connective tissues, tendons, ligaments, etc. It may be obtained by prolonged action of boiling water or of dilute acetic acid. The percentage composition is O 25.24 per cent, H 6.56 per cent, N 17.81 per cent, C 50 per cent, SO 25 per cent. It contains more nitrogen and less carbon and sulphur than proteids. It is amorphous, and trans- parent when dried. It does not dialyze; it is insoluble in cold water, but swells up to about six times its volume; it dissolves readily on the addition of very dilute acids or alkalies. It is soluble in hot water, and forms a jelly on cooling, even when only i per cent of gelatin is present. It is also soluble in hot salt solution. Prolonged boiling in dilute acids or in water destroys the power of forming a jelly on cooling. On decomposition it gives 2 per cent of leucin and 2.6 per cent of argenin, but no tyrosin, and a large amount of glycocoll (amido-acetic acid or glycin), a crystalline substance. ELASTIN 87 A fairly strong solution of gelatin, 2 per cent to 4 per cent, gives the xanthoproteic test, but with no previous precipitate by nitric acid; the biuret test, the Millon's test, but with no precipitate. It is precipitated with tannic acid, with alcohol and picric acid. It is not precipitated with acetic acid, hydrochloric acid, mercuric chloride, nor with potassium ferrocyanide, and acetic acid. Elastin is found in elastic connective tissue, in the ligamenta subflava, ligamentum nuchae, etc. It is insoluble in all ordinary reagents, but swells up both in cold and hot water. It is slowly soluble in strong caustic soda, when heated. It is precipitated by tannic acid and does not gelatinize. It gives the proteid reactions with strong nitric acid and am- monia, and imperfectly with Millon's reagent. On decomposition it gives 4.5 per cent of leucin, a small amount of argenin, and a mere trace of tyrosin. It is prepared by boiling with water, then treating with artificial gastric and pancreatic juices, then boiling again in water, and then extracting with acids, alcohol, and ethers; the remainder is elastin. Chondrin is found in the condition of chondrigen in cartilage. It is obtained from chondrigen by boiling. It is soluble in hot water, and in solutions of neutral salts, e.g., sulphate of sodium, in dilute mineral acids, caustic potash, and soda. It is insoluble in cold water, alcohol, and ether. It is precipitated from its solutions by dilute mineral acids (excess redis- solves it), by alum, by lead acetate, by silver nitrate, and by chlorine water. On boiling with strong hydrochloric acid, it yields grape-sugar and certain nitrogenous substances. Prolonged boiling in dilute acids, or in water, destroys its power of forming a jelly on cooling. Keratin is obtained from hair, horns, finger-nails, etc. Its com- position is very similar to that of ordinary albumin and is approximately €49.5, H 6.5, N 16.8, S 4, O 23.2; the keratins obtained from the various substances are distinct and differ slightly though closely related. Sulphur is the characteristic body found in keratin and occurs as a sulphur-contain- ing radicle. A large amount of mercaptan sulphur can usually be obtained. On decomposition, keratin yields argenin 2.26 per cent, leucin 10 per cent, and tyrosin 4 per cent. Keratin is insoluble in water, salt, sodium carbonate, and dilute hydro- chloric acid. It is slowly soluble when warmed in caustic potash or sul- phuric acid. It gives Millon's and the xanthoproteic reactions. Neurokeratin is a form of keratin which is found in the white substance of Schwann around the axis-cylinders of nerves. It yields argenin 5 per cent, leucin 10 per cent, and tyrosin 3.5 per cent. Products of Proteid Decomposition. The products of proteid de- composition under the influence of oxidizing and hydrolyzing agents are of the greatest significance in indicating the character and composition of the proteid molecule. Cleavage-products of widely varying degrees of com- 88 THE CHEMICAL COMPOSITION OF THE BODY plexity are obtained. But, running through the cleavage compounds are certain nuclei or constitution complexes, which in all probability are found in the proteid itself, in fact form the basic structure of the molecule. The following account is taken from the excellent discussion by Witthaus (" The Medical Student's Manual of Chemistry"): "Active oxidizing agents attack the proteid molecule profoundly, yield- ing products which are for the most part far removed from the original sub- stance, and which are themselves products of decomposition of the 'atomic complexes' above referred to; acids and aldehydes of the fatty, oxalic, and benzoic series and their nitrils, including hydrocyanic acid, ketones, amido- acids, carbon dioxid, and ammonia. With HNO3 various nitro derivatives are obtained, and with Cl, Br, and I halid derivatives. By oxidation with K2Mn2O8 an acid, oxyprotosulfonic, containing the sulfonic group, is formed, and by continued oxidation peroxyprotonic acid. In oxidation with BaMn2O8 guanidin is one of the products. " Fusion with caustic alk'alies also causes deep decomposition, the prod- ucts being ammonia, mercaptan, fatty acids, amido fatty acids, tyrosin, indol, and skatol. " By boiling with dilute mineral acids, or with HC1 -j- SnQ2, the pro- teids are hydrolyzed with formation of hydrogen sulfid, ethyl sulfid and ammonia as simple products, and amido-acids, hexon bases, pyrrolidin and oxypyrrolidin carboxylic acids, and melanoidins, the last-named being also products of decomposition of the melanins, substances to which the hair and other dark portions of the body owe their color. The amido-acids, including serin, tyrosin, and cystin, produced in this and other hydrolytic decompositions probably exist in the proteids as polypeptids, formed by the union of several amido-acid complexes. " Considering the nitrogen which is split off, in more or less complex combination, on hydrolysis of proteids by boiling with dilute acids, it appears to have existed in the parent proteid in five forms of combination, corre- sponding to five classes of decomposition products: i, Easily separable, so-called amino-nitrogen, given off as NH3; 2, Urea-forming nitrogen, in the guanidin remainder of argenin; 3, Basic nitrogen, or diamido-nitrogen, contained in basic nitrogen compounds, precipitable by phosphotungstic acid; 4, Monamido-nitrogen, in monamido-acids; 5, Humus nitrogen, in humus-like melanoidins, dark-colored, amorphous, nitrogenous remainders. " The quantitative distribution of nitrogen in these five groups differs in different proteids : i. Is entirely absent in protamins; i to 2 per cent in gela- tin; 5 to 10 per cent in other animal proteids; 13 to 20 per cent in vegetable proteids. 2, In protamins 22 to 44 per cent; in histons 12 to 13 per cent; in gelatin 8 per cent; in other proteids 2 to 5 per cent. 3, In protamins 63 to 88 per cent; in histons 35 to 42 per cent; in other animal proteids 15 to 25 per cent; in vegetable proteids 5 to 37 per cent. 4, The greater PRODUCTS OF PROTEID DECOMPOSITION 89 part of the nitrogen, 55 to 76 per cent, in proteids other than protamins is in this form. 5, Varies within wide limits. "The sulfur, the amount of which varies greatly in different proteids, is given off on hydrolysis as cystin, cystein, a-thiolactic acid, mercaptans, and ethyl sulfid. "The nitrogen-containing products of hydrolysis of proteids may be thus classified: I. Aliphatic. A. Containing no sulfur: 1, Guanidin remainder. H2N.C : NHj (-f-ornithin=argenin); 2, Monobasic monamido acids: glycocoll, alanin, amido-valerianic acid, leucin, serin; 3, Dibasic monamido-acids: aspartic and glutamic; 4, Monobasic diamido-acids: ornithin, lysin; B. Containing nitrogen and sulfur: Cystin, cystein; II. Carbocyclic: phenylamidopropionic acid, tyrosin; III. Heterocyclic : A. Pyrrol derivatives: pyrrolidin and oxypyrrolidin carboxylic acids; B. Glyoxalin derivatives (?): histidin; C. Indole derivatives: indol, skatol, tryptophane." The amido-acids, although belonging to the different seriesf are, accord- ing to Fischer's views, supposed to be combined into more and more com- plex groupings. In the simplest combinations two or more molecules of the same or of different amido-acids combine with the elimination of water. This is the reverse of the hydrolytic process and results in Fischer's peptids. Protamin, the simplest of the proteids, yields a relatively simple series of amido-acids and according to Taylor's work, already referred to, is evidently a polypeptid of comparatively complex structure. "All proteids except the protamins and some of the peptones contain sulfur. One fraction of this, referred to as 'loosely combined' sulfur, is given off as hydrogen sulfid by boiling with alkaline solutions. It is this fraction which causes the formation of a brown or black color, or even a black precipitate, .when a proteid is heated with a solution of caustic alkali in the presence of lead acetate, in the 'sulfur test' for the proteids. The second fraction is not separable in this manner, but only, as a sulfate, by fusion with saltpeter and sodium carbonate, or, as a sulfid, by fusion with caustic potash. The ratio of loosely combined sulfur to total sulfur varies notably in different proteids, from § in serum to f in hemoglobin. It would appear from this constant difference in separability of different portions of sulfur from proteids that the molecules of these substances must contain at least two atoms of sulfur in different forms of combination. This conclu- sion, is, however, invalidated by the fact that both cystin and cystein only give off one-half of their sulfur, and that very slowly, by boiling with alka* 90 THE CHEMICAL COMPOSITION OF THE BODY line solutions, yet the two atoms of sulfur in cystin are symmetrically com- bined, and the molecule of cystein contains but one sulfur atom. "Many proteids, not only the glycoproteids, but also true albumins, as egg albumin, serum albumin, serum globulin, the nucleoproteids, etc., re- act with Molisch's reagent, and, on hydrolysis, split off a carbohydrate group, which is an amido-sugar, usually glucosamin, CHO.CHNH2 (CHOH)3- CH2OH, probably existing in the proteid as a polysaccharid complex. Some of the nucleoproteids yield a pentose group, others laevulinic acid. Other proteids, as casein, myosin, and fibrinogen, yield no carbohydrate. "The decomposition of proteids by the proteolytic enzymes, pepsin, trypsin, and papain, consists of a series of hydrolyses, and results first in the formation of albumoses and peptones, and later by trypsin, particularly of polypeptids, amido acids, hexon bases, tryptophane, amins, diamins, and ammonia. These changes occur in the processes of digestion." The Pigments, etc. A number of pigments make their appear- ance in the body; for example, bilirubin, C16H18N2O3, is the common bile pigment. Its crystals are bluish-red in color and are probably derived from hematin of the blood. Biliverdin, C16H18N2O4, is an oxidation product of bilirubin. Urochrome and Urobilin occur in bile and in urine; the latter is prob- ably identical with stercobilin, which is found in the feces. Uroerythrin is one of the coloring matters of the urine. It is orange red and contains iron. Melanin is a dark brown or black pigment which occurs especially in epidermal tissues, where it is associated with keratin. It is found in the lungs, bronchial glands, hair, choroid, skin, etc.; also in the urine and in melanotic diseases, e.g., sarcoma. It is a transformation product of pro- teids, from which it can be derived by boiling proteid with sulphuric acid. Lipochromes are pigments, usually yellow or yellowish-red, which are associated with fat, being almost always present in adipose tissue. Little is known about them, but they are thought to consist only of C, H, and O. OILS AND FATS. The animal oils and fats are for the most part mixtures of tri-palmitin, C3H5(O.C16H310)3, tri-stearin, C3H5(O.C18H35O)3, zndtri-olein, C3H5(O.C18- NsaO);,, in different proportions. They are formed by the union of three molecules of fatty acid with one molecule of the triatomic alcohol, glycerin, C3H5(OH)3, and are ethereal salts or esters of that alcohol. Palmitic acid is C15H31COOH, stearic acid is C^H^COOR; oleic acid is Cl7HnCOOH. Human fat consists of a mixture of tri-palmitin, tri-stearin, and tri-olein, of which the two former contribute three-quarters of the whole. Olein is the only liquid constituent. The fat of milk (and butter) is tributyrin; butyric acid is C4H8O2. CARBOHYDRATES 91 Fats are insoluble in water and in cold alcohol; soluble in hot alcohol, ether, and chloroform. Colorless and tasteless ; easily decomposed cr saponi- fied by alkalies or superheated steam into glycerin and the fatty acids. Certain of the monatomic Fatty Acids are found in the body, viz., Formic CH2O2, acetic C2H4O2, and propionic C3H3O3, present in sweat, but normally in no other human secretion. They have been found else- where in diseased conditions. Butyric acid, C4H8O2, is found in milk and in sweat. Various others of these acids have been obtained from blood, muscular juice, feces, and urine. Of the diatomic fatty acids, one acid, Lactic acid, C3H6O3, exists in a free state in muscle-plasma, and is increased in quantity by muscular con- traction, but is never contained in healthy blood. Soaps. The fatty acids in combination with soda or potash, or similar bases, form soaps which are soluble in water, while the fats are not soluble. CARBOHYDRATES. The carbohydrates are bodies composed of C, H, and O, as aldehydes and ketols. They are classified as monosaccharides, dextrose, galactose, etc. These are the simplest molecules of the hexoses. They are sweet, odorless, soluble in water, and oxidize readily, hence their reducing power. They form crystalline osazones. They rotate polarized light. Their for- mula is C6H12O6. Disaccharides, maltose, saccharose, lactose, etc. They are formed by the union of two simpler molecules and the elimination of a molecule of water. They have the formula C12H.22On. And poly saccharifies, glycogen, starch, dextrin, gum, etc. They are much less soluble, can be hydrolyzed into the simpler forms, and have the formula (C6H10O5)n. Monosaccharides are especially soluble and polysaccharides are espe- cially insoluble; monosaccharides and disaccharides do not give colored solutions with iodine, while polysaccharides do; monosaccharides and (ex- cept saccharose) disaccharides reduce Fehling's solution, while polysaccha- rides do not. Of these the most important are: Starch. It is contained in nearly all plants, and in many seeds, roots, stems, and some fruits. It is a soft white powder composed of granules having an organized structure, consisting of granulose .(soluble in water) contained in a coat of cellulose (insoluble in water); the shape and size of the granules vary according to the source whence the starch has been obtained. It is not crystalline and will not dialyze. It is insoluble in cold water, in alcohol, and in ether; it is soluble after boiling for some time, and may be filtered, in consequence of the swelling up of the granulose, which bursts the cellulose coat, and, becoming free, is entirely dissolved in water. This solution is a solution of soluble starch or amydin. It gives a blue color- 92 THE CHEMICAL COMPOSITION OF THE BODY ation with iodine, which disappears on heating and returns on cooling. It is converted into maltose by diastase, and by boiling with dilute acids into dextrose. Glycogen. Glycogen is a polysaccharide contained in the liver, and also present in all muscles, but especially in those of very young animals, in the placenta, in colorless corpuscles, and in embryonic tissues. It is sometimes called animal starch and gives many reactions proper to starch itself. It is freely soluble in water, and its solution looks opalescent; it gives a port-wine coloration with iodine, which disappears on heating and returns on cooling. It is precipitated by basic lead acetate and is insoluble in absolute alcohol and in ether. It exists in the liver during life, but very soon after death is changed into sugar. It may be prepared by grinding muscle with sand till a pasty mass is formed, boiling the mass in water for twenty minutes, filtering, and then precipitating the glycogen from the filtrate by adding a little more than an equal quantity of 95 per cent alcohol. It is converted into sugar by diastase ferments, or into dextrose by boiling with dilute acids. Dextrin. This substance is made in commerce by heating dry potato-starch to a temperature of 400°. It is also produced in the .process of the conversion of starch into sugar by diastase, and by the salivary and pancreatic ferments. A yellowish amorphous powder, soluble in water, but insoluble in absolute alcohol and in ether. It corresponds almost ex- actly in tests with glycogen; but one variety (achroo-dextrin) does not give the port-wine coloration with iodine. Cane-Sugar, or Saccharose. It is contained in the juices of many plants and fruits, and is extracted from the sugar-cane, from beet-root, or from the maple. It is crystalline and is precipitated from concentrated solutions by absolute alcohol. It has no power of reducing copper salts on boiling. It is dextro-rotatory. It is not subject to alcoholic fermenta- tion, until by inversion it is converted into glucose, it chars on addition of sulphuric acid, and on heating with potassium or sodium hydrate. Lactose. Lactose is the chief carbohydrate of milk. It is less soluble in water than glucose; it is not sweet, and is gritty to the taste; but it is insoluble in absolute alcohol. In digestion it yields a molecule of dex- trose and a molecule of galactose. It undergoes alcoholic fermentation with extreme difficulty; gives the tests similar to glucose, but less readily. It is dextro-rotatory + 59°. Maltose. This sugar is produced by the action of the saliva and pancreatic juice on starch. It is also formed by the action of malt upon starch by the action of the ferment diastase. It is converted into dextrose by dilute sulphuric acid. It is dextro-rotatory; ferments with yeast; reduces copper salts; and crystallizes in fine needles. Dextrose, or Glucose. Dextrose pccurs widely diffused in the INORGANIC PRINCIPLES 93 vegetable kingdom, in diabetic urine, in the blood, etc. It is usually ob- tained from grape-juice, honey, beet-root, or carrots. As prepared, it really is a mixture of two isomeric bodies, Dextrose or grape-sugar, which turns a ray of polarized light to the right (-f- 56°), and L&vulose or fruit-sugar, which turns the ray to the left. It is easily soluble in water and in alcohol; not so sweet as cane-sugar; the relation of its sweetness to that of cane-sugar is as 3 to 5. It is not so easily charred by strong sulphuric acid as cane-sugar. It is not entirely soluble in alcohol. It undergoes alcoholic fermentation with yeast. Dextrose is the characteristic carbohydrate of the blood. It has the power of reducing the salts of silver, bismuth, mercury, and copper, either to the form of the metal in the first three cases, or to the form of the sub- oxide in the case with cuprous salts. Upon this property the chief tests for the sugar, e.g., Trommer's and Bottcher's, depend. It undergoes alcoholic fermentation with yeast, and lactic-acid fermentation with bacteria lactis. It forms caramel when strongly heated, and is also charred with strong acids. Levulose is one of the products of the decomposition of cane-sugar by means of dilute mineral acids, or by means of the ferment invertin in the alimentary canal. It reacts to the same test as glucose, but is non-crystal- lizable, and is laevo-rotatory. It is soluble in water and in alcohol. Its com- pound with lime is solid, whereas that with dextrose is not. Galactose. This monosaccharid is formed from lactose by the action of dilute mineral acids, or inverting ferments; it may also be ob- tained from cerebrin. It undergoes alcoholic fermentation, and reduces copper salts to the suboxide. Inosite. Inosite occurs in the heart and voluntary muscles, as well as in beans and other plants. It crystallizes in the form of large color- less monoclinic tables, which are soluble in water, but insoluble in alcohol or ether. It has the formula of glucose, but is not a sugar. Inosite may be detected by evaporating the solution containing it nearly to dryness, and by then adding a small drop of solution of mercuric nitrate, and afterward evaporating carefully to dryness, a yellowish-white residue is obtained; on further cautiously heating, the yellow changes to a deep rose-color, which disappears on cooling, but reappears on heating. If the inosite be almost pure, its solution may be evaporated nearly to dryness. After, the addition of nitric acid, the residue mixed with a little ammonia and calcium chloride, and again evaporated, yields a rose-red coloration. INORGANIC PRINCIPLES. Salts. The inorganic principles of the human body are numerous. They are derived, for the most part, directly from food and drink, and pass through the system unaltered. But some salts are decomposed on their 94 THE CHEMICAL COMPOSITION OF THE BODY way, as chloride of sodium, of which only four-fifths of the quantity ingested are excreted in the same form. Some are newly formed within the body- as, for example, a part of the sulphates and carbonates. Much of the inorganic saline matter found in the body is a necessary constituent of its structure, as necessary in its way as albumin or any other organic principle. Another part is important in regulating or modifying various physical processes, as absorption, solution, and the like. A part must be reckoned only as matter which is, so to speak, accidentally present, whether derived from the food or the tissues, and which will, at the first opportunity, be excreted from the body. The principal salts present in the body are: Sodium and Potassium Chlorides. These salts are present in nearly all parts of the body. The former seems to be especially necessary, judging from the instinctive craving for it on the part of animals in whose food it is deficient, and from the diseased condition which is consequent on its with- drawal. The quantity of sodium chloride in the blood is greater than that of all its other saline ingredients taken together, but it is present chiefly in the fluids of the body. In the tissues, the muscles for example, the quantity of sodium chloride is less than that of the chloride of potassium, which forms a constant ingredient of protoplasm. Calcium Fluoride. It is present in minute amount in the bones and teeth, and traces have been found in the blood and some other fluids. Calcium, Potassium, Sodium, and Magnesium Phosphates. These phos- phates are found in nearly every tissue and fluid. In- some tissues — the bones and teeth — the phosphate of calcium exists in very large amount. The phos- phate of calcium is intimately incorporated with the organic basis or matrix, but it can be removed by acids without destroying the general shape of the bone. After the removal of its inorganic salts, a bone is left soft, tough, and flexible. Potassium and sodium phosphates, with the carbonates, maintain the alkalinity of the blood. Calcium Carbonate. It occurs in bones and teeth, but in much smaller quantity than the phosphate. It is found also in some other parts. The small concretions of the internal ear (otoliths) are composed of crystalline calcium carbonate, and form the only example of inorganic crystalline matter existing as such in the body. Potassium and Sodium Carbonates and Sulphates. These are found in the blood and most of the secretions and tissues. Silicon. A very minute quantity of silica exists in the urine and in the blood. Traces of it have been found also in bones, hair, and some other parts. Iron. The especial place of iron is in hemoglobin, the coloring-matter of the blood, of which a full account will be given with the chemistry of the blood. Iron is found, in very small quantities, in the ashes of bones, mus- LABORATORY EXPERIMENTS 95 cles, and many tissues, and in lymph and chyle, albumin of serum, fibrin, bile, milk, and other fluids. A salt of iron, probably a phosphate, exists in the hair, black pigment, and other deeply colored epithelial or horny substances. Water. Water forms a large proportion, more than two-thirds, of the weight of the whole body. Its relative amount in some of the principal solids and fluids of the body is shown in the following table (from Robin and Verdeil): Quantity of Water in Per Cent. Teeth 10.0 Bile 88.0 Bones 13.0 Milk 88.7 Cartilage 55 -° Pancreatic juice 9°-° Muscles 75-° Urine 93-6 Ligament 76.8 Lymph 96.0 Brain 7&-9 Gastric juice 97-5 Blood 79 . 5 Perspiration 98 . 6 Synovia 80.5 Saliva 99-5 In all the fluids and tissues of the body — blood, lymph, muscle, gland, etc. — water acts the part of a general solvent, and by its means alone circula- tion of nutrient matter is possible. It is the medium also in which all fluid and solid aliments are dissolved before absorption, as well as the means by which all, except gaseous, excretory products are removed. All the various processes of secretion, transudation, and nutrition depend of necessity on its presence for their performance. The greater part, by far, of the water present in the body is taken into it as such from without, in the food and drink. A small amount, however, is the result of the chemical union of hydrogen with oxygen in the oxida- tions of the body. The loss of water from the body is intimately connected with excretion from the lungs, skin, and kidneys, and, to a less extent, from the alimentary canal. The loss from these various organs may be thus apportioned (quoted by Dalton from various observers): From the Alimentary canal (feces) 4 per cent " Lungs 20 " " Skin (perspiration) 30 " " Kidneys (urine) 46 " LABORATORY EXPERIMENTS ON THE CHEMISTRY OF THE BODY. Proteid General Reactions. Certain tests depending on the pres- ence of one or more of the constituent groups in the proteid molecule, while not conclusive each in itself, when taken together serve for proteid 96 THE CHEMICAL COMPOSITION OF THE BODY identification. Dilute some white of egg with ten volumes of water, filter off the precipitated globulin, and use the egg albumin in the following tests: 1. Color Reactions of Proteids. a. Xanthoproteic. Add concentrated nitric acid to 2 c.c. of the egg albumin in a test tube, a lemon-yellow color appears on gently heating. Add excess of ammonia, the color deepens to orange, or with potassium hydrate to reddish brown. Egg albumin is also precipitated by the acid, but peptone gives only the color change. This re- action depends upon the presence of the tyrosin nucleus, or that of indol, in the proteid molecule. b. Milton's reaction. Millon's reagent (mercuric and mercurous nitrate in weak nitric-acid solution) added to albumin solution gives a white co- agulum in the cold which turns purple-red on heating to 70° C. or more. The reaction is due to the tyrosin grouping. c. The biuret reaction. Excess of sodium or potassium hydrate with a few drops of 2 per cent copper sulphate in albumin solution when heated gives a violet color. Albumoses give a pinkish violet, and peptones a pink color in this reaction, but care must be taken not to use an excess of copper sulphate. The reaction seems to depend on the presence of the polypeptid groups. d. Adamkiewicz reaction. If dilute glyoxylic acid be added to proteid solution, and concentrated sulphuric acid run under the mixture, a ring of colors is produced at the junction of the layers when gentle heat is applied; red at the bottom, then green and violet. When shaken the whole becomes violet. The reaction depends upon the tryptophane group. 2. Precipitations, a. Acid precipitation. Proteids form insoluble salts with tannic acid, phospho-tungstic acid, hydroferrocyanic acid, picric acid, etc. The proteid is changed in the reaction and cannot be recovered by breaking up the salt. Strong mineral acids, hydrochloric acid, nitric acid, etc., precipitate proteids, but the peptones are soluble in excess. b. Heavy metal precipitation. Proteids form insoluble compounds with mercuric chloride, lead acetate, copper sulphate, silver nitrate, etc. c. Alcohol. Proteids are precipitated and coagulated by an excess of alcohol. Peptone alone is recoverable from alcoholic precipitation. d. Heat coagulations. Make the egg-albumin very faintly acid with 2 per cent acetic and heat to boiling, a white cloudy coagulum appears. Albumoses and peptones are not heat-coagulated. e. Precipitation by neutral salts. Add crystals of ammonium sulphate to egg albumin solution to saturation, a white flocculent precipitate forms. The precipitate can be recovered as unchanged albumin by removing the excess of salt by dialysis. Reactions Characteristic of Individual Proteids. The proteid groups most often met by the student are the albumins, globulins, albumi- nates, albumoses, peptones, enzyme-coagulated proteid, and heat-coagulated proteid. Each has certain characteristics. REACTIONS CHARACTERISTIC OF INDIVIDUAL PROTEIDS 97 3. Albumins, a. Solubility in water and in neutral salts. Test each statement. Albumin is soluble in distilled water, dialyze out the traces of salts. It is soluble in saturated sodium chloride and saturated magnesium sulphate. It is insoluble in saturated ammonium sulphate. b. Heat coagulation. Mount a test tube containing 5 c.c. faintly acid egg-albumin in a 500 c.c. beaker of water which is supported by a gauze and ring stand. Suspend a thermometer bulb in the middle of the albumin solution. Gradually heat the beaker of water, stirring constantly, thus uni- formly heating the albumin. Coagulation takes place at from 73° to 75° C., but turbidity a little earlier. 4. Globulins, a. Solubility in water and in neutral salts. Test the following statements, using serum globulin. Globulin is insoluble in distilled water. It is soluble in dilute neutral salt solutions — sodium chlo- ride, magnesium sulphate, ammonium sulphate. Globulin is precipitated by adding sodium chloride or magnesium sulphate to complete saturation. Fibrinogen is precipitated by half -saturated magnesium sulphate. Globulins are precipitated by adding to their solution an equal volume of saturated ammonium sulphate, i.e., by half -saturated solution. b. Heat coagulation. Test the temperature at which globulins are heat coagulated by the method described above, on a sample of salted plasma for nbrinogen which coagulates at 56° C., and on serum globulin which coagulates at 73° C. 5. Albuminates. Digest egg albumin in 0.2 per cent hydrochloric acid for an hour and test: a. Solubility. It is insoluble in neutral solutions and in saturated neu- tral salts, but soluble in dilute acids and alkalies. b. Heat coagulation. It is not coagulated by heat. 6. Albumoses and Peptones. These proteids are formed in the alimentary canal in the process of digestion under the influence of the enzymes, pepsin and trypsin. Make a 5 per cent solution of Armour's pep- tone (which contains chiefly albumoses) and test: a. Heat coagulation. These proteids are not coagulated. b. Alcohol. When added to excess, a precipitate occurs, but when collected on a filter the precipitate may be redissolved in water. c. General proteid reactions. These proteids fail to give many of the precipitations, but give the color changes. The biuret test yields a rose pink color. d. Neutral salts. Albumoses are insoluble in saturated ammonium sulphate. Filter and test the filtrate for proteid. It gives the biuret test. This is due to peptones which are soluble in all salt solutions. 7. Ferment and Heat-Coagulated Proteids. Boiled egg white should be used for the example of the former, and fibrin for the latter. Test for the color reactions, experiment i, which they both give. These pro- 7 98 THE CHEMICAL COMPOSITION OF THE BODY teids are insoluble in the usual solvents, though fibrin is slightly soluble in 10 per cent sodium chloride. Carbohydrate Reactions. The carbohydrate representatives that should be examined are: 8. Starch. Make a solution of starch by boiling i gram of starch in 100 c.c. of distilled water and test. a. Iodine test. Shake up three or four drops of dilute iodine solution with 2 c.c. starch. A deep blue color appears. The color is discharged in dilute alkali and reappears on acidifying again. Heat also discharges the color. b. Fehling's test. Commercial starch often contains reducing sugar. Boil 2 c.c. of starch solution with i c.c. of fresh Fehling. If a reddish-yellow precipitate settles on standing, the starch contains reducing sugar as an impurity. Starch does not reduce copper in the presence of an alkali. c. Hydrolysis of starch. Boil starch solution with 5 per cent sulphuric acid for fifteen minutes. Test with Fehling's solution, first neutralizing the excess of acid. A copious precipitate of cuprous oxide shows that the starch has been converted to reducing sugar. 9. Dextrin. Make a 5 per cent solution of dextrin in distilled water and test: a. Iodine. This gives a rich reddish-brown color which is characteristic. b. Fehling. Not reduced by dextrin. 10. Dextrose. Test a 5 per cent solution of dextrose: a. Iodine test. No reaction. b. Trommer's test. Add caustic soda in excess and a few drops of 2 per cent copper sulphate and boil, or use Fehling's solution. A reduction of the copper takes place. Barfoid's solution also is reduced by dextrose, but not by maltose. 11. Glycogen. Make up 10 c.c. of a i per cent solution of gly- cogen and repeat the tests: a. Iodine. This gives a wine-red color very much like that given by dextrin. The color is discharged by heating, but reappears on cooling. b. Lead acetate. It gives a precipitate, but one must guard against the presence of proteid as an impurity. c. Trommer's test. Glycogen does not reduce copper. The Fats. The common fats are the oleins, palmitins, and stearins. These are glycerin salts of the fatty acids. The animal fats are mixtures of these fats in different proportions. 12. Neutral Fat. a. Melting-point. Compare neutral olive oil, some fresh rendered lard, and some tallow. The former is fluid at ordinary room temperature. Determine the melting-points of the lard and of the tallow by the method of Wiley. Fill a test tube, one-half full of water and add a two-inch top layer of alcohol. Prepare a thin flake of fat and suspend it in the test tube at the dividing line of the water and alcohol. Insert the FAT ACIDS 99 bulb of a thermometer at the same level. Mount the test tube with the thermometer in a beaker on a ring stand, fill the beaker with water above the level of the content of the test tube, and gradually heat with stirring of the water in the beaker. At the melting temperature the flake of fat will run into a round drop. b. Solubility. Fat is insoluble in water, but soluble in ether, chloro- form, benzol, and in alcohol. c. Saponification. Heat some fat in an evaporating-dish, add sodium hydrate, and boil. Saponification takes place. The soap is soluble in water. Add 25 per cent sulphuric acid to some of the soap, the fatty acid is liber- ated and collects on the surface of the solution. 13. Fat Acids. Collect some of the fatty acids, wash to remove excess of alkali, and dissolve in ether. a. Acid reaction. Add ether solution of the fatty acid to neutral litmus, or to faintly alkaline phenolphthalein. The former turns red, and the red of the latter is discharged, the acid reaction. b. Acrolein test. Evaporate the ether from 2 c.c. of the solution, add potassium bisulphate crystals to the acid in a test tube, and raise to a high heat over a bunsen. No acrolein is given off. Repeat on neutral fat and on glycerin. Both liberate the irritating fumes of acrolein. 14. Emulsification. a. Shake up neutral olive oil and water, no emulsion is formed and the oil quickly separates. b. Add a couple of drops of fatty acid, a very good but temporary emul- sion is now formed. c. Use rancid fat, a temporary emulsion is formed. d. Add a little soap to either of the above, i.e., c. A good permanent emulsion is now formed. 15. The Salts. A goodly series of salts is present in the body, the most important elements of which are sodium, potassium, calcium, mag- nesium, and iron, as chlorides, sulphates, and phosphates. Burn 50 c.c. of blood at a dull red heat, take up in water and test: a. Chlorides. Add i per cent nitrate of silver, a white precipitate, in- soluble in nitric acid, soluble in ammonia, and reprecipitated by nitric acid. b. Sulphates. Add barium chloride, a white precipitate, which quickly settles and is insoluble in nitric acid. c. Phosphates. Add nitric acid and a few drops of i per cent ammonium molybdate, a yellow granular precipitate of phosphorus. It is soluble in ammonia, reprecipitated in nitric acid. d. Calcium. Make a hydrochloric acid extract of the ash of blood above, add ammonia to excess, then a solution of ammonium oxalate, a deli- cate white precipitate where traces are present. e. Iron. Add hydrochloric acid and a few drops of ferrocyanide of po- tassium. A blue color indicates the presence of iron. PLATE II VARIETIES OF LEUCOCYTES a. Polymorphonuclear Neutrophiles. Note the varieties in size and shape of gran- ules, the regular staining of the nuclei, the light space around them, their relatively central position in the cell. b. Myelocytes. Note the identity of granules with those just described; the even, pale stain of nuclei, their position near the surface (edge) of the cell. The two cells figured indicate the usual variations in size of the whole cell. c. Small Lymphocytes. In the cell at the left note the transparent protoplasm; in the cell next to it note the very pale pink of protoplasm around the nucleus which is deeply stained, especially at the periphery. The next cell has an indented nucleus; its protoplasm relatively distinct. The cell on the extreme right shows no protoplasm and is probably necrotic. In all note absence of granules with this stain. With basic stains a blue net- work appears in the protoplasm. d. Large Lymphocytes. Note the pale stain of nuclei and protoplasm, regularity of outline; indented nucleus in one. Every intermediate stage between these and the "small " lymphocytes occurs, and the distinction between them is arbitrary. e. Eosinophile. Note regular shape, loose connection of granules, their copper color, their uniform and relatively large size, and spherical shape. /. Eosinophilic Myelocyte. Note similarity to the ordinary myelocytes 6, except as regards granules. Color of granules may be, as in e, ordinary eosinophile. All the above were stained with the Ehrlich triacid stain, and drawn with camera lucida. Oil immersion objective ^ and ocular No. iii. of Leitz. ^ Cabot.) CHAPTER IV THE BLOOD THE blood is the fluid medium of which all the tissues of the body are nourished. By means of the blood materials absorbed from the alimentary canal as well as oxygen taken from the air in the lungs are carried to the tissues, while substances which result from the metabolism of the tissues are carried to the excretory organs to be removed from the body. The blood also acts as a medium of exchange for products of glandular activity between the various tissues themselves, internal secretions, and it is a factor in the regulation of body temperature. The blood is a somewhat viscid fluid, and in man and in all other vertebrate animals, with the exception of two of the lowest, is red in color. The exact color of the blood is variable; that taken from the systemic arteries, from the left side of the heart and from the pulmonary veins is of a bright scarlet hue; that obtained from the systemic veins, from the right side of the heart, and from the pulmonary artery is of a much darker color, which varies from bluish-red to reddish-black. At first sight the red color appears to belong to the whole mass of blood, but on further examination this is found not to be the case. In reality blood con- sists of an almost colorless fluid, called plasma or liquor sanguinis, in which are suspended numerous minute masses of protoplasm, called blood-corpus- cles. The corpuscles are of the two varieties, the white ameboid corpuscles, or leucocytes, and the red corpuscles, erythrocytes. The latter compose by far the larger mass of blood-cells and contain the red pigment, hemoglobin, to which the color of the blood is due. The plasma or fluid part of the blood is a remarkably complex chemical mixture. It is kept in constant rapid circulation through the blood-vessels of the body and is, therefore, thoroughly mixed and homogeneous in character. Quantity of the Blood. The quantity of blood in any animal under normal conditions bears a fairly constant relation to the body weight. The amount of blood in man averages -£•$ to YJ of the body weight. In other mammals the proportion of blood is also fairly constant, varying from ^ to -^g- of the body weight. In many of the lower vertebrates the relative quantity of blood is very much less. An estimate of the quantity in man which corresponded very nearly with this proportion has been more than once made by methods illustrated by the following data: A criminal was weighed before and after decapita- 101 THE BLOOD tion; the difference in the weight representing the quantity of blood which escaped. The blood-vessels of the head and trunk were then washed out by the injection of water until the fluid which escaped had only a pale red or straw color. This fluid was then also weighed, and the amount of blood which it represented calculated by comparing the proportion of solid matter contained in it with that of the first blood which escaped on decapitation. Two experiments of this kind gave precisely similar results (Weber and Lehmann). This quantity of blood is distributed in the different parts of the body, chiefly in the muscles, the liver, the heart, and larger blood-vessels, as shown by the following figures determined on the rabbit by Ranke (from Vierordt) : Per cent. Spleen 0.23 Brain and cord i . 24 Kidney i . 63 Skin 2.10 Abdominal viscera 6. 30 Cartilage 8 . 24 Heart, lungs, and large blood-vessels 22.76 Resting muscle 29 . 20 Liver 29.30 It should be remembered, in connection with these estimations, that the quantity of the blood must vary very considerably, even in the same animal, with the amount of both the ingesta and egesta of the period im- mediately preceding the experiment. It has been found, for example, that the quantity of blood obtainable from the body of a fasting animal rarely exceeds a half of that which is present soon after a full meal. COAGULATION OF THE BLOOD. The most characteristic property which the blood possesses is that of clotting or coagulating. This phenomenon may be observed under the most favorable conditions in blood which has been drawn into an open vessel. In about two or three minutes, at the ordinary temperature of the air, the surface of the fluid is seen to become semi -solid or jelly-like, and this change takes place, in a minute or two afterward, at the sides of the vessel in which it is contained and then quickly extends throughout the entire mass. The time which is occupied in these changes is about eight or nine minutes. The solid mass is of exactly the same volume as the previously liquid blood, and adheres so closely to the sides of the containing vessel that if the latter be inverted none of its contents escape. The solid mass is the crassamentum or dot. If the clot be watched for a few minutes, drops of a light, straw- colored fluid, the serum, may be seen to make its appearance on the surface, and, as it becomes greater and greater in amount, to form a complete super- COAGULATION OF THE BLOOD 103 ficial stratum above the solid clot. At the same time the fluid begins to transude at the sides and at the under surface of the clot, which in the course of an hour or two floats in the liquid. The appearance of the serum is due to the fact that the clot contracts, thus squeezing the fluid out of its mass. The first drops of serum appear on the surface about eleven or twelve minutes after the blood has been drawn; and the fluid continues to transude for from thirty-six to forty-eight hours. The clotting of blood is due to the development in the plasma of an in- soluble substance called -fibrin. This fibrin forms threads or strands through the mass in every direction. The strands adhere to each other wherever they come in contact, thus forming a very dense tangle and meshwork which incloses within itself the blood-corpuscles. The clot when first formed, therefore, includes the whole of the blood in an apparently solid mass, but soon the fibrinous meshwork begins to contract and the serum is squeezed out. When a large part of the serum has been squeezed out the clot is found to be smaller, but firmer and harder, as it is now made up largely of fibrin and blood-corpuscles. Thus in coagulation there is a rearrangement of the constituents of the blood; liquid blood being made up of plasma and blood- corpuscles, and clotted blood of serum and clot. Liquid Blood. Plasma. Corpuscles. Serum. Fibrin. I Clot. Clotted Blood. The rapidity with which coagulation takes place varies greatly in different animals and at different times in the same animal. Where coagulation is very slow the red corpuscles, which are somewhat heavier than plasma, often have time to settle considerably before the fibrin is formed. If the blood is rapidly cooled to something approaching o° C. then the clot is very greatly delayed. Horse's blood is particularly favorable for demonstrating this point. In it clotting occurs so slowly that very often the red corpuscles will completely settle out, and when the blood is again warmed and the clotting takes place there is a superficial stratum differing in appearance from the rest of the clot, and is of a grayish-yellow color. This is known as the buffy coat or crusla phlogistica. The buffy coat, produced in the manner just described, commonly contracts more than the rest of the clot, on account of the absence of colored corpuscles from its meshes. When the clot is allowed to stand the white corpuscles migrate to the surface by ameboid movement, 104 THE BLOOD often in such numbers that they form a distinct superficial layer, grayish- white in appearance. That the clotting of blood is due to the gradual appearance in it of fibrin may be easily demonstrated. For example, if recently drawn blood be whipped with a bundle of twigs or wires, the fibrin may be withdrawn from the blood before it can entangle the blood-corpuscles within its meshes, as it adheres to the twigs in stringy threads relatively free from corpuscles. The blood from which the fibrin has been withdrawn no longer exhibits the power of spontaneous coagulability and it is now called defibrinated blood. Although these facts have long been known, the closely associated problem as to the exact manner in which fibrin is formed is by no means so simple. Fibrin is derived from the plasma. Pure plasma may be procured by delaying coagulation in blood by keeping it at a temperature slightly above -4V FIG. 107. — Reticulum of Fibrin, from a Drop of Human Blood, after Treatment with Rosanilin. (Ranvier.) freezing point, until the colored corpuscles have subsided to the bottom of the containing vessel. The blood of the horse is specially suited for the pur- poses of this experiment. A portion of the colorless supernatant plasma, if decanted into another vessel and exposed to the ordinary temperature of the air, will coagulate, producing a clot similar in all respects to blood clot, except that it is colorless from the absence of red corpuscles. If some of the plasma be diluted with twice or three times its bulk of normal saline solution (0.9 per cent), coagulation is delayed, and the stages of the gradual formation of fibrin in it may be conveniently watched. The viscidity which precedes the complete coagulation may be actually seen to be due to the formation of fibrils of fibrin — first of all at the edge of the fluid-containing vessel, and then gradually extending throughout the mass. If a portion of plasma, diluted or not, be whipped with a bundle of twigs the fibrin may be obtained as a solid, stringy mass, just in the same way as from the ei .ire THEORIES OF COAGULATION 105 blood, and the resulting fluid no longer retains its power of spontaneous coagulability. Theories of Coagulation. It is evident that the blood plasma contains some substance or substances which take part in the formation of fibrin. By numerous investigations it has been found that the direct ante- cedent of the fibrin is the proteid substance, fibrinogen. This fibrinogen exists in the blood plasma at all times, but is somewhat increased under certain conditions. The fibrinogen is reacted on by another substance known as thrombin, or by the historical term fibrin ferment. We shall not present the numerous theories which have been held concerning blood coagu- lation, many of which have been more or less disproven, but shall try to present Blood Tissue Cells Plasma Blood Plates Corpuscles Neutral Salts Fibrinogen Calcium Salts (for dissolving fibrinoRen) Fibrin-globulin Prothrombin Thrombokinase Thrombin Fibrin FIG. 108. — Schema of Coagulation. the condensed statement of the present explanations of this intricate phenom- enon. One may start from the statement that the fibrinogen of the plasma when acted upon by the thrombin, also of the plasma, produces an insoluble substance, fibrin. The chief interest centers around the origin and char- acter of the fibrinogen, the origin and nature of the thrombin, and the condi- tions which influence its activity. The fibrinogen is present in blood plasma of the circulating blood of the body at all times. It can be separated from plasma by various chemical means, and when purified can be made to form fibrin under proper conditions. All observers are agreed that this proteid is the immediate precursor of the insoluble fibrin. Its origin in the blood has been traced with some degree of certainty to the disintegration of the white blood-corpuscles. The thrombin is the substance which reacts on the fibrinogen in the proc- esses of fibrin formation. It does not exist in the living blood-vessels, or at THE BLOOD least is present only in minute traces, but makes its appearance immediately the blood is drawn. Its origin is therefore of peculiar interest. It has been claimed by some, notably Peckelharing, that thrombin is a calcium compound. At any rate, it is definitely proven that calcium is a necessary element in the formation of the clot. The substance thrombin, fibrin ferment, quickly appears in consider- able quantity when blood is drawn under ordinary conditions. Its appearance is due to at least three antecedent substances, prothrombin (thrombogen), calcium, and thrombokinase. The sources of these substances and the part taken by each in the process of coagulation are as follows: If blood be drawn, centrifugalized, and the blood plates separated, freed from plasma, and suspended in water, their solution will cause the formation of fibrin from fibrinogen in the presence of calcium and thrombokinase. The blood platelets are, therefore, the source of the thrombogen. The thrombokinase can be traced to its origin in the tissue cells and the formed elements of the blood, especially the leucocytes. If blood is drawn from the vessels with due precautions not to allow it to come in contact with the cut vessel, or other tissue, clotting is very much delayed. The plasma if separated by the cen- trifuge will remain unclotted for a long time as shown by Howell for the terrapin's plasma. This plasma will quickly clot at any time if a few drops of tissue extract in salt solution be added. A solution of extract of washed white corpuscles acts to increase the rapidity of coagulation. If precautions are taken to draw the blood in such a manner as to remove the calcium from the plasma, no clot is formed. The calcium which exists in solution in the plasma to the extent of 0.026 per cent can be removed by precipitation with oxalate solution, or by fluorides. Oxalate plasma contains both prothrombin and thrombokinase, and when- ever calcium chloride is added to slight excess coagulation takes place. In fluoride plasma one must add both calcium and thrombokinase as that sub- stance seems to prevent the setting free of thrombokinase from the corpuscles. The prothrombin is not interfered with by fluoride. In a word, one may say that the coagulation of the blood takes place because of the formation of fibrin from fibrinogen by the action of thrombin. The fibrinogen is constantly present in the plasma. The thrombin is formed by the interaction of three substances, prothrombin, thrombokinase, and cal- cium. The prothrombin arises chiefly from the disintegration of the blood platelets when the blood leaves the blood-vessels. The thrombokinase originates in tissue cells of the blood and of the organs of the body in general. The calcium is present in the blood plasma at all times. Conditions Affecting Coagulation. From the preceding discussion it is evident that the rapidity of the coagulation of the blood will be influenced by anything that will influence the formation of the fibrin factors or their interaction. The most important influences are the following:— MORPHOLOGY OF THE BLOOD 107 Temperature. Cold retards coagulation. Gentle warmth, 40° C., hastens but a temperature above 56° C. destroys clotting, since that temperature heat- coagulates the fibrinogen. Contact with Foreign Bodies. Such contact hastens clotting. This is due to the influence of such bodies on the formation of fibrin factors, es- pecially the substances that arise from the disintegration of the leucocytes. Condition of the Blood-Vessel Walls. Intra vascular clotting often takes place upon injury of the endothelial lining of the blood-vessel, probably from the liberation of thrombokinase in quantity too great for elimination by the healthy portion of the wall. The healthy endothelium no doubt is an important factor in eliminating the small amounts of the fibrin factors that must be constantly forming. The open wounds and lacerations of tissue that accompany the loss of blood by accident are the very conditions most favorable to clotting, since large amounts of tissue extract, thrombo- kinase, are formed under these conditions. Neutral Salts. The addition of neutral salts in the proportion of 2 or 3 per cent and upward. When added in large proportions, most of these saline substances prevent coagulation altogether. Coagulation, however, ensues on dilution with water. The time during which salted blood can be thus preserved in a liquid state, and coagulated by the addition of water, is quite indefinite. Oxalates and Fluorides. These and other precipitants of calcium pre- vent clotting by removing this substance. Peptone. The injection of commercial peptone in the blood-vessels of an animal to the extent of 0.5 gram of peptone per kilo weight of the body of the animal will deprive the blood of the power of coagulation. If a smaller quantity be injected the coagulation of the blood will be delayed. If peptone blood is drawn and centrifuged, the plasma obtained, which is called peptone plasma, can be made to coagulate by diluting sufficiently with water and letting it stand a long time. Peptone plasma in the blood-vessels of the ani- mal gradually regains the power to coagulate. MORPHOLOGY OF THE BLOOD. The corpuscles floating in the fluid plasma of the blood, when separated by a centrifugal machine are found to make up 45 to 50 per cent of the total mass of the blood. These corpuscles, or formed elements, are of three varieties, the red corpuscles or erythrocytes, the wrhite corpuscles leucocytes, and the blood platelets which have been called thrombocytes . Red Corpuscles or Erythrocytes. Human red blood-corpuscles are circular, biconcave discs with rounded edges, from 7 /j. to 8 p. in diameter, and about 2 p. in thickness. When viewed singly they appear of a pale yellowish tinge; the deep red color which they give to the blood being ob- 108 THE BLOOD servable in them only when they are seen en masse. They are composed of a colorless, structureless, and transparent filmy framework or stroma, infiltrated in all parts by the red coloring matter, the hemoglobin. The stroma is tough and elastic, so that as the corpuscles circulate they admit of elongation and other changes of form in adaptation to the vessels, yet recover their natural shape as soon as they escape from compression. Number and Character of the Red Corpuscles. The normal number of red blood-cells in a cubic millimeter of human blood was estimated by Welcker, in 1854, to be 5,000,000 in men and 4,500,000 in women. Numerous recent observations, however, have shown that these estimates are a little low, especially in men, and the average number has been placed by different authorities at various points between 5,000,000 and 5,500,000. Still the original numbers as given by Welcker are accepted at the present day as being sufficiently accurate for ordinary purposes. It has been also shown that there are many distinct physiological variations in the number, depending FIG. 109. FIG. no. FIG. 109. — Red Corpuscles in Rouleaux. The rounded corpuscles are white or uncolored. FIG. no. — Corpuscles of the Frog. The central mass consists of nucleated colored corpuscles. The other corpuscles are two varieties of the colorless form. on the time of day, digestion, sex, etc. The number of red cells usually diminishes in the course of each day, while the leucocytes increase in number. It has been suggested that this is due to the influence of digestion and exercise. It has generally been found that within half an hour or an hour after a full meal the number of red cells begins to diminish, and that this keeps up for from two to four hours, when it is followed by a gradual rise to the normal. The usual fall is 250,000 to 750,000 per cubic millimeter. These results are most marked after a largely fluid meal, and are probably due to dilution of the blood as a result of the absorption of fluids. In animals the number of red cells is increased by fasting, but in man the results are variable, some authorities claiming an increase and others a decrease. In childhood there RED CORPUSCLES OR ERYTHROCYTES 109 is no difference between the sexes in the number of red cells per cubic milli- meter, but after menstruation is established a relative anemia develops in women. Welcker's original estimate placed the difference at 500,000 per cubic millimeter, and these figures have been generally accepted, though Leichtenstein asserts that the difference is 1,000,000. Menstruation in healthy subjects has practically no effect, as not more than ico-200 cubic centimeters of blood are lost normally in the course of FIG. in. — The Illustration is Somewhat Altered from a Drawing by Gulliver, in the Proceed. Zool. Society, and exhibits the typical characters of the red blood-cells in the main Divisions of the Vertebrata. The fractions are those of an inch, and represent the average diameter. In the case of the oval cells, only the long diameter is here given. It is remarkable, that although the size of the red blood-cells varies so much in the different classes of the vertebrate kingdom, that of the white corpuscles remains comparatively uniform, and thus they are, in some animals, much greater, in others much less, than the red corpuscle existing side by side with them. several days. Under such circumstances the normal diminution of red cells per cubic millimeter is probably less than 150,000, though Sfameni has placed the loss at about 225,000. In fact an increase has been claimed. The leucocytes are slightly increased during menstruation. It is now the general opinion that pregnancy has little or no effect on the number of red cells, and 110 THE BLOOD that any anemia must be due to abnormal conditions. Post-partum anemia should not last longer than two weeks. The red corpuscles are not all alike. In almost every specimen of blood a certain number of corpuscles smaller than the rest may be observed. They are termed microcytes, or hematoblasts, and are probably immature corpuscles. A peculiar property of the red corpuscles, which is exaggerated in in- flammatory blood, may be here again noticed, i.e., their great tendency to adhere together in rolls or columns (rouleaux), like piles of coins. These rolls quickly fasten together by their ends, and cluster; so that, when the blood is spread out thinly on a glass, they form a kind of irregular network, with crowds of corpuscles at the several points corresponding with the knots of the net, figure 109. Hence the clot formed in such a thin layer of blood looks mottled with blotches of pink upon a white ground. The red corpuscles are constantly undergoing disintegration in different parts of the circulatory system, particularly in the spleen. The liberated hemoglobin contributes to the formation of the bile pigments in the liver. Development of the Red Blood-Corpuscles. — The first formed blood-corpuscles of the human embryo differ much in their general characters FIG. 112. — Part of the Network of Developing Blood- Vessels in the Vascular Area of aGuinea- Pig. bl, Blood-corpuscles becoming free in an enlarged and hollowed-out part of the network; a, process of protoplasm. (E. A. Schafer.) from those which belong to the later periods of intra-uterine, and to all periods of extra-uterine life. Their manner of origin is at first very simple. Surrounding the early embryo is a circular area, called the vascular area, in which the first rudiments of the blood-vessels and blood-corpuscles are developed. Here the nucleated embryonal cells of the mesoblast, from which the blood-vessels and corpuscles are to be formed, send out processes in various directions, and these, joining together, form an irregular mesh- work. The nuclei increase in number, and collect chiefly in the larger masses of protoplasm, but partly also in the processes. It appears that hemo- DEVELOPMENT OF THE RED BLOOD-CORPUSCLES 111 globin then makes its appearance in certain of these nucleated embryonal cells, which thus become the earliest red blood-corpuscles. The proto- plasm of the cells and their branched network in which these corpuscles lie then become hollowed out into a system of canals enclosing fluid, in which the red nucleated corpuscles float. The corpuscles at first are from about 10 /A to 16 p, in diameter, mostly spherical, and with granular contents, and a well-marked nucleus. Their nuclei, which are about 5 p in diameter, FIG. i PIG. 114. FIG. 113.— Multiplication of the Nucleated Red Corpuscles. Marrow of young kitten after bleeding, showing above karyo kinetic division of erythroblast, and below the formation of mature from immature erythrocytes. (Howell.) FIG. 114. — Shows the Way in which the Nucleus Escapes from the Nucleated Red Corpuscles. 1,2,3, 4, represent different stages of the extrusion noticed upon the living corpuscles, a, Specimen from the circulating blood of an adult cat, bled four times; b, specimen from the circulating blood of a kitten forty days old, bled twice; c, specimens from the blood of a fetal cat, 9 cm. long. Others from the marrow of an adult cat, two of the figures showing the granules present in the corpuscles, which have been interpreted erroneously as a sign of the disintegration of the nucleus. (Howell.) are central, circular, very little prominent on the surfaces of the corpuscles, and apparently slightly granular. The corpuscles then strongly resemble the colorless corpuscles of the fully developed blood but for their color. They are capable of ameboid movement and multiply by division. When, in the progress of embryonic development, the liver is formed, the multiplication of blood-cells in the whole mass of blood ceases, and new blood-cells are produced by this organ, and also by the spleen. These are at first colorless and nucleated, but afterward acquire the ordinary blood tinge, and resemble very much those of the first set. They also multiply by division. The bone marrow also begins to form red corpuscles, though at first in small amounts only. This function develops rapidly, however, so that at birth the marrow represents the chief seat of production of the red cells. Never- theless, nucleated red cells are usually found at birth, sometimes in con- siderable quantities in the liver and in the spleen. Non-nucleated red cells begin to appear soon after the first month of fetal life, and gradually increase so that at the fourth month they form one-fourth of the whole amount of 112 THE BLOOD colored corpuscles. At the end of fetal life they almost completely replace the nucleated cells. In late fetal life the red cells are formed in almost the same way as in extra-uterine life. Various theories have prevailed as to the mode of origin of the non-nu- cleated colored corpuscles. For a time it was thought that they were of endoglobular origin, and merely fragments of some original cell, being pro- duced by subdivision of the cell body itself. This theory easily accounted for the absence of the nuclei, but it has not been supported by recent investi- gations. At present it is the general belief that the non-nucleated cells, or erythrocytes, are derived from nucleated cells by a process of mitotic division, and further that their nuclei gradually shrink or fade and are then extruded. FIG. itc — Colored Nucleated Corpuscles, from the Red Marrow of the Guinea-Pig. (E. A. Schafer.) The use of some of the more recent stains seems to prove that there are traces of nuclear material in the non-nucleated corpuscles. After infancy and early childhood the origin of erythrocytes is practically limited to the red marrow of the bones. The mother cells, or erythroblasts, are constantly forming and setting free erythrocytes, the rate varying greatly at different periods. The Colorless Corpuscles or Leucocytes. In human blood the white corpuscles, leucocytes, are nearly spherical masses of granular proto- plasm without cell wall. In all cases one or more nuclei exist in each cor- puscle. The corpuscles vary considerably in size but average 10 p, in diameter. The number of leucocytes in a cubic millimeter of blood is estimated at 7,500 to 8,000. The proportion of white corpuscles to red, therefore, is about one of the former to 700 of the latter. This proportion is not very constant in health and great variations cccur under the influence of disease, especially in certain infectious diseases in which the number of wrhite corpus- cles is markedly increased. After a full meal the white cells in a healthy adult are increased in number about one-third, the increase beginning within an hour, attaining a maxi- mum in three or four hours, and then gradually falling to normal. This process is frequently modified by the character of the food, the greatest increase occurring with an exclusively meat diet, while a purely vegetarian diet has usually no effect. The increase is also more marked in children, and especially in infants. The essential factor is probably the absorption of albuminous matter in considerable quantities. This causes proliferation of leucocytes in the adenoid tissue of the gastro-intestinal tract. In pregnancy there is often a moderate increase in the number of white THE COLORLESS CORPUSCLES OR LEUCOCYTES 113 cells during the later months. This does not begin until after the third month, and is most marked and constant in primiparse. After parturition the leucocytes gradually diminish under normal conditions, and usually reach the normal within a fortnight. The essential factor is probably the general stimulation in the maternal organism. It is well established that the white cells are very numerous in the new-born, though different observers have made very conflicting estimates. Still all agree that there is a very rapid decrease in their numbers during the first few days, and that this is followed by a less marked increase, which continues for many months. According to Rieder, who is perhaps the most reliable, there are at birth from 14,200 to 27,400 per cubic millimeter, and after the fourth day from 12,400 to 14,800. Varieties of Leucocytes, The colorless corpuscles present greater diversi- ties of form than the red ones, plate II. They are usually classified according to their reaction to staining agents, or to the presence or absence of granules in their cytoplasm. Kanthack and Hardy offer the following classification, based upon both phenomena: Leucocytes. A. Oxyphile (staining with acid dyes). . . J1' Finel>r granular. | 2. Coarsely granular eosmopmle. B. Basophile (staining with basic dyes) . . i. Finely granular. C. Hyaline .. . . J T' Sma11 lymphocyte. ( 2. Large myelocyte. The finely granular oxyphile constitutes 75 per cent of all leucocytes. It has an average diameter of 10 ^it, and possesses phagocytic action to a marked degree — that is, it possesses the power of ingesting foreign particles. Its nucleus consists of several lobes united by threads of chromatin. This cell was formerly known under the term neutrophile, because of its supposed reaction to neutral dyes. The coarsely granular form of eosinophile constitutes only 2 per cent of the leucocytes. It has a diameter of 12 p, and a reniform nucleus. The basophile cell is rarely found in normal blood. It may occur occa- sionally during periods of digestion. It is a small, spherical cell, with an irregular nucleus and a diameter of 7 p,. The small hyaline leucocyte is also called a lymphocyte, because of the large numbers found in adenoid tissue, and is supposed to be an immature form. The nucleus is proportionally large, and is surrounded by but little protoplasm in which no granules can be detected. The cell is about the size of a red blood-cell, and constitutes from 10 to 20 per cent of all leucocytes. The large hyaline or myelocyte varies in diameter from 8.5 to 10 p,. Its nucleus is spherical or reniform, and is surrounded by more protoplasm than in the case of the lymphocyte. It forms about 10 per cent of the leucocytes. Ameboid Movement of Leucocytes. The remarkable property of the color- 8 114 THE BLOOD less corpuscles of spontaneously changing their shape was first demonstrated by Wharton Jones in the blood of the skate. If a drop of blood be examined with a high power of the microscope, under conditions by which loss of mois- ture is prevented, and at the same time the temperature is maintained at about that of the body, 37° C., the colorless corpuscles will be observed slowly to alter their shapes, and to send out processes at various parts of their \ C FIG. 116. — (a) Red blood- corpuscle for comparison; (b) small hyaline cell or lymphocyte; (c) large hyaline cell or myelocyte; (d) fine granular oxyphile; (e) coarse granular oxyphile or eosino- phile; (;) basophile. (F. C. Busch.) circumference. The ameboid movement which can be demonstrated in human colorless blood-corpuscles, can be most conveniently studied in the newt's blood. Processes are sent out from the corpuscle. These may be withdrawn, but more often the protoplasm of the whole corpuscle flows gradually forward to the position occupied by the process, thus the corpuscle changes its position. The change of position of the corpuscle can also take place by a flowing movement of the whole mass, and in this case the loco- FIG. 117. — Human Colorless Blood-Corpuscle, Showing its Successive Changes of Outline Within Ten Minutes when kept Moist on a Warm Stage. (Schofield.) motion is comparatively rapid. The activity both in the processes of change of shape and also of change in position is much more marked in some cor- puscles than in others. Klein states that in the newt's blood the changes are especially noticeable in a variety of the colorless corpuscle, which consists of a mass of finely granular protoplasm with jagged outline and contains CHEMICAL COMPOSITION OF THE BLOOD 115 three or four nuclei, or in large irregular masses of protoplasm containing from five to twenty nuclei, The property which the colorless corpuscles possess of passing through the walls of the blood-vessels will be described later on. The Blood Plates or Thrombocytes. A third variety of corpuscle found in the blood is known as the blood plate. They are circular or elliptical in shape, of nearly homogeneous structure, and vary in size from 0.5 to 5^,. FIG. 118. — Blood Plates, Showing Chromatic Centers Regarded by some as Nuclei, and Ex- hibiting Ameboid Movement. (Schafer, from Kopsch.) Hence they are smaller than the red corpuscles. They vary in number from 5,000 to 45,000 per cubic millimeter and are preserved by drawing fresh blood directly into Hayem's or other preserving fluid. Chemically they contain a nucleo-proteid, *and it is supposed that they take part in the phe- nomenon of coagulation. According to Deetjen and others, ameboid move- ment has been demonstrated in these bodies. CHEMICAL COMPOSITION OF THE BLOOD. In considering the chemical composition of the blood, it will be convenient to take in order the composition of the various chief factors into which the blood may be separated, viz., The Plasma ; The Serum ; The White Cor- puscles ; The Red Corpuscles. The Composition of the Plasma. The plasma is the liquid part of the blood in which the corpuscles float. It contains the fibrin factors, inasmuch as when drawn from the blood- vessels it undergoes coagulation and splits up into fibrin and serum. It differs from the serum in containing fibrinogen, but in appearance and in reaction it closely resembles that fluid. Its alkalinity, however, is greater than that of the serum obtained from it. It may be freed from corpuscles by the centrifugal machine, or by the other means enumerated below. 116 THE BLOOD The chief methods of obtaining plasma free from corpuscles are: i. By cold. The temperature should be about o° C. and may be two or three degrees higher, but not lower. 2. The addition of neutral salts, in certain proportion, either as solids or in solution, e.g., of sodium sulphate, if solid i part to 12 parts of blood; if a saturated solu- tion i part to 6 parts of blood. Or magnesium sulphate, saturated solution i part to 4 of blood. 3. By mixing frog's blood with an equal part of a 5 per cent solution of cane sugar, and getting rid of the corpuscles by nitration. 4. By the injection of com- mercial peptone into the veins of certain mammals previous to bleeding them to death, allowing the corpuscles to subside or by subjecting the blood to the action of a centrif- ugal machine by the rapid rotation of which the whole of the solids are driven to the outer end of the tubes in which the blood is placed. PERCENTAGE COMPOSITION OF PLASMA. Water 90.29 Solids— 1. Proteids — Fibrinogen } Paraglobulin I 8.289 Serum albumin ) 2. Extractives 566 3. Inorganic salts 8 ;o 9.71 Water. The water of the plasma varies in amount according to the amount of food, drink, and exercise, or other circumstances. It amounts to about 90 per cent. Proteids. Fibrinogen is the substance in plasma which is converted into fibrin on coagulation. It belongs to the class of proteids called globulins. It is precipitated from plasma with serum globulin by saturation with MgSO4 and NaCl. It is soluble in dilute salt solutions but is not soluble in water. It can be distinguished from serum globulin by a number of special reactions; i. Its coagulation temperature is lower, 55° to 56° C. 2. It is completely precipitated by saturation with NaCl as well as with MgSO4. 3. It gives rise to an insoluble proteid, fibrin. It may be, however, that fibrinogen is not a simple proteid, but a mixture or loose chemical combination of two or more proteids. Fibrinogen is present in plasma to the extent of 0.2 to 0.5 per cent. Serum globulin or paraglobulin is similar to fibrinogen in its reactions. It is completely precipitated by MgSO4; incompletely by NaCl, and co- agulates at a temperature of 75° C. It is likewise soluble in dilute salt solu- tions but insoluble in water. It is present in plasma in from 3.5 to 4 per cent. Serum albumin is the proteid which predominates in human plasma. It is readily obtained in crystalline form; is soluble in MgSO4 and NaCl solutions, but insoluble in saturated ammonium sulphate solutions; and coagulates in neutral or acid solutions at from 73° to 75° C. Extractives. The extractives are the nitrogen-containing substances such as urea, uric acid, creatin, creaiinin, etc.; glycogen, dextrose, choles- THE COMPOSITION OF THE WHITE CORPUSCLES 117 terin, etc., a total of 0.5 to 0.6 per cent. The dextrose content amounts to from o.i to 0.15 per cent. Ferments are also found in blood; first, a diastatic ferment converting amyloids into sugars; second, a glycolytic ferment causing a disappearance of sugar; third, a fat-splitting ferment, lipase; and fourth, fibrin ferment (thrombin), or its 'precursor, prothrombin. Inorganic Substances. The blood plasma contains about 0.8 per cent of inorganic salts distributed as follows, the sodium chloride predominating: Parts in 1,000 of plasma. Chlorine 3-536 Sulphuric acid 1 29 Phosphoric acid 145 Potassium 314 Sodium 3-410 Phosphate of lime 298 Phosphate of magnesia 218 Oxygen 455 The Serum. The serum is the liquid part of the blood or of the plasma which remains after the fibrin has been formed and removed. It is a transparent, yellowish, faintly alkaline fluid, with a specific gravity of from 1025 to 1032. Serum may be obtained from blood-corpuscles by allow- ing blood to clot in large test tubes, or by subjecting test tubes of whipped blood to the action of a centrifugal machine for some time. Serum is chemi- cally very much the same as plasma except that it has lost the fibrinogen in the process of clotting and has gained the by-products of that process — throm- bin, thrombokinase, and fibrin-globulin. The salts of serum are practically those of plasma. The Composition of the White Corpuscles. The white corpuscles are comparatively undifferentiated cellular elements, hence possess the chemi- cal composition of protoplasm. Lillienfeld has made an analysis of the leucocytes of thymus gland from the calf, which contain 11.49 Per cent of solids, as follows: In 100 Parts of Dry Substance of Corpuscles of Calf. Per cent. Proteid i . 76 Leuconuclein 68. 78 Histon 8.76 Lecithin 7.51 Fat 4-02 Cholesterin 4.40 Glycogen 0.80 96.03 118 THE BLOOD The most noteworthy substance in this table is the nucleohiston content, first isolated by Kossel and Lillienfeld. Beside the substances in the above table, the white corpuscles contain salts of potassium, sodium, calcium, and magnesium. The potassium phosphate is present in greatest amount. The Composition of the Red Corpuscles. Analysis of a thousand parts of moist blood-corpuscles shows the following result: Water 688 Solids- Organic 303.88 ) Mineral 8.12 f 3» = i,ooo Of the solids the most important is Hemoglobin, the substance to which the blood owes its color. It constitutes, as will be seen from the appended table, more than 90 per cent of the organic matter of the corpuscles. Be- sides hemoglobin the corpuscles contain proteid and fatty matters, the former chiefly consisting of globulins, and the latter of cholesterin and lecithin. In 1,000 parts of organic matter are found: Hemoglobin 905 .4 Proteids 86. 7 Fats 7.9 = 1,000 Of the inorganic salts of the corpuscles, the iron omitted, there are present, in 1,000 parts of corpuscles (Schmidt): Potassium chloride 3 . 679 Potassium phosphate 2 . 343 Potassium sulphate 132 Sodium phosphate 633 Calcium phosphate 094 Magnesium phosphate 060 Soda 341 — 7 . 282 Hemoglobin. Of the substances in the erythrocytes, by far the most important from every point of view is the pigment, hemoglobin. It composes about 90 per cent of the total solids of the corpuscles; there- fore, between 14 and 15 per cent of the blood itself. Hemoglobin is the most complex compound in the body, having a molecule of the enormous molec- ular weight of 16,669. Hemoglobin is intimately distributed throughout the stromaof the corpuscle, and when dissolved out it undergoes crystallization. Its percentage composition is C 53.85; H 7.32; N 16.17; O 21.84; S 0.63; Fe 0.42. Jacquet gives the empirical formula for the hemoglobin of the dog, C758H1203N195S3FeO218. The most interesting of the properties of hemoglobin are its powers of crystallizing and its attraction for oxygen and other gases. Hemoglobin Crystals. The hemoglobin (oxyhemoglobin) of the blood of various animals possesses the power of crystallizing to very different ex- HEMOGLOBIN 119 tents. In some the formation of crystals is almost spontaneous, whereas in others it takes place either with great difficulty or not at all. Among the animals whose blood coloring-matter crystallizes most readily are the guinea-pig, rat, squirrel, and dog; and in these cases to obtain crystals it is generally sufficient to dilute a drop of recently drawn blood with water FIG. 119. — Crystals of Oxyhemoglobin — Prismatic, from Human Blood. and to expose it for a few minutes to the air. In many instances other means must be adopted, e.g., the addition of alcohol, ether, or chloroform, rapid freezing, and then thawing, the application of an electric current, a tempera- FIG. 120. — Oxyhemoglobin Crystals — Tetrahedral, from Blood of the Guinea-pig. ture of 60° C., the addition of sodium sulphate, or the addition of decom- posing serum of another animal. .The hemoglobin of human blood crystallizes with difficulty, as does also that of the ox, the pig, the sheep, and the rabbit. 120 THE BLOOD The forms of hemoglobin crystals, as will be seen from figures 119 and 120, differ greatly. Hemoglobin crystals are soluble in water. Both the crystals themselves and also their solutions have the characteristic color of arterial blood. A dilute solution of oxyhemoglobin gives a characteristic appearance with the spectroscope. Two absorption bands are seen between the solar lines D, which is the sodium band in the yellow, and E, see the frontispiece, one in the yellow, with its middle line some little way to the right of D. This band is very intense, but narrower than the other, which lies in the green near to the left of E. Each band is darkest in the middle and fades away at the sides. As the strength of the solution increases, the bands become broader and deeper. Both the red and the blue ends of the spectrum be- come encroached upon until the bands coalesce to form one very broad band when only a slight amount of the green and part of the red remain unab- FIG. 121. — Hexagonal Oxyhemoglobin Crystals, from Blood of Squirrel. On these hex- agonal plates prismatic crystals, grouped in a stellate manner, not unfrequently occur (after Funke) . sorbed. Any further increase of strength leads to complete absorption of the spectrum. If crystals of hemoglobin are exposed to an atmosphere of oxygen they take up oxygen and form oxyhemoglobin, each gram of the pigment fixing a definite amount of oxygen, see chapter on Respiration. When subjected to a mercurial air pump the oxygen is given off, and the crystals become of a purple color. A solution of the oxyhemoglobin in the blood-corpuscles may be made to give up oxygen, and to change color in a similar manner. One gram of oxyhemoglobin liberates 1.59 c.c. oxygen, or according to Hiif- ner's later determinations, 1.34 c.c. This change may be also effected by passing through the solution of blood or of oxyhemoglobin, hydrogen or nitrogen gas, or by the action of ACTION OF GASES ON HEMOGLOBIN 121 reducing agents, of which Stokes's fluid* or ammonium sulphide are the most convenient. With the spectroscope, a solution of deoxidized or reduced hemoglobin is found to give an entirely different appearance from that of oxidized hemo- globin. Instead of the two bands at D and E we find a single broader but fainter band occupying a position midway between the two, and at the same time less of the blue end of the spectrum is absorbed. Even in strong solu- tions this latter appearance is found, thereby differing from the strong solu- tion of oxidized hemoglobin which lets through only the red and orange rays; accordingly, to the naked eye the one (reduced-hemoglobin solution) appears purple, the other (oxy hemoglobin solution) red. The deoxidized crystals or their solutions quickly absorb oxygen on exposure to the air, becoming scarlet. If solutions of blood be taken instead of solutions of hemoglobin, results similar to the whole of the foregoing can be obtained. Venous blood never, except in the last stages of asphyxia, fails to show the oxyhemoglobin bands, inasmuch as the greater part of the hemoglobin even in venous blood exists in the more highly oxidized condition. Action of Gases on Hemoglobin. Carbonic oxide gas passed through a solution of hemoglobin causes it to assume a cherry-red color and to present a slightly altered spectrum; two bands are still visible but are slightly nearer the blue end than those of oxyhemoglobin, see plate I. The amount of carbonic oxide taken up is equal to the amount of the oxygen displaced. Although the carbonic-oxide gas readily displaces oxygen, the reverse is not the case, and upon this property depends the dangerous effect of coal-gas poisoning. Coal-gas contains much carbonic oxide, and, when breathed, the gas combines with the hemoglobin of the blood and produces a compound which cannot easily be reduced. This compound (carboxyhemo- globin) is not an oxygen-carrier, and death may result from suffocation due to the want of oxygen, notwithstanding the free entry of pure air into the lungs. Crystals of carbonic-oxide hemoglobin closely resemble in form those of oxyhemoglobin. Nitric oxide produces a similar compound to the carbonic-oxide hemo- globin, which is even less easily reduced. Nitrous oxide reduces oxyhemoglobin, and therefore leaves the reduced hemoglobin in a condition actively to take up oxygen. Sulphuretted hydrogen, if passed through a solution of oxyhemoglobin, reduces it and an additional band appears in the red. If the solution be then shaken with air, the two bands of oxyhemoglobin replace that of re- duced hemoglobin, but the band in the red persists. * Stokes's Fluid consists of a solution of ferrous sulphate, to which ammonia has been added and sufficient tartaric acid to prevent precipitation. Another reducing agent is a solution of stannous chloride, treated in a way similar to the ferrous sulphate, and a third reagent of like nature is an aqueous solution of yellow ammonium sulphide, NH4HS. THE BLOOD Methemoglobin. If an aqueous solution of oxyhemogJobin is ex- posed to the air for some time, its spectrum undergoes a change; the two d and e bands become faint, and a new line in the red at c is developed. The solution, too, becomes brown and acid in reaction, and is precipitable by basic lead acetate. This change is due to the decomposition of oxyhemoglobin, and to the production of methemoglobin. On adding ammonium sulphide, reduced hemoglobin is produced, and on shaking this up with air, oxyhemo- globin is again produced. Methemoglobin is probably a stage in the deoxida- tion of oxyhemoglobin. It appears to contain less oxygen than oxyhemo- tio. 122. — rleischl's Hemoglobinometer. globin, but more than reduced hemoglobin. Its oxygen is in more stable combination, however, than is the case with the former compound. Estimation of Hemoglobin. The most exact method is by the esti- mation of the amount of iron (dry hemoglobin containing 0.42 per cent of iron) in a given specimen of blood, but as this is a somewhat complicated process, various methods have been proposed which, though not so exact, have the advantage of simplicity. Of the several varieties of hemoglobinom- eter, one of the best adapted to its purpose is that invented by Professor Fleischl, of Vienna. In this instrument the amount of hemoglobin in a solution of blood is estimated by comparing a stratum of diluted blood with a standard solid substance of uniform tint similar spectroscopically to diluted blood. The Fleischl instrument has been recently modified and made more accurate by Miescher. The Fleischl-Miescher apparatus consists of a stand with a metal plate having a circular opening and a plaster mirror below, S, figure 122, which casts light through the opening. Beneath the plate is a metal framework containing a colored glass wedge, and along the side of ESTIMATION OF HEMOGLOBIN 123 the same is a scale graduated so as to indicate the percentage of hemoglobin corresponding to the shades of the different parts of the wedge. This frame- work can be moved by the wheel T which fits into a rack on its lower surface. The scale can be read through a small opening M in the plate. Into the large circular opening of the plate fits a cylindrical metal cell G with a glass bottom and divided by a metal partition into two equal parts. One of these halves lies over the wedge and is filled with distilled water. The other con- tains the solution of blood in which the hemoglobin is to be estimated. The apparatus is usually supplied with three cells. Of these, the first two are used in estimating the hemoglobin according to Miescher's modification of FleischPs original method. This is the method now generally used. These cells are furnished with a glass cover having a groove which fits upon the partition of the cell. Over this cover is placed a diaphragm with a longitudinal slit, which only permits of the central part of each side of the cell being seen. The third cell is for use when the original Fleischl method is employed. The patient's ear or finger is pricked, and the blood from the wound sucked up into the graduated pipet until it reaches the mark £, §, or |, a one per cent solution of sodium carbonate is then sucked in until the upper mark is reached. The pipet is then well shaken in order to mix the blood thoroughly. One-half of each of the two cells, which are respectively 12 and 15 millimeters high, are then filled with the mixture, the other half being filled with water. An important point is that the liquids should com- pletely fill the cells. The cover-glasses and diaphragms are then applied and the cells are ready for examination. This must be done by artificial light. Moreover, in order to have accurate results, light of the same inten- sity should be always used. One of the cells is placed on the plate and the wheel T turned until the colors of the two halves exactly correspond. When this point is reached, the result is read off on the scale through the opening M. This should be repeated several times with each of the cells, and the average of the readings taken. The result obtained with the 12-millimeter cell should be multiplied by J to bring it up to that of the larger. For example, suppose the result of several readings to be: With the large cell (15 mm.) 54-°° With the small cell (12 mm.) 42.00 If the readings obtained with the large cell are exactly correct, then the read- ings with the smaller one should be 43.2, since 54 X £=43.2. Or, if the readings with the smaller cells are exact, the readings with the larger should be 52.5, since 42X1=52.5. Hence the mean of 54 and 52.5, namely 53.25, should be taken as the correct figure. On looking at the corrected table of hemoglobin values supplied with each instrument, we would find that this number on the scale corresponds to a solution containing 400 milligrams 124 THE BLOOD of hemoglobin per 1,000 cubic centimeters of solution. But our original dilution was either i : 200, i : 300, or i : 400, according as our pipet had been filled with blood up to the mark ^, §, or ^; so that in order to obtain the actual percentage of hemoglobin in the blood under examination we should be obliged to multiply our result by 200, 300, or 400. In the example we have taken, the amount of hemoglobin would be, if our dilution was i : 200, 400 X 200=80,000 milligrams = 80 grams in 1,000 cubic centi meters — 8 grams in 100 cubic centimeters, or 8 per cent. Another very simple method of approximately determining the hemo- globin percentage is the hemoglobin scale devised by T. W. Talquist. This consists of a series of shades of color corresponding to undiluted blood of various hemoglobin values, ranging from ten to one hundred per cent of an arbitrary scale. This scale is included in a book, the remaining pages of which consist of filter paper, which is used for absorbing the specimen of blood whose hemoglobin percentage is to be estimated. The blood-stained filter paper is compared with the hemoglobin scale by direct daylight until a shade is found with which it corresponds. For approximate results this method has proved very satisfactory. Derivatives of Hemoglobin. Hematin. By the action of heat cr of acids or alkalies in the presence of oxygen, hemoglobin can be split up into a substance called Hemaiin, which contains all the iron of the hemo- globin from which it was derived, and a proteid residue. Of the latter it is impossible to say more than that it probably consists of one or more bodies of the globulin class. If there be no oxygen present, instead of hematin a body called hemochr onto gen is produced, which, however, will speedily under- go oxidation into hematin. Hematin is a dark brownish or black non-crystallizable substance of metallic luster. Its percentage composition is C, 64.30; H, 5.50; N, 9.06; Fe, 8.82; O, 12.32; which gives the formula C^HyoNgFeaO^ (Hoppe- Seyler). It is insoluble in water, alcohol, and ether; soluble in the caustic alkalies; soluble with difficulty in hot alcohol to which is added sulphuric acid. The iron may be removed from hematin by heating it with fuming hydrochloric acid to 160° C., and a new body, hematoporphyrin, the so-called iron-free hematin, is produced. Hematoporphyrin (C^^NgO^, Hoppe- Seyler) may also be obtained by adding blood to strong sulphuric acid, and if necessary filtering the fluid through asbestos. It forms a fine crimson solution, which has a distinct spectrum, viz., a dark band just beyond D, and a second all but midway between D and E. It may be precipitated from its acid solution by adding water or by neutralization, and when redissolved in alkalies presents four bands, a pale band between C and D, a second between D and E, nearer D, another nearer E, and a fourth occupying the chief part of the space between b and F. Hematin in Acid Solution. If an excess of acetic acid is added to DERIVATIVES OF HEMOGLOBIN 125 blood, and the solution boiled, the color alters to brown from decomposition of hemoglobin and the setting free of hematin; by shaking this solution with ether, a solution of hematin in acid solution is obtained. The spectrum •of the ethereal solution shows no less than four absorption bands, viz., one in the red between C and D, one faint and narrow close to D, and then two broader bands, one between D and E, and another nearly midway between b and F. The first band is by far the most distinct, and the acid aqueous solution of hematin shows it plainly. Hematin in Alkaline Solution. If a caustic alkali is added to blood and the solution is boiled, alkaline hematin is produced, and the solution becomes clive green in cclor. The absorption band of the new compound is in the red, near to D, and the blue end of the spectrum is absorbed to a considerable extent. If a reducing agent be added, two bands resembling those of oxy- FIG. 123. — Hematoidin Crystals. (Frey.) FIG. 1233.. — Hemin Crystals. (Frey.) hemoglobin, but nearer to the blue, appear; this is the spectrum of reduced hematin, or hemochromogen. On violently shaking the reduced hematin with air or oxygen the two bands are replaced by the single band of alkaline hematin. Hematoidin. This substance is found in the form of yellowish crystals, figure 123, in old blood extravasations and is derived from the hemoglobin. Their crystalline form and the reaction they give with fuming nitric acid seem to show them to be closely allied to Bilirubin, the chief coloring matter of the bile, and in composition they are probably either identical or isomeric with it. Hemin. One of the most important derivatives of hematin is hemin. It is usually called Hydrochloride of Hematin, but its exact chemical com- position is uncertain. Its formula is said to be C32H30N4FeO3HCl, and it contains 5.18 per cent of chlorine, but by some it is looked upon as simply crystallized hematin. Although difficult to obtain in bulk, a specimen may be easily made for the microscope in the following way: — A small drop of dried blood is finely powdered with a few crystals of common salt on a glass slide and spread out; a cover-glass is then placed upon it, and glacial acetic acid added by means of a capillary pipet. The blood at once turns a brownish color. The slide is then heated, and the acid mixture evaporated to dryness 126 THE BLOOD at a high temperature. The excess of salt is washed away with water from the dried residue, and the specimen may then be dried and mounted. A large number of small, dark, reddish black crystals of a rhombic shape, sometimes arranged in bundles, will be seen if the slide be subjected to micro- scopic examination, figure 1233,. The formation of these hemin crystals is of great interest and importance from a medico-legal point cf view, as it constitutes the most certain and delicate test we have for the presence of blood (not of necessity the blood of man) in a stain on clothes, etc. It exceeds in delicacy even the spectro- scopic test. Compounds similar in composition to hemin, but containing hydrobromic or hydriodic acid, instead of hydrochloric, may be also readily obtained. Variations in the Composition of Healthy Blood. The conditions which appear most to influence the composition of the blood in health are these : Diet, Exercise, Sex, Pregnancy, and Age. Sex. The blood of men differs from that cf women, chiefly in being of somewhat higher specific gravity, from its containing a relatively larger quantity of red corpuscles. Pregnancy. The blood cf pregnant women has rather lower than the average specific gravity. The quantity of the colorless corpuscles is increased in the later months, especially in primiparae; it is also claimed that the fibrin is increased in amount. Age. The blood of the fetus is very rich in solid matter, and especially in colored corpuscles; and this condition, gradually diminishing, continues for some weeks after birth. The quantity of solid matter then falls during childhood below the average, rises during adult life, and in old age falls again. Diet. Such differences in the composition of the blood as are due to the temporary presence of various matters absorbed with the food and drink, as well as the more lasting changes which must result from generous or poor diet respectively, need be here only referred to. Effects oj Bleeding. The result of bleeding is to diminish the specific gravity of the blood, and so quickly that in a single venesection the portion of blood last drawn has often a less specific gravity than that of the blood that flowed first. This is, of course, due to absorption of fluid from the tissues of the body. The physiological import of this fact, namely, the instant absorption of liquid from the tissues, is the same as that of the intense thirst which is so common after either loss of blood, or the abstraction from it of watery fluid, as in cholera, diabetes, and the like. For some little time after bleeding, the want of colored corpuscles is well marked, but with this exception: no considerable alteration seems to be produced in the composition of the blood for more than a very short time; the loss of the other constituents, including the colorless corpuscles, being very quickly repaired. VARIATIONS IN THE COMPOSITION OF HEALTHY BLOOD 127 Variations in Different Parts of the Body. The composition of the blood, as might be expected, is found to vary in different parts of the body. Thus arterial blood differs from venous; and although its composition and general characters are uniform throughout the whole course of the systemic arteries, they are not so throughout the venous system, the blood contained in some veins differing markedly from that in others. Differences between Arterial and Venous Blood. The differences between arterial and venous blood are these: Arterial blood is bright red, from the fact that almost all its hemoglobin is combined with oxygen, oxyhemoglobin, while the purple tint of venous blood is due to the deoxidation of a certain quantity of its oxyhemoglobin, and its consequent reduction to the purple variety (deoxidized, or purple hemoglobin). Arterial blood coagulates somewhat more quickly. Arterial blood contains more oxygen than venous, and less carbonic acid. Some of the veins contain blood which differs from the ordinary standard considerably. These are the Portal, the Hepatic, and the Splenic veins. Portal Blood. The blood which the portal vein conveys to the liver is supplied from two chief sources; namely, from the gastric and mesenteric veins, which contain the soluble elements of food absorbed from the stomach and intestines during digestion, and from the splenic vein. It must, there- fore, combine the qualities of the blood from each of these sources. The blood in the gastric and mesenteric veins will vary much according to the stage of digestion and the nature of the food taken, and can therefore be seldom exactly the same. Speaking generally, and without considering the sugar and other soluble matters which may have been absorbed from the alimentary canal, this blood appears to be deficient in solid matters, especially in colored corpuscles, owing to dilution by the quantity of water absorbed, to contain an excess of proteid matter, and to yield a less tenacious kind of fibrin than that of blood generally. The blood of the portal vein, combining the peculiarities of its two factors, the splenic and mesenteric venous blood, is usually of lower specific gravity than blood generally, is more watery, contains fewer colored corpuscles, more proteids, and yields a less firm clot than that yielded by other blood, owing to the deficient tenacity of its fibrin. Guarding (by ligature of the portal vein) against the possibility of an error in the analysis from regurgitation of hepatic blood into the portal vein, recent observers have determined that hepatic venous blood contains less water, proteids, and salts than the blood of the portal veins ; but that it yields a much larger amount of extractive matter, in which is one constant element, namely, grape-sugar, which is found, whether saccharine or farinaceous matter has been present in the food or not. 128 THE BLOOD GLOBULOCIDAL AND OTHER PROPERTIES OF SERUM. Cytolysis. It has been known for some time that the sera of certain animals when injected into the circulation of animals of another species will cause destructive changes in the blood-corpuscles, accompanied by symptoms of poisoning, which may even end fatally. These results served to bring into disrepute the use of foreign blood in transfusion, which has consequently been practically abandoned. This discharge of the hemoglobin of the red blood-corpuscles and solution in the plasma (laking) is now included in the general term Cytolysis, and more specifically known as Hemolysis. Agents which produce such an effect are known as hemolytic or hemotoxic agents. Sera of one species are not hemolytic for blood of all other species, but the serum of one animal may be made to acquire such properties for the blood of another. This adaptation is brought about in the following way: For instance, the blood of the guinea-pig, which is not normally lytic for the red cells of the rabbit, may be adapted to the latter by previously, at several successive intervals (three to seven days) injecting into the abdominal cavity or sub- cutaneous tissues of the guinea-pig small quantities of rabbit's blood. If now a small quantity of serum be obtained from the guinea-pig by the usual methods and mixed in a test tube with some of the rabbit's blood diluted with physiological salt solution, hemolysis occurs. That is, the coloring matter of the rabbit's red blood-cells goes into solution and the cells appear under the microscope as shadow corpuscles or ghosts, devoid of hemoglobin. Such an artificially produced hemolytic serum is only lytic for the blood of the animal species for which it has been adapted. It is true that it may also show slightly lytic properties for closely allied species. It has therefore been suggested as a possible valuable aid in determining relationships of various animal species. Concerning the nature of the lytic substance, it has been found that it probably consists of two bodies acting conjointly, for if the serum be heated to 56° C. for a short time, its lytic powers are lost, but may be restored by adding a little serum of another animal of the same species which has not been adapted, and whose serum is consequently not in itself lytic. Of these two bodies, therefore, one is stable and is formed only in the adapted serum, while the other is more unstable or labile (destroyed at 56° C.) and exists normally iri the blood plasma. The former is known as the immune body and the latter as alexin. Lysis occurs only when both are present at the same time, and not through the agency of one or the other singly. This cytolytic adaptation has been extended to include other cells besides the red blood-corpuscles. Thus in a similar manner leucolytic, hepatolytic, nephrolytic, and a number of other lytic sera have been developed. It is further possible, under certain circumstances, that substances may AGGLUTINATIVE SUBSTANCES 120 be developed in the tissues which are lytic for other .tissue cells of the same animal, autolytic substances. This may be an important physiological process in the elimination of worn-out tissue cells, cellular elements in injury, in- flammation, etc. Agglutinative Substances. A further property of adapted sera is that of agglutination. The adaptation is secured in the same way as in the production of cytolysins. In fact, both cytolysis and agglutination may occur at the same time. The normal blood serum of some animals may be agglutinative for the blood-cells of some other species. In normal serum, agglutinative and cytolytic properties may be present together or one only may be normally present. The activity of agglutinative substances is not destroyed at a tempera- ture of 56° C. They do become inert, however, at 70° C., and, furthermore, they cannot be restored by adding normal serum, as is the case with cytolysins. Precipitins. Other forms of adaptive substances which may be found in animal serum are these which, when mixed with the substances by means of which adaptation has been secured, form a precipitate. By this means blood of different species cf animals may be detected even when in a dried state. It has been suggested as a possible valuable aid in medico- legal cases, since human blood in a dilution of i to 50,000 has been recognized by this means. Physical Factors. Diffusion, Osmosis, Dialysis. The term diffusionhzs long been applied to the regular mixing cf the molecules of two gases when brought into contact in a confined space, this interpenetration being due to the to-and-fro movements of their molecules. More recently it has been applied to the mixing of the molecules of two solutions when brought into contact, as it has been found that they act in the same way and obey the same laws as gases. If, however, the two solutions are separated by a membrane, perme- able to the solutions, diffusion will still occur. To this form of diffusion the term Osmosis has been applied in the case of water, and Dialysis in the case of diffusible substances. All bodies can be divided into two groups, crystalloids and colloids. To the for- mer group belong bodies having a crystalline form, which readily go into solution in water. All such bodies are diffusible (dialyz- -T FIG. 124. FIG. 125. 130 THE BLOOD able), their power of dialysis, however, varying considerably. To the second group belong such bodies as have no crystalline form (amorphous). These are generally bodies with a large molecule, which form colloidal suspensions in water, and are only slightly or not at all diffusible. An exception to this second group is hemoglobin, which has a very large mole- cule but is crystalline and is diffusible. The following may serve as simple illustrations: Take a jar and divide it in two equal parts by an animal membrane, M, figure 143, and place an equal amount of distilled water in the two sides, A and B. Now, since the molecules of water act like those of a gas, and are continually moving to and fro, bombarding all the surfaces of their retainer, the molecules of water in A and B will be continually striking all the surfaces of A and B ; but since the membrane is permeable to the water molecules, there will be a continual interchange of molecules between A and B. If now, in one side A we place a solution of sodium chloride, still keeping water in B, the membrane being permeable to the sodium chloride, the first thing we should notice would be an increase in the amount of water in A . Formerly it would have been said that " the salt had attracted the water." Now we should say that the salt had a cer- tain osmotic pressure. The salt, however, being able to pass (dialyze) through the mem- brane, will do so, and this will continue until the strength of the two salt solutions, and therefore the osmotic pressure on both sides, is equal. Osmotic Pressure. If now in A we place a solution of some soluble colloidal sub- stance to which the membrane is impermeable, or else replace the membrane, M, we used in our former experiment by one which is not permeable to the sodium chloride, and arrange our jar as in figure 1 25, so as to be able to read off any increase of water which may pass into .4, we will notice that the amount of liquid in A will continue to increase up to a certain point. Once that point is reached, there will be no further change, since the sub- stance in solution, in A , cannot pass through the membrane as in the previous example. This pressure can be measured and expressed in millimeters of mercury. It is constant for all solutions of this substance that are of the same concentration when measured under like conditions of temperature and pressure, and is called the Osmotic pressure of this solution. Of the numerous explanations regarding the nature of osmotic pressure which have been more or less satisfactory, a simple one, and one that can be easily understood, is as follows: In figure 125 one surface of the membrane is being bombarded by the molecules of a non-diffusible substance mixed with those of a diffusible one (water) ; while the other surface is being bombarded entirely by water molecules. The former condition per- mits less water to diffuse out, since fewer molecules get to the surface of the membrane; while the latter permits all of the molecules which reach it to pass through. Osmotic pressure can be estimated in several different ways in addition to the above, viz., the determination of the freezing point of the solution, determination of the boiling point, determination of the electrical conductivity. The results obtained with the various methods agree very closely. The following solutions have the same osmotic pressure: Sodium chloride, 0.64 per cent; potassium nitrate, 1.09 per cent; sugar 5.5 per cent. Isotonic Solutions. Solutions that have the same osmotic pressure are called iso- tonic. The term isotonic is a relative one, implying a comparison with some other solu- tion taken as a standard. In physiology it has been customary to take blood-plasma as a standard. A solution of 0.64 per cent sodium chloride is isotonic for the blood -plasma of the frog, and a 0.9 per cent solution for that of man. Further, any solution which is of a lower osmotic pressure than the standard solution is said to be hypoisotonic (hypotonic) in relation to that solution. A solution of a higher osmotic pressure is said to be hyper- isotomc (hypertonic). Water passes in the Direction of the Arrows. Hypertonic saline solution (2 per cent) I Blood -plasma ft Isotonic saline solution (0.64 per cent) I Hypotonic saline solution (0.3 per cent) THE CHARACTER AND COMPOSITION OF LYMPH 131 If a hypotonic solution be mixed with blood, water from the hypotonic solution passes through the cell membrane of the red corpuscles into the stroma, and causes it to swell. The hemoglobin at the same time passes out and goes into solution in the diluted plasma. On the other hand, the addition of a hypertonic solution to the plasma causes the red cor- puscles to lose their water and become crenated. The principles of osmosis have been derived from the action of substances separated by dead animal or plant membranes. It must be, however, remembered that in the application of these principles to processes occurring in the living organism, the cells, forming the various membranes, are an im- portant modifying factor. It is probable that physico-chemical processes, occurring in the protoplasm the cell, may change its permeability to the same substance at different THE CHARACTER AND COMPOSITION OF LYMPH. The lymph is the fluid which immediately surrounds the tissue cells of the living body. It fills up the spaces between the cells themselves and between the cells and the blood-vessels which ramify among the cell-masses. The lymph, therefore, is an intermediate fluid between blood-plasma on the one hand, and the tissue cells on the other, receiving its ingredients by the passage of fluid from the plasma through the walls of the finer blood-vessels in the one direction, and by the discharge of the substances from the cells themselves in the other. The Chemical Composition of the Lymph. Since the chief source of the lymph is the blood-plasma, one would naturally expect that its chemical composition would be very similar to that of plasma, which is in fact the case. The variations that are noted in lymph taken from definite sources no doubt have their origin in the fact that the lymph passes through these organs slowly, and that ingredients peculiar to the necessities of the function and growth of the differentiated tissue of the organ are taken from the lymph in special organs. Lymph obtained from a human lymphatic fistula has been analyzed; the figures from Hammarsten are as follows, though considerable variations appear in the analyses from other authorities: ANALYSIS OF LYMPH. Per cent Water .• 94.5 to 96.5 Solids 3.7 to 5.5 Albumins 3.4 to 4.1 Ethereal extract 0.06 to 0.13 Sugar o.i Salts 0.8 to 0.9 Sodium chloride '. 0.55 to 0.58 Sodium carbonate 0.24 Disodic phosphate 0.028 The most notable fact to be derived from this composition table is the low percentage of proteids present in the lymph. The Formation of Lymph. The manner in which the substances in the lymph pass through the walls of the capillaries from the plasma is a 132 THE BLOOD question which has been surrounded with considerable difficulty. It is thought by Ludwig and many of his followers that the process involved is merely one of nitration. Certainly the blood pressure in the capillaries is in the main greater than that of the pressure of the lymph in the surround- ing tissues, and this positive pressure will contribute so much to the direct ingredients of the blood-plasma through the capillary walls. It is true, as a matter of experiment, that anything which contributes to an increase in the capillary pressure is very apt to produce an edema of the corresponding tissues. Since the colloidal materials represented by the proteid are non- diffusible, one would by this theory expect to find a diminished percentage in the lymph, which is true, though not to the extent which the theory demands. Heidenhain was the first to question the adequacy of the blood pressure and filtration hypothesis. He showed that many of the conditions under which lymph formation takes place are not sufficient to produce filtra- tions of the material found. He advanced the hypothesis that the living endothelial lining of the blood-vessels exerted a secretory activity in lymph production. He discovered that various substances known as lymphagogues when introduced into the circulatory system produce a remarkable increase in the flow of lymph from the thoracic duct. Further, he noticed that the concentration of the lymph was changed, i.e., increased. It has been sug- gested that these substances act to change the normal resistance of the endo- thelial cells, and this has been offered as a criticism. Nevertheless many drugs act to increase the flow of lymph in a way which cannot be presumed to be other than normal, i.e., they stimulate the physiological processes going on in the endothelial cells. Such observations contribute strongly to the view advanced by Heidenhain. Many investigations have been brought to the support of the hypothesis that lymph formation is largely a process of secretion, yet it seems at the present time that we cannot wholly deny that filtration and osmosis play a part in the processes. Certainly the permea- bility or activity of the endothelial lining of the blood-vessels varies greatly at different times in the life of an individual, and this variation in function is associated with the marked change in the character and quantity of lymph produced. The second factor in lymph formation, the activity of the tissue in taking up or discharging materials into the lymph-mass, must not be ignored alto- gether. LABORATORY EXPERIMENTS FOR THE EXAMINATION OF THE BLOOD. i. Microscopical Examination of the Blood. Mount a drop of frog's blood in 0.7 per cent sodium chloride and examine with the low power of a compound microscope. The red corpuscles will appear as oval nucleated iCTION OF FLUIDS ON THE BED CORPUSCLES 133 discs with a faint yellowish color, figure no. Here and there white granular cells of irregular outline will be noted, the white corpuscles. Examine the drop of blood with a high magnifying power and sketch the outline of the blood cells. Select the white corpuscle which is most irregular in outline and make a series of outline drawings once every minute to show its ame- boid movements, figure 117. Draw a drop of your own blood by puncturing the tip of the finger, under sterile conditions, and mount in a drop of 0.9 per cent physiological saline. Examine with a high power, note the small biconcave red corpuscles which appear faintly yellow in color and even adhere in rouleaux, figure 109. The white corpuscles will appear as somewhat larger granular discs differing in form and size. By mounting a drop of blood on a warm stage the ameboid movements of the white corpuscles can be observed with comparative ease. 2. Action of Fluids on the Red Corpuscles. Water. When water is added gradually to frog's blood, the oval disc-shaped corpuscles become spherical and gradually discharge their hemoglobin, a pale, transparent stroma being left behind. Human red blood cells change from a discoidal o FIG. 126. FIG. 127. FIG. 128. FIG. 129. FIG. 126. — Effect of Hypertonic Salt-Solution on the Red Blood-Corpuscles of Man. FIG. 127. — Effect of Acetic Acid. FIG. 128. — Effect of Tannin. FIG. 129. — Effect of Boric Acid. to a spheroidal form and discharge their cell-contents, becoming quite trans- parent and all but invisible (ghost corpuscles). Hypertonic Salt-Solutions. Mount a drop of human blood in 2 per cent sodium-chloride solution. The red blood cells lose their disc shape and be- come sp*herical with spinous projections or crenations, figure 126. The original form of the red blood cells can be restored by transferring them to isotonic salt-solution. Dilute Acetic Acid. This reagent causes the nucleus of the red blood cells in the frog to become more clearly defined; if the action is prolonged, the nucleus becomes strongly granulated, and all the coloring matter seems to be concentrated in it, the surrounding cell-substance and outline of the cell becoming almost invisible; after a time the cells lose their color altogether. The cells in figure 127 represent the successive stages of the change. A similar loss of color occurs in the red cells of human blood, which, from the absence of nuclei, seem to disappear entirely. Alkalies. Alkalies cause the red blood-corpuscles to absorb water and finally to disintegrate, 134 THE BLOOD Chloroform and Ether. These reagents when added to the red blood cells of the frog cause them to part with their hemoglobin; the stroma of the cells becomes gradually broken up. A similar effect is produced on the human red blood cell. Tannin and Boric Acid. When a 2 per cent fresh solution of tannic acid is applied to frog's blood it causes the appearance of a sharply denned little knob, projecting from the free surface (Roberts' macula). The coloring matter becomes at the same time concentrated in the nucleus, which grows more distinct, figure 128. A somewhat similar effect is produced on the human red blood-corpuscle. A 2 per cent solution of boric acid applied to nucleated red blood cells of the frog will cause the concentration of all the coloring matter in the nucleus; the colored body thus formed gradually quits its central position, and comes to be partly, sometimes entirely, protruded from the surface of the now colorless cell, figure 129. The result of this experiment led Briicke to dis- tinguish the colored contents of the cell (zooid) from its colorless stroma (ecoid). When applied to the non-nucleated mammalian corpuscle its effect merely resembles that of other dilute acids. 3. Phagocytosis in White Corpuscles. Mix some very fine pigment granules, powdered vermilion, or charcoal with a few drops of frog's blood, let stand for 10 or 20 minutes, then mount a drop on the glass slide and ex- amine under a high-magnifying microscope. In a favorable field here and there will be found some white corpuscles which have taken up the pigment. Colored corpuscles have been observed with fragments of pigment embedded in their substance. White corpuscles have also been seen in diseased states of the body to contain micro-organisms, for example, bacilli, and are said to have the power of destroying these organisms, which gives them the name phagocytes. 4. Enumeration of the Blood-Corpuscles. Several methods are employed for counting the blood-corpuscles, most of them depending upon FIG. 130. — Thoma-Zeiss Hemacytometer, glass slide. the same principle, i.e., the dilution of a minute volume of blood with a given volume of a colorless solution similar in specific gravity to blood-plasma, so that the size and shape of the corpuscles are altered as little as possible. A minute quantity of the well-mixed solution is then taken, examined under the microscope, either in a flattened capillary tube (Malassez) or in a cell (Hayem and Nachet, Gowers) of known capacity, and the number of corpus- cles in a measured length of the tube, or in a given area of the cell, is counted. The length of the tube and the area of the cell are ascertained by means of a micrometer scale in the microscope ocular; or in the case of Gowers' modi- THE PERCENTAGE OF CORPUSCLES AND PLASMA 135 fication, by the division of the cell area into squares of known size. Having ascertained the number of corpuscles in the diluted blood, it is easy to find out the number in a given volume of normal blood. The hemacytometer, which is most used at the present time, is known as the Thoma-Zeiss hemacytometer. It consists of a carefully graduated pipet, in which the dilution of the blood is done; this is so formed that the capillary stem has a capacity equalling one-hundredth of the bulb above it. If the blood is drawn up in the capillary tube to the line marked i, figure 131, the saline solution may afterward be drawn up the stem to the line 101; in this way we have 101 parts of which the blood forms i. As the content of the stem can be displaced unmixed we shall have in the mixture the proper dilution. The blood and the saline solution are well mixed by shaking the pipet, in the bulb of which is contained a small glass bead for the purpose of aiding the mixing. The other part of the instrument consists of a glass slide, figure 130, upon which is mounted a covered disc, m, accurately ruled so as to present one square millimeter divided into 400 squares of one-twentieth of a millimeter each. The micrometer thus made is surrounded by another annu- lar cell, c, which has such a height as to make the cell project exactly one-tenth millimeter beyond m. If a drop of the diluted blood be placed upon w, and c be covered with a perfectly flat cover-glass, the volume of the diluted blood above each of the squares of the mi- crometer, i.e., above each 4^-0", will be 4-0 ~o of a cubic millimeter. An average of ten or more squares is then taken, and this num- ber multiplied by 4000 X 100 gives the number of corpuscles in a cubic millimeter of undiluted blood. A separate pipet is used for making dilu- tions for counts of leucocytes. In this, the dilution is made of one part of blood and ten parts of diluting fluid. Acetic acid, 0.2 of one per cent, is usually employed for this purpose. 5. The Percentage of Corpuscles and Plasma in Human Blood. Fill the two graduated capillary tubes of a hematocrite with blood drawn from the tip of your own finger, insert into the instrument, and centrifuge as rapidly as possible. The experiment must be performed within the time limit of clotting in order to be successful. The corpuscles will be thrown down and the percentage of plasma and corpuscles can be read off directly. Should one fail to fill the tube exactly full, then the percentage of plasma and corpuscles can be calculated from the proportion which each bears to the quantity in the tube, FIG. 131. — Thoma- Zeiss Hemacytometer, pipet. 136 THE BLOOD 6. Estimation of the Percentage of Hemoglobin. The per cent of hemoglobin in a sample of blood can be obtained by the instrument known as Fleischl's hemometer, see figure 122. The principle of this instrument rests on a comparison of the color of the sample of dilute blood with a stand- ard glass wedge of uniform tint similar to that of blood. Fill one of the chambers in the cells of the instrument half full with a 2 per cent solution of sodium carbonate. Now draw a drop of blood from the tip of a finger. Touch the drop with the end of the standardized capillary tube, using care to fill it accurately. Quickly wash this sample of blood out in the carbonate solution in the cell and finish filling the cell. Put distilled water in the other half of the cell, mount in the instrument, and examine in a dark room, using candle-light. The glass wedge is graduated in percentage which can be read off directly. This instrument is usually provided with several cells, in which case as many samples may be taken and the average of the readings used to determine the percentage. Perhaps a more convenient and certainly a quicker method for deter- mining the percentage of hemoglobin is Talquist's hemoglobinometer. By this method a drop of blood is drawn directly on to absorbent paper furnished with the instrument, and the resulting stain is compared directly with a paper color scale which is graduated in percentage. In this method the comparison is made in ordinary daylight, and because of its rapidity it is very convenient for clinical examinations. 7. Reaction of Blood-Plasma. Wet a piece of neutral litmus paper (some prefer glazed paper), then touch one end of the strip with a drop of blood drawn from your finger under sterile conditions. After a few moments wash off the excess of corpuscles in neutral distilled water. The deeper blue at the point of contact with the blood indicates alkalinity. 8. The Specific Gravity of Blood. From standard mixtures of chloroform and benzol with specific gravity of 1.050, 1.060, and 1.070 make up a set of specific-gravity solutions of 1.050, 1.052, 1.054, etc., to 1.070. These standards may be kept in stoppered 4-dram vials, or in test tubes. The specific gravity of blood is determined by inserting with a pipet a drop of freshly drawn blood into the middle of one of the solutions, say 1.056. Since the blood does not mix with the chloroform and benzol the drop will rise or sink according to its relative specific gravity. By a few trials one may quickly find a specific gravity in which the drop of blood floats without rising or sinking. This represents the specific gravity of the drop of blood. This method permits rapid clinical application and has proven of con- siderable interest in the hands of clinists. 9. The Isotonicity of Blood. The absorption or loss of water by the corpuscles of blood in solutions of other concentrations than that of blood-plasma can be used as a means of determining the isotonicity of blood. COAGULATION OF BLOOD 137 Make up a series of solutions of sodium chloride, varying by tenths, from 0.5 to 1.2 per cent. Prepare a series of slides with vaseline rings and mount drops of human blood in drops of saline of 0.6, 0.7, 0.8, 0.9, i, and i.i per cent, examine every ten minutes under a high-power microscope. The corpuscles of some of the slides will swell up and may disintegrate, others will show crenation as in figure 126. In the isotonic solutions the corpus- cles will appear of their normal size and condition. 10. Coagulation of Blood, a. Normal Clot. Anesthetize a dog, insert a cannula into the carotid or femoral artery, and draw samples of blood into two or three clean, dry test tubes. Draw one sample into a test cube that has had its sides oiled. Note the exact time at which the blood was drawn into the test tubes and set the test tubes in a test-tube rack. Ex- amine at intervals of 30 seconds by gently inclining the test tubes. Presently FlG. 132. — Miscroscopic View of Clot Showing Fibrin Network. it will be noted that the blood becomes more viscous and does not flow freely up the sides of the test tubes. Later the whole mass will become jelly-like and will retain the form of the test tube. Note the time of the first slight change, and also when the clot becomes more perfect. The sample in the oiled test tube will be found to clot more slowly. If the test tubes of clotted blood are left standing for a day, the coagulum will become similar in size and a transparent yellowish blood will make its appearance on the surface or between the sides of the clot and the test-tube wall. This fluid is the serum and it is squeezed out by the shrinking of the fibrin which holds the corpuscles in its meshes. b. Microscopic Examination of the Process oj Clotting. Take a drop of 138 THE BLOOD fresh blood from the tip of your finger under sterile conditions and mount on a microscopic slide in a few drops of salt-solution, and examine immediately under the high power. Small threads of fibrin will presently be seen to form across the field, usually being most clearly obvious where fragments of white corpuscles are noted, see figures 107 and 132. The threads of fibrin become more apparent when stained with rosanilin. c. Whipped Blood. Draw a sample of blood into a glass tumbler, enough to fill it one-half or two-thirds full. Immediately begin vigorously stirring the blood with a bunch of stiff wires or a pencil, and keep it up until the time of clotting has passed, 5 or 10 minutes. In this instance the wires will break up and collect the fibrin as fast as it forms, and no firm mass will be produced. The remaining fluid is called whipped blood. The fibrin can be removed from the wires and washed in tap water until all the adherent red corpuscles are removed. This mass of fibrin is white, elastic, and com- posed of a network of thread-like fibers. It is these fibers extending through and through the mass of blood which makes it retain the form of the vessel when undisturbed clotting occurs. d. The Influence of Salt-Solution on Blood-Clotting. Add 20 c.c. of satu- rated magnesium sulphate, i per cent sodium oxalate, and 2.5 per cent of sodium chloride in each of 3 beakers. Draw into each beaker 50 to 60 c.c. of blood and immediately mix thoroughly and let stand. The magnesium and oxalate beakers will not coagulate even though they stand for days, but the sodium-chloride blood will clot in a few minutes. The magnesium-sulphate blood will coagulate if diluted with a sufficient amount of distilled water or physiological saline solution. Make a series of dilutions and note when coagulation takes place. The sodium-oxalate blood will coagulate when a sufficient excess (i per cent) of calcium chloride is added to neutralize the excess of sodium oxalate. Demonstrate this on a series of samples. If a liter or so of magnesium or oxalate blood is secured and separated by a centrifuge, or by leaving stand for a sufficient time, a sample of salted plasma will be obtained. This sample will coagulate when it is treated as just described for salted blood, showing that the antecedents of fibrin are found in the plasma. e. Action of Tissue Extracts on Coagulation. Wash out the blood of a small animal by circulating 0.9 per cent saline through the arteries until the outflowing fluid from the veins is clear. Take an organ, the liver for example, grind it up in a sausage mill by running it through the mill two or three times, then extract with 0.9 per cent physiological saline. The macerating mass should be shaken up at intervals, and may be kept from spoiling by adding an excess of chloroform or by keeping on ice. A few cubic centimeters of this fluid extract added to a sample of freshly drawn blood will very greatly hasten the rapidity of coagulation. This tissue ex- THE CHEMISTRY OF BLOOD-PLASMA 139 tract is called thrombokinase, as it is an activator which hastens the formation of thrombin from thrombogen. 11. The Chemistry of Blood-Plasma (or Serum). The blood- plasma contains all the chemical substances which are utilized by the tissues in their nutrition or which are thrown off by the tissues as a re- sult of their activity. It is therefore a very complex mixture. The serum contains the same substances in the same proportion, with the exception of the antecedents of fibrin. It may, therefore, be used as a substitute for plasma in most cases. a. Proteids oj Plasma. There are three principal proteids in blood- plasma: serum-albumin, serum-globulin, and fibrinogen. These may be isolated as follows: To a sample of blood-plasma add an equal quantity of sodium-chloride solution that has been saturated at 40° C. A white floccu- lent precipitate of fibrinogen comes down. Filter off, and add to the nitrate an equal volume of saturated ammonium sulphate. A second heavier pre- cipitate of serum-globulin separates out. When this is separated, and crys- tals of ammonium sulphate are added to the nitrate to complete saturation at 40° C., a third precipitate of serum-albumin separates. Each of these precipitates may be redissolved and purified by reprecipi- tation and can be tested by the characteristic proteid reactions, see page 96, which they all give. b. Sugars of Blood-Plasma or Serum. If a quantity of blood-serum is diluted with about 5 to 10 times its' volume of water, and the proteids are removed by slight acidulation with acetic acid and boiling and filtering, the filtrate will contain reducing sugar and the various solids of blood-plasma. To a concentrated sample of the filtrate add Fehling's solution and boil. A reddish precipitate indicates the presence of reducing sugar. If this ex- periment is done quantitatively, about from o.i to 0.2 per cent of sugar will be found. c. The Salts oj Blood-Plasma. The salts of blood-plasma are tested best by evaporating some of the blood serum to dryness, and burning the residue to oxidize the organic matter and dissolving the ash in water. Test as follows: To a sample add i per cent of silver nitrate; a white precipitate soluble in an excess of ammonia, but not soluble in nitric acid, indicates chlorides. To a second sample add i per cent barium chloride. If sulphates are present there will be a white precipitate which settles out quickly. Acidify a third sample with nitric acid and add ammonium molybdate and heat. A yellow precipitate indicates the presence of phosphates. To the fourth sample add an excess of strong ammonia and i per cent ammonium oxalate, heat. A white precipitate indicates the presence of calcium. 12. Blood-Corpuscles. The characteristic substance in the composi- 140 THE BLOOD tion of the corpuscles is the pigment known as hemoglobin, and this is the only chemical factor that will be considered in these experiments. a. Hemoglobin Crystals. Take a sample of dog's blood, or if a centri- fuge is available separate and wash the sample of blood-corpuscles, and mix with about three volumes of saturated ether water, or if blood is used dilute with two or three volumes of water and add about 10 per cent of pure ether and shake thoroughly. Crystals of oxyhemoglobin will be formed, and this can be mounted and examined with a microscope. b. Spectrum of Hemoglobin and its Compounds. 1. Oxyhemoglobin. Dilute a sample of defibrinated blood with about ten volumes of distilled water. From this stock solution make five solutions all differing by 33^ per cent. Examine these with a direct-vision spectroscope. Make a drawing showing the absorption spectrum of each sample as com- pared with the solar spectrum. Compare with the spectrum shown in the frontispiece. 2. Hemoglobin. The oxygen can be driven out from the hemoglobin by adding to the above samples a few drops of ammonium sulphide and gently warming. Re-examine with the direct-vision spectroscope and map as before. 3. Carbon-Monoxide Hemoglobin. Pass a stream of ordinary illumi- nating gas through the dilutions of hemoglobin. The carbon monoxide of the gas will form a compound with the hemoglobin, which now turns a bright scarlet color. When examined with the spectroscope, the absorp- tion bands are found to be very similar to those of oxyhemoglobin. How- ever, map the spectrum to the scale as usual. Add the reducing agent, warm, and shake vigorously and re-examine. It is very difficult to break up the combination of hemoglobin with carbon monoxide, hence the poisonous action of this gas. CHAPTER V THE CIRCULATION OF THE BLOOD THE blood is contained in a system of closed vessels through which it is kept in circulation during the life of an individual. The energy to keep up this motion is supplied by the heart, which is a large muscular organ con- sisting of four great divisions, the right and left auricles and right and left ventricles. The right ventricle discharges its blood into the pulmonary artery, FIG. 133.— Diagram of the Circulation in an Animal with a Completely Separated Right and Left Ventricle and a Double Circulation. (After Huxley.) Ad, Right auncle receiving the superior and inferior venae cavae, Vcs and Vci; Dth, thoracic duct, the main trunk of the lymphatic system; Ad, right auricle; Vd, right ventricle; Ap, pulmonary artery; P, lung; Vp, pulmonary vein; As, left auricle; Vs, left ventricle; A o, aorta; D, intestine; L, liver; Vp, portal vein; Lv, hepatic vein. through which it passes to the lungs, returning through the pulmonary veins to the left auricle, and into the ventricle. From the left ventricle the blood fc pumped into the great aorta, and through its branches distributed to the entire body. The terminal arteries are continuous with the general capillaries of the 141 142 THE CIRCULATION OF THE BLOOD body, and these in turn with the veins, which conduct the blood back to the right side of the heart again. It will be seen, therefore, that the circulatory apparatus consists of two great divisions, the pulmonary and the systemic cir- culation. This arrangement is illustrated by the accompanying figure. A study of this figure will show that in certain regions of the systematic circu- lation there are two capillary beds between the main arteries and the main veins. This subordinate stream through the liver is called the portal cir- culation, and the similar arrangement existing in the kidney is called the renal circulation. This, in general, is the outline of the course of the blood in its circulation. To make a study of the various phenomena manifested in the physiology of the circulatory apparatus, it is obvious that we have to do with certain fundamental activities; first, the physiology of the pumping organ, the heart; second, the behavior of the blood in the arteries, capillaries, and veins; third, the coordination of these various divisions of the apparatus through the nervous system. To understand this it will be necessary to have in mind in detail the anatomical structure of the apparatus itself. ANATOMICAL CONSIDERATIONS. The Heart. The heart is contained in the chest or thorax, and lies between the right and left lungs, figure 134, enclosed in a membranous sac, the pericardium. The pericardium is made up of two distinct parts, an external fibrous membrane, and an internal serous layer, which not only lines the fibrous sac, but als6 is reflected on to the heart, which it completely invests. These form a closed sac, the cavity of which contains just enough fluid to lubricate the two surfaces, and thus to enable them to glide smoothly over each other during the movements of the heart. The vessels passing in and out of the heart receive investments from this sac to a greater or less degree. The heart is situated in the chest behind the sternum and costal carti- lages, being placed obliquely from right to left. It is of pyramidal shape, with the apex pointing downward, outward, and toward the left, and the base backward, inward, and toward the right. The heart is suspended in the chest by the large vessels which proceed from its base, but, excepting at the base, the organ itself hangs free within the sac of the pericardium. The part which rests upon the diaphragm is flattened, and is known as the posterior surface, while the free upper part is called the anterior surface. On examination of the external surface, the division of the heart into parts which correspond to the chambers inside of it may be traced, for a deep transverse groove, called the auriculo-ventricular groove, divides the auricles from the ventricles; and the interventricular groove runs between the ventricles, both in front and in the back, separating the one from the other. The anterior groove is nearer the left margin, and the posterior nearer THE HEART 143 the right, as the front surface of the heart is made up chiefly of the right ventricle and the posterior surface of the left ventricle. The coronary ves- sels which supply the tissue of the heart with blood run in the furrows or grooves; also the nerves and lymphatics, which are embedded in more or less fatty material, are found in this groove. The Chambers oj the Heart. The interior of the heart is divided by a longitudinal partition in such a manner as to form two chief chambers or cavities, the right and the left. Each of these chambers is again subdivided transversely into an upper and a lower portion, called respectively the auricle FIG. 134. — Outline of Heart, Lungs, and Liver to Show their Relations to each other and to the Chest Wall. (Heusman and Fisher's "Anatomical Outlines.") and the ventricle, which freely communicate. The aperture of communica- tion, however, is guarded by valves so disposed as to allow blood to pass freely from the auricle into the ventricle, but not in the opposite direction. There are thus four cavities ;*i the heart, the auricle and ventricle of one side being quite separate from those on the other, figure 135. The right auricle, the right part of the base of the heart as viewed from the front, is a thin-walled cavity of more or less quadrilateral shape, prolonged at one corner into a tongue-shaped portion, the right auricular appendix, which slightly overlaps the exit of the aorta from the left ventricle. The interior of the auricle is smooth, being lined with the general lining membrane of the heart, the endocardium. The superior and inferior venae cavse open into the auricle. The opening of the inferior cava is protected and partly covered by a membrane called the Eustachian valve. In the posterior wall of the auricle is a slight depression called the fossa ovalis, 144 THE CIRCULATION OF THE BLOOD which corresponds to an opening between the right and left auricles, exist- ing in fetal life. In the appendix are closely set elevations of the muscular tissue, covered with endocardium, and on the anterior wall of the auricle are similar elevations arranged parallel to one another, called musculi pectinati. FIG. 135. — The Right Auricle and Ventricle Opened and a Part of their Right and Anterior Walls Removed so as to Show their Interior, i, Superior vena cava; 2, inferior vena cava; 2', hepatic veins cut short; 3, right auricle; 3', placed in the fossa ovalis, below which is the Eustachian valve; 3", is placed close to the aperture of the coronary vein; t, t, placed in the auriculo- ventricular groove, where a narrow portion of the adjacent walls of the auricle and ventricle has been pre- served; 4, 4, cavity of the right ventricle, the upper figure is immediately below the semilunar valves; 4', large columna carnea or musculus papillaris; 5, 5', 5", tricuspid valve; 6, placed in the interior of the pulmonary artery, a part of the anterior wall of that vessel having been removed and a narrow portion of it preserved at its commencement where the semilunar valves are attached ; 7, concavity of the aortic arch close to the cord of the ductus arteriosus; 8, ascending part or sinus of the arch covered at its commencement by the auricular appendix and pulmonary artery; 9, placed between the innominate and left carotid arteries; 10, appendix of the left auricle; n, n, outside of the left ventricle the lower figure near the apex. (Allen Thomson.) The right ventricle forms the right margin of the heart. It takes no part in the formation of the apex. On section its cavity is semilunar or crescentic, figure 137. Into it are two openings, the auriculo-ventricular orifice at the base, and the opening of the pulmonary artery, also at the base but more to the left. The part of the ventricle leading to the pulmonary artery is called the conus arteriosus or infundibulum; both orifices are guarded by valves, the former called the tricuspid and the latter the semilunar. THE HEART 145 In this ventricle are also the projections of the muscular tissue called the columncE carnecB. The left auricle is situated at the left and posterior part of the base of the heart. The left auricle is only slightly thicker than the right and its FIG. 136.— The Left Auricle and Ventricle Opened and a Part of Their Anterior and Left Walls Removed. Magnified £. The pulmonary artery has been divided at its commencement; the opening into the left ventricle is carried a short distance into the aorta between two of the segments of the semilunar valves; and the left part 9f the auricle with its appendix has been removed. The right auricle is out of view, i, The two right pulmonary veins cut short; their openings are seen within the auricle; i', placed within the cavity of the auricle on the left side of the septum and on the part which forms the remains of the valve of the foramen ovale, of which the crescentic fold is seen toward the left hand of i'; 2, a narrow portion of the wall of the auricle and ventricle preserved round the auriculo- ventricular orifice; 3, 3', the cut surface of the walls of the ventricle, seen to become very much thinner toward 3", at the apex; 4, a small part of the anterior wall of the left ventricle which has been preserved with the principal anterior columna carnea or musculus papil- laris attached to it; 5, 5, musculi papillares; 5', the left side of the septum, between the two ven- tricles, within the cavity of the left ventricle; 6, 6', the mitral valve; 7, placed in the interior of the aorta near its commencement and above the three segments of its semilunar valve which are hang- ing loosely together; 7', the exterior of the great aortic sinus; 8, the root of the pulmonary artery and its semilunar valves; 8', the separated portion of the pulmonary artery remaining attached to the aorta by 9, the cord of the ductus arteriosus; 10, the arteries rising from the summit of the aor- tic arch. (Allen Thomson.) form and structure" are the same as in the right. The left auricula-ventricu- lar orifice is oval and a little smaller than that on the right side of the heart. There is a slight vestige on the septum of the foramen between the auricles. 10 146 THE CIRCULATION OF THE BLOOD The left ventricle occupies the posterior and apical portion of the heart, and is connected directly with the great aorta. It is separated from the auricle by the bicuspid or mitral valves, and the opening into the great aorta is guarded by the semilunar valves. The walls of the left ventricle are two or three times as heavy as those of the right, and may be as much as half an inch in total thickness. The left ventricle is capable of containing 90 to 120 c. c. of blood. The capacity of the auricles is considerably less after death owing to their con- tracted condition. The whole heart is about 12 cm. long by 8 cm. at its greatest width, and 6 cm. in thickness. The average weight in the adult is about 300 grams. The walls of the heart are constructed almost entirely of layers of muscu- lar fibers; but a ring of connective tissue, to which some of the muscular fibers are attached, is inserted between each auricle and ventricle and forms FIG. 137. — Cross-section of a Completely Contracted Human Heart, at the Level of the Lower and Middle Thirds. (According to Krehl.) the boundary of the auricula-ventricular opening. Fibrous tissue also exists at the origins of the pulmonary artery and aorta. The muscular fibers of each auricle are in part continuous with those of the other, and in part separate; and the same holds true for the ventricles. The fibers of the auricles are, however, quite separate from those of the ventricles, the bond of connection between them being the fibrous and the embryonic muscular tissue of the auriculo-ventricular rings and the bundle of His in the septum. The development of the heart shows that it is derived from an embryonic tube, which in its growth becomes twisted upon itself and divided into the THE HEART 147 two main divisions that we know in the adult. Anatomical dissections have shown that the muscles of the ventricles form spiral sheaths extending from FIG. 138. FIG. 138. — Cardiac Muscle Cells, Showing their Form, Branches, Nuclei, and Striae. From the heart of a young rabbit. Magnified 425 diameters. (Schafer.) a, Line of junction between the cells (intercellular cement) ; b, c, branches of the cells. FIG. 139.— Cardiac Muscle Cells of the Left Ventricle of a Child at Birth (full term), to show the form of the cells, their structural details, their relations to one another, and their general agree- ment with those of cold-blooded vertebrates. A, Large cell with two nuclei; this cell has nearly the proportions of those of the adult; B, group of cells in their natural relatipn. At the right of the middle cell are two spaces or fissures, n. Nucleus. The transverse striations cross the nuclei in all the cells, and each nucleus possesses several nucleoli. (Gage.) FIG. 140. FIG. 141. FIG. 140. — Diagram of the Course 9f the Superficial Muscle Layers Originating in the Right and Left Auriculo- ventricular Rings and in the Posterior Half of the Tendon of the Conus. (After MacCallum.) C, Anterior papillary muscle. FIG. 141. — Diagram of the Course of the Superficial Muscle Layers Originating in the Anterior Half of the Tendon of the Conus. (After MacCallum. ) A , Posterior papillary muscle; B, papillary muscle of the septum. 148 THE CIRCULATION OF THE BLOOD the base of the two ventricles in spiral bands toward the apex. These bands of muscle are wound about the surface of the ventricles in the right-to-left direction. At the apex they extend up into the deeper tissue. If the super- ficial muscles are dissected off, there is left a great central core of muscle, FIG. 142. FIG. 143- FIG. 142. — Diagram of the Course of the Layer Superficial to the Deepest Layer of the Muscle of the Left Ventricle, which is shown in outline. The deepest layer is also shown. (After Mac- Callum.) A, Posterior papillary muscle; B, papillary muscle of the septum. FIG. 143. — Diagram of a Layer still more Superficial to that Shown in Fig. 142, and Ending in the Anterior Papillary Muscle. The deeper layers are represented in dotted lines. (After MacCallum.) A, Posterior papillary muscle; B, papillary muscle of septum; C, anterior papillary muscle. which is described by MacCallum as running more transversely around the wall of one ventricle, then through the septum and around the other in a reverse scroll, figure 142. The Valves of the Heart. The valves of the heart are arranged so that the blood can pass only in one direction. These are the tricuspid valve, between the right auricle and right ventricle, figure 135, and the semi- lunar valves of the pulmonary artery, the mitral valve between the left auricle and ventricle, and semilunar valves of the aorta. The bases of the tricuspid, figure 152, and mitral valves are attached to the walls of the auriculo-ven- tricular rings, respectively. Their ventricular surfaces and borders are fastened by slender tendinous fibers, the chorda tendinece, to the internal surface of the walls of the ventricles at points which project into the ventricu- lar cavity in the form of bundles or columns, the columns carnece. The semilunar valves guard the orifices of the pulmonary artery and of the aorta. They are nearly alike on both sides of the heart, but the aortic valves are altogether thicker. Each valve consists of three parts which are of semilunar shape, the convex margin of each being attached to a fibrous ring at the place of junction of the artery to the ventricle, and the concave or nearly straight border being free, so as to form a little pouch like a pocket, 7, figure 136. In the center of each free edge of the valves which contains a fine cord of fibrous tissue, is a small fibrous nodule, the corpus Arantii. THE ARTERIES 149 The Arteries. The arterial system begins at the left ventricle in a single large trunk, the aorta, which, almost immediately after its origin, gives off in the thorax three large branches for the supply of the head, neck, and upper extremities; it then traverses the thorax and abdomen, giving off branches, some large and some small, for the supply of the various organs and tissues it passes on its way. In the abdomen it divides into two chief branches. The arterial branches, wherever given off, divide and subdivide until the caliber of each subdivision becomes very minute. These smallest arteries are called arterioles. These arterioles are continuous with the capil- laries. Arteries frequently communicate or anastomose with other arteries. The arterial branches are usually given off at an acute angle, and the areas of the branches of an artery generally exceed that of the parent trunk, and, , , m FIG. 144. FIG. 145. FIG. 146. FIG. 144. — Minute Artery Viewed in Longitudinal Section, e, Nucleated endothelial mem- brane, with faint nuclei in lumen, looked at from above; *', thin elastic tunica intima; ra, muscular coat or tunica media; a, tunica adventitia. (Klein and Noble Smith.) FIG. 145. — Transverse Section through a Large Branch of the Inferior Mesenteric Artery of a Pig. e, End9thelial membrane; *", tunica elastica interna, no subendothelial layer is seen; m, muscular tunica media, containing only a few wavy elastic fibers; e, c, tunica elastica externa, di- viding the media from the connective-tissue adventitia, a. (Klein and Noble Smith.) Magnifica- tion 350 diameters. FIG. 146. — Muscular Fiber Cells from Human Arteries. Magnified 350 diameters. (Kolliker.) a, Nucleus; B, a fiber cell treated with acetic acid. as the distance from the origin is increased, the area of the combined branches is increased also. As regards the arterial system of the lungs, the pulmonary artery and its subdivisions, they are distributed in much the same manner as the arteries belonging to the general systemic circulation. The walls of the arteries are composed of three principal coats, the ex- ternal or tunica adventitia, the middle or tunica media, and the internal or tunica intima. The external coat, figures 144 and 145, a, the strongest and toughest part of the wall of the artery, is formed of areolar tissue, with which is mingled throughout a network of elastic fibers. The middle coat, figure 150 THE CIRCULATION OF THE BLOOD 145, m, is composed of both muscular and elastic fibers with a certain pro- portion of areolar tissue. In the larger arteries, figure 145, its thickness is comparatively as well as absolutely much greater than in the small arteries, constituting, as it does, the greater part of the arterial wall. The muscular fibers are unstriped, figure 146, and are arranged, for the most part, trans- versely to the long axis of the artery, figure 144, m, while the elastic element, taking also a transverse direction, is disposed in the form of closely inter- woven and branching fibers intersecting in all parts the layers of muscular fiber. In arteries of various size there is a difference in the proportion of FIG. 147. — Vein and Capillaries. Silver-nitrate and hematoxylin stain, to show outlines of endothelial cells and their nuclei. (Bailey.) the muscular and elastic element, elastic tissue preponderating in the largest arteries and unstriped muscle in those of medium and small size. The arteries are quite elastic in both large and small vessels. The internal coat is formed by a layer of elastic tissue, called the jenestrated membrane of Henle. It is peculiar in its tendency to curl up when peeled off from the artery, and FIG. 148.— Network of Capillary Vessels of the Air Cells of the Horse's Lung Magnified, a, a, Capillaries proceeding from b, b, terminal branches of the pulmonary artery. (Frey.) in the perforated and streaked appearance which it presents under the micro- scope. The inner surface of the artery is lined with a delicate layer of elon- gated endothelial cells, figure 145, e, which make it smooth and polished and furnish a nearly impermeable surface along which the blood may flow with the smallest possible amount of resistance from friction. THE CAPILLARIES 151 Nerves. Most of the arteries are surrounded by a plexus of nerves or nerve fibers, which twine around the vessel. The smaller arteries also have a delicate network of similar nerve fibers many of which appear to end near the nuclei of the transverse muscular fibers. The Capillaries. In all vascular textures, except some parts of the corpora cavernosa of the penis, of the uterine placenta, and of the spleen, FIG. 149. — Capillaries of Striated Muscular Tissue. From a cat. Magnified 300 diameters. (Heitzmann.) A, Artery; V, vein. the transmission of the blood from the minute branches of the arteries to the minute veins is effected through a network of capillaries. They may be seen in all minutely injected preparations. The point at which the arteries terminate and the capillaries commence cannot be exactly defined, for the transition is gradual. The capillaries maintain essentially the same diameter throughout. The meshes of the network that they compose are more uniform in shape and size than those formed by the anastomoses of the minute arteries and veins. 152 THE CIRCULATION OF THE BLOOD The walls of the capillaries are composed of a single layer of elongated or radiate, flattened and nucleated endothelial cells, so joined and dove- tailed together as to form a continuous transparent membrane, figure 147. Outside these cells in the larger capillaries there is a structureless supporting membrane on the inner surface of which they form a lining. The diameter of the capillary vessels varies somewhat in the different textures of the body, the most common size being about 12 micromillimeters, -joinr °f an mcn- Among the smallest may be mentioned those of the brain and of the follicles of the mucous membrane of the intestines; among the largest, those of the skin, and especially those of the medulla of the bones. The form of the capillary network differs in the different organs of the body, but is usually adjusted to the structural arrangement of the cells of any given organ. The capillary network is closest in the lungs and in the choroid coat of the eye. In the human liver the interspaces are of the same size, or even smaller than the capillary vessels themselves. In the human lung the spaces are smaller than the vessels; in the human kidney, and in the kidney of the dog, the diameter of the injected capillaries, compared with that of the inter- spaces, is in the proportion of one to four, or of one to three. The brain receives a very large quantity of blood; but its capillaries are very minute and are less numerous than in some other parts. In the mucous mem- branes, for example in the conjunctiva and in the cutis vera, the capillary vessels are much larger than in the brain and the interspaces narrower, namely, not more than three or four times wider than the vessels. In the periosteum and in the external coat of arteries the meshes are much larger, their width being about ten times that of the vessels. It may be held as a general rule that the more active the functions of an organ are, the more vascular it is. The Veins. The venous system begins in small vessels which are slightly larger than the capillaries from which they spring. These vessels are gathered up into larger and larger trunks until they terminate in the two venae cavse and the coronary vein which enter the right auricle, and in' four pulmonary veins which enter the left auricle. The total capacity of the veins diminishes as they approach the heart; but their capacity exceeds by two or three times that of their corresponding arteries. The pulmonary veins, however, are an exception to this rule. The veins are found after death more or less collapsed, and often contain blood. They are usually distributed in a superficial and a deep set which communicate frequently in their course. The coats of veins bear a general resemblance to those of arteries, figure 150. Thus, they possess outer, middle, and inner coats. The outer coat is constructed of areolar tissue like that of the arteries, but is thicker. In some veins it contains muscular cells arranged longitudinally. The middle coat THE VEINS 153 is considerably thinner than that of the arteries; it contains circular un- striped muscular fibers mingled with a large proportion of yellow elastic and white fibrous connective tissue. In the large veins near the heart the middle FIG. 150. — Transverse Section through a Small Artery and Vein of the Mucous Membrane of a Child's Epiglottis; the artery is thick- walled and the vein thin- walled. A, Artery; the letter is placed in the lumen of the vessel, e, Endothelial cells with nuclei clearly visible; these cells appear very thick from the contracted state of the vessel. Outside it a double wavy line marks the elastic tunica intima. m. Tunica media consisting of unstriped muscular fibers circularly ar- ranged; their nuclei are well seen, a, Part of the tunica adventitia, showing bundlespf connective- than that of the artery. X 350. (Klein and Noble Smith.) FIG. 151. — A, Vein with valves open. B, vein with valves closed; stream of blood passing off by lateral channel. (Dal ton. ) 154 THE CIRCULATION OF THE BLOOD coat is replaced for some distance from the heart by circularly arranged striped muscular fibers continuous with those of the auricles. The internal coat of veins consists of a fenestrated membrane lined by endothelium. The fenestrated membrane may be absent in the smaller veins. The veins are supplied with valves in certain regions of the body, especially in the veins of the arms and legs. The general construction of these valves is similar to that of the semilunar valves of the aorta and pulmonary artery already described. Their free margins are turned in the direction toward the heart, so as to prevent any movement of blood backward. They are commonly placed in pairs, at various distances in different veins. In the smaller veins single valves are often met with, and three or four are sometimes placed together or near one another in the larger veins such as in the subclavians at their junction with the jugular veins. During the period of their in- action, when the venous blood is flowing in its proper direction, they lie by the sides of the walls of the veins; but when in action, they come together like valves of the arteries, figure 151. Their situation in the superficial veins of the forearm is readily discovered by pressing along its surface, in a direction opposite to the venous current, i.e., from the elbow toward the wrist, when little swellings, figure 151, B, will appear in the position of each pair of valves. Lymphatic spaces are present in the coats of both arteries and veins; but in the tunica adventitia or external coat of the large vessels they form a distinct plexus of more or less tubular vessels. In smaller vessels they appear as sinus spaces lined by endothelium. Sometimes, as in the arteries of the omentum, mesentery, and membranes of the brain, the pulmonary, hepatic, and splenic arteries, the spaces are continuous with vessels which distinctly ensheath them, perivascular lymphatic sheaths. Lymph channels are said to be present also in the tunica media. THE ACTION OF THE HEART. The heart's action in propelling the blood consists in the successive alter- nate contraction, systole, and relaxation, diastole, of the muscular walls of the auricles and the ventricles. This activity furnishes the power which keeps the blood moving through the arteries, capillaries, and veins. The heart in its activity is like a great force pump in that it injects a certain quan- tity of blood at each contraction into the great arteries. Owing to the inter- action between this heart-beat and the peripheral resistance to the flow of blood, together with the elasticity of the vessels themselves, a high pressure in the arteries is maintained all the time. The heart's contractions then, pumping against this high arterial tension, are sufficient to maintain a constant flow of blood through the capillaries, and, therefore, through the active tissues. The heart beats at an average rate of about 72 times per minute during ACTION OF THE HEART 155 life. Each successive contraction really begins in the great veins, which are muscular, and extends over the auricles and ventricles in regular sequence. The contraction of each successive part is called its systole and the relaxation its diastole. The diastole covers the period of active relaxation of the muscle and the pause before beginning its next contraction. Each muscular cham- ber of the heart may, therefore, be said to have its systole and diastole. The whole series of events from the beginning of one contraction until the cor- responding event in the next contraction is described as the cardiac cycle. Action of the Auricles. The description of the action of the heart may be commenced at that period in each cycle in which the whole heart is at rest. The heart is then in a passive state. The auricles are gradually filling with the blood flowing into them from the veins, and a portion of this blood is passing at once through the auricles into the ventricles, the opening between the cavity of each auricle and that of its corresponding ventricle being free during the entire pause. The auricles, however, receiving more blood than at once passes through them to the ventricles, become, near the end of the pause, passively distended. At this moment a contraction wave begins on the bases of the venae cavae and, running down from the walls of the veins, passes to the muscular walls of the auricle. The contraction of the auricles, the right and left contracting at the same time, forces the blood into the ventricles. The contraction of the muscular walls of the great veins maintains a condition of constriction of these veins during the time of the auricular con- traction. This hinders the reflux of blood from the auricles into the veins during the auricular systole. Any slight regurgitation from the right auricle is limited by the valves at the junction of the subclavian and internal jugular veins beyond which the blood cannot move backward, and by the coronary vein which is supplied with a valve at its mouth. The force of the blood propelled into the ventricle at each auricular systole is transmitted in all directions, but, being insufficient to open the semilunar valves, it is expended in distending the walls of the ventricle. Action of the Ventricles. The dilatation of the ventricles which occurs during the latter part of the diastole of the auricles, is completed by the forcible injection of the contents of the latter. The ventricles, now dis- tended with blood, immediately begin to contract. The tricuspid valves are closed by the initial reflux of blood, or possibly by the currents of blood formed by the sudden injection of the ventricles by the auricular contraction. The ventricular systole follows the auricular systole so closely that it seems continuous with it. As a result of the ventricular systole sufficient pressure is produced on its contents to overcome the pressure against the semilunar valves of the aorta, and the pulmonary artery and the ventricles are thus emptied completely. After the whole of the blood has be",n expelled from the ventricles, the walls remain contracted for a brief period. 156 THE CIRCULATION OF THE BLOOD The form and position of the fleshy columns on the internal walls of the ventricles no doubt help to produce the obliteration of the ventricular cavity during contraction. The completeness of the closure may often be observed on making a transverse section of a heart shortly after death in any case in which rigor mortis is very marked, figure 137. In such a case only a central fissure may be discernible to the eye in the place of the cavity of each ventricle. The arrangement of the muscles of the heart, as described on page 148, is such as to expend the whole force of the contraction in diminishing the cavity of the ventricle, or, in other words, in expelling its contents. On the conclusion of the systole the ventricular diastole begins. The muscular walls relax and, by virtue of their elasticity, a slight negative press- ure is set up. This negative or suctional pressure on the left side of the heart is of importance in helping the pulmonary circulation. It is some- what inconstant in appearance, but has been found to be equal to as much as 20 mm. of mercury, and is said to be quite independent of the aspiratory power of the thorax itself, which will be described in a later chapter. The ventricles now remain in a state of relaxation or rest until the next systole begins. The duration of the ventricular systole and diastole has been variously estimated. A computation of the time of these two phases, for man, in figure 153, reproduced from Hurthle, gives for the systole 0.38 of a second, and for the diastole 0.4 of a second, with a total of 0.78 of a second. This is equivalent to a rate of 77 per minute. Variations in the time of the systole and the diastole of the ventricle falls chiefly on the pause of the diastole. The ventricles undergo little or no change of shape in the unopened chest. At the moment in the systole when the ventricles begin to discharge their contents into the aorta and pulmonary arteries, respectively, there is a sharp decrease in size of the ventricles. This decrease takes place in all dimensions. Action of the Valves. The Auriculo-ventricular Valves. Dur- ing the diastole of both auricles and ventricles blood flows directly through the auricles into the ventricles, the auricles during this period acting as continuations of the large veins which empty into them. At the end of the period the ventricle on each side has already been filled and distended by the pressure of blood from the veins. The systole of the auricle com- pletes this filling and slightly overdistends the ventricle. When the force of the auricular contraction is spent, the ventricular walls rebound slightly toward their former position and in so doing exert some pressure upon the ventricular side of the auriculo-ventricular valves which floats them upward toward the auricle. In this connection another force comes into play, viz., vortex or back currents resulting from the flow of blood into the ventricle under the pressure of the auricular systole. These currents aid in floating the valve leaflets into apposition. Thus, the auriculo-ventricular openings are closed at the end of the auricular systole, i.e., the end of the ventricular diastole. The ventricular systole which follows simply serves to place the ACTION OF THE VALVES 157 valves under greater tension, thus closing them still more firmly. It should be recollected that the diminution in the breadth of the base of the heart in its transverse diameters during the ventricular systole is especially marked in the neighborhood of the auriculo-ventricular rings, and this aids in render- ing the auriculo-ventricular valves competent to close the openings by greatly diminishing the diameter. The cusps of the auriculo-ventricular valves meet not by their edges only, but by the opposed surfaces of their thin outer borders. The margins of the valves are still more secured in apposition with one another by the simultaneous contraction of the muscular papillae, FIG. 152. — The Tricuspid Valves of the Ox, Closed. Vertical section. (Krehl.) whose chordae tendineae have a special mode of attachment for this very object. They compensate for the shortening of the ventricular walls and thus prevent the valves from being everted into the auricle, an event that does occur in certain valvular lesions. The actions of the tricuspid and mitral valves on the right and left sides of the heart are essentially the same. The Semilunar Valves. The commencement of the ventricular systole precedes the opening of the semilunar valves by a fraction of a second. The intraventricular pressure increases with the progress of the systole until there is a distinct increase over the arterial pressure, then the opening of the valves takes place at once. They remain open as long as this difference continues. When the diastole of the ventricle begins and the arterial blood pressure exceeds the intraventricular pressure, there is an initial reflux of blood toward the heart which closes the semilunar valves. 158 THE CIRCULATION OF THE BLOOD The dilatation of the arteries is peculiarly adapted to bring -this about. The lower borders of the semilunar valves are attached to the inner surface of the tendinous ring which bounds the orifice of the artery. The tissue of this ring is tough and inelastic and the valves are equally inextensible, being formed mainly of tough fibrous tissue with strong interwoven cords. The effect, therefore, of each propulsion of blood from the ventricle is to dilate the wall of the first portion of the artery in the three pouches behind the valves, while the free margins of the valves are drawn inward toward its center. This position of the valves and arterial walls is maintained while the ventricle continues in contraction; but as soon as it relaxes, and the dilated arterial walls can recoil by their elasticity, the blood is forced backward toward the ventricles and onward in the course of the circulation. Part of the blood thus forced back lies in the pouches (sinuses of Valsalva) between the valves and the arterial walls; and the valves are pressed together till their thin lunated margins meet in three lines radiating from the center to the circum- ference of the artery, 7 and 8, figure 136. The corpora Arantii at the middle of the free margins insure a more effective closure. The Sounds of the Heart. When the ear is placed over the region of the heart, two sounds may be heard at every beat. They follow in quick succession, and are succeeded by a pause or period of silence. The first sound is dull and prolonged; its commencement coincides with the impulse of the heart against the chest wall, and just precedes the pulse at the wrist. FIG. 153. — Simultaneous Tracings of the Cardiac Impact, or Cardiogram (lower), and the Heart Tones (upper), of Man. The cross strokes at the beginning of the cardiac sound tracing and on the cardiogram mark the synchronous events. (Hurt hie.) The second is shorter and sharper, with a somewhat flapping character. The periods of time occupied respectively by the two sounds taken together and by the pause between the second and the first are unequal. According to Foster, the interval of time between the beginning of the first sound and the second sound is 0.3 of a second, while between the second and the suc- ceeding first it is nearly 0.5 of a second, see figures 153, 154, and 158. The relative length of time occupied by each sound, as compared with the other, may be best appreciated by considering the different forces concerned in the production of the two sounds. In one case there is a strong, compara- tively slow contraction of a large mass of muscular fibers, urging forward THE SOUNDS OF THE HEART 159 a certain quantity of fluid against considerable resistance; while in the other it is a strong but shorter and sharper recoil of the elastic coat of the large arteries — shorter because there is no resistance to the flapping back of the semilunar valves as there was to their opening. The sounds may be ex- pressed by the words lubb — dUp. The beginning of the -first sound cor- responds in time with the beginning of the contraction of the ventricles, the closure of the auriculo-ventricular valves, and the first part of the dilatation of the auricles. The sound continues through a somewhat longer interval than the second sound. .The second sound, in point of time, immediately FIG. 154. — Simultaneous Tracings of the Heart Tone and Pulse of the Carotid in the Dog. A i and Az, First and second sounds; P, pulse; S, time in tenths and fiftieths of a second. (Ein- thoven and Geluk.) follows the cessation of the ventricular contraction, and corresponds with the commencing dilatation of the ventricles and the opening of the auriculo- ventricular valves, figure 154. The exact cause of the first sound of the heart is not known. Two factors probably enter into it. First, the vibration of the auriculo-ventricular valves and of the chordse tendineae. Second, the vibration of the muscular mass of the ventricles themselves. The same mechanical conditions produce equal tension on the ventricular muscle itself and, according to the second view, this is sufficient to account for the first sound. Looking upon the contraction of the heart as a simple contraction and not as a series of con- tractions, or tetanus, it is at first sight difficult to see why there should be any muscular sound when the heart contracts. The cause of the second sound is more simple and definite than that of the first. It is entirely due to the vibration consequent on the sudden closure of the semilunar valves when they are pressed down across the orifices of the aorta and pulmonary artery. The influence of these valves in producing the sound was first demonstrated by Hope who experimented with the hearts of calves. In these experiments two delicate curved needles were inserted, one into the aorta, and another into the pulmonary artery below the line of 160 THE CIRCULATION OF THE BLOOD attachment of the semilunar valves. After being carried upward about half an inch the needles were brought out again through the coats of the respective vessels, so that in each vessel one valve was held back against the arterial walls. Upon applying the stethoscope to the vessels it was found that after such an operation the second sound had ceased to be audible. Tube to communicate with the tambour \ Ivory Tape to attach knob instrument to the chest Tympanum FIG. iS5- — Cardiograph. (Sanderson's.) Disease of these valves, when sufficient to interfere with their efficient action, also demonstrates the same fact by modifying the second sound or destroying its distinctness. The Cardiac Impulse. The heart may be felt to beat with a slight shock or impulse against the walls of tlie chest at the level of the fifth inter- Screw to adjust the lever i Writing lever Tambour Tube to the cardiograph FIG. 156. — Marey's Tambour, to which the Movement of the Column of Air in the Cardiograph is Conducted by a Tube, and from which it is Communicated by the Lever to a Revolving Cylinder so that the tracing of the movement of the cardiac impulse is obtained. costal space on the left side. Its extent and character vary in different individuals, a factor of considerable clinical significance, and therefore es- pecially discussed in works on clinical diagnosis. The cause of the cardiac impulse has been variously described. It will be remembered that during THE CARDIAC IMPULSE 161 the period which precedes the ventricular systole the quiet heart rests with its apex against the wall of the chest. When the ventricles contract, their walls suddenly become firm and tense. Being firmly attached at the base the effect of the movement is to press the hardened ventricle against the chest wall. The discharge of the contents of the ventricle into the curved aorta intensi- fies this pressure by its mechanical effect in tending to straighten the curve of that vessel and thus holds the ventricle in firm contact with the chest. It is this sudden pressure of the contracting heart against the chest wall that is felt on the outside. The impact or shock is possibly more distinct because of the partial rotation of the whole heart toward the right and front along its long axis. The movement of the chest wall produced by the ventricular contraction against it may be registered by means of an instrument called the cardiograph; and the record or tracing, called a cardiogram, corresponds FIG. 157. — Tvpical Cardiogram (upper trace) from the Dog. Taken simultaneously with the aortic pressure (middle) and intra ventricular pressure (lower) tracings. Time in o.oi of a second. (HUrthle.) almost exactly with a tracing obtained by an instrument applied over the contracting ventricle itself. The cardiograph, figure 156, consists of a cup-shaped metal box over the open front of which is stretched an elastic India-rubber membrane upon which is fixed a small knob of hard wood or ivory. This knob, however, may be attached, as in the figure, to the side of the box by means of a spring, and may be made to act upon a metal disc attached to the elastic membrane. The knob is for application to the chest wall over the place of the greatest impulse of the heart. The box or tambour communicates by means of an air-tight tube with the interior of a second or recording tambour supplied with a long and light writing lever. The shock of the heart's impulse being communicated to the ivory knob, and through it to the first tambour, the effect is, of course, at once transmitted by the column of air in the elastic 11 162 THE CIRCULATION OF THE BLOOD tube to the interior of the second recording tambour, also closed, and through the elastic and movable disc of the latter to the writing lever which is ad- justed to a registering apparatus. This latter generally consists of a cylinder or drum covered with smoked paper and revolving by clock-work with a definite velocity. The point of the lever writing upon the paper produces a tracing of the heart's impulse or cardiogram. Endocardiac Pressure. The effect of the muscular contractions and relaxations of the walls of the heart during its systole and diastole is to FIG. 158. — Double Cardiac Sound for Simultaneous Registration of the Blood Pressure in the Right Auricle and Ventricle, or in the Aorta and Left Ventricle. (Hiirthle.) produce varying changes of pressure on its content of blood. When this pressure is measured by the proper instrument it is found that the pressure in the left ventricle varies between wide ranges. With the beginning of the muscular contraction, the pressure rises till it slightly exceeds that of the pressure of the aorta, remains high for a brief interval of time, then slowly and quietly decreases to less than that of atmospheric pressure and remains low until the beginning of the next systole. For the right ventricle the events and variations are relatively the same. ENDOCARDIAC PRESSURE 163 In order to determine the endocardiac pressure communication must be established with the cavities of the heart. This is accomplished by a tube known as a sound, which is introduced into the left ventricle by passing FIG. 159. — Simultaneous Registration of Curves of the Left Intraventricular Pressure (lower), the Aortic Pressure (middle), and the Cardiac Impact (upper). Time o.oi of a second. (Hiirthle.) Systole Diastole/. FIG. 160. — Schematic Cardiogram I, and Intraventricular Pressure Curves from the Dog. (Hiirthle.) The ventricular pressure curve of the descending type is represented by the dotted line. Pressure in millimeters of mercury, time in tenths of a second. it down the common carotid artery, or into the right auricle and ventricle through the jugular vein. When such tubes are introduced and connected with some form of pressure-recording apparatus, accurate tracings of the variations in pressure during the heart-beat are obtained. 164 THE CIRCULATION OF THE BLOOD Chauveau and Marey have been able to record and measure with much accuracy the variations of the endocardiac pressure and the comparative duration of the contractions of the auricles and ventricles. They placed three small India-rubber air-bags or sounds in the interior, respectively, of the right auricle, the right ventricle, and in an intercostal space in front of FIG. 161. — Apparatus of MM. Chauveau and Marey for Estimating the Variations of Endo- cardiac Pressure, and Production of the Impulse of the Heart. the heart of living animals — the horse. These bags were connected by means of long narrow tubes with three levers arranged one over the other in connection with a registering apparatus, figure 161. The synchronism of the impulse with the contraction of the ventricles is also well shown by FIG. 162. — Tracings of i, Intra-auricular; 2, Intraventricular Pressures; and 3, of the Cardiac Impulse of the Heart. To be read from left to right. Obtained by Chauveau and Marey. means of the same apparatus, and the causes of the several vibrations of which it is really composed have been demonstrated. In the tracing, figure 162, the intervals between the vertical lines rep- resent periods of a tenth of a second. The parts on which any given vertical line falls represent simultaneous event?. It v/iU be seen that tt.° Contraction ENDOCARDIAC PRESSURE 165 of the auricle, indicated by the marked curve at A in the first tracing, causes a slight increase of pressure in the ventricle which is shown at Ar in the second tracing, and produces also a slight impulse, which is indicated by A" in the third tracing. The closure of the semilunar valves causes a momentarily increased pressure in the ventricle at D', affects the pressure in the auricle D, and is also shown in the tracing of the cardiac impulse D". The large curve of the ventricular and the impulse tracings, between A' and Z>', and A" and D", are caused by the ventricular contraction, while the smaller undulations, between B and C, Bf and C', B" and C", are caused FIG. 163. — '•Apparatus for Recording the Endocardiac Pressure. (Rolleston.) by the vibrations consequent on the tightening and closure of the auriculo- ventricular valves. It seems by no means certain that Marey's curves properly represent the variations in intraventricular pressure. Objection has been taken to his method of investigation: First, because his tambour arrangement does not admit of both positive and negative pressure being simultaneously re- corded; second, because the method is applicable only to large animals, such as the horse; third, because the intraventricular changes of pressure are communicated to the recording tambour by a long elastic column of air; and fourth, because the tambour arrangement has a tendency to record inertia vibrations. H. D. Rolleston, who has pointed out the above im- perfections of Marey's method, has reinvestigated the subject with a more suitable apparatus. 166 THE CIRCULATION OF THE BLOOD The method adopted by Rolleston is as follows: A window is made in the chest of an anesthetized and curarized animal, and an appro- priately curved glass cannula introduced through an opening in the auricular appendix. The cannula is then passed through the auriculo-ventricular orifice without causing any appreciable regurgitation, into the auricle, or it may be introduced into the cavity of the right or left ventricle by an opening made in the apex of the heart. In some experiments the trocar is pushed through the chest wall into the ventricular cavity. His apparatus FIG. 164. — Endocardiac Pressure Curve from the Left Ventricle of the Dog. The thorax was opened and a cannula introduced through the apex of the ventricle; the abscissa is the line of at- mospheric pressure. G to D represents the ventricular contraction; from D to the next rise at G represents the ventricular diastole. The notch, at the top of which is F, is a post- ventricular rise in pressure from below that of the atmosphere, and not a presystolic or auricular rise in pressure. is filled with a solution of leech extract in 0.75 per cent saline solution, or with a solution of sodium bicarbonate of specific gravity 1083. The animals employed were chiefly dogs. The movement of the column of blood is communicated to the writing lever by means of a vulcanite piston which moves with little friction in a brass tube connected with a glass cannula by means of a short connecting tube. When the lower part of the tube, A , is placed in communication with one of the cavities of the heart, the movements of the piston are recorded by means of the lever, C. Attached to the lever is a section of a pulley, H, the axis of which coincides with that of the steel rib- FlG. 165. — Curve with a Dicrotic Summit from the Left Ventricle; the Abscissa Shows the At- mospheric Pressure. bon, E ; while, firmly fixed to the piston, is the curved steel piston rod, /, from the top of which a strong silk thread, /, passes downward into the groove on the pulley. This thread, /, after being twisted several times round a small pin at the side of the lever, enters the groove in the pulley from above downward, and then passes to be fixed to the lower part of the curve on the piston rod as shown in the smaller figure. The movement of the lever, C, is controlled by the resistance to torsion of the steel ribbon, E, to the middle of which one end of the lever is securely fixed by a light screw clamp, F. At some distance from this clamp, the distance varying with the degree of re- ENDOCARDIAC PRESSURE 167 sistancc which it is desired to give to the movements of the lever, are two holders, G, G', which securely clamp the steel ribbon. As the torsion of a steel wire or strip follows Hooke's law, the torsion being proportional to the twisting force, the movements of the lever point are proportional to the force em- ployed to twist the steel strip of ribbon — in other words to the pressures which act on the piston, B. To make it possible to record satisfactorily the very varying ventricular and auricular pressures, the resistance to torsion of a steel ribbon adapts itself very conven- iently. This resistance can be varied in two ways, ist, by using one or more pieces of steel ribbon or by using strips of different thicknesses; or, 2d, by varying the distance between the holders, G, G', and the central part of the steel ribbon to which the lever is attached. Rolleston's conclusions are: That there is no distinct and separate auricular contraction marked in the pressure curves obtained from the right or the left ventricle, the auricular and ventricular rises of pressure being merged into one continuous rise. He concludes that the auriculo-ventricular FIG. 166. — Hiirthle's Spring Manometer. A, Viewed from the side; B, viewed from the top. valves are closed before any great rise of pressure within the ventricle above that which results from the auricular systole, a, figure 165. The closure of the valve "occurs probably in the lower third of the rise AB, figure 165, and does not produce any notch or wave. It is shown that the semilunar valves open at the point in the ventricular systole, situated at C, about or a little above the junction of the middle and upper thirds of the ascending line AB, and the closure about or a little before the shoulder, D. The figures show, finally, that the minimum pressure in the ventricle may fall below that of the atmosphere, but that the amount varies considerably. On the whole, the most satisfactory recording instrument for the measure- ment of endocardiac pressures is the membrane manometer devised by Hiirthle. This instrument avoids mechanical errors in a most satisfactory manner. By simultaneous tracings of the pressure in the ventricle and in the aorta by Hurthle's differential manometer, the exact moment of the 168 THE CIRCULATION OF THE BLOOD opening and closing of the semilunar valves has been determined. By similar methods we have been able to fix synchronism between other events occurring during the beat. These we will summarize in the following section. Cardiac Cycle. The entire series of occurrences in a single heart- beat is called the Cardiac Cycle. If the condition of the heart is considered at that moment when its muscular walls are at rest it will be found that the auriculo-ventricular valves are open, that the blood is flowing from the great PAUSE DIASTOLE AURICLE VENTRICLE IMPULSE FIG. 167. — Diagrammatic Representation of the Events of the Cardiac Cycle. For events which occur in sequence, read in the direction of the curved arrow; for synchronous events, read from the center to the periphery in any direction. (Coleman.) veins into the auricle and ventricle, which form a continuous cavity, and that the pressure is about that of the atmosphere, but slowly rising. Now a wave of contraction begins on the great veins and extends toward the auri- cles, which immediately contract and discharge their blood into the ventri- cles, somewhat distending their walls. At this moment the ventricular systole begins, the tricuspid (and mitral) valves are closed, the flow of blood into the ventricles is checked, and the first heart sound is heard. The con- traction of the ventricles produces a rapidly rising pressure on the enclosed CARDIAC CYCLE 169 contents until the pressure exceeds that in the pulmonary artery (and aorta), the semilunar valves open, and the blood is discharged into the arteries. The ventricles ordinarily remain contracted for a brief moment after their contents are emptied. The ventricular diastole begins next and with the initial relaxation, and the first slight fall of the intraventricular pressure below that of the aorta, the semilunar valves close and the second sound is heard. The relaxation rapidly proceeds and the intraventricular pressure drops to below atmos- pheric pressure, the auriculo-ventricular valves fall open, the blood that has been accumulating in the auricles flows into the ventricles, and the whole heart is in the state of pause described as the point of beginning. The duration of the cardiac cycle varies with the heart rate. With a rate of 75 per minute, the cardiac cycle will take 0.8 of a second. In round numbers the systole of the auricle takes o.i of a second with a diastole of 0.7 of a second, 0.6 of which is in the pause or rest period. The ventricle requires about 0.3 of a second for the systole, 0.5 of a second for the dias- tole, with 0.2 to 0.3 of this for the pause. It is evident that the whole heart is at rest at the same instant for from o.i to 0.2 of a second. The relations of the cardiac sounds to the systole and the diastole have been graphically recorded by Hiirthle, figure 153, page 158, and by Einthoven and Geluk, figure 154, page 159. The former found that in a heart-beat last- ing 0.76 of a second the interval of time between the beginning of the first and second sounds was 0.25 of a second, and that the sounds occur just at the beginning of the ventricular systole and diastole respectively. During the cardiac cycle the ventricles are completely closed from the moment of the beginning of the ventricular systole until the pressure amounts to a little greater than the pressure in the corresponding arteries, which takes about 0.2 of a second. From the opening of the semilunar valves until the closure of those valves, about 0.15 of a second, the ventricular cavity is in open communication with the arteries. There is, during the diastole, a second moment of complete closure of the ventricles, from the time of the closing of the semilunar valves until the ventricular pressure falls below the auricular pressure which permits the auriculo-ventricular valves to open. The Force of the Cardiac Action. In estimating the amount of work done by a machine it is usual to express it in terms of work units. A convenient work unit for this purpose is the amount of energy required to lift a unit of weight, i.e., i gram or i kilogram, through a unit of height, i.e., i centimeter or i meter, the work required being i gramcentimeter for small units, and i kilogrammeter for large units, respectively. The average work done by the heart at each contraction can be readily computed by multi- plying the weight of blood expelled by the ventricle by the height through which it would have to be lifted to overcome the resistance to its discharge from the cavities into the arteries. 170 THE CIRCULATION OF THE BLOOD The quantity of blood expelled and the pressure of the arteries can only be estimated for man. But the computations from indirect observations on other mammals indicate that the quantity of blood discharged from each ventricle at a single contraction is from 80 to 100 c.c. The pressure of the aorta, see page 192, is an average of say 150 mm. of mercury, or 200 cm. of blood. The pressure in the pulmonary artery is much less, say 30 mm. (20 to 40), of mercury or 40 cm. of blood. Collecting these facts we have the following computation: The left ventricle The right ventricle Blood Discharged. 90 C.C. go c.C. Against Pressure Column of Blood. 200 cm. 40 cm. Work in Gramcenti- meters. 18,000 •? 600 Total 90 c.c. 240 cm. 21,600 This computation shows that each heart- beat expends 21,600 gramcenti- meters (21.6 grammeters) of work. The amount of energy developed in the contractions of the auricles may be ignored in this calculation, which is at best only of relative value. Calculations based on the determinations of Vierordt, also other earlier determinations, give much higher figures than are presented here. The Properties of the Heart Muscle. It is evident that if we are to arrive at any adequate explanation of the action of the heart, one of the first questions that must be considered is, what are the fundamental properties of heart muscle, as such? It has already been shown, page 61, that the muscular fibers of the heart differ in structure from skeletal muscle fibers on the one hand, and from unstriped muscle on the other, occupying an intermediate position between the two varieties. The heart muscle, however, possesses a property which is not possessed by skeletal muscle, or by unstriped muscle to such a degree, namely, the property of contracting rhythmically. Rhythmicity. The property of rhythmic contraction is shown by the action of the heart within the body; its systole is followed by its diastole in regular sequence throughout the life of the individual. The force and fre- quency of the systole may vary from time to time as occasion requires, but there is no interruption to the action of the normal heart or any interference with its rhythmical contractions. Further, in an animal rapidly bled to death, the heart continues to beat for a time, varying in duration with the kind of animal experimentally dealt with and depending on whether or not there is entire absence of blood within the heart chambers. Furthermore, if the heart of an animal be removed from the body, it still continues, for a varying time, its alternate systolic and diastolic movements. Thus we see that the power of rhythmic contraction depends neither upon connection with the central nervous system nor yet upon the stimulation produced by THE PROPERTIES OF THR HEART MUSCLE 171 the presence of blood within its chambers. Whether or not rhythmicity is a property of heart muscle, as such, was conclusively settled by Gaskell and by numerous later investigators by a very simple process. Gaskell cut thin FIG. 168. FIG. 169. FIG. 168. — The Heart of a Frog (Rana esculentd), from the Front. V, Ventricle; Ad, right auricle; As. left auricle; B, bulbus arteriosus, dividing into right and left aortae. (Ecker.) FIG. 169. — The Heart of a Frog (Rana esculentd), from the Back. s. v., Sinus venosus opened; c. s. s., left vena cava superior; c. s. d., right vena cava superior; c. i., vena cava inferior; v. p., vena pulmonales; A. d., right auricle; A. s. left auricle; A. p., opening of communication between the right auricle and the sinus venosus. X 2^-3. (Ecker.) strips of the apex of the ventricle of the terrapin, which is free from the nerve cells, at least nerve ganglia, and found that they contracted rhythmically for hours. This experiment has become a classic one for the study of the car- FIG. 170. — Automatic Contractions of Sinus Muscle from the Terrapin's Heart in 0.7 per cent Sodium Chloride. Time in minutes. (New figure by L. Frazier.) diac muscular tissue. Strips of cardiac muscle cut from the auricle and from the contractile walls of the venae cavse, or sinus venosus, of the terra- pin also contract rhythmically. If the strips of muscle are kept moist with the same blood or serum, then the rhythm of the sinus is greater than that of the 172 THE CIRCULATION OF THE BLOOD s-g 6| Ja g-o 1° C/2 « s«> °.s 8,1 o o II auricle, and that of the auricle greater than that of the ventricle, a difference that is based on a physiological differentiation of the tissue. The sinus muscle is also more delicately responsive to stim- uli than is the ventricular muscle, i.e., it is more irritable. Porter has performed the more difficult ex- periment of isolating a small disc of muscle from the ventricle of the dog, leaving only the delicate nutrient artery through which the muscle was fed with defibrinated blood. This isolated small piece of ventricle contracted vigorously for many minutes. We may conclude, then, that the mammalian heart muscle is also automatically rhythmic. Tonicity. Cardiac muscle is characterized by its maintaining a constant degree of partial con- traction described as muscle tone, or tonicity. This property is possessed by all parts of the heart. In the auricle, however, and especially in the muscular walls of the sinus and veins, there is considerable variation in tonicity. Botazzi showed that in the auricle of the toad the variations of tone were wave-like and periodic, even though the auricle were contracting with its ordinary funda- mental rhythm. Howell has published numerous experiments showing tone waves in auricular and sinus muscle of the terrapin, in which muscle there may or may not be occurring at the same time the ordinary fundamental rhythmic contractions, figure 170. Irritability of Heart Muscle. Mention was made above of the difference in irritability of heart muscle chosen from different parts of the heart. The irritability of the muscle of each part also varies during the different stages of the contrac- tion. When a contraction occurs, experiment shows that the muscle is not irritable to a special stimulus applied at any time from the beginning of the contraction until the summit of the con- traction is reached. This is called the refractory period. From the summit, through the relaxation and succeeding pause, the irritability rapidly in- creases until the beginning of the next contraction. J8S *> o • 3 >» &$~ •*-, * <0 a|§ Us |.0g ill THE PROPERTIES OF THE HEART MUSCLE 173 Considering the automatically contracting muscle, the point in which the automatic contraction is released, i.e., begins, is the point of maximal irri- tability. It is the moment when the irritability is so great that the muscular equilibrium is no longer stable, and the physiological contraction results. FiG.^72. — Automatic C9ntractions of a Strip of Ventricular Muscle from the Apex of the Terrapin's Heart contracting in 0.7 percent Sodium Chloride; from -j- to + 0.03 per cent Potassium Chloride is added to the Sodium Chloride. The rhythm is recovered very slowly when the muscle isreturnedto o.y-per-cent sodium chloride. Time in minutes (upper) and seconds (lower stroke). (New figure by Watkins and Elliott.) The irritability of heart muscle is very sharply influenced by its condition of nutrition, especially by the inorganic salts present in the blood and lymph, see page 1 78. The salt content of the blood comprises about 0.7 per cent sodium FIG. 173. — Automatic Contractions of a Strip of Ventricular Muscle from the Apex of the Terrapin's Heart, a. Contracting in 0.7 per cent sodium chloride; b, when 0.03 per.cent calcium- chloride solution is added. Time in minutes. (New figure by L. Frazier.) chloride, 0.03 per cent potassium chloride, and 0.025 to 0.03 per cent cal- cium (phosphate probably), as well as traces of other metal bases. The heart muscle has been shown by numerous investigators to be delicately 174 THE CIRCULATION OF THE BLQOD responsive to the proportions of these salts in the blood, or in any artificial solution which may be substituted for blood. If the rhythm is to be taken as an index of the irritability, then an increase of sodium and calcium salts increases the irritability (rhythm), while the influence of an increase in potas- sium is to depress the irritability (rhythm). Cardiac Contractions Always Maximal. The heart muscle exhibits another property which distinguishes it from ordinary skeletal muscle, viz., the way in which it reacts to stimuli. The latter, Chapter XIII, reacts slightly to a stimulus little above the minimal, and with an increase of the strength of the stimulus will give contractions of increasing amplitude until the maxi- mum contraction is reached. In the case of the heart-beats this is not so, FIG. 174. — Refractory Period in the Ventricular Strip of the Terrapin. since the minimal stimulus which has any effect is followed by the maximum contraction; in other words, the weakest effectual stimulus brings out as great a contraction as the strongest. If a contraction is induced earlier than it would automatically occur, then the succeeding pause is longer, i.e., there is a compensatory pause. Also the contraction induced is smaller and the one following the compensatory pause is proportionately larger. This ob- servation can easily be demonstrated on the heart strip, see figure 174, or on the whole ventricle of the frog, which was originally used by Bowditch. Nerve influence, nutrition, temperature, etc., will of course affect the extent of the contractions, but under a given set of conditions it is held that the contractions which occur are maximal for the particular state. This is more readily understood when taken in connection with the fact that when a contraction originates in a cardiac cell it is conducted throughout the ex- tent of all the cells of the muscular mass. Theories of the Heart-Beat. The cause of the rhythmic power of the heart as a whole has been the subject of much discussion and experi- mental observation. Two leading hypotheses have given inspiration to THEORIES OF THE HEART-BEAT 175 investigators, and now one, now the other theory has attracted followers as new facts have been discovered. The hypotheses that have been ad- vanced to explain the heart-beat are known as the neurogenic theory and the myogenic theory, respectively. The heart has long been known to have the power of rhythmic contrac- tions after removal from the body and after all connection with the central nervous system has been destroyed. The isolated heart, even of man, will contract with good rhythm when kept at the proper temperature and given the proper nutritive fluid. The Neurogenic Theory, The neurogenic theory attributes the remark- able power of the heart to continue its contractions after removal from the body, and presumably while in the body, to the presence of the local collec- tions of nerve cells. The local nervous mechanism in the frog consists of FIG. 175. — Course of the Nerves in the Auricular Partition, Heart of a Frog, d, Wall of the dorsal branch; v, ventral branch. (Ecker.) three chief groups of cells or ganglia. The first group is situated in the wall of the sinus venosus at the junction of the sinus with the right auricle, Remak's ganglia; the second group is placed near the junction between the auricles and ventricles, Bidder's ganglia; and the third in the septum between the auricles, von Bezold's ganglia. Small ganglia have been de- scribed for the base of the ventricle, but no ganglia are present in the apical part of the ventricles, though isolated cells have been found. The nerve- cells of which these ganglia are composed are generally unipolar, seldom bipolar. Sometimes two cells are said to exist in the same envelope, con- stituting the twin cells of Dogiel. The cells are large, and have very large round nuclei and nucleoli, figure 176. As regards the automatic move- ments of the heart when removed from the body, our knowledge has been derived from the study of the hearts of the frog, tortoise, dog, cat, and rabbit. 176 THE CIRCULATION OF THE BL(X)J) If removed from the body entire, the frog's or terrapin's heart will con- tinue to contract for many hours and even days, and the contraction has no apparent difference from the contraction of the heart before removal; it will take place, as we have mentioned, without the presence of blood or other fluid within its chambers. Not only is this the case, but the auricles and ventricle may be cut of! from the sinus, and both parts continue to pul- sate; and, further, the auricles may be divided from the ventricle, with the same result. If the heart be divided lengthwise, its parts will continue to pulsate rhythmically. The ventricle remains comparatively quiet, contrac- tions occurring at longer intervals, if at all. However, the ventricle remains irritable so long as bathed in blood, and will contract upon receiving a slight stimulus; in fact a single stimulus will often call forth a series of contractions of the ventricle. The frog's ventricle, when its muscular and nervous con- FIG. 176. — Isolated Nerve Cells from the Frog's Heart. /, Usual form; II, twin cell; C, capsule; N, nucleus; P, process. (From Ecker.) nections with the auricle are physiologically severed, as by crushing, will remain quiet when fed by its own blood, but contracts rhythmically when fed with physiological salt-solution. It will be thus seen that the rhythmical movements appear to be more marked in the parts supplied by the ganglia, that ventricular pieces con- tract when still connected with the auricles, and that rhythmic contractions of the ventricles do not readily occur in the ordinary condition when irri- gated with blood. These are regarded as facts peculiarly in favor of the neurogenic theory. The Myogenic Theory. In the myogenic theory the heart's rhythmical contractions are explained as due to the inherent property of the cardiac muscle itself. Most convincing facts in support of this theory have been arrived at by a study of cardiac muscle, as such, and by studies on the whole heart, particularly by Gaskell's method of blocking. The term blocking is explained as follows: It will be remembered that under normal conditions the wave of the contractions in the heart starts at the sinus and travels down over the auricles to the ventricles, the irritability of the muscle THEORIES OF THE HEART-BEAT 177 and its power of rhythmic contractions being greatest in the sinus, less in the auricles, and least in the ventricles. By an arrangement of ligatures or by a system of clamps, one part of the heart may be more or less isolated from any other portion. With such a clamp the contraction waves can be more or less completely interrupted in their passage from the sinus end of the heart past the clamp toward the ventricular end. If the clamp is com- plete, so as to interrupt the physiological continuity between the parts, then any contractions in the apical portion will be entirely independent of those in the sino-auricular portion. If the blocking is partial only, then the ventric- ular end of the heart always contracts in unison with the sino-auricular, although its rate may be as i to i, i to 2, i to 3, etc. In other words, only every second or every third sino-auricular contraction will be able to pass the block. The effects of blocking are due to the interruption of muscle continuity rather than nerve continuity. This is beautifully demonstrated by an experi- ment of zigzag cutting of the ventricle in the terrapin, since it cannot be supposed that any nerves would pass through the ventricular mass by such a zigzag course. In this experiment the contraction wave passes down over the muscle and around the end of the cuts until it reaches the apex, and the apex contracts in sequence with the auricle and base of the ventricle. If the zigzag cuts are made almost complete so as to reduce to a minimum the muscular tissue which bridges from one cut to the next, then it happens that occasional contractions will be unable to pass and the apex contracts in the ratio of i to 2, or i to 3, etc., as described above. Thus, division of the muscle has the same effect as partial clamping in the same position. It was thought for a long time that in the mammal there is no mus- cular continuity between the auricles and ventricles to conduct the contrac- tion wave, but a well-marked muscular bridge, the bundle of His, has been shown to pass between these two parts. This fact has proven to be of strongest support to the myogenic theory. Erlanger has recently shown, by an in- genious device for partially clamping this muscular band, that even the mammalian ventricle exhibits the phenomenon of heart block. In his experi- ments the ventricle contracts in unison with every auricular contraction, or only every second or every third, according to the degree of blocking. It was shown long ago that the isolated apex of the ventricle of the frog remains quiet when filled with blood, but readily gives good rhythmic con- tractions in physiological saline and other artificial solutions. The inac- tivity in blood is not necessarily, therefore, due to nervous isolation from the ganglionated parts of the heart. Contractions occur in the small bits of ventricular muscle as isolated by Gaskell, and these may continue for hours. It is well known also that the embryonic heart contracts rhythmically before nerve cells have reached the organ. The phenomena of heart block, the contractions of the ventricular apex 12 178 THE CIRCULATION OF THE BLOOD when physiologically isolated from the parts of the heart which contain the ganglia, the behavior of isolated strips of the heart, especially of the ventricle, and the rhythm of the embryonic heart are all held to be in favor of the myo- genic theory. Automaticity of the Heart. Whether one adopts the neurogenic or myogenic theory of the heart's beat, he has still to explain the origin of the heart's rhythm. In the former case one must look to the nervous apparatus for the origin of the rhythm; in the latter case, the muscular ap- paratus, a fact to which Brown-Sequard long ago called attention. In the former view the problem is to explain not only the periodic origin of the nerve discharges from local cardiac ganglia, but also to explain the orderly discharge of nerve impulses which maintains the proper sequence between sinus, auricle, and ventricle. To perhaps the majority of physiologists the facts are best explained by the myogenic theory. The origin of the rhythm is here supposed to be due to the automatic property of the muscle itself. The sequence is ex- plained on the observed facts, first, that muscular contraction in cardiac muscle is conducted throughout the continuity of the mass, and second, the most highly rhythmic part of the muscular tissue of the heart, the sinus, sets the rhythm for the entire heart. The function of the nervous system, by this view, is not to originate the rhythm, but to regulate it, the detail of which will be discussed below. Relation of Rhythm to Nutrition. The whole heart, like the muscular parts of which it is composed, responds delicately to its condition of nutrition. In the frog's and turtle's hearts the muscular fibers are brought in intimate contact with the blood contained within its cavities. In the mammalian heart, on the other hand, a distinct system of vessels, the coronary vessels and the vessels of Thebesius, supply blood to the organ. If the heart is supplied with nutrient fluid similar to its normal blood, and with proper aeration to insure plenty of oxygen, it contracts with a strong rhythm for many hours. This rhythm, however, responds quickly to changes in the composition of the nutrient fluid. An abundant supply of oxygen is absolutely necessary to the maintenance of rhythm in the mammalian heart, though the heart, especially a cold-blooded heart, will contract for a time in an atmos- phere of hydrogen. No doubt the organic constituents of blood are very essential to the prolonged maintenance of rhythm in the heart, but the heart is not dependent on these ingredients for its immediate reactions. The in- organic salts seem to be peculiarly closely related to the development and character of the cardiac rhythm, figures 172 and 173. Both the cold- blooded heart and the mammalian heart respond very quickly to the influ- ence of these salts. The details of this influence have been discussed on page 173. It is somewhat surprising, however, that the highly organized mammalian heart will contract rhythmically for hours on purely inorganic INFLUENCE OF THE CENTRAL NERVOUS SYSTEM 179 nutrient fluid, provided only that the oxygen be supplied in sufficient quantity and under high enough tension. THE REGULATIVE INFLUENCE OF THE CENTRAL NERVOUS SYSTEM ON THE HEART. The heart is capable of automatic rhythmic movement, yet while in the body its beats are under the constant control of the central nervous system. The influence which is exerted by the central nervous system is of two kinds: first, in the direction of slowing or inhibiting the beats, and, second, in the direction of accelerating or augmenting the beats. The influence of the first kind is brought to bear upon the heart through the fibers of the pneumo- gastric or vagus nerves, and that of the second kind through the sympathetic nerves. The Inhibitory Nerves. It has long been known, indeed ever since the experiments of the Weber brothers in 1845, tnat stimulation of one or both vagi produces slowing of the rhythm of the heart. It has since been FIG. 177. — Effect on the Heart Rate and on the Arterial Blood Pressure of Stimulating the Right Vagus of the Dog. Stimulus applied at the mark " on " and removed at " off." Pressure in millimeters of mercury shown by the scale to the left. Time in seconds. (New figure by Hill and Chilton.) shown, in all of the higher vertebrate animals experimented with, that this is the normal reaction to vagus stimulation. Moreover, . a section of one vagus, or at any rate of both vagi, produces acceleration of the pulse; and stimulation of the distal or peripheral end of the divided nerve normally produces slowing or stopping of the heart's beats. 180 THE CIRCULATION OF THE BLOOD It appears that any kind of stimulus, either chemical, mechanical, elec- trical, or thermal, produces the same effect, but that of these the most potent is a rapidly interrupted induction current. A certain amount of confusion has arisen as to the effects of vagus stimulation in consequence of the fact that fibers of the sympathetic nerve run within the trunk of the vagus nerves of some animals. The result of stimulation also depends, to some extent, upon the exact position of the application, of the stimulus. Speaking generally, however, FIG. 178. — Tracing Showing Actions of the Vagus on the Heart of the Frog. Aur, Auricular; vent, ventricular tracing. The part between perpendicular lines indicates a period of vagus stimu- lation. C. 8 indicates that the secondary coil was 8 cm. from the primary. The part of tracing to the left shows the regular contractions of moderate height before stimulation. During stimu- lation, and for some time after, the beats of auricle and ventricle are arrested. After they com- mence again they are single at first, but soon acquire a much greater amplitude than before the application of the stimulus. (After Gaskell.) excitation of any part of the trunk of the vagus produces inhibition, the stimulus being particularly potent if applied to the points where the nerves enter the substance of the heart at the situation of the sinus ganglia. The stimulus may be applied to either vagus with like effect. The effect of the stimulus of the vagus is twofold — to slow the rate, or even to bring the heart to a complete standstill, and to produce a decrease FIG. 179. — Tracing Showing Diminished Amplitude and Slowing of the Pulsations of the Auricle and Ventricle without Complete Stoppage during Stimulation of the Vagus. (After Gaskell.) in the amplitude. The slowing does not take place until after the lapse of a short latent period during which one or more contractions may occur. The stoppage may be due either to prolongation of the diastole or to diminu- tion of the systole. Vagus stimulation inhibits the spontaneous beats of the heart only, it does not entirely suppress the irritability of the heart-muscle, THE INHIBITORY NERVES 181 since mechanical stimulation may bring out a beat during the pause caused by vagus stimulation. The inhibition of the beats varies in duration accord- ing to the strength of the stimulus and the animal stimulated. The heart of the terrapin can be completely inhibited for hours with a strong stimulus. The heart of a dog escapes from inhibition in a few seconds. When the beats reappear, the first few are usually feeble, and may be auricular only; after a time the contractions become more and more strong, and very soon exceed both in amplitude and frequency those which occurred before the application of the stimulus. This phenomenon is shown in figure 178, which illustrates the action of the vagus on the frog's heart. The inhibitory fibers have their origin in nerve cells in the motor nucleus of the vagus and of the glosso-pharyngeal located in the floor of the fourth ventricle. These cells have not been exactly identified, but the center is FIG. 1 80. — Arterial Blood Pressure of the Dog, Showing the Effect on the Heart Rate of Cutting both Vagus Nerves as marked. The scale to the left shows the pressure in millimeters of mercury. Time in seconds. The momentary inhibition just before the nerves were cut is probably due to mechanical stimulation of the nerves. (New figure by Hill and Chilton.) called the cardio-inhibitory center. The center is a bilateral one and the fibers from it pass into the great vagus trunk to be distributed to the heart through superior and inferior cardiac branches which help to form the cardiac plexus. Within the heart the inhibitory fibers form synapses with cells whose axones reach the cardiac muscle cells. The cardiac-inhibitory center is in constant tonic activity, and the tonic influence is eliminated when both nerves are cut, figure 180. The center is also influenced by afferent impulses which may reach it from the heart itself, by the depressor nerve, or from other parts of the body. These reflex stimulations of the heart through the vagus center are constantly occurring during our daily life and are the most potent factor in the coordi- nations going on between the heart and the rest of the body. Rhythmical alterations of the heart rate occur in association with the effects of the mechanical variations of pressure of the thorax on the heart and blood-vessels. Apparently the cardio-inhibitory center is stimulated 182 THE CIRCULATION OF THE BLOOD during the fall of blood pressure. The activity of the center produces a slower rate of the heart during expiration, shown in figure 241. This vari- ation in heart rate disappears when the vagi are cut off from the center. FIG. 181. — Diagrammatic Representation of the Origin and Course of the Cardiac Nerves in the Dog. Vag. Syn, Vago-sympathetic nerve; D1, D6, first to fifth dorsal spinal nerves. In- hibitory fibers in red, accelerators in black. (Modified from Moret.) The Accelerator Nerves. The influence of the accelerator nerves reaching the heart through the sympathetic is the reverse of that of the vagus. Stimulation of the sympathetic, even of one side, produces acceleration of the rate of the heart-beats, and, according to certain observers, section of the nerve produces slowing. The acceleration produced by stimulation of the sympathetic fibers is accompanied by increased force, and so the action of the nerve is more properly termed augmentor. The sympathetic differs from the vagus in several particulars other than the augmentation which it produces; first, the stimulus required to produce any effect must be more THE ACCELERATOR NERVES 183 powerful than is the case with the vagus stimulation; second, a longer time elapses before the effect is manifest; and third, the augmentation is followed by exhaustion, the beats being after a time feeble and less frequent. The stimulation of the vago-sympathetic in the frog, which usually produces inhibition, will occasionally produce acceleration, especially if the heart is beating feebly at the time of the stimulation. The fibers of the sympathetic system, which influence the heart-beat in the frog, leave the spinal cord by the anterior root of the third spinal nerve. They pass by the ramus communicans to the third sympathetic ganglion, thence to the second ganglion, the annulus of Vieussens (around the subclavian artery), through the first ganglion, and along the main trunk of the sympathetic to near the exit of the vagus from the cranium. There the two nerves join and run down to the heart within a common sheath, forming the vago-sympathetic trunk. In the dog the augmentor fibers leave the cord by the anterior roots of the second and third dorsal nerves, and possibly also by the first, fourth, and fifth dorsal nerves. They pass by the rami communicantes to the gan- glion stellatum, or first thoracic ganglion, around the annulus of Vieussens to the inferior cervical ganglion of the sympathetic. Fibers from the annulus or from the inferior cervical ganglion proceed to the heart, figure 181. The course of the augmentor fibers in the spinal cord is not so well known except that they originate in an augmentor center in the medulla. The circulation of venous blood appears to stimulate the augmentor center, and of highly oxygenated blood the inhibitory center. The accelerator center, like the inhibitory, is in constant tonic activity; and the cardiac acceleration on cutting the vagi, shown in figure 180, is in part to be ascribed to this tone. When both nerves are stimulated together, the resulting rate is the algebraic sum of the opposed influences, according to Hunt. The accelerator center is influenced by afferent impulses arising throughout the body, and these reflexes contribute to the general coordina- tion of the chest with the activities of the body. In addition to direct and reflex stimulation, impulses passing down from the cerebrum may have a similar effect. Other Influences Which Affect the Heart. A great variety of spe- cial conditions influence the heart's action in the normal body, conditions that are not discussed directly under any of the categories treated above. Of these may be mentioned the coronary circulation, temperature, mechanical tension, age, sex, etc. The Coronary Circulation. The contractions of the heart cannot long be maintained without a due supply of blood or other nutrient fluid. The nutrient fluid for the heart of man and the mammals is supplied from the coronary arteries and the vessels of Thebesius. The coronary arteries arise from the base of the aorta, where they receive the benefit of the highest arterial 184 THE CIRCULATION OF THE BLOOD pressure. The coronary arteries are terminal arteries; that is, they do not permit the establishment of a collateral circulation when one of their branches is blocked. If the block be complete, that portion of the heart wall supplied by the branch dies. The immediate effect of the closure of a large coronary branch, in the dog, may be occasional and transient irregularity, or arrest of the ventricular contractions preceded by irregularities in the force of the contractions and a diminution in the amount of work performed. The force, rather than the rate, of the ventricular contractions is closely dependent upon the blood supply to the coronary arteries. Porter and others have shown that the pressure in the coronary vessels follows closely the pressure in the aorta and that there is not, as formerly claimed, a closure of these vessels by the pressure of the systole of the ventricle. The vessels of Thebesius, which have been demonstrated to open both into the auricular and ventricular cavities, must now be looked upon, ac- cording to the investigations of Pratt, as an important source of cardiac nutrition. Blood may pass through them by way of connecting branches to the coronary arteries and veins. Pratt succeeded in maintaining cardiac contractions for several hours when the only source of nutrition was from these vessels. This source of nutrition may account for the survival of hearts for years where pronounced arterio-sclerosis of the coronary arteries exists. Alteration of Temperature. The effect of cold is to slow the rate of the heart-beat, and if the heart of a frog be cooled down to o° C. it will stop beat- ing. It is said that the frog's heart may be frozen, and when thawed will renew its spontaneous beats. The effect of heat is to quicken and shorten the heart-beats, but at a moderate temperature, 20° C., the contractions are increased in force. The isolated mammalian heart is influenced by temperature variations in much the same way as that of the frog. It will contract slowly in a low temperature and rapidly in a temperature higher than that normal to the body. The very rapid heart in some high fevers is in part due to the in- crease in temperatures which affects the heart directly. Mechanical Tension. The mechanical factors produced by the heart beat are so prominent that it would be surprising indeed if there were no reaction of these mechanical conditions on the heart itself. The isolated cardiac muscle responds very quickly to variations in tension. Beginning with a low tension the activity of heart muscle is increased up to a certain optimum tension, after which further increase is unfavorable to the develop- ment of automatic rhythm. A quite strong stretching will paralyze the muscle. Tension on the whole heart influences its activity, not only through the effects on the muscle, but indirectly through the nervous mechanism. High tension, such as contracting against a high aortic pressure, stimulates sensory nerves of the heart which, acting through the depressor nerve on the inhibitory OTHER INFLUENCES WHICH AFFECT THE HEART 185 center, produce reflex slowing of the heart, as well as reflex vaso-dilatation, both of which relieve the high tension. This nerve reaction takes place with a tension which still mechanically stimulates the cardiac-muscle substance, and the inhibitory effects must therefore first overcome the direct stimulating effect of the tension on the muscle fibers. Age, Sex, etc. The average heart rate for the normal adult man is 72 times a minute, but this rate will vary much in different individuals accord- ing to the age, sex, size, and personal equation. The frequency of the heart's action gradually diminishes from the commencement to near the end of life, but is said to increase again somewhat in extreme old age, thus: Before birth the average number of pulsations per minute is 150 Just after birth 130 to 140 During the first year 115 to 130 During the second year 100 to 1 15 During the third year 90 to 100 About the seventh year 85 to 90 About the fourteenth year 80 to 85 In adult age 70 to 80 In old age 60 to 70 In decrepitude 65 to 75 The heart rate is greater in woman than in man. It is also greater in small than in large individuals. The rate varies from the type in certain individuals where no cause can be assigned other than personal equation. Poisons and Other Chemical Substances. A large number of chemical substances have a distinct effect upon the cardiac contractions. Of these the most important are atropine, muscarine, digitalis, barium, etc. FIG. 182. — The Effect of an Intravenous Injection of Atropine on the Dog's Heart Rate Meas- ured by Means of a Blood-Pressure Curve. (New figure by Doolev.) Atropine produces considerable augmentation of the heart-rate, and when acting upon the heart prevents inhibition by vagus stimulation. Its effects are produced by poisoning the nerve endings of the vagus within 186 THE CIRCULATION OF THE BLOOD the heart. With these endings poisoned, stimuli arising in the inhibitory center of the medulla (tonic activity), or artifically applied to the vagus, cannot reach the heart muscle, and inhibition is impossible. Muscarine, which is obtained from various species of poisonous fungi, produces marked slowing of the heart-beats, and, in larger doses, stoppage of the heart. It produces an effect similar to that of prolonged vagus stimu- lation. The effect can be removed by the action of atropine, hence is supposed to stimulate the nerve endings of the vagus. Digitalis slows the heart by stimulating the vagi at their origin in the inhibitory center in the medulla. The heart muscle itself is also rendered more excitable. Veratrine and aconitine have a somewhat similar effect. THE CIRCULATION THROUGH THE BLOOD-VESSELS. Blood Pressure. The subject of blood pressure has been already incidentally mentioned more than once in the preceding pages ; the time has now arrived for it to receive more detailed consideration. That the blood exercises pressure upon the walls of the vessels containing it is due to the following facts: The heart at each contraction forcibly injects a considerable amount of blood, 80 to 100 c.c., suddenly and quickly into the arteries. The arteries are highly distensible and stretch to accommodate the extra amount of blood forced into them. The arteries are already full of blood at the commencement of the ventricular systole, since there is not sufficient time between the heart-beats for the blood to pass into the veins. There is a distinct resistance interposed to the passage of the blood from the arteries into the veins by the enormous number of minute vessels, small arteries (arterioles) and capillaries, into which the main artery has been ultimately broken up. The sectional area of the capillaries is several hundred times that of the aorta, and the friction generated by the passage of the blood through these minute channels opposes a considerable hindrance or resistance in its course. The resistance thus set up is called peripheral resistance. The friction is greater in the arterioles, where the current is comparatively rapid, than in the capillaries, where it is slow. The interaction of these factors — heart-beat, elastic vessels, and periph- eral resistance — is sufficient to maintain a continuous flow of blood through the entire circulatory system. It is the interrelation of these factors which maintains an even and steady flow through the capillaries and past the tissues, where it is desirable that the conditions of blood flow should be most con- stant. In fact, we shall find that it is through the interaction of this same group of factors, together with the possibility of variations through the regu- lation of their nerve-motor mechanisms, that we have the great variations ARTERIAL BLOOD PRESSURE 187 and adjustments of blood pressure, speed of flow, volume of flow, and the regulation of volume in particular parts of the body. Arterial Blood Pressure. That the blood exerts considerable pres- sure upon the arterial walls in keeping them in a stretched or distended condition may be readily shown by puncturing any artery; the blood is instantly projected with great force through the opening, and the jet rises to a considerable height, the exact level of which varies with the size of the artery experimented upon. If a large artery be punctured the blood may be pro- jected upward for several feet, whereas if it is a small artery the jet does not rise so high. Another characteristic of the jet of blood from a cut artery, particularly well marked if the vessel be a large one and near the heart, is the intermittent character of the outflow. If the artery be cut across, the jet issues with force, chiefly from the central end. If there is considerable anastomosis of vessels in the neighborhood the jet from the peripheral end may be as forcible and as intermittent as that from the central end. The intermittent flow in the arteries which is due to the action of the heart, and which represents the systolic and diastolic alterations of blood pressure, may be felt if the finger be placed upon a sufficiently superficial artery. The finger is apparently raised and lowered by the intermittent distention of the vessel occurring at each heart-beat. This intermittent distention of the artery is what is known as the Pulse, to the further consideration of which we shall presently return, but we may say here that in the normal condition the pulse is a characteristic of the arterial, and is absent from the venous, flow. At the same time it must be recollected that in the veins also the blood exercises a pressure on its containing vessel which is small when compared with the arterial pressure. As might be expected, therefore, the blood is not expelled with so much force if a vein be punctured or cut. The flow from the cut vein is continuous and not intermittent, and the greater amount of blood comes from the peripheral and not from the central end, as is the case when an artery is severed. Methods of Measuring Arterial Blood Pressure. The pressure in an artery may be measured by cutting the vessel and introducing into it a glass tube which has a tall vertical limb. A column of blood will rise in the tube at once to the height that can be supported by the pressure in that par- ticular vessel. If the vessel be an artery, the blood will rise several feet, according to the distance of the vessel from the heart, and when it has reached its highest point it will be seen to oscillate with the heart-beats. This ex- periment shows that the pressure which the blood exerts upon the walls of the contained artery equals the pressure of a column of blood of a certain height. In the case of the rabbit's carotid it is equal to 90 to 120 cm. of blood, or rather more than the same height of water. In the case of the vein, if a similar experiment be performed, blood will rise in the tube only for 8 or 10 cm. or less. 188 THE CIRCULATION OF THE BLOOD The usual method of estimating the amount of blood pressure differs somewhat from the foregoing simple experiment. Instead of a simple straight tube of glass inserted into the vessel, a U-shaped tube containing mercury, the mercurial manometer, is employed. The artery is connected with the manometer by means of a small cannula which is inserted into the vessel, an arrangement being made whereby the cannula, tubes, etc., are filled with a saturated saline solution to prevent the clotting of blood when it is allowed FIG. 183. — Diagram of Ludwig's Kymograph and Mercurial Manometer. A, Revolving cylin- der, worked by a clock-work arrangement contained in the box (B), the speed being regwlated by a fan above the box; cylinder supported by an upright (b), and capable of being raised or lowered by a screw (a), by a handle attached to it; D, C, E, represent a mercurial manometer, a somewhat different form of which is shown in the next figure. to pass from the artery into the apparatus. The loss of blood is prevented during the preparation of the details of the experiment by a clamp or bull- dog forceps. The free end of the U-tube of mercury contains a very fine glass or metal rod with a bulb which floats upon the surface of the mercury and oscillates with the oscillations of the mercury. As soon as there is free communication between the artery and the tube of mercury, the blood rushes out and pushes before it the column of mercury. The mercury will there- fore rise in the free limb of the tube, and will continue to do so until a point is reached which corresponds to the mean pressure of the blood-vessel used. The blood pressure is thus communicated to one limb of the mercurial column; METHODS OF MEASURING ARTERIAL BLOOD PRESSURE 189 and the depth to which the latter sinks, added to the height to which it rises in the other limb, the weight of the saline solution being substracted, will give the height of the mercurial column which the blood pressure balances. For the estimation of the amount of blood pressure at any given moment, no further apparatus than this is necessary; but for accurately noting the variations of pressure in the arterial system, as well as its absolute amount, the instrument is usually combined with a recording apparatus, called a kymograph, figure 183, and permanent records are made of the observations. The recording apparatus consists of a revolving cylinder, figure 183, A, which is moved by clock-work, and the speed of which is capable of regula- tion. The cylinder is covered with glazed paper, blackened in the flame of a lamp, and the mercurial manometer is so fixed, figure 183, D, that its FIG. 184. — Ludwig's Mercury Manometer. The manometer is shown in figure 183, D, C, E. The mercury which partially fills the tube supports a float in the form of a piston, nearly filling the tube; a wire is fixed to the float, and the writing style or pen is guided by passing through the brass cap of the manometer tube; the pressure is communicated to the mercury by means of a flexible metal tube filled with fluid. float, provided with a style, writes on the cylinder as it revolves. There are many ways in which the mercurial manometer may be varied; in figure 184 is seen a form which is known as Ludwig's. In order to obviate the necessity of a large quantity of blood entering the tube of the apparatus, it is usual to have some arrangement by means of which the mercury may be made to rise in the tube of the manometer to the level corresponding to approxi- mately the mean pressure of the artery experimented with, so that the writing style simply records the variations of the blood pressure above and below the mean pressure. This is done by causing the saline solution, generally a saturated solution of sodium carbonate or a 10 per cent magnesium sul- 190 THE CIRCULATION OF THE BLOOD phate, to fill the apparatus from a bottle suspended at a height about that of the pressure to be measured, and capable of being raised or lowered as required for the purpose. The cannula inserted and tied into the artery may be of several different kinds. A glass T-tube with the end drawn out FIG. 185. — Arterial Cannula. T-form for convenience in washing out clots. and cut so that it is oblique, and provided with a slightly constricted neck to prevent its coming out of the artery easily, is a very convenient form, figure 185. Of the two free ends of the T-cannula one is connected with the manometer, the other with the pressure bottle. The peripheral end of the to *-*-* FIG. 186. — Tracing of Normal Arterial Pressure in the Dog, Obtained with the Mercurial Man- ometer. The smaller undulations correspond with the heart-beats; the larger curves with the re- spiratory movements. Pressure is in millimeters of mercury as shown by the scale to the left. Time in seconds. (New figure by March and Nugent.) cut artery is tied to obviate the escape of blood. By this means, the pressure communicated to the column of mercury is the forward, and not the lateral, pressure of blood, but there is very little difference. As soon as the experiment is begun, the writing float is seen to oscillate METHODS OF MEASURING ARTERIAL BLOOD PRESSURE 191 in a regular manner, and a curve of blood pressure is traced upon the smoked paper by the style (or, if a continuous roll of unsmoked paper be used, the trace is made by an inked pen) when a figure similar to figure 186 will be obtained. This indicates two main variations of the blood pressure. The smaller excursions of the lever correspond with the systole and diastole of the heart, and the larger curves correspond with the respirations, being called the respiratory undulations of blood pressure, to which attention will be directed in the next chapter. Of course, the undulations spoken of are seen only in records of arterial blood pressure. They are more clearly marked in the ar- teries nearer the heart than in those more remote. The amount of the pressure in the smaller arteries as well as the indication of the systolic rise of pressure is, comparatively speaking, small. In order to record the details of the undulations of arterial pressure, it is better for some purposes to use the Hiirthle membrane manometer than the mercurial manometer. Two views of this instrument are shown in figure 166. FIG. 187.— Tracing of Normal Arterial Pressure Taken from the Rabbit with a Hiirthle Manom- eter. The horizontal lines show zero pressure. Time in seconds. (Dreyer.) The instrument consists of a hollow tube and cup covered with rubber sheet against which a disc supported by a metal spring is adjusted. The apparatus is filled with fluid, the interior of which is connected with the artery by means of a metal tube and cannula. The pressure transmitted to the apparatus tends to stretch the rubber and bend the spring, and the movement thus produced is communicated by means of a lever to a writing style and so to a recording apparatus. This instrument obviates the errors which might be caused by the inertia of the mercury in the mercurial manometer; it also shows in more detail the variations of the blood pressure in the vessel during and after each individual beat of the heart. As regards the actual amount of blood pressure, from observations which have been made by means of the mercurial manometer, it has been found 192 THE CIRCULATION OF THE BLOOD that the pressure of blood in the carotid of a rabbit is capable of supporting a column of 90 to 120 mm. of mercury; in the dog 100 to 175 mm.; in the horse 152 to 200 mm.; and in man the pressure is estimated to be about the same as in the horse. To measure the absolute amount of this pressure in any artery multiply the area of its transverse section by the height of the column of mercury which is already known to be* supported by the blood pressure in any part of the arterial system. The weight of a column of mercury thus found will represent the absolute pressure of the blood. Calculated in this way, the blood pressure in the human aorta is equal to 1.93 kilogrammeters; that in the aorta of the horse being 5.2 kilo- grammeters; and that in the radial artery at the human wrist only 0.08 kilogrammeter. Supposing the muscular power of the right ventricle to be only one-fourth that of the left, the blood pressure in the pulmonary artery will be only 0.5 kilogrammeter. The amounts above stated represent the arterial tension at the time of the ventricular contraction. The arterial pressure is greatest at the beginning of the aorta, and de- creases toward the capillaries. It is greatest in the arteries at the period of the ventricular systole, and least during the diastole. The blood pressure gradually lessens as we proceed from the arteries near the heart to those more remote, and again from these to the capillaries, as it does, also, from the capillaries along the veins to the right auricle. Arterial Blood Pressure Measurements in Man. A number of instruments have been devised for estimating blood pressure in man for FIG. 1 88.— Riva-Rocci Apparatus (schematic) for Determining Blood Pressure in Man. PRESSURE MEASUREMENTS IN MAN 193 clinical purposes. Some of these, though excellent in principle, are too com- plicated for general use. The first simple and approximately accurate form of apparatus was that devised by Riva-Rocci in 1896. This has been modi- FIG. 189. — Erlanger's Sphygmomanometer, Shown with the Rubber Bag Attached to the Arm. The picture is taken at the end of an experiment after the pressure in the instrument is run up again to above the systolic pressure. The upper part of the cylinder shows a sphygmogram taken with the instrument. (Experiment and photo by Hill and Watkins.) fied and improved in minor points since, but the principles of the original instrument remain practically the same. In brief, the apparatus, figure 188, consists of an elastic tube ending in a rubber bag which can be adjusted about the arm or forearm, and a mercury manometer connected with this tube and also with some form of air pump used for inflating the tube about the arm and thus exerting pressure upon its blood-vessels. The elastic tube is covered by some inelastic tissue, usually a leather cuff, in order that the inflation of the bag may cause the full increase of pressure to be exerted upon the encased arm. By inflating the bag until the pulse at the wrist just disappears, and reading the height of the column of mercury in the manometer, the maximum or systolic pressure is obtained 13 194 THE CIRCULATION OF THE BLOOD in millimeters of mercury. If now the pressure on the arm is reduced until the widest oscillations of the mercury column are obtained, the lowest position of the mercury meniscus represents the diastolic pressure. The apparatus depends on the principle that an external pressure just equal to the maximal pressure within an artery will hold the vessel in the collapsed condition, a fact that has been proven for vessels that are exposed. An external pressure that will just equal the minimal or diastolic pressure will cause a complete collapse of a vessel during diastole and will allow a complete expansion of an artery to ib maximal limits during the systolic period of pressure. In other words, the mercury of the manometer will oscillate to its maximal. If the pressure is reduced to a still lower point, it will not be sufficient to compress the artery completely, and the mercury oscillations will again become smaller. In applying the instrument to the FIG. 190. — Tracing taken with Erlanger's Sphygmomanometer. The figures indicate pres- sure in millimeters of mercury. Systolic pressure, 160; diastolic pressure, 120. (New figure by Hill.) brachial artery, one must, of course, deal with a vessel deeply buried in mus- cular and other tissues. These latter tissues probably consume a certain small percentage of the pressure, an error which may be ignored for all com- parative purposes. Erlanger has perfected a form of sphygmomanometer which contains a very ingenious and compactly arranged recording device, figure 189. This instrument has a mercury manometer from which the pressures are read off directly. On a side limb of the manometer there is a rubber bag enclosed in a glass bell. The cavity of the bell outside of the rubber bag is connected with a recording tambour, the entire apparatus being fully supplied with the necessary valves and adjusting devices which make it mechanically very perfect. The instrument is mounted on a stand with a small clock and recording cylinder adapting it to convenient clinical use. The brachial arterial pressure of man when taken by this form of appara- tus has been found to vary greatly, but Erlanger gives no mm. of mercury as the average of observations on young adults in the determination of the VENOUS BLOOD PRESSURE AND CAPILLARY PRESSURE 195 systolic pressure, i.e., the maximal arterial pressure. He gives for the dias- tolic pressure 40 to 45 mm. of mercury below the systolic pressure. Other observers using the same method find a somewhat higher average pressure, see figure 190, which represents a fair type of observation. The Venous Blood Pressure and Capillary Pressure. The blood pressure in the veins is nowhere very great, but is greatest in the small veins, while in the large veins near the heart the pressure may become negative, or, in other words, when a vein is put in connection with a mercurial manom- eter the mercury may fall in the arm farthest away from the vein and will rise in the arm nearest the vein, the action being that of suction rather than pressure. In the large veins of the neck the tendency to suck in air is es- pecially marked, and is the cause of death in some accidents or operations in that region. The amount of pressure in the brachial vein is said to support 9 mm. of mercury, whereas the pressure in the veins of the neck may fall to a negative pressure of from — 3 to — 8 mm. The variations of venous pressure during systole and diastole of the heart are very slight, and a distinct pulse is never seen in veins except under extraordinary circumstances. In certain forms of cardiac valvular insuffi- ciency there may be considerable regurgitation of the blood with a strong venous pulse. Careful observations upon the web of the frog's foot, the tongue and mesen- tery of the frog, the tails of newts and small fishes, and upon the skin of the finger behind the nail (von Kries) ; as well as estimations of the amount of pressure required to empty the vessels of blood under various conditions, all indicate that the capillary blood pressure is subject to very great varia- tions. Apparently the variations follow the variations of pressure in the arteries, though the measurements of the capillary pressure of the skin in man indicate that it is occasionally markedly influenced by the venous pressure variations. The pulse in the arterioles, capillaries, and venules becomes more and more evident as the extravascular pressure is increased. The pressure in the web of the frog's foot has been found to be equal to about 14 to 20 mm. of mercury; in other capillary regions the pressure is found to be equal to from one-fifth to one -half of the ordinary arterial pressure. General Variations in Blood Pressure. The arterial blood pressure may be made to vary by alterations in either of the chief factors upon which the pressure in the vessels depends, but primarily by the cardiac contrac- tions and the peripheral resistance. Thus, increase of blood pressure may be brought about by either, i, a more frequent or more forcible action of the heart, or, 2, by an increase of the peripheral resistance. On the other hand, diminution of the blood pressure may be produced, either by 0, a diminished force or frequency of the contractions of the heart, or by b, a diminished peripheral resistance. These different factors, however, although 196 THE CIRCULATION OF THE BLOOD varying constantly, are so combined that the general arterial pressure re- mains fairly constant. For example, the heart may, by increased force or frequency of its contractions, distinctly increase the blood pressure, but this increased action is almost certainly followed by diminished peripheral re- sistance, and thus the two altered conditions may balance, with the result of bringing back the blood pressure to what it was before the heart began to beat more rapidly or more forcibly. It will be clearly seen that the circulation of the blood within the blood vessels must depend upon the diminution of the pressure from the heart to the capillaries, and from the capillaries to the veins, the blood flowing in FIG. 191. — Schema Showing the Relation between Blood Pressure, Velocity of Flow, and Vascular Area, in the Arteries, Capillaries, and Veins. Ordinates represent height of pressure and speed of flow. The abscissa, b-c, represents zero pressure and speed. Space between lines a-b and d-e represents arterial system ; between d-e and f-g, capillary system, and between f-g and /»-*', the venous system. Line A-B equals pressure; line C-D, speed of flow; and line E-F, vascular area. (Modified from Gad.) the direction of least resistance. We shall presently see further that the local flow also depends upon the relations between the heart's action and the peripheral resistance both general and local. The Arterial Flow. The character of the flow of blood through the arterial system depends to a very considerable extent upon the structure of the arterial walls, and particularly upon the elastic tissue which is so highly developed in them. The elastic tissue of the arteries, first of all, guards them from the sud- denly exerted pressure to which they are subjected at each contraction of the ventricles. In every such contraction, as is above seen, the contents of the ventricles are forced into the arteries more quickly than they are discharged through the capillaries. The blood, therefore, being for an instant resisted in its onward course, a part of the force with which it is impelled is directed against the sides of the arteries; under this force their elastic walls dilate, THE ARTERIAL FLOW 197 stretching enough to receive the blood, and becoming more tense and more resisting as they stretch. Thus by yielding they break the shock of the force impelling the blood. On the subsidence of the pressure, should the ventricles cease contracting, the arteries are able by the same elasticity to resume their former caliber. The elastic tissue in the same way equalizes the current of blood by main- taining pressure on it in the arteries during the period at which the ventri- FIG. 192. — Cross Section of the Aorta to Show Elastic Tissue; e, elastic elements. (Bailey.) cles are at rest or are dilating. If the arteries were rigid tubes, the blood, instead of flowing as it does in a constant stream, would be propelled through the arterial system in a series of spurts corresponding in time to the ventric- ular contractions and with intervals of almost complete rest during the in- action of the ventricles. But in the actual condition of the vessels, the force of the successive contractions of the ventricles is expended partly in the direct propulsion of the blood, and partly in the dilatation of the elastic ar- teries; and in the intervals between the contractions of the ventricles, the force of the recoil is employed in continuing the flow onward. Of course the pressure exercised is equally diffused in every direction, and the blood 198 THE CIRCULATION OF THE BLOOD tends to move backward as well as onward. All movement backward, however, is prevented by the closure of the semilunar valves, which takes place at the very commencement of the recoil of the arterial walls. The Arterial Flow is Rhythmic. By the exercise of the elasticity of the arteries, all the force of the ventricles is expended upon the circulation. That part of the force which is used up or rendered potential in dilating the arteries is restored or made active or kinetic when they recoil. There is no loss of force, neither is there any gain; for the elastic walls of the artery cannot originate any force for the propulsion of the blood; they only restore that which they receive from the ventricles. Since the ventricular discharge is intermittent, there will be intermittent accessions of pressure, and therefore the flow of blood in the arteries will be periodically accelerated. The volume of blood discharged from a cut artery increases and decreases with the systole and diastole of the ventricles, or with the systolic and diastolic pressures of the arteries themselves, see page 187. This equalizing influence of the resistance of the successive arterial branches reacts so that at length the intermittent accelerations produced in the arterial flow by the discharge of the heart cease to be observable, and the jetting stream is converted into the continuous and even movement of the blood which we see in the capillaries and veins. In the production of a continuous stream of blood in the smaller arteries and capillaries, the resist- ance which is offered to the blood stream in these vessels is a necessary agent. Were there no greater obstacle to the escape of blood from the larger arteries than exists to its entrance into them from the heart, the stream would be intermittent, notwithstanding the elasticity of the walls of the arteries. The muscular element of the middle coat cooperates with the elastic in adapting the caliber of the vessels to the quantity of blood which they contain ; for the amount of fluid in the blood-vessels varies quite considerably even from hour to hour, and can never be quite constant; and were the elastic tissue only present, the pressure exercised by the walls of the containing vessels on the contained blood would be sometimes very small, and some- times inordinately great. The presence of a muscular element, however, provides for a certain uniformity in the amount of pressure exercised; and it is by this adaptive, uniform, gentle muscular contraction that the normal tone of the blood-vessels is maintained. Deficiency of this tone is the cause of the soft and yielding arterial pulse, and the sluggish blood flow through the arterioles. Incidentally it may be mentioned that the elastic and muscular contrac- tion of an artery may also be regarded as fulfilling a natural purpose when, the artery being cut, the sudden contraction at first limits, and then, in con- junction with the coagulated fibrin, completely arrests, the flow of blood. It is only in consequence of such contraction and coagulation that we are THE VELOCITY OF THE ARTERIAL BLOOD FLOW 199 free from danger through even very slight wounds; for it is only when the artery is closed that the processes for the more permanent and secure pre- vention of bleeding are established. The Velocity of the Arterial Blood Flow. The velocity of the blood current at any given point in the various divisions of the circulatory system is inversely proportional to their united sectional area at that point. If the united sectional area of all the branches of a vessel were always the same as that of the vessel from which they arise, and if the aggregate sectional area of the capillary vessels were equal to that of the aorta, the mean rapidity of the blood's motion in the small arteries and in the capillaries would be the same as in the aorta. If a similar correspondence of capacity existed in the veins there would be an equal correspondence in the rapidity of the circula- tion in them. But the arterial and venous systems may be represented by two truncated cones with their apices directed toward the heart ; the area of their united bases, the sectional area of the capillaries, being four hundred to eight hundred times as great as that of the truncated apex representing the aorta. Thus the velocity of blood in the smallest arterioles and the capillaries is not more than one-four-hundredth of that in the aorta. The velocity of the stream of blood is greatest in the neighborhood of the heart. The rate of movement is greatest during the ventricular systole and diminishes during the diastole. The rate of flow also decreases along the arterial system, becoming least in the parts of the system most distant from the heart. Chauveau has estimated the rapidity of the blood stream in the carotid of the horse at over 20 inches per second during the heart's systole, and nearly 6 inches during the diastole (520-150 mm.), see figure 191. The Capillary Flow. It is in the capillaries that the chief resistance is offered to the progress of the blood; for in them the friction of the blood is greatly increased by the enormous multiplication of the surface with which it is brought in contact. When the capillary circulation is examined in any transparent part of a full-grown living animal by means of the microscope, figures 193, 194, the blood is seen to flow with a constant equable motion; the red blood-corpus- cles moving along, mostly in single file, and bending in various ways to ac- commodate themselves to the tortuous course of the capillary, but instantly recovering their normal outline on reaching a wider vessel, At the circumference of the stream and adhering to the walls of the larger capillaries, but especially well marked in the small arteries and veins, there is a layer of plasma which appears to be motionless. The existence of this still layer, as it is termed, is inferred both from the general fact that such a one exists in all fine tubes traversed by fluid, and from what can be seen in watching the movements of the blood-corpuscles. The red corpuscles occupy the middle of the stream and move with comparative rapidity; the color- less corpuscles run much more slowly by the walls of the vessels; while next 200 THE CIRCULATION OF THE BLOOD to the wall there is a transparent space in which the fluid appears to be at rest; for if any of the corpuscles happen to be forced within it, they move more slowly than before, rolling lazily along the side of the vessel, and often adhering to its wall, figure 194. Part of this slow movement of the colorless corpuscles and their occasional stoppage may be due to their having a tend- ency to adhere to the walls of the vessels. Sometimes, indeed, when the motion of the blood is not strong, many of the white corpuscles collect in a capillary vessel, and for a time entirely prevent the passage of the red corpuscles. When the peripheral resistance is greatly diminished by the dilatation of the small arteries and capillaries, so much blood passes on from the arteries into the capillaries at each stroke of the heart that there is not sufficient remaining in the arteries to distend them. Thus, the intermittent current of the ventricular systole is not always converted into a continuous stream by the elasticity of the arteries before the capillaries are reached; and so intermittency of the flow occurs both in capillaries and veins and a venous pulse is produced. The same 'phenomenon may occur when the arteries FIG. 193. — Capillary Network from Human Pia Mater, Showing also an Arteriole in " Optical Section "; and a Small Vein. X 35°. A, Vein; B, arteriole; C, large capillary; D, small capillaries. (Bailey.) become rigid from disease, and when the beat of the heart is so slow or so feeble that the blood at each cardiac systole has time to pass on to the capil- laries before the next stroke occurs; the amount of blood sent at each stroke being insufficient properly to distend the elastic arteries. It was formerly supposed that the occurrence of any transudation from the interior of the capillaries into the midst of the surrounding tissues was confined, in the absence of injury, strictly to the fluid part of the blood; in THE CAPILLARY FLOW 201 other words, that the corpuscles could not escape from the circulating stream, unless the wall of the containing blood-vessel was ruptured. It is true that the English physiologist Augustus Waller affirmed in 1846 that he had seen blood-corpuscles, both red and white, pass bodily through the wall of the capillary vessel in which they were contained (thus confirming what had been stated a short time previously by Addison), and that as no opening could be seen before their escape, so none could be observed afterward, so rapidly was the part healed. But these observations did not attract much notice until the phenomenon of escape of the blood-corpuscles from the capil- laries and minute veins, apart from mechanical injury, was rediscovered by Cohnheim in 1867. Cohnheim's experiment demonstrating the. pas- sage of the corpuscles through the wall of the blood- vessel is performed in the following manner: A frog is curarized, that is to say paralysis is produced by injecting under the skin a minute quantity of the poison called curari. The abdomen is then opened, a portion of the small intestine is drawn out, and its transparent mesentery spread out under a microscope. After a variable time, occupied by dilatation following contraction of the minute vessels and the accom- panying quickening of the blood stream, there ensues a retardation of the current and the red and white blood-corpuscles begin to make their way through the capillaries and small veins. The white corpuscles pass through the capillary wall chiefly by the ame- boid movement with which they are endowed. This migration occurs to a limited extent in health, but in inflammatory conditions is much increased. The process of diapedesis of the red corpuscles, which occurs under cir- cumstances of impeded venous circulation, and consequently increased blood pressure, resembles closely the migration of the leucocytes, with the exception that they are squeezed through the wall of the vessel, and do not, like the leucocytes, work their way through by ameboid movement. Various explanations of these remarkable phenomena have been sug- gested. Some believe that pseudo-stomata between contiguous endothelial cells provide the means of escape for the blood-corpuscles. But the chief share in the process is probably due to mobility and contraction of the parts concerned, both of the corpuscles and of the capillary wall itself. The Speed of the Blood in the Capillaries. The velocity of the blood through the capillaries must, of necessity, be largely influenced by that which occurs in the vessels on both sides of them, in the arteries and FIG. 194. — A Large Cap- illary from the Frog's Mesentery Eight Hours after Irritation had been set up, Showing Emigra- tion of Leucocytes. a, Cells in the act of travers- ing the capillary wall; b, some already escaped. (Frey.) 202 THE CIRCULATION OF THE BLOOD the veins, their intermediate position causing them to respond at once to any alteration in the size or rate of the arterial or venous blood stream. Thus, the apparent contraction of the capillaries, on the application of certain irritating substances or during certain mental states, and their dilatation in blushing may be referred primarily to the corresponding action of the small arteries. The Measurement of Velocity in the Capillaries. The observation of Hales, E. H. Weber, and Valentin agree very closely as to the rate of the blood current in the capillaries of the frog; and the mean of their estimates gives the velocity of the systemic capillary circulation at about 0.5 mm. per second. The velocity in the capillaries of warm-blooded animals is greater, in the dog 0.5 to 0.75 mm. per second. This may seem inconsistent with the facts, which show that the whole circulation is accomplished in about half a minute. But the whole length of capillary vessels, through which any given portion of blood has to pass, probably does not exceed 0.5 mm. There- fore the time required for each quantity of blood to traverse its own appointed portion of the general capillary system will scarcely amount to more than a second. This comparatively slow velocity is evidently favorable to the nutritive interchanges that go on through these thin-walled vessels between the blood within the capillaries and the outside active tissues. The Venous Flow. The blood current in the veins is maintained, a, primarily by the contractions of the left ventricle ; but very effectual assist- ance to the flow is afforded, b, by the action of the muscles capable of pressing on the veins with valves, and c, by the aspiration of the thorax and possibly, d, by the aspiration of the heart itself. The effect of muscular pressure upon the circulation may be thus ex- plained: When pressure is applied to any part of a vein, and the current of blood in it is obstructed, the portion behind the seat of pressure becomes swollen and distended as far back as the next pair of valves, which are in consequence closed. Thus, whatever force is exercised by the external pressure of the muscles on the veins, is distributed partly in pressing the blood onward in the proper course of the circulation, and partly in pressing it backward and closing the valves behind. The circulation might lose as much as it gains by such an action, if it were not for the numerous communications, or venous anastomoses; for owing to these anastomoses the closing up of the venous channel by the backward pressure is prevented from being any serious hindrance to the circulation, since the blood which is arrested in its onward course by the closed valves can at once pass through some anastomosing channel, and proceed on its way by another vein. Thus the effect of muscular pressure upon veins which have valves is turned almost entirely to the advantage of the circula- tion; the pressure of the blood onward is all advantageous, and the pressure of the blood backward is prevented from being a hindrance by the closure of the valves and of the anastomoses of the veins. THE VELOCITY IN THE VEINS 203 The venous flow is also assisted by the aspiration of the thorax and to some extent by that of the heart, since at some time during every cardiac cycle the intraauricular and intraventricular pressure falls below that of the atmosphere. This activity will be considered more fully in the chapter on Respiration. In this connection it may be said, however, that the pressure in the great veins falls during inspiration and rises during expiration. The Velocity in the Veins. The velocity of the blood is greater in the veins than in the capillaries, but less than in the arteries; this fact depending upon the relative capacities of the arterial and venous systems. If an accurate estimate of the proportionate areas of arteries and the veins corresponding to them could be made, we might, from the velocity of the arterial current, calculate that of the venous. The usual estimate is that the capacity of the veins is about two or three times as great as that of the arteries, and that the velocity of the blood's motion is, therefore, about one-half or one-third as great in the veins as in the arteries, i.e., 200 mm. a second. The rate at which the blood moves in the smallest venules is only slightly greater than that in the capillaries, but the speed of flow gradually increases the nearer the vessel approaches to the heart, for the sectional area of the venous trunks, compared with that of the branches opening into them, be- comes gradually smaller as the trunks advance toward the heart, figure 191. The Velocity of the Circulation as a Whole. It would appear that a portion of blood can traverse the entire course of the circulation, in the horse, in half a minute. Of course it would require longer to traverse the vessels of the most distant part of the extremities than to go through those of the neck, but taking an average length of the vessels to be traversed it may be concluded that half a minute represents the average rate. Stewart estimated that the circulation time in man is probably not less than twelve nor more than fifteen seconds. Satisfactory data for these estimates are afforded by the results of experi- ments to ascertain the rapidity with which chemicals introduced into the blood are transmitted from one part of the vascular system to another. The time required for the passage of solutions of potassium ferrocyanide, mixed with the blood, from one jugular vein, through the right side of the heart, the pulmonary vessels, the left cavities of the heart, and the general circulation, to the jugular vein of the opposite side, varies from twenty to thirty seconds in the dog. The same substance is transmitted from the jugular vein to the great saphenous vein in twenty seconds; from the jugular vein to the mes- enteric artery in between fifteen and thirty seconds; to the facial artery, in one experiment, in between ten and fifteen seconds; in another experi- ment, in between twenty and twenty-five seconds; in its transit from the jugular vein to the metatarsal artery, it occupies between twenty and thirty seconds. The result is said to be nearly the same whatever the rate of the heart's action. In more recent methods some innocuous dye like methylene 204 THE CIRCULATION OF THE BLOOD blue is used, since it permits the determination without the loss of blood, the change in color being visible through the walls of the blood-vessels. Stewart has made most accurate measurements of the circulation time by the electrical-resistance method. Strong salt solutions injected into the jugular vein on one side when they reach the other jugular (or any other vessel) are instantly detected by a decrease in the electrical resistance through the vessel when it is laid between the poles of the proper conductivity apparatus. In all these experiments it is assumed that the substance injected moves with the blood and at the same rate, and does not move from one part of the organs of circulation to another by diffusing itself through the blood or tissues more quickly than the blood moves. The assumption may be ac- cepted that the times above mentioned as occupied in the passage of the in- jected substances are the times in which the portion of blood itself is carried from one part to another of the vascular system. Another mode of estimating the general velocity of the circulating blood is by calculating it from the quantity of blood supposed to be contained in the body, and from the quantity which can pass through the heart in each of its contractions. But the conclusions arrived at by this method are less satisfactory. For the total quantity of blood, and the capacity of the cavities of the heart, have as yet been only approximately ascertained. Still the most careful of the estimates thus made accord very nearly with those already mentioned; and it may be assumed that the blood may all pass through the heart in about twenty-five seconds. THE PULSE. The most characteristic feature of the arterial pressure and blood flow is its intermittency, and this intermittent flow is seen or felt as waves of change in diameter of the arteries, known as the Pulse. The pulse is generally described as a wave-like expansion of the artery produced by the injection of blood at each ventricular systole into the already full aorta. The force of the left ventricle is expended in pressing the blood forward and in dilating the aorta. With the injection of each new quantity of blood into the aorta there is a wave of dilatation which passes on, expanding the arteries as it goes, running as it were over the more slowly traveling blood contained in them, and producing the pulse as it proceeds. -A sharp dis- tinction must be made between the passage of the pulse wave along an artery and the rate of flow of the blood in the vessel. The pulse produced by any given beat of the heart is not felt at the same moment in all parts of the body. Thus, it can be felt in the carotid a short time before it is perceptible in the radial artery, and in this vessel before it occurs in the dorsal artery of the foot. Careful measurements of the intervals between the time of the pulse THE SPHYGMOGRAPH 205 at the carotid and at the wrist shows that the delay in the beat is in proportion to the distance of the artery from the heart. The difference in time between the pulse of any two arteries probably never exceeds one-sixth to one-eighth of a second. The rate at which the pulse travels in the arteries is from five to ten meters per second. The distention of each artery increases both its length and its diameter. In their elongation the arteries change their form, the straight ones becoming slightly curved, and those already curved becoming more so; but they re- cover their previous form as well as their diameter when the ventricular contraction ceases, and their elastic walls recoil. The increase of their curves which accompanies the distention of arteries, and the succeeding recoil, may be well seen in the prominent temporal artery of an old person. In feeling the pulse, the finger cannot distinguish the sensation produced by the dilatation from that produced by the elongation and curving. That which it perceives most plainly, however, is the dilatation and return more or less to the cylindrical form of the artery, which has been partially flattened by the finger. The Sphygmograph. Much light has been thrown on what may be called the form of the pulse wave by an instrument called the sphygmo- FIG. 195. — Diagram of the Lever of the Sphygmograph. graph, figures 195 and 196. The principle on which it acts will be seen on reference to the figures. A small button replaces the finger in the act of taking the pulse. This button is made to rest lightly on the artery the pulsations of which it is de- sired to investigate. The up-and-down movement of the button is com- municated to the lever, to the hinder end of which is attached a light spring. The spring is adjusted to the proper tension to follow the movements of the artery wall during the pulse wave. The Sphygmograph is bound on the wrist while taking a record. It is evident that the beating of the pulse will cause an up-and-down movement of the lever, the pen of which will write the effect on a smoked card moved by the clock-work of the instrument. 206 THE CIRCULATION OF THE BLOOD Thus a tracing of the pulse is obtained, and in this way much more deli- cate changes can be seen than can be felt by the mere application of the finger. The principle of the sphygmometer of Roy and Adami is shown in the diagram, figure 197. The apparatus consists of a box, a, which is moulded to fit over the end of the radius so as to oriage over the radial artery. Within this is a flexible bag, b, filled with water, and connected by a T-tube with a rubber bag, h, and mercurial manometer. The fluid in the box may be raised to any desired pressure, and may then be shut off by tap, c. At the upper part of the box is a circular opening, and resting upon b is a flat button, d, which by means of a short light rod, e, communicates the movement of b to the lever, /. At the axis of rotation of this lever is a spiral watch-spring, g, which can be tightened at will, so that the lever can be made to take a vertical position at any desired hydrostatic FIG. 196. — Dudgeon's Sphygmograph. pressure within the box. The movements of the lever are recorded upon a piece of black- ened glazed paper made to move in a vertical direction past it. When in use, the box is fixed upon the wrist by an appropriate holder, and the pressure is raised to any desired height to which the lever is adapted by tightening or slackening the spring; the tap, c, is then closed. The pressure within the box acts in all directions, and is correctly indicated by the manometer. Sphygmogram. The tracing of the pulse obtained by the use of the sphygmograph, called a sphygmogram, differs somewhat according to the artery from which it is taken, but its general characters are much the same in all cases. It consists of a sudden upstroke, or anacrotic limb, figure 198,^4, which is somewhat higher and more abrupt in the pulse of the carotid and of other arteries near the heart than in the radial and other arteries more remote; and a gradual decline or catacrotic limb, B, less abrupt, and taking a longer time than A. It is seldom, however, that the decline is an uninterrupted fall; it is usually marked about half-way by a distinct notch, SPHYGMOGRAM 207 C, called the dicrotic notch, followed immediately by a second more or less marked ascent of the lever called the dicrotic wave, D. Not infrequently there is also at the beginning of the descent a slight wave previous to the dicrotic notch; this is called the pre-dicrotic wave, and in addition there may be one or more slight waves after the dicrotic, called post-dicrotic, E. The interruptions in the downstroke are called the catacrotic waves to dis- tinguish them from an interruption in the upstroke, called the anacrotic wave, which is sometimes met with. The explanation of these tracings presents some difficulties, not, how- ever, as regards the two primary factors, viz., the upstroke and downstroke, To manometer. FIG. 197. — Diagrammatic Sectionr.l Representation of the Sphygmometer. a, Box by which the portion of the artery is covered; b, thin- walled india-rubber bag filled with water, and com- municating through tap, c, with the manometer and thick- walled rubber bag, h ; d, piston con- nected by rod, e, with recording lever, /; g, spiral spring, attached to axis of lever, and by which the pressure in b, against the piston, d, is counterbalanced; k, skin and subcutaneous tissue; m, end of radius seen in section; n, radial artery seen in section. (Roy and Adami.) because they are universally taken to mean the sudden injection of blood into the already distended arteries, and the gradual recovery of the arteries by their recoil. These points may be demonstrated on a system of elastic tubes, with a pump to inject water at regular intervals, just as well as on the radial artery, or on the arterial schema, a more complicated system of tubes in which the heart, the arteries, the capillaries and veins are represented. If we place two or more sphygmographs upon such a system of tubes at in- creasing distances from the pump, we may demonstrate, first, that the rise of the lever commences earliest in that nearest the pump, and, second, that it is higher and more sudden. So in the arteries of the body the wave gradu- ally gets less and less as we approach the periphery of the arterial system, and is lost in the capillaries. 208 THE CIRCULATION OF THE BLOOD The origin of the secondary waves is to some extent a matter of uncer- tainty. The anacrotic wave occurs when the peripheral resistance is high; that is, when, for some time during the systole, the flow from the aorta toward the periphery is slower than the flow from the ventricle into the aorta. Thus it is seen in some cases of nephritis where the arteries ase rigid and the periph- eral resistance is high. The dicrotic wave is the most important of the secondary waves, and has been the subject of much discussion. It is constantly present in pulse- FIG. 198. — Diagram of Pulse Tracing. A , upstroke or anacrotic limb; B, downstroke or kat- acrotic limb; C, pre-dicrotic wave; D, dicrotic; E, post-dicrotic wave. tracings, but varies in height. In point of time the dicrotic wave occurs immediately after the closure of the aortic semilunar valves. In certain conditions, generally of disease, it becomes so marked as to be quite plain to the unaided finger. Such a pulse is called dicrotic. The generally ac- cepted view of the cause of the dicrotic wave is that it represents a rebound from the closed aortic valves. During systole, as the blood is forcibly in- jected into the aorta, there is an overdistention of the artery. The systole suddenly ends, the aorta by reason of its elasticity tends to recover itself, FIG. 199. — Sphygmogram from the Radial Artery Taken with Marey's Sphygmograph. (Langendorff.) the blood is driven back against the semilunar valves, closing them and at the same time giving rise to a wave, the dicrotic wave, which begins at the heart and travels onward toward the periphery like the primary wave. Ac- cording to Foster, the conditions favoring the development of dicrotism are: i, a highly extensible and elastic arterial wall; 2, a comparatively low mean blood pressure, leaving the extensible reaction free scope to act; 3, a vigorous and rapid stroke of the ventricle discharging into the aorta a considerable PERIPHERAL REGULATION OF THE FLOW OF BLOOD 209 quantity of blood. The other secondary waves are probably due to the os- cillations in the elastic recoil of the arteries, though some of them at least may be due to the inertia of the instruments used. In the use of the sphygmograph care must be taken in the regulation of the pressure of the spring. If the pressure be too great, the characters of 23456 7 B FIG. 200. — A, Normal Pulse- Tracing from Radial of Healthy Adult Obtained by the Sphyg- mometer; B, from same artery, with the same extra-arterial pressure, taken during acute nasal catarrh. the pulse may be almost entirely obscured, or the artery may be completely obstructed and no tracing is obtained. On the other hand, if the pressure is too slight, a very small part of the characters may be represented on the tracing. THE PERIPHERAL REGULATION OF THE FLOW OF BLOOD. The flow of blood through the circulatory system depends on the inter- action of several factors which have already been mentioned in another con- nection: The rate and volume of the heart-beat, the elasticity of the blood- vessels, the resistance of the microscopic peripheral vessels, and the volume of blood in the body. We have already learned, page 179, that both the rate and the volume of the contractions of the heart are under very minute and intimate regulation and control through the cardiac nervous mechanism. Also we have found that there is intimate coordination between the activity of the circulatory and the activity of all other parts of the body, a coordina- tion accomplished through the, nervous system. All regulation which affects 14 210 THE CIRCULATION OF THE BLOOD the heart must of necessity affect the general blood pressure and, therefore, not directly any particular part. The general elasticity of the blood-vessels, and of the arteries in par- ticular, which makes the general arterial pressure possible, is dependent primarily on the presence of a large amount of elastic connective tissue in the walls of the vessels. The elasticity of this tissue is a purely passive property which can be utilized only by some positive source of energy, in this instance the heart. The Variations in Peripheral Resistance. Certain arteries and veins, especially the smallest ones, the arterioles, are supplied with muscular tissue in their walls. The activity of these muscles in the vascular com- plex makes the peripheral regulation of the flow of blood possible. They supply a tissue which not only exhibits a passive elasticity comparable to that of the yellow elastic connective tissue, but upon the proper stimulation they actively contract or relax, thus securing to the peripheral resistance an active adjustment to the ever- varying dynamic conditions of the vascular apparatus. The muscular tissue in the walls of the vessels increases relatively in amount as the arteries become smaller, so that in the arterioles it is developed out of all proportion to the other elements. In fact, in passing from the arterioles to the capillary vessels, made up as we have seen of endothelial cells with a supporting ground substance only, the last change on the side of the arteries, which occurs as the vessels become smaller, is the disappear- ance of muscular fibers. The office of the muscular coat is to adjust the size of the arterioles and, therefore, the flow of the blood, to regulate the quantity of blood to be received by each part or organ, and to adjust the quantity to the requirements of each, according to various circumstances, but chiefly according to the degree of activity which each organ at different times exhibits. The amount of work done by each organ of the body constantly varies, and the variations often quickly succeed each other, so that, as in the muscles for example, within the same hour a part may be now very active and now quite inactive. In all its active exercise of function, such an organ requires a larger supply of blood than is sufficient for it during the times when it is comparatively inactive. It is evident that the heart cannot regulate the blood supply to each part of the body at different periods independently of the other parts. Neither could this be regulated by any general and uniform contraction of the arteries. But it may be regulated by the power which the arteries of each part have, through their muscular tissue, of contracting or relaxing so as to diminish or increase the supply of blood, according to the requirements of the par- ticular part of the body to which the vessels are distributed. Thus, while the ventricles of the heart determine the total quantity of blood to be sent onward at each contraction, and the force of its propulsion, and while the DISCOVERY OF THE VASO-MOTOR NERVES 211 large and merely elastic arteries distribute the blood and equalize its stream, the smaller arteries by means of their muscular tissue regulate and deter- mine the proportion of the whole quantity of blood which shall be distributed to each particular organ. The variation of the size of arterioles and, therefore, of the resistance to the flow of the blood in them is secured by the muscular tissue, but the muscles are regulated in their contraction by the nervous system. The muscular tissue in the blood-vessels of the different organs of the body is also coordinated by the same regulative and controlling influence of the nervous system. The Discovery of the Vaso-motor Nerves. More than half a century ago it was shown by Claude Bernard that if the cervical sympathetic nerve is divided, the blood-vessels of the corresponding side of the head and FIG. 201. — Small Artery and Vein of the Frog's Web. A, Under normal conditions; B, upon stimulation of the sciatic nerve; A -, artery; V, vein. In this experiment the vein also showed well-marked vaso- constriction. (New figure by Greene.) neck become dilated. This effect is best seen in the ear, which if held up to the light is seen to beceme redder, and the arteries to become larger. The whole ear is distinctly warmer than the opposite one. This effect is pro- duced by removing the arteries from the influence of the central nervous sys- tem, which influence normally passes along the course of the divided nerve. If the peripheral end of the divided nerve be stimulated in its course toward the organ, i.e., that farthest from the brain, the arteries which were before dilated return to their natural size, and the parts regain their former condition. And, besides, if the stimulus is very strong or very long continued, THE CIRCULATION OF THE BLOOD the amount of normal constriction is passed and the vessels become much more contracted than before. The natural condition, which is midway between extreme contraction and extreme dilatation, is called the natural tone of an artery. If this is not maintained, the vessel is said to have lost FIG. 202. — Arm Plethysmograph. Apparatus for measuring the change in volume in the arm due to variation in the blood supply. The arm is enclosed in a glass cylinder which is com- pletely filled with fluid, the opening through which the arm is inserted being closed by a rubber sleeve, A . The cavity of the glass cylinder communicates through the tube, F, G, with the test tube M, which is supported in the jar, P. Any variation in volume in the arm will cause water to flow out or into the test tube, M, which is lowered as the tube fills, and raised as it empties. The rise and fall of the test tube, M, is communicated over the pulley, L, to the writing-pen, N, which re- cords the movements on the smoked cylinder. Kymograph not shown. (Mosso.) tone, or, if it is exaggerated, the tone is said to be too great. The effects described as having been produced by section of the cervical sympathetic and by subsequent stimulation are not peculiar to that nerve and the vessels to which it is distributed. It has been found that for every part of the body, except the brain, there exists a nerve the division of which produces the same effects, viz., dilatation of the vessels. Such may be cited as the case with the sciatic, the splanch- nic nerves, and the nerves of the brachial plexus; when these are divided, dilatation of the blood-vessels in the parts supplied by them takes place. It appears, therefore, that nerves exist which have a distinct control over the vascular supply of every part of the body. These are called vaso-motor or vaso-constrictor nerves. But the arterioles are also under the influence of VASO-CONSTRICTOR NERVES 213 a second set of nerves, also discovered by Claude Bernard, which produce exactly the opposite influence, i.e., dilatation. These nerves are called vaso- dilator nerves. Mall has also shown that veins, at least the portal vein, possess a vaso- motor nerve supply as well as arteries. Vaso- constrictor Nerves. The presence of vaso-constrictor nerves can be shown in several different ways, of which the most convincing is that of direct inspection. If a vascular membrane, like the web of the frog's foot or the bat's wing, be adjusted on the stage of a microscope for direct inspection, and the smaller arterioles are under observation, then upon the stimulation of the general nerve supplying the part these arterioles will sharply decrease in size. In fact the vaso-constriction is often so great as com- FIG. 203.— Plethysmogram of the Hind Limb of a Cat, showing Vaso-constriction upon Stimu- lating the Sciatic 64 times per second. To be read from right to left. (Bowditch and Warren.) pletely to occlude the vessel. Very soon after the stimulation the vessel again dilates to its normal size. The presence and course of the vaso-constrictor nerve supply to the organs of the body have been demonstrated not by direct inspection, but by the use of various forms of the plethysmograph. A plethysmograph is an instrument designed to measure the variations in the volume of an organ. If the finger, the whole hand, the spleen, or the kidney be placed in such an instrument and the proper steps be taken to record the volume changes, it will be found that the volume of the enclosed organ is constantly changing with every variation of the blood pressure. If the nerves to the organ are stimulated by the usual rapidly interrupted induction current, for example, the splanchnics to the kidney, then there is a decrease in the volume of the organ. This decrease takes place even when there is a simultaneous in- crease of the arterial blood pressure, a result that can be explained only on the assumption of vascular decrease in the organ. The decrease in the flow of blood to the specific organ can be induced only by a great decrease in the size of the arterioles produced by contractions of the circular muscles of their walls. 214 THE CIRCULATION OF THE BLOOD Vaso-motor Tone. Vaso-constrictor changes are constantly occur- ring in the blood-vessels of the organs of the body, a fact that has been abundantly demonstrated by the plethysmographic experiments just men- tioned. Direct inspection of the ear of an albino rabbit will show that the arteries, and veins as well, are now full and large and red, and the interspaces filled with blood, and now pale and constricted, and the interspaces apparent- ly bloodless. If the cervical sympathetic is cut as in Bernard's experiment, then the ear vessels remain dilated, that is, they lose their tone, showing that the condition is dependent primarily on the constant discharges cf nerve impulses from the nervous system. It is said that the vessels regain their tone after a time when the nerves are cut. The regained power may be ascribed to the muscle fibers themselves. Vaso-constrictor Center. When the tonic in- fluence exerted by the nerve-fibers on the arterioles is traced back into the central nervous system, it is found to be associated with the activity of certain groups of nerve-cells, or centers, which are called the vasp-constrictor centers. This determination is made in part by the method of sectioning. A lesion of the cerebro-spinal axis below the corpora quad- rigemina is followed by partial or complete general dilatation of the blood-vessels and great fall of blood pressure. This is due to the isolation of the vaso- constrictor center, which lies in the floor of the fourth ventricle, a millimeter or two caudal to the corpora quadrigemina, and extends longitudinally over an area of about three millimeters. Owsjannikow has shown that the center is composed of two halves, each half lying in the lateral column to the side of the median line. This center is in constant action during life, and its discharges are responsible for the vascular tone described in the previous paragraph. The vaso-constrictor center varies in its activity, sometimes producing wave-like contractions with relaxations of the arterial walls, producing variations in the blood pressure known as Traube-Hering waves. They are more often observed in mammalian blood-pressure experiments after prolonged operations, when the center may be supposed to be itself in a weakened condition. Secondary vaso-motor centers are present in the spinal cord as proven by Goltz. Under normal conditions they do not act independently of the medullary center; but when the function of the latter has been interrupted FIG. 204. — Diagram Showing the Paths of the Vaso- constrictor Fibers along the Cervical Sympa- thetic and the Abdominal Splanchnic. Aur, Artery of ear; G.Cs, superior cervical ganglion; An. V, annulus of Vieussens; G.St. stellate ganglion; D.I, D.I I, D.V, thoracic spinal nerves; Abd. Spl, abdomi- nal splanchnic. The arrows indicate the direction of vaso-constrictor impulse. VASO-CONSTRICTOR REFLEXES 215 by section of the cord, then after a few days the spinal cells below the section take on central functions and bring about a re-establishment of the lost vascular tone. If these centers be destroyed by the destruction of the cord, then the tone of the vessels immediately disappears but is regained after the lapse of a much longer time. This can be ascribed to the presence of possi- ble sympathetic constrictor centers or more probably to a fundamental prop- erty of the muscles themselves. This experiment was carried out by Goltz and Oswald, who found that after destruction of the lower part of the spinal cord, the tone of the vessels of the hind limbs, lost as a result of the opera- tion, was later re-established. Vaso- constrictor Reflexes. Under normal conditions the medul- lary center responds to afferent stimuli by vaso-motor reflexes. The second- ary vaso-motor centers in the spinal cord, when removed from the influence of the bulbar center, can and do respond to afferent impulses by similar vaso-motor action. The afferent impulses which excite reflex vaso-motor action may proceed from the terminations of sensory nerves in general, or possibly from the blood-vessels themselves, and the constriction which follows generally occurs in the area whence the impulses arise. Yet the reflex may appear elsewhere. Impulses proceeding to the vaso-motor center from the cerebrum may cause vaso-dilatation, as in blushing, or vaso-constriction, as in the pallor of fear or of anger. Afferent influence upon the vaso-motor centers is well shown by the action of the depressor nerve, the existence of which was demonstrated by Cyon and Ludwig. The depressor is a small afferent nerve which passes up to the medulla from the heart, in which it takes its origin. It runs upward in the sheath of the vagus or in the superior laryngeal branch of the vagus or as an independent branch, as in the rabbit, communicating by filaments with the inferior cervical ganglion as it proceeds from the heart. If, in a rabbit, this nerve be divided and the central end stimulated during a blood- pressure observation, a remarkable fall of blood pressure takes place, figure 205. The cause of the fall of blood pressure is found to proceed primarily from the dilatation of the vascular district within the abdomen supplied by the splanchnic nerves, in consequence of which the vessels hold a much larger quantity of blood than usual. The engorgement of the splanchnic area very greatly diminishes the amount of blood in the vessels elsewhere, and so materially diminishes the blood pressure. The function of the de- pressor nerve is that of conveying to the vaso-motor center afferent nerve impulses from the heart, which produces an inhibition of the tonic activity of the vaso-motor center and, therefore, a diminution of the tension in the blood-vessels, thus relieving the heart from the overstrain of propelling blood into the already too full or too tense arteries. It has been shown by Porter and Beyer that the fall in blood pressure, following stimulation of the depres- 216 THE CIRCULATION OF THE BLOOD sor nerve, will still occur, even when the abdominal vaso-constriction is kept constant by a simultaneous stimulation of the splanchnics. It is therefore evident that the inhibitory effect of depressor-nerve stimulation is a general one and not confined to the splanchnic area alone. The action of the depressor nerve in causing an inhibition of the vaso- motor center illustrates the more unusual effect of afferent impulses, that is, inhibition of the vaso-constrictor tone. As a rule, the stimulation of the central end of an afferent nerve, such as the sciatic or the internal saphenous, produces the reverse, i.e., a pressor effect, and increases the tonic influence FIG. 205. — Blo9 4, 5, 6, 7, 8, 9, i°> " D \ solar and celiac ganglia. ; 4, 5, 6, 7, 8, 9, 10, n, 12, 130, i, 2, 3, { Splanchnic and celiac Kidnev \ 4 L \ ganglia. < Inferior splanchnic and in- Pelvic viscera. . . . i, 2, 3, 4~L -j ferfor mesenteric ganglia. The Vascular Nerves for the External Genital Organs. The vaso- dilators for these organs arise from the second and third sacral nerves and pass to the organs by the nervi erigentes and the pelvic plexus. They form the second great exception to the region of general outflow of vascular nerves. The constrictors, on the other hand, arise in the spinal nerves from the last dorsal and first four lumbar. They run the same course as given in the table for the pelvic viscera. The greatest variations in the quantity of blood contained at different times in the external genital organs are found in certain structures which contain what is known as erectile tissue. These organs, under ordinary cir- cumstances, are soft and flaccid, but at certain times they receive an un- usually large quantity of blood, become distended and swollen by it, and pass into the state termed erection. Such structures are the corpora cavernosa and corpus spongiosum of the penis of the male, and the clitoris in the female. The nipple of the mammary gland in both sexes, and, according to some authors, certain nasal membranes contain erectile tissue. The corpus cavernosum of the penis, which is the best example of an erectile structure, has an external fibrous membrane or sheath. From the inner surface of the sheath numerous fine lamellae project into the cavity, dividing it into small compartments, like cells when they are inflated. Within these cells there is a plexus of veins upon which the erectile property of the organ mainly depends. The plexus consists of short veins with very close interfacings and anastomoses with very elastic walls admitting of great varia- tions in size. They collapse in the passive state of the organ, but are capable of an amount of dilatation which exceeds beyond comparison that of the arteries and veins which convey the blood to and from them. The strong fibrous tissue lying in the intervals of the venous plexuses, and the external fibrous membrane or sheath with which it is connected, limit the distention of the vessels and give to the organ its condition of tension and firmness. The same general condition of vessels exists*in the corpus spongiosum urethrae, VASCULAR NERVES FOR THE TRUNK AND LIMBS 225 but the fibrous tissue around the urethra is much weaker than around the body of the penis, while around the glans there is none. The venous blood is returned from the plexuses by comparatively small veins; all of which are liable to the pressure of muscles when they leave the penis. The mus- cles chiefly concerned in this action are the erector penis and accelerator urinae. Erection results from the distention of the venous plexuses by a sudden influx of blood resulting from the action of the nervous vascular re- flexes. It is facilitated by the special muscular mechanism which prevents the outflow of blood. The Vascular Nerves for the Trunk and Limbs. The skin and muscles of the trunk receive their cutaneous and motor nerves by a seg- mental arrangement in which the innervation is by bands corresponding FIG. 210. — Plan of Distribution of Vaso-constrictor Nerves for the Fore Limbs. An. vi, Annulus of Vieussens. (Modified from Moret.) with the segments of the cord and the spinal nerves. It is much the same with the vascular nerves; they are distributed to the skin and walls of the trunk in the same segment in which they arise. Langley says that the suc- cessive bands overlap somewhat. In the fore legs or arms the vascular nerves arise from the first to the fifth dorsal spinal nerves, run to the stellate ganglia, then by the gray rami 15 226 THE CIRCULATION OF THE BLOOD back through the ramus vertebralis to join those cervical nerves that enter into the brachial plexus, figure 210. The nerves for the blood-vessels of the lower limbs arise from the tenth dorsal to the second lumbar nerves. These pass to the ganglionic chain, and gray rami are given off which join the lumbar plexus and run with the divisions of that nerve complex to their distribution in the skin and muscles. Vaso-constrictors and vaso-dilators have a common course to the lower limbs. The Vaso- constrictor Nerves for the Veins. Mall has proven that vaso-constrictors are present for the portal vein. These fibers are present in the splanchnic nerves. Other evidences have been observed which render the view probable that vaso-motors for the veins in general exist. Hough, for example, in an extended study of the capillary pressure found many variations which were readily explained only on the assump- tion of veno-motor activity, see figure 201. LABORATORY EXPERIMENTS ON THE CIRCULATION. 1. The Rate of the Human Heart-beat. Determine the rate of the heart-beat per minute by counting the radial pulse, using a watch for the time. Make the determination after sitting quietly in a chair for five minutes. Take the average of at least ten determinations for your own case. Determine the heart-rate under the same conditions for as many different persons as you can. Tabulate these determinations in a table which shows age, sex, weight, and height of the different individuals, and compute a general average for your entire set. Note the effect on the averages obtained above after the person lies down for five minutes, after standing quietly for the same time, and after five minutes' brisk walk. Tabulate as directed. Count the heart-rate immediately after two minutes' fast running, allow- ing the person immediately to sit in a chair. Count the rate by two minutes until there is a complete return to the normal, as determined above. Tabu- late these results and compare the figures obtained from several different individuals. Count your own heart-rate at intervals during one entire day, giving special attention to the rate just before and just after meals, but in every case make the count after sitting quietly for five minutes. A marked diurnal variation will usually appear. Determine these rates on several individuals, and tabulate as before. 2. Human Cardiogram. Apply a Burdon-Sanderson cardiograph to the thorax over the point between the fifth and sixth ribs of the left side, at which point the cardiac impulse is felt most distinctly. Connect the cardiograph with a recording tambour, Marey's form, adjust the tension of the cardiograph and the pressure of the air within the system, and take a THE FROG S HEART 227 tracing of the movements of the lever of the recording tambour on the smoked paper of the kymograph. The kymograph cylinder should travel at the rate of about two to three centimeters per second. Take the time of the move- ments of the kymograph by means of an electric magnet connected with an electric clock beating seconds. After the record is secured the proper de- scription should be written with a pencil on the smoked paper, and the paper removed from the kymograph carefully and the whole record fixed in shellac. When the record is dry, count the rate of the heart-beat from the record and measure the time of the cardiac systole and diastole, and the time of pause at the end of the diastole. If these facts are taken from records secured under different conditions of exercise, etc., as outlined in the preceding ex- periment, then they may be brought together in a table for convenience of inspection. A comparison of such results will usually show that with the higher heart-rates the decrease of the time of the cardiac cycle is at the ex- pense of the time of the diastole; in other words, the time of the systole re- mains fairly constant while the time of the diastole increases or decreases with the rate, a fact to which Hiirthle has drawn attention, figure 157. 3. The Rate and Sequence of the Contractions of the Frog's Heart. Destroy the brain of the frog and open the thorax, but do not destroy the pericardium. Count the rate of the heart per minute, then FIG. 2ii.— Heart Lever for Frog or Turtle Hearts. remove the pericardium and make a second determination after the heart is exposed to the air. The different parts of the heart when exposed are easily identified and the contractions which take place in definite sequence can be determined without difficulty. Make this determination for the ventricle, auricle, and sinus venosus by direct observation. 228 THE CIRCULATION OF THE BLOOD Prepare a cardiac lever as shown in figure 211, taking special care to ar- range the foot so that it will not bind on the lever when in motion. Adjust the foot of the lever on the exposed ventricle and bring its point to write on the smoked paper of a recording cylinder. This cylinder should travel at the rate of about i cm. per second and its speed be determined by the writing point of an electric magnet which is connected with the electric-clock circuit marking seconds. Take care to adjust the time magnet in a vertical line with the writing point of the heart lever, placing the heart lever about i cm. above the magnet lever. The tracing of the ventricle's movement, or cardio- gram, will show alternate contraction, relaxation, and pause of the ventricle. It will also enable one to measure the exact proportion of the total time of the FIG. 212. — Cardiogram Showing Contractions of the Auricle, a, and Ventricle, v, of a Frog. Time in seconds. The record shows the sequence of the auricle and ventricle. (New figure by Dooley.) cardiac cycle consumed by the systole and diastole, and also that portion of the diastole in which the ventricle is wholly at rest. After one has obtained the ventricular tracings and has learned the diffi- culties of adjusting the apparatus, a second heart lever should be adjusted so that its foot rests upon the auricle, and the auricular movements may therefore be traced on the smoked paper of the recording cylinder at the same time as those of the ventricle. If some care is taken to adjust these two writing points in a vertical line a splendid tracing showing synchronism between auricle and ventricle is obtained. Measure the rate and the time of the different phases of the contraction of the auricle and ventricle and tabulate them in the following form, always expressing fractions in the decimal system: Rate per Minute. Time of Systole in Seconds. Time of Diastole in Seconds. Time of Pause , in Seconds. Auricle Ventricle 4. The Contractions of the Excised Heart of the Frog. Pith a frog and expose the heart, as described in the preceding experiment. Re- INFLUENCE OF DIFFERENT NUTRIENT1 FLUIDS 229 move it completely from the body by first cutting the arteries at their branch- ing in front of the bulbus arteriosus, then carefully lifting up the parts of the heart and cutting away the great veins where they enter the sinus. This will remove the entire heart, including all its contractile parts. The frog's heart when thus removed and still wet with its own blood will continue con- tracting rhythmically and in its natural sequence for some hours. Place such an isolated heart in a watch-glass and take a record of its contractions, by the apparatus described in the preceding experiment. Set this watch-glass on the metal warming-box supplied, and arrange for the circulation of water of different temperatures through the box. Vary the temperature of the box, and therefore of the heart placed upon it, by allowing water of o° C., 10° C., 20° C., 30° C., 40° C. to flow through it. Record the contractions of the heart at each of these temperatures on the recording drum as described in experiment 3 above. The heart being ex- posed will not take the same absolute temperature as the box, but the relative temperature will be decreased or increased. Tabulate the rates at these different temperatures by the plan previously described. 5. The Influence of Different Nutrient Fluids on the Excised Heart. Expose a frog's heart, as previously described, and insert a can- nula into the ascending vena cava just where it enters the sinus. Ligate the descending vena cava, introduce a cannula into one of the branches of the aorta, and carefully separate the heart from the body without injuring its cavities within the points of ligature. Or the ligatures may be laid and the cannulae inserted without separating the heart from the body. Connect the venous cannula with a Mariotte's bottle filled with physiological saline, 0.7 per cent sodium chloride. Adjust the constant level tube for a pressure of 6 cm. of fluid and allow the saline to flow through the heart. The arterial cannula should be connected with a short rubber tube the mouth of which allows the fluid to flow into a beaker or glass tumbler. The outlet of the arterial tube should be about 2 cm. above the level of the heart so that the heart must work against a slight pressure. The heart will continue its contractions in good sequence and with a fairly rapid rate. Record the contractions on the smoked paper of the recording drum, together with a time tracing in seconds, the drum traveling at the rate of about 2 to 5 mm. per second. Use the tracing obtained under the influence of physiological saline solution as a normal and compare with it the rate and amplitude of the contractions when the heart is perfused with Ringer's solution; with Locke's solution; with saline and potassium in the proportion found in Ringer's solution; with saline and calcium in the proportion found in Ringer's solution; with milk diluted 6 vols. with saline; with normal serum or blood; with blood or serum diluted four times with saline. Tabulate the rates and amplitude of the heart under these different influences by the method previously followed. 6. The Heart Volume. Isolate a frog's heart by the method de- 230 THE CIRCULATION OF THE BLOOD scribed for irrigating it with fluid in the preceding experiment. Connect it up in a Roy's tonometer, see figure 213, adjust the lever of the tonometer for a tracing on the smoked paper of the recording cylinder. Use a time- marker. This instrument records the change in volume with each heart FIG. 213. — Roy's Tonometer. contraction. The influence of pressure, varied between 2 and 10 cm., and of nutrient fluids on the heart volume may be determined. 7. The Isolated Heart of the Terrapin. The heart of the terrapin, being somewhat larger and somewhat more responsive than the heart of the frog, may be substituted in the two immediately preceding experiments. The facts obtained from it will be essentially the same as those obtained from the frog's heart. 8. The Isolated Mammalian Heart. The mammalian heart may be isolated from the body and kept alive and contracting for many hours, as has been demonstrated by numerous recent observations. It is only necessary to keep the temperature approximately that of the normal body and to irrigate the hear: through the coronary circulation with blood, or diluted blood, containing sufficient hemoglobin to supply the heart with the requisite amount of oxygen. Or, the heart may be kept alive on the inorganic salt solutions, provided these are supplied with oxygen under considerable tension (Porter, Howell). Even the human heart has been isolated and kept contracting for seme hours in the above manner (Kuliabko). The method used is to insert a supply cannula into the aorta and irrigate the heart through the coronary circulation, as described by Langendorff. Many in- teresting experiments and demonstrations can be made on the mammalian AUTOMATIC CONTRACTIONS OF THE CARDIAC MUSCLE 231 heart, but, as this experiment is usually a demonstration experiment, the detail of procedure is left to be supplied by the demonstrator. 9. Automatic Contractions of the Cardiac Muscle. Isolated por- tions of the dog's ventricle have been kept in rhythmic contraction by Porter, but the best laboratory material is supplied by the heart of the terra- pin. Cut a strip from the ventricle of the terrapin extending around its curved apex, as shown by the dotted line in the accompanying figure, 214. Split this strip longitudinally into two parts, each of which will then be about 3 to 5 mm. in diameter. Use care to cut smooth, straight strips. Tie a silk thread around the extreme tips of each end of the strip, tying a loop of about i cm. long at one end, and about locm. long at the other. Suspend the strip over a glass hook, figure 215, by the short loop, and connect it with a heart lever by the long loop, as shown in the same figure. Use a tension of one gram. Contractions of this strip as arranged will be recorded with a mag- nification of about five and with the upstroke of the lever, which is convenient FIG. 214. — Heart of the Terrapin to Show the Method of Cutting the Apex Strip. V, Ventricle; Au, auricles; Vc, venae cavae; Ao, aorta. for reading and interpretation. The strip may be kept moist with physio- logical saline in a specimen tube of about i by 3 inches in size, and the arrangement of apparatus figured makes it possible easily and quickly to change this solution for any other that may be desirable. Contractions of the ventricular strip in saline usually begin in from 10 to 40 minutes after the preparation is made and go through a regular sequence of slight increase in rate and amplitude for from 10 to 20 minutes, followed by a very constant rate, but gradually decreasing amplitude for a period of from 2 to 3 hours, figure 171. This preparation makes possible many instructive experiments tending to show fundamental properties of cardiac muscle. The preparation con- 232 THE CIRCULATION OF THE BLOOD tains no nervous mechanism and its behavior may be safely attributed to the muscle substance itself. Try the following experiments: Submit the strip to saline solutions of different temperatures, varying through steps of 5 degrees from o° C. to 40° C. Try the effect of the different ingredients in Ringer's solution; com- bine potassium with saline, figure 172; calcium with saline, figure 173; and potassium, calcium, and saline. Also try Locke's solution; solution of blood diluted with saline; solution of milk with saline in the proportion of one part milk to four of saline. Cut and mount strips from the auricle and from the sinus, letting the latter extend out on to the vena cava. In these last preparations care must be taken to balance the lever, as a slight overtension paralyzes the muscle. Immerse these strips in pure serum, compare their behavior FIG. 215. — Arrangement of Apparatus for Studying the Contractions of the Strip of the Apex of the Ventricle. with that of the ventricle in pure serum. The sinus and usually the auricle will be found rhythmic in serum, while the ventricle, if it contracts at all, will contract with a very slow rhythm. Often there is a distinct progressive decrease in the rhythm, the sinus having the same rhythm as the whole heart, the auricle a considerably slower rhythm, and the ventricle with a very slow rhythm or even quiet. The sinus preparation will show beside the funda- mental rhythm a characteristic slow contraction and relaxation, which has been described as tone, figure 170. 10. Influence of the Cardiac Nerves on the Frog's Heart. Care- fully pith a frog so as not to break the blood-vessels at the base of the brain, and thus permit the loss of the blood of the animal. Expose the heart as previously described, make a cut through the manubrium, continue it througn INFLUENCE OF THE CARDIAC NERVES ON THE FROG'S HEART 233 the skin and muscles, at the angle of the jaw, thus exposing the vagus nerve. The vagus runs diagonally downward and backward along the edge of the delicate muscle toward the heart. The glossopharyngeal is just in front of the vagus and the hypoglossal just behind it. The latter runs parallel with the vagus near its origin, but lower down turns across the vagus and runs to its distribution in the tongue muscles. These two nerves serve to aicl the student in the identification of the vagus, see figure 216. It is usually better to cut the hypoglossal away, and also to cut the brachial and the laryngeal nerves. Prepare an induction coil, see Laboratory experiments on muscle. Use platinum electrodes of the Harvard pattern, set the coil for a mild stimulus when tested by the lips or the tongue, lift up the vagus gently and lay it on the platinum tips of the electrodes, taking care that the electrodes do not come in contact FIG. 216. — Diagram Showing the Relations of the Vago-sympathetic Nerve to the Heart, in the Frog. Hy, Hypoglossal; Gl, glosso-pharyngeal; Lar, laryngeal; V, vago- sympathetic; H, heart; L, lung. with the adjacent tissue. Arrange a signal magnet as shown in the diagram, so that the signal magnet and the stimulating key of the induction coil may be closed and opened at the same instant. When all is ready stimulate the vagus for five to ten seconds, recording the time with the signal magnet and allowing the record to continue until the heart has returned to its normal rate and amplitude. Most students fail in this experiment by not allowing sufficient time in the record for a normal before stimulation, and by not allowing sufficient time after stimulation for a return to the normal. It will be better to take one good tracing, showing the facts of the experiment, than several partial tracings, none of which are complete. With these sugges- THE CIRCULATION OF THE BLOOD tions in mind, repeat the above experiment, using stimulating currents of increasing intensity until complete cardiac inhibition is produced. Perform experiments showing the influence of the time of the stimulus on the inhibi- tion, i.e., stimuli of i second, 2 seconds, 10 seconds, and 30 seconds. In the frog the vagus or inhibitory, and sympathetic or accelerator fibers, are found in one trunk, the vago-sympathetic, but the stimuli will usually produce inhibitions and not acceleration. Occasionally with very weak preparations direct acceleration may be produced. To get the pure inhibi- tory or pure accelerator effects one must dissect back to the origin of the vagus before it is joined by the sympathetic fibers; or to the sympathetic trunk between the third spinal nerve and the point where it joins the vagus trunk. In the study of the conditions in the above experiments one should note the rate per minute and the amplitude in the normal, the period just before stimulation, the rate and amplitude during the period of stimulation, and the same at different times after the stimulation until constant results are ob- tained. A tabulation of these results will usually enable one to judge the influence of each of the various factors recommended in the experiment. 11. Influence of the Cardiac Nerves on the Terrapin's Heart. Instead of the frog one may use the terrapin in the above experiment. In this animal the sympathetic can very readily be isolated, and accelerator fibers have been described for it. In the experience of the laboratory of the author no experiments have yet demonstrated unquestionable cases of cardiac acceleration. The vagus produces inhibitions which differ from the effects in the frog in that complete inhibitions of the ventricle are followed by contractions that are apparently at once maximal. In the frog the con- tractions when they reappear are at first slight, but gradually increase in amplitude until they have their former value. 12. The Arterial Blood Pressure in a Mammal. The arterial blood pressure may be measured on the anesthetized cat, dog, or rabbit. Simple blood pressure was originally measured by Bale's method of connect- ing the artery with a vertical tube and allowing the blood to flow freely into the tube until a column was raised to the height which balanced the pressure in the vessel. This simple method is decidedly the best for the beginner, since it does not necessitate the use of very complicated apparatus. At the same time it gives practice in anesthesia and in operations of vivisection, and therefore serves as a good preparation for the more complicated ex- periments which follow. The necessary apparatus should be prepared first, as follows: A vertical tube supported on a stand with a scale graduated in the metric system, as- sorted cannulae of approximately the size of the carotid artery of the animal to be operated on, linen thread ligatures, dissecting set in good condition, an animal-holder with strings or straps firmly to fasten the anesthetized animal, a chloroform -ef>er mixture for dogs (or other anesthesia according ARTERIAL BLOOD PRESSURE IN A MAMMAL 235 to the animal to be used). Four men should be assigned to perform this experiment. While two are anesthetizing and preparing the animal, two should arrange the apparatus as nearly ready for connecting with the artery as possible. When all the apparatus is arranged and the animal anesthetized, it should be tied firmly to the animal-holder. Let one experimenter attend strictly and at all times to anesthetizing the animal; recovery jrom the anesthesia must not occur. Let the operator quickly expose about 3 cm. of the carotid artery by making an incision through the skin of the neck 5 cm. long, and dissecting down between the muscles. Separate the carotid from the adherent vagus nerve by tearing the connective tissue with the scalpel handle, freeing the vessel from about 2 to 3 cm. cf its length. Lay two loose ligatures of linen thread around the vessel, place a small bulldog forceps on the exposed artery nearest the heart, and ligate the end nearest the head with one of the ligatures. Take up the intervening artery with strong forceps and make a V-shaped cut near the ligature, pointing the cut toward the heart, and letting it extend about half way across the artery. Introduce a cannula through the opening toward the heart, and tie it firmly with the second liga- ture. Connect the cannula with the rubber tubing to the vertical glass tube. When all is ready remove the bulldog forceps on the artery, following which the blood will flow freely from the artery into the tube until the pressure from the column of liquid is just equal to that inside the artery itself. If an anti-coagulating fluid, 10 per cent magnesium sulphate, is first introduced into the vertical tube of fortunate height little blood will be lost and probably clotting at the cannula will be delayed for some minutes. The mounting t of the blood into the empty tube makes indeed a more striking demonstration, but it has the disadvantage of quickly forming a clot which stops the experi- ment itself. An accurate measure of the height of the top of the column above the level of the cannula at the artery represents the arterial blood pressure in terms of blood, or of 10 per cent magnesium sulphate. The specific gravity of magnesium sulphate is 1.030; of blood 1.056; of mercury 13.6. Record the pressure you obtain in terms of blood and of mercury. Note also the variations in pressure and account for the rhythm of each. There will be a general variation of pressure, depending upon the degree of anesthesia. If anesthesia is light and muscular movements happen, there will be an in- crease in the blood pressure. If the anesthesia is heavy, then the blood pres- sure falls. These points of variation should be marked, or recorded at once in note-books. Make full notes of all accessory facts which would aid you to explain the variation in blood pressure, such as size of the animal, rate of res- piration, rate of heartbeat, the variations in anesthesia, the presence of the reflexes, etc., etc. Chloroform the animal to kill it, and note the change in blood pressure during the process 236 THE CIRCULATION OF THE BLOOD 13. The Circulation Time. The circulation time is most satis- factorily determined in the laboratory by introducing a saline solution of methylene blue into the jugular vein on one side. Note directly the time with a stop-watch until the color appears in the jugular artery and the jugular vein of the opposite side. Anesthetize a cat or dog with a chloroform-ether mixture, tie it on the animal-holder and, when the eye reflexes are lost, expose the jugular vein on the right side, the carotid artery and the jugular vein on the left. Fill a 2-cm. hypodermic syringe with i per cent methylene blue in physiological saline, insert the needle into the right jugular vein, pointing it toward the heart. Lift the left carotid artery and place under it a strip of moist white paper 2 cm. wide; prepare the left jugular vein in the same way. Place the animal so that these vessels are lighted to the best advantage. At a given moment inject the contents of the hypodermic syringe, noting the time with a stop- watch. Observe the color of the left carotid and the left jugular, respec- tively, very carefully, and take the time when the first appearance of the methylene blue is noted. The color will appear first in the artery, second in the vein. The difference in time between the moment of injection and the moment of color in the artery represents, with a slight correction, the circulation time of the pulmonary or lesser circulation. The time from the injection until the color in the jugular vein represents the total time of circu- lation. Stewart has made these determinations even more correctly by the elec- trical-resistance method. He injected 10 per cent salt solution and deter- mined the variation in resistance by a galvanometer. If the galvanometer is available, then check the above determinations by the electrical method, arranging the apparatus under the direction of an instructor. 14. The Blood -Pressure Model. An artificial model of the cir- culatory apparatus, which illustrates all mechanical parts involved, has been arranged by Porter, figure 217. Other forms, which show these as well, are usually available or can be easily constructed. The model should have the following possibilities: A pump, which permits of rhythmic action at a varying rate and varying force; a resistance to the outflow liquid, which can be increased or decreased; and an elastic set of vessels into which the pump discharges. If Porter's schema is used, determine the following points: The pressure in terms of mercury in the arterial and venous limbs of the apparatus when the pump makes a rate of 72 per minute; the influence on these two pressures when the rate is increased, when it is decreased ; the effect on these pres- sures when the peripheral resistance is great, when it is low. If a sphygmo- graph is available, take a tracing of the pulse in the elastic tube representing the arterial side of the schema. If an ordinary bulb syringe and simple apparatus is used, then deter- THE ARTERIAL PULSE 237 mine the following: The character and rate of the outflow when water is pumped into the rigid glass tube with no resistance to the outflow; when a glass tube of smaller caliber is connected with the end of the larger glass tube so as to produce, high resistance to the outflow. Pump the water into a rubber tube of smalle^ ^ize and compare with the proceeding in which there is no resistance to the outflow ; also when a glass tube of small caliber is introduced into the end in order to produce high resistance to the outflow. Determine the amount of resistance necessary to produce a constant out- flow when the pump has a rate of 72 beats per minute. In this experiment what effect is produced on the outflow if you vary the rate of the pump ? if you vary the force of the stroke? if you vary the elasticity of the rubber tube representing the artery? if you vary the resistance represented by the size of the glass tube at the outflow ? 15. The Arterial Pulse. The form of the arterial pulse may be taken by one of the various sphygmographs applied to the radial artery at the wrist or the common carotid in the neck. If the tambour method is used, apply a sphygmograph tambour on the wrist with the central pressure over the radial artery. Fasten it in place by the proper bands, adjusting the tension by flexing the wrist. Connect the receiving tambour with a delicately balanced, small-sized recording tambour, which should write its movements on a cylinder revolving at the rate of i to 2 cm. per second. A more convenient clinical instrument is the Dudgeon or the Jacquet sphygmograph. These are to be applied at the wrist and give tracings showing delicate variations in the form of the pulse wave with great magnifi- cation and a considerable degree of accuracy. Make a comparison of the form of the pulse wave from tracings taken from at least six different individuals. The sphygmogram from the carotid artery may best be taken by apply- ing a tambour sphygmograph to the neck over the carotid and fastening it in position, usually by a spring. 16. The Rate of Propagation of the Pulse Wave. Apply tambour sphygmographs to the carotid in the neck and to the radial at the wrist, and make simultaneous record on a recording drum, adjusting the writing levers of the two recording tambours in an exact "vertical line. Let the recording drum travel at the speed of 2 cm. or more per second, and record the speed by a 50 double-vibration tuning-fork. The carotid pulse will be found to precede the radial pulse by the fraction of a second. This short interval, which can be determined in hundredths of a second by comparison with the time tracing below, represents the time required for the pulse wave to travel the distance from the carotid to the radial. Measure the distance on the individual used in the experiment and calculate the rate of propagation of the pulse wave in centimeters per second. 238 THE CIRCULATION OF THE BLOOD If the writing points of the recording levers in this experiment are made of very delicate strips of note paper, so as to offer little resistance to the sur- face of the drum, the detail of the pulse wave at the two points will be accurately transcribed and may be compared. 17. The Capillary Circulation. The capillary circulation is best demonstrated in the laboratory by direct observation on the web of the frog's foot by the use of the compound microscope. Give a 40-gram frog a hypo- dermic injection of 0.3 c.c. of ether under the skin of the back. Wet a piece of cheese cloth the size of a handkerchief with tap water and wrap the etherized frog so as to cover the entire body with the exception of the foot. When the anesthesia has progressed so as to destroy voluntary movements, bind the foot on an ordinary frog board and spread the web over the window in the board. Choose an area of the skin which shows small arteries, capillaries, and veins, and in which the blood is flowing freely and rapidly. Examine with a low-power compound microscope. In a favorable field small arteries, capillaries, and veins with blood flowing rapidly through them will be easily found. Choose one such field, cover with, a piece of thin cover glass, moisten- ing with a drop of water if necessary, and examine with a high powrer. Note in the small artery the pulsating current; the border of clear fluid along the side of the main stream of blood; the slight pulsations; and the white cor- puscles that will be found flowing along the borders of the current. In the small veins there are usually no pulsations and the speed of the current is somewhat less. In the capillaries a careful examination will reveal a deli- cate wall, the individual corpuscles, and the fact that the red .corpuscles are actually larger than the diameter of the capillary at some points and must be bent to pass through. Note that the capillaries form an intricate and anastomosing network; ttiat the current may occasionally reverse itself in some of the anastomoses. The anesthetizing effect of the dose of ether recommended will usually con- tinue about 15 to 20 minutes. If the observation is more prolonged a second dose of ether should be given. The capillaries in the tails of small fish are of ten very readily observed and these may be substituted for the frog's web. 18. Capillary Blood Pressure. Measure the capillary blood pres- sure in your own finger by von Krie's method. This apparatus consists of a small piece of glass an inch square, or less, which is placed across the knuckle of the finger just back of the nail. A small weight pan is suspended by a loop of thread over this glass plate so that weights put in the pan will bring varying pressure on the plate above. Add weights to the pan until an area of the skin, about 5 mm. in diameter, is blanched by the pressure. Mark the outline of this bloodless area on the glass, take off the apparatus and measure the exact area of glass so marked, weigh the entire apparatus and compute the pressure per square centimeter for the area. This pres- sure in terms of mercury represents the capillary blood pressure in the vessels BLOOD PRESSURE IN A MAMMAL AND ITS REGULATION 239 of the skin of the finger at that level. Vary the experiment by measuring the pressure with the finger held at the level of the top of the head; with the finger held as low as possible; held at the level of the heart. Tabulate the measurements. The capillary blood pressure at the level of the heart is usually from 40 to 50 mm. of mercury. 19. The Arterial Blood Pressure in a Mammal and Its Nervous Regulation. After the student has measured the arterial blood pres- sure by Hale's method, described above, he is in a position to study the variations and coordinations in the blood circulatory apparatus. The re- cording apparatus consists of writing pens, seconds time marker, signal marker, blood-pressure manometer preferably Ludwig's mercury manometer, and a continuous paper kymograph preferably Ludwig's weight-driven form for a continuous record of the arterial blood pressure. Connect the cannula with the mercury manometer which is provided with a pressure bottle. Use a cannula of the form shown in figure 185, connecting the side limb of the cannula with the mercury manometer, and the end limb with the pressure bottle. When the apparatus is ready anesthetize a mammal (dog, cat, or rabbit), and bind it down to the animal-holder. Let one operator attend strictly and at all times to the anesthetic, for the animal must not under any condition recover consciousness during the experiment. Expose the carotid artery in the neck, as described in experiment 12 above, arrange it with ligatures for inserting the cannula, expose the vagus nerve with the same care, and throw ligatures around it for convenience in lifting it out of its bed. Make in the carotid a V-shaped cut directed toward the heart, insert and ligate the cannula as previously described. Before begin- ning the experiment one should see that all the tubes are filled with the anti- coagulating liquid and that the manometer is under pressure from 100 to 150 mm. mercury. When all is ready start the kymograph, ink the recording pens, see that they are recording properly and that the adjustments are se- cured, remove the bulldog forceps from the artery, and the pressure record begins. 1. Take a tracing of the normal arterial pressure and heart rhythm with the recording paper moving at the rate of 0.5 cm. per second. 2. Stimulate the vagus nerve with a mild-strength induction current. If this stimulus is strong enough to produce change in blood pressure or in- hibitions of the heart rate, then allow sufficient time following the stimulus for the blood pressure to return to the previous normal. Observing these rules, vary the intensity of the stimulus from that which produces no ap- parent effect to that which produces complete inhibition of the heart. Vary the time of the stimulus from i to 10 seconds, using different strengths. 3. Allow the vagus to fall back in its warm bed and stimulate the skin of the animal at some sensory surface, say the lips, the ear, or the foot. By varying the intensity of the stimulus, a strength will be found which will 240 THE CIRCULATION OF THE BLOOD produce no reflexes of the voluntary muscles, but which will produce marked effects on the heart rate and on the blood pressure. Expose the sciatic nerve, or any other general nerve trunk, cut it, and stimulate the central end for 5 seconds. With a proper strength of stimulus a greater effect is produced on the heart and on the blood pressure than by stimulating a small spot of skin. 4. Cut the right vagus nerve and mark the exact time on the tracing by the signal marker. After 10 to 15 seconds cut the left vagus, marking the time of cutting with the same care on the tracing. As soon as the nerves are cut, the heart-rate will be observed to increase sharply and the blood pressure to rise. The respirations also change in rate and depth, a fact which can be noted on the blood-pressure tracing. Do not disturb the animal or record until stable equilibrium is again reached. 5. Now lift up the distal end of the divided vagus, and stimu- late it with an electric current of the strength which previously just produced inhibition. Repeat the experiment on the proximal end of the divided vagus. The stimulation of the proximal end of the vagus produces no direct effect on the heart rate when both vagi are cut, but does produce profound changes on the blood pressure owing to vaso-motor effects. 6. If the rabbit is used, stimulate the depressor nerve, which produces marked fall in blood pressure from reflex effects. 7. Repeat the stimulation of the central end of the sciatic as described in 3, now that the vagus nerves are cut. The stimulation of this nerve no longer produces changes in the heart-rate, but the blood pressure is influenced as before, showing that the vaso-motor centers are reflexly stimulated. 8. When you have finished the outline of experiments, give an excess of the anesthetic to kill the animal and continue the record until the animal is dead. The blood pressure will fall rapidly, the heart-rate will become slower but does not cease for a long time. Should a clot form in the cannula, put a bulldog forceps on the artery, disconnect the manometer tube, and wash the clot out by a stream of liquid from the pressure bottle. Use care not to allow this fluid to enter the ex- posed wound. Represent the results of each individual experiment in the above series in tabulated form which shall show i, the blood pressure and heart rate just before each experiment; 2, during the experiment; and 3, at different times after the experiment until the normal is reached. After the facts are taken from the tracings and arranged in tabular form, make a study of these facts and draw all the conclusions you can concerning the nervous regula- tions of the heart and of the blood pressure. 20. Arterial Blood Pressure in Man. The arterial blood pressure in man can be measured only indirectly by measuring the pressure which it takes around the arm completely to close the artery. Some form of the Riva-Rocci apparatus, preferably Erlanger's sphygmomanometer, should VASO-MOTOR CHANGES IN THE FINGER 241 be used. Adjust the rubber bag and leather sleeve of the Erlanger appara- tus, figure 189, to an arm, and connect it to the sphygmomanometer, set the valve and quickly pump the pressure up to a point which occludes the pulse. Adjust the writing point of the recording tambour to the smoked paper on the cylinder, then lower the pressure by lo-mm. steps until the first pulse appears. Now proceed with care, changing the pressure by 5-mm. steps until a record has been obtained which passes the maximal amplitude. Now release the pressure from the arm. The first point in the decreasing pressure at which the pulse tracing begins to increase is known as the systolic pres- sure; the point in the pressure which records the highest point in the ampli- tude of the pulse wave is known as the diastolic pressure. The systolic pressure will vary from 120 to 150 mm. of mercury; the diastolic from 90 to 120 in different individuals of the average physiology class. 21. The Vaso-motor Changes in the Finger, the Plethysmogram. Insert the finger in the Porter finger plethysmograph, fill the tube with water, and connect it with a small-sized air tambour. The variations in volume of the finger are slight, so that one must use a rather long, delicately balanced recording lever. Take a tracing on a recording cylinder moving at a slow speed, i mm. per second. The finger and its plethysmograph should be supported by a swinging support so that no mechanical move- ments will destroy the accuracy of the record. Observations through several minutes will usually show variations in volume of the finger, which will be recorded by the tambour. Cold air in the face or cold water on the hand will usually be marked by a decrease in volume indicating vaso-constriction. Application of heat to other fingers of the same hand will lead to in- crease m volume. 22. The Vaso-motors of the Frog's Web. Prepare a frog for ob- servation of the circulation of the web under the microscope, as described above; but give it just enough i per cent curari to destroy voluntary move- ments. Quickly dissect the sciatic nerve in the thigh, using extreme care not to interfere with the circulation. Mount the preparation, pick out an active field of capillaries, small arteries, and veins with the low power of the microscope, then adjust the high power to a field which shows one or more small arteries. Make a drawing of a diameter of these arteries, using pig- ment cells for land-marks. Now quickly stimulate the exposed sciatic nerve while keeping the selected artery under constant observation. After a short stimulation the diameter of the vessels will be seen to decrease considerably, sometimes to the point of complete occlusion. When the stimulation ceases, the vessel will remain contracted for a few seconds, then will slowly regain its usual caliber, figure 201 . This is an exceptionally good method for direct observation of the vaso-motor changes in the smaller vessels. 23. The Plethysmogram of the Kidney. Anesthetize a dog or cat, see experiments 12 and 19 above, and take blood-pressure tracings on the con- 16 THE ciftcyLATioN OF THE BLOOD tinuous-paper kymograph. Now open the abdominal wall by an incision along the median line, expose the left kidney and carefully dissect off its cap- sule, taking care not to injure its artery and vein. Enclose the kidney in the renal onkometer, fill the onkometer with oil, and connect it with a record- ing apparatus. Brodie's bellows recorder is probably the best recording apparatus for this purpose. Adjust the recording apparatus in the vertical line with the manometer and signal pens. Stimulation of the nerves which affect the general blood pressure through the medium of the heart will be found to produce changes in the volume of the kidney in the same direction as the blood-pressure change. On the other hand, stimuli which give variations of the blood pressure without direct change in the heart itself affect the volume of the kidney independent of the blood pressure: 1. Dissect out and stimulate the splanchnic nerves just where they pass through the pillars of the diaphragm. Stimulation of these nerves will cause vaso-constriction in the kidney, which takes place without sharply affecting the blood pressure. 2. Stimulate the depressor nerve or the central end of the divided vagus. In this case the volume of the kidney will increase though the general blood pressure decreases, showing that the fall of blood pressure is due to periph- eral vascular dilatation. 3. Stimulate the peripheral end of the divided vagus so as to slow or even completely stop the heart. 'The sharp fall in blood pressure is now accompanied by decrease in the volume of the kidney, showing that the kidney change is merely passively following that of the blood pressure. CHAPTER VI RESPIRATION THE maintenance of animal life necessitates the continual absorption of oxygen and the excretion of carbon dioxide by the living tissues. The blood is the medium, in all animals which possess a well-developed blood-vascular system, by which these gases are carried. Oxygen is absorbed by the blood from without and conveyed to all parts of the organism; and carbon dioxide which comes from the cells within is carried by the blood to the surfaces, from which it may escape from the body. The two processes — absorption of oxygen and excretion of carbon dioxide — are complementary, and their sum is termed the process of Respiration. In all Vertebrata, and in a large number of Invertebrata, certain parts, either lungs or gills, are specially constructed for bringing the blood into proximity with the aerating medium (atmospheric air, or water containing air in solution). In some of the lower Vertebrata (frogs and other naked Amphibia) the skin is important as a respiratory organ, and is capable of supplementing to some extent the functions of the proper breathing ap- paratus. A lung or a gill is constructed essentially of a fine transparent membrane, one surface of which is exposed to the air or water, as the case may be, while on the other surface is a network of blood-vessels. The only separation be- tween the blood and aerating medium is the thin wall of the blood-vessels and the fine membrane on which the vessels are distributed. The difference between the simplest and the most complicated respiratory membrane is one of degree only. In the mammals and the higher vertebrates the respiratory membrane is included within a respiratory cavity, the chest or thorax, which carries on regular movements, the respiratory movements, to bring changes of air into close contact with the respiratory surface. The complexity of the respiratory membrane, the kind of aerating medium, and the respiratory movements are not, however, the only conditions which cause a difference in the respiratory capacity of different animals. The quantity and composition of the blood, especially as regards the number and size of the red corpuscles, and the vigor and efficiency of the circulatory apparatus in driving the blood to and fro between the lungs and the active tissues, these are conditions of equal, if not greater, importance. It may be as well to state here that the lungs are only the medium for the 243 244 RESPIRATION exchange, on the part of the blood, of carbon dioxide for oxygen. The living tissues are the seat of those combustion processes which consume oxygen and produce carbon dioxide. These processes occur in all parts of the body in the substance of the living active tissues, and are the true respira- tory processes, sometimes called internal or tissue respiration. THE RESPIRATORY APPARATUS. The object of the respiratory movements being the interchange of gases in the lungs, it is necessary that the atmospheric air shall pass into them and that the changed air shall be expelled from them. The lungs are con- tained in the chest or thorax, which is a closed cavity having no communica- FIG. 218. — Outline Showing the General Form of the Larynx, Trachea, and Bronchi, as seen from Before, h, The great cornu of the hyoid bone; e, epiglottis; t, superior, and *', inferior cornu of the thyroid cartilage; c, middle of the cricoid cartilage; tr, the trachea, showing sixteen cartilag- inous rings; b, the right, and b', the left bronchus. X £. (Allen Thomson.) THE LARYNX 245 tion with the outside except by means of the respiratory passages. The air enters these passages through the nostrils or through the mouth, thence it passes through the larynx into the trachea or windpipe, which about the middle of the chest divides into two tubes, the bronchi, one to each lung. The Larynx. The upper part of the passage which leads exclu- sively to the lung is formed by the thyroid, cricoid, and arytenoid carti- lages, figure 218, and contains the vocal cords, by the vibration of which the voice is chiefly produced. These vocal cords are ligamentous bands covered with mucous membrane and attached to certain cartilages which are capable of movement by muscles. By their approximation the cords can entirely close the entrance into the larynx; but under ordinary conditions the entrance of the larynx is formed by a more or less triangular opening between them, called the rima glottidis. Projecting at an acute angle between the base of the tongue and the larynx, to which it is attached, is a leaf-shaped cartilage with its larger extremity free. This is called the epiglottis. The whole of the larynx is lined by mucous membrane, which, however, is extremely thin over the vocal cords. At its lower extremity the larynx joins the trachea. Taste buds have been found in the epithelium of the posterior surface of the epiglottis, and in several other situations in the laryngeal mucous mem- brane. The Trachea and Bronchi. The trachea extends from the cricoid cartilage, which is on a level with the fifth cervical vertebra, to a point oppo- site the third dorsal vertebra, where it divides into the two bronchi, one for each lung, figure 218. The trachea measures, on an average, four or four and a half inches, 12 to 14 cm., in length, and from three-quarters of an inch to an inch, 2 to 2.5 cm., in diameter, and is essentially a tube of fibro-elastic membrane within the layers of which are enclosed a series of cartilaginous rings, from sixteen to twenty in number. These rings extend only around the front and sides of the trachea, about two-thirds of its circumference, and are deficient behind; the interval between their posterior extremities being bridged over by a continuation of the fibrous membrane in which they are enclosed, figure 219, h. Immediately within this tube and at the back is a layer of unstriped muscular fibers. This muscular layer extends transversely between the ends of the cartilaginous rings to which it is attached, and also opposite the intervals between them; its evident function being to diminish the caliber of the trachea by approximating the ends of the cartilages. Outside there are a few longitudinal bundles of muscular tissue, which, like the preceding, are attached both to the fibrous and to the cartilaginous framework. The mucous membrane, figures 219 and 220, consists largely of adenoid tissue, separated from the stratified columnar epithelium, which lines it, by a homogeneous basement membrane. This is penetrated here and there by channels which connect the adenoid tissue of the mucosa with the inter- 246 RESPIRATION cellular substance of the epithelium. The stratified columnar epithelium is formed of several layers, of which the most superficial layer is ciliated and the cells often branched downward. Many of the superficial cells are of the goblet variety. In the deeper part of the mucosa are many elastic fibers between which lie connective-tissue corpuscles and capillary blood-vessels. Numerous mucous glands are situated on the exterior and in the substance of the fibrous framework of the trachea; their ducts perforating the various FIG. 219. — Section of the Trachea, a, Columnar ciliated epithelium; bandc, proper structure of the mucous membrane, containing elastic fibers cut across transversely; d, submucous tissue containing mucous glands, e, separated from the hyaline cartilage, g, by a fine fibrous tissue, /, h, external investment of fine fibrous tissue. (S. K. Alcock.) structures which form the wall of the trachea, and opening through the mucous membrane into the cavity of the trachea. The two bronchi into which the trachea divides resemble the trachea in structure, with the difference that in them there is a distinct layer of un- striped muscle arranged circularly beneath the mucous membrane, forming the, muscularis mucosa. On entering the substance of the lungs the carti- laginous rings, although they still form only larger or smaller segments of THE TRACHEA AND BRCNCHI £47 a circle, are no longer confined to the front and sides of the tubes, but are distributed impartially to all parts of their circumference. The bronchi divide and subdivide in the substance of the lungs into smaller and smaller branches, which penetrate into every part of the organ FIG. 220. — Ciliary Epithelium of the Human Trachea, a. Layer of longitudinally arranged elastic fibers; b, basement membrane; c, deepest cells, circular in form; d, intermediate elongated cells; e, outermost layer of cells fully developed and bearing cilia. X 350. (Kolliker.) until at length they end in the smaller subdivisions of the lungs called lobules. All the larger branches have walls formed of tough membrane, contain- ing portions of cartilaginous rings, by which they are held open, and un- striped muscular fibers, as well as longitudinal bundles of elastic tissue. FIG. 22i. — Transverse Section of a Bronchus, about $ inch in Diameter, e, Epithelium (ciliated); immediately beneath it is the mucous membrane or internal fibrous layer, of varying thickness; m, muscular layer; 5. m, submucous tissue; /, fibrous tissue ; c, cartilage enclosed within the layers of fibrous tissue; g, mucous gland. (F. E. Schulze.) They are lined by mucous membrane, the surface of which, like that of the larynx and trachea, is covered with ciliated epithelium; but the several layers become less and less distinct until the lining consists of a single layer of more or less cubical cells covered with cilia, figure 221. The mucous membrane is abundantly provided with mucous glands. £48 RESPIRATION As the bronchi become smaller and smaller and their walls thinner, the cartilaginous rings become fewer and more irregular, until in the smaller bronchial tubes they are represented only by minute and scattered cartilag- inous flakes. And when the bronchi by successive branches are reduced to about ^Q- of an inch, c.6 mm., in diameter, they lose their cartilaginous ele- ment altogether and their walls are formed only of a tough, fibrous, elastic membrane with circular muscular fibers. They are still lined, however, by a thin mucous membrane with ciliated epithelium, the length of the cells bearing the cilia having become so far diminished that the cells are almost cubical. In the smaller bronchi the circular muscular fibers are relatively more abundant than in the larger bronchi and form a distinct circular coat. The Lungs and Plurae. The lungs occupy the greater portion of the thorax. They are of a spongy elastic texture, and on section appear to the naked eye as if they were in great part solid organs, except where branches of the open bronchi or air-tubes may have been cut across and show on the surface of the section. In fact, however, the lungs are hollow organs FIG. 222. — Transverse Section of the Chest. composed of a mass of air cavities all of which communicate finally with the common air-tube, the trachea. Each lung is enveloped by a serous membrane, the pleura, which ad- heres closely to its surface and provides it with its smooth and slippery covering. This same membrane lines the inner surface of the chest wall. The continuity of this membrane, which forms a closed sac as in the case of other serous membranes, will be best understood by reference to figure 222. The appearance of a space, however, between the pleura which covers the lung, visceral layer, and that which lines the inner surface of the chest, parietal layer, is inserted in the drawing only for the sake of distinctness. These layers are, in health, everywhere in contact, one with the other; and between them is only just as much fluid as will insure frictionless movement in their expansion and contraction. THE FINER STRUCTURE OF THE LUNG 249 When considering the subject of normal respiration, one may discard altogether the notion of the existence of any space or cavity between the lungs and the wall of the chest. If, however, an opening be made so as to permit air or fluid to enter the pleural sac, the lung in virtue of its elasticity recoils, and a considerable space is left between it and the chest wall. In other words, the natural elasticity of the lungs would cause them at all times to contract away from the ribs were it not that the contraction is resisted by atmospheric pressure which bears only on the inner surface of the air-tubes and air-cells. The pulmonary pleura consists of an outer or denser layer and an inner looser tissue in which there is a lymph-canalicular system. Numerous lym- phatics are to be met with, which form a dense plexus of vessels, many of which contain valves. They are simple endothelial tubes, and take origin in the lymph-canalicular system of the pleura proper. Scattered bundles of unstriped muscular fiber occur in the pulmonary pleura. They are es- pecially strongly developed on the anterior and internal surfaces of the lungs, the parts which move most freely in respiration. Their function is doubt- less to aid in expiration. The Finer Structure of the Lung. Each lung is partially subdi- vided into separate portions called lobes; the right lung into three lobes, FIG. 223. FIG. 224. FIG. 223. — Terminal Branch of a Bronchial Tube, with its Infundibula and Air-cells, from the Margin of the Lung Injected with Quicksilver; Monkey, a, Terminal bronchial twig; b, b, in- fundibula and air-cells. X 10. (F. E. Schulze.) FIG. 224. — Two Small Infundibula, a, a, with air-cells, b, b, and the ultimate bronchial tubes, c, c, with which the air-cells communicate. From a new-born child. - (Kolliker.) and the left into two. Each of these lobes, again, is composed of a large num- ber of minute parts, called lobules. Each pulmonary lobule may be considered to be a lung in miniature, consisting, as it does, of a branch of the bronchial tube, of air-cells, blood-vessels, nerves, and lymphatics, with a small amount of areolar tissue- 250 RESPIRATION On entering a lobule, the small bronchial tube, the structure of which has just been described, #, figure 210, divides and subdivides; its walls at the same time becoming thinner and thinner, until at length they are formed only of a thin membrane of areolar and elastic tissue, lined by a layer of squamous epithelium, no longer provided with cilia. At the same time they are altered in shape; each of the minute terminal branches widening out funnel-wise, and its walls being pouched out irregularly into small saccular dilatations, called air-cells, figure 223, b. Such a funnel-shaped terminal branch of the bronchial tube, with its group of pouches or air-cells, has been Called an infundibulum, figures 223 and 224, and the irregular oblong space in its center, with which the air-cells communicate, an intercellular passage. FIG. 225.— From a Section of the Lung of a Cat, Stained with Silver Nitrate. A. D, Alveolar duct or intercellular passage; S, alveolar septa, N, alveoli or 'air-cells, lined with large flat, nuleated cells, with some smaller polyhedral nucleated cells; M, unstriped muscular fibers Cir- cular muscular fibers are seen surrounding the interior of the alveolar duct, and at one part is seen a group of small polyhedral cells continued from the bronchus. (Klein and Noble Smith.) An inflated and dried turtle's lung is the homologue of a lobule. Such a preparation can be cut across to illustrate the intercellular passage, the in- fundibulum, and the air-cells. The air-cells, or air-vessels, are sometimes placed singly, like recesses from the intercellular passage, but more often they are arranged in groups or even rows, like minute sacculated tubes, so that a short series of vesicles all communicating with one another open by a common orifice into the tube. The vesicles are of various forms according to the mutual pressure to which THE FINER STRUCTURE OF THE LUNG 251 they are subject. Their walls are nearly in contact, and they vary from 0.5 to 0.3 mm. in diameter. Their walls are formed of fine membrane similar to that of the intercellular passages and continuous with it. The membrane is folded on itself so as to form a sharp-edged border at each circular orifice of communication between contiguous air-vesicles, or between the vesicles and the bronchial passages. Numerous fibers of elastic tissue are spread out in the walls between contiguous air-cells, and many of these are attached to the outer surface of the wall of which each cell is composed, imparting to it additional strength and the power of recoil after distention. The air-cells are lined by a layer of epithelium, figure 225, the cells of which are very thin and plate-like. The thin epithelial membrane is free on one side, where it comes in contact with the air of the lungs, but on the other FIG. 226. — Section of Injected Lung, Including Several Contiguous Alveoli. (F. E. Schulze.) Highly magnified, a, a, Free edges of alveoli; c, c, partitions between neighboring alveoli, seen in section; b, small arterial branch giving off capillaries to the alveoli. The looping of the vessels to either side of the partitions is well exhibited. Between the capillaries is seen the homogeneous alveolar wall with nuclei of connective-tissue corpuscles and elastic fibers. side a network of pulmonary capillaries is spread out so densely, figure 226, that the interspaces or meshes are even narrower than the vessels. These are on an average -g-oVo of an inch, or 8 micromillimeters, in diameter. Be- tween the atmospheric air-cells and the blood in these vessels, nothing in- tervenes but the thin walls of the cells and capillaries. The exposure of the blood to the air is the more complete because the wall between contiguous air-cells, and often the spaces between the walls of the same, contain only a single layer of capillaries both sides of which are at once exposed to the air, 252 RESPIRATION The air-vesicles situated nearest to the center of the lung are smaller and their networks of capillaries are closer than those nearer to the circum- ference. The vesicles of adjacent lobules dp not communicate. Those of the same lobule or proceeding from the same intercellular passage com- municate as a general rule only near angles of bifurcation, so that when any bronchial tube is closed or obstructed the supply of air is lost for all the blood- vessels of that lobule and its branches. Blood-supply. The lungs receive blood from two sources: a, the pulmonary artery; b, the bronchial arteries. The former conveys venous blood to the lungs for its oxidation, and this Wood takes no share in the nutrition of the deeper pulmonary tissues through which it passes. The branches of the bronchial arteries are nutrient arteries which ramify in the FIG. 227. — Capillary Network of the Pulmonary Blood-vessels in the Human Lung. X 60. (Kolliker.) walls of the bronchi, in the walls of the larger pulmonary vessels, and in the interlobular connective tissue, etc. The blood of the bronchial vessels is re- turned chiefly through the bronchial, but partly through the pulmonary, veins. Lymphatics. The lymphatics are arranged in three sets: i. Ir- regular lacunae in the walls of the alveoli or air-cells. The lymphatic vessels which lead from these accompany the pulmonary vessels toward the root of the lung. 2, Irregular anastomosing spaces in the walls of the bronchi. 3, Lymph-spaces in the pulmonary pleura. The lymphatic vessels from all these irregular sinuses pass in toward the root of the lung to reach the bronchial glands. Nerves. The nerves of the lung are to be traced from the anterior and posterior pulmonary plexuses, which are formed by branches of the vagus and sympathetic. The nerves follow the course of the blood-vessels and bronchi, and many small ganglia are situated in the walls of the latter. INSPIRATION 253 THE MOVEMENTS OF THE RESPIRATORY MECHANISM. Respiratory movement consists of the alternate expansion and contrac- tion of the thorax, by means of which air is drawn into or expelled from the lungs. A movement of the side walls or floor of the chest to increase its diameter or length will enlarge the capacity of the interior. By such an increase of capacity there will be of course a diminution of the pressure of the air in the lungs, and a fresh quantity of air will enter through the larynx and trachea to equalize the pressure on the inside and outside of the chest. This move- ment is called inspiration. The movement which diminishes the capacity of the chest and increases the pressure in the interior expels air until the pressure within and that without the chest are again equal. This movement is called expiration. In both cases the air passes through the trachea and larynx, whether in entering or FIG. 228. — Schematic Representation of Diaphragm. In expiration (7), quiet inspiration (//), and deep inspiration (///). (After Schaffer.) leaving the lungs, there being no other communication with the exterior of the body. And the lung, for the same reason, remains closely in contact with the walls and floor of the chest under all the circumstances described. To speak of expansion of the chest is to speak also of expansion of the lung, and vice versa. Inspiration. The enlargement of the chest during inspiration is due to muscular action, which brings about an increase in the size of the chest cavity through the contraction of the inspiratory muscles, the role played by the lungs being a passive one. The chest cavity is increased in* its three axes, the vertical, lateral, and antero-posterior diameters. The muscles engaged in ordinary inspiration are: the diaphragm, the external inter- costals, and the scaleni and levatores costarum. During forced inspiration 254 RESPIRATION every muscle is brought into play which by its contraction tends to elevate the ribs and sternum or which will fix points against which these muscles can act. This includes almost every muscle of the trunk and neck. Changes in the vertical diameter are due, first, to the contraction of the diaphragm. This muscle has the shape of a flattened dome, its highest Esophagus Left subclavian artery Left common carotid artery Left superior intercostal vein Left innominate vein Parietal pleura (cut edge) Pericardium Parietal pleura (cut edge) Aortic arch Pulmonary artery Bronchus Pulmonary veins Esophagus Diaphragm FIG. 229. — Thorax from the Left, Showing Left Pleural Sac, and the Diaphragm. The lung is removed. point being the central tendon. While passive, its lower portions are in apposition with the chest walls, figure 228, 7. On contraction, the dome is pulled downward and the lower portion is pulled away from the chest walls, the downward displacement varying from 6 to 12 mm. in normal respira- tion, and in forced respiration may amount to as much as 45 mm. The tendency of the diaphragm to pull the lower ribs and lower part of the sternum INSPIRATION 255 'nward is counteracted by the outward pressure of the' abdominal viscera, and by the action of the quadrati himborum, which by their attachment to the last ribs fix these and, in case of deep inspiration, may even pull them downward. The serrati postici inferiores also aid, being attached to the four lower ribs. Changes in the lateral and antero-posterior diameters are effected by the raising of the ribs, which are attached very obliquely to the spine and sternum. The elevation of the ribs takes place both in front and at the sides — the hinder ends being prevented from performing any upward movement by their pivot attachment to the spine. The movement of the front extremities of the ribs is of necessity limited by an upward and forward movement of the PIG. 230. — Diagram of Axes of Movement of Ribs. sternum to which they are attached, the movement being greater at the lower end than at the upper end of the sternum. The axes of rotation in these movements are two: one corresponding with a line drawn through the two articulations which the rib forms with the spine, a, b, figure 230, and the other with a line drawn from one of these (head of rib) to the sternum, A B, figure 230; the motion of the rib around the latter axis being somewhat after the fashion of raising the handle of a bucket. The elevation of the ribs is accompanied by a slight opening out of the angle which the bony part forms with its cartilage, and thus an additional means is provided for increasing the antero-posterior diameter of the chest. The movements of all the ribs except the twelfth consist of a rotation up- ward, forward, and outward. The twelfth presents only rotation down- ward and backward. 256 RESPIRATION The muscles involved in these movements of the ribs are the external intercostals and the part of the internal intercostals situated between the costal cartilages. Their action is to widen the intercostal spaces. The scaleni fix the first and second ribs, thereby making a fixed point of action for the other muscles involved. The serrati postici superiores assist the above and also raise the third, fourth, and fifth ribs. The levatores costarum longi and brevi elevate and evert all the ribs from the first to the tenth. In extraordinary or forced inspiration, which may be due either to violent exercise or to interference with the due entrance of air into the lungs, all the above muscles act more strongly. The diaphragm descends lower, the scaleni raise the first and second ribs instead of merely fixing them, as in ordinary respiration, as do also the sterno-cleido-mastoids. These, together with the erector spina, which straighten the spine, increase the vertical diameter. The trapezii and the rhomboidii assist in increasing the antero-posterior and lateral diameters by fixing the shoulders and thus giving a fixed point for the action of the pectorals and latissimi dorsi. The enlargement of the chest during inspiration presents peculiarities in different persons. In children of both sexes the principal muscle in- volved seems to be the diaphragm, and this type of breathing is known as abdominal breathing. In men, the chest and sternum, together with the front wall of the abdomen, are subject to a wide movement; this type of breathing is called the inferior costal. In women, the movement appears less extensive in the lower and more extensive in the upper part of the chest, which is called the superior costal type. This has been shown to be due rather to mode of dress than to a real difference in the sexes (Mosher). Expiration. Quiet expiration is a passive act due to the return of the thorax and its contained lungs to their normal position when the mus- cles involved in inspiration relax. This elastic recoil is sufficient in ordinary quiet breathing to expel air from the lungs. In forced expiration, however, which may occur to a slight degree in speaking, singing, etc., as well as in the case of many involuntary and reflex acts, such as coughing, sneezing, etc., other muscles are involved. Of these the principal are the abdominal muscles, obliquus externus and internus, rectus abdominis, transfer salis ab- dominis and pyramidalis. These act, first, by pressing the abdominal viscera against the diaphragm and thereby forcing it up, their descent into the pelvic cavity being prevented; second, by their attachments to the lower ribs and cartilages, they draw these downward and inward, thereby lessening the size of the thoracic cavity; lastly, by their contraction, they form a fixed point for the action of that part of the internal intercostals, not involved in inspiration, to approximate the ribs. When by the efforts of the expiratory muscles the chest has been squeezed to less than its average diameters, it again, on relaxation of the muscles, returns to the normal dimensions by virtue of its elasticity. The construe- RECORDING RESPIRATORY MOVEMENTS 257 tion of the chest walls, therefore, admirably adapts them for recoiling against and resisting as well undue contraction as undue dilatation. Respiratory Movements of the Nostrils and of the Glottis. During the action of the inspiratory muscles which directly draw air into the chest, those which guard the opening through which the air enters are also active. In hurried breathing the dilatation of the nostrils is well seen, although under ordinary conditions it may not be noticeable. The opening at the upper part of the larynx, however, the rima glottidis, is dilated at each in- spiration for the more ready passage of air, and becomes smaller at each expiration; its condition, therefore, corresponds during respiration with that of the walls of the chest. There is a further likeness between the two acts in that, under ordinary circumstances, the dilatation of the rima glot- tidis is a muscular act and its contraction chiefly an elastic recoil; although, under various special conditions to be hereafter mentioned, there may be considerable muscular contraction exercised. Methods of Recording Respiratory Movements. The movements of respiration may be recorded graphically in several ways. The ordinary method is to introduce a tube into the trachea of an animal, and to connect this tube by some gutta-percha tubing with a T-piece, the side branch of which is connected with a Marey's tambour, which may be made to write on a recording surface, figure 173. If the tube attached to the free limb of the T-piece be partially closed with a screw compress, the movements of inspiration FIG. 23 1 . — Stethogr-vph or P -eumograph. h. Tambour fixed at right angles to plate of steel, f ; c and d, arms by which i strument is attached to chest by belt, e. When the chest expands, the arms are pulled asunder, which bends the steel plate, and the tambour is affected by the pressure of 6, which is attached to it on the one hand, and to the upright in connection with horizontal screw, g. (Modified from Marey's instrument.) and expiration are larger than if it were open. The alteration of the pressure within the lungs on inspiration and expiration is shown by the movement of the column of air in the trachea and in its extension to the T-piece. By these means a record of the respiratory movements may be obtained. Various instruments have been devised for recording the movements of the chest by application of apparatus to the exterior. Such is the stethometer of Burdon-Sanderson, figure 233. This consists of a frame formed of two parallel steel bars joined by a third 17 258 RESPIRATION at one end. At the free end of the bars is attached a leather strap, by means of which the apparatus may be suspended from the neck. Attached to the inner end of one bar is a tambour and ivory button, to the end of the other an ivory button. The apparatus is suspended with the transverse bar posteriorly, the button of the tambour is placed on the part of the chest the movement of which it is desired to record, and the other button is made to press upon the corresponding side of the chest, so that the chest is held as between a pair of calipers. The receiving tambour is connected through a T-piece with a recording tambour of Marey's, and with a bulb by means of which air can be squeezed into the cavity of the tympanum. When adjusted, the tube connected with the air ball is shut off by means of a screw clamp. The movement of the chest is thus communicated to the recording tambour. A simpler form of this apparatus, called a pneumograph or stethograph, consists of a thick India-rubber bag of elliptical shape about three inches long, to one end of which a rigid gutta-percha tube is attached. This bag may be fixed at any required place on the chest by means of a strap and buckle. By means of the gutta-percha tube the variations of the pressure of air in the bag, produced by the movements of the chest, are communicated FIG. 232. — Tracing of Thoracic Respiratory Movements obtained by means of Marey's Pneu- mograph. (Foster.) A whole respiratory phase is comprised between a and a; inspiration during which the lever descends, extending from a to b, and expiration from b to a. The undulations at c are caused by the heart's beat. to a recording tambour. This principle is applied in a modified form in Marey's pneumo- graph, figure 231. The variations of intrapleural pressure may be recorded by introducing a cannula into the pleural or pericardial cavity. The cannula should be previously connected with a mercury or other form of manometer by tubing filled with physiological saline. Finally, it has been found possible in various ways to record the diaphragmatic move- ments. This can be done by inserting a receiving tambour into the abdomen below the diaphragm, by the insertion of needles into different parts of the diaphragm and recording the movement of the free ends of needles about the fulcrum formed where the chest wall is pierced, or by recording the contraction of isolated strips of the diaphragm directly. These records all give an accurate picture of the movements of the diaphragm. The Relative Time of Inspiration and Expiration and the Respira- tory Movement. The acts of inspiration and expiration take up, un- der ordinary circumstances, a nearly equal time. The time of inspiration, however, especially in women and children, is a little shorter than that of expiration, and there is commonly a very slight pause between the end of expiration and the beginning of the next inspiration, see figure 232. The ratio of the respiratory rhythm may be thus expressed: Inspiration 6 Expiration 7 to 8 Pause Very slight QUANTITY OF AIR BREATHED 259 If the ear be placed in contact with the wall of the chest, or be separated from it only by a good conductor of sound or a stethoscope, a faint respiratory murmur is heard during inspiration. This sound varies somewhat in different parts, being loudest or coarsest in the neighborhood of the trachea and large bronchi (tracheal and bronchial breathing), and fading off into a faint sighing as the ear is placed at a distance from these (vesicular breathing). It is heard best in children. In them a faint murmur is heard in expiration also. The cause of the vesicular murmur has received various explanations. Most Tambour. Ivory button. Tube to commu- nicate with re- cording tam- bour, Ball to fill appa- ratus-With air. FIG. 233. — Stethometer. (Burdon- Sanderson.) observers hold that the sound is produced in the glottis and larger bronchial tubes, but that it is modified in its passage to the pulmonary alveoli. In disease of the lungs the vesicular murmur undergoes various modifica- tions, for a description of which one must consult text-books on physical diagnosis. The Quantity of Air Breathed. Tidal air is the quantity of air which is habitually and almost uniformly changed in each act of breathing. In a healthy adult man it is about 30 cubic inches, or about 500 c.c. or half a liter. In college students the tidal air is somewhat less, varying from 300 to 400 c.c. The Complemental Air is the quantity of air which can be drawrn into the lungs by the deepest inspiration over and above that which is in the lungs 260 RESPIRATION at the end of an ordinary inspiration. Its amount varies, but may be reck- oned as 100 cubic inches, or about 1,600 c.c. The Reserve Air is that which may be expelled by a forcible and deeper expiration, after an ordinary expiration, such as that which expels the tidal air. The reserve air amounts to from 1,200 to 1,500 c.c. This is also termed the supplemental air. The Residual Air is the quantity which still remains in the lungs after the most violent expiratory effort. Its amount depends in great measure FIG. 234. — Tracing of the Normal Diaphragm Respirations of the Rabbit, a, With quick movement of drum; b, with slow movement; /, inpiration; E, expiration. To be read from left to right. (Marckwald.) on the absolute size of the chest, but may be estimated at about 1,000 c.c. to 1,200 c.c. The total quantity of air which passes into and out of the lungs of an adult, at rest, in 24 hours, is about 686,000 cubic inches. This quantity, however, is largely increased by exertion; the average amount for a hard- working laborer in the same time being 1,568,390 cubic inches. The Respiratory Capacity. The greatest respiratory capacity or vital capacity of the chest is indicated by the quantity of air which a person can expel from his lungs by a forcible expiration after the deepest possible in- spiration. The vital capacity is the sum of the reserve, tidal, and comple- mental airs. It expresses the power which a person has of breathing in the emergencies of active exercise, violence, and disease. The average capacity of an adult, at 15.4° C. (60° F.), is about 225 to 250 cubic inches, or 3,500 to 4,000 c.c. THE RESPIRATORY CAPACITY 261 The respiratory capacity, or as John Hutchinson called it, vital capacity, is usually measured by a modified gasometer or spirometer, into which the experimenter breathes, making the most prolonged expiration possible after the deepest possible inspiration. The quantity of air which is thus expelled from the lungs is indicated by the height to which the air chamber of the spirometer rises; and by means of a scale placed in con- nection with this, the number of cubic inches or centimeters is read off. In healthy men, the respiratory capacity varies chiefly with the stature, weight, and age. Circumstances Affecting the Amount of Respiratory Capacity. For every inch of height above the standard the respiratory capacity is increased, on an average, by eight inches; and for every inch below, it is diminished by the same amount. The influence of weight on the capacity of respiration is less manifest, and consider- ably less than that of height. It is difficult to arrive at any definite conclusions on this FIG. 235. — Diagram of Hutchinson's Spirometer. (Landois.) A , Graduated cylinder serving as a receiver for the breath; it is supplied with a stopcock at the top for the ready expulsion of air, and is balanced by weights passing over pulleys. B, Mouthpiece with tube reaching nearly to the top of the graduated receiver (A) when the latter is sunk in the reservoir ready for an experiment; there is a stopcock in this tube near the first angle, to prevent regurgitation of air. C, Reservoir for the graduated receiver. In using the spirometer the reservoir and graduated receiver are filled with water, or, to prevent the absorption of carbon dioxide, with a saturated aqueous solution of common salt (NaCl). When ready for an experiment, the stopcock at the top of the receiver is closed and that in the tube of the mouthpiece opened, and the breath forced into the receiver. The receiver rises as fast as the breath displaces the water. After the breath is forced into the re- ceiver the stopcock in the tube of the mouthpiece is closed, and the water outside and inside the receiver brought to the same level, so that the air within the receiver shall be at the atmospheric pressure. The amount of breath within the receiver is then read directly from the scale attached to the receiver. For accurate measurement the breath should stand a few minutes to acquire the temperature of the liquid over which it is collected ; then the various corrections for aqueous vapor tension, and the variations from the standard temperature and pressure, should be made. point, because the natural average weight of a healthy man in relation to stature has not yet been determined. By age, the capacity appears to be increased from about the fifteenth to the thirty- fifth year, at the rate of five cubic inches per year; from thirty-five to sixty-five it di- minishes at the rate of about one and a half cubic inches per year; so that the capacity of respiration of a man sixty years old would be about thirty cubic inches less than that of a man forty years old, of the same height and weight. (John Hutchinson.) RESPIRATION The number of respirations in a healthy adult person usually ranges from 14 to 1 8 per minute. It is greater in infancy and childhood. It varies also much according to different circumstances, such as exercise or rest, health or disease, etc. Variations in the number of respirations correspond ordinarily with similar variations in the pulsations of the heart. In health the proportion is about i to 4, or i to 5 ; and when the rapidity of the heart's action is increased, that of the chest movement is commonly increased also, but not in every case in equal proportion. It happens occasionally in disease, especially of the lungs or air-passages, that the number of respiratory acts increases in quicker proportion than the beats of the pulse; and, in other affections, much more commonly, that the number of the pulses is greater in proportion than that of the respirations. The Force of Inspiratory and Expiratory Muscles. The force which the inspiratory muscles are capable of exerting on the chest is greatest in individuals of the height of from five feet seven inches to five feet eight inches, and is equal to a column of three inches of mercury. Above this height the force decreases as the stature increases; so that the average power of men of six feet is measured by about two and a half inches of mer- cury. The force manifested in the strongest expiratory acts is, on the average, one-third greater than that exercised in inspiration. But this difference is in a great measure due to the power exerted by the elastic reaction of the walls of the chest; and it is also much influenced by the disproportionate strength which the expiratory muscles attain from their being called into use for other purposes than that of simple expiration. The force of the inspiratory act is, therefore, better adapted than that of the expiratory for testing the muscular strength of the body (John Hutchinson). It has been shown that within the limits of ordinary tranquil respiration the elastic resilience of the walls of the chest favors inspiration; and that it is only in deep inspiration that the ribs and rib-cartilages offer an opposing force to their dilatation. In other words, the elastic resilience of the lungs, at the end of an act of ordinary exhalation has drawn the chest walls within the limits of their normal degree of expansion. Under all circumstances, of course, the elastic tissue of the lungs opposes inspiration and favors expiration. It is possible that the contractile power which the bronchial tubes and air-vesicles possess, by means of their muscular fibers may assist in expiration. But it is more likely that its chief purpose is to regulate and adapt, in some measure, the quantity of air admitted to the lungs, and to each part of them, according to the supply of blood. The muscular tissue contracts upon and gradually expels collections of mucus, which may have accumulated within the tubes, and which cannot be ejected by forced expiratory efforts, owing to collapse or other morbid conditions of the portion of lung connected with the obstructed tubes (Gairdner). Apart from any of the before-mentioned COMPOSITION OF THE ATMOSPHERE 263 functions, the presence of muscular fiber in the walls of a hollow viscus, such as a lung, is only what might be expected from analogy with other organs. Subject as the lungs are to such great variation in size, it might be antici- pated that the elastic tissue, which enters so largely into their composition, would be supplemented by the presence of much muscular fiber. RESPIRATORY CHANGES IN THE AIR BREATHED. Composition of the Atmosphere. The atmosphere we breathe has, in every situation in which it has been examined in its natural state, a nearly uniform composition. It is a mixture of oxygen, nitrogen, carbon dioxide, and watery vapor, with, commonly, traces of other gases, as argon, ammonia, sulphureted hydrogen, etc. Of every 100 volumes of pure at- mospheric air, 79 volumes, on an average, consist of nitrogen and argon, the remaining 21 of oxygen. The proportion of carbon dioxide is extremely small; 10,000 volumes of atmospheric air contain only about 3 of that gas. The quantity of watery vapor varies greatly according to the tem- perature and other circumstances, but the atmosphere is never without some. In this country the average quantity of watery vapor in the atmos- phere varies greatly according to the region. In some of our Western arid plains in the dry season the air is almost free of moisture. Composition of Air which Has Been Breathed. The changes effected by respiration in the atmospheric air are: i, an increase of tem- perature; 2, an increase in the quantity of carbon dioxide; 3, a diminution in the quantity of oxygen; 4, a diminution of volume; 5, an increase in the amount of watery vapor; 6, the addition of a minute amount of organic matter and of free ammonia. Temperature of the Expired Air. Expired air, after its contact with the interior of the lungs, is hotter (at least in most climates) than the inspired air. Its temperature varies between 36° and 37.5° C. (97° and 99.5° F.), the lower temperature being observed when the air has remained but a short time in the lungs. Whatever may be the temperature of the air when inhaled, it acquires nearly that of the blood before it is expelled from the chest. The Carbon Dioxide of Expired Air. The percentage of carbon dioxide is increased, but the quantity exhaled in a given time is subject to change from various circumstances. From every volume of air inspired 4 to 5 per cent of oxygen is abstracted; while a rather smaller quantity, 4.38 per cent, of carbon dioxide is added in its place; the expired air will contain, there- fore, 438 volumes of carbon dioxide in 10,000. The total quantity of carbon dioxide exhaled into the air breathed by a healthy adult, calculating that 15.4 c.c.of the 35oc.c.of the average air breathed out at each expiration con- sists of carbon dioxide, and that the rate of respiration is on an average 16, would be about 400 liters in the twenty-four hours. From actual experiment this 264 RESPIRATION amount seems to be a trifle too great, since from the average of many inves- tigations the total amount of carbon dioxide excreted per day by the entire body has been found to be about 400 liters, weighing 800 grams, and con- sisting of 218 grams of carbon, and 582 grams of oxygen. From the 218 grams of carbon must be deducted about 10 grams excreted in other ways FIG. 236.— Apparatus for Estimating Oa and CO2 in Expired Air. (Waller.) than by the lungs, which leaves about 215 grams as the amount of carbon ex- creted by the average healthy man by respiration each day and night. These quantities must be considered approximate only, inasmuch as various cir- cumstances, even in health, influence the amount of carbon dioxide excreted, and, correlatively, the amount of oxygen absorbed. Circumstances Influencing the Amount of Carbon Dioxide Excreted. Age and Sex. The quantity of carbon dioxide exhaled into the air breathed by males, regularly in- creases from 8 to 30 years of age; from 30 to 50 the quantity, after remaining stationary for a while, gradually diminishes, and from 50 to extreme age it goes on diminishing, till it scarcely exceeds the quantity exhaled at 10 years old. In females (in whom the quantity exhaled is always less than in males of the same age) the same regular increase in quantity goes on from the 8th year to the age of puberty, when the quantity abruptly ceases to in- crease, and remains stationary so long as they continue to menstruate. When menstrua- tion has ceased, the carbon dioxide output soon decreases at the same rate as it does in old men. AMOUNT OF CAKbONT DIOXIDE LXCU171KD 265 Respiratory Movements. The quicker the respirations, the smaller is the percentage of carbon dioxide contained in each volume of the expired air. Although the propor- tionate quantity of carbon dioxide is thus diminished, tne absolute amount exhaled within a given time is increased thereby, owing to the larger quantity of air which is breathed in the time. The last half of a volume of expired air contains more carbonic acid than the half first expired; a circumstance which is explained by the later portion of air coming from the remote part of the lungs, where it has been in more immediate and prolonged contact with the blood than the first portion exhaled has, which comes chiefly from the larger bronchial tubes. External Temperature. The observation made by Vierordt at various temperatures between ^.4°-2^.8° C. (38° F. and 75° F.) show, for warm-blooded animals, that within this range every rise equal to 5.5° C. (10° F.) causes a diminution of about 33 c.c. (2 cubic inches) in the quantity of carbon dioxide exhaled per minute. Season of the Year. The season of the year, independently of temperature, materi- ally influences the respiratory phenomena since it influences the metabolism of the body; spring being the season of the greatest, and autumn of the least, activity of the respira- tory and metabolic functions. Purity of the Respired A ir. The average quantity of carbon dioxide given out by the lungs constitutes about 4.38 per cent of the expired air; but if the air which is breathed be previously impregnated with carbon dioxide (as is the case when the same air is fre- quently respired), then the quantity of carbon dioxide exhaled becomes relatively much greater. Hygrometric State oj the Atmosphere. The amount of carbon dioxide exhaled is con- siderably influenced ty the degree of moisture of the atmosphere, much more being given off when the air is moist than when it is dry. Period of the Day. The respiratory quotient, i.e., the ratio between carbon dioxide eliminated and oxygen absorbed, is greater during the day than during the night. In the day, therefore, the COa exhaled in relation to the O2 absorbed is increased, and it is diminished during the night. This is probably due to the increased production of COa as a result of increased tissue activity during the day, and, consequently, the breaking down or catabolism of more substances. Food and Drink. By the use of food the quantity of CO2 is increased, while by fast ing it is diminished; it is greater when animals are fed on farinaceous food than wheif fed on meat. The effects produced by spirituous drinks depend much on the kind ot drink taken. Pure alcohol in very small amounts tends rather to increase than to lessen respiratory changes, and the amount, therefore, of carbon dioxide expired. Rum, ale, and porter, also sherry, have very similar effects. On the other hand, brandy, whisky, and gin in greater amounts almost always lessen the respiratory changes, and, consequently, the amount of the gas exhaled. This is primarily due to their influence on the rate of metabolism in each instance. Exercise. Bodily exercise, in moderation, increases the quantity of CO 2 expired by at least one-third more than it is during rest. For about an hour after exercise the volume of the air expired in the minute is increased nearly 2,000 c.c., or 118 cubic inches; and the quantity of carbon dioxide about 125 c.c., or 7.8 cubic inches per minute. Violent exercise, such as full labor or athletic competition, still further increases the amount of the carbonic acid exhaled. The Oxygen is Diminished. Pettenkofer and Voit have found that the mean consumption of oxygen during 24 hours, by a man weighing 70 kilos, is about 700 grams or 490 liters. The quantity of oxygen absorbed increases with muscular exercise, and falls during rest. In general terms the quantity absorbed varies with the activity of the metabolic processes, following very closely the variation of carbon dioxide under the conditions outlined above. The Volume of the Respired Air is Diminished. When allowance has been made for the expansion in heating, the volume of expired air is decreased. 266 RESPIRATION the loss being due to the fact that a portion of the oxygen absorbed is not returned in the form of carbon dioxide. Since the oxygen of a given volume of carbon dioxide would have the same volume as the carbon dioxide itself at a given temperature and pressure, a portion of the oxygen absorbed must be used for other purposes than the formation of carbon dioxide. In fact, some of it is used in the formation of urea, some in the formation of water, etc. The oxygen in the carbon dioxide exhaled, divided by the oxygen absorbed, gives what is known as the respiratory quotient ; thus CO3 exhaled Oa absorbed Normally in man on a mixed diet the respiratory quotient is 4.0 to 4.5 — = 0.8 to 9.9. But it is subject to variation through several causes. For example, through variation in diet. On a pure carbohydrate diet the respiratory quotient will rise above 0.9, i.e., to i.o, since carbohydrates contain enough oxygen to oxidize the hydrogen in their molecule. On a diet containing much fat it is lowest, since relatively more oxygen is needed completely to oxidize fat. The theoretical respiratory quotient for fats is 0.7. The same is true, but to a less degree, in the case of proteids which also require much oxygen for their complete oxidation. Muscular exertion raises the respiratory quotient, because in its performance carbohydrates are used up in relatively greater quantity. The Watery Vapor in Respired Air is Increased. The quantity emitted is, as a general rule, sufficient to saturate the expired air, or very nearly so. Its absolute amount is, therefore, influenced by the following circumstances: i, By the quantity of air respired; for the greater this is, the greater also will be the quantity of moisture exhaled; 2, By the quantity of watery vapor contained in the air previous to its being inspired; because the greater this is, the less will be the amount to complete the saturation of the air; 3, By the temperature of the expired air; for the higher this is, the greater will be the quantity of watery vapor required to saturate the air; 4, By the length of time which each volume of inspired air is allowed to remain in the lungs; for although, during ordinary respiration, the expired air is always saturated with watery vapor, yet, when respiration is performed very rapidly, the air has scarcely time to be raised to the highest temperature or be fully charged with moisture ere it is expelled. The quantity of water exhaled from the lungs in 24 hours ranges (accord- ing to the various modifying circumstances already mentioned) from about 200 to 800 c.c., the ordinary quantity being about 400 to 500 c.c. Some of this is probably formed by the chemical combination of oxygen with hydro- gen in the system; but the far larger proportion of it is water which has been PRESSURE AND DIFFUSION OF THE AIR 267 absorbed, as such, into the blood from the alimentary canal, and which is exhafed from the surface of the air-passages and cells, as it is from the free surfaces of all moist animal membranes, particularly at the high tempera- ture of warm-blooded animals. A Small Quantity of Ammonia is added to the ordinary constituents of expired air. It seems probable, however, both from the fact that this sub- stance cannot be always detected and from its minute amount when present, that the whole of it may be derived from decomposing particles of food left in the mouth, or the teeth, and that it is, therefore, only an accidental con- stituent of expired air. The Quantity of Organic Matter in Expired Air is Increased. It was formerly supposed that this organic matter was injurious and gave rise to the unpleasant symptoms which are experienced in badly ventilated rooms. But this has been strongly questioned so that the matter cannot be considered settled at the present time. THE RESPIRATORY CHANGES IN THE BLOOD. Pressure and Diffusion of the Air. It must be remembered that the tidal air in the lungs amounts only to from 300 to 500 c.c. at each in- spiration. This amount at once mixes with the reserve and the residual air already in the lungs. The mixture is facilitated by the air currents set up in the deeper parts of the lungs by the sudden entrance of the tidal air; but, after all is considered, it will be found that diffusion is the greatest factor in producing a uniform mixture of the gases in the alveoli and in the air-cells of the lungs. Just as a fresh supply of oxygen introduced within the door of a closed room will quickly diffuse throughout the space of the entire room so will the fresh tidal air diffuse into the space of the lungs. When the tidal air is expired its average composition has been changed so it has only about 1 6 per cent of oxygen instead of the usual 20.96 per cent of oxygen in air. The oxygen content of the air still left in the lungs is probably some- what less than the percentage in this expired air for the reason that the air of the respiratory tree, the trachea, bronchi, and bronchioles, is never fully mixed with the alveolar air. The partial pressure of the oxygen of the air measured under standard conditions is 159 mm. of mercury, that is, 20.96 per cent of 760 mm. of mer- cury, the standard pressure of one atmosphere. The partial oxygen pressure in expired air with 16 per cent of oxygen is only 122 mm. of mercury. These figures show a diffusion pressure of at least 37 mm. of mercury to carry oxygen into the deeper recesses of the lungs. The constant loss of oxygen to the blood probably keeps the mean difference greater. The Gases of the Blood. Turning now to the consideration of the gases of the blood in the lungs, a somewhat different picture presents RESPIRATION itself. The blood is a mass of corpuscles floating in the fluid plasma. An analysis of the blood shows that it contains oxygen, carbon dioxide, and nitrogen, the gases of the air. The usual method is completely to extract the blood gases by an air-pump, figure 237, and determine the quantities in cubic centimeters per 100 c.c. of blood. The Extraction of the Gases from the Blood. As the ordinary air-pumps are not suf- ficiently powerful for the purpose, the extraction of the gases from the blood is accomplished by means of a mercurial air-pump, of which there are many varieties, those of Ludwig, Alvergnidt, Geissler, and Sprengel being the chief. The principle of action in all is much the same. Ludwig's pump, which may be taken as a type, is represented in figure 237. It consists of two fixed glass globes, C and F, the up- per one communicating by means of the stopcock, D, and a stout India-rubber tube with another glass globe, L, which can be raised or lowered by means of a pul- ley; it also communicates by means of a stopcock, B, and a bent glass tube, A , with a gas receiver (not repre- sented in the figure), A dipping into a bowl of mercury, so that the gas may be received over mercury. The lower globe, F, communicates with C by means of the stopcock, E, with / in which the blood is contained by the stopcock, G, and with a movable glass globe, My similar to L, by means of the stopcock, H, and the stout India-rubber tube, K. In order to work the pump, L and M are filled with mercury, the blood from which the gases ire to be extracted is placed in the bulb 7, the stopcocks H, E, D, and B being open, and G closed. M is raised by means of the pulley until F is full of mercury, and the air is driven out. E is then closed, and L is raised so that C becomes full of mercury, and the air driven off. B is then closed. On lowering L the mercury runs into it from C, and a vacuum is established in C. On opening E and lowering M, a vacuum is similarly established in F ; if G be now opened, the blood in 7 will enter ebullition, and the gases will pass off into F and C, and on raising M and then L, the stopcock B being opened, the gas is driven through A, and is received into the receiver over mercury. By repeating the ex- periment several times the whole of the gases of the specimen of blood is obtained, and may be estimated. FIG. 237. — Ludwig's Gas -pump. Pfluger's analysis of the arterial blood of the dog gave the following volumes per cent: oxygen 22.6, carbon dioxide 34.3, and nitrogen 1.8. The analysis for the venous blood gives a very much lower oxygen and a higher carbon dioxide per cent. The average oxygen content of venous blood is 10 to 12 per cent and the carbon dioxide 45 per cent. The blood in different veins of the body varies within wide limits as regards its gas content. Oxygen. 100 c.c. Arterial blood 22.6 c.c. 100 c.c. Venous blood 12. c.c. Carbon Dioxide. 34 C.C. 45 c-c- Nitrogen. 1.7 c.c. 1.7 c.c. COMBINING POWER OF HEMOGLOBIN WITH OXYGEN The large quantity of oxygen found in arterial and in venous blood is the more striking when the facts of absorption of gases by liquids are reviewed. A liquid such as water will, when exposed to a gas, take up the gas by absorp- tion according to definite physical laws. Under constant temperature the amount of gas absorbed, oxygen for example, varies directly as the pressure of the gas, or partial pressure if ,the gas is a mixture. The oxygen absorbed by water from pure air as compared with expired air is in direct proportion to the partial pressure of oxygen in the two airs, which is as 159 to 122. The amount of gas absorbed for a unit of fluid under standard tempera- ture and pressure (one atmosphere at o° C.), called its absorption coefficient, is about the same for blood-plasma as for water. Before one can determine the actual amount of oxygen in the plasma, the tension or absorption pressure must be determined. The tension of the oxygen in arterial blood is found by an instrument which enables one to measure the pressure at which oxygen is neither ab- sorbed nor given off. The instrument commonly used is called an aerotonom- eter. The principle of the instrument depends upon the fact that blood exposed to mixtures of the gases in air tends to give up or absorb gases from the air until complete equilibrium is established. By this means observers have measured the tensions of the blood gases. The results have not been very constant, but the oxygen tension has been found to be from 4 (Strassburg) to 10 (Herter) per cent of an atmosphere. Many determinations have been given of both lower and higher percentages, but, accepting the above limits for a working average, the oxygen tension in arterial blood would be from 30.4 to 76 mm. of mercury. Blood-plasma exposed to an air with a partial pressure of 30.4 to 76 mm. of mercury would absorb only from o.i to 0.3 (0.26 c.c. Pfliiger) of a cubic centimeter of oxygen for 100 c.c. of blood. As a matter of fact, 100 c.c. of whole blood contains from 20 to 22 c.c. of oxygen. It is evident that blood cannot hold the oxygen in simple solution, but must retain it in chemical combina- tion. The red blood-corpuscles have been shown to carry the excess of oxygen by virtue of the special respiratory pigment, hemoglobin. Combining Power of Hemoglobin with Oxygen. One hundred cubic centimeters of blood contain about 14 grams of hemoglobin, page 120. Each gram of hemoglobin, when fully saturated with oxygen, according to Hufner's earlier determination, combines with 1.56 c.c. of oxygen. By later more careful work he gets the determination of 1.34 c.c. for hemoglobin of ox blood. This last figure indicates that the combining power of the hemo- globin is dependent upon the iron in the molecule, in which one atom of iron combines with one atom of oxygen. The later investigation of the conditions under which hemoglobin combines with oxygen are by Hiifner, on the one hand, and Loewy, on the other. The former worked with purified solutions of hemoglobin, the latter with blood. The average results of the investigations 270 RESPIRATION of these two observers show that when the oxygen tension in the air, which is in contact with the blood, is lowered below a certain point, the amount of oxygen which will be liberated from combination with hemoglobin will be very great, whereas a lowering of the tension of oxygen by an equal amount where the pressures are relatively high leads to practically no liberation of hemoglobin, and the converse is equally true. The critical oxygen pressure in so far as its combination with hemoglobin is concerned varies according to observers. With Loewy the critical dissociation pressure is at or below 76 mm. of mer- cury, 10 per cent of an atmosphere. Strassburg gives the oxygen tension of arterial blood as 29.64 mm. of mercury, and for venous blood 22.04 mm. of mercury. That is to say, during the brief interval in which the blood is in the pulmonary capillaries the oxygen tension has increased by 7.6 mm. of mercury, an increase of tension which would produce very little increase in simple absorption of oxygen. Yet is it sufficient to cause fixation of from four to five volumes per cent of oxygen by the hemoglobin. Oxygen Pressure in the Atmosphere 159 mm. of mercury " " " Alveolar air 122 mm. of mercury i " " " Venous blood 22.04 mm. of mercury It is evident that there will be diffusion of oxygen from the high tension toward the lower and in the direction indicated by the arrows in the table above. As fast as the oxygen diffuses into the venous blood, thus tending to raise the pressure of the gas in solution, it is taken up and fixed by the hemo- globin. This process proceeds during the interval the blood is fh the pul- monary capillaries far enough to raise the oxygen tension from 22.04 mm. of mercury to 29.64 mm. of mercury, and far enough to permit of the fixation of from four to five volumes per cent of oxygen. Liberation of Oxygen in the Tissue Capillaries. When the arterial blood reaches the capillaries of the tissues, then the situation which we have just found holding good in the lungs is reversed. As rapidly as the oxygen reaches the living protoplasm of the tissues it enters into fixed combination, thus rendering it inert. The oxygen tension in the tissue cells will, there- fore, be zero. Under these conditions the difference in pressure level be- tween the oxygen tension in the blood and that in the tissues is sufficient to cause a rapid diffusion of oxygen through the capillary walls with correspond- ing liberation of the oxygen from the hemoglobin according to the laws of combination given in the table above. The total effect of this process is to maintain a relatively high diffusion pressure of the oxygen in the blood. During the time the blood remains in the capillaries the total oxygen tension will have been lowered from 29.64 to 22.04 mm- of mercury, yet this slight lowering of tension is sufficient to liberate from four to five volumes per cent of oxygen. This figure, of course, is comparative. In many of the very active ELIMINATION OF CARBON DIOXIDE 271 tissues, such as in muscle, a much larger per cent of oxygen will have been disassociated and the oxygen tension correspondingly lowered so that the venous blood returning through such an active organ may not have more than half the average amount of oxygen found in venous blood. Considering the pressure relations of oxygen from the time of its intro- duction into the body with the fresh air to its fixation in the tissues we have the following schema: Oxygen Pressure in the Atmosphere 159 mm. I Alveolar Air 122 mm. i Venous Blood 22 .04 mm. Tension of Oxygen in the Arterial Blood 29 .64 mm. i " " " Tissues o.oo mm. Elimination of Carbon Dioxide by the Blood and the Respiratory Apparatus. The principles of absorption of gas by liquids discussed in the preceding pages apply equally well for carbon dioxide with the exception that carbon dioxide is about three times as soluble in blood as is oxygen. The carbon dioxide results from the oxidative processes going on in the tis- sues, and this gas is present in large quantities in the tissues and their im- mediately surrounding lymph. An analysis of the carbon-dioxide content of venous blood reveals the presence of about 45 c.c. of the gas in 100 c.c. of blood. This gas, like oxygen, is held in such large quantity by virtue of the fact that it forms loose chemical combinations in the blood. Of the total quantity not more than 5 per cent is held in simple solution. From 10 to 15 per cent of the total volume is found in firm combination in such forms as carbonates, bicarbonates, etc. The remaining 80 and more volumes per cent is held in loose chemical combination, a combination which is broken up under the same conditions of variation in carbon-dioxide tension as were found to exist for oxygen in combination with hemoglobin. In the case of carbon dioxide an analysis of plasma reveals the fact that the gas is in com- bination with some compound of the plasma, probably a proteid. In fact, there is some evidence to show that carbon dioxide combines with the globulin group. Carbon dioxide also forms loose chemical compounds with the con- stituents of the red corpuscles, probably with the proteid portion of the hemo- globin molecule. The pressure relations of this gas as regards its diffusion in the process of elimination are shown in the following table: Carbon -dioxide Tension in the Tissues 58 mm. of mercury i " " " " Venous Blood 41 " " I " « " " Alveolar Air ,23 to 38mm. of " i « « " " Expired Air 5.8 mm. " " 272 RESPIRATION Theories of Interchange of Gases in the Lungs and in the Tissues. The above discussion is on the basis of the mechanical interpretation of the transfer of gases in the lungs and in the tissues. By this theory it is assumed that the oxygen passes from the air in the lungs through the moist pulmonary membrane of the alveoli to the capillary walls into the blood-plasma, obeying the physical laws of gas diffusion. Likewise in the tissues this theory pre- supposes the difference in the mechanical tension in the capillary blood- plasma, the lymph, and the living tissue will lead to diffusion of the oxygen in the direction of lowest pressure. Some facts have indicated that we cannot account for the transference of oxygen by the purely mechanical theory. The idea has been advanced that the living epithelial wall of the lung, as well as that of the capillary, exerts a distinct influence on the passage of oxygen of such nature as might be re- garded as a secretion of this gas. This theory finds some additional support in the fact that in the air bladders of certain fishes a distinct secretion of oxygen has been proven. THE NERVOUS REGULATION OF THE RESPIRATORY APPARATUS. Like all other functions of the body the discharge of which is necessary to life, the respiratory movement is essentially an involuntary act. Unless this were the case, life would be in constant danger, and would cease on the loss of consciousness for a few moments, as in sleep. It is, however, of ad- vantage to the body that respiration should be to some extent under the control of the will. For, were it not so, it would be impossible to perform those respiratory acts such as speaking, singing, and the like. The Respiratory Nerve Center. It has been known for centuries that there exists a region of the central nervous system on the destruction of which both respiration and life cease. Flourens, 1842, after many series of experiments as to the exact position of what he called the "knot of life" (nceud vital], placed it in the fourth ventricle, at the point of the V in the gray matter at the lower end of the calamus scriptorius; a district of consider- able size, 5 mm., on both sides of the middle line. Observers subsequent to Flourens have attempted to show that the chief respiratory center, on the one hand, is situated higher up in the nervous system, in the floor of the third ventricle (Christiani), or in the corpora quadrigemina (Martin and Booker, Christiani, and Stanier), or lower down in the spinal cord. The balance of experimental evidence, however, is to prove that the sole centers for respira- tion are in a limited district in the medulla oblongata in close connection with the vagus nucleus on each side, with which they are probably identical. The destruction of this region stops respiration. If the center be left in connection with the muscles of respiration by their nerves, although the THE RESPIRATORY NERVE CENTER 273 remainder of the central nervous system be separated from it, respiration continues. It may be considered almost certain that the medullary center is the only true respiratory center. Langendorff states that in newly born animals in which the medulla has been immediately cut across at a level a few millimeters below the point of the calamus scriptorius, respiration con- tinues for some time, but this is questionable. Normal respiration does not occur after separation of the bulb from the cord, and the so-called respiratory movements noticed by Langendorff are merely tetanic contrac- tions of the respiratory muscles in which often enough other muscles take part. The action of the medullary center is to send out impulses during in- spiration, which cause contractions of the inspiratory muscles — a, of the nostrils and jaws, through the facial and inferior division of the fifth nerves; b, of the glottis, chiefly through the inferior laryngeal branches of the vagi; c, of the intercostal and other muscles which produce raising of the ribs, chiefly through the intercostal nerves, and d, of the diaphragm, through the phrenic nerves. If any one of these sets of nerves be divided, respiratory movements of the corresponding muscles cease. Similarly it may be supposed that the center sends out impulses during expiration to certain other muscles. It has been suggested, however, that the center is double, that it is made up of inspiratory cells which are constantly in action, and of an expiratory group of cells which act less generally, inasmuch as ordinary tranquil expiration is seldom more than an elastic recoil, and not a muscular act to any marked degree. The respiratory center is also bilateral, as has been proven by the method of antero-posterior section of the medulla. The tracts from each half of the center are separate and distinct. If the cervical cord be split into a right and left half, and one side sectioned at the level of the second cervical verte- bra, then the respiratory movements of that side of the diaphragm cease while on the opposite side they continue their rhythm. Assuming this view of the quadruple nature of the respiratory centers to be correct, there is some difference of opinion of the exact mode of action; it is thought that the center may act automatically, but normally is influenced by afferent impulses from the periphery, as well as by impulses passing down from the cerebrum. The center is, in other words, both automatic and reflex. It will be simplest to discuss its reflex function first. Action of Afferent Stimuli on the Respiratory Rhythm. Action of the vagi. If both vagi be divided in the neck, the respirations become much slower and deeper. This may be the case, but to a less marked degree, if one of the nerves is divided instead of both. If the central end of the divided nerve be stimulated with a weak but properly adjusted strength of interrupted current, the effect is that the respirations are quickened, and if the stimuli are properly regulated the normal rhythm of respiration may 18 274 RESPIRATION be resumed. If the stimuli be repeated with stronger currents, the breathing is brought to a standstill, sometimes at the height of inspiration, by tetanus of the diaphragm. Usually, however, stimulation of the central end of the divided vagus produces still greater slowing than that which follows the division so that the respirations cease with the diaphragm in a condition of complete relaxation. The action of the vagus may be to call forth either inspiration or expira- tion— the impulses passing up the vagi being necessary to the production of the normal respiratory rhythm. The fibers of the vagus are used under the following circumstances: those fibers which tend to inhibit expiration and to stimulate inspiration are stimulated at their origin in the lung when the on- off FIG. 239. — The Effect of Stimulating the Vagus Nerve on Respiratory Rate. The stimulus was applied between the points " on " and " off." The inhibition lasts some seconds after the stim- ulus is removed. Time in seconds. The intratracheal pressure is recorded. lung is empty and in a condition of expiration, and the fibers which tend to inhibit inspiration and to promote expiration are stimulated when the lung is fully expanded. The afferent impulses by this view are the results of mechanical stimulation, and do not depend altogether upon the chemical nature of the gases within the pulmonary alveoli. Action of the Superior Laryngeal Nerves. If the superior laryngeal branch of the vagus be divided, which usually produces no apparent effect, and the central end be stimulated, the effect is very constant, — respirations are slowed, but there is a tendency toward expiration, as is shown by the contraction of the abdominal muscles. Thus, the vagus contains fibers which stimulate inspiration and inhibit expiration, as well as other fibers which have the reverse effect ; while the superior laryngeal fibers inhibit in- spiration and stimulate expiration. The superior laryngeal nerves are true expiratory nerves, and are nor- mally set in action when the mucous membrane of the larynx is irritated. They are not in constant action like the vagi. Action of the Glosso-pharyngeal Nerves. It has been ascertained, by the researches of Marckwald, that while division of the glosso-^)haryngeal nerves produces no effect upon respiration, stimulation of them causes in- hibition of inspiration for a short period. This action accounts for the very necessary cessation of breathing during swallowing. The effect of the stimu- lation is only temporary, and is followed by normal breathing movements. Action of Other Sensory Nerves. The respiratory center is in- AUTOMATIC ACTION OF THE RESPIRATORY CENTERS 275 fluenced strongly by afferent nerve impulses having their origin in general sensory nerves, particularly the nerves of the skin. Cold water suddenly applied to the surface of the skin is almost invariably followed by a deep inspiration. Stimulation of the splanchnics and of the abdominal branches of the vagi produces expiration. Stimulation of the isolated sciatic nerve of the dog or the rabbit causes a marked acceleration both of the rate and the amplitude of the respiratory movements, see figure 246. This accelera- tion is due to afferent impulses which reach the respiratory center in the me- dulla over sensory paths, paths which are not necessarily special respiratory afferent paths, but rather are general afferent paths which affect the respira- tory center through their numerous collaterals in the brain stem. It must be remembered that, although on stimulation many sensory nerves may be made to produce an effect upon the respiratory centers, there is no evidence to show that any one of them, except the vagi, is constantly in action. The vagi indeed are, as far as we know, the normal regulators of respiratory movements, yet one must remember that it is possible reflexly to influence the respiration rate and depth through reflexes that may have their sensory origin in any part of the body. The respiratory center is also influenced by nerve activity of the cerebral cortex, psychic activity. This is illustrated by the limited voluntary control of the respiration movements. Automatic Action of the Respiratory Centers. Although it has been very definitely proved that the respiratory centers may be affected by afferent stimuli, and particularly by those reaching them through the vagi, there is reason for believing that the center is capable of sending out efferent impulses to the respiratory muscles without the action of any afferent stimuli. Thus, if the brain be removed above the bulb, respiration continues. If the spinal cord be divided immediately below the bulb, the facial and laryngeal respiratory movements continue, although no afferent impulses can reach the center except through the cranial sensory nerves, and these indeed may be divided without producing any effect, when the bulb and cord are intact. As has been shown, too, respiration continues when the vagi are divided. Isolation of the respiratory center from its sensory relations does not destroy respiratory movements so long as the motor paths through the phrenic nerve are intact. All of these experiments render it highly probable that afferent impulses are not required in order that the respiratory centers should send out efferent impulses to the respiratory muscles. The center, then, is auto- matic. Method of Automatic Stimulation of the Respiratory Center. The respiratory center is capable of working automatically apart from afferent impulses, and this fact has been explained by the supposition that it is stimu- lated to action by the condition of the blood circulating through it. When the blood becomes more and more venous the action of the center becomes 276 RESPIRATION more and more energetic, and if the air is prevented from entering the chest, the respiration in a short time becomes very labored. If the aeration of the blood is much interfered with, not only are the ordinary respiratory muscles employed, but also those muscles of extraordinary inspiration and expira- tion which have been previously enumerated. Thus, as the blood becomes more and more venous, and by venous we mean that the blood contains a relatively large amount of carbon dioxide and a diminished amount of oxygen, the action of the medullary center becomes more and more profound. The question has been much debated as to what quality of the venous blood it is which causes this increased activity; whether it is its deficiency of oxygen or its excess of carbon dioxide. It has been answered to some extent by ex- periments which offer no obstruction to the exit of carbon dioxide, as when an animal is placed in an atmosphere of nitrogen. Under these conditions dyspnea occurs, showing that blood which contains a diminished amount of oxygen stimulates the cells of the respiratory center. On the other hand, if the normal amount of oxygen is supplied while the carbon dioxide of the blood is prevented from escaping and thus allowed to accumulate in the blood, there is also a great increase in the respiratory activity of the center; an excess of carbon dioxide in the blood, flowing through the respiratory center, stimulates the cells to greater activity. It is highly probable, there- fore, that the respiratory centers may be stimulated to action both by the absence of sufficient oxygen in the blood circulating in it, and by the presence of an excess of carbon dioxide. These facts are particularly well supported by the experiments of Zuntz who varied the oxygen and the carbon-dioxide content of the air breathed, and measured the volume breathed per minute. When the oxygen of the air breathed was reduced by 10 to 50 per cent, the air breathed was increased only slightly, 5 to 10 per cent. When the oxygen of the air was reduced by 60 per cent, the volume of air breathed was increased 30 to 40 per cent, and even more. Other observations show us that the oxygen in the blood in these experiments will fall in much less per cent than the reduction in the oxygen of the air would lead us to suspect. When Zuntz kept the oxygen content of the air about constant, but in- creased the carbon-dioxide content, then the amount of air breathed was greatly increased. Air containing 18.4 per cent of oxygen and 11.5 per cent of carbon dioxide increased the amount breathed per minute from 7.5 liters to 32.5 liters. These experiments indicate that within the limits of the normal variations in blood the carbon dioxide has a much greater influ- ence than oxygen on the irritability of the cells of the respiratory center. But this is not all, since it has been observed by Marckwald that the medullary center is capable of acting for some time in the absence of any circulation, and after excessive bleeding. The view taken by this author with regard to the action of the center is as follows: The respiratory center RESPIRATORY MOVEMENTS AT BIRTH 277 is set to act by the condition of its metabolism, much in the same way as the heart is set to beat rhythmically. When anabolism is completed, catab- olism or discharge occurs, and this alternate but crude and spasmodic action will occur without a definite blood supply so long as the centers are properly nourished and stimulated by their own intercellular fluid. It is unreasonable to think, however, that the respiratory center is independent of the character of the blood supply, either as regards quantity or quality of the blood. It has also been shown that the presence of the products of great muscular metabolism in the blood will greatly increase the irritability of the respiratory center, even if the blood itself be not particularly venous in character. The Establishment of Respiratory Movements at Birth. From the preceding paragraph it appears that the regulation of the respiratory movements is normally due to the automaticity of the respiratory center as influenced, first, by the blood flowing through it and, second, by the afferent nerve impulses which reach the center. The fetus in the womb is supplied by arterial blood from the blood-vessels of the mother. The fetus does not ordinarily give respiratory movements before birth, but it may be made to do so by experimental procedure. At birth the placental circulation is sud- denly interrupted, and the blood rapidly increases in venosity until the skin, lips, and mucous membranes are very cyanotic in appearance. It is at this time that the respiratory center begins its rhythmic discharges, being aroused by the direct stimulating effects of the strongly venous blood. It is more than possible that the irritability of the center is also increased by the stimu- lation of the skin by the air, the contact with clothing, and the hands of the nurse. We have already seen that cutaneous stimulation leads to increase in both respiratory rate and amplitude even in the adult. The primary stimulus for the establishment of the respiratory rhythm at birth, then, is the venosity of the blood, but this cause is supported by the general reflexes which reach the respiratory center. Certain Special Types of Respiration. Whatever the exact quality of the venous blood which excites the respiratory center to produce normal respirations, there can be no doubt that, as the blood becomes more and more venous from obstruction to the entrance of air into the lung, or from the blood not taking up from the air its usual supply of oxygen, the respiratory center becomes either less or more active and excitable. Conditions ensue which have received the names Apnea (diminished breathing), Hyper pnea (excessive breathing), Dyspnea (difficult breathing), and Asphyxia (suffoca- tion). Apnea. This is a condition of diminished respiratory movement. When we take several deep inspirations in rapid succession by voluntary effort, we find that we can do without breathing for a much longer time than usual; in other words, several rapid respirations seem to inhibit for a time normal 278 RESPIRATION respiratory movements. The reason for this partial cessation of respira- tion, or apnea, is not that we overcharge our blood with oxygen, as was once thought, for Hering has shown that animals in a condition of apnea may have less oxygen in their blood than in a normal state, although the carbon dioxide is less. It is probable that the cause of apnea is that by rapid in- flations of the lungs impulses pass up by the vagi, by means of which in- spiration is after a while inhibited; or that by the repeated stimulation of the center by vagus impulses which result in rapid respiratory movements, anabolism is at last arrested. Apnea is with difficulty produced, if at all, when the vagi are divided. Asphyxia. The condition of stress in the respiratory apparatus brought about by insufficient respiratory activity leads to a condition of asphyxia. Progressive asphyxiation may be brought on by anything which interferes with the normal interchange of the respiratory gases of the blood. Asphyxia may be produced by the prevention of the due entry of oxygen into the blood, either by direct obstruction of the trachea or other part of the respiratory passages, or by introducing instead of ordinary air a gas devoid of oxygen, or, by interference with the due interchange of gases between the air and the blood. The symptoms of asphyxia may be divided into three groups, which correspond with the stages of the condition which are usually recognized; these are: i, the stage of exaggerated breathing, hyperpnea; 2,. the stage of convulsions, dyspnea; 3, the stage of exhaustion, asphyxiation. In the first stage the breathing becomes more rapid and at the same time deeper than usual, the inspirations at first being especially exaggerated and prolonged. This is soon followed by a similar increase in the expiratory efforts being aided by the muscles of extraordinary expiration. This stage is usually called hyperpnea. Hyperpnea soon passes into a condition of labored breathing in which there is marked increase of the force of the expiratory as well as the inspiratory act, a condition described as dyspnea. All the muscles capable of aiding either directly or indirectly in respiration are ulti- mately brought into action. These respiratory convulsions are followed by rather sudden onset of paralysis of the respiratory center and death. The conditions of the vascular system in asphyxia are: i, more or less interference with the passage of the blood through the systemic and the pul- monary blood-vessels; 2, accumulation of blood in the right side of the heart and in the systemic veins; 3, circulation of impure (non-aerated) blood in all parts of the body, especially through the respiratory center. Cheyne-Stokes' breathing is a rhythmical irregularity in respirations which has been observed in various diseases. Respirations occur in groups; at the beginning of each group the inspirations are very shallow, but each succes- sive breath is deeper than the preceding, until a climax is reached, after which the inspirations become less and less deep, until they cease altogether for EFFECTS OF VITIATED AIR 279 a time, after which the cycle is repeated. This phenomenon appears to be due to the want of action of some of the usual cerebral influences which pass to and regulate the discharges of the respiratory center. Effects of Vitiated Air. Ventilation. As the air expired from the lungs contains a large proportion of carbon dioxide and a minute amount of organic matter, it is obvious that if the same air be breathed again and again, the proportion of carbon dioxide and organic matter in it will con- stantly increase till it becomes unfit to breathe; long before this point is reached, however, uneasy sensations occur, such as headache, languor, and a sense of oppression. It is a remarkable fact, however, that the organism after a time adapts itself to a very vitiated atmosphere, and that a person soon comes to breathe, without sensible inconvenience, an atmosphere which, when he first enters it, feels intolerable. Such an adaptation, however, can take place only at the expense of a depression of all the vital functions, which must be injurious if long continued or often repeated. This power of adapta- tion is well illustrated by an experiment of Claude Bernard. If a sparrow is placed under a bell-glass of such size that it will live for three hours, be taken out at the end of the second hour (when it could have survived another hour), and a fresh healthy sparrow introduced, the latter will die at once. It must be evident that provision for a constant and plentiful supply of fresh air, and the removal of that which is vitiated, are of greater importance than the actual cubic space per person of occupants. Not less than 2,000 cubic feet per individual should be allowed in sleeping apartments (barracks, hos- pitals, etc.), and with this allowance the air can be maintained at the proper standard of purity only by such a system of ventilation as provides for the supply of 1,500 to 2,000 cubic feet of fresh air per person per hour. Effects of Breathing Gases Other than the Atmosphere. Asphyxiation is produced by the direct poisonous action of such gases as carbon monoxide, which is contained to a considerable amount in common coal gas. The fatal effects often produced by this gas (as accidents from burning charcoal stoves in small, close rooms) are due to its entering into combinations with the hemoglobin of the blood-corpuscles and thus preventing the formation of oxyhemoglobin because of the more stable carbon-monoxide hemoglobin. The partial pressure of oxygen in the atmosphere may be considerably in- creased without much effect in displacing the carbon monoxide, hence this is rapidly fatal when breathed. Hydrogen may take the place of nitrogen with no marked ill effect, if the oxygen is in the usual proportions. Sul- phureted hydrogen destroys the hemoglobin of blood and thus produces oxygen starvation. Nitrous oxide acts directly on the nervous system as a narcotic, and may also form a compound with hemoglobin. Certain gases, such as carbon dioxide in more than a certain proportion, sulphurous acid gases, am- monia, and chlorine, produce spasmodic closure of the glottis and prevent respiration. 280 KESPIRATION Alteration in the Atmospheric Pressure. The normal condition of breath- ing is that the oxygen of the air breathed should be at the pressure of 20.96 per cent of the atmosphere, that per cent of 760 mm. of mercury, or 159 mm. But it is found that life may be carried on by gradual diminution of the oxygen pressure to considerably less than one-half of this, to a partial pressure of 76 mm. of oxygen, i.e., the oxygen of one-half an atmosphere. This pressure is reached at an altitude above 15,000 feet.* Any pressure less than this may begin to produce alterations in the relations of the gases in the blood, and if an animal is subjected suddenly to a marked decrease of barometric pressure, and so of oxygen pressure (below 7 per cent of oxygen), it is thrown into convulsions. It is found that the gases are set free in the blood-vessels, no doubt carbon dioxide and oxygen as well as nitrogen, although the latter is the only one of the three gases the presence of which has been proven in the vessels in death from this condition of affairs. The other gases are said to be reabsorbed. Other derangements may precede this, bleeding from the nose, dyspnea, and vascular incoordina- tion, etc. On the other hand, the oxygen may be gradually increased to a con- siderable extent without marked effect, even to the extent of 8 or 10 atmos- pheres, but when the oxygen pressure is increased up to 20 atmospheres the animals experimented upon by Paul Bert died with severe tetanic convulsions. THE EFFECT OF RESPIRATION ON THE CIRCULATION. As the heart, the aorta, and pulmonary vessels are situated in the air- tight thorax, they are exposed to a certain alteration of pressure when the capacity of the latter is varied in respiration. The disturbance of pressure which occurs during inspiration causes, first, a decrease in the intrathoracic cavity, a decrease in pressure which affects all the organs of the thorax — the lungs, the great blood-vessels, the heart. The expansion of the elastic lungs counterbalances this change in pressure in part, but it never does so entirely, since part of the pressure within the lungs is expended in overcoming their elasticity. The amount thus used up increases as the lungs become more and more stretched, so that the intrathoracic pressure during inspiration, as far as the heart and great vessels are concerned, never quite equals the intra- pulmonary pressure, and at the conclusion of inspiration is considerably less than the atmospheric pressure. It has been ascertained that the amount of the pressure used up in the way above described varies from 5 to 7 mm. of mercury in ordinary inspiration, to 30 mm. of mercury at the end of a deep inspiration. So it will be understood that the pressure to which the heart and great vessels are subjected diminishes as inspiration progresses, and at * For an interesting account of the symptoms produced by diminished atmospheric pressure by very high altitudes, consult Whymper's "Travels amongst the Andes of the Equator." EFFECT OF RESPIRATION ON THE CIRCULATION 281 its minimum is less by from 7 to 30 mm. than the normal atmospheric pres- sure, 760 mm. of mercury. It will be understood from the accompanying diagram how an increase in the volume of the thorax will have the effect of pumping blood into the heart from the veins. During inspiration the pressure outside the heart and great vessels is diminished, and they, by virtue of their elasticity, have therefore a tendency to expand and to diminish the intra- vascular pressure. The diminution of pressure within the veins passing to the right auricle and within the right auricle itself, will draw the blood into the thorax, and so assist the circulation. This suction action of the thorax is the cause of the slight negative pressure of the ventricle previously de- scribed. The effect of more blood in the right auricle will, cczteris paribus, increase the amount passing through the right ventricle, and through the lungs into the left auricle and ventricle, and thus into the aorta. This all tends to increase the blood pressure. The effect of the FIG. 240. — Diagram of an Apparatus Illustrating the Effect of Inspiration upon the M >art and Great Vessels within the Thorax. I, The thorax at rest; II, during inspiration; D represents the diaphragm when relaxed; D', when contracted (it must be remembered that this position is a mere diagram), i.e., when the capacity of the thorax is enlarged; H, the heart; V, the veins entering it, and A, the aorta; Rl, LI, the right and left lung; T, the trachea; M, mercurial manometer in connection with pleura. The increase in the capacity 9f the box representing the thorax is seen to dilate the heart as well as the lungs, and so to pump in blood through V, whereas the valve pre- vents reflux through A . The position of the mercury in M shows also the suction which is taking place. (Landois.) diminished pressure upon the pulmonary vessels will also help toward the same end, an increased flow through the lungs, so that, as far as the mechani- cal effects on the heart and its veins are concerned, inspiration increases the blood pressure in the arteries. The effect of inspiration upon the aorta and its branches within the thorax would be, however, contrary; for as the external pressure is diminished, the vessels would tend to expand, and thus to diminish the tension of the blood within them, but, inasmuch as the rela- tive variation in pressure on the large arteries is slight, the diminution of arterial tension caused bv this means will be insufficient to counteract the 282 RESPIRATION increase of blood pressure produced by the effect of inspiration upon the volume of discharge of the veins of the chest, and the balance of the whole action would be in favor of an increase of blood pressure during the inspira- tory period. When a blood-pressure tracing is taken at the same time that the respiratory movements are being recorded, it will be found that, although, speaking generally, the arterial tension is increased during inspiration, the maximum of arterial tension does not correspond with the acme of inspira- tion, figure 241. In fact, at the beginning of inspiration the pressure con- tinues to fall for a brief moment, then gradually rises until the end of inspiration, and continues to do so for a moment after expiration has com- menced. For explanation of the influence of heart rate- in this variation of blood pressure, associated with the respiratory movement, see page 181. In ordinary expiration all this would be reversed, but if the abdominal muscles are violently contracted, as in extraordinary expiration, the same FIG 241. — Comparison of Blood -Pressure Curve with Curve of Intrathoracic Pressure (To be read from left to right.) a is the curve of blood pressure with its respiratory undulations, the slower beats on the descent being very marked; b is the curve of intrathoracic pressure obtained by connecting one limb of a manometer with the pleura! cavity. Inspiration begins at * and expira- tion at e. ihe intrathoracic pressure rises very rapidly after the cessation of the inspiratory ettort, and then slowly falls as the air issues from the chest; at the beginning of the inspiratory effort the fall becomes more rapid. (M. Foster.) relative effect would be produced as by inspiration. The immediate effect during inspiration of the diminished intrathoracic pressure upon the pul- monary vessels is to produce an initial dilatation of both artery and veins, and this delays for a moment the passage of blood toward the left side of the heart, resulting in an initial fall in the arterial pressure, but the fall of blood pressure is immediately followed by a steady rise, since the flow is increased by the initial dilatation of the vessels. The converse is the case with ex- piration. As, however, the pulmonary veins are more easily dilatable than the pulmonary artery, their greater distensibility increases the flow of blood as inspiration proceeds, while during expiration, except at its beginning, this property of theirs acts in the opposite direction, and diminishes the flow. Thus, at the beginning of inspiration the diminution of blood pressure, which LABORATORY EXPERIMENTS 283 commenced during expiration, is continued, but after a time the diminution is succeeded by a steady rise. The reverse is the case with expiration — at first a rise and then a fall. As regards the effect of expiration, the capacity of the chest is diminished and the intrathoracic pressure returns to the normal, which is still slightly below the atmospheric pressure. The effect of this on the veins is to in- crease their extravascular and so their intravascular pressure, and to di- minish the flow of blood into the left side of the heart, and with it the general blood pressure. Ordinary expiration does not produce a distinct obstruction to the circulation, as even when the expiration is at an end the intrathoracic pressure is less than the extrathoracic. The effect of violent expiratory efforts, however, does have a distinct action in obstructing the current of blood through the lungs, as seen in the congestion in the exaggerated con- dition of straining, this condition being produced by pressure on the entire group of pulmonary vessels. There are other mechanical factors, such, for example, as the effect of the abdominal movements, both in inspiration and in expiration, upon the arteries and veins within the abdomen and of the lower extremities, and the influence of the varying intrathoracic pressure upon the pulmonary vessels, both of which ought to be taken into consideration. As regards the first of these, the effect during inspiration — as the cavity of the abdomen is diminished by the descent of the diaphragm — should be twofold: on the one hand, blood would be sent upward into the chest by compression of the vena cava. inferior; on the other hand, the passage of bbod down- ward from the chest in the abdominal aorta, and upward in the veins of the lower extremity, would be to a certain extent obstructed. LABORATORY EXPERIMENTS IN RESPIRATION. 1. Respiratory Rate in Man. Count your respirations for from 2 to 4 minutes while sitting quietly, and determine the average number per minute. Repeat the counting after standing for 5 minutes, and after brisk exercise. These determinations involve the element of consciousness, under which condition it is difficult for a person to breathe with his normal rate and depth. Make a series of determinations of respiratory rates of persons who are sitting quietly but unconscious of your determinations. Count the rates in a number of persons of different ages; where possible, take into considera- tion height, weight, etc. Tabulate the results for a comparison and for future reference. 2. The Character of Respiratory Movements in Man. A number of instruments have been devised for measuring human respiratory move- ment, many of which measure the change in diameter of the chest in respira- 284 RESPIRATION tory movemen- Adjust one of these, for example Burdon-Sanderson's stethograph, to the thorax, and record the movement of the receiving tam- bour on a smoked-paper kymograph which travels at the rate of i cm. per second. This record, called a stethogram, will exhibit the respiratory rate, the relative time of the inspiratory and expiratory phases, and the character of each. 3. The Actual Change of Diameter in the Chest in Respiration. Use a caliper provided for the purpose and measure the dorso-ventral diam- eter of the chest at a series of points along the sternum, taking the reading FIG. 242. — Change in Diameter of the Body in Respiration, Costal Type, a, Outline of the body in forced expiration. In the heavy continuous line, b, the outer margin indicates the contour of the body in ordinary inspiration and the inner margin that of ordinary expiration, c, Contour of forced inspiration. (After Hutchinson.) at the height of the inspiratory phase and of the expiratory phase in ordi- nary respiration. Repeat the measurement in forced respiration. Map the results on millimeter paper, as indicated in figure 242. Repeat these measurements in the transverse diameter at the first, fifth, and tenth ribs. Using the chest pantograph, figure 243, record the outline of the chest at the level of the middle of the sternum during expiration and at the end of inspiration. 4. The Volume of Air Breathed by Man. Determine the average volume of air breathed per respiration, using Hutchinson 's spirometer, figure 235, set the instrument at the zero point, exhale into the instrument through the tube, using all possible care to breathe with your normal rate and depth. Better results will be obtained by taking the average from sets of ten consecu- tive inspirations into the instrument. From the average of the volume per VITAL CAPACITIES 285 respiration, and the average number of respirations per minute, determined in experiment i, calculate the amount of air breathed per hour and per day. 5. Vital Capacities. Using the spirometer as in the preceding experiment, set the instrument at zero and exhale into it: a, Begin with the fullest possible inspiration and exhale the greatest possible amount of air from the lungs. This is known as the vital capacity. b, Beginning at the end of an ordinary expiration exhale into the instru- ment the greatest possible amount. This is called the reserve air. c, Following ordinary inspiration exhale into the instrument until you reach the ordinary state of expiration. This involves the conscious fixing of two points in the respiratory act, namely, the summit of inspiration and expiration, which are ordinarily automatically adjusted by the body. The error of the determination is therefore great. It is better to make this measure- ment in sets of ten, as in the preceding experiment, and take the average. FIG. 243. — The Chest Pantograph for Recording the Outlines of the Chest. The fixed point in the instrument is /; the points a, b, x, y, are movable joints; when point t is made to trace the outline of the chest, point r will give a corresponding movement and can be made to trace this movement on recording paper. (Hall.) This reduces the error. This quantity of air is known as the tidal air. One can measure the tidal air and the reserve air together, check them against the sum of the twro, as in a and b separately. The sum of the tidal and reserve air taken from the vital air will leave the amount which one may inspire over and above that in the chest at the end of ordinary inspiration. This is called complemental. The complemental can be measured by inspiring the air from the spirometer, but this is not good hygiene where large numbers are using the same instrument, unless the instrument be thoroughly cleaned before the inspiration is taken. 6. The Respiratory Pressure in Man. Measure the respiratory pressure, the pressure of the air in the air- passages, by means of the mercury manometer, or by a graduated Marey's tambour. Connect the piece of 280 RESPIRATION gas tubing with the proximal limb of the mercury manometer and provide it with a glass mouthpiece. Insert this mouthpiece well back into the cavity of the mouth, closing the lips firmly about it, leaving the pharyngeal muscles relaxed. Note the variations in pressure at the height of ordinary inspiration and expiration, with the nasal passages open. Repeat with forced inspiration and expiration, close the nasal passages, and make the maximal expiratory and inspiratory effort. The manometer may be ad- justed to write on the smoked paper, or one may read the variations directly from the manometer schedule, in which case it facilitates the reading if one clamps the rubber tube at the moment the reading is desired. 7. Demonstration of Carbon Dioxide in Expired Air. Arrange two flasks, as in figure 244, filling each one-third full of baryta water, or FIG. 244. — Apparatus for Demonstrating Excess of CO2 in Expired Air. Flasks filled with lime-water. lime-water. Close the lips around the mouthpiece of the apparatus and inhale and exhale the air through it; close the nostrils if necessary. The inspired air will come through a, the expired air out through b. The baryta water in b will quietly become clouded with a white precipitate, while that in a will remain clear or only very slightly clouded, showing the excess of carbon dioxide in expired air. 8. Quantitative Determination of Carbon Dioxide and Oxygen in Inspired Air and in Expired Air, by HempePs Method. Inspired Air. Fill a gas buret, see figure 236, with water and close the pinch- cock. Fill it with air taken outside the laboratory. Measure the vol- ume of gas contained at the ordinary temperature and barometric pressure of the laboratory. Connect with a potash pipet, drive the air over into the bulb of the pipet, shake it up until all the carbon dioxide is absorbed. Draw the air back into the buret and measure. The amount of carbon dioxide in the external air is usually so small that it is difficult to measure by this method. Now connect the buret with a pipet containing pyrogallic acid, run the air over into the pyrogallic-acid bulb and shake up thoroughly until no further excess is absorbed, then remeasure the excess in the buret. The loss in volume is due to the absorption of oxygen; the air remaining in the RESPIRATORY MOVEMENTS IN THE MAMMAL 287 huret is nitrogen. Compute the amount of carbon dioxide, oxygen, and nitrogen from the results of your test. Expired Air. Take a large sample of expired air by breathing through a large tube into a gallon aspirator bottle. This is large enough to hold six or eight expirations. Now fill the gas buret with a sample of this expired air and analyze as before, first for carbon dioxide, then for oxygen; com- pute the percentage of each gas, including nitrogen. The expired air will usually be found to have lost from 4 to 5 per cent of oxygen and have gained a little more than that quantity of carbon dioxide. From the percentages obtained in these experiments, and the volume of air breathed per unit of time, computed in experiment 4 above, determine the amount of carbon dioxide exhaled per hour per kilogram of weight for your own body. Compute also the amount of oxygen consumed. 9. The Rate and Character of ttie Respiratory Movements in the Mammal, a, The rate of respiration can be best determined by direct count per minute, an effort being made to keep the animal under as FIG. 245. — Arrangement of Tracheal Cannula and Marey's Tambour for Recording the Changes in Intratracheal Pressure during Respiration. (Langendorff.) nearly normal conditions as possible; make the same determinations on a cat, a dog, and guinea-pig, b, The character of the respiratory movements can be recorded by one of the various forms of stethograph adapted to the size of the animal, or by the arrangement shown in figure 245. It is usually better to make the determination with the animal under the influence of an anesthetic. 10. The Determination of Carbon Dioxide Given Off in the Mam- mal. This determination can be made only by placing the animal in a respiratory calorimeter, and making the following measurements: a. The amount of air which passes through the animal chamber, the calorimeter. b. The percentage of carbon dioxide in the air which is in the chamber. 288 RESPIRATION c. The percentage of carbon dioxide in the air which leaves the chamber. If the animal is small enough, for example, the guinea-pig or a mouse, the absorption tubes may be constructed of proper size to absorb all the carbon dioxide passing through the chamber, and the total quantity of any unit of time determined directly in grams. If now the animal is weighed at the moment it is introduced into the cage, then the amount of carbon dioxide per kilo weight can be quickly computed. Calorimeters for larger animals require a larger volume of ventilation, and the usual procedure is to measure the percentage in a sample as directed above. ii. The Nervous Mechanism of Respiratory Movement. a. The Effect oj Stimulating Cutaneous Nerves. Use a small dog or a cat for this experiment; anesthetize and introduce a tracheal tube with a side branch adapted for measuring the variations of pressure during respira- tion. Connect the free limb of the tracheal tube with an ether apparatus and adjust to secure constant anesthesia. Connect the side branch of the on FIG. 246.— ^Change in Respiration on Stimulating the Central End of the Sciatic Nerve. The rate is sharply increased and the amplitude more than doubled. The stimulation is between the points marked on and off, time in seconds. The inspiratory movement following the stimulation was greater than the limit of the recording tambour. tracheal tube with a Marey's recording tambour of medium size and supply with a comparatively delicate membrane. The amplitude of the move- ments of the tambour may be regulated by a screw compress on a connecting tube. Arrange an induction coil with platinum electrodes in the usual manner, figure 318, for stimulating, by means of the interrupted current. Record the results of the experiment along with the variations of blood pres- sure on a continuous-paper kymograph; the instrument should be supplied with a time signal, a stimulating signal, etc. DEMONSTRATION OF APNEA, DYSPNEA, AND ASPHYXIA 289 Now stimulate the skin of the abdominal region, the groin, with a com- paratively strong induction current, figure 246. Dissect out the sciatic nerve, cut it, stimulate the central end with a mild to medium strength of current. The stimulus should be graduated carefully, for there is often such a great increase in respiratory rate and volume that the animal may become overanesthetized. b. The Effect oj Stimulating the Vagus Nerve. Isolate and stimulate the vagus nerve with a medium strength of stimulus. The effect is usually complete inhibition of respiratory movements. By means of graduated stimuli one may demonstrate the accelerator effects from the stimulation of the vagus. Stimulate also the superior laryngeal, and compare with the effects of stimulating the whole vagus. c. The Effect oj Cutting the Vagus Nerves. Isolate both vagus nerves and section them as nearly at the same moment as possible. Be sure to mark on the tracing the exact moment at which the nerves are cut. This experiment should be performed with every accessory condition as constant as possible, and the animal should not be disturbed for one or two minutes so that the effects of the section will be recorded uncomplicated. The re- sult is always a marked deepening and slowing of the respiratory movements. d. The Effect oj Stimulating the Central End oj the Vagus. Upon stimu- lating the central end of the vagus after section, the respiration rate will be inhibited as in b, showing that the vagus nerves carry afferent respiratory fibers, figure 239. e. The Effect oj Stimulation oj the Phrenic Nerves. Isolate the right phrenic nerve at its origin from the brachial plexus and stimulate it with a medium strength of stimulus. Upon stimulating a nerve the diaphragm will remain in contraction and the record will show that the thorax is in the inspiratory phase. Section this nerve and note the change in the character of respiratory movements; make direct observations on the diaphragm, examining from the abdominal side. 12. Demonstration of Apnea, Dyspnea, and Asphyxia. Produce deep anesthesia, then disconnect the ether bottle and connect the tracheal tube with a hand bellows. Produce deep and forced artificial respiration for twenty to thirty seconds. Stop the artificial respiration ; the animal will re- main quiet without any effort at breathing. This is the condition of apnea. Allow the animal to recover its normal respiration rate and again produce deep anesthesia. Now clamp off the tracheal tube so that the animal can no longer receive air and leave it so until death. As the blood becomes more and more venous there will first be a marked increase in the respiration rate and depth. This is known as hyperpnea. This stage is followed by one of increasing respiratory amplitude in which the accessory respiratory mus- cles not previously active are brought into forcible contractions, both inspira- 19 290 RESPIRATION tory and expiratory phases are now forced, dyspnea. The movements con- tinue to increase, and the muscles of the neck, larynx, mouth, and nostrils now take part. There is rather a sudden decrease in the respiratory move- ments, an extension of the limbs, and gasping movements of the mouth, after which the animal remains quiet, death being produced by asphyxia. 13. Respiratory Interchange, Calorimetry. The experiments are conducted in such a manner that comparative analyses may be made between the air inspired and that expired. Generally an animal is placed in a cham- ber, called the respiratory chamber, which is then closed except for two openings, one for the entrance of the inspired air, the other for the escape of expired air. Some form of pump is used for renewing the air in the chamber. . Both the inspired and expired air is made to pass through agents which will absorb the contained carbon dioxide, such as baryta water or soda lime, and in turn through agents which will absorb the watery vapor. When the experiment is completed the differences between the two are determined. The difference in oxygen has to be calculated, and is open to error. The famous respiratory chamber of Pettenkofer is large enough to per- form such experiments on man, and is of very elaborate construction. But the most perfect apparatus assembled for this purpose is the respira- tion calorimeter of Atwater constructed for man, and the respiration ap- paratus of Armsby for cattle. CHAPTER VII SECRETION IN GENERAL ALL tissues of the body produce certain chemical changes as a result of their protoplasmic activity. But in certain cells chemical elaborations have come to be the chief function, the cells have been differentiated in that direc- tion, and the name secreting tissue or gland tissue is applied. The end result of metabolism in gland tissue is the extrusion on the free borders of the cells of the products of their metabolism. The products are known as secretions and the process itself is the act of secretion. Certain secretions which are in the nature of waste products to the body as a whole, such as urine in the kidney, are often called excretions, but the use of the term should not be allowed to confuse the general similarity of this to other secretions as regards the physiological changes involved in its production. Most secretions accomplish some definite office in the economy of the body. Those that are discharged on some free mucous surface, as the saliva, gastric juice, tears, etc., are called external, or true secretions, or merely secre- tions. Substances that are discharged back into the blood stream later to influence the metabolism of tissues other than the ones which produced them, are called internal secretions. Gland cells, like other tissues, draw their nourishment from the blood and lymph. The product or secretion of gland cells may, in fact usually does, contain some of the substances found in the blood, but there are also present new materials elaborated by the cells, and even where the same sub- stance exists both in the secretion and in the blood and lymph it can make its appearance in the secretion only, under the control of the protoplasm of the gland cells. The saliva secreted by the salivary cells, for example, con- sists of about 98 to 99 per cent water containing in solution small quantities of certain salts, also found in the lymph, and a small percentage of the en- zyme, ptyalin. This enzyme is peculiar to the salivary secretion and is manu- factured by the salivary-cell protoplasm. As is well known, it acts vigorously in extreme dilution, hence the high per cent of water in the secretion. The passage of water from a solution as concentrated as blood plasma to a solu- tion as dilute as saliva requires a high amount of osmotic energy, an amount that can be supplied only from the chemical energy liberated by the cell in its protoplasmic activity. After the removal of the special organ by which each secretion is manufactured, the secretion is no longer formed. Cases 291 SECRETION IN GENERAL sometimes occur in which the secretion continues to be formed by the natural organ, but, not being able to escape toward the exterior, on account of some obstruction, is reabsorbed and accumulates in the blood. It may be dis- charged from the body in other ways; but these are not instances of true vicarious secretions, and must not be so regarded. Organs and Tissues of Secretion. The principal secreting organs are the following: i, The serous and synovia! membranes; 2, The mucous mem- branes with their special glands, e.g., the buccal, gastric, and intestinal glands; 3, The salivary glands and pancreas; 4, The liver; 5, The mammary glands; 6, The lachrymal glands; 7, The kidney and skin; and 8, the testes and ovaries. The special structure and functions of the secreting organs will be given in greater detail in the chapters which immediately follow. The general types of structure and general conditions that influence the functions are introduced at this point. Structural Types of Secreting Organs. Serous and Synomal Type. The serous membranes form closed sacs lining visceral cavities like the abdominal, pericardial, or pleural cavities. The organs are, as it were, pushed into this s:ic and carry before them an investment of membrane. The serous membranes consist of a single layer of flattened polygonal cells resting on a supporting membrane of connective tissue, supporting a ramification of blood- vessels, lymphatics, and nerves. In some instances, i.e., synovial membranes, the secreting layer is in- creased by finger-like elevations. This type of secreting organ producer ordinarily only enough secretion to keep the surface moist. The Mucous Type. The mucous tracts, and different portions of e::ch of them, present certain structural peculiarities, adapted to the functions which each part has to discharge; yet in some essential characters the mucous membrane is the same, from whatever part it is obtained. In all the princi- pal and larger parts of the several tracts it presents an external layer of epithe- lium, situated upon a basement membrane, and beneath this a stratum of vascular tissue of variable thickness, containing lymphatic vessels and nerves. The vascular stratum, together with the basement membrane and epithelium, in certain cases is elevated into minute papillae and villi, in others depressed into involutions in the form of glands. But in the invaginations of the secreting membrane of gland cells, the supporting basement membrane and the network of capillaries are still reta ined in their relative position. With increasing complexity of involution the simple mucous membrane becomes packed away in an ap- parently solid mass. The equivalent of a large amount of secreting surface is thus condensed into a small space. In the process of invagination some differentiation occurs in that certain of the gland tubes become conducting and have their secretory activity somewhat reduced. But there is no distinc- tion that can be drawn between simple mucous membranes and gland cells. SECRETING GLANDS 293 Secreting Glands. The secreting glands present, amid manifold diversities of form and composition, a general plan of structure; but all are constructed with particular regard to the arrangement of the cells which has just been described. Secreting glands are classified according to certain structural types, as: i. The simple tubular gland, A, figure 247, examples of which are furnished by the follicles of Lieberkiihn, and the tubular peptic glands of the stomach. FIG. 247. — -Plans of Extension of Secreting Membrane by Inversion or Recession in the Forms of Cavities. A, Simple glands, viz., g, straight tube; h, sac; i, coiled tube. B, Multilocular crypts: k, of tubular form; /, saccular. C, Racemose or saccular compound gland : m, entire gland, show- ing branched duct and lobular structure; n, a lobule, detached with o, branch of duct proceeding from it. D, Compound tubular gland. (Sharpey.) They are simple tubes of mucous membrane, the walls of which are lined with secreting cells arranged as an epithelium. To the same class may be referred the elongated and tortuous sudoriferous glands. 2. The compound tubular glands, D, figure 247, form another division. These consist of main gland tubes, which divide and subdivide. Each gland may be made up of the subdivisions of one or more main tubes. The ulti- 294 SECRETION IN GENERAL mate subdivisions of the tubes are sometimes highly convoluted. They are formed of epithelium of various forms, supported by a basement membrane. The larger tubes may have an outside coating of fibrous areolar or muscular tissue. The salivary glands, pancreas. Brunner's glands, kidney, testes, with the lachrymal and mammary glands, are examples of this type, but presf nt more or less marked variations among themselves. 3. The racemose glands, in which a number of vesicles or acini are arranged in groups of lobules, C, figure 247. The Meibomian follicles are examples of this kind of gland. There seem to be glands of mixed character, com- bining some of the characters of the tubular with others of the racemose ty pe ; these are called tubulo-racemose or tubulo-acinous glands. The acini are formed by a kind of fusion of the walls of several vesicles, which thus combine to form one large cavity with recesses lined or filled with secreting cells. The smallest branches of the gland-ducts sometimes open into the centers of these cavities; sometimes the acini are clustered round the extremities, or by the sides of the ducts; but, whatever secondary arrangement there may be, all have the same essential character of rounded groups of vesicles containing gland-cells, and opening by a common central cavity into minute ducts, which in the large glands converge and unite to form larger and larger branches, and at length one common trunk which opens on a free surface. The Process of Secretion. The process of secretion is dependent upon the activity of the secreting cells. In the case of the water and salts the physical processes of filtration and diffusion may play a part. The chemical processes constitute the process of secretion properly so called, as distinguished from mere transudation spoken of above. In the process of secretion, various materials which do not exist as such in the blood are manu- factured by the agency of the gland-cells, using as a nutrient fluid the blood, or, to speak more accurately, the lymph which fills the interstices of the gland textures. Evidences in favor of this view are: i. That gland cells are constituents of ah1 glands, however diverse their outer forms and other characters, and they are placed in all glands on the surfaces or in the cavity whence the secre- tion is poured. 2. That certain materials of secretions are visible with the microscope in the gland cells before they are discharged. Thus, granules probably representing the precursors of the ferments of the pancreas may be discerned in the cells of that gland. Granules of uric acid are found in the cells of the kidneys of birds and fish, and fatty particles, like those of milk, in the cells of the mammary gland. Certain secreting cells, like the cells of the sebaceous glands, appear to develop, grow, and attain their individual perfection by appropriating nutri- ment from the fluid exuded by adjacent blood-vessels and building it up so that it shall form part of their own substance. In this perfected state the cells subsist for some brief time and then appear to dissolve, wholly or in part, and CIRCUMSTANCES INFLUENCING SECRETION 295 yield their contents to the peculiar material of the secretion. The changes which have been noticed from actual experiment in the cells of the salivary glands, pancreas, and peptic glands will be described more fully in the chapter on Digestion. Discharge of secretions from the glands may either take place as soon as formed, or the secretion may be long retained within the gland or its ducts. The former is the case with the sweat glands. But the secretions of those glands whose activity of function is periodical are usually retained in the cells in an undeveloped form during the period of the gland's inaction. When discharged into the ducts, the further course of secretions is affected: (1) partly by the pressure from behind; the fresh quantities of secretion pro- pelling those that were formed before. In the larger ducts, its propulsion is (2) assisted by the contraction of their walls. All the larger ducts, such as the ureter and common bile-duct, possess in their coats plain muscular fibers; they contract when irritated, and sometimes manifest peristaltic movements. Rhythmic contractions in the pancreatic and bile ducts have been observed, and also in the ureters and vasa deferentia. It is probable that the contractile power extends along the ducts to a considerable distance within the substance of the glands whose secretions can be rapidly expelled. Saliva and milk, for instance, are sometimes ejected with much force. Circumstances Influencing Secretion. The principal conditions which influence secretion are variations in the quantity of blood, and varia- tions in nerve impulses passing to the gland cells over secretory nerve fibers. An increase in the quantity of blood traversing a gland, as in nearly all the instances before quoted, coincides generally with an augmentation of its secretion. Thus the mucous membrane of the stomach becomes florid when, on the introduction of food, its glands begin to secrete. The mammary gland becomes much more vascular during lactation. All circumstances which give rise to an increase in the quantity of material secreted by an organ produce, coincidently, an increased supply of blood. But we shall see that a discharge of saliva may occur under extraordinary circumstances without increase of blood-supply, and so it may be inferred that this condition of increased blood- supply is not absolutely essential to the immediate formation of secretion, but that it favors the prolonged activity of glands. Influence of the Nervous System on Secretion. The process of secretion is largely regulated through the nervous system. The exact mode in which the influence is exhibited must still be regarded as somewhat obscure. In part, it exerts its influence by increasing or diminishing the quantity of blood supplied to the secreting gland, in virtue of the power which it exercises over the contractility of the smaller blood-vessels. It also has a more direct influence, as is described at length in the case of the ^ubmaxillary gland, upon the secreting cells themselves. This may be called trophic influence. Its influence over secretion, as \veil as over other functions of the body, may be 296 SECRETION IN GENERAL excited by causes acting directly upon the nervous centers, upon the nerves going to the secreting organ, or upon the nerves of other parts. In the latter case a reflex action is produced: thus the impression produced upon the sen- sory nerves by the contact of food in the mouth leads to afferent nerve impulses to the secretory center in the central nervous system which is reflected by the nerves supplying the salivary glands, and produces, through these, a more abundant secretion of the saliva. Through the nerves, various conditions of the brain also influence the secretions. Thus, the thought of food may be sufficient to excite an abundant flow of saliva. And, probably, it is the mental state which excites the abun- dant secretion of urine in hysterical paroxysms, as well as the perspirations, and occasionally diarrhea, which ensue under the influence of terror, and the tears excited by sorrow or excess of joy. The quality of a secretion may also be affected by mental conditions, as in the cases in which, through grief or passion, the secretion of milk is altered, and is sometimes so changed as to produce irritation in the alimentary canal of the child. CHAPTER VIII FOOD AND DIGESTION THE term digestion includes those changes taking place in the body which bring the materials of the food into such condition that they may be taken up by the blood and lymphatic vessels and thus rendered available for the metab- olism of the tissues. In the process the foods are rendered more soluble and more diffusible. Certain bodies which are already soluble and diffusible are converted into forms which are more available for the tissues; as an ex- ample cane-sugar, although both soluble and diffusible, cannot be readily used by the body until it is converted from a disaccharide to a monosaccharide. In fact few of the food materials are fit for immediate use when taken into the body and are therefore practically useless until digested. FOOD AND FOOD PRINCIPLES. We have been accustomed to classify foods into certain main groups, chiefly according to their chemical character, as follows : Proteids. Such as albumin, myosin, gluten, casein, etc.; gluco- proteid, nucleoproteid, etc.; gelatin, elastin, etc. These furnish nitrogen in available form. Carbohydrates. Such as starch, dextrose, cane-sugar, etc. Fats. Such as olein. Minerals. The various salines found in animal and vegetable food. Water. The classes of foods just enumerated usually exist in mixtures rather than in simple forms, as, for example, a beef roast contains a representative of each of the five classes enumerated, though it is composed chiefly of proteids and fats. The human body is capable of using materials of a great variety of forms, but most of these have the foods mixed in such a way as to give repre- sentatives of each of the classes above in certain general proportions. Nitrogenous Foods. The Flesh of Animals, e.g., beef, veal, mutton, pork, bacon, ham, chicken, eggs, milk, etc., are typical nitrogenous foods. Of these, beef and eggs are richest in nitrogenous matters, containing about 20 per cent. Mutton contains about i8 per cent, veal 16.5, and pork 10. Beef is firmer, more satisfying, and is supposed to be more strengthening than 297 298 FOOD AND DIGESTION mutton, whereas the latter is more digestible. The flesh of young animals, such as lamb and veal, is less digestible and less nutritious. Pork contains a large amount of fat and is, therefore, comparatively indigestible. PERCENTAGE COMPOSITION AND FUEL VALUE PER POUND OF SOME COMMON FOOD STUFFS. (AT WATER AND BRYANT.) Water. Per Cent. Proteid. Per Cent. J *£ si &* && Ash. Per Cent. Fuel Value. Per Cent. Meat (Beef round) 73.6 22.6 2.8 I ? CAO 52.0 16.6 30.1 I .O I, ego Fish (King salmon) ....... 63.6 17.8 17.8 I i i 080 73-7 J3-4 10.5 I.O 720 Milk (Cow's) 87.0 3-3 4.0 s.o 0.7 ^2S Milk (Human) .... 89.7 2 .O 7.1 6.0 O 2 Cheese (American) 31.6 28.8 7C.Q o. 3 3-4 2 O^ ? Butter II. O I.O 85.0 3-O 3,6o5 Bread (White) 33-2 IO.Q I . -? « 6 I O I 2x- J)1Ulk. FIG. 268. — Three Curves Showing the Secretion of Pancreatic Juice upon a Diet (i) of 600 c.c. of milk; (2) of 250 gm. of bread; (3) of too gm. of meat. The divisions along the abscissa repre- sent hours after the beginning of the meal; the figures along theordinates represent the quantity of the secretion in cubic centimeters. (Walter.) has found a certain amount of adaptation not only of the quantity but of the enzyme composition of the pancreatic secretion to the kind and character of the food (in dogs). Action of the Enzymes of Pancreatic Juice. The secretion of the pancreas accomplishes its digestive action by means of the enzymes given above, viz., trypsin, amylopsin, steapsin, and maltase. Trypsin. Trypsin is a proteolytic enzyme. Strange to say it does not exist in the fresh pancreatic juice as such, but makes its appearance only when there 336 FOOD AND DIGESTION is an admixture with the secretion of the mucous membrane of the intestine. The succus entericus contains an activating enzyme, enterokinase, which converts the inactive and stable trypsinogen of the pancreatic juice into the active but less stable trypsin. This fact is another of the wonderful series of contributions to the exact knowledge of the subject of digestion made from Pawlow's laboratories. Trypsin converts proteids into proteases and peptones. The process is both more rapid and more complete than in gastric digestion, so that, in the final result, the peptones are greatly in excess of the proteoses. The proteids pass through the same preliminary stages as in gastric digestion, being split at first into alkali-albumin, then into primary proteoses, both proto-proteose and hetero-proteose, and then into deutero-proteose. The first stages are so transient that it is difficult to detect either the alkali-albumin or primary pro- teose. The deutero-albumoses are easily demonstrated in the earlier stages, but become very scanty later. Anti-albumid is found as a side product in artificial digestion, but is not present in normal digestion. Trypsin also has the power of splitting a certain proportion of peptones, the hemi-peptones, into simpler bodies such as leucin or amido-caproic acid, tyrosin or paraoxyphenyl-amido-propionic acid, lysin, lysatinin, tryptophan, and some other bodies. In the cleavage of the proteid molecule there is prob- ably left a complex nucleus which may yet serve as a synthetic center for the rebuilding of the proteid molecule. This nucleus is called a polypeptid. Leucin and tyrosin have been found in the intestinal contents, so that this destruction of hemipeptone in artificial tryptic digestion must take place to a certain extent within the body as well. In laboratory experiments only about one-half of the peptones can be changed in this way. The more stable portion which cannot be changed is usually known as antipeptone. There are several theories as to the reason or use of this change into leucin, tyrosin, etc. One of the most plausible is that it saves the body from needless work when too much proteid food has been taken; the breaking down in the intestine of bodies only slightly removed from urea relieves the liver and other glandular organs from the strain of converting an excess of absorbed proteid material into a form in which it can be excreted. Another theory is that leucin, tyrosin, etc., are essential for the physiological working of the body in some unknown way, just as are the products of the thyroid gland. The formation of the decomposition products, indol and skatol, is caused by the action of bacteria on proteids. The albu- minous or proteid substances which have not been converted into peptone in the stomach, and the partially changed substances, i.e., the proteoses, are con- verted into peptone by the pancreatic juice, and then in part into leucin and tyrosin, etc. The ferment trypsin acts best in an alkaline medium, but will act also in a neutral medium, or in the presence of a small amount of combined acid; ACTION OF THE ENZYMES OF PANCREATIC JUICE S3? it will not work in the presence of free acid. It therefore differs from pepsin in being able to act without the aid of any other substance than water. In the process of tryptic digestion, proteid matter does not swell up at first, but seems to be corroded at once. Amylopsin. Starch is converted into maltose in an exactly similar manner to that which happens with saliva, erythro-dextrin and one or more achroo- dextrins being the intermediate products. The amylolytic enzyme of the pancreatic juice, which cannot be distinguished from ptyalin, is called amyl- opsin. The maltose thus formed is converted to dextrose by the maltase, in which form it is ultimately absorbed. Pancreatic juice, according to certain observers, possesses the property of curdling milk. It contains a special ferment, rennin, for that purpose. The ferment is distinct from trypsin, and will act in the presence of an acid (W. Roberts). The milk-curdling ferment of the pancreas is, in some pan- creatic extracts, said to be quite powerful, insomuch that i c.c. of a brine ex- tract will coagulate 50 c.c. of milk in a minute or two. Steapsin or Lipase. Oils and fats are emulsified and saponified by the pan- creatic secretion. The terms emulsification and saponification may need a little explanation. The former is used to signify an important mechanical change in oils or fats, whereby they are made into an emulsion, or in other words are minutely subdivided into small particles. If a small drop of an emulsion be looked at under the microscope it will be seen to be made up of an immense number of minute rounded particles of oil or fat, of varying sizes. The more complete the emulsion the smaller are these particles. An emulsion is formed at once if oil or fat, which when old is slightly acid from the presence of free fatty acid, is mixed with an alkaline solution. Saponification signifies a distinct chemical change in the composition of oils and fats. An oil or a fat being made up chemically of glycerin, a triatomic alcohol, and one or more fatty-acid radicles, when an alkali (potassium hydrate) is added to it and heat is applied, two changes take place : first, the oil or fat is split up into glycerin and its corresponding fatty acid ; second the fatty acid combines with the alkali to form a soap which is chemically known as stearate, oleate, or palmitate of potassium. Saponification thus means a chemical splitting up of oils or fats into new compounds, and emulsification means merely a mechanical splitting up into minute particles. The pancreatic juice has been for many years credited with the possession of a special ferment, which was called by Claude Bernard steapsin, and which is a lipase or fat-splitting fer- ment. This ferment has not been isolated, but its presence may be demon- strated by adding portions of the fresh pancreas to butter or other fat and maintaining the proper temperature. Its action is made manifest by the libera- tion of butyric acid, which smells like rancid butter. The generally accepted theory is that only a small portion of the fat which is eaten is thus changed into soap, and that the function of the saponified fat 22 338 FOOD AND DIGESTION is to assist in the emulsification of the major part, a process which is favorably influenced by the bile. The proper emulsification of fat is a necessary pre- liminary to its absorption, for when in disease the entrance of the pancreatic juice and of the bile to the intestine is interfered with, the feces contain a great excess of fat. Some recent experiments, however, tend to prove that the entire fat of the food is changed in the intestine into fatty acids and glycerin; that the fatty acids are entirely, or in part, changed to soaps; and that these soaps, or mixture of soaps and free fatty acids, are absorbed in solution. The chief facts favoring this view are that: (i) The action of steapsin is sufficiently rapid to allow the saponification of a full fatty meal within the ordinary period of digestion; (2) histological examination has never shown that fat par- ticles can pass into a columnar cell, and none have ever been found in the broad striated border of the cell; (3) the fat globules found in columnar cells after a fatty meal grow steadily larger as the period of absorption' progresses, indicating that they are deposited from solution; (4^ the fatty acids are easily soluble in bile solutions, and the solubility of the soaps is greatly increased by the presence of bile. The fat constituents, according to this theory, are recombined in the columnar cells to form neutral fats. Conditions which Influence the Action of the Pancreatic Enzymes. The various pancreatic enzymes are influenced by heat, by the presence of an excess of digestion products, etc., in the same way as ptyalin and pepsin. Pancreatic enzymes act in a neutral but best in an alkaline solution. The trypsin, strange to say, is quickly destroyed -by the alkaline solution (Bayliss and Starling). The pancreatic juice offers the special case of a secretion of proenzyme which is stable in alkaline solution until acted on by enterokinase, and the amount of kinase present will, therefore, markedly influence the amount of digestion of proteid per unit of time. The Secretions of the Liver. The liver, the largest gland in the body, situated in the abdomen on the right side chiefly, is an extremely vascu- lar organ, and receives its supply of blood from two distinct sources, viz., 44* L.L. FIG. 269. — The Liver from Below and Behind. L. S., Spigelian lobe; L. C., caudate lobe; L. (?., quadrate lobe; R. L., right lobe; L.L., left lobe; g. bl., gall-bladder; v.c.i., inferior vena cava; u.f., umbilical fissure; f.d.v., fissure of the ductus venosus; p, portal fissure with portal vein, hepatic artery and bile-duct. (Wesley, from a His model.) STRUCTURE OF THE LIVER 339 from the portal vein and from the hepatic artery, while the blood is returned from it into the vena cava inferior by the hepatic veins. Its secretion, the bile, is conveyed from it by the Hepatic duct, either directly into the intestine, or, when digestion is not going on, into the cystic duct, and thence into the gall- FIG. 270. — Portion of a Lobule of Liver, a, Bile capillaries between liver cells, the network in which is well seen; b, blood capillaries. X 350. (Klein and Noble Smith.) bladder, where it accumulates until required. The portal vein, hepatic artery, and hepatic duct branch together throughout the liver, while the hepatic veins and their tributaries run by themselves. The interstices of these vessels are filled by the liver cells. Structure of the Liver. The liver is made up of small roundish or oval portions called lobules, each of which is about ^V of an inch (about FIG. 271. — Hepatic Cells and Bile Capillaries, from the Liver of a Child Three Months Old. Both figures represent fragments of a section carried through the periphery of a lobule. The red corpuscles of the blood are recognized by their circular contour; vp, corresponds to an interlobular vein in immediate proximity with which are the epithelial cells of the biliary ducts. (E. Hering.) i mm.) in diameter, and includes the minute hepatic artery and hepatic duct. The hepatic cells, which form the glandular or secreting part of the liver, are of spheroidal form, somewhat polygonal from mutual pressure, about 340 FOOD AND DIGESTION 25 to 30 /j. in diameter, and possess one, sometimes two nuclei. The cell-sub- stance contains a variable amount of glycogen and often some fatty molecules, and possibly some granules of bile pigment. The bile capillaries commence between the hepatic cells, and are bounded by a delicate membranous wall of their own. They appear to be always FIG. 272. — Section of Liver. X 80. P, Portal vein; H, hepatic artery; B, bile-duct, drickson.) (Hen- bounded by hepatic cells on all sides, and are thus separated from the nearest blood capillary by at least the breadth of one cell, figures 271 and 272. The gall-bladder, g. bl, figure 269, is a pyriform sac attached to the under surface of the liver, and supported also by the peritoneum. The larger end, or fundus, projects beyond the front margin of the liver, while the smaller end contracts into the cystic duct. It is a muscular walled reservoir covered with a serous epithelium and lined by mucous membrane. The function of the gall-bladder is to retain the bile during the interval of digestion. The Bile. The bile is a somewhat viscid fluid, of a yellow, reddish- yellow, or green color, a strongly bitter taste, and, when fresh, with a scarcely perceptible odor; it has a neutral or slightly alkaline reaction, and its specific gravity is about 1020. Its color and consistency vary much, quite independent THE BILE 341 of disease; but, as a rule, bile becomes gradually more deeply colored and thicker as it advances along its ducts, or when it remains long in the gall- bladder where it becomes more viscid and ropy, darker, and more bitter. This is on account of its greater degree of concentration, from resorption of its water, and also from being mixed with mucus. CHEMICAL COMPOSITION OF HUMAN BILE. (FRERICHS.) Water 859.2 Solids — Bile salts 91.5 Fat 9.2 Cholesterin 2.6 Mucus and coloring matters 29 .8 Salts 7.7 Bile salts can be obtained as colorless, exceedingly deliquescent crystals, soluble in water, alcohol, and alkaline solutions, giving to the watery solution the taste and general characters of bile. They consist of sodium salts of gly- cocholic and taurocholic acids; the formula of the former being C26H42NaNO6, and of the latter C26H44NaNO7S. The bile acids are easily decomposed by the action of dilute acids or alkalies thus: C26H43NO6 + H2O = C2H5NO2 -f C24H4oO6 Glycocholic Acid. Glycin. Cholic Acid. and C26H45NO7S + H2O = C2H7NO3S -f C24H4oO5 Taurocholic Acid. Taurin. Cholic Acid. Glycin is amido-acetic acid, i.e., acetic acid C2H4O2, with one of the atoms of H re- placed by the radical amidogen NH2C2H3(NH2)O2, C2H5NO2. Taurin likewise is amido-isethionic acid. Isethionic acid is sulphurous acid H2SO3, in which an atom of H is replaced by the monatomic radicle oxy-ethylene, C2H4OH, viz., H(C2H4OH)SO3, and in amido-isethionic acid, the OH hydroxyl in this radicle is replaced by amidogen NH2, thus H(C2H4NH2)SO3 = C2H7NSO3. The proportion of these two salts in the bile of different animals varies, e.g., in the ox bile the glycocholate is in great excess, whereas the bile of the dog, cat, bear, and other carnivora contains taurocholate alone. In human bile the glycocholate is in excess (4.8 to 1.5). The yellow coloring matter of the bile of man and the Carnivora is termed Bilirubin, C16H18N2O3, is crystallizable and insoluble in water, and soluble in chloroform or carbon disulphide. A green coloring matter, Biliverdin, C16Hlg- N2O4, which always exists in large amount in the bile of Herbivora, is formed from bilirubin on exposure to the air, or by subjecting the bile to any other oxidizing agency, as by adding nitrous acid. Biliverdin is soluble in alcohol, glacial acetic acid, and strong sulphuric acid, but insoluble in water, in chloro- form, and ether. It is usually amorphous, but may sometimes crystallize in green rhombic plates. There is a close relationship between the coloring matters of the blood and of the bile, and it may be added, between these and that of the urine, 342 FOOD AND DIGESTION urobilin, and of the feces, stercobilin. It is probable they are, all of them, varieties of the same pigment, or derived from the same source. Cholesterin, C27H45OH, and lecithin, C42H84NPO9 are constant constituents of bile. Iron is found among the salts of the ash. FIG. 273. — Crystalline Scales of Cholesterin. The Role of Bile in Intestinal Digestion. Though it is not a true digestive fluid, in that it has no ferment and digests nothing itself, yet it must be regarded as an important aid to digestion for the following reasons: (a) Bile assists in emulsifying the fats of the food, and thus renders them capable of passing into the lacteals by absorption. For it has appeared in some experi- ments in which the common bile-duct was tied, that, although the process of digestion in the stomach was unaffected, chyle was no longer well formed; the contents of the lacteals consisting of clear, colorless fluid, instead of being opaque and white, as they ordinarily are after feeding. It is, however, the combined action of the bile with the pancreatic juice to which the emulsifica- tion is due rather than to that of the bile alone. The bile itself has a very feeble emulsifying power. If the theory be accepted that fats are absorbed as fatty acids and soaps, in solution, the action of the bile becomes very im- portant because solutions of bile salts have the power of dissolving the fatty acids. The moistening of the mucous membrane of the intestines with bile, for this very reason, facilitates absorption of fatty matters through it. (b) The bile, like the gastric fluid, has a certain but not very considerable antiseptic power, and may serve to prevent the decomposition of food during the time of its sojourn in the intestines. Experiments show that the contents of the intestines are much more fetid after the common bile-duct has been tied than at other times. Moreover, it is found that the mixture of bile with a fermenting fluid stops the process of fermentation. Bile is also an excretive fluid carrying waste products thrown off by the liver. The liver during fetal life is proportionately larger than it is after birth, and the secretion of bile is active, although there is no food in the in- testinal canal upon which it can exercise any digestive property. At birth, MODE OF SECRETION AND DISCHARGE OF BILE 343 the intestinal canal is full of concentrated bile, mixed with intestinal secretion, and this constitutes the meconium, or feces of the fetus. In the fetus, therefore, the main purpose of the secretion of bile must be directly excretive. Probably all the bile secreted in fetal life is incorporated in the meconium, and with it discharged. Mode of Secretion and Discharge of Bile. The secretion of bile is continually going on, but is retarded during fasting, and accelerated on taking food. This is shown by tying the common bile-duct of a dog, and estab- lishing a fistulous opening between the skin and gall-bladder, whereby all the bile secreted is discharged at the surface. When the animal is fasting, some- times not a drop of bile is discharged for several hours. In about ten minutes after the introduction of food into the stomach, the bile begins to flow abun- dantly, and continues to do so during the period of digestion. The bile is constantly being formed in the hepatic cells; thence, being dis- charged into the minute hepatic ducts, it passes into the larger trunks, and from the main hepatic duct may be carried at once into the duodenum. This probably happens only while digestion is going on, i.e., for five to seven hours after the introduction of food into the stomach. During fasting, it flows from the common bile-duct through the cystic duct into the gall-bladder, where it accumulates till, in the next period of digestion, it is discharged into the intes- tine. The gall-bladder thus acts as a reservoir for the bile during the intervals when digestion is not in progress. The mechanism by which the bile passes into the gall-bladder is simple. The orifice through which the common bile-duct communicates with the duodenum is narrower than the duct, and appears to be closed, except when FIG. 274. — Transverse Section through Four Crypts of Lieberkiihn, from the Large Intestine of the Pig. They are lined by columnar epithelial cells, the nuclei being placed in the outer part of the cells. The divisions between the cells are seen as lines radiating from L, the lumen of the crypt; G, epithelial cells, which have become transformed into goblet cells. X 350. (Klein and Noble Smith.) there is sufficient pressure behind to force the bile through it. The pressure exercised upon the bile secreted during the intervals between periods of diges- tion appears insufficient to overcome the force of the sphincter by which the orifice of the duct is closed; and the bile in the common duct traverses the 344 FOOD AND DIGESTION cystic duct and so passes into the gall-bladder, being probably aided in this retrograde course by the peristaltic action of the ducts. The bile is discharged from the gall-bladder and enters the duodenum on the introduction of food into the small intestine. It is pressed on by the contraction of the coats of the gall-bladder, and of the common bile-duct. Their contraction is excited by the stimulus of the food in the duodenum acting through a reflex arc to produce contractions, the force of which is sufficient to open the orifice of the common bile-duct. When the discharge of the bile into the intestine is prevented by an ob- struction of some kind, as by a gall-stone blocking the hepatic duct, it is reab- FIG. 275. — Longitudinal Section of Fundus of Crypt of Lieberkiihn. b, Goblet cell showing mitosis; e, epithelial cell; k, cell of Paneth; /, leucocyte in epithelium; m, mitosis in epithelial cell. Surrounding the crypt is seen the stroma of the mucous membrane. X 530. (Kolliker.) sorbed in great excess into the blood, and, circulating with it, gives rise to the well-known phenomena of jaundice. This is explained by the fact that the pressure of secretion in the ducts, although normally very low, not exceeding 15 millimeters of mercury in the dog, is still higher than that of the portal veins. If the pressure exceeds 15 mm. the secretion continues to be formed but passes into the blood-vessels through the lymphatics. The Intestinal Secretion, or Succus Entericus. It is impossible to isolate the secretion of the glands of Brunner or of the glands of Lieberkiihn, but the total secretion of the intestinal mucosa can be secured by isolating a loop of intestine by the operation known as the Thiry fistula. A few drops DIGESTIVE CHANGES IN THE SMALL INTESTINE 345 of secretion, the succus entericus, can be obtained by this means. Intestinal juice is a yellowish alkaline fluid with a specific gravity of ion and con- tains about 2.5 per cent of solid matters. Intestinal juice has only slight digestive action. It contains a weak pro- teolytic enzyme and a weak amylolytic enzyme. Maltase is also present. But the chief and most profound importance is given to the intestinal juice by the discovery of the activating enzyme, enterokinase. This specific activating enzyme for the trypsinogen of the pancreatic juice places the intestinal secre- tion in the rank of necessary secretion for efficient digestion. Enterokinase can be prepared by extracting the superficial scrapings of the intestinal mucous coat. The duodenal region is richest in enterokinase, but the secretion of the lower intestinal lengths also contains the enzyme. Extracts of the mucosa of the intestine have been found to contain another substance which has the specific action of splitting peptones into simpler amino bodies. This substance has been called erepsin. There are, therefore, three important new substances in the succus en- tericus (or in the extract of the glands), secretin, erepsin, and enter -okinase, in addition to the proteolytic and diastatic enzymes. Summary of the Digestive Changes in the Small Intestine. The thin chyme which, during the whole period of gastric digestion, is being con- stantly squeezed or strained through the pyloric orifice into the duodenum, consists of albuminous matter that is broken down, dissolving and half dis- solved; of fatty matter broken down and melted, but not dissolved at all; of starch in various stages of the process of conversion into sugar, and as it becomes sugar dissolving in the fluids with which it is mixed; while with these are mingled gastric juice and fluid that has been swallowed, together with such portions of the food as are not digestible. The chyme in the duodenum is subjected to the influence of the bile and pancreatic juice and also to that of the succus entericus. All these secretions have a more or less alkaline reaction, and neutralize the acid of the gastric chyme. The special digestive changes in the small intestine are: (i) The fats are changed by the bile and pancreatic juice in two ways, (a) They are chemically decomposed by the alkaline secretions, and a soap and glycerin are the result. (b) They are emulsified, i.e., their particles are minutely subdivided and dif- fused, so that the mixture assumes the condition of a milky fluid or emulsion. (2) The albuminous substances which have been partly dissolved in the stomach are subjected chiefly to the action of the pancreatic juice. The pepsin is rendered inert by the bile. The pancreatic trypsin proceeds with the fur- ther conversion of the proteoses into peptones, and part of the peptones (hemipeptones) into leucin, tyrosin, and other amino bodies. (3) The starchy portions of the food are now acted on briskly by the pancreatic juice and the succus entericus, and are changed to maltose and dextrose. (4) Salines 346 FOOD AND DIGESTION and other soluble matters, such as common salt, are usually in a state of solution before they reach the intestine. Digestive Changes in the Large Intestine. The changes which take place in the chyme in the large intestine are probably only the continuation of the same changes that occur in the course of the food's passage through the upper part of the intestinal canal. No special enzymes have been clearly shown for the mucous membrane of the large intestine. The enzymes of the small intestine may continue their action here, being hindered only by the acid developed from fermentation processes. Action of Micro-organisms in the Intestines. Certain changes take place in the intestinal contents independent of, or at any rate supple- mental to, the action of the digestive ferments. These changes are brought about by the action of micro-organisms or bacteria. We have indicated else- where that the digestive ferments are examples of unorganized ferments, so bacteria are examples of organized ferments. Organized ferments, of which & c « I ' ! o°°, SJ 0, FIG. 276. — Types of Micro-organisms, a, Micrococci arranged singly; in tW9s, diplococci — if all the micrococci at a were grouped together, they would be called staphylococci — and in fours, sarcinse; b, micrococci in chains, streptococci; c, and d, bacilli of various kinds, one is represented with flagellum; e, various forms of spirilla; /, spores, either free or in bacilli. the yeast plant may be taken as a typical example, consist of unicellular vege- table organisms, which when introduced into a suitable medium grow with re- markable rapidity. By their growth they produce new substances from those supplied to them as food. Thus, for example, when the yeast cell is introduced into a solution of grape-sugar, it grows, and alcohol and carbon dioxide are produced. These substances probably arise from the formation by the cell ac- tivity of some chemical substances which are allied to the unorganized ferments and which greatly increase in amount with the multiplication of the original cell. In all such fermentative processes organisms analogous to the yeast cell are present, and it is not strange that if the ferment cell is introduced into a suitable medium it may by its rapid growth convert an unlimited amount of one substance into another. Speaking generally, a special variety of cell is concerned with each ferment action, thus one variety has to do with alcoholic, another with lactic, and another with acetous fermentation. THE FECES 347 A considerable number of species of bacteria exist in the body during life, chiefly in connection with the mucous membranes, particularly of the digestive tract. Many forms of bacteria have been isolated from the mouth, a few varieties from the stomach, and a very large number from the intestines. It is only in the last-named locality that their multiplication has much effect from a physiological point of view. The normal (hydrochloric-acid) acidity of the stomach usually destroys all the micro-organisms taken in with the food, but when the amount of this acid is deficient (and sometimes even when it is nor- mal) some of the spores may escape. On reaching the small intestine these spores begin to develop in its alkaline medium, and may increase to such an extent as to stop all intestinal digestion; the point where this occurs varies from day to day. The large intestine always swarms with micro-organisms, though they do not readily pass the ileo-cecal valve into the small intestine. The bacteria found in the intestine are anaerobic, i.e., they do not develop in the presence of free oxygen. The changes induced in the intestine by the activity of micro-organisms are of two kinds, fermentation and putrefaction; the former of these results in the breaking down of carbohydrate matter, and the latter in the disintegra- tion of proteid matter. The process of fermentation is the less complex and probably occurs normally in the small intestine to a certain extent. The lactic- acid fermentation is the most important, though the butyric-acid fermentation is next; under their influence the carbohydrates are broken down into lactic and butyric acids, and perhaps into acetic acid also. Carbonic acid gas may be formed at the same time and cause flatulence. Cellulose and other in- soluble carbohydrates are decomposed, with the formation of marsh gas and hydrogen, which escape by the rectum. In putrefaction the process is similar to that in tryptic digestion, the pro- teids being broken down into peptones, leucin, tyrosin, and a long row of similar substances. It also results in the production of various gases, such as carbon dioxide, sulphureted hydrogen, ammonia, hydrogen and methane (marsh gas), and of a high percentage of the volatile fatty acids, valerianic and butyric. Of the aromatic substances the most important are indol and skatol, though their toxicity has been greatly overestimated. Some undergo oxidation, indol and skatol forming indoxyl and skatoxyl; they are usually carried off in the feces, but when the bowel is obstructed they are absorbed and eventually appear in the urine, indoxyl and skatoxyl forming respectively indoxyl- and skatoxyl-sulphuric acids and their salts. Tyrosin is further broken down into para-oxy-phenol-propionic acid, paracresol, and phenol; para-oxy-phenol- acetic acid is also formed. Experiments have been performed to determine whether or not the intestinal bacteria are neccessary to normal digestion. The weight of evidence is in favor of the view that they are not. The Feces. The contents of the large intestine, as they proceed toward the rectum, become more and more solid, lose more liquid and nutrient 348 FOOD AND DIGESTION parts, and gradually acquire the odor and consistency characteristic of jeces. After a sojourn of uncertain duration in the sigmoid flexure of the colon, or in the rectum, they are finally expelled by the act of defecation. The average quantity of solid matter evacuated by the human adult in twenty-four hours is about 200 to 250 grams, but the amount and character vary exceedingly ac- cording to the food eaten. Vegetable foods contain much indigestible matter, while meats and meat diets leave very little unabsorbed material to be ex- pelled in the feces. TABLE OF COMPOSITION OF FECES. The amount of water varies considerably, from 68 to 82 per cent and upward. The following table gives about an average composition: Water Solids, comprising: a. Insoluble residues of the food, uncooked starch, cellulose, woody fibers, cartilage, horny matter, mucin, seldom mus- cular fibers and other proteids, fat, and cholesterin ...... b. Certain substances resulting from decomposition of foods, indol, skatol, fatty and other acids; calcium and mag- nesium soaps ..................................... c. Special excretions, — Excretin, excretoleic acid (Marcet), and stercorin (Austin Flint) .......................... d. Salts, — Chiefly phosphate of magnesium and phosphate of calcium, with small quantities of iron, soda, lime, and silica ............................................ e. Insoluble substances accidentally introduced with the food f. Mucus, epithelium, altered coloring matter of bile, fatty acids, etc ......................................... g. Varying quantities of other constituents of bile and secre- tions . . ............... 733-°° 267.00 Intestinal Gases. Under ordinary circumstances, the alimentary ca- nal contains a considerable quantity of gases. The presence of gas in the 0000006 FIG. 277. — Diagram Illustrating the Segmentation of the Food in the Small Intestine. (Cannon.) intestines is so constant and the amount in health so uniform that there can be no doubt that its existence is a normal condition. The gas contained in the stomach and bowels is from air swallowed with MOVEMENTS OF THE INTESTINES 349 either food or saliva, gases developed by the decomposition of foods, or of the secretions and excretions thrown into the intestines. The decomposition of foods is the chief source. The following table, compiled by Brinton, is a col- lection of analyses that have been made and is chiefly valuable as showing the kinds of gases present: GASES FOUND IN THE ALIMENTARY CANAL. Composition by Volume Whence obtained. Oxygen. Nitrog. Carbon. Acid. Hydrog. Carburet. Hydrogen. Sulphuret. Hydrogen. Stomach ii 71 14 4 Small intestines 32 3O 38 "| Cecum 67 12 8 1 3 1 i Colon •} e r i 6 8 }- Trace. Rectum 46 42 1 1 1 Expelled per anum. . . . — 22 40 19 !Q ) °-5 The amounts of the gases vary with the diet. An analysis of the intestinal gases (Ruge, copied by Halliburton) in man is as follows: Gases. Milk Diet. Meat Diet. Vegetable Diet. Carbon dioxide ..... 9 to 1 6 8 to 13 21 to 34 Hydrogen 43 to ?4 0.7 to •? 1.5 to 4 Carbureted hydrogen 0.9 26 to 37 44 to ZZ Nitrogen 36 to -?8 45 to 64 10 to 19 The carbon dioxide arises from the carbonates and lactates in food, from fermentation and putrefaction of carbohydrates and proteids, and from butyric-acid fermentation. The hydrogen is derived from butyric- and lactic-acid fermentations, and carbureted hydrogen comes from the decomposition of acetates and lactates and from cellulose. The nitrogen is derived from the swallowed air. MOVEMENTS OF THE INTESTINES. The muscular activity of the intestines accomplishes two important func- tions, i.e., it thoroughly mixes the digesting food and secretions and it carries the content along the tract. Intestinal peristalses have been described for a long time. These peristalses begin as contractions of the circular muscles, producing ring-like constrictions that are propagated as waves over the intestine 350 FOOD AND DIGESTION from above downward. Such constrictions carry the intestinal contents forward. The longitudinal muscles by their contraction produce pendular motion of the intestine. A most instructive contribution to the knowledge of intestinal movements has been made by Cannon. He fed cats food mixed with 10 to 33 per cent of subnitrate of bismuth, and observed the shadows of the food when subjected to the Roentgen rays. A length of food in the intestine was seen to be con- stricted into a series of oval masses, figure 277. Each of these oval masses is quickly constricted in the middle, and neighboring halves of adjacent masses flow together. After this process is repeated a number of times a peristaltic wave of the type previously described sweeps the whole content of the loop down the intestinal tract. Peristaltic contractions of the same general type as in the small intestine also occur in the large intestine. Cannon has noted a variation here, also. The ascending and the transverse loops of the colon exhibit rhythmic antiperistalses which keep the content moving against the ileocecal valve for several minutes at a time. From time to time strong general contractions, in the cecum and ascending colon, force some of the food onward. When material has accumu- lated in the transverse colon, deep successive tonic constrictions appear and force its contents into the descending colon. When sufficient material has ac- cumulated here, it is evacuated by strong peristalses combined with compres- sion by the contracting abdominal muscles. Reverse or antiperistalsis does not commonly occur in the small intestine, but large nutrient enemata introduced into the rectum and colon may be forced by antiperistaltic waves in the large intestine to and through the ileocecal valve into the small intestine. Here they are treated in the same way as food which has been introduced in the normal way. Influence of the Nervous System on Intestinal Peristalsis. As in the case of the esophagus and stomach, the peristaltic movements of the in- testines may be directly set up in the muscular fibers by the presence of food acting as the stimulus. Few or no movements occur when the intestines are empty. The intestines are connected with the central nervous system both by the vagi and by the splanchnic nerves, as well as by other branches of the sympathetic which come to them from the celiac and other abdominal plexuses. The relations of these nerves respectively to the movements of the intestine and the secretions are probably the same as in the case of the stomach already considered. The vagus fibers are described as the motor fibers for the intestine, while the sympathetic are said to be at least in part inhibitory. Various states of the central nervous system, such as fear, anger, etc., inhibit the intestinal move- ments. The intestine carries out peristalses when isolated from the body so that the central connections do not originate, but are only regulative. The intestinal movements are essentially automatic, depending on the rhyth- SALIVA AND SALIVARY DIGESTION 351 mic property of the muscle itself but coordinated by the complex local nervous mechanism. The innervation of the large intestine is also double in character and the relations are doubtless the same as in the small intestine. Defecation. The emptying of the rectum is essentially an involun- tary act which has acquired a certain amount of voluntary regulation. The act is accomplished wholly reflexly in dogs with isolated lumbar cord, in fact has been observed when the lumbar spinal a rd was removed. In the latter case defecation occurs by automatic peristalsis of the rectum, while in the former cases reflexes through the lumbar cord carry out the act. The stimulus of the feces against the rectum and the internal sphincter initiate the movement. Normally in man the rectal stimulus gives rise to the consciousness of the desire to defecate and the initiation of efferent nerve impulses that may increase the contraction of the external sphincter and inhibit the act tempo- rarily. During defecation, however, the voluntary effort leads to relaxation of the external sphincter, and the normal peristalsis of the rectum is supported by contractions of the abdominal musculature so as greatly to increase the abdominal pressure, thus aiding the involuntary reflex. LABORATORY EXPERIMENTS IN DIGESTION. I. SALIVA AND SALIVARY DIGESTION. 1. Reflex Salivary Secretion. Saliva, which is the mixed secretion of the salivary and buccal glands, is produced more or less intermittently. Ex- amine, taste, or smell appetizing food, for example, an apple, the salivary glands begin to discharge secretion which is poured into the mouth more rapidly than under ordinary conditions. This increased activity is a reflex secretion. It is brought about by the stimulation of sensory structures which lead to afferent nerve impulses reacting on nerve centers in the medulla to cause secretory nerve impulses to the glands. The stimulating effect of food in the mouth causes the most rapid reflex secretion, which may last through several minutes, or even hours. Especially stimulating substances are, beside food, such substances as tartaric acid, lemon juice, ether, alcohol, etc., in fact any- thing that produces strong local irritation will lead to reflex secretion. 2. The Secretory Nerves of the Salivary Glands of the Dog. The nervous mechanism for the salivary gland is well known, and the anatomical relations are such as to make this gland a favorable one for studying the nerv- ous mechanism of glands in general. Anesthetize a dog and bind it to a suitable holder. Expose the nerves to the submaxillary gland as follows: cut through the skin of the lower jaw along the inner border for about 3 inches. Isolate and double ligate the jugular vein and any other veins in the field except the ones coming from the sub- 352 FOOD AND DIGESTION maxillary gland. Isolate and cut the digastric muscle, also the mylo-hyoid, using pains not to injure the duct of the gland or its arteries. When the muscles are laid back, the artery and accompanying sympathetic nerve branches, the hypoglossal and the lingual nerves, the submaxillary duct and the submaxillary gland, will all be exposed. Isolate and introduce a very fine glass cannula into the submaxillary duct. A small nerve filament branches from the lingual nerve and runs to the hilus of the gland, the chorda tympani. Carefully expose the chorda, place a silk ligature under it for con- venience in handling. Also expose the sympathetic filaments with the artery. Stimulate the chorda tympani with a mild induction current for a few minutes at a time at intervals, and note that the secretion which is absent or forming slowly before stimulation now gathers quickly and leaves the end of the cannula in a series of drops. Collect the saliva in a small beaker. One can measure the rate of flow by collecting the saliva in a small graduated cylinder, or, by changing the beaker every ten minutes, making a record of the quantity of secretion formed. Stimulate the sympathetic fibers, cutting the hypoglossal nerve if necessary, and note that the secretion is very slightly in- creased, but the increase lasts for only a few minutes. If the sympathetic fibers are stimulated before the chorda, then the sympathetic secretion is relatively less than if the order of stimulation is reversed. During stimulation of the nerves, note the relative flow of blood through the organ. During chorda stimulation the flow is increased; during sympa- thetic stimulation it is decreased, as these nerves contain vaso-dilator and vaso-constrictor fibers, respectively. 3. Microscopic Changes in the Gland Cells. Make a histological preparation (by any standard method of fixing and staining) of the submaxil- lary gland of the cat, a, taken after a period of several hours' fasting when the gland cells may be assumed to be at rest; and 5, immediately after a period of activity (from eating, or activity secured by the stimulation of the chorda tympani) and note: a, The cells from the resting gland are relatively larger, the nuclei are pushed back against the basement membrane, they have sparsely sustaining protoplasm, and the cells are crowded with large gran- ules, which in a fortunate preparation fill the entire cell. The outlines of the cells are relatively indistinct and the lumen of the gland is small. Z>, The cells of the active gland are relatively small, the nuclei are centrally placed, the protoplasm stains more definitely, the granules are usually present but limited to the side of the cell next to the lumen, the outlines of the cells are distinct, and the lumen is often quite large. 4. The Chemical Composition of Saliva. Collect several cubic cen- timeters of saliva as follows: Wash the mouth thoroughly with water, then induce secretion of saliva by chewing a bit of paraffin or a piece of thoroughly washed rubber. The inhalation of ether vapor will often facilitate the reflex secretion. One should avoid strong acids to induce secretion unless their DIGESTIVE ACTION OF SALIVA ON STARCH 353 presence is to be taken into consideration afterward. Make the following tests: Reaction. A slip of neutral litmus paper when introduced into freshly collected saliva, or for convenience simply taken into the mouth during sali- vary secretion, shows an alkaline reaction. Mucin. To 3 or 4 c.c. of saliva add 2 per cent acetic acid drop by drop until distinct acidity is obtained. On stirring the saliva with a glass rod a sticky mucin makes its appearance. Potassium Sulphocyanide. To 2 c.c. of saliva in a test tube add 2 or 3 drops of ferric-chloride solution, slightly acidulated with hydrochloric acid, a reddish-brown coloration indicates the presence of potassium sulphocyanide. One should run a blank test on distilled water for comparison. Chlorides. Add silver nitrate to 2 c.c. of saliva after first removing the proteids. A white, cloudy precipitate, which disappears on adding ammonia and reappears on adding nitric acid, indicates the presence of chlorides. Proteids. Remove the mucin from a sample of saliva, as above, and test by the characteristic proteid reactions. A faint trace of proteid can usually be demonstrated. 5. Digestive Action of Saliva on Starch. Review the test for starch, dextrin, and dextrose, as preparation for an identification of these prod- ucts of salivary digestion. To 50 c.c. of i per cent starch paste in the water bath at 40° C. add 5 c.c. of saliva, and mix thoroughly with a glass rod. Immediately begin two series of tests: a, for the presence of starch; b, for the presence of reducing sugar. The tests for starch can be made by adding to 3 drops of starch, on a porcelain plate, an equal quantity of dilute iodine in potassium iodide solution. Use a glass rod. Make the tests every 2 minutes for 20 minutes. The tests for reducing sugar are best made by placing 2 c.c. of Fehling's solution in each of a series of test tubes and adding, at intervals of 5 minutes, i c.c. from a dropping-pipet and boiling. If the tests are set away as fast as they are prepared, a reddish-yellow cuprous oxide will settle out, and the series will give a rough comparison as to the quantity of reducing sugar present. In the first series the deep blue of the starch reaction quickly changes to a reddish-blue, a red, a reddish-brown, until finally no change in color other than that produced by the mixture of the iodine occurs, showing that the starch has passed the second stage of erythro-dextrin in its disappearance. The indication of reducing sugar in the second series shows that this erythro- dextrin has been transformed into reducing sugar, and also that the amount of sugar is greatly increased during the progress of the test. 6. The Influence of Temperature on Salivary Digestion. Prepare three test tubes, a, b, c, containing 4 c.c. each of saliva. Boil a, place b in a water bath at 40° C., and place c in ice water. After c has been cooled down to the temperature of the ice bath add to each 2 c.c. of i per cent starch solu- 23 354 FOOD AND DIGESTION tion and mix. At intervals of 2 to 5 minutes test these 3 samples for the dis- appearance of starch and appearance of reducing sugar, as in experiment 5. No change will take place in a; b will be quickly digested; and the digestion in c will be slight or suspended. Upon placing c in a warm bath digestion will quickly occur. 7. Influence of Acids and Alkalies on Salivary Digestion. To each of 5 test tubes, a, b, c, d, e, add 5 c.c. of saliva. Leave a for the normal; make b strongly alkaline; c exactly neutral; d acid to the extent of 0.2 to 0.3 per cent hydrochloric acid; e strongly acid. Place all in the water bath at 40° C. Add to each 2 c.c. of i per cent starch paste and mix. Test for starch and for reducing sugar at intervals of 20 minutes and compare, noting the results in the following table: A B C D E Prepare and set in water bath at 40 C. 5 c.c. saliva 5 c.c. saliva and i c.c. strong KOH 5 c.c. saliva exactly neutralized 5 c.c. saliva and i c.c. 0.2 per cent hydro- chloric acid 5 c.c. saliva and i c.c. strong hydrochlo- ric acid Then add . ... 2 c.c. i per 2 c.c. i per 2 c.c. i per 2 c.c. i per 2 c.c. i per cent starch cent starch cent starch cent starch cent starch Test for starch and sugar im- mediately. After 20 minutes. After 40 minutes. The results obtained in the experiments 5, 6, and 7 show that starch is converted into reducing sugar, and furthermore that the conditions for its conversion indicate that the change is accomplished by an amylolytic enzyme which in this case is called ptyalin. 8. The Action of Ptyalin is Favored by the Removal of the End Products. Place 50 c.c. of 2 per cent starch paste in a dialyzing tube or paper, suspend in a beaker of running water. Take 50 c.c. of the same solution in a beaker, to each add 2 c.c. of saliva and mix thoroughly. Test for the dis- appearance of starch at intervals of 20 minutes. The starch in the dialyzing tube will disappear first because the reducing sugar passes out through the dialyzer, while in the beaker it is retained and hinders the further action of ptyalin. GASTRIC DIGESTION 355 II. GASTRIC JUICE AND GASTRIC DIGESTION. 9. The Secretion of Gastric Juice. The conditions which influence gastric secretion can be readily observed on the dog with a gastric fistula. Take a dog which has had a gastric fistula prepared some weeks before and which is in a condition of hunger, place him in a holder with a cup suspended to collect the gastric juice, and exhibit before the dog some fresh meat or other food which he enjoys, but do not allow him to eat it. After teasing the animal for 5 or 10 minutes, an abundant flow of gastric juice will begin. Paw- low calls this the psychic secretion. If an esophageal fistula has also been performed on the animal the dog may be allowed to eat the meat, of course swallowing it out of the esophageal FIG. 278. — Operation on the Stomach to Form an Isolated Pouch with Nerves Intact. S, Isolated sac; V, cavity of stomach; A, A, opening at the abdominal wall. fistula back into the- plate. In this experiment an abundant flow of gastric secretion takes place and may continue for an hour or more. If a gastric pouch has been performed by Pawlow's method, the animal may be allowed to eat the food, swallowing it into the stomach. In this case the reflex secretion just described takes place as usual, but is followed after an hour or an hour and a half by a second increase in the quantity of secretion. This second increase has been ascribed to the reflexes originating in the stomach, possibly from the reflex stimulating action of the digestive products themselves. 10. Composition of Gastric Juice. Test a sample of gastric juice obtained from a gastric fistula, as follows: Reaction. Gastric juice is strongly acid. Test for free hydrochloric acid 356 FOOD AND DIGESTION as follows: Gastric juice turns congo-red to a blue color. Organic acids pro- duce violet. Gastric juice plus 0.5 per cent alcoholic solution of dimethyl- amido-azobenzol develops a cherry-red color, a reaction that is given by free hydrochloric acid. Combined hydrochloric acids and organic acids do not give the color. Giinzburg's reagent, consisting of 2 per cent phloroglucin and i per cent vanillin in 80 per cent alcohol, produces a rose-colored mirror on porcelain in the presence of free hydrochloric acid. The test is very delicate. Proteids. The usual proteid tests can be applied to gastric juice and show that it contains small quantities. 11. Artificial Gastric Juice. An active principle, pepsin, of gastric juice can be obtained by extracting the gastric mucous membrane of the dog, pig, etc. Scrape off the mucous membrane, grind it to a fine pulp by repeatedly running it through a sausage machine, or by pounding in a mortar with clean sand. The mucous membrane should be allowed to stand for three or four hours before extraction, otherwise the zymogen, and not the enzyme, will be obtained. Extract a portion of this gastric pulp in water, and filter. Or extract with glycerin for several weeks and filter. Either of these extracts contains the enzyme. A solution of the glycerin extract in 0.2 per cent hydrochloric acid contains all the properties of gastric juice. This is known as artificial gastric juice. Commercial pepsin already prepared can be obtained on the market. Artificial gastric juice is made from commercial pepsin by adding 3 to 5 grams to a liter of 0.2 per cent hydrochloric acid. 12. Digestive Action of Gastric Juice, or Artificial Gastric Juice. The digestive action of gastric juice is limited to proteids. Shreds of fibrin which permit the gastric juice to come in intimate contact with all parts of the material, form the best proteid for testing the action of this enzyme. Prepare a series of test tubes, a, b, c, d, each containing 5 c.c. of artificial gastric juice. Add to a some shreds of fibrin; to b some boiled white of an egg; to c some fibers of boiled meat; to d some fibers of raw meat; place in a warm bath at 40° C. and examine at intervals of 20 minutes. Tabulate the results by the plan indicated in experiment 13, noting particularly the rapidity with which the proteid goes into solution. 13. Conditions Affecting the Enzyme Action of Gastric Juice. Prepare a series of test tubes containing 5 c.c. each of gastric juice, according to the table on the following page. Add a definite quantity of fibrin to each and note the changes at intervals of 20 minutes. 14. Cleavage Products of Gastric Digestion. Add 5 to 10 grams of fibrin to 100 c.c. of artificial gastric juice in a flask and place in a water bath at 40° C. After one hour filter off 40 c.c. Exactly neutralise this filtrate with i per cent potassium hydrate. A precipitate makes its appearance, and can be collected on the filter paper, washed with distilled water, and dis- ACTION OF RENNIN 357 solved in i per cent dilute hydrochloric acid, acid albumin. Test for the pro- teid reactions. After two hours filter the remaining 60 c.c., exactly neutralize to remove any traces of acid albumin, and filter. The filtrate contains proteoses. Con- centrate the filtrate over a water bath to one-fourth its volume, add an equal quantity of saturated ammonium-sulphate solution, a sticky precipitate of primary proteoses separates out. Collect on a filter paper, wash with half- saturated ammonium sulphate, redissolve in very dilute salt-solution, and test for proteid reactions. The primary proteoses are precipitated by nitric acid. To the filtrate from the half -saturated ammonium sulphate add crystals of ammonium sulphate until complete saturation with salt. Deutero-albumoses A B C D E Prepare 5 c.c. gas- tric juice at 5 c.c. neutral gastric juice 5 c.c. alka- line gastric 5 c.c. boiled gastric juice 5 c.c. gastric 40° 'C. at 40° C. juice at 40° C. at 40° C. juice at o° C. Then add Fibrin Fibrin Fibrin Fibrin Fibrin Note after 20 minutes. After 40 minutes. After 60 minutes. separate out. Collect on a filter paper, wash, dissolve, and test for proteids. The secondary proteoses are not precipitated by nitric acid. Finally the filtrate contains peptone. It can be isolated and tested by concentrating over the water bath, adding barium hydrate to slight excess to remove the sulphate, filtering, and precipitating the excess of barium by exact neutralization with i per cent sulphuric acid. Test for proteid reac- tions. Peptone gives a rose color in the biuret reaction. The xanthoproteic reaction gives the color change, but not the usual precipitate. Peptone is re- dissolved from its alcoholic precipitate without change. It is dialyzable. 15. Action of Rennin. Add a solution of commercial rennin (jun- ket powder), or of the extract of gastric mucous membrane of the fourth stomach of a calf, to 5 c.c. of milk and let stand for a few minutes. Repeat the test with artificial gastric juice. Also with neutral gastric juice. In each case the milk will form a jelly-like clot, which is firmer in the test tube contain- ing commercial rennin. In the test tube containing artificial gastric juice, 358 FOOD AND DIGESTION the milk is first coagulated, then slowly dissolved or digested. This clotting is due to the special coagulating enzyme, rennin. III. PANCREATIC JUICE AND PANCREATIC DIGESTION. 1 6. The Secretion of Pancreatic Juice. If a dog containing a pan- creatic fistula made by Pawlow's method is available, then try the experi- ment of feeding the animal and noting the rate of secretion of pancreatic juice through a period of two hours. When the gastric digestion has proceeded to the point where the acid chyme may be supposed to have entered the duo- denum, then a sharp increase in the flow of pancreatic juice takes place. This increased activity will last through a period of two or three hours or more. It is produced either by nerve reflexes (Pawlow) or by the influence of the secretion produced by the gastric mucous membrane when stimulated by acid. 17. Influence of Secretin on the Rate of Secretion. Make an ex- tract of the intestinal mucous membrane, preferably from the duodenum, by scraping off the membrane, grinding it to a pulp, and extracting it over a water bath in 0.2 per cent hydrocholoric acid, and filtering. Anesthetize a large dog, open the abdomen, isolate the pancreatic duct, introduce a cannula, and arrange for the collection of pancreatic juice. Intro- duce a cannula into the saphenous vein and connect it with a buret containing the extract of secretin already prepared. Inject 5~c.c. quantities of the secretin solution into the vein at intervals of ten minutes. Measure the rate of secretion of pancreatic juice by counting the drops per minute, or if the secretion is rapid enough, by collecting it at intervals of five or ten minutes and measuring it in a graduated pipet. This method will often yield enough pancreatic juice in the course of a couple of hours to make the pancreatic experiments which follow. Bayless and Starling call it secretin juice. 1 8. Chemical Characters of Pancreatic Juice. Test the reaction, proteid, salt, etc., content of the sample of pancreatic juice collected in the last experiment. 19. Artifical Pancreatic Juice. Artificial pancreatic juice can be prepared from the pancreas by grinding and macerating and extracting a pancreas with water or glycerin, as described for the gastric glands in experi- ment ii above. Commercial preparations of pancreatic enzyme can be ob- tained on the market. A solution of glycerin extract of pancreatic gland or of commerical pancreatin in 0.2 per cent sodium carbonate is known as arti- ficial pancreatic juice. 20. The Enzymes of Pancreatic Juice. The pancreatic juice con- tains enzymes which have exerted a digestive action on starches, fats, and proteids. This fact can be tested as follows : a, To 5"c.c. of artificial pancreatic juice add 2 c.c. of i percent starch paste, mix and set in the water bath at 40° C. ACTION OF THE ENZYMES OF PANCREATIC JUICE 359 b, To i c.c. of pancreatic juice (artificial juice is not active), collected in experi- ment 17, add 0.5 c.c. of neutral olive oil, and place over a water bath, c, To 5 c.c. of artificial pancreatic juice add a few flocks of fibrin. Test the digestive action on starch by the iodine test for the disappearance of starch, or by the copper-reduction test for the presence of reducing sugar. Test the fat by its reaction, noting that the neutral or slightly alkaline solution has become acid, also by the fact that an emulsion has been formed. Note that the proteid has gone into solution. The digestive action on starch is due to the enzyme amylopsin, or pan- creatic diastase, as it is sometimes called. The fat-splitting effect is due to the enzyme lipase, and the solution of the fibrin is accomplished by the proteolytic enzyme, trypsin. 21. Conditions which Influence the Action of the Enzymes of Pancreatic Juice. To each of 5 test tubes, a, b, c, d, e, add 5 c.c. of artificial pancreatic juice. Place a, b, c, d in the water bath at 40° C., and e into an ice bath. Leave a normal, make b exactly neutral, add to c i c.c. of 2 per cent hydrochloric acid, and boil d. Add to each tube 2 c.c. of i per cent starch paste. Follow the digestive changes by the tests previously outlined. Tabulate according to the following scheme: A B C D E Take 5 c.c. pan- creatic Neutralize 5 c.c. pan- 5 c.c. pancre- atic juice and i c.c. of 2 per 5 c.c. pan- creatic 5 c.c. pan- creatic juice 40° C. creatic juice 40° C. cent hydro- chloric acid 40° C. juice and boil. juice at o° C. Then add 2 c.c. of starch 2 C.C. Of starch 2 C.C. of starch 2 C.C. Of starch 2 C.C. Of starch Note after 20 minutes. After 40 min- utes. After 60 min- utes. - Repeat this experiment with a second set of test tubes containing fibrin. Lipase is not very active in artificial pancreatic juice and may be omitted. If pancreatic juice is available make a third set containing fat. 22. Cleavage Products of Pancreatic Digestion. To 200 c.c. of arti- 360 FOOD AND DIGESTION ficial pancreatic juice add 25 grams of moist fibrin and place in a water bath at 40° C., add 7 c.c. of chloroform to prevent putrefactive changes. After three or four hours filter off 80 c.c. and place the remainder on the water bath for two or three days. Test the filtrate for alkali albumin, albumoses, and pep- tones, by the method outlined in experiment 14 above. Filter the second portion and concentrate to a syrupy mass on the water bath. Crystals make their appearance. Pour off the fluid, wash the crystals with cold water, and examine under the microscope for sheaves of tyrosin. The filtrate contains leucin. If the digestion had been allowed to proceed without the chloroform, bacteria would have appeared in the solution, and proteid cleavage products, due to their action, would be found, notably indol. IV. BILE AND INTESTINAL JUICE. 23. Bile. Secure bile from the gall-bladder of a pig or dog, or, if it is possible, a sample of human bile. Test the reaction which, in fresh bile, is neutral. Test for mucin; albumin; and for iron; hydrochloric acid and ferrocyanide of potassium give a blue color when iron is present. Bile Salts. Evaporate 10 c.c. of bile to complete dryness, mix with animal charcoal, add 50 c.c. of absolute alcohol, filter; add an excess of ether to the filtrate, which gives a white precipitate of bile salts. Crystals will form on standing in a well-stoppered flask for a day or two. Bile Acids. A drop of syrup of cane-sugar in a test tube of bile forms a deep red-purple color at the line of separation from concentrated sulphuric acid. Furfur aldehyde with cholalic acid gives the color. Bile Pigments. With i c.c. of bile in a test tube strong nitroso-nitric acid produces a play of colors beginning with green, blue, red, and yellow— Gmelin's test. Bile does not contain digestive enzymes, but the bile wets the mucous surface of the intestine and facilitates the solution of fats and fatty acids. 24. Intestinal Juice. The secretion of the mucous membrane of the small intestine has been proven to have a weak digestive action on pro- teids and perhaps on starches. It can be obtained from an intestinal fistula. Its chief digestive importance consists in the presence of the activating enzyme, enterokinase. Enterokinase can be prepared by extracting the mucous mem- brane of the small intestine by the method outlined for making a pancreatic extract. To two test tubes containing 5 c.c. of artificial pancreatic juice, or pref- erably containing secretin pancreatic juice, add flocks of fibrin. Keep one for the control, to the other add 2 c.c. of enterokinase solution. The test tube containing enterokinase will digest more rapidly and more effectively than the other. CHAPTER IX ABSORPTION ABSORPTION in its restricted use means the process by which the digested foods pass through the walls of the alimentary canal and into the circulation. In its more general meaning absorption is the process by which substances pass from one part of the body to another by means other than the blood- and lymph-vessels. Usually the absorption takes place from a free surface, such as the alimentary canal, the skin, and the lungs. The alimentary canal is lined throughout with a continuous layer of epi- thelial tissue. This layer is only a single cell thick in most of its extent, but nevertheless it effectively separates the food inside the canal from the lymph in the tissue interspaces on the outside of the mucous membrane. These spaces are separated from the blood in the adjacent blood-vessels by a second continuous layer, the endothelial walls of the capillaries. The food, therefore, in its absorption, must pass through two layers of tissue to reach the blood stream. But the submucous lymphatic spaces and vessels furnish channels which may carry substances into the blood by way of the thoracic duct. The mucous membrane is, therefore, the one strict barrier through which the food must pass in the act of absorption. The exact methods by which absorption takes place have long been a subject of controversy and of research. But this problem is of such diffi- culty that it is yet, in the main, unsolved. Known physical and chemical laws were thought to explain the facts of absorption. Some of the known physical factors concerned in absorption and elimination have already been considered in a former chapter, osmosis and diffusion, Chapter IV. A third factor, filtration, consists in the passage of a fluid under pressure through a membrane. These factors undoubtedly play an important role in the passage of solutions through the alimentary mucous membrane and the walls of the blood-vessels. The part which the physical factors play is probably more pronounced in the absorption of water and crystalloids. The nature of the fluid within the digestive tract, and the movements of the walls of the stomach and intestines by means of which the material to be absorbed is brought into intimate contact with the absorbing membrane, are additional factors which influence absorption. But the mechanical and physical factors do not fully explain the observed facts of absorption. It becomes more and more evident that there is an 361 362 ABSORPTION unexplained factor bound up in the characteristics of the living protoplasm of the epithelial cells themselves. When isotonic blood serum is introduced into the intestine the salts and water are at once absorbed, also the albumins, but more slowly. In this experiment the osmotic conditions are in balance and the pressure is greater on the side of the blood-vessels, so that absorption takes place with the actual expenditure of energy. The important fact here is that the absorption through a living membrane is influenced by the membrane in ways that we cannot yet explain. It is this factor which de- termines the different rate of absorption and the so-called selective absorp- tion in different regions of the alimentary canal. As a rule, the current of absorption is from the stomach or intestine into the blood; but the reversed action may occur, as, for example, when sulphate of magnesium is taken into the alimentary canal. In this case there is a rapid discharge of water from the blood-vessels into the canal. The rapidity with which matters may be absorbed and diffused through the textures of the body has been found by experiment. It appears that lithium chloride may be diffused into all the vascular textures of the body, and into some of the non-vascular, as the cartilage of the hip joint, as well as into the aque- ous humor of the eye, in a quarter of an hour after being given by way of the mouth and on an empty stomach. Lithium carbonate, when taken in five- or ten-grain doses on an empty stomach, may be detected in the urine in five or ten minutes; or, if the stomach be full at the time of taking the dose, in twenty minutes. Absorption in the Mouth. The epithelial lining of the mouth is of the thicker stratified type and the conditions are otherwise unfavorable for absorption. Little, if any, absorption normally takes place in the mouth, and the same is true for the esophagus. Absorption in the Stomach. The mucous and sub mucous coats of the stomach, see figure 258, are well supplied with blood-vessels and lym- phatics. The mucous membrane is, however, so crowded with the peptic glands that the relative amount of absorbing surface is small. It is limited to the mucous membrane around the mouths of the glands. Recent experiments have shown that though absorption does take place in the stomach, it is not as active as was formerly supposed, even in the case of water. Von Mering has found that water begins to pass from the stomach into the intestine almost as soon as it is swallowed, and that very little of it is absorbed from the stomach. Of 500 c.c. given by the mouth to a large dog with a duodenal fistula, only 5 c.c. were absorbed in 25 minutes, the rest having passed into the intestine. Peptones, sugars, and salts are ab- sorbed in the stomach, but only to a limited extent. Peptones are not ab- sorbed in appreciable amount unless present to as much as 5 per cent or more. Examination of the mucous membrane during the stage of active digestion has revealed the presence of albumoses. Sugars, like peptones, are ABSORPTION IN THE INTESTINES absorbed by the stomach only to a slight extent in the weaker solutions, but are readily absorbed when the more concented solutions are introduced into the stomach, five per cent and over (von Mehring). Fats are not absorbed at all in the stomach. Even salts in the stomach are not readily absorbed until this concentration is from three to four times that of the blood. This fact is in direct opposition to the popular views on the subject. While some absorption does take place in the stomach it is evidently not of any great importance under normal conditions. The presence of alcohol has been shown to increase the amount of absorption, and pepper, mustard, and such drugs as produce mild local irritation accomplish the same result. Absorption in the Intestines. The products of digestion are all absorbed in the small intestine, as is abundantly shown by experiments. '• FIG. 279. — Scheme of Blood-vessels and Lymphatics of Human Small Intestine, a, Central lacteal of villus; b, lacteal; c, stroma; d, muscularis mucosae; e, submucosa; /, plexus of lymph- vessels; g, circular muscle layer; h, plexus of lymph- vessels; *', longitudinal muscle layer; /, serous coat; k, vein; /.artery; m, base of villus; n, crypt; {o, artery of villus; p, vein of villus; g, epithe- lium. (Mall.) Absorption from the small intestine has been studied in the human subject in the case of a patient who had a fistulous opening in the lower part of the ileum. For example, 85 per cent of the proteid of a test meal was absorbed before the food reached the fistuh. The food passes slowly down the length 364 ABSORPTION of the small intestine, and the digestive changes produce a series of cleavages which have known osmotic and diffusion properties. The question has been to determine which of the cleavage products are most favorable for absorp- tion and the details of the mechanism. The mucous membrane of the small intestine possesses special structures for absorption, the villi. Each villus projects as a finger-like process into the lumen of the intestine. Its single-layered covering of epithelial cells supported by a connective-tissue framework brings a relatively large extent Lymphatic of head and neck, right Right internal jugular vein Right subclavian vein Lymphatics of right arm Receptaculum chyli Lymphatics of lower extrem- ities Lymphatics of head and neck, left Toracic duct Left subclavian vein Thoracic duct Lacteals Lymphatics of lower ex- tremities FIG. 280. — Diagram of the Principal Groups of Lymphatic Vessels. (From Quain.) of surface into contact with the digesting food, which is thus separated from a loop of capillaries and lymphatic radicals. The capillaries of the villus are connected with the veins which contribute to the portal vein, hence carry blood to the liver. The lacteals of the villus contribute to the mesenteric lacteal system, hence the chyle and lymph pass through the mesenteric glands and the portal duct to the subclavian vein in the neck. There are thus two routes by which absorbed foods may reach the general circulation. These paths can be independently isolated; and a ABSORPTION OF PROTEIDS FROM THE INTESTINES 365 study of the composition of their discharge during active absorption con- tributes to our knowledge of the course taken by the different absorption products. Absorption of Proteids from the Intestines. Proteid is absorbed chiefly in the small intestine, though just exactly how cannot at present be affirmed. In the preceding chapter the cleavage products of proteid diges- FIG. 281. FIG. 282. FIG. 281. — Superficial Lymphatics of the Forearm and, Palm of the Hand, J.— 5; Two small glands at the bend of the arm; 6, radial lymphatic vessels; 7, ulnar lymphatic vessels; 8, 8, palmar arch of lymphatics; 9, 9', outer and inner sets of vessels; b, cephalic vein; d, radial vein; e, median vein; /, ulnar vein. The lymphatics are represented as lying on the deep fascia. (Mascagni.) FIG. 282. — Lymphatic Vessels of the Head and Neck and the Upper Part of the Trunk. (Mas- cagni.) $. — The chest and pericardium have been opened on the left side, and the left mamma de- tached and thrown outward over the left arm, so as to expose a great part of its deep surface. The principal lymphatic vessels and glands are shown on the side of the head and face, and in the neck, axilla, and mediastinum. Between the left internal jugular vein and the common carotid artery, the upper ascending part of the thoracic duct marked i, and above this, and descending to 2, the arch and last part of the duct. The termination of the upper lymphatics of the diaphragm in the mediastinal glands, as well as the cardiac and the deep mammary lymphatics, is also shown. 366 ABSORPTION tion have been discussed. It was shown there that albumoses, peptones, peptids, and the amido-acids are derived from the proteids as digestion products. It has, in the past, been assumed that peptone represents the form most freely absorbed. No peptone has, however, been isolated from the blood or lymph on the vascular side of the epithelial membrane. But the same may be said with equal truth of the other cleavage products. The present supposition is that the proteids are taken up by the epithelium and synthesized into other and more complex forms before being discharged into the blood; or that the digestion cleavages are further broken down in FIG. 283. — A Small Portion of Medullary Substance from a Mesenteric Gland of the Ox. d, d, Trabeculae; a, part of a cord of glandular substances from which all but a few of the lymph-cor- puscles have been washed out to show its supporting meshwork of retiform tissue and its capillary blood-vessels (which have been injected and are dark in the figure); b, b, lymph-sinus, of which the retiform tissue is represented only at c, c. X 300. (Kolliker.) the liver into elimination forms, such as urea, ammonium carbonate, etc. If the intestinal epithelium produces change in the proteid on its passage through, then it is evident that absorption of proteids is more than mere osmosis and filtration. This idea is further strengthened by the known power of the intestines to absorb certain albumins, egg albumin for example, which is non-diffusible and non-dialyzable. In animal foods, such as eggs, meat, etc., it is estimated that about 98 per cent of the proteid is absorbed; whereas in vegetable foods, where the pro- teid is often protected from the action of the digestive enzymes, there may be 10 to 15 per cent loss. Analysis of the total lymph discharge of the thoracic duct fails to show any increase of proteids during active digestion, from which it is inferred that proteids pass by way of the liver. ABSORPTION OF CARBOHYDRATES BY THE INTESTINES 367 From 12 to 15 per cent of the proteid remains in the food as it passes the ileocecal valve. This amount, less the loss in the feces, is absorbed in the large intestine. Absorption of Carbohydrates by the Intestines. Carbohydrates are broken down to dextrose, levulose, etc., and are absorbed as such. Even the soluble cane-sugar is split by the invertase of the intestine into the mono- saccharides, dextrose and levulose. Starch is the source of most of the 500 grams of dextrose absorbed in an average diet per day. During the absorp- tion of a carbohydrate meal the percentage of dextrose in the blood of the portal vein is increased over the normal which is o.i to 1.5 per cent. This excess of dextrose passes through the liver and is temporarily stored in the FIG. 284. — Section of the Villus of a Rat Killed during Fat Absorption, ep. Epithelium; sir, stri- ated border; c, lymph-cells; c', lymph-cells in the epithelium; /, central lacteal containing disinte- grating lymph-corpuscles. (E. A. Schafer.) liver cells as glycogen. In the case of a fistula in the receptaculum chyli, the chyle contained less than a half per cent of the total dextrose absorbed. Experiments on the rate of absorption of the different sugars seem to indicate that their absorption does not follow known physical laws and that we must assume an unknown chemical factor in the living protoplasm. Dextroses are absorbed readily by the large intestine. Fermentation process from bacterial growth produces certain acids from the carbohydrates, chiefly in the large intestine. These are readily absorbed. Absorption of Fats by the Intestines. Fats reach the absorbing epithelium in two forms, as soluble glycerin and soaps and as finely emulsi- fied fats. The first two are taken up by the epithelium readily enough, S68 ABSORPTION but in the last the process of absorption is not so clear. It is comparatively easy to demonstrate the presence of microscopic globules of fat, both in the intercellular substance and in the epithelial cells themselves. But it has been constantly noticed that there is a clear zone along the free borders of the cells. Fat drops exist in the adjacent digesting mass, and in the deeper parts of the cells, but not in this border zone. Since the demonstration of the reversible action of lipase, the view has been strengthened that in the very act of absorption the emulsified fats are decomposed and passed through the cell border only to be resynthesized in the cell protoplasm. This is of course against the strictly mechanical view. The decreasing efficiency of fats when the bile, which wets the mucous surface and dissolves the fatty acids, is withheld from the intestine also supports this view. As absorption progresses the size of the fat drops in the epithelial cells increases, a fact FIG. 285. — Mucous Membrane of Frog's Intestine during Fat Absorption, ep, Epithelium; sir, striated border; C, lymph-corpuscles; /, lacteal. (E. A. Schafer.) that is readily explained by supposing a continued synthesis and accumula- tion of fat. The fat drops are ultimately discharged into the connective-tissue spaces and finally pass into the lymph channels, the thoracic duct, and into the blood of the subclavian vein. This is the course taken by the larger per- centage of the fat. However, some of the fat is absorbed into the capillaries of the villi and passes through the liver. The presence of fat drops in the liver cells at certain times can be ascribed to storage of this absorbed fat. It is said that the more readily emulsified fats, those that melt readily at the body temperature, are the more completely absorbed. The efficiency of absorption is as high as 96 to 98 per cent for the oils, and decreases sharply for such fats as the tallows. The large intestine is capable of absorbing fats, though not so readily as the small intestine. Absorption of Minerals and Water in the Intestines. The salts common in the foods are most of them readily soluble, dissociate quite com- pletely in the dilute solutions, and diffuse and dialyze readily. Of the salts of the foods, the sodium and potassium cations and chlorine anion are the most readily dissociated and are most diffusible, while the calcium and ABSORPTION FROM THE SKIN, THE LUNGS, ETC. 369 magnesium cations and the sulphate anion are least diffusible. These sub- stances pass through the intestinal, epithelial cells and the intercellular sub- stance; at least salts easily recognized by microchemical means have been found in both localities during absorption. It seems probable that the forces concerned are largely osmosis and diffusion. Yet observers have not been able to show that the rate and character of the absorption of even the salines obey the known physical laws. In fact there is evidence that some of the salts, iron for example, are taken up as organic compounds (hematogens of Bunge). The activity of the epithelial cells is to be taken into account, even in the absorption of salts. Water, which we have seen is not absorbed in the stomach, is readily absorbed in the small intestine. Perhaps the bulk of the water taken into the system is absorbed in the upper part of the small intestine. In the large intestine, too, it is absorbed with facility and in considerable quantities. The content of the bowel is still quite fluid when it enters the ascending colon, but the feces are quite firm on discharge from the rectum. There are many analogies by which we may suppose a controlling influence of the epithelium over the process of water-absorption. Among the fishes there are species, the salmon for example, in which the blood maintains a relatively constant osmotic pressure, and therefore salt content. In the salmon this is about the same as that of human blood. The blood is separated in the gills by an extremely thin epithelium from the water in which the animals live, yet these fishes go with impunity from sea water, with two and a half times more salt than the blood, to fresh water with practically no salt at all. The epi- thelium of the gills permits the passage of oxygen, but it does not permit the diffusion or dialysis of the salts or the water in either direction. It is possible that there is a certain amount of resistance to the passage of water through the walls of the stomach, while the intestinal epithelium permits water to pass readily. The factors active in absorption are under searching investigation at the present time, so that it is reasonable to hope that the near future will give a more exact understanding of this intricate subject. ABSORPTION FROM THE SKIN, THE LUNGS, ETC. The dry corneous stratified epithelium covering the human body pos- sesses great resistance to the absorption of most substances. The sebaceous secretion keeps the surface slightly oily. Watery sclutions do not readily wet the surface and therefore do not penetrate. There is some absorption of water on prolonged contact with the skin, but the amount is insignificant. Medicated baths, especially hot baths, may be accompanied by some slight absorption of the substances dissolved in the waters; though it must be confessed that the good effects of such treatment come from other sources. 24 370 ABSORPTION On the other hand, oily substances come in more intimate contact with the skin and penetrate deeper and more readily. Therefore lotions con- taining medicines are occasionally applied to the skin, and slow but gradual absorption occurs. The volatile oils penetrate the skin readily. The epithelial lining of the lungs seems peculiarly adapted to the quick absorption of all gases and volatile substances. This is illustrated by the rapidity with which anesthesia may be accomplished by breathing the vapors of ether or chloroform. Solutions injected into or otherwise brought into contact with the sub- dermal connective tissue, the body of a muscle, or the peritoneal or thoracic cavity, very quickly pass into the general circulation. They are practically injected into the lymphatic intercellular spaces in these instances and, of course, are very readily carried through the lymphatic vessels, figures 280 and 282, to the thoracic duct and into the blood. -Comparing the rapidity of ab- sorption in the cases mentioned, that from the muscle is most rapid, a fact of medical importance in the use of the hypodermic needle for the giving of medicines in emergency. CHAPTER X EXCRETION EVERY substance taken into the body, in whatever form, must, in the end, be cast off again, no matter how great the change that may be wrought during its sojourn. We have already found that in the lungs the expired air, and in the intestine the feces, carry from the body waste matters of no further use. We have now to find that the urine separated by the kidney and the sweat and sebum of the skin are likewise channels by which the body throws off water, salts, and broken-down organic matters of no further use to the organism. Of these two organs, the skin and the kidney, the latter is by far the more important in so far as the quantity and complexity of its secretion is concerned. STRUCTURE AND FUNCTION OF THE KIDNEYS. General Structure. The kidneys are. two in number, and are situated deeply in the lumbar region of the abdomen on either side of the spinal column behind the peritoneum. They correspond in position to the last two dorsal and two upper lumbar vertebrae, the right slightly below the left in consequence of the position of the liver on the right side of the abdomen. They are about 4 inches long, 2^ inches broad, and i^ inches thick. The weight of each kidney is about 4^ ounces, 140 grams. On dividing the kidney into two equal parts by a section carried through its long convex border, figure 286, the main part of its substance is seen to be composed of two chief portions called respectively cortical and medullary, the latter being also sometimes called pyramidal, from the fact of its being composed of about a dozen conical bundles of uriniferous tubules, each bun- dle forming what is called a pyramid. The upper part of the ureter, or duct of the organ, is dilated into the pelvis ; and this, again, after separating into two or three principal divisions, is finally subdivided into 8 to 12 smaller portions, calyces, each of which receives the pointed extremity or papilla of a pyramid. Sometimes, however, more than one papilla is received by a calyx. The kidney is a compound tubular gland. Both its cortical and its medul- lary portions are composed essentially of numerous tubes, the tubuli urinijerit 371 372 FXCRETION which begin at the opening on the Malpighian pyramid and, after a devious course, end in the capsule of the glomerulus. Tubuli Uriniferi. The tubuli uriniferi, figure 287, are composed of a nearly homogeneous membrane, and are lined internally by epithelium. They vary considerably in size in different parts of their course, but are, on an average, about 40 fj. in diameter, and are found to be made up of several distinct sections. The first section or part to be identified is the Malpi- FIG. 286. — Longitudinal Section of Kidney through Hilum. a, Cortical pyramid; b, medullary ray; c, medulla; d, cortex; e, renal calyx; f, hilum; g, ureter; h, renal artery; *, obliquely cut tubules of medulla; / and k, renal arches; /, column of Bertini; m, connective tissue and fat surrounding renal vessels; n, medulla cut obliquely; o, papilla; p, medullary pyramid. (Merkel-Henle.) ghian, or Bowman's, capsule, figure 287. It is composed of a hyaline membrana propria, thickened by a varying amount of fibrous tissue, and lined by flattened nucleated epithelial plates. This capsule is the dilated extremity of the uriniferous tubule which is invaginated to receive the glomerulus of con- voluted capillary blood-vessels. The invaginated portion of the tubule is of particular importance since it is the membrane through which a large part of the urine is secreted. The glomerulus is connected with an efferent and an afferent blood-vessel. The Malpighian capsule is connected by a con- stricted neck, figure 287, N, with the proximal convoluted tubule. This forms TUBULI URINIFERI 373 several distinct curves and is lined with short columnar cells. The tube next passes almost vertically downward toward the medulla, forming the spiral tubule, still within the cortex of the kidney, which is of much the same diameter. The loop of Henle, L, in the medulla, is a very narrow tube lined with flattened nucleated cells. Passing vertically upward from the loop of LABYRINTH \MED.RAY\ LABYR. Pelvit FIG. 287. — Scheme of Uriniferous Tubule and of the Blood- vessels of the Kidney, Showing Their Relation to Each Other and to the Different Parts of the Kidney. G, Glomerulus; BC, Bowman's capsule; TV, neck, PC, proximal convoluted tubule; S, spiral tubule; D, descending arm of Henle's loop; L, Henle's loop; A, ascending arm of Henle's loop; IDC, distal convoluted tubule; AC, arched tubule; SC, straight collecting tubule; ED, duct of Bellini; A, arcuate artery, and V, arcuate vein, giving off interlobular vessels to corte.x and vasa recta to medulla; a, afferent vessel of glomer- ulus; e, efferent vessel of glomerulus; c\ capillary network in cortical labyrinth; s, stellate veins; vr, vasa recta and capillary network of medulla. (Pearsol.) Henle, the tubule varies somewhat in histological character, but the irregular tubule and the distal convoluted tube, identical in all respects with the prox- imal convoluted tube, are to be noted. The proximal convoluted tube passes into the curved and straight collecting tubes, the latter running vertically downward to the papillary layer, and, joining with other collecting tubes, form larger ducts which finally open at the apex of the papilla. These collecting tubes are lined with nucleated columnar or cubical cells. 374 EXCRETION Renal Blood Supply. The renal artery divides into several branches which pass in at the hilus of the kidney and are covered by a fine sheath of areolar tissue derived from the capsule. They enter the substance of the organ chiefly in the intervals between the papillae and at the junction between the cortex and the boundary layer. The main branches then pass almost horizontally, forming more or less complete arches and giving off branches upward to the cortex and downward to the medulla. The former are for the most part straight; they pass almost vertically to the surface of the kidney, giving off laterally in all directions longer and shorter branches, which ulti- FIG. 288. — From a Vertical Section through the Kidney of a Dog, the Capsule of which is Sup- posed to be on the Right, a, The capillaries of the Malpighian capsule, the glomerulus, are arranged in lobules; n, neck of capsule; c, convoluted tubes cut in various directions; b, irregular tubule: d, e, and / are straight tubes running toward capsules forming a so-called medullary ray; d, collect- ing tube; e, spiral tube; f, narrow section of ascending limb. X 380. (Klein and Noble Smith.)] mately supply the glomerulus. The small afferent artery, figures 287, a, 290, d, which enters the Malpighian capsule, breaks up in the interior into a dense convoluted and looped capillary plexus, which is ultimately gathered up again into several small efferent vessels, comparable to minute veins, which leave the capsule at one or more places near the point at which the afferent artery enters it. On leaving, they do not immediately join other small veins as might have been expected, but again break up into a second set of capillary vessels which form an interlacing network around the urinif- erous tubules. This second capillary plexus terminates in small veins which, by union with others, help to form the radicles of the renal vein. RENAL, BLOOD SUPPLY 375 These form venous arches corresponding to the arterial arches situated between the medulla and cortex. Thus, in the kidney, the blood entering by the renal artery traverses two sets of capillaries before emerging by the renal vein, an arrangement which may be compared to the portal system. The tuft of vessels within the Malpighian capsule in the course of de- velopment has been thrust into the dilated extremity of the urinary tubule, which finally completely invests it. Thus within the Malpighian capsule there are two layers of squamous epithelium, a parietal layer lining the cap- sule proper, and a visceral or reflected layer immediately covering the vas- cular tuft, figure 290, and sometimes dipping down into its interstices. This FIG. 289. — Transverse Section of a Renal Papilla, a, Large tubes or papillary ducts; b, c.and d, smaller tubes of Henle; e, f, blood capillaries, distinguished by their natter epithelium. (Cadiat.) reflected layer of epithelium is readily seen in young subjects, but cannot always be demonstrated in the adult, figures 290 and 291. The vessels which enter the medullary layer break up into smaller arte- rioles, which form a fine arterial meshwork around the tubes of the papillary layer and end in a similar plexus from which the venous radicles arise. The vessels do not form a double set of capillaries. Besides the small afferent arteries of the Malpighian bodies there are, of course, others which are distributed in the ordinary manner, for the nutri- tion of the different parts of the organ; and there are numerous straight vessels, the vasa recta, in the pyramids between the tubes. Some of these are branches of the vasa efferentia from Malpighian bodies, and therefore comparable to the venous plexus around the tubules in the cortical portion, while others arise directly as small branches of the renal arteries. 376 EXCRETION Renal Nerves. Vaso-constrictor and vaso-dilator nerves are sup- plied to the blood-vessels of the kidney, but no clearly denned secretory nerves have yet been demonstrated for the organ. The vascular nerves arise out of the anterior spinal roots (Bradford), chiefly the eleventh to the FIG. 290.— Malpighian Capsule and Tuft of Capillaries, Injected through the Renal Artery with Colored Gelatin, a, Glomerular vessels; b, capsule; c, anterior capsule; d, glomerular artery; e, efferent veins; /, epithelium of tubes. (Cadiat.) FIG. 291. — Diagrams Illustrating Stages in the Development of the Malpighian Capsule. In i and 2 the developing blood-vessel is approaching the blind end of the capsule. In 3 the tubule is beginning to invaginate and enclose the capillary. In 4 and 5 later stages are shown. The cells forming the two layers of the capsule grow very thin. (Bailey.) thirteenth dorsal nerves. They reach the kidney by way of the splanchnic nerves and the renal plexus to the renal artery along which they run into the substance of the kidney. Berkeley has demonstrated nerve plexuses about the arterioles and around Bowman's capsule. Terminal knob-like THE URETERS AND URINARY BLADDER 377 endings of nerve fibrils were shown. Some authors have claimed renal vaso- constriction following vagus stimulation, but the fact seems not to be uni- versally admitted. The Ureters and Urinary Bladder. The duct of each kidney, the ureter, is a tube about the size of a goose-quill and from twelve to sixteen inches in length. It is continuous above with the pelvis of the kidney, and ends below by obliquely perforating the walls of the bladder and opening on its internal surface. It has three principal coats, an outer fibrous, a middle muscular, of which the fibers are unstriped and arranged in three layers. The fibers of the central layer are circular, and those of the other two layers longitudinal in direction. It has an internal mucous lining con- tinuous with that of the pelvis of the kidney above and the lining of the urinary bladder below. The urinary bladder, which forms a receptacle for the tem- porary lodgment of the urine in the intervals of its expulsion from the body, is more or less pyriform. Its widest part, which is situated above and be- hind, is termed the jundus; and the narrow constricted portion in front and below, by which it becomes continuous with the urethra, is called its cervix or neck. It is constructed of four principal coats: serous, muscular, areolar or submucous, and mucous. The fibers of the muscular coat deserve special mention. They are unstriped, are arranged in three principal layers, of which the external and internal have a general longitudinal, and the middle layer a circular, direction. The latter are especially developed around the cervix of the organ, and are described as forming a sphincter vesicae. The mucous membrane is provided with mucous glands, which are more numer- ous near the neck of the bladder. The bladder is well provided with blood- and lymph-vessels, and with nerves. The latter are from the sacral plexus (spinal) and hypogastric plexus (sympathetic). Ganglion-cells are found, here and there, in the course of the nerve fibers. THE URINE. Quantity and General Properties. Healthy urine is a perfectly transparent amber-colored liquid, with a peculiar but not disagreeable odor, a bitterish salty taste, and a specific gravity of from 1020 to 1025. The urine consists of water holding in solution certain organic and saline matters as its ordinary constituents, and occasionally various other matters. Some of the latter are indications of diseased states of the system, and others are derived from unusual articles of food or drugs taken into the stomach. The total quantity of urine passed in twenty-four hours is influenced by numerous circumstances. In adults of average size and medium ac- tivity the daily amount of urine may be given as from 1,200 c.c. to 1,500 c.c. In Chittenden's recent observations on nine athletic students and on eight 3 78 EXCRETION soldiers the average daily output of urine through a period of about five months was for the students 1,215 c-c- witn average specific gravity of 1020, and for the soldiers 1,042 c.c. with specific gravity of 1023. GENERAL CHEMICAL COMPOSITION OF THE URINE. Water 967 Solids: Urea 14.230 Other nitrogenous crystalline bodies : -^ Uric acid, principally in the form of alkaline Urates, a trace only free ( fi Kreatinin, Xanthin, Hypoxanthin f Hippuric acid Mucus, Pigments, and ferments J Salts: Inorganic: Principally Sulphates, Phosphates, and Chlorides of So-^j dium and Potassium, with Phosphates of Magnesium and Calcium, traces of Silicates ! R Organic: Lactates, Hippurates, Oxalates, Acetates, and Formates, which appear only occasionally . J - 33 Sugar a trace sometimes. Gases (nitrogen and carbonic acid principally). Reaction. The normal reaction of the urine is slightly acid. This acidity is due to carbonic acid and to acid phosphate of sodium, and is less marked soon after meals. After standing for some time the acidity increases from a kind of acid fermentation, due in all probability to the presence of mucus and fungi, and acid urates or free uric acid is deposited. After a time, varying in length according to the temperature, the reaction becomes strongly alkaline from the change of urea into ammonium carbonate, due to the presence of one or more specific micro-organisms (micrococcus urece). In the process of fermentation the urea takes up two molecules of water, a strong ammoniacal and fetid odor appears, and there are deposits of triple phosphates and alkaline urates. This does not occur unless the urine is freely exposed to the air, or, at least, until air has had access to it. In most herbivorous animals the urine is alkaline and turbid. The difference depends not on any peculiarity in the mode of secretion, but on the difference in the food on which the two classes of animals subsist; for when carnivorous animals, such as dogs, are restricted to a vegetable diet, their urine becomes pale, turbid, and alkaline like that of herbivorous animals, while the urine voided by the Herbivora, e.g., rabbits, fed for some time exclusively upon animal substances, presents the acid reaction and other qualities of the urine of Carnivora, and its ordinary alkalinity is again restored only OP the substitution of a vegetable for the animal diet. Human urine is not usually rendered alkaline by vegetable diet, but it becomes so SPECIFIC GRAVITY OF URINE 379 after the free use of alkaline medicines, or of the alkaline salts with carbonic or vegetable acids; for these latter are changed into alkaline carbonates previous to elimination by the kidneys. Specific Gravity of Urine. The average specific gravity of the human urine is about 1020 to 1025. The relative quantity of water and of solid constituents of which it is composed is materially influenced by the condition and occupation of the body during the time at which it is secreted; by the length cf time which has elapsed since the last meal; by the amount of water taken; and by several other less important circumstances. The morning urine is the best adapted for analysis in health, since it represents the simple secretion unmixed with the elements of food or drink. If it is not used the whole of the urine passed during a period of twenty-four hours should be taken. The specific gravity of the urine may thus, consistently with health, range widely on both sides of the usual average. It may vary from 1015 in the winter to 1025 in the summer; but variations of diet and exercise, and many other circumstances, may make even greater differences than these. The variations may be extreme in disease, sometimes decreasing in albuminuria to 1004, and frequently increasing in diabetes, when the urine is loaded with sugar, to 1050 or even to 1060. AVERAGE DAILY QUANTITY OF THE CHIEF URINARY CONSTITUENTS. (MODIFIED FROM PARKES.) Per Kilo of Body Weight. 2 3. oooo grams 0.8800 .5000 .0140 .0084 .0060 .1510 .0480 -0305 .1260 Water -- 1,500. c.c. Solids 72. grams Urea 33 J8o Kreatinin. .910 Uric Acid 555 Hippuric Acid -400 Pigment and Extractives IO.OOO M Sulphuric Acid 2.012 ' Phosphoric Acid 3-l64 < Chlorine. . 7.000 I Ammonia 77° 1 Potassium 2.500 ( Sodium . . 11.090 " Calcium. . .260 1 207 " Variations in the Constituents of Urine. Most of the constituents are, even in health, liable to variations from the proportions given in the above table. The variations of the quantity of water in different seasons, and according to the quantity of drink and exercise, have just been men- tioned. The water of the urine is also liable to be influenced by the condi- tion of the nervous system, being sometimes greatly increased, e.g., in hysteria and in some other nervous affections, and at other times diminished. The increase in water may be either attended with an augmented quantity of solid matter in some diseases, as in ordinary diabetes, or may be nearly the sole 380 EXCRETION change, as in the affection termed diabetes insipidus. A febrile condition almost always diminishes the quantity of water; and a like diminution is caused by any affection which draws off a large quantity of fluid from the body through any other channel than that of the kidneys, e.g., the bowels or the skin. In disease or after the ingestion of special foods, various abnormal sub- stances occur in urine, of which the following may be mentioned. Serum- albumin, Globulin, Ferments (apparently present in health also), Proteoses, Blood, Sugar, Bile acids and pigments, Casts, Fats, various Salts taken as foods or as medicines, Micro-organisms of various kinds. The Nitrogenous Substances in Urine. The nitrogenous waste prod- ucts which are formed in the body in the metabolism of the proteid foods are ultimately eliminated chiefly through the kidney, to some extent through the bowel, and slightly through the skin. The total nitrogen in the urine and in the feces multiplied by the factor 6.25 is a measure of the nitrogenous FIG. 292. — Crystals of Urea. foods, i.e., proteids, metabolized by the body. The nitrogen excreted in the urine is in the form of urea 87.5 per cent, ammonia 4.3 per cent, kreatinin 3.6 per cent, uric acid 0.8 per cent, and undetermined forms 3. 73 per cent, according to Folin. The total quantity of nitrogen eliminated in all these forms per day is given as about 18 grams. In Chittenden's recent experi- ments this quantity is reduced to as low as 6 grams or even less per day. Urea. Urea, CON2H4, is the principal solid constituent of the urine, forming nearly one-half of the total quantity. It is also the most important ingredient, since it is the chief form in which the waste nitrogen which is derived from proteid metabolism is excreted from the body. Properties. Urea, like other solid constituents of the urine, exists in a state of solution. When in the solid state, it appears in the form of delicate silvery acicular crystals, which, under the microscope, are seen as four- sided prisms, figure 292. It readily combines with some acids, like a weak base, and may thus be conveniently procured in the form of crystals of nitrate or oxalate of urea, figures 293 and 294. THE FORMATION OF UREA 381 Urea is colorless when pure; when impure it may be yellow or brown. It is without smell and of a cooling niter-like taste. It has neither an acid nor an alkaline reaction, and deliquesces in a moist and warm atmosphere. At 15° C. it requires for its solution less than its own weight of water. It is soluble in all proportions of boiling water, and requires five times its weight of cold alcohol for its solution. It is insoluble in ether. At 120° C. it melts without undergoing decomposition; and at a still higher temperature ebulli- tion takes place, and carbonate of ammonium sublimes. Urea is decomposed by sodium hypochlorite of hypobromite or by nitrous acid, with evolution of nitrogen. It forms compounds with acids, of which the chief are urea hydrochloride, CON2H4.HCL; urea nitrate, CON2H4.- HNO3; and urea phosphate, CON2H4.H3PO4. It forms compounds with FIG. 293. — Crystals of Urea Nitrate. FIG. 294. — Crystals of Urea Oxalate. metals such as HgO.CON2H4, with silver, CON2H2Ag2. Urea is isomeric with ammonium cyanate, NH4CNO, and was first prepared artificially from that substance. The Formation of Urea. Proteids in the body have their nitrog- enous moiety broken down to ammonia, by what Folin considers essentially a series of hydrolytic cleavages, which is then built up into urea, as described more fully in the chapter on Metabolism. This last step is essentially a synthetic process which, from the fact that ammonium carbonate introduced into the blood is eliminated as urea, may be supposed to occur as follows: NH2 NH2 / / CO — H2O =CO \ \ ONH4 NH2 Ammonium Carbamate Urea Urea is present in varying amounts in all organs and fluids of the body, as shown by the following determinations of Schoendorff on the dog: Per cent of Organ. Urea. Blood 0.116 Muscle 0.080 Kidney o. 670 Liver 0.112 Heart o. 173 Brain o. 128 Spleen 0.122 382 EXCRETION It has been proven that the kidney does not form urea; in fact the kid- neys may be removed from the body, and urea will continue to accumulate in the blood. Urea is formed chiefly in the liver, but may in part be con- structed in other organs, as described more fully on page 411. It follows that the kidney is only the channel for the elimination of this nitrogenous compound. Decomposition of the urea with development of ammonium carbonate takes place from the action of bacteria (micrococcus ureafi) when urine is kept for some days after being voided, which explains the ammoniacal odor then evolved. The urea is sometimes decomposed before it leaves the bladder, when the mucous membrane is diseased and the mucus secreted by it is abundant; but decomposition does not occur unless atmospheric germs have had access to the urine. Quantity Excreted. The quantity of urea excreted is, like that of the urine Itself, subject to considerable variation. For a healthy adult about 30 grams \ er day may be taken as rather a high average. Its percentage in healthy urine is from 2 to 2.5. Its amount is materially influenced by diet, being greater on a diet of high proteid content. The quantity of urea excreted by children, relatively to their body-weight, is much greater than by adults; thus the quantity of urea execreted per kilogram of weight was found to be, in a child, 0.8 gram; in an adult only 0.4 gram. Regarded in this way, too, the excretion of carbonic acid gives similar results, the proportions in the child and adult being as 82 to 34. Uric Acid. Uric acid, C5H4N4O3, is rarely absent from the urine of man or animals, though in the feline tribe it seems to be sometimes entirely replaced by urea. In birds and reptiles uric acid or its salts is the chief form in which nitrogen is eliminated from the body. Properties. Uric acid is a colorless, crystalline compound of the purin group, figure 295. It is odorless and tasteless. It is very slightly soluble in water, quite insoluble in alcohol and ether, and freely soluble in solutions of the alkaline carbonates and other salts. A study of the elimination of nitrogen in birds, i.e., geese, has shown that uric acid, like urea in mammals, is formed largely in the liver from antecedent proteid nitrogen. In man the elimination of uric acid increases or decreases with the proteid content of the daily diet. It does not, however, follow the variations of the food nitrogen so closely as in the case of urea. Any food with a rich nuclein content increases the excretion of uric acid. This ob- servation has led to the inference that uric-acid nitrogen is derived from nuclear metabolism, page 413. Other representatives of the purin group are adenin, guanin, xanthin, hypoxanthin, etc. Chemically, caffeine from coffee is a trimethyl xanthin. The most common form in which uric acid is deposited in urine is that of a brownish or yellowish powdery substance, consisting of granules of HIPPURIC ACID ammonium or sodium urate. When deposited in crystals, it is most fre- quently in rhombic or diamond-shaped laminae, but other forms are not uncommon, figure 295. When deposited from urine, the crystals are gener- ally more or less deeply colored, from being combined with the coloring principles of the urine. Hippuric Acid. This compound, C9H9NO3, has long been known to exist in the urine of herbivorous animals in combination with soda. It also exists naturally in the urine of man, in a quantity equal to or rather ex- FIG. 295. — Various Forms of Uric Acid Crystals. FIG. 296. — Crystals of Hippuric Acid. ceeding that of the uric acid. The quantity excreted is increased by a vegetable diet. Hippuric acid appears to be formed in the body from benzoic acid or from some allied substance. The benzoic acid unites with glycin, and hip- puric acid and water are formed thus: C6H5.COOH + CH2.NH2.COOH = C6H5.CO.NH.CH2.COOH + H2O. Benzoic Acid Glycin Hippuric Acid Hippuric acid is the one substance which has been clearly demonstrated to be formed by the kidney itself. Kreatinin. This substance is present in urine in a remarkably constant quantity, as shown recently by Folin's analyses. Its daily excre- tion quantity is from i to 15 grams according to the amount of active tissue in the individual. It is of especial importance as a measure of the metab- olism of muscle protoplasm. Ammonia. A considerable daily quantity of ammonia in com- bination is found in the urine, showing that this is an important method of nitrogen elimination. Pigments. The pigments of the urine are the following: i, Uro- chrome, a yellow coloring matter, giving no absorption band; of which but little is known. Urine owes its yellow color mainly to the presence of this body. 2, Urobilin, an orange pigment, of which traces may be found in nearly all urines, and which is especially abundant in the urines passed by 384 EXCRETION febrile patients. It is characterized by a well-marked spectroscopic ab- sorption band at the junction of green and blue. Those who believe urobilin to be identical with hydrobilirubin suppose that the bilirubin is reduced by the putrefactive processes in the intestines, and is conveyed in its reduced form by the blood stream to the kidneys. 3, Uroerythrin, occasionally found. And, 4, Uromelanin. Mucus. Mucus sediment in the urine consists principally of the epithelial debris from the mucous surface of the urinary passages. Parti- cles of epithelium, in greater or less abundance, may be detected in most samples of urine, figure 297. As urine cools, the mucus is sometimes seen suspended in it as a delicate opaque cloud, but generally it falls. In inflam- FIG. 297. FIG. FIG. 297. — Urinary Deposit of Mucus, etc. FIG. 298.— Urinary Sediment of Triple Phosphates (large prismatic crystals) and Urate of Amonium, from urine which had undergone alkaline fermentation. matory affections of the urinary passages, especially of the bladder, mucus is secreted in large quantities and speedily undergoes decomposition. Saline Matter. Sulphuric acid, in the form of salts, is taken in very small quantity with food. Sulphur is also a constituent part of the proteid molecule; hence its elimination, like that of nitrogen, gives a certain measure of proteid metabolism. It is excreted as inorganic sulphates of sodium and potassium, and as ethereal sulphates, compounds of phenol, cresol, skatol, i.e., cresol sulphuric acid (C7H?OSO2OH), etc. The phosphoric acid in the urine is combined partly with the alkalies, partly with the alkaline earths — about four or five times as much with the former as with the latter. In blood, saliva, and other alkaline fluids of the body phosphates exist in the form of alkaline, neutral, or acid salts. In the urine they are acid salts, viz., the sodium, ammonium, calcium, and magne- sium phosphates, the excess of acid being (Liebig) due to the appropriation of the alkali with which the phosphoric acid in the blood is combined, by the several new acids which are formed or discharged at the kidneys, namely the uric, hippuric and sulphuric acids, all of which are neutralized with soda. OCCASIONAL CONSTITUENTS OF URINE 385 The phosphates are taken largely in both vegetable and animal food. Some are excreted at once; others only after being transformed and incor- porated with the tissues. Calcium and magnesium phosphates form the principal earthy constituents of bone, and from the decomposition of the osseous tissue the urine derives a quantity of this salt. The decomposition of other tissues also furnishes large supplies of phosphorus to the urine, which phosphorus is supposed, like the sulphur, to be united with oxygen, and then combined with bases. The quantity is, however, liable to considerable variation. The earthy phosphates are more abundant after meals, whether of animal or vegetable food, and are diminished after long fasting. The alkaline phosphates are increased after animal food, diminished after vegetable FIG. 299. — Crystals of Cysttn, FIG. 300. — Crystals of Calcium Oxalate. food. Phosphorus uncombined with oxygen appears, like sulphur, to be ex- creted in the urine. When the urine undergoes alkaline fermentation phos- phates are deposited in the form of a urinary sediment, consisting chiefly of ammonio-magnesium phosphates (triple phosphate), figure 298. The Chlorine of the urine occurs chiefly in combination with sodium. Next to urea, sodium chloride is the most abundant solid constituent of the urine. As the chlorides exist largely in food, and in most of the animal fluids, their occurrence in the urine is easily understood. Occasional Constituents of Urine. Cystin, C3H7NSO2, figure 299, is an occasional constituent of urine. It resembles taurin in containing a large quantity of sulphur — more than 25 per cent. It does not exist in healthy urine. Another common morbid constituent of the urine is Oxalic acid, which is frequently deposited in combination with calcium, figure 300, as a urinary sediment. Like cystin, but much more commonly, it is the chief constituent of certain calculi. Dextrose and albumin are sometimes present in pathological urine, and are of particular interest from the clinical point of view. See the subject Gly- cosuria, page 418. 25 386 EXCRETION THE METHOD OF EXCRETION OF URINE. The secretion of urine is an act the complexity of which can be profitably discussed only after a clear understanding of three main factors which have already been presented, viz., the chemical composition of the urine secreted, the structure of the kidney tubule as a secreting organ, and, finally, the chemi- cal composition of the blood which supplies the materials to the kidney for the formation of the urine. The substances found in the urine are for the most part also to be found in the blood-plasma. But the relative percentage composition is very different. The amount of urea in the blood is only a fractional part as concentrated as in the urine, while albumins and sugars, which are so plentiful in the blood, are normally present in the urine only in traces. The presence of the glomerulus with its special vascular supply, and the different loops of the tubule, with its gland-like epithelial wall, would, a priori, lead one to suspect special functions for each. Theories of the Secretion of Urine. Bowman in 1842, wholly on structural grounds, advanced a theory of urinary secretion which has more recently been restated and given an experimental basis by Heidenhain. This view as given by Heidenhain is as follows: i, The secretion in the kidney depends upon the physiological activity of special secreting cells which are of two kinds. 2, The first type of cell is represented by the single layer of epithelium covering the glomerular capil- laries. These cells secrete especially water and salts. 3, The second type of cell is represented by the gland-like epithelial cells which form the convo- luted tubules and the loop of Henle. These cells secrete the urea, uric acid, and other specific constituents of the urine. 4, The activity of each kind of cell is influenced by the chemical composition of the blood and by the flow of blood through the kidney. 5, The relative secretory activity of the glomer- ular cells and the tubule cells is sufficient to account for the variation in the chemical composition of the urine. Ludwig in 1844 advanced a strictly mechanical theory of urine secretion based on his own experiments. He considered the glomerulus and Bowman's capsule as a filtering apparatus in which substances present in the blood are driven through the epithelium of the capsule into the renal tubule by the positive pressure of the blood in the glomerular capillaries. This very dilute urine in the capsule is supposed to be concentrated by the resorption of water as it flows down the tubule. Ludwig originally considered this resorption of water an imbibition process in which the greater saturation of salts in the blood caused water to be taken up through the renal tubule walls, an osmotic process. At present most observers who accept the view that filtration takes place at the glomerulus explain the resorption of water down the tubules as an act of cellular resorption or secretion. Experimental Observations. There are numerous nerves to the EXPERIMENTAL OBSERVATIONS 387 kidney, but no proven secretory influence has been shown. The variations in the secretion of urine that follow nervous stimulation are quite satisfactorily explained by the changes in the blood flow. The kidney can be placed in an onkometer and its variation in volume measured directly, figures 301 and 302. This volume measurement, when taken with the arterial pressure, gives a very good index of the volume of blood flowing through the kidney. Now when the kidney is inserted in an onkometer and the urine collected from the ureter, it is found in general that the greater the pressure and flow of blood the greater the secretion of urine, as would follow if the glomerulus were a filtering mechanism. However, if the renal vein is partially obstructed, even though the blood pressure be in- creased, the amount of urine secreted is sharply decreased. If the vein is FIG. 301. — Diagram of Roy's Onkometer. a Represents the kidney enclosed in a metal box, which opens by hinge /; b, the renal vessels and ducts. Surrounding the kidney are two chambers formed by membranes, the edges of which are firmly fixed by being clamped between the outside and inside metal capsules (the latter not represented in the figure), the two being firmly screwed together by screws at h, and on the opposite side. The membranous chamber below is filled with a varying amount of warm oil, according to the size of the kidney experimented with, through the opening then closed with the plug *'. After the kidney has been enclosed in the capsule, the mem- branous chamber above is filled with warm oil through the tube e, which is then closed by a tap (not represented in the diagram); the tube d communicates with a recording apparatus, and any alteration in the volume of the kidney is communicated by the oil in the tube to the chamber d of the Onkograph, figure 302. completely occluded, the secretion of urine not only ceases for the time but does not immediately begin again when the blood pressure and flow are re- established. The closure of the vein for only one or two minutes is said to stop the flow of urine for as much as forty-five minutes. This short inter- ruption of the circulation is sufficient to bring about other changes in the glomerular epithelium, for it now excretes albumin, which it did not previously let pass. Therefore, it is not pressure merely that favors the secretion, but there must be an efficient flow of blood. The secretion is influenced espe- cially by the amount of blood flowing through the kidney in a given time. 388 EXCRETION In the frog the kidney has a double blood supply. The renal artery supplies the glomeruli, while a branch of the renal-portal vein supplies the tubules. Nussbaum ligated the renal artery in one kidney of the frog, while leaving the circulation of the other kidney undisturbed. He found that the operated kidney secreted little or no urine, but that it could be made to secrete by injections of urea, but not by injections of albumin or sugar as in the nor- mal kidney. Ligation of the renal-portal vein, which supplies the tubules in the frog, caused a decrease in the quantity of the secretion, whereas, accord- ing to Ludwig's view, it ought to have increased the quantity, since obviously resorption could not take place with any degree of efficiency. In the main, the evidence is in favor of the view that even the glomerular epithelium does FIG. 302. — Roy's Onkograph, or Apparatus for Recording Altera^ns in the Volume of the Kid- ney, etc., as shown by the onkometer. a. Upright, supporting recording lever /, which is raised or lowered by the needle b, which works through /, and which is attached to the piston e, working in the chamber d, with which the tube from the onkometer communicates. The oil is prevented from being squeezed out as the piston descends, by a membrane, which is clamped between the ring- shaped surfaces of the cylinder by the screw * working upward ; the tube h is for filling the instru- ment. not filter merely, but that it, as living protoplasm, regulates and controls the quantity and kind of material passing through it. Micro-chemical observations have been enlisted to demonstrate more fully, if possible, the activity of the differem parts of the epithelial tubule. Heiden- hain, by injections of indigo-blue into the blood stream, followed by rapid fixation of the kidney in alcohol at the proper stage of elimination, has de- monstrated crystals of the pigment in the renal epithelial cells and in the lumen of the tubule. He concluded that these cells were actively eliminating the pigment by a secretory process. This observation has been questioned. But Heidenhain's view is strengthened by Bowman's observation that in birds crystals of uric acid are to be seen in the cells of the convoluted tubules, and in the lumen adjacent. Only traces of the sugars and proteids of the blood are found in normal urine, but when either cane sugar, peptone, or egg albumin is introduced into the blood it is rapidly eliminated by the kidney. Egg albumin is not essen- DIURETICS 389 tially different from the serum albumin of the blood, but the serum albumin is not excreted. These are both non-dialyzable compounds. Sugar and urea, both readily dialyzable, present the same comparison, i.e., urea is ex- creted, while sugar is not. If, however, the percentage of sugar is high, 0.25 per cent or more, it is then eliminated. The excretion of the highly diffusible sodium chloride bears a similar quantitative relation to excretion. If present in the blood in relatively low amounts it is not secreted, while if the concentra- tion is slightly greater it may be quickly eliminated. Other inorganic salts, present only in traces, are meanwhile rapidly eliminated. Even the rapid elimination of a slight excess of water in the blood can scarcely be explained on purely physical grounds. To discharge the water across the glomerulus from the blood to the urine requires an expenditure of osmotic pressure much greater than that balanced by the blood pressure. That is, the epithelial cells must do work, and the energy is dependent on metabolism in the cells. At FIG. 303. — Curve Taken by Renal Onkometer Compared with that of an Ordinary Blood- pressure Curve, a, Kidney curve; b. blood -pressure curve. (Roy.) least one substance, hippuric acid, is built up chemically by the renal cells and secreted as such. It would seem, therefore, that the separation of urine in the kidney is a secretory process dependent on the protoplasmic activity of the living renal cells, that the apparent selective property of the cells is a manifestation of such activity, and that even water is secreted. Diuretics. Certain substances increase the flow of urine and are called diuretics. They act directly on the renal epithelium, for example, urea, or indirectly on the circulatory system to increase the flow of blood. Digitalis is a well-known diuretic which increases the efficiency of the circula- tion. It also stimulates the renal epithelium with the production of a marked increase in the flow of urine. Caffeine diuresis can best be explained on an assumed stimulating action on the renal epithelium. Urea introduced into the blood produces a copious secretion of urine. Both urea and the saline diuretics induce a flow of urine out of all proportion to the osmotic changes produced, and they may be regarded as direct stimulators of the renal epithe- lium. 390 EXCRETION THE DISCHARGE OF THE URINE. As each portion of urine is secreted, it propels that which is already in the uriniferous tubes onward into the pelvis of the kidney. Thence it passes through the ureter into the bladder, from which at intervals it is discharged to the exterior. The rate and mode of entrance of urine into the bladder has been watched in cases of ectopia vesicae, i.e., cases in which fissures in the anterior or lower part of the walls of the abdomen and of the front wall of the bladder expose to view the orifices of the ureters. The urine does not enter the bladder at any regular rate, nor is there a synchronism in its move- ment through the two ureters. Ordinarily two or three drops enter the bladder every minute, each drop as it enters first raising up the little papilla on which the ureter opens, and then passing through the orifice, which at once again closes like a sphincter. Its flow is aided by the peristaltic con- tractions of the ureters, and is increased in deep inspiration or by straining. The urine collected in the bladder is prevented from regurgitation into the ureters by the mode in which these pass through the walls of the bladder, namely, by their lying a half to three-quarters of an inch between the muscu- lar and mucous coats before they turn rather abruptly forward and open through the latter into the interior of the bladder. Micturition. The contraction of the muscular walls of the bladder may by itself expel the urine with little or no help from other muscles. The vesicular pressure is increased in the voluntary act by the contraction of the abdominal and other expiratory muscles which bear on the abdominal viscera, thus aiding in the expulsion of the contents of the bladder. The diaphragm is at the same time fixed in contraction and the sphincter of the bladder relaxes. The pressure within the bladder under the combined con- tractions of these expulsive muscles sometimes amounts to 8 to 10 cm. of mercury. The act is completed by the accelerator urinae muscle, which, as its name implies, quickens the stream and expels the last drop of urine from the urethra. The act is under the regulative control of a nervous center in the lumbar spinal cord, through which, as in the case of the similar center for defecation, the various muscles concerned are coordinated in their action. It is well known that the act may be reflexly induced, e.g., in children who suffer from intestinal worms or other such irritation. Generally the afferent impulses which set up the reflexes leading to the desire to micturate are ex- cited by overdistention of the bladder, or sometimes by a few drops of urine passing into the urethra. This impulse passes up to the lumbar center or centers, and reflexly produces on the one hand inhibition of the sphincter and on the other contraction of the necessary muscles for the expulsion of the contents of the bladder. In the voluntary act these motor centers are stimulated to activity by impulses coming from the higher cerebral centers. STRUCTURE AND FUNCTIONS OF THE SKIN 391 THE STRUCTURE AND EXCRETORY FUNCTIONS OF THE SKIN. The skin serves, i, as an external integument for the protection of the deeper tissues, and 2, as a sensitive organ in the exercise of touch, a subject to be considered in the chapter on the Special Senses. It is also, 3, an im- portant secretory and excretory organ; and 4, an absorbing organ. 5, It plays an important part in the regulation of the temperature of the body by controlling the loss of heat, i.e., a temperature-regulating function, discussed in the chapter on Animal Heat. Structure. The skin consists principally of a vascular tissue named the corium, derma, or cutis vera, and of an external covering of epithe- lium termed the epidermis or cuticle. Within and beneath the corium are embedded several organs with special functions, namely, sudoriferous glands, FIG. 304. — Vertical Section of the Epidermis of the Prepuce, a, Stratum corneum, of very few layers, the stratum lucidum and stratum granulosum not being distinctly represented; b, c, d, and e, the layers of the stratum Malpighii, a certain number of the cells in layers, d, and e showing signs of segmentation; layer c , consists chiefly of prickle or ridge and furrow cells; /, basement membrane; g, cells in cutis vera. (Cadiat.) sebaceous glands, and hair follicles ; and on its surface are sensitive papilla. The so-called appendages of the skin — the hair and nails — are modifications of the epidermis. The epidermis is composed of several strata of cells of various shapes and sizes; it closely resembles in its structure the epithelium of the mucous mem- brane that lines the mouth or covers the cornea. The following four layers may be distinguished; 392 EXCRETION The Stratum lucidum, a bright homogeneous membrane, consisting of squamous cells closely arranged, in some of which a nucleus can be seen. Stratum granulomm, consisting of one layer of flattened, fusiform, distinctly nucleated cells. Stratum Malpighii or Rete mucosum consists of many strata of cells. The deepest cells, placed immediately above the cutis vera, are columnar with oval nuclei, succeeded by a number of layers of more or less FIG. 305. — Vertical Section of Skin. A, Sebaceous gland opening into hair follicle; B, mus- cular fibers; C, sudoriferous or sweat gland; D, subcutaneous fat; E, fundus of hair-follicle, with hair- papillae. (Klein.) polyhedral cells with spherical nuclei; the more superficial layers are con- siderably flattened. The deeper surface of the rete mucosum is accurately adapted to the papillae of the true skin, being, as it were, moulded on them. It is very constant in thickness in all parts of the skin. The cells of the middle layers of the stratum Malpighii are connected by processes, and thus form prickle cells, figure 28. The pigment of the skin, in the deeper cells of rete mucosum, causes the various tints observed in different individuals and differ- ent races. The epidermis maintains its thickness in spite of the constant wear GLANDS OF THE SKIN 393 and tear to which it is subjected. The columnar cells of the deepest layer of the rete mucosum elongate, multiply by division, the new cells produced being pushed toward the free surface of the skin. There is thus a constant production of fresh cells in the deeper layers, and a constant throwing off of old ones from the free surface. When these two processes are accurately balanced, the epidermis maintains its thickness. When by intermittent pressure a more active cell-growth is stimulated, the production of cells ex- ceeds their waste and the epidermis increases in thickness, as we see in the horny hands of the laborer. The dermis, or cutis vera or true skin, is a dense and tough, but yielding and highly elastic structure supporting the epidermis. It is composed of areolar connective tissue interwoven in all directions and forming numerous spaces by its interlacements. These areolae in the deeper layers of the cutis are usually filled with little masses of fat, figure 305. Unstriped muscu- FIG. 306. — Terminal Tubules of Sudoriferous Glands, Cut in Various Directions. From the skin of the pig's ear. (V. D. Harris.) lar fibers are also abundantly present, especially in the skin of animals which erect the hairs with greater ease than is usually the case with man. There is a rich network of blood-vessels to the dermis. In the dermal papillcc and about the sweat glands there are special loops of capillaries. Nerve fibers are also distributed to the papillae. The special nerve terminations in the skin have been described on page 72. Glands of the Skin. The skin possesses glands of two kinds: Sudoriferous or Sweat Glands, and the Sebaceous or Oil Glands. A Sudoriferous or Sweat Gland consists of a small lobular mass, formed of a coil of tubular gland-duct, surrounded by blood-vessels, and embedded in the subcutaneous adipose tissue, figure 305, C. The duct ascends from this coiled mass for a short distance in a spiral manner through the cutis and the epidermis, and then opens on the surface of the skin. In the parts where the epidermis is thin, the ducts themselves are thinner and more nearly straight in their course, 394 EXCRETION The duct is lined with a layer of columnar epithelium continuous with the epidermis. The coiled or secreting portion of the gland is lined with at least two layers of short columnar cells with very distinct nuclei, figure 306. The lumen is distinctly bounded by a special lining of cuticle. The sudoriferous glands are abundantly distributed over the whole sur- face of the body; but are especially numerous, as well as very large, in the skin of the palm of the hand and of the sole of the foot. The glands by which the peculiarly odorous matter of the axillae and groin is secreted form a nearly complete layer under the cutis, and are like the ordinary sudoriferous glands, except in being larger and having very short ducts. The peculiar bitter yellow substance secreted by the skin of the external auditory passage is named cerumen, and the glands themselves ceruminous glands; but they do not much differ in structure from the ordinary sudorif- erous glands. The sebaceous glands, figures 305 and 306, like sudoriferous glands, are abundant in most parts of the surface of the body, particularly in parts largely FIG. 307. — Sebaceous Gland from Human Skin. (Klein and Noble Smith.) supplied with hair, as the scalp and face. They are thickly distributed about the entrances of the various passages into the body, as the anus, nose, lips, and external ear. They are entirely absent from the palmar surface of the hand and the plantar surface of the foot. They are racemose glands com- posed of an aggregate of small tubes or sacculi lined with columnar epithelium EXCRETORY FUNCTION OF THE SKIN 395 and filled with an opaque white substance, like soft ointment, which consists of broken-up epithelial cells which have undergone fatty degeneration. Mi- nute capillary vessels overspread them; and their ducts open on either the surface of the skin, close to the hair, or, which is more usual, directly into the follicle of the hair. In the latter case, there are generally two or more glands to each hair, figure 306. The story of the structure and development of such epithelial struc- tures as the hair and the nails is best left to the histologist, to whom the student is referred. The Excretory Function of the Skin. The function of the skin which is of special interest to this chapter is that of the excretion of the sweat. The fluid secreted by the sweat glands is usually formed so gradually that the watery portion of it escapes by evaporation as fast as it reaches the surface. But during strong exercise, exposure to great external warmth, in some diseases, and when evaporation is prevented, the secretion becomes more sensible and collects on the skin in the form of drops of fluid. The perspiration, as the term is sometimes employed in physiology, in- cludes all that portion of the secretions and exudations from the skin which are thrown on the surface by the sweat glands. As a matter of fact, this is mingled with various substances lying on the surface of the skin. The con- tents of the sweat are, in part, matters capable of assuming the form of vapor, such as carbonic acid and water, and in part other matters which are depos- ited on the skin, and mixed with the sebaceous secretions. The secretion of the sebaceous glands and hair-follicles consists of cast- off epithelium cells, with nuclei and granules, together with an oily matter, extractive matter, and stearin. In certain parts, also, it is mixed with a peculiar odorous principle, which contains caproic, butyric, and rutic acids. It is similar in composition to the unctuous coating, or vernix caseosa, which is formed on the body of the fetus while in the uterus, and which contains ordinary fat. This sebaceous secretion serves the purpose of keeping the skin moist and supple, and, by its oily nature, of both hindering the evapora- tion from the surface and guarding the skin from the effects of the long-con- tinued action of moisture. But while it thus serves local purposes, its re- moval from the body entitles it to be listed among the excretions of the skin. CHEMICAL COMPOSITION OF SWZAT. Water 995 Solids: 5 Organic acids (formic, acetic, butyric, propionic, caproic, caprylic) 0.9 Salts, chiefly sodium chloride - 1.8 Neutral fats and cholesterin 0.7 Extractives (including urea) , with epithelium 1.6 1000 EXCRETION The sweat* is a colorless, slightly turbid fluid, alkaline, neutral or acid in reaction, of a saltish taste, and peculiar characteristic odor. Of the several substances it contains, however, only the carbonic acid and water need particular consideration. The quantity of watery vapor excreted from the skin is, on an average, between 750 and 1,000 cubic centimeters daily. This subject has been very carefully investigated by La cisier and Sequin. The latter chemist enclosed his body in an air-tight bag provided with a mouthpiece. The bag was closed by a strong band above, and the mouthpiece adjusted and gummed to the skin around the mouth. He was weighed, then remained quiet for several hours, after which time he was again weighed. The difference in the two weights indicated the amount of loss by pulmonary exhalation. Having taken off the air-tight dress, he was immediately weighed again, and a fourth time after a certain interval. The difference between the two weights last ascertained gave the amount of the cutaneous and pulmonary exhalation together; by subtracting from this the loss by pulmonary exhalation alone, while he was in the air-tight dress, he ascertained the amount of cutaneous transpiration. The average loss by cutaneous and pulmonary exhalation in a minute during a state of rest is eighteen grains, — the minimum eleven grains, the maximum thirty-two grains. Of the eighteen grains, eleven pass off by the skin and seven by the lungs. The quantity of watery vapor lost by transpiration is of course influenced by all external circumstances which affect the exhalation from evaporating surfaces, such as the temperature, the hygrometric state, and the stillness of the atmosphere. But, of the variations to which it is subject under the influence of these conditions, no calculation has been exactly made. The quantity of carbonic acid exhaled by the skin on an average is said to be about one-two-hundredth of that eliminated by the pulmonary respiration. The cutaneous exhalation is most abundant in the lower classes of ani- mals, more particularly the naked amphibia, as frogs and toads, whose skin is thin and moist, and readily permits an interchange of gases between the blood circulating in it, and the surrounding atmosphere. Bischoff found that, after the lungs of frogs had been tied and cut out, from 3 to 4 c.c. of car- bonic-acid gas was exhaled by the skin in eight hours. And this quantity is very large, when it is remembered that a full-sized frog will generate only about 10 c.c. of carbonic acid by his lungs and skin together in six hours. The importance of the respiratory function of the skin, which was once thought to be proved by the speedy death of animals whose skins, after re- moval of the hair, were covered with an impermeable varnish, has been shown by further observations to have no foundation in fact. The immediate cause of death in such cases is the loss of temperature. A varnished animal is said to have suffered no harm when surrounded by cotton padding, and to have died when the padding was removed. INFLUENCE OF THE NERVOUS SYSTEM ON SWEAT SECRETION 3P7 Influence of the Nervous System on Sweat Secretion. The secre- tion of sweat is closely connected with the quantity of blood flowing through the cutaneous vessels. The quantity of sweat increases with vaso-dilatation and diminishes with vaso-constriction. The sweat glands are also under the control of efferent impulses passing to them from the special sweat centers in the brain and spinal cord through special sweat nerves. Thus, if the sciatic nerve be divided in a cat and the peripheral end be stimulated, beads of sweat are seen to appear upon the pad of the corresponding foot. The sweat ap- pears even though at the same time the blood-vessels are constricted, or the blood flow entirely stopped by compression of the aorta, whereas if atropin is injected previously to the stimulation, no sweat appears, although dilatation of the vessels may be present. Secretion of sweat, too, may be brought about reflexly. The circulation of venous blood in the spinal bulb causes the sweating of phthisis and of dyspnea generally, by stimulating the sweat center. If the cat whose sciatic nerve is divided be rendered dyspneic, abundant sweat occurs upon the foot of the uninjured, and none on the injured, side. The effect of heat in producing sweating may be both local and general, and, again, the various drugs which produce an increased secretion of sweat do not all act in the same way; thus, there is reason for thinking that pilocarpine acts upon the local apparatus, that strychnine and picrotoxin act upon the sweat centers, and that nicotine acts both upon the central and upon the local apparatus. The special sweat-nerves appear to issue from the spinal cord, in the case of the hind limb of the cat, by the last two or three dorsal and first two to four lumbar nerves, pass to the abdominal sympathetic, and from thence to the sciatic nerve, the general course of the autonomic nerves for this region. In the case of the fore limb, the nerves leave the cord by the first to the sixth dorsal nerves, pass into the thoracic sympathetic, and then join the brachial plexus, reaching the arm through the median and ulnar nerves. It will be as well to repeat here the other functions which the skin sub- serves. In addition to its excretory office, we have seen that it acts as a channel for absorption. It is also concerned with the special senses, that of touch and temperature, to the consideration of which as well as to its function of regulating the temperature of the body we shall presently return. By its general impermeability it prevents the loss of moisture of the body by direct evaporation from the tissues. It should be recollected, however, that apart from these special functions, by means of its toughness, flexibility, and elastic- ity, the skin is eminently qualified to serve as the general integument of the body, for defending the internal parts from external violence, while readily yielding and adapting itself to their various movements and changes of position. 398 EXCRETION LABORATORY EXPERIMENTS IN EXCRETION. PHYSIOLOGICAL REACTIONS i. The Relation of Blood Flow through the Kidney to the Secre- tion of Urine. Properly to check this experiment one should make three determinations: i, the general blood pressure; 2, the volume of the kidney; 3, the amount of urine secreted. Anesthetize a dog and arrange the apparatus for taking the blood pressure as directed in experiment 19. Prepare a renal onkometer, see figures 301 and 302, and an onkograph for recording the variations in the volume of the kidney. The renal onkometer consists of a double metal box to fit the form of a kidney. The inner halves of this box should be covered so loosely with very thin sheet rubber that the rubber can be fitted into the bottom of the cup without undue tension. The rubber must be sealed to the outer edges of this inner cup with rubber cement and allowed to dry. When it is completely dried the inner cup should be adjusted to the outer, and the spaces enclosed by the rubber sheet filled with water. Or the onkometer may be closed with parchment and filled with oil as de- scribed in experiment 23 on the Circulation. The half of the onkometer that comes against the wall of the body cavity of the animal should be completely closed with a stopper before the instrument is adjusted to the kidney. Now adjust the onkometer to the kidney, taking care to place the renal arteries, veins, and ureter in the tube in such a way as not to compress them. Fill the outer cup with water and connect this cavity by a two-way cannula with the recording onkograph. In practice it is more satisfactory if one introduces between the onkometer and onkograph an over- flow bottle or bulb, adjusted to maintain the constant pressure on the kidney. This direction varies from the usual one in that rubber sheeting instead of parchment is used to cover the inner cup of the onkometer, a method that permits the use of water instead of oil. Isolate and insert a small cannula into the ureter. This cannula should be clamped in a stand at a level as little above that of the kidney as possible. The urine secreted may be collected in a 10 c.c. graduated cylinder and measured at intervals of 5 or 10 minutes. Or, if the outflow is scanty, it may be allowed to drop on a tambour recording apparatus, the rate of dropping being indicative of the rapidity of secretion. Determine the normal rate of secretion of a dog under constant anesthesia. The anesthesia should be medium to light, but should be kept very uni- form so as to maintain a strong blood pressure. Note the effect on secre- tion and the corresponding effect on blood pressure and the kidney volume produced by vagus inhibitions. Section the vagus nerves and produce in- hibition by stimulating the peripheral end of the vagus. In this instance there are no reflexes to complicate the experiment, so that the fall in blood SECRETORY NERVES FOR THE SWEAT GLANDS 399 pressure is a direct cardiac effect. Stimulate the central end of the vagus which produces a fall of blood pressure through the vaso-motor system. There should be a normal period of at least ten minutes following each experi- ment to allow the secretion of the kidney to return to the normal. Expose the splanchnic nerves at the point where they pass beneath the diaphragm into the abdominal cavity. Adjust a pair of shielded electrodes, close the cavity, and, when the animal has returned to the normal uniform rate of secretion and of blood pressure, stimulate the splanchnic nerves. The splanchnics contain vaso-constrictor nerves for the kidney. The onkom- eter experiment should, therefore, demonstrate a sharp decrease in the vol- ume of the organ, while the blood pressure is only slightly changed. The rate of secretion should be followed for at least twenty minutes after stimula- tion of the splanchnics. This test should be repeated two or three times. In this connection demonstrate the influence of deep chloroform anesthesia on urinary secretion. The chloroform should be pushed to the danger limit and maintained there for a couple of minutes or more. Compare the rapidity of the recovery of blood pressure with the recovery of the rate of secretion. 2. Secretory Nerves for the Sweat Glands. Langley has mapped out the paths of the secretory nerves for the sweat glands. He has shown that in the cat these fibers are distributed to the hind limb through the sciatic. Anesthetize a half -grown cat, isolate the sciatic nerve, cut it and stimulate the peripheral end with a medium to strong induction current. After a few moments beads of perspiration will appear on the pads of the foot, which should therefore be carefully examined before the experiment. URINE ANALYSIS. 3. Daily Quantity. Determine the total quantity, for 24 hours, of urine secreted through a period of 3 or 4 days, beginning and ending the period at a definite hour in the day, preferably on rising in the morning. The daily secretion varies through wide extremes, depending upon the quan- tity of liquid taken in the food, the daily exercise, the temperature, etc., etc. In the analysis of urine it is always better to take a mixed 24-hour sample. 4. Specific Gravity. Determine the specific gravity of 24-hour urine. This is done by the instrument known as the urinometer which carries a graduated scale at the neck. Care should be taken to float the urinometer so that it does not come in contact with the measuring cylinder. The scale should be read at the bottom of the meniscus. 5. Reaction. Determine the reaction of perfectly fresh urine, using litmus paper. The normal urine is slightly acid under ordinary conditions, due to the presence of acid phosphates or perhaps in some cases to traces of free organic acid. After standing some time the reaction is usually alkaline, owing to fer- 400 EXCRETION mentation processes. The reaction may vary also according to the food, vegetable foods tending to produce alkaline urine, while with animal foods the reaction is acid. 6. The Total Quantity of Solids. Determine the solids of urine by evaporating 25 c.c. of a mixed sample of urine to dryness in a weighed platinum or porcelain dish over a water bath. The residue should be dried to constant weight in a drying •oven at 105° C. A useful rule for approximately estimating the total solids in any given specimen of healthy urine is to multiply the last two figures representing the specific gravity by 2.33. Thus, in urine of specific gravity 1025, 2.33 X 25 = 58.25 grains of solids are contained in 1,000 grains of the urine. Or the total solids are 5.825 per cent. In using this method it must be remembered that the limits of error are much wider in diseased than in healthy urine. The solids of urine consist of inorganic salts of sodium, potassium, and calcium, and of a long list of organic compounds, chiefly nitrogenous. 7. Chlorides. Large quantities of sodium chlo- ride are always present in the normal urine. Add ammonia to 25 or 50 c.c. of albumin-free urine and heat to precipitate earthy phosphates, filter. To a sample of the filtrate add an excess of strong nitric acid and a few drops of i per cent silver nitrate. A white flocculent precipitate of silver chloride comes down. This precipitate is soluble in an excess of ammonia. Reprecipitate by adding nitric acid again. The test may be made without removing the phosphates, though in this case, upon adding ammonia, the disappearance of the silver precipitate is complicated by the appearance of insoluble phosphates. The chlorides may be estimated quantitatively by Volhard's method, or some one of its modifications, which depends upon the determination of the amount of chlorine precipitated by the silver. The student is referred to chemical text-books for this and other quantitative methods. 8. Sulphates. Sulphates exist in the urine both in inorganic and organic compounds, chiefly the former. Add a few drops of hydro- chloric acid to a sample of urine in a test tube, then a solution of barium chloride, the insoluble barium sulphate settles out. If the test is made on the normal urine without the addition of the acid, the inorganic sulphate will be precipitated, while the ethereal or compound sulphate will remain in solution and can be filtered off. This filtrate, when boiled with strong hydrochloric acid to 10 per cent over a water bath for a short time, will have the sulphates FIG. 308. — The Urinometer. PHOSPHATES 401 split off from the organic radicle and may be precipitated by the addition of barium chloride in hot solution. 9. Phosphates. The phosphates of urine consist of the earthy and alkaline salts, the latter predominating. Take a 50 c.c. sample of urine, add strong ammonia, and heat. The phosphates of calcium and magnesium separate out, as they are insoluble in alkaline solution. Filter. To the filtrate add a solution of magnesium sulphate. This precipitates the sodium and potassium phosphates as a triple phosphate of magnesium, which is insoluble. Tests for phosphates in general are: Add nitric acid to a sample of urine, warm gently, then add a few drops of 10 per cent ammonium molybdate; a yellow precipitate of ammonium phospho-molybdate is formed. Or, add acetic acid, then a few drops of FIG. 309. — Doremus' Ureometer. uranium acetate; a bright yellow precipitate of uranium ammonium phosphate is formed. These two reactions are used as the basis for a quantitative de- termination of phosphorus. 10. The Preparation of Urea. Take zooc.c. of normal urine, evap- orate to one-half its quantity, and precipitate the phosphates and sulphates by adding a mixed solution of barium hydrate and nitrate. Filter, evaporate the filtrate to dryness, take up in warm 95 per cent alcohol, and refilter. Crys- tals of urea separate out when the alcohol is evaporated off. Evaporate a large sample, 200 c.c., of urine to a syrupy mass, add nitric acid. Crystals of urea nitrate are formed. Wash the crystals in dilute nitric acid, then dissolve in water. The urea is set free by adding barium carbonate 26 402 EXCRETION until the carbon dioxide ceases to come off. Filter, evaporate over a water bath to dryness, and dissolve the urea in 95 per cent alcohol; decant, and re- crystallize by evaporating off the alcohol. 11. Urea Determination by Doremus' Ureometer. Fill the ureo- meter with hypobromite of sodium solution. Take a sample of urine in the pipet which accompanies the instrument, drawing it in exactly to the mark. Insert the pipet past the bend of the ureometer and slowly empty the urine carefully so as not to lose any of the liberated nitrogen. The instru- ment is graduated to read off the percentage of urea directly. 12. Uric Acid. Concentrate over a water bath 500 c.c. of urine to 100 c.c. and boil with 10 c.c. or more of strong hydrochloric acid. Upon cooling, crystals of uric acid are formed. Decant the supernatant liquid and wash the crystals with a few cubic centimeters of 10 per cent hydrochloric acid. . Dissolve the crystals and test. The Murexide Test. Add to 2 c.c. of uric acid solution in a test tube an equal quantity of nitric acid. Heat gently, a reddish ring forms at the point of contact between the nitric acid and uric acid solution. Cool and add ammonia carefully. The color ring deepens to a purple color. This test succeeds well by evaporating a few drops of uric acid on a porcelain plate. Add to the stain a drop of concentrated nitric acid and evaporate. Concen- tric rings of reddish color will be formed. This color deepens to reddish- purple when a drop of ammonia is added. 13. Creatinin. Test 20 c.c. of urine in a beaker for creatinin by adding a cubic centimeter of dilute solution of sodium nitroprusside and then weak sodium hydrate. A ruby-red color, which quickly turns yellow, indi- cates the presence of creatinin. (Weyl's reaction.) If the yellow solution has an excess of acetic acid added and is then boiled, it turns first green and later blue, forming ultimately a precipitate of Prussian blue. Urine mixed with picric acid gives a red coloration when made alkaline with caustic alkali solution. 14. Total Nitrogen in Urine. Determine the total nitrogen in a sample of urine by the Kjeldahl method. This method depends upon the conversion of nil the nitrogen to ammonia, the distillation of this ammonia into a known quantity of sulphuric acid, and the final titration of the excess of sulphuric acid when the distillation is complete. The computation is made on the basis that i c.c. of a normal sulphuric acid is equivalent to i c.c. normal sodium hydrate, and that in turn to i c.c. of ammonium hydrate. The ammonia neutralizes a portion of the sulphuric acid in the distillation. One c.c. of normal ammonium hydrate contains 0.014 gram nitrogen, from which the total nitrogen in the sample used can be readily computed. 15. Pigments of Urine. The normal color of the urine is due to the presence of a pigment, urobilin. Prepare urobilin by adding lead acetate ALBUMIN IN THE to a 200 c.c. sample of urine. A precipitate forms which carries down the coloring matter. Filter. Add acid alcohol to the precipitate to extract the coloring matter, refJter, which gives a deep yellow solution. Shake up with a few cubic centimeters of chloroform which dissolves the pigment. Draw off the chloroform solution and allow to evaporate. The residue is a brown- ish mass of urobilin. ABNORMAL CONSTITUENTS OF URINE. Many abnormal constituents may appear in the urine under pathological conditions, only two of which will be mentioned here. 1 6. Albumin in the Urine. The detection of the presence of albu- min, albuminuria, is of considerable clinical importance. The following are the standard tests which present no special difficulty except when traces only are present. Heat Coagulation. To a half test tube of urine add a drop of dilute acetic acid and boil. A white coagulum indicates the presence of albumin. A faint cloudy appearance indicates traces. Nitric Acid Test. To 5 c.c. of strong nitric acid in a conical test tube add 10 or 15 c.c. of urine, pouring it gently down the inclined side of the glass. Allow the glass to stand for a few minutes, when a white coagulum appears just above the line of contact of the acid with the urine. This test, known as Heller's test, will usually indicate the presence of traces of albumin. Picric Acid Test. Add picric acid to a sample of urine. A whitish precipitate of albumin will appear at the line of contact, as in the preceding test. Citric acid two parts and picric acid one part, when boiled with urine will coagulate minute traces of the proteid. 17. Detection of Sugar in the Urine. Trommers Test. The presence of sugar in the urine can usually be detected by Trommer's test, which depends upon the reduction of copper sulphate in the presence of strong alkali. Boil fresh Fehling's solution and add to it a few cubic centi-^ meters of urine. When sugar is present a reddish-yellow precipitate of copper oxide comes out. The test should be set away for a few minutes when, if only traces of the reduction are present, a reddish-brown stain will appear on the bottom of the test tube. Uric acid, if present in excess, may produce a slight precipitation of the copper. Fermentation Test. If sugars are present in the urine, they can be de- tected by adding yeast to a fermentation tube filled with urine, the liberation of carbon dioxide indicating the presence of sugar. Cane sugar does not support the growth of yeast, so it forms an exception by this test. Phenyl-Hydrazin Crystals. Phenyl-hydrazin forms crystals of phenyl- glucosazone. To 10 c.c. of urine in a small beaker add o.i of a gram of phenyl-hydrazin hydrochloride and a double quantity of sodium acetate. 404 EXCRETION Heat in the water bath for 20 minutes. Upon cooling a deposit of yellow crystals of phenyl-glucosazone takes place, if glucose is present. 1 8. Quantitative Determination of Sugar in the Urine. Fill a 10- c.c. graduated pipet with freshly prepared Fehling's solution. Take 10 c.c. of urine, measured with a dropping-pipet into a small beaker, and boil. While continuing to boil, add Fehling's solution slowly and cautiously so long as the color is discharged. The amount of Fehling's required to reduce the sugar is a measure of the quantity of reducing sugar present — i c.c. of Fehling's being equivalent to 5 milligrams of dextrose. For the presence of blood pigments and other abnormal constituents of the urine, the student is referred to special handbooks on the subject. CHAPTER XI METABOLISM, NUTRITION, AND DIET THE term metabolism means, literally, an exchange of material. In its broadest physiological sense it includes the study of the exchange of material between the living tissues of the body and their surrounding media. This includes the study of the income and outgo of material; the storing of energy- yielding materials in the body; the transfer of this potential energy into kinetic energy; and the nutritional processes within the various tissues. The building up of absorbed food material into the protoplasm of the cell or of simpler com- pounds into more complex ones, which may be stored in the cell, is known as anabolism, and the compounds themselves as anabolites. The breaking down of these substances into simpler forms, whereby the potential energy of the anabolites is transformed into kinetic energy, is known as catabolism, and its products as catabolites. In order to form an estimate of these processes going on in the body, the amount and nature of the ingested material must be known, as well as the amount of refuse or unused material that passes out of the alimentary canal as feces, and the amount of excreted material from the various excretory organs. It is also necessary to know the potential energy of the ingested materials, and the possible potential energy must be checked against the ac- tual energy liberated. The food is intended to supply the place of the material which has been utilized by the body, and, in a simpler form, eliminated in the excretions. But in the choice of a diet this is not enough; the food should be sufficient to supply such need without waste and without unduly increasing the output of excreta, while at the same time the body should be maintained in health, without increase or loss of weight. The food must also supply the energy liberated without undue waste of the tissues themselves. These requisites of a diet scale then allow for wide alterations in the amount of different kinds of foods under different circumstances. Numerous and most valuable experiments have been performed in recent years to determine just what each article of the common food materials contributes to the growth of the tissues and to the kinetic energy liberated by the tissues. The potential energy of the food can also be checked against the kinetic energy liberated. A single illustration of this class will serve. In an experiment with mixed food lasting through four days, on a man with body weight of 64 kilograms, and doing a minimum amount of work, Atwater made the following determinations : 405 • 406 METABOLISM, NUTRITION, AND DIET WEIGHT, COMPOSITION, AND HEAT OF COMBUSTION OF FOODS AND EXCRETA PER DAY. Weight per day. Water. Protein. 2 & Carbohy- drates. % Carbon. Hydrogen. Heat of com-| bustion. Food Beef Grams. IOO Grams. 61.2 Grams. 35.1 Grams. 3.1 Grams. Grams. 5.62 Grams. 20.0< Grams. 2.90 Calo- ries. 227 Butter 25 2.6 .5 21. I .08 15.77 2.50 194 Whole milk 850 726.8 32-3 45.1 39-9 23Q7 Total excreta per day. 2322.6 17.08 243.27 4.40 2642 Balance — 1.04 -7-l8 -1-30.42 — 123 Careful analyses of the excreta, many of which we have already had oc- casion to call attention to, show that they are made up, besides water, chiefly of the chemical elements carbon, hydrogen, oxygen, and nitrogen, but that they also contain, to a less extent, sulphur, phosphorus, chlorine, potassium, sodium, calcium, magnesium, iron, and certain other of the elements. Since this is the case it must be evident that, to balance this waste, foods must be supplied containing all these elements to a certain degree, and some of them in large amount, viz., those which take a principal part in forming the excreta. The waste products of the body are eliminated through the lungs, the skin, the alimentary canal, and the kidney. In the lungs the chief waste prod- uct is water, carbonic-acid gas, and traces of ammonia compounds which are composed of the elements carbon, oxygen, nitrogen, and hydrogen. Traces of carbonic-acid gas and small quantities of urea and salts are eliminated through the skin. From the alimentary canal there are lost, through the feces, the indigestible and unabsorbed substances from the food, together with products secreted into the canal by the liver, pancreas, and mucous membrane. METABOLISM, NUTRITION, AND DIET 407 The secretion lost daily by the kidney, aside from a large quantity of water, consists of nitrogenous waste products, chiefly urea, and inorganic solids, as were mentioned in the chapter on Excretion. The relations between the amounts of the chief elements contained in these various excreta in twenty-four hours may be thus summarized: Water. C. H. N. O. By the lungs 33O 248 8 6ci ic By the skin 660 2 6 72 By the urine. . . 1,708 Q 8 3J i^ 8 II I By the feces I2O 20 30 30 12 O Grams 2 818 28l 2 6 i 18 8 681 AC From the water in this table should be subtracted the 296 grams of water which are produced by the union of hydrogen and oxygen in the body during the process of oxidation, and there should be added to the respective columns the corresponding amounts of the constituent elements, i.e., 33 grams of hydro- gen and 262 grams of oxygen. There are 26 grams of salts eliminated through the urine, and 6 by the feces; a total of 32 grams. The quantity of carbon daily lost from the body amounts to about 281.2 grams and of nitrogen 18.8 grams, and if a man could be fed by these elements, as such, the problem would be a very simple one; a corresponding weight of charcoal and, allowing for the oxygen in it, of atmospheric air would be all that is necessary. But an animal can live upon these elements only when they are arranged in a particular manner with others, in the form of such food stuffs as we have already enumerated, page 297 el seq.; moreover, the relative proportion of carbon to nitrogen in either of these compounds alone is by no means the proportion required in the diet of man. Thus, in proteid, the proportion of carbon to nitrogen is only as 3.5 to i. If , therefore, a man took into his body, as food, sufficient proteid to supply him with the needed amount of carbon, he would receive more than four times as much nitrogen as is needed; and if he took only sufficient to supply him with nitrogen, he would be starved for want of carbon. It is plain, therefore, that he should take with the albuminous part of his food, which contains so large an amount of nitrogen in proportion to the carbon he needs, substances in which the nitrogen exists in relatively much smaller quantities than the carbon. It is, therefore, evident that the diet must consist of several compounds, not of one alone. Many valuable observations have been made with a view of ascertaining the effect upon the metabolism of a variation in the amount and nature of food. These are of great assistance in the consideration of dietetics. 408 METABOLISM, NUTRITION, AND DIET METABOLISM OF PROTEIDS. Nitrogenous Equilibrium. Experiments have been made, to a con- siderable extent upon dogs, which demonstrate the necessity for proteid food. After a preliminary period without food, during which the output of nitrogen as shown by the urea has diminished to a comparatively constant amount, an animal is fed with a diet of lean meat which would suffice to pro- duce the amount of urea, and so of flesh, which it has been losing during its starvation period. The effect of this, however, is at once to send up the amount of urea excreted to a point above that which had been lost previous to the commencement of the flesh diet. Thus the output of nitrogen still exceeds its income, and the weight of the animal continues slowly to diminish. It is only after a considerable increase of the flesh given in the food that a point is reached where the income and expenditure of nitrogen are equal, and at which the animal is not using up quickly or slowly the nitrogen of its own tissue, and is no longer losing flesh. This condition in which the nitro- gen of the egesta equals the nitrogen of the ingesta is known as nitrog- enous equilibrium. EXPERIMENT IN NITROGENOUS EQUILIBRIUM. DAYS OF EXPERIMENT. N Intake. Grams. N Output. Grams. JPer cent Differ- ence. S Intake. Grams. S Output. Grams. I. i-c go OO 89 8l O 2 I 6-12 131 60 IT.2 ?c; H-o 88 II 1-2 or go ^6 16 — |- I OO 7— II 144. 5°° " " " severe " 4,500 " The daily output of energy for the adult man is, according to McKendrick, as follows: Kilogrammeters. Calories. Work of heart per day 88,000 Work of respiratory muscle 14,000 Eight hours' active work 213,344 315,334 or 743 Amount of heat produced in 24 hours 1,582,700 or 3,724 ,034 or 4,467 THE INFLUENCE OF THE DUCTLESS GLANDS ON METABOLISM 427 This estimate is relatively high for ordinary activity as determined by Atwater and others. It is indeed more energy than the standard diets in the table given on page 423 will yield to the body. For example, Voit's diet yields 3,055 Calories, and the average of the table is only 3,125 Calories. THE INFLUENCE OF THE DUCTLESS GLANDS ON METABOLISM. A further question to be considered is the relationship between the metab- olism of one tissue and the products of the metabolism of other tissues. The metabolism of one tissue may produce products, proteid or otherwise, which when taken up by the blood and carried to other tissues supply ex- actly what is necessary for their complete anabolism. The physiology of the internal secretions has revealed a number of such influences that are best explained on the assumption of the presence of spe- cial products. The Thyroid. The thyroid gland is situated in the neck. It con- sists of two lobes, one on each side of the trachea, extending upward to the FIG. 311. — Part of a Section of the Human Thyroid, a, Fibrous capsule; b, thyroid vesicles filled with, e, colloid substances; c, supporting fibrous tissue; d, short columnar cells lining vesicles; /, arteries; g, veins filled with blood; h, lymphatic vessel filled with colloid substance. (S. K. Alcock.) thyroid cartilage, covering its inferior cornu and part of its body; these lobes are connected across the middle line by a middle lobe or isthmus. The 428 METABOLISM, NUTRITION, AND DIET thyroid is covered by the muscles of the neck. It is highly vascular, and varies in size in different individuals. The gland is encased in a thin transparent layer of dense areolar tissue, free from fat, containing elastic fibers. These gland vesicles are each lined with a single layer of cubical cells and are filled with transparent nucleo-albuminous colloid material. Accessory Thyroids. The accessory and the parathyroids possess the structure of the thyroid and apparently perform the same function. The accessory thyroids undergo hypertrophy when the thyroid has been removed. The colloid material which is formed within the thyroid vesicles, and is believed to be their secretion, finally ruptures through their walls into the lymph channels and thus gains entrance to the circulation. The secretion of the thyroid falls intq> the class known as internal secretions, and exerts a profound influence upon the metabolic processes of the body, probably through its influence on the central nervous system. Complete extirpation of the thyroid, at least in some animals, produces death, preceded by a group of characteristic symptoms. In man and the monkey the symptoms after re- moval come on slowly and resemble the disease known in man as myxedema. This disease is known definitely to be due to disease of the thyroid, where- by its function is interfered with. Moreover, if a piece of thyroid of sufficient size be grafted into an animal from which the glands have been removed, and the graft takes, the symptoms of thyroid removal are lessened in inten- sity or disappear altogether. Thyroid feeding or the administration of thyroid extracts relieves the symptoms of the disease myxedema. The above facts show that the thyroid gland must perform some im- portant function in the animal economy, and it is believed that this is accom- plished by virtue of its internal secretion. The colloid material of the gland has been submitted to much chemical study, and a substance called iodo- thyrin has been isolated as its active principle. Baumann and Roos state that iodothyrin exists in the gland in combination with proteid bodies. lodo- thyrin relieves the symptoms of thyroid removal much to the same extent as thyroid feeding. It is a very resistant substance, and is not injured by the action of the gastric juice or by boiling with 10 per cent sulphuric acid for a long time. The Suprarenal Capsules or Adrenals. These are two flattened, more or less triangular or cocked-hat shaped bodies, resting by their lower border upon the upper border of the kidneys. The gland tissue proper consists of an outside firmer cortical portion, and an inside soft dark medullary portion, figure 312. The adrenals are very abundantly supplied with nerves, chiefly com- posed of medullated fibers. These fibers are derived from the solar and renal plexuses and the vagi, but the method of their termination is unknown. A vast amount of information has been given concerning the function of THE SUPRARENAL CAPSULES OR ADRENALS 429 the suprarenal capsules within the last few years by the researches of Schafer and Oliver, Zyboulski, Abel, and others. Brown-Sequard, it is true, showed by experiment as early as 1856 that removal of the suprarenals is followed by the death of the animal, but his experiments were repeated by others who ^L A FIG. 312. — Vertical Section of Adrenal. A, Capsule; B, cortex; C, medulla; a, glomerular zone; b, f ascicular zone ; c, reticular zone; v, vein in medulla. (Merkel-Henle.) did not obtain the same results; and it was concluded that the suprarenal capsules had no function, or at least that their function was not known. Death was preceded in the case of Brown-Sequard's animals by symptoms somewhat analogous to those of the disease of man known as Addison's disease. The failures to produce symptoms after attempted removal of the glands have probably resulted from incomplete removal or the presence of 430 METABOLISM, NUTRITION, AND DIET accessory bodies. Accessory suprarenal capsules are commonly present in some animals and are sometimes found in man. Further, if one gland is removed, the other hypertrophies. The experiments of all recent observers confirm the original experiments of Brown-Se'quard. The presence of the suprarenal capsules is essential to life. Schaffer and Oliver found that injections of suprarenal extract produced marked effects upon the muscular layer of the arteries, the muscular tissue of the heart, and the skeletal muscles. The muscular layer of the arteries is markedly contracted, causing vaso-constriction and a rise of blood pressure. FIG. 313. — Injection of Suprarenal Extract. pressure, after section of cord and vagi. (Reduced to one-half.) Effect upon the heart, limb, spleen, and blood (Schaffer.) When the heart is freed from nervous control its contractions are increased both in force and frequency, still further raising blood pressure. If the vagi are undisturbed the heart beats more slowly, showing an increase of vagus tone due to stimulation of the vagus center in the medulla. The contraction of the skeletal muscles in response to a single stimulus is increased. Very small doses of suprarenal extract are sufficient to produce marked effects. Thus Schaffer states that less than TTGITO g^111 ("g^ir 8ram) °f tne desiccated gland is sufficient to produce an effect upon the heart and arter- ies of an adult man. It is a curious fact that only extracts of the medullary portion of the gland THE PITUITARY BODY 431 are active. It has been further shown, by Christian! and others, that if only small portions of the medulla remain, the animal operated upon survives; while if all the medullary substance be removed, even though large portions of the cortex remain, the animal invariably dies. Abel has succeeded in separating the blood-pressure-raising constituent of the extract, and calls it epinephrin, C10H13NO3 JH2O. Adrenalin was isolated by Takamine and assigned the formula C9H13NO3. The hydro- chloride salt is prepared commercially and produces all the vascular effects assigned to the gland. Destruction of the suprarenal capsules through disease in man results in the production of a group of symptoms known as Addison's disease. The administration of suprarenal extract to these cases sometimes results bene- ficially, but not so uniformly as thyroid feeding does in myxedema. Dreyer has given evidence that the products of this gland are discharged into the blood of the adrenal vein in increased quantity on splanchnic stim- ulation. This gland furnishes, on the whole, very conclusive evidence of the pres- ence of an internal secretion that is absolutely necessary to the normal metab- olism of other organs. The Pituitary Body. This body is a small reddish-gray mass, occupying the sella turcica of the sphenoid bone. It consists of two lobes, a small posterior one of nervous tissue, and an anterior one resembling the thyroid in structure. The gland spaces are oval, nearly round at the periphery, spherical toward the center of the organ, and are filled with nucleated cells of various sizes and shapes not unlike gan- glion cells. The function of the pituitary body has not yet been fully established. It has been supposed that the pituitary body has a function associated with that of the thyroid. On the other hand, tumors or other disease of the pitui- tary body have been found after death in association with a disease known as acromegaly, in which the bones and soft parts undergo great hypertrophy. Howell has found that extracts of the glandular lobe are inactive, but that extracts of the infundibular lobe, when injected into the circulation, produce marked rise of blood pressure, increase of vagus tonic ' inhibition, and an augmentation of the heart's force. The Internal Secretion of the Pancreas. Minkowski and von Mering have shown that total extirpation of the pancreas is followed in all cases by the appearance of sugar in the urine in the course of a few hours. The amount of sugar which appears is considerable, from 5 to 10 per cent. This experimental disease is accompanied by an increase in the quantity of urine and by abnormal thirst and appetite, and proves fatal in fifteen days or less. These results are obtained only when the entire gland or more than nine-tenths of it have been removed. If one-tenth or more of the gland be left 432 METABOLISM, NUTRITION, AND DIET behind, sugar appears in the urine when carbohydrates are eaten, but not otherwise. Nor is it necessary that the remaining portion of the gland be in its normal situation. Successful grafts of pancreas under the skin of the abdomen or elsewhere will prevent the appearance of sugar in the urine and the other symptoms. If, however, the graft be subsequently removed, the sugar in the urine and the other symptoms reappear, and the experimental disease proceeds to a rapidly fatal issue. The symptoms produced by total extirpation of the pancreas do not de- pend upon the loss of the pancreatic juice proper to the organism. This secretion may be diverted from the intestine through a pancreatic fistula without the production of diabetes. Moreover, Hedon and Thiroloix have rendered the acini of the gland functionally inactive, and ultimately de- stroyed them, by the injection of paraffin or other substances into the duct of Wirsung, without the supervention of diabetes. These experiments have shown that the ordinary secreting cells degener- ate and the islands of Langerhans increase in size, leading to the conclusion that these are the structures that produce a special internal secretion which influences or controls carbohydrate metabolism in the body. Whether this hypothetical substance is necessary to the dehydration and synthesis of dex- trose in the body or whether it is necessary to the complete oxidation of carbo- hydrate is at present a matter of inference. The Reproductive Glands. The ovary and the testes are un- doubtedly concerned with metabolism in the body. It has been shown repeatedly that extracts of the testes when injected into the system lead to increased vigor, both of the muscular and of the nervous systems. Ergograms show an increase in muscular power. Spermin isolated from the testes is claimed by its discoverer to produce the beneficial effects described. The re- moval of the testes in domestic animals is followed by an entire change in the character of the development of the animal, especially in the so-called second- ary sexual characters. Such animals show less vigor and muscular power. The removal of the ovaries in women, through surgical operation, has resulted in very marked nervous symptoms. These symptoms are reduced or entirely disappear on grafting a portion of the gland, and the disturbed menstruation following ovariotomy becomes regular again. Experiments by Loewy and Richter indicate that oxidations in the body are greatly increased on feeding ovarian extract to ovariotomized animals. There are other organs whose function is still obscure but in which the indirect evidence points to an influence on metabolism at one stage or another of the existence of the animal body. Enough has been given here to show that the interrelation of the organs is extremely complex in so far as the metabolism is concerned. It is not enough simply to know the foods and their composition. The whole complex of intermediary metabolism and their influence must constantly be taken into consideration. CHAPTER XII ANIMAL HEAT HEAT is produced by the metabolism of the tissues of the body. In man and in such animals as are called warm-blooded, i.e., only mammals and birds, there is an average body temperature which is maintained with only slight variations in spite of changes in their environment. The possible variations above and below this average are comparatively slight. The average temperature in all mammals and birds is not the same, for, as we shall see, the average temperature of man is 37° C. (98.6° F.), in some birds it is as high as 44° C., while in the wolf it is said to be under 36° C. The average temperature of the human body in those internal parts which are most easily accessible, as the mouth and rectum, is from 36.9° to 37.4° C. (98.5° to 99.5° F.). In different parts of the external surface of the human body the temperature varies only to the extent of one or two degrees centi- grade, when all are alike protected from cooling influences; and the differ- ence which under these circumstances exists depends chiefly upon the different degrees of blood supply. In the axilla and in the groin, the most convenient situations, under ordinary circumstances, for examination by the thermometer, the average temperature is 37° C. (98.6° F.). In different internal parts, the variation is one or two degrees; those parts and organs being warmest which contain most blood, and in which there occurs the greatest amount of chemical change, e.g., the muscles and the glands. The temperature is highest when they are in a condition of activity. Those tis- sues which subserve only a mechanical function and are the seat of least ac- tive circulation and chemical change are the coolest. These differences of temperature, however, are actually but slight, on account of the provisions which exist for maintaining uniformity of temperature in different parts. The average temperature of a healthy body varies somewhat according to age, sex, time of day, climate, etc. The mean temperature is said to be slightly higher, 0.5° C., in young children and in old persons than in adults. It is perhaps very slightly higher in women than in men, in warm climates than in cold, in winter than in summer. It varies slightly at different times in the day, especially during sleep when metabolism is at a low ebb. Heat-producing Organs. Heat is liberated in the body wherever oxidative metabolism takes place. Of all the tissues of the body muscular tissue is conspicuous for its mass and for its activity. It is evidently the great 28 433 434 ANIMAL HEAT heat-producing tissue. The manifestation of muscular energy is always ac- companied by the evolution of heat and the production of carbon dioxide. This production of carbon dioxide goes on while the muscles are in mechanical rest, only in a less degree than that which is noticed during muscular activity, and so it is certain that an active catabolism is going on in resting as well as in contracting muscles. This catabolism is a source of much heat, and so the total amount of heat produced in the muscular tissues per day must be very great. It has been calculated that, even neglecting the heat produced by the quiet catabolism of muscular tissue, the amount of heat generated by muscular activity would supply the principal part of the total heat produced within the body. The heart, as a special muscle, deserves particular mention since it is in constant vigorous activity. All its energy is ultimately converted into heat, accounting for about 5 per cent of the total heat of the body. The secreting glands, and principally the liver as being the largest and most ac- tive, come next to the muscles and heart as heat-producing tissues. It has been found by experiment that the blood leaving the glands is considerably warmer than that entering them. The metabolism in the glands is very active; and the more active the catabolism, the greater the heat produced. It must be remembered, however, that although the organs mentioned are the chief heat-producing parts of the body, all living tissues contribute their quota, and this in direct proportion to their activity. The blood itself is also the seat of catabolism, and, therefore, of the production of heat; but the share which it takes in this respect, apart from the tissues in which it circu- lates, is very inconsiderable. Regulation of the Temperature of the Human Body. The average temperature of the body is maintained under different conditions of external circumstance by mechanisms which permit of (i) variation in the loss of heat, and (2) variations in the production of heat. In healthy warm-blooded ani- mals the loss and gain of heat are so nearly balanced one by the other that, under all ordinary circumstances, a uniform temperature, within a degree or two, is preserved. Variation in the Loss of Heat. The loss of heat from the human body is principally regulated by the amount given off by radiation and con- duction from its surface, by means of the constant evaporation of water from the same part, heat being thus rendered latent, and to a much less degree by loss from the air-passages. In each act of respiration, heat is lost to a greater or less extent according to the temperature of the atmosphere; unless indeed the temperature of the surrounding air exceeds that of the blood. We must remember, too, that all food and drink which enter the body at a lower tem- perature abstract a small measure of heat; while the urine and feces which leave the body at about its own temperature are also means by which a certain small amount of heat is lost. Heat Lost from the Surface of the Body. By far the most impor- HEAT LOST FROM THE SURFACE OF THE BODY 435 tant loss of heat from the body, probably 90 per cent and upward of the whole amount, is that which takes place by radiation, conduction, and the evapora- tion of moisture from the skin. The actual figures are as follows: For every 100 calories of heat produced, 2.6 are lost in heating the food and drink; 2.6 in heating the air inspired; 14.7 in evaporation; and 80.1 by radiation and conduction. The means by which the skin is able to act as one of the most important organs for regulating the temperature of the blood, are, i, that it offers a large surface for radiation, conduction, and evaporation; 2, that it contains a large but adjustable amount of blood, and the quantity of blood is greater under those circumstances which demand a loss .of heat from the body, and vice versa ; 3, that it contains the sweat glands, which discharge a quantity of moisture to be evaporated from its surface. The circumstance which directly determines the quantity of blood in the skin is that which governs the supply of blood to all the tissues and organs of the body, namely, the power of the vaso-motor nerves to cause a greater or less tension of the muscular element in the walls of the arteries, and, in correspondence with this, a lessening or increase of the caliber of the vessel, accompanied by a less or greater current of blood. A warm or hot atmos- phere so acts on the sensory nerves of the skin as to lead them reflexly to cause a relaxation of the muscular fiber of the blood-vessels; as a result, the skin becomes full-blooded, relatively hot, and moist from sweating; and much heat is lost. With a low temperature, on the other hand, the blood- vessels shrink, and with the consequently diminished blood supply, the skin becomes pale, cold, and dry, an effect produced through the vascular centers in the medulla and spinal cord. The activity of the sweat glands of the skin is also regulated reflexly through the sweat centers. The increased blood supply just described is favorable to increased production of sweat by the sweat glands. Thus, by means of the self-regulation the skin becomes the most important of the means by which the temperature of the body is regulated. The relative loss of heat by the means given, i.e., radiation, conduction, and evaporation, will depend on two factors: first, the relative temperature of the body to the surrounding air; and, second, the humidity of the air. If the atmospheric temperature is the same as that of the body, of course there will be no loss of heat by radiation and convection; if the air temperature is higher, there will be an actual gain. When the humidity of the air is great, there will be reduced evaporation of perspiration and consequent diminished heat loss by this means. If we assume a moisture-saturated air at the body temperature, then heat loss becomes impossible and the temperature of the body will rise. This is why a hot moist climate is so oppressive, while a hot but dry atmosphere is readily borne by the human body. The increased evaporation of perspiration compensates for the decreased loss by radiation and convection. 436 ANIMAL HEAT Many examples may be given of the power -which the body possesses of resisting the effects of a high temperature, in virtue of evaporation from the skin. Blagden and others supported a temperature varying between 92° to 100° C. (i98°-2i2° F.) in dry air for sev- eral minutes; and in a subsequent experiment he remained eight minutes in a temperature of I26.5°C. (260° F.). " The workmen of Sir F. Chantrey were accustomed to enter a furnace, in which his molds were dried, while the floor was red-hot, and a thermometer in the air stood at 177.8° C. (350° F.), and Chabert, the fire-king, was in the habit of entering an oven the temperature of which was from 2O5°-3i5° C. (4oo°-6oo° F.)." (Carpenter.) But such heats are not tolerable when the air is moist as well as hot, so as to prevent evaporation from the body. C. James states that in the vapor baths of Nero he was al- most suffocated in a temperature of 44.5° C. (112° F.), while in the caves of Testaccio, in which the air is dry, he was but little incommoded by a temperature of 80° C. (176° F.). In the former, evaporation from the skin was impossible; in the latter it was abundant, and the layer of vapor which would rise from all the surface of the body would, by its very slowly conducting power, defend it for a time from the full action of the external heat. Man is able by suitable clothing to increase or to diminish the amount of heat lost by the skin. There are baths and other means which man and animals instinctively adopt for lowering the temperature when necessary. Although under any ordinary circumstances the external application of cold only temporarily depresses the temperature to a slight extent, it is otherwise in cases of high temperature in fever. In these cases a cool bath may reduce the temperature several degrees, and the effect so produced lasts in some cases for many hours. Extreme heat and cold produces effects too powerful, either in raising or lowering the heat of the body, to be controlled by the proper regulating ap- paratus. Walther found that rabbits and dogs kept exposed to a hot sun, reached a temperature of 46° C. (114.8° F.), and then died. Cases of sun- stroke furnish us with several examples in the case of man; for it would seem that here death ensues chiefly or solely from elevation of the temperature. The effect of mere loss of bodily temperature in man is less well known than the effect of heat. From experiments by Walther it appears that rab- bits can be cooled down to 8.9° C. (48° F.) before they die, if artificial respira- tion be kept up. Cooled down to 17.8° C. (64° F.), they cannot recover unless external warmth be applied together with the employment of artificial respiration. Rabbits not cooled below 25° C. (77° F.) recover by external warmth alone. Loss of Heat from the Lungs. The lungs and air-passages are very inferior to the skin as a means for lowering the temperature. In giving heat to the air breathed, the lungs stand next to the skin in importance. As a regulating power, the inferiority is very marked. The air which is ex- pelled from the lungs leaves the body at about the temperature of the blood, and is 'always saturated with moisture. No inverse proportion, therefore, exists, as in the case of the skin, between the loss of heat by radiation and conduction, on the one hand, and by evaporation, on the other. The colder the air and the drier, for example, the greater will be the loss in all ways. Neither is the quantity of blood which is exposed to the cooling influence of VARIATION IN THE PRODUCTION OF HEAT 437 the air diminished or increased in the lungs, so far as is known, in accordance with any need in relation to temperature. It is true that by varying the number and depth of the respirations, the quantity of heat given off by the lungs may be made to vary also for a few minutes. But the respiratory passages, while they must be considered important means by which heat is lost, are altogether subordinate, in the power of actively regulating the tem- perature. The loss of heat used to warm foods is an obvious method of expenditure of heat which may be resorted to, especially in certain fevers. The loss of heat by the excreta discharged from the body at a high temperature must be of little use as a means of regulating the temperature, since the amount so lost must be capable of little variation. Variation in the Production of Heat. It may seem to have been assumed, in the foregoing pages, that the only regulating apparatus for tem- perature required by the human body is one that shall, more or less, produce a cooling effect; as if the amount of heat produced were always, there- fore, in excess of that which is required. Such an assumption would be in- correct. The body has the power of regulating the production of heat, as well as its loss. The production of heat in the body is apparently different for each ani- mal; i.e., the absolute amount of heat set free by different animals in a given period varies. Each individual has his own coefficient of heat production. From all that has been said on the subject it will be seen that the amount of heat for all practical purposes depends upon the metabolism of the tissues of the body ; everything, therefore, which increases that metabolism will increase the heat production; so, therefore, the absolute amount of heat produced by a large animal, having a larger amount of tissues in which metabolism may go on, will be, c&teris paribus, greater than that of a small animal. But the activity of the tissue change in a small animal may be greater than in a large one, as measured per kilo of body-weight, and naturally no strict line can be drawn between the two. HEAT PRODUCED PER KILO PER HOUR. (MUNK.) Man 1.5 calories Dog (large) 1.7 Dog (small) 3.8 Guinea-pig 7.5 Rat 11.3 Mouse 19.0 Sparrow 35.5 The ingestion of foods increases the metabolism of the tissues. As one would expect, the rate of heat production is found by experiment upon the dog to be increased after a meal, reaching its height about six hours after a meal. 438 ANIMAL HEAT It has also been experimentally ascertained that the rate of heat produc- tion varies with the kind of food taken: for example, if sugar be added to the meal of meat given to the dog, the height of maximum production is reached. It is often said that the various nations have found by experience what food is most suitable for the climate in which they live, and that such experience can be trusted to regulate the quantity consumed. Although there have been no very conclusive experiments to prove the view, yet it is a matter of general observation that in northern climates and in colder seasons the quan- tity of food takerris greater than in warmer climates or in warmer seasons. Moreover, the kind of food is different. For example, persons living in the colder climates require much fat in order to produce the requisite amount of heat. Influence of the Nervous System on Heat Production. The in- fluence of the nervous system in modifying the production of heat must be very important, as upon the nervous influence depends the amount of the metab- olism of the tissues. The experiments and observations which best illus- trate it are those showing, first, that, when the supply of nerves to a part is cut off, the temperature of that part falls below its ordinary degree after a time; and, second, that when there is severe injury to or removal of the nervous centers the temperature of the body rapidly falls, even though arti- ficial respiration be performed, the circulation maintained, and to all appear- ance the ordinary conditions for chemical changes in the body be com- pletely maintained. There is a heat-regulating nervous apparatus closely comparable to that which regulates the secretion of saliva or of sweat, by means of which the pro- duction of heat in the warm-blooded animals is increased or diminished, as occasion requires. This apparatus probably consists of a center or centers in the brain which may be reflexly stimulated, as, for example, by impulses from the skin, and which act through special nerves supplied to the various tissues. The evidence upon which the existence of this regulating appara- tus depends is the marked effect in the increase of the oxygen consumed by a warm-blooded animal when exposed to cold, and the corresponding increase in the output of carbon dioxide, indicating that there is an increase of the metabolism and so an increased production of heat under such circumstances, and not a mere diminution of the amount of heat lost by the skin, etc. A cold-blooded animal reacts very differently to exposure to cold; instead of increasing the metabolism as in the case of the warm-blooded animal, cold diminishes the metabolism of its tissues. It is clear, therefore, that in warm- blooded animals there is some apparatus not possessed by cold-blooded ani- mals, which counteracts the effects of cold. In warm-blooded animals poi- soned by curara, or in which section of the medulla has been done, it has been found that this regulating apparatus is no longer in action, and under such circumstances no difference appears to exist between such animals and those INFLUENCE OF NERVOUS SYSTEM ON HEAT PRODUCTION 439 which are naturally cold-blooded. Warmth increases their temperature, and cold lowers it, and with this there is, of course, evidence of diminished metabolism. The explanation of these experiments is that in such animals the connec- tion between the skin and the muscles through the nervous chain, such as a thermotaxic nervous apparatus might be supposed to afford, is broken either at the termination of the nerves in the muscles (curara) or at the sec- tioned point of the bulb. The position of these hypothetical centers is a matter of some difference of opinion. It has been demonstrated that stimulation of certain parts of the brain may, among other symptoms, produce increased metabolism of the tissues with increased output of carbon dioxide and a raised temperature: the parts of which this may be asserted are parts of the corpus striatum and of the optic thalamus. The general thermogenic centers are probably closely associated with the motor centers of the cord and brain stem. The thermo- regulative centers are the nuclei in the corpus striatum and optic thalamus. Assuming a constant or tonic activity of the thermogenic regulative centers, it is easy to understand the fall of temperature on their destruction or on the destruction of the nerve path to the active tissues. Experimental observations, such as have been made upon animals, receive confirmation from the observations on patients who suffer from fever or pyrexia; in them the temperature of the body may be raised several de- grees, as we have already pointed out. This increase of temperature might, of course, be due to diminished loss of heat from the skin, but this, although a factor, is not the only cause. The amount of oxygen taken in and the amount of carbon dioxide given out are both increased, and with this there must be increased metabolism of the tissues, and particularly of the muscular tissues, since at the same time the amount of urea in the urine is increased. Every one is familiar with the rapid wasting which is such a characteristic of high fever; it must indicate not only too rapid metabolism of the body, but also insufficient time for the tissues to build themselves up. In fever, then, there may be supposed to be some interference with the ordinary reflex channel by which the skin is able to communicate to the nervous sys- tem the necessity of an increased or diminished production of heat in the muscles and other tissues. In consequence of this, and in spite of the con- dition of increased heat of the body, both at the surface and in the deeper tissues, the production of heat goes on at an abnormal rate. It is not certain whether the pathological condition is one which stimulates the thermogenic center by means of which the metabolism of the tissues is increased, or whether the normal reflexes which ordinarily inhibit the activity of the center v/hen the temperature rises fail to bring about their usual reaction. The first is the probable explanation of the high fevers of certain toxemias, CHAPTER XIII MUSCLE-NERVE PHYSIOLOGY CHEMICAL COMPOSITION OF MUSCLE Muscle Plasma. The principal substance which can be extracted from muscle, when examined after death, is the proteid body, myosin, some of the reactions of which have been already discussed. This body appears to bear somewhat the same relation to the living muscle that fibrin does to the living blood, since the coagulation of muscle after death is due to the formation of myosin. Thus, if coagulation be delayed by removing the muscles immediately that an animal is killed, and rapidly cooling them to a temperature below o° C. before the muscles themselves lose their irritability, it is possible to express from them a viscid fluid of slightly alkaline reaction, called muscle plasma (Kiihne, Halliburton). Muscle plasma, if exposed to the ordinary temperature of the air (or more quickly at 37° to4o°C.), undergoes coagulation much in the same way as does blood plasma under similar cir- cumstances when separated from the blood-corpuscles at a low temperature. The appearances presented by the fluid during the process are also very similar to the phenomena of blood-clotting, viz., first of all an increased viscidity appears on the surface of the fluid, and at the sides of the containing vessel, which gradually extends throughout the entire mass, un'il a fine transparent clot is obtained. In the course of some hours the clot begins to contract, and to squeeze out of its meshes a fluid corresponding to blood serum. In the course of coagulation, therefore, muscle plasma separates into muscle clot and muscle serum. The muscle clot contains the substance myosin. It differs from fibrin in being easily soluble in a 2 per cent solution of hydrochloric acid, and in a 10 per cent solution of sodium chloride. It is insoluble in distilled water, and its solutions coagulate on application of heat; in short, it is a globulin. During the process of clotting the reaction of the fluid becomes distinctly acid. The coagulation of muscle plasma can be prevented not only by cold, but also, as Halliburton has shown, by the presence of neutral salts in certain proportions; for example, of sodium chloride, magnesium sulphate, or sodium sulphate. It will be remembered that this is also the case with blood plasma. Dilution of the salted muscle plasma will produce its slow coagulation, which is prevented by the presence of the neutral salts in strong solution. 440 MUSCLE SERUM 441 It is highly probable that the formation of muscle clot is due to the presence of a ferment, myosin jerment. The antecedent myosin in living muscle has received the name of myosinogen, in the same way that the fibrin-forming element in the blood is called fibrinogen. Myosinogen is, however, a mixture of two globulins which coagulate at the temperatures 47° C. and 56° C. re- spectively. Myosin may also be obtained from dead muscle after all the blood, fat, and fibrous tissue, and substances soluble in water have been removed by subjecting it to a 10 per cent solution of sodium chloride, or a 5 per cent solution of mag- nesium sulphate, or a 10 to 15 per cent solution of ammonium chloride, filtering and allowing the filtrate to drop into a large quantity of water. The myosin separates out as a white flocculent precipitate. The precipitate gives all the globulin reactions. Muscle Serum. Muscle serum is acid in reaction, and almost col- orless. It contains three proteid bodies, viz.: A globulin (my o globulin), which can be precipitated by saturation with sodium chloride, or magnesium sulphate, and which can be coagulated at 63° C.; serum albumin (myo- albumin), which coagulates at 73° C., but is not precipitated by saturation with either of those salts ; and myo-albumose, which is neither precipitated by heat nor by saturation with sodium chloride or magnesium sulphate, but may be precipitated by saturation with ammonium sulphate. It is closely connected with, even if it is not itself, myosin ferment. Neither casein nor peptone has been found by Halliburton in muscle extracts. In extracts of muscles, especially of red muscles, there is a certain amount of hemoglobin, and also of a pigment' special to muscle, called by McMunn myo-hematin, which has a spectrum quite distinct from hemoglobin, viz., a narrow band just before D, two very narrow bands between D and E, and two other faint bands, near E b, and between E and F close to F. Other Constituents of Muscle. In addition to muscle ferments, already mentioned, muscle extracts contain certain small amounts of pepsin and fibrin ferment and an amylolytic jerment. Certain acids are also present, particularly sarco-lactic, as well as traces of acetic and formic. Of carbohydrates, glycogen and glucose (or maltose) and inosite are present. Glycogen is present in considerable amount, especially in the muscles of well-nourished young animals. The glycogen is converted to mal- tose in the muscles on standing some hours after death. Nitrogenous crystalline bodies, such as creatin, creatinin, xanthin, hypo- xanthin, or carnin, taurin, urea in very small amount, uric acid, and inosinic acid, are all found on extracting dead muscle. Salts of potassium and calcium are present in muscle, the chief of which is potassium phosphate. 442 MUSCLE-NERVE PHYSIOLOGY THE PROPERTIES OF LIVING MUSCLE. Elasticity. Muscle has a certain amount of elasticity during rest. It admits of being considerably stretched, but returns readily and completely to its normal condition. In the living body the muscles are always stretched somewhat beyond their natural length, they are always in a condition of slight tension; an arrangement which enables the whole force of the con- traction to be utilized in approximating the points of attachment. If the ex- tensibility of a given muscle be measured by adding to it equal increments of weight, it will be found that the extension or stretching is considerable at first, but that the amount decreases with each additional weight. If the figures obtained be plotted on coordinate paper, a curve approaching a parab- ola is obtained, whereas a steel spring is perfectly elastic and gives a straight line. When the weights are removed from a stretched muscle, one by one, the muscle regains its original length, though slowly. Extreme fatigue greatly decreases the elasticity, while an increase of temperature increases it. Cardiac muscle and smooth muscle both manifest elasticity in the same manner as skeletal muscle. In fact the elasticity of the arterioles is chiefly due to the smooth muscle in their walls, a fact that is of great importance in the adaptability of the circulatory apparatus. The flexibility of the stomach, the urinary bladder, etc., is traceable to the same property of their muscular walls. Contractility and Irritability of Muscle. The property of muscular tissue by which its peculiar functions are exercised is its contractility, which is excited by all kinds of stimuli applied either directly to the muscles or in- directly to them through the medium of their motor nerves. The property of the muscle which enables it to respond to a stimulus is called its irritability. This property, although commonly brought into action through the nervous system, is inherent in the muscular tissue. This is proven: i, By the fact that contractility is manifested in a muscle which is isolated from the influence of the nervous system by division of the nerves supplying it so long as the natu- ral tissue of the muscle is duly nourished. 2, It is manifested in a portion of muscular fiber in which, under the microscope, no nerve fiber can be traced. 3, Substances such as curara, which paralyze the nerve endings in muscles, do not at ad diminish the irritability of the muscle itself. 4, When a muscle is fatigued, a local stimulation is followed by a contraction of a small part of the fiber in the immediate vicinity, without any regard to the distribution of nerve fibers. Forms of Stimuli for Muscle or Nerve. The power of contraction in voluntary muscles is normally called forth in the body by nerve impulses which reach the muscles over the motor nerves. But a muscle will respond to stimuli of various kinds, and these stimuli may be applied directly to the muscle or indirectly to the nerve supplying it. There are distinct advantages, FORMS OF STIMULI FOR MUSCLE OR NERVE 443 however, in applying the stimulus to the nerve, as it is more convenient, as well as more potent. The stimuli which will produce contraction in a muscle are: 1. Mechanical Stimuli. A blow, pinch, prick of the muscle or its nerve will produce a contraction, repeated on the repetition of the stimulus. If applied to the same point for a number of times such stimuli will soon destroy the irritability of the preparation. 2. Thermal Stimuli. If a needle or glass rod be heated and applied to a muscle or its nerve, the muscle will contract. A temperature of over 45° C. will cause the muscles of a frog to pass into a condition known as heat rigor. The sudden change of temperature acts as a stimulus. 3. Chemical Stimuli. A great variety of chemical substances will excite the contraction of muscles, some substances being more potent in irritating the muscle itself, and other substances having more effect upon the nerve. Of the former may be mentioned dilute acids, salts of certain metals, e.g., zinc, copper, and iron; to the latter belong strong glycerin, strong acids, ammonia, bile salts in strong solution, etc. 4. Electrical Stimuli. Any form of electrical current may be employed to stimulate a muscle to contract, but either galvanism or the induced current is usually chosen. For experimental purposes electrical stimuli are most frequently used, as the strength of the stimulus may be conveniently regulated. In order that a stimulus shall be effective, it must have a certain amount of energy and the application to the muscle must have a certain abruptness. For example, a comparatively weak galvanic current suffices to stimulate a muscle to action when suddenly applied in full force. But if the electric current be applied very gradually, a current many times stronger will fail to arouse contraction of a muscle. Necessary Apparatus used to Produce and Record a Muscle Contraction. Galvanic currents are usually obtained by the employment of a continuous-current cell such as that of Daniell, by which an electrical current which varies but little in intensity is obtained. The cell (figure 314 A) consists of a positive plate of well-amalgamated zinc im- A B Fig. 314.— Diagram of a Darnell's Cell A, Dry Cell B, 444 MUSCLE-NERVE PHYSIOLOGY mersed in a porous cell containing dilute sulphuric acid; and this cell is again contained within a large copper vessel (forming the negative plate) containing a saturated solution of copper sulphate. The electrical current is made continuous by the use of the two fluids in the following manner. The action of the dilute sulphuric acid upon the zinc plate partly dissolves it, and liberates hydrogen, and this gas passes through the porous vessel, and decomposes the copper sulphate into copper and sulphuric acid. The former is deposited upon the copper plate, and the latter passes through the porous vessel to renew the sulphuric FIG. 315. — Du Bois Raymond's Key. acid which is being used up. The copper-sulphate solution is renewed by crystals of the salt, which are kept on a little shelf attached to the copper plate and slightly below the level of the solution in the vessel. The current of electricity supplied by this cell will continue without variation for a considerable time. Other cells, such as the dry cell (which, however, is adapted to open-circuit work) may be used in place of Daniell's. The FIG. 316. — Mercury Key. way in which the apparatus is arranged is to attach wires to the copper and zinc plates, and to bring them to a key, connecting the wires of the battery. One often employed is Du Bois Reymond's, figure 315. It consists of two pieces of brass about an inch long, in each of which are two holes for wires and binding-screws, to hold them tightly. These pieces of brass are fixed upon a vulcanite plate to the under surface of which is attached a screw APPARATUS USED TO PRODUCE MUSCLE CONTRACTION 445 clamp by which it can be secured to the table. The interval between the pieces of brass can be bridged over by means of a third thinner piece of similar metal fixed by a screw to one of the brass pieces, and capable of movement by a handle at right angles, so as to touch the other piece of brass. If the wires from the battery are brought to the inner binding- screws, and the bridge connects them, the current passes across it and back to the battery. Wires are connected with the outer binding-screws, and the other ends are joined together for about two inches, but, being covered except at their points, are insulated; the un- covered points are about an eighth of an inch apart. These wires are the electrodes, and the electrical stimulus is applied to the muscle through them, if they are placed behind its nerve. When the connection between the two brass plates of the key is broken by depress- ing the handle of the bridge, the key is then said to be opened. An induced current is developed by means of an apparatus called an induction coil, and the one most employed for physiological purposes is Du Bois Reymond's, the one seen in figure 317. Wires from a battery are brought to the two binding-screws, d' and d, a key intervening. These binding-screws are the ends of a coil of coarse covered wire, c, called the primary coil. FIG. 317. — Du Bois Reymond's Induction Coil. The ends of a coil of finer covered wire, g, are attached to two binding-screws to the left of the figure, one only of which is visible. This is the secondary coil, and is capable of being moved nearer to c along a groove and graduated scale. To the binding-screws to the left of g, the wires or electrodes used to stimulate the muscle are attached. If the key in the cir- cuit of wires from the battery to the primary coil (primary circuit) be closed, the current from the battery passes through the primary coil, and across the key to the battery, and continues to pass as long as the key continues closed. At the moment of closure of the key, at the exact instant of the completion of the primary circuit, an instantaneous current of electricity is induced in the secondary coil, g, if it be sufficiently near and in line with the primary coil; and the nearer it is to c, the stronger is the current induced. The current is only momentary in duration and does not continue during the whole of the period while the primary circuit is complete. When, however, the primary current is broken by open- ing the key, a second current, also momentary, is induced in g. The former induced cur- rent is called the making and the latter the breaking shock; the former is in the opposite direction to, and the latter in the same direction as, the primary current. The induction coil may be used to produce a rapid series of shocks by means of the accessory apparatus at the right of the figure, called the magnetic interrupter. If the wires from a battery are connected with the two pillars by the binding-screws, one below c, and the other at a, the course of the current is indicated by the arrows in figure 318. The cur- rent passes up the pillar from e, and along the springs if the end of d' is close to the spring, 446 MUSCLE-NERVE PHYSIOLOGY then to the primary coil c, and to wires covering two upright pillars of soft iron, b, to the pillar a, and out by the wires to the battery. In passing along the wire b the soft iron is converted into a magnet, and so attracts the hammer, /, of the spring, breaks the connection of the spring with df, and so cuts off the current from the primary coil, and also from the electro-magnet. As the pillars, b, are no longer magnetized the spring is released, and the current passes in the first direction, and is in like manner interrupted. At each make and break of the primary current, currents corresponding are induced in the secondary coil. These currents are opposite in direction, but are not equal in intensity, the break shock being greater. In order that the shocks should be nearly equal at the make and break, a wire, figure 318, e, connects e and d', and the screw d' is raised out of reach of the spring, and d is raised as in figure 318, so that part of the current always passes through the primary coil and electro-magnet. When the spring touches d the current in b is diminished, FIG. 318. — Diagram of the Course of the Current in the Magnetic Interrupter of Du Bois Reymond's Induction Coil. (Helmholz's modification.) but never entirely withdrawn, and the primary current is altered in intensity at each con- tact of the spring with d, but never entirely broken. Preparation of a Muscle for Contraction under Stimuli. The muscles of the frog are most convenient for the purpose of recording contractions. The frog is pithed, that is to say, its central nervous system is entirely destroyed by the insertion of a stout needle into the spinal cord, and the parts above it. One of its lower extremities is used in the following manner. The large trunk of the sciatic nerve is dissected out at the back of the thigh, and a pair of electrodes is inserted behind it. The tendo Achillis is divided from its attachment to the os calcis, and a ligature tightly tied round it. This is the tendon of the gastrocnemius, which arises from above the condyles of the femur. The femur is now fixed to a board covered with cork, and the ligature attached to the tendon is tied to the upright of the muscle lever, figure 319, B. When the muscle contracts the lever is raised. It is necessary to attach a small weight to the lever. In this arrangement the muscle is in situ, and the nerve disturbed from its relations as little as possible. The muscle may, however, be detached from the body with the lower end of the femur from which it arises, and the nerve going to it may be taken away with it. The femur should be divided at about the lower third, and the bone fixed in a firm clamp ; the nerve is placed upon two electrodes connected with an induction apparatus, and the lower end of the muscle is connected by its tendon with a lever which can write on a recording apparatus. To prevent evaporation this so-called muscle-nerve preparation is placed under a glass cover (moist chamber, figure 350). The air in the moist chamber is kept moist by means of water adherent to its sides. Recording the Effects of a Single Induction Shock. With a muscle-nerve preparation arranged in either of the above ways, on closing or opening the key in the primary circuit we obtain and can record a contraction, and if we use the clock-work apparatus revolving rapidly, a curve is traced such as is shown in figure 320. CONDUCTIVITY IN MUSCLE 447 Another way of recording the contraction is by use of the pendulum myograph, figure 352. Here the swing of the pendulum along a certain arc is substituted for the clock- driven movement of the other apparatus. The pendulum carries a smoked-glass plate upon which the writing lever of a myograph is made to mark. The opening or breaking shock FIG. 319. — Arrangement of the Apparatus Necessary for Recording Muscle Contractions with a Revolving Cylinder Carrying Smoked Paper. A, Revolving cylinder; B, the frog arranged upon a cork-covered board which is capable of being raised or lowered on the upright, which also can be moved along a solid triangular bar of metal attached to the base of the recording ap- paratus—the tendon of the gastrocnemius is attached to the writing lever, properly weighted, by a ligature. The electrodes from the secondary coil pass to the apparatus — being, for the sake of convenience, first of all brought to a key, D (Du Bois Reymond's); C, the induction coil; F, the battery (in this figure a bichromate one); E, the key (Morse's) in the primary circuit. is sent into the nerve-muscle preparation by the pendulum in its swing opening a key, figure 352, C, in the primary circuit. A muscle or its nerve is more irritable to an opening shock than it is to a closing shock of the same strength, because the duration of the former is shorter than that of the latter. Conductivity in Muscle. In an ameba or other simple undiffer- entiated contractile protoplasmic unit a stimulus applied at any point is quickly transmitted throughout the entire mass. Just so is it with differenti- ated muscle. A stimulus applied at any point of a muscle will quickly be propagated through the mass as far as there is protoplasmic continuity. In cardiac muscle and in smooth muscle there is uninterrupted conduction from cell to cell. But in voluntary muscle each fiber is physiologically isolated from its neighbors. When a voluntary muscle fiber is stimulated either at the ex- tremities or at its middle, the effect of the stimulus quickly passes through the entire fiber, whether it arouses a distinct act of contraction or not. 448 MUSCLE-NERVE PHYSIOLOGY The rate at which conduction takes place when a contraction accompanies it has been carefully measured by numerous observers. It varies greatly in the different kinds of muscle, from two-tenths of a meter per second in the rabbits' ureter (Engelmann ) to ten meters per second in the voluntary muscles of man. SINGLE MUSCLE CONTRACTIONS. Characteristics of a Single Contraction. The Myogram. The con- traction of a muscle in response to a single effective stimulus of short duration is called a simple muscle contraction. A record of such a contraction is called a myogram. The character of the myogram, and therefore the facts revealed by it, are dependent on whether or not the record is made on a rapidly moving recording surface. If the myogram is made on a recording surface that is standing still, then it shows merely the extent of shortening of the muscle. The amount of shortening for a given muscle will depend on a series of conditions, such as nutrition, load, temperature, etc., all of which will be discussed presently. When the record is made on a rapidly moving drum or on the pendulum myograph, it is revealed that the simple contraction occupies a definite period >f time with well-marked periods or phases. Although the stimulus may be FIG. 320.— Record of a Simple Contraction of the Gastrocnemius of the Frog. Time in .01 seconds. St, Moment of stimulation. Record taken on a rapid drum that was provided with an automatic key. - practically instantaneous, the contraction lasts a considerable fraction of a second, in the frog's gastrocnemius about o.i of a second. It will be observed that after the stimulus has been applied, as indicated by the vertical line St, there is an interval before contraction commences. This interval, termed the latent period, when measured by the number of vi- brations of the tuning-fork directly beneath, is found to be about o.oi of a second. The latent period is longer in some muscles than in others, and differs also according to the condition of the muscle and the kind of stimulus employed. During the latent period there is no apparent change in the CHANGE IN SHAPE DURING MUSCULAR CONTRACTION 449 muscle. The second part of the record shows the contraction phase proper. The lever is raised by the sudden shortening of the muscle. The contrac- tion is at first very rapid, but then progresses more slowly to its maximum. It occupies on an average 0.04 of a second in the frog's gastrocnemius. The third stage is the relaxation phase. After reaching its highest point, the lever begins to descend, in consequence of the elongation of the muscle. At first the fall is rapid, but it then becomes more gradual until the lever reaches the abscissa or base line, when the muscle has attained its precontraction length. The stage occupies 0.05 of a second. Usually after the contraction proper is over the lever oscillates below and above the base line in a series of dimin- ishing waves, the elastic rebound following movement of the simple contrac- tion. These are, of course, wholly passive and would occur equally well if we should lift the weight to the height of the contraction, then simply let it fall while taking a record. Change in Shape during Muscular Contraction. There is a consider- able difference of opinion as to the mode in which the transversely striated mus- cular fibers contract. The most probable account is that the contraction is FIG. 321. — The Microscopic Appearances During a Muscular Contraction in the Individual Fibrillae, after Engelmann. i. A passive muscle-fiber; c to c/=doubly refractive discs, with median disc a & in it; k and g are lateral discs; f and e are secondary discs, only slightly doubly refractive; figure on right same fiber in polarized light. The bright part is doubly refracted, black ends not so. 2. Transition stage. 3. Stage of entire contraction. In each case the right-hand figure repre- sents the effect of polarized light. (Landois, after Engelmann.) effected by an approximation of the constituent parts of the fibrils, which, at the instant of contraction, without any alteration in their general direction, become closer, flatter, and wider, a condition which is rendered evident by the approxi- mation of the transverse striae seen on the surface of the fasciculus, and by its in- creased breadth and thickness. The appearance of the zigzag lines into which it was supposed the fibers are thrown in contraction is due to the relaxation of a fiber which has been recently contracted and is not at once stretched again by some antagonist fiber, or whose extremities are kept close together by the contractions of other fibers. The contraction is therefore a simple and, ac- cording to Edward Weber, a uniform, simultaneous, and steady shortening of each fiber and its contents. What each fibril or fiber loses in length, it gains in thickness. The contraction is a change of form, not of size; it is, therefore, not attended with any diminution in bulk from condensation of the tissue. 29 450 MUSCLE-NERVE PHYSIOLOGY This has been proved for entire muscles, by making a mass of muscles, or many fibers together, contract in a vessel full of water, with which a fine, perpen- dicular, graduated tube communicates. Any diminution of the bulk of the contracting muscle would be attended by a fall of fluid in the tube; but when m FIG. 322. — Reflecting Galvanometer. (Thomson.) A, The galvanometer, which consists of two systems of small astatic needles suspended by a fine hair from a support, so that each set of needles is within a coil of fine insulated copper wire; that forming the lower coil is wound in an opposite direction to the upper. Attached to the upper set of needles is a small mirror about K inch in diameter ; the light from the lamp at B is thrown upon this little mirror, and is reflected upon the scale on the other side of B, not shown in figure. The coils u are arranged upon brass uprights, and their ends are carried to the binding-screws. The whole apparatus is placed upon a vulcanite plate capable of being leveled by the screw supports, and is covered by a brass-bound glass shade, /, the cover of which is also of brass, and supports a brass rod, b, on which moves a weak curved magnet, m. C is the shunt by means of which the amount of current sent into the galvanom- eter may be regulated. When in use, the scale is placed about three feet from the galvanometer, which is a ranged east and west, the lamp is lighted, the mirror is made to swing, and the light from the lamp is adjusted to fall upon it, and it is then regulated uncil the reflected spot of light from it falls upon the zero of the scale. The wires from the non-polarizable electrodes touching the muscle are attached to the outer binding-screws of the galvanometer, a key intervening for short-circuiting; or if a portion only of the current is to pass into the galvanometer the shunt should intervene as well with the appropriate plug in. When a current passes into the galvanometer the needles and, with them, the mirror are turned to the right or left according to the direction of the cur- rent. The amount of the deflection of the needle is marked on the scale by the spot of light traveling along it. the experiment is carefully performed, the level of the water in the tube re- mains the same, whether the muscle be contracted or not. In thus shortening, muscles appear to swell up, becoming rounder, more prominent, harder, and apparently tougher. But this hardness of muscle in the state of contraction is not due to increased firmness or condensation of the CHEMICAL CHANGES IN CONTRACTING MUSCLE 451 muscular tissue, but to the increased tension to which the fibers, as well as their tendons and other tissues, are subjected from the resistance ordinarily opposed to their contraction. When no resistance is offered, as when a muscle is cut off from its tendon, not only is no hardness perceived during contraction, but the muscular tissue is even softer and more extensible than in its ordinary uncontracted state. During contraction in each fiber it is said that the aniso- tropous or doubly refractive elements become less refractive and the singly refractive more so, figure 321. Chemical Changes in Contracting Muscle, i. The reaction of the muscle, which is normally alkaline or neutral, becomes decidedly acid during contraction, from the development of sarcolactic acid. 2. The muscle gives out carbon dioxide gas and takes up oxygen. The amount of the carbon dioxide given out does not appear to be entirely dependent upon the oxygen taken in, and so doubtless in part arises from some other source. Muscle contracts in FIG. 323.— Diagram of Du Bois Raymond's Non-polarizable Electrodes, a, Glass tube filled with a saturated solution of zinc sulphate, in the end, c, of which is china clay drawn out to a point; in the solution a well-amalgamated zinc rod is immersed and connected, by means of the wire which passes through a, with the galvanometer. The remainder of the apparatus is simply for convenience of application. The muscle and the end of the second electrode are to the right of the figure. an atmosphere of hydrogen, showing that oxygen is present in fixed combina- tion. A muscle, however, contracts for a longer time in an atmosphere of oxygen. 3. Certain imperfectly understood chemical changes occur, in all probability connected with i and 2, in which glycogen is diminished, and glucose and muscle sugar, inosite, appear. The nitrogenous extractives are also increased. Electrical Changes in Contracting Muscle. Resting muscles un- injured in the body have a uniform potential, are isoelectric. But when removed from the body they are more or less injured and, therefore, show differences of electrical potential between different points on the muscle, called currents of injury or demarcation currents. 452 MUSCLE-NERVE PHYSIOLOGY The Demonstration of Muscle Currents. The demonstration of electrical currents in muscle requires a galvanometer and non-polarizing electrodes. A muscle prism is insulated, and a pair of non-polarizable electrodes connected with a very delicate galva- nometer, figure 322, are applied to various points of the prism; and by a deflection of the needle to a greater or less extent in one direction or another, the strength and direction of the currents in the piece of muscle can be determined. It is necessary to use non-polariz- able and not metallic electrodes in this experiment, as otherwise there is no certainty that the whole of the current observed is communicated from the muscle itself and not derived from the metallic electrodes and arising in consequence of the action of the saline juices of the tissues upon them. The form of the non-polarizable electrodes is a modification of Du Bois Reymond's apparatus, figure 323, which consists of a somewhat flattened glass cyl- inder, a, drawn abruptly to a point, and fitted to a socket capable of movement, and at- tached to a stand, A , so that it can be raised or lowered as required. The lower portion of the cylinder is filled with china clay moistened with saline solution, part of which projects through its drawn-out point; the rest of the cylinder is filled with a saturated solution of zinc sulphate into which dips a well -amalgamated piece of zinc connected by means of a wire with the galvanometer. In this way the zinc sulphate forms a homogeneous and non- polarizable conductor between the zinc and the china clay. A second electrode of the same kind is, of course, necessary. Recently Porter has devised a boot-shaped clay electrode that is burned and hence has the immense advantage of permanency. Currents of Injury, or Demarcation Currents. If a segment is cut out of a living gastrocnemius, its cut ends present regions of maximal injury. Such a preparation is called a muscle prism. If the points on the surface of a muscle prism be connected with the gal- vanometer by non-polarizable electrodes, it will be found that the currents pass from point to point, as shown in the diagram, figure 324. FIG. 324. — Diagram of the Currents in a Muscle Prism. (Du Bois -Raymond.) The strongest currents pass from the equator to a point representing the middle of the cut ends; currents also pass from points nearer the equator to those more remote, but not from points equally distant, which are isoelectric points. The cut ends are always negative to the equator. The currents are in all probability due to chemical changes going on in the muscles at the in- jured ends. Action Currents. When a muscle is made to contract the demar- cation current undergoes a sharp decrease as shown by the deflection of the galvanometer needle, which swings back in the direction of equilibrium. HEAT PRODUCED IN A SIMPLE CONTRACTION 453 This deflection, originally called the current of negative variation, has been shown to be due to the processes going on in the muscle during contraction and is therefore called the action current. It occurs where no previous demar- cation current exists. For the study of the action current the capillary electrometer is very con- venient. The hearts of cold-blooded animals, because of their slow con- traction, serve well for demonstration. The muscle contraction passes over the ventricle in the form of a wave, the electric potential of the muscle changing as it becomes active or passive. For any two points on the heart muscle, therefore, there will be two changes of potential, the active part first becom- ing negative to the inactive, and then, as the wave passes down and the in- FIG. 325. — Figure for Work Energy, Showing Height of the Contraction of the Gastrocnemius of the Frog with Loads Increased by Ten Grams at a Time. active part becomes active, the current is reversed. This is known as a diphasic current. In certain fishes definite electrical organs exist, organs which are derived from muscle-like tissues and which may be regarded morphologically as mus- cles highly specialized for the production of energy in the form of electricity. Heat Produced in a Simple Contraction. Becquerel and Breschet found, with the thermo-multiplier, about 0.5° C. of heat produced by each forcible contraction of a man's biceps; and when the actions were long con- tinued, the temperature of the muscle increased i° C. In the frog's muscle a considerable number of contractions have been found to produce an ele- vation of temperature equal on an average to less than 0.2° C., while a single contraction produces, according to R. Heidenhain, from 0.001° to 0.005° C- One gram of frog's muscle will produce in a single maximal contraction about 0.003 calorie or the equivalent of 126 gramcentimeters of work energy (since i calorie = o.425 kilogrammeter of work). The cause of the rise of tempera- ture is the increased chemical activity at the time of 'contraction. As we have already seen, in the chapter on Animal Heat, muscles have the power of producing heat even when not contracted. 454 MUSCLE-NERVE PHYSIOLOGY The amount of heat energy developed during a single contraction will vary sharply according to the tension under which the muscle contracts. The heat production follows closely the energy of work produced, and apparently obeys the same laws. The Work Energy Liberated by a Simple Muscle Contraction. When a muscle contracts against a resistance and a load is moved, work energy is liberated. In fact the liberation of work energy and heat energy are the specific functions of the muscles among the warm-blooded animals. A frog's gastrocnemius weighing i gram and loaded with 50 grams will contract from 0.5 to 0.6 cm, i.e., will do 25 to 30 gramcentimeters of work for each simple contraction. The amount of work done is intimately associ- TABLE SHOWING THE RELATION BETWEEN LOAD AND WORK. Load or Tension. Height Lifted. Work Done. Grams. Centimeters. Gramcentimeters. o 1.2 O 40 0.8 32 80 0.5 40 120 O.4 48 160 0.2 32 200 O.I 2O 240 o.o o ated with the tension under which the muscle contracts. As the tension in- creases from no load up to 100 or 150 grams (for a i-gram muscle), the work increases. But as the tension continues to increase, the work "falls off until a point is reached at which the load is not lifted at all. CONDITIONS WHICH AFFECT THE IRRITABILITY OF THE MUSCLE AND THE CHARACTER OF THE CONTRACTION. There are a number of conditions which influence both the irritability of a muscle and the power and character of its contractions. Irritability and contractility may vary independently, but as a rule any condition which decreases the one also decreases the other. The most important of these conditions are: relation of the muscle to the central nervous system, con- dition of nutrition, stimulus, temperature, fatigue, drugs, disease, etc. Effect of the Strength of Stimulus. A strength of current that is just sufficient to give the contraction of a muscle is called a minimal stimulus. This is a comparatively weak induction current, one which can scarcely be detected by the tip of the tongue. As the strength of the current is very gradually increased,' the height of the contraction curve increases until the maximal stimulus is reached, which produces a contraction of an amplitude beyond which no increase occurs even though the strength of the stimulus be THE INFLUENCE OF REPEATED ACTIVITY 455 multiplied many fold. The range between the strengths of the minimal and maximal stimuli is very restricted indeed. The absolute strength of a mini- mal stimulus varies exceedingly for a given muscle, depending on its degree of irritability. This narrow range between minimal and maximal stimuli serves as a convenient means for detecting the variations in irritability. One should count on a continued decrease in irritability in isolated muscles, hence FIG. 326.— Contraction of the Gastrocnemius Under the Influence of Variation of Strength of Stimulus. The muscle was stimulated by Petr.old's inductorium, graduated to show units of current. The figures 6, 7, 8, 9, 10, etc., indicate relative strength of stimulus. should choose a supramaximal stimulus for all such preparations when other conditions surrounding the muscle are under investigation. The Influence of Repeated Activity. The irritability of muscle is decreased by undue functional activity. The cause of the diminished ir- ritability is twofold: when a muscle contracts, part of its substance is ex- pended, part of its store of nutriment is exhausted, and it cannot contract so vigorously again until the loss is made up. To this extent fatigue has much the same effect as cutting off or diminishing the blood supply. The other cause for the diminution of irritability is the accumulation of poisonous prod- ucts in the muscle, substances generated during contraction, probably sar- colactic acid chiefly. In a living animal these poisonous products exert their influence not only upon the muscle or muscles immediately concerned in contraction, but upon the musculature of the body generally, and the effect remains until they are eliminated from the body. Massage of the muscles increases the passage of waste products into the general blood stream and the rapidity of their elimination. In the first few simple contractions, repeated in series, there is an increase in the amplitude of the contractions resulting in the phenomenon known as staircase contractions or "Treppe." This stage is followed by a period 456 MUSCLE-NERVE PHYSIOLOGY of sustained contractions, and this finally by a diminishing series of amplitudes until the muscle fails to respond. After a few minutes' rest a muscle will again give strong contractions, but only for a brief series. If the time of the simple contractions is measured, it will be found, figure 327, that not only is the amplitude decreased but the duration is greatly increased as the contractions are repeated. The latent period changes very little. The contraction phase is considerably prolonged, but the relaxation phase is very greatly increased. As fatigue progresses, the total time of the simple contraction may be two or three times longer than the normal. The FIG. 327. — Contractions of the Gastrocne"mius Muscle to Show Fatigue. The numbers printed on the figure indicate the contractions in the series which is recorded. (Lee.) ability of the muscle to do work falls off rapidly, of course; and the greater the load during the time fatigue is coming on, the more quickly complete fatigue approaches. The Influence of Temperature. The irritability of muscle is in- creased by raising its temperature slightly above that of the animal from which it has been taken, while it is decreased by cooling. If, however, the FIG. 328. — Contractions of the Gastrocnemius Muscle to Show the Influence of Temperature on the Amplitude'of the Contractions. At 40° C. the muscle has begun to pass into rigor mortis, yet is able to give short contractions. The steps on the curve of rigor at the right occur at tem- peratures of 41°, 42°, and 43° C. THE INFLUENCE OF TEMPERATURE 457 temperature be raised too high (40° C. fcr frog, 50° C. for mammal), the muscle enters into a condition of heat rigor and its irritability is forever lost. After cooling, unless the cold be too severe and prolonged, the irritability re- turns as the temperature is raised. A series of vertical records of simple contrac- tions beginning at room temperature and decreasing with a contraction at each fall of one degree reveals the fact that the amplitude falls off slowly until a temperature of 12° to 10° C. is reached, then as gradually increases until 4° to 2° C., after which the amplitude drops off sharply to about — 1° C. However, this phenomenon is partly one of irritability, since a very strong stimulus will produce a vigorous contraction until the muscle begins to freeze. If at the freezing temperature the muscle be slowly and carefully increased in tem- perature it will recover from the effects of the cooling without apparent injury, and will give a reverse series to the one obtained by decreasing the temperature. FIG. 329. — Influence of Temperature on the Duration of the Contraction of the Frog's Gastrocnemius. As the increase of temperature is continued above room temperature the amplitude of the contractions very greatly increases (also the elasticity), reaching a maximum in the frog's gastrocnemius at about 35° to 36° C. The amplitude sharply decreases above 35° C. up to 37° to 38° C., where heat rigor begins and the muscle permanently shortens. Heat rigor is usually 458 MUSCLE-NERVE PHYSIOLOGY complete at 40° to 41° C. A muscle cannot recover its irritability after heat rigor has set in strongly. If the time of the contraction is measured at different temperatures it will be found to be greatly delayed at 2° to 4° C., and very much quicker than nor- mal at 33° to 35° C. As in fatigue, the effect falls chiefly on the contraction and relaxation phases and only slightly on the latent period. The latent period is more sharply influenced by temperature than by fatigue. Influence of Blood Supply. In the normal human muscle there is a delicately balanced vaso-motor mechanism by which the amount of blood flowing through a muscle is immediately increased when the muscle is in con- traction. This blood stream is of course carrying nutritive materials to the muscle and taking away wastes. If the blood supply to a muscle is cut off, then the muscle can only draw on its stored supply of potential energy, which in active contraction is sooner or later exhausted. Under such conditions the muscle increases in irritability for a few minutes and then gradually loses both its irritability and its power to contract. Even mammalian muscles have been kept alive and normal in their activity for several hours by irrigat- ing them with defibrinated and aerated blood (von Frey). Mammalian muscles will remain irritable for 30 minutes, or longer if cooled, after being shut off from their blood supply and isolated from the body, but both irrita- bility and contractility soon disappear entirely. Effect of Nerve Supply. The voluntary or skeletal muscle normally contracts in the body only when stimulated through its motor nerve. If the motor nerve is severed, the muscle is cut off from its normal source of activity, hence will undergo the changes resulting from disuse, which will be presently discussed. Aside from this, it is held by most observers that there are dis- tinct nutritive or trophic nerves which exercise a controlling influence over the growth, development, and general nutritive processes going on in muscle. When a motor nerve is cut, the muscle at first exhibits heightened irrita- bility to all forms of stimuli. In a couple of weeks it decreases in its power to respond to rapidly changing stimuli like induced currents. It responds more readily to mechanical shocks and to galvanic currents for six or seven weeks, then gradually loses the power of contracting through as many months. The changes are due to protoplasmic degeneration. It is not clear in what degree these changes are due to loss of trophic nerve influence, to inac- tivity, and to changes in nutritive conditions. Since degeneration occurs when the vascular supply is maintained, it would seem that the nutritive con- dition must be chargeable to one or the other of the first two factors, probably to both. Use of muscle increases its power and also its irritability. A properly regulated exercise is well known to contribute to the health and development of muscles. In cases of paralysis, mechanical or electrical stimulation is applied directly to the muscle in an effort to supply artificial exercise until the THE EFFECT OF DRUGS 459 nerves are regenerated and motor connections reestablished. If such stim- ulation is not applied, the muscle degenerates from disuse and loses its irri- tability often before the nerves regenerate. The Effect of Drugs. Drugs affect the irritability of muscle, some augmenting, others depressing it. Voluntary muscle, which does not ordina- rily contract except when stimulated, can be made so irritable by certain salts that it contracts automatically like heart muscle, and the converse. Ether, chloroform, etc., anesthetize muscle just as they do nerve, suppressing both irritability and contractility. Suprarenal extract increases the ampli- tude of contraction, as do also caffeine, digitalis, nicotine, and others. Ver- atrine is well known greatly to prolong the relaxation phase of the simple contraction without materially affecting the contraction phase, or the latent period. TETANIC AND VOLUNTARY MUSCULAR CONTRACTIONS. Effect of Rate of Stimulation. If we stimulate the muscle-nerve preparation with two induction shocks, one immediately after the other, when the point of stimulation of the second one corresponds to the crest of the con- traction of the first, a second curve, figure 330, will occur, which will commence near the highest point of the first and will rise nearly as much higher, so that the sum of the height of the two curves almost exactly equals twice the height of the first. This phenomenon is called summation. If a third FIG. 330.— Tracing of a Double Muscle-Curve. To be read from left to right. While the muscle was engaged in the first contraction (whose complete course, had nothing intervened, is indicated by the dotted line), a second induction shock was thrown in, at such a time that the second contraction began just as the first was beginning to decline. The second curve is seen to start from the first, as does the first from the base line. (M. Foster.) and fourth shock be passed, a similar effect will ensue, and curves one above the other will be traced, the third being slightly lower than the second, and the fourth than the third. If a continuous series of shocks occur, however, the lever after a time ceases to rise any further, and the con- traction, which has reached its maximum, is maintained. The condition which ensues is called Tetanus. A tetanus is really a summation of contrac- 460 MUSCLE-NERVE PHYSIOLOGY tions, but unless the stimuli become very rapid indeed, the muscle will still be in a condition of vibratory contraction and not of unvarying contraction. If the shocks, however, be repeated at very short intervals, varying, in the frog, from eighteen to thirty per second, the muscle contracts to its utmost at once and continues at its maximum contraction for some time. The lever rises almost perpendicularly and then describes a straight line, figure 331, c. The rate of stimulation required increases with the rapidity of the simple contraction. If the stimuli are not so rapid, the line of maximum con- traction becomes wavy, indicating a tendency of the muscle to relax during FIG. 331.— a, Frog's gastrocnemius muscle stimulated with four induction shocks per second, showing complete relaxation between stimuli ; b, same muscle stimulated eight times per second, showing partial relaxation between stimuli (incomplete tetanus); c, same muscle stimulated twelve times per second, showing development of an almost complete tetanus. the intervals between. the stimuli, figure 331, b. As the muscle becomes fatigued, a less rapid rate of stimulation is required to produce a complete tetanus, owing to the prolongation of the relaxation period in such a muscle. The height of the contraction, however, is lessened. This condition of pro- longed relaxation is known as contracture. Coordinated Muscular Contractions. In the human body the skel- etal muscles contract only on stimulation through their motor nerves, i.e., under the influence of nerve impulses that have their origin in the central MUSCLE IN RIGOR MORTIS 461 nervous system. Such motor impulses may arise through reflexes, through automatic activity of the nerve center, or by higher cerebral origin associated with conscious psychic effort. In either case the apparatus consists of one or more central neurones, an anterior-horn motor cell, and the muscle itself. Conscious or voluntary effort may be taken as a type. Simple contractions are possible to human muscles, but undoubtedly tetanic contractions are the rule. If one holds the arm out at right angles to the trunk, the movement requires the continuous or tetantic contraction of the deltoid and the series of extensor muscles. If the arm is retained in the extended position long enough, extreme fatigue is felt and presently one can no longer maintain the position. Yet, if the muscles involved are immediately stimulated directly with an electric current, they contract, showing that such exhaustion as exists is not wholly due to the muscle. Mosso's ergograph was devised for the specific purpose of studying the character of fatigue of voluntary effort. This apparatus is adapted to the study of the fatigue of the flexors of the middle finger, or, in the newer in- strument devised by Storey, to the abductor of the index finger. Numerous studies have shown, apparently, that the fatigue of voluntary effort involves, first, the nervous apparatus and, later, the muscle; that the muscle still retains a considerable reserve of energy \vhen the apparatus as a whole is exhausted. Muscle in Rigor Mortis. After the muscles of the dead body have lost their irritability or capability of being excited to contraction by the ap- plication of a stimulus, they spontaneously pass into a state of contraction apparently identical in effect with that which ensues during life. It affects all the muscles of the body, and, when external circumstances do not. prevent it, commonly fixes the limbs in that which is their natural posture of equilibrium or rest. From the simultaneous contraction of all the muscles of the trunk, a general stiffening of the body is produced, which constitutes the rigor mortis or post-mortem rigidity. When this condition has set in, the muscle becomes acid in reaction (due to development of sarcolactic acid), gives off carbonic acid in great excess, diminishes in 'volume slightly, becomes shortened and opaque, its substance sets in a firm coagulatio. Rigor comes on much more rapidly after muscular activity, and is hastened by warmth. The immediate cause of rigor seems to be a chemical one, namely, the coagulation of the muscle plasma. We may distinguish three main stages; i. Gradual coagulation. 2. Contraction of coagulated muscle clot (myosin), and 3, squeezing out of muscle serum. During the first stage, restoration is possible, by the circulation of arterial blood through the muscles; and even when the second stage has set in, vitality may be restored by dissolving the coagulum of the muscle in salt solution, and passing arterial blood through the vessels. After the second stage is advanced, recovery is impossible. 462 MUSCLE-NERVE PHYSIOLOGY It has been noticed that the relaxation in muscles after rigor sometimes occurs too quickly to be caused by putrefaction. The suggestion that in such cases the relaxation is due to a ferment-action is very plausible. It is known that pepsin is present in muscles, and that this ferment will act in an acid medium. The conditions for the solution of the coagulated myosin are therefore present since the reaction of muscle in rigor is acid. Subjecting fresh muscle to the action of heat (50° to 60° C.) or immersing it in distilled water causes a similar coagulation to that of rigor mortis. The former is known as heat rigor, and the latter as witer rigor. FIG. 332. — Curve of Shortening of the Gastrocnemius Muscle of the Frog, During Heat Rigor. The numbers indicate degrees centigrade. The muscles are not affected simultaneously by rigor mortis. It affects the neck and lower jaw first; next, the upper extremities, extending from above downward; and, lastly, reaches the lower limbs. In some rare instances cnly, it affects the lower extremities before or simultaneously with the upper extremities. It usually ceases in the order in which it begins: first at the head, then in the upper extremities, and lastly in the lower extremities. It never ordinarily commences earlier than ten minutes, and never later than seven hours after death; and its duration is greater in proportion to the lateness of its accession. Heat is developed during the passage of a muscular fiber into the condition of rigor mortis. Since rigidity does not ensue until muscles have lost the capacity of being excited by external stimuli, it follows that all circumstances which cause a speedy exhaustion of muscular irritability induce an early occurrence of the rigidity, while conditions by which the disappearance of the irritability is delayed are succeeded by a tardy onset of the rigidity of rigor. This is the explanation of its speedy occurrence, and equally speedy departure, in the bodies of persons exhausted by chronic diseases; and its tardy onset and long MUSCULAR METABOLISM DURING CONTRACTION 463 continuance after sudden death from acute diseases. In some cases of sudden death from lightning, violent injuries, or paroxysms of passion, rigor mortis has been said not to occur at all ; but this is not always the case. It may, indeed, be doubted whether there is really a complete absence of the post-mortem rigidity in any such cases; for the experiments of Brown-Sequard make it probable that the rigidity may supervene immediately after death, and then pass away with such rapidity as to be scarcely observable. The occurrence of rigor mortis is not prevented by the previous existence of paralysis in a part, provided the paralysis has not been attended with very imperfect nutrition of the muscular tissue. The rigidity affects the involuntary as well as the voluntary musclesr whether they be constructed of striped or unstriped fibers. The rigidity of involuntary muscles with striped fibers is shown in the contraction of the heart after death. The contraction of the muscles with unstriped fibers is shown by an experiment of Valentin, who found that if a graduated tube be connected with a portion of intestine taken from a recently killed animal, and the intestine be tied at the opposite end, and filled with water, the water will in a few hours rise to a considerable height in the tube, owing to the con- traction of the intestinal walls. It is still better shown in the arteries, of which all that have muscular coats contract after death, and thus present the roundness and cord-like feel of the arteries of a limb lately removed, or those of a body recently dead. Subsequently they relax, as do all the other mus- cles, and feel lax and flabby and lie as if flattened, and with their walls nearly in contact. Muscular Metabolism During Contraction. The question of the metabolism of muscle both in a resting and in an active condition has for many years occupied the attention of physiologists. It cannot be said even now to be thoroughly understood. Most of the facts with reference to the subject have been already mentioned. We may shortly recapitulate them here : First, muscle during rest absorbs oxygen and gives out carbon dioxide. This has been shown by an analysis of the gases of the blood going to and leaving muscles. During activity, e.g., during tetanus, the same interchange of gases takes place, but the quantities of the oxygen absorbed and of the carbon dioxide given up are increased, and the proportion between them is altered thus : Venous Blood. O2, less than in Arterial Blood. CO2, more than in Arterial Blood. Of resting muscle 9 per cent 6.71 per cent Of active muscle 12.26 per cent 10.79 Per cent 464 MUSCLE-NERVE PHYSIOLOGY There is then a greater proportion of carbon dioxide produced in muscle during activity than during rest. During rigor mortis there is also an increased production of carbon dioxide. Second, muscle during rest produces nitrogenous crystallizable substances, such as creatin, from the metabolism which is constantly going on in it during life; in addition there are formed, in all probability, sarcolactic acid and other non-nitrogenous matters. During activity the nitrogenous substances, such as creatin, undergo very slight, if any, increase — about the amount produced during rest — but the sarcolactic acid is distinctly increased; sugar (glucose) is also increased, whereas the glycogen is diminished. During rigor mortis the sarcolactic acid is increased, and in addition myosin is formed. From these data it is assumed that the processes which take place in resting and active muscles are somewhat different, at any rate in degree. From actively contracting muscle, also, there are obtained an increased amount of heat and mechanical work; potential energy is converted into kinetic energy. Many theories have been proposed to explain the facts of muscular energy. It has been suggested by Herman that muscular activity depends upon the splitting up and subsequent re-formation of a complex nitrogenous body, called by him Inogen. When this body so splits up there result from its decomposition carbon dioxide, sarcolactic acid, and a gelatino-albuminous body. Of these the carbon dioxide is carried away by the blood stream; the albuminous substance and possibly the acid, at any rate in part, go to re- form the inogen. The other materials of which the inogen is formed are supplied by the blood; of these* materials we know that some carbohydrate substance and oxygen form a part. The decomposition, although taking place in resting muscle, reaches a climax in active muscle, but in that con- dition the destruction of inogen largely exceeds restoration, and so there must be a limit to muscular activity. But this is not the only change going on in muscle, there are others which affect the nitrogenous elements of the tissue, and from them result the nitrogenous bodies of which creatin is the chief; these changes may be unusually large during severe exercise. It has been further suggested as myosin is undoubtedly formed in rigor mortis when the muscle becomes acid and gives off carbon dioxide, and since myosin is formed also when muscle contracts, that the phenomenon of contraction is a condition akin to partial death. The electrical reactions appear to justify this; both contracted and dead muscle are negative to living muscle when at rest. What happens to the myosin which is formed when muscle contracts, if this view be the correct one, is unknown. Halli- burton suggests that the myosin, which can be made to clot and unclot easily enough outside the body, is able to do the same thing in the body. It is pos- CONTRACTION IN INVOLUNTARY MUSCLE AND IN CILIA 465 sible that the clotting of myosinogen which is supposed to occur during con- traction is not of the same intensity or extent as that which occurs post mortem. The relation of the hypothetical inogen to the rest of the muscle fiber is unde- termined. It may be that the inogen is formed by the activity of the muscle- protoplasm and stored up within itself, and that during rest of muscle it is gradually used up, whereas in activity it is suddenly and explosively decom- posed. In the rest of the fiber the nitrogenous metabolism continues much the same during activity. THE TYPE OF CONTRACTION IN INVOLUNTARY MUSCLE AND IN CILIA. Cardiac Muscle. Some detail concerning the action of cardiac mus- cle has already been given in connection with the chapter on Circulation. As compared with the activity of skeletal muscle, cardiac muscle differs most strikingly in that it is automatic. A strip of heart muscle taken from any part of the heart, under proper conditions, gives off a series of contrac- tions, whether it receives any special stimulus or not, whereas we have just found that skeletal muscle under similar conditions remains quiet unless stimu- lated in some special way. The fibers of skeletal muscle are more or less physiologically isolated from each other, and one fiber may contract without involving contractions of the others. Cardiac muscle, on the other hand, when stimulated at any point conducts the change produced throughout the continuity of the mass. Cardiac muscle contractions are influenced by tension, temperature, fatigue, etc., apparently, in the same way as skeletal muscle. When the contraction occurs it is always maximal. The actual am- plitude of the contraction is dependent on the condition of nutrition of the cardiac muscle. If the contractions are at a rapid rate they will be relatively of less amplitude. If an extra contraction is induced in an automatic series, so that the interval between two contractions is similar, then the amplitude will be correspondingly reduced. Such an extra contraction is followed by a delayed automatic contraction, the phenomenon of compensatory pause. The contractions in cardiac muscle are simple contractions. In fact, it is said to be impossible to produce a tetanus except in certain invertebrate hearts. This possibility depends upon the fact that during the time of a single contrac- tion there is a certain interval between the beginning and the crest of the con- traction, figure 174, in which the heart muscle is not irritable. This is known as the refractory phase. The duration of the contraction of heart muscle is much greater than the contraction of skeletal muscle. The total time of a contraction in a frog's gastrocnemius is o.i of a second, while the time of a contraction of the ven- tricle in the same animal is at least 0.7 to 0.8 of a second. In the terrapin's 30 466 MUSCLE-NERVE PHYSIOLOGY cardiac muscle the time of a contraction is over a second, but in the warm- blooded cardiac muscle the time is shorter, perhaps from 0.4 to 0.5 of a second for the human ventricular muscle. Smooth Muscle. The physiology of smooth muscle has been given to some extent in previous chapters, particularly in connection with the move- ments of the stomach and intestines. As compared with skeletal and cardiac muscle it is a much more slowly acting contractile tissue. Isolated strips of smooth muscle, as a rule, contract only when stimulated, though preparations of certain tissues, like the stomach muscle of the frog, give off rhythmic con- tractions occasionally. In this regard smooth muscle stands intermediate between skeletal and cardiac muscle ; the former is normally never automatic, the latter always. Smooth muscle requires a different type of stimulus to produce contraction ; the stimulus must be more prolonged and more intense. For example, FIG. 333- — Contraction Area in Smooth Muscle. A, Showing the contraction nodes of the fibers, the deep staining of the nodes, the condensation of surrounding connective tissue; B, diagrammatic, showing the thickening of the longitudinal fibrillae. Intestine of dog. (Unpub- lished figure by Caroline McGill.) smooth muscle is not readily responsive to induction currents of short duration, but is readily stimulated by galvanic currents or induction currents of longer duration. The stimulus must be applied through a longer interval of time. CHANGES DURING THE CONTRACTION OF SMOOTH MUSCLE 4G7 Preparations of the stomach muscle can scarcely be made to contract by a single induction current, no matter how intense. Such muscle in the body is always associated with the local nervous apparatus which plays an indeter- minate part in its activity. The ureters and gall-bladder are the parts most difficult to excite by stimuli ; they do not act at all till the stimulus has been long applied, and then con- tract feebly and to a small extent. The contractions of the cecum and stomach are quicker, and still quicker those of the iris and of the urinary bladder. The contractions of the small and large intestines, of the vas deferens, and of the pregnant uterus, are yet more regular and more sustained. Changes During the Contraction of Smooth Muscle. The dura- tion as well as type of contraction in smooth muscle is very markedly differ- ent from that of voluntary muscle. A contraction in smooth muscle is i FIG. 334. — Enlarged Detailed Drawing of the Nucleus of Smooth Muscle in the Relaxed and in the Contracted State. Intestine of Necturus. Zeissobj. 2, oc. 8. (Unpublishedfigure by Caro- line McGill.) characterized by a very long latent period, a slowly developed contraction phase, and an extremely delayed relaxation, figure 355. The amount and duration of the contractions are dependent upon the strength and duration of the stimulus, though the curve of contraction itself does not in other respects differ sharply from the type of curve of the simple muscle contraction. Owing to the apparently different structural type of smooth muscle, es- pecial interest attaches to the changes which occur during its contraction. Caroline McGill has recently re-examined the histological structure and in- vestigated the function of this type of muscle, and we are able to present a figure showing the changes. The longitudinal fibrillae, which are readily stained with iron hematoxylin, show distinct shortening and thickening at the 468 MUSCLE-NERVE PHYSIOLOGY nodes of contraction of the muscle, figure 333, B. The whole fiber is thick- ened at the contraction nodes and stains very readily and usually uniformly. However, by certain stains the fibrillse can be traced through the node. The node is an apparent area of chemical differentiation. There is a marked con- densation of the intermuscular fibrous tissue, which is doubtless purely a passive phenomenon. The most striking change during contractions is observed in the nucleus, figure 333, A, and figure 334. The nucleus during rest is a long slender oval or spindle with a general chromatic network. "During contraction, the smooth muscle nuclei shorten and thicken by an active process. The chromatin collects, chiefly at the two ends of the nucleus, leaving a relatively clear area in the center." Ciliary Motion. Ciliary motion, which is closely allied to ameboid and muscular motion, is alike independent of the will, of the direct influ- ence of the nervous system, and of muscular contraction. It may continue for several hours after death, or removal of the ciliated tissue, provided the portion of tissue under examination be kept moist. Its independence of the nervous system is shown also in its occurrence in the lowest invertebrate animals which are apparently unprovided with anything analogous to a nervous system, and in its persistence when the ciliated cells are completely separated from each other by teasing out in serum or other physiological solution. The vapor of chloroform arrests the motion; but it is renewed on the discontinuance of the application of the anesthetic. The movement ceases when the cilia are deprived of oxygen (although it may continue for a time in the absence of free oxygen) but is revived on the admission of this gas. Carbon dioxide also stops the movement. The contact of various substances, e.g., bile, strong acids, and alkalies, will stop the motion altogether; but this depends chiefly on destruction of the delicate substance of which the cilia are composed. Temperatures above 45° C. and below o° C. stop the movement, whereas moderate heat and faintly alkaline solutions are favorable to the action and revive the movement after temporary cessation. The exact explanation of ciliary movement is not known. Whatever may be the exact explanation, the movement must depend upon some changes going on in the cells of which the cilia are a part and not on changes limited to the cilia themselves, since, when the latter are cut off from the cell the movement ceases, and when severed so that portions of the cilia are left attached to the cell, the attached and not the severed portions continue the movement. Ciliary contraction is to be regarded as a type of motor activity carried out in a spe- cialized form of motor apparatus. The changes going on in the cell must be classed with similar changes in heart or skeletal muscle. Ciliary tissue is like cardiac in at least two characteristics: the cells are capable of conducting a stimulus from cell to cell, and ciliary activity is automatic. As a special illustration of cilia-like action may be mentioned the motion of spermatozoa, which are cells with a single cilium. THE FUNCTION OF NERVE FIBER 469 THE FUNCTION OF NERVE FIBER. The Nerve Impulse. The motor nerve fibers of the muscle-nerve preparation are of the medullated type described on page 64. But the es- sential structure, possessed by all fibers, is the axis cylinder. The peculiar function of the nerve fiber, i.e., of the axis cylinder, is its power to conduct a physiological change along its extent, a phenomenon known as a nerve impulse. A normal nerve impulse in a motor nerve has its origin in the motor cell of the central nervous system of which the fiber is an outgrowth. The manner in which such discharge from the cell takes place will be discussed later. But nerve impulses may be aroused by various artificial means, they are influenced by certain conditions in the environment, and possess certain other properties that may be discussed at this point. Nerve Stimuli. Nerve fibers like skeletal muscle require stimu- lation before they can manifest any of their properties, since they have no power of themselves of originating nerve impulses. The stimuli which are capable of exciting nerves to action are, as in the case of muscle, very diverse. The mechanical, chemical, thermal, and electrical stimuli which may be used in the case of muscles are also, with certain differences in the methods em- ployed, efficacious in stimulating the nerve. The chemical stimuli are chiefly these: withdrawal of water as by drying; strong solutions of neutral salts of potassium, sodium, etc.; free inorganic acids, except phosphoric; and some organic acids. The electrical stimuli employed are the induction and con- tinuous currents concerning which the observations in reference to muscular irritability should be consulted. Galvanic currents stimulate nerves only at the moment of turning on the current and of turning it off. Weaker electrical stimuli will excite nerves than will excite muscles; the nerve impulse appears to gain strength as it descends, and a weaker stimulus applied far from the muscle will have the same effect as a slightly stronger one applied to the nerve near the muscle. Characteristics of the Nerve Impulse. When a nerve impulse is aroused in a motor nerve, as by stimulating a nerve in its course by an induced current of medium strength, it is propagated along the axis cylinder to the muscle where it arouses a contraction of the muscle fiber. In the contraction of the muscle we have indirect but conclusive evidence of the passage of the nerve impulse, for it can be readily proven that the electrical current does not escape to the muscle. In this instance it can be shown that there is a nerve impulse passing from the point of stimulation in the direction away from the muscle; i.e., the artificially aroused nerve impulse passes over the entire extent of the fiber stimulated. In fact, a nerve impulse is known to travel from its point of origin over the entire neurone affected. This antidro- mal nerve impulse, of course, does not exist in the normal case, since the nor- 470 MUSCLE-NERVE PHYSIOLOGY mal nerve impulse arises in the nerve-cell body and passes out over the fiber from its origin to its extremity. The nerve impulse travels over the nerve fiber with a velocity that was first determined by Helmholtz. He found that in the sciatic of the frog the nerve impulse travels at the rate of twenty-seven meters per second. The rate has been measured in a number of animals and varies between wide limits. In human nerves the rate is variously given, but thirty meters per second may be taken as a fair average. The presence of the nerve impulse can be detected by the action current, which exists in nerve as in muscle (see page 451 for methods of detecting the action current). Rheoscopic Frog. The action current may be demonstrated by means of the follow- ing experiment: The muscle current produced by stimulating the nerve of one muscle-nerve preparation may be used to stimulate the nerve of a second muscle-nerve preparation. The hindleg of a frog with the nerve going to the gastrocnemius cut long is placed upon a glass plate and arranged in such way that its nerve touches in two places the gastrocnemius muscle, exposed but preserved in situ in the opposite thigh of the frog. The electrodes from an induction coil are placed behind the sciatic nerve of the second preparation, high up. On stimulating it with a single induction shock, the muscles not only of the same leg are found to undergo a twitch, but also those of the first preparation, although this is not near the electrodes. The stimulation cannot be due to an escape of the stimulating current into the first nerve, but is due to the action current of the second muscle. This experi- ment is known under the name of the rheoscopic frog. When the nerve impulse is studied by means of the action current it is found that a nerve impulse can be aroused by a weaker stimulus than is re- quired to produce a minimal contraction of a muscle. The response of the nerve to graduated strengths of the stimulus is increased very rapidly with slight increase of strength of the stimulus, the augmentation extending through a somewhat greater range than for muscle. If the stimulus is still further in- creased there is only slight increase of the resulting nerve impulse. Fatigue of Nerve Fiber. Many efforts have been made to dis- cover evidences of fatigue of nerve fiber, with practically complete negative results. A difficulty has been to secure means of measuring change in intensity of the nerve impulse. The muscle quickly fatigues so that the character of the muscle response cannot be taken when measured in the ordinary way. An effective method used by Howell, Budgett, and Leonard consists in cooling a segment of nerve to suspend its conductivity, during stimulation of the free end ; and periodically warming up the cooled segment of nerve to test the strength of nerve impulse passing through it to the unfatigued muscle beyond. By this and other methods it has been found that a motor nerve is not fatigued by at least ten hours' continuous stimulation with induction currents. One must hesitate to draw the conclusion, however, that the nerve fiber conducts the nerve impulse without loss of energy. The fiber can be anesthe- tized, it responds to temperature changes, and gives other evidences of sus- THE EFFECTS OF BATTERY CURRENTS ON NERVE-FIBER 471 ceptibility to conditions which influence metabolism in other forms of proto- plasm. Perhaps the nerve fiber is capable of repairing its wastes as rapidly as they occur. The Effects of Battery Currents on Nerve Fiber. Galvanic currents influence nerves in ways that call for special discussion. A constant cur- rent, say from a Daniell battery, can be introduced into the nerve of a muscle-nerve preparation by means of a pair of non-polarizable electrodes, figure 3 2 3, and a convenient key arranged for turning the current on or off the nerve. It will be found that with a current of moderate strength there will be a contraction of the muscle, both at the closing and the opening of the key (called respectively making and breaking contractions), but that during the interval between these two events the muscle remains flaccid, provided the battery cur- rent continues of constant intensity. If the current be a very weak or a very strong one, the effect is not quite the same; one or the other of the contractions may be absent. Which of these contractions is absent depends upon another circumstance, viz., the direction of the current. The direction of the current may be ascending or descending: If ascending, the anode or positive pole is nearer the muscle than the cathode or negative pole, and the current to return to the battery has to pass up the nerve; if descending, the position of the elec- trodes is reversed. It will be necessary before considering this question further to return to the apparent want of effect of the constant current during the interval between the make and the break contraction. To all appear- ances no change is produced, but in reality a very important alteration of the irritability and conductivity is brought about in the nerve by the passage of this constant or polarizing current. A second way of showing the effect of the polarizing current is by stimu- lating the nerve by a pair of electrodes from an induction coil, while the polar- izing current from the battery is flowing through the nerve. If the strength of stimulus required in order that a minimum contraction be obtained by the induction shock before the polarizing current is applied, and the secondary coil be removed slightly further from the primary, the induction current cannot now produce a contraction. If now the polarizing current be sent in a descending direction, that is to say, with the cathode nearest the muscle, and the induction current which was before insufficient be applied between the cathode and the muscle, it will now prove sufficient to cause a contraction. This indicates that with a descending current the irritability of the nerve is increased at the cathode. If instead of applying the induction electrodes below the polarizing electrodes, they are applied above them, the irritability of the nerve is found to be decreased. If the polarizing current is reversed, i.e., made ascending, then the condition of irritability of the nerve is reversed. Both methods show that the polarization consists in an increase in irritability at the cathode, called catelectrotonus, and a decrease at the anode called anelectrotonus. The total change is called by the term electrotonus. As there 472 MUSCLE-NERVE PHYSIOLOGY is between the electrodes both an increase and a decrease of irritability on the passage of a polarizing current, it is evident that there must be a neutral point where there is neither increase nor decrease of irritability. The position of this neutral point is found to vary with the intensity of the polarizing current ; when the current is weak the point is nearer the anode, when strong nearer the FIG. 335- — Diagram Illustrating the Effects of Various Intensities of the Polarizing Currents. n, n', Nerve; a, anode; k, cathode; the curves above indicate increase, and those below decrease of irritability, and when the current is small the increase and decrease are both small, with the neutral point near a, and so on as the current is increased in strength. cathode, figure 335. When a constant current passes into a nerve, therefore, if a contraction result, it may be assumed that it is due to the increased irritability produced in the neighborhood of the cathode, but the breaking contraction must be produced by a rise in irritability from a lowered state to the normal in the neighborhood of the anode. The contractions produced in the muscle of a muscle-nerve preparation by a constant current have been arranged in a table which is known as Pfluger's Law of Contractions. It is really only a statement as to when a contrac- tion may be expected: DESCENDINC ; CURRENT. ASCENDING CURRENT. STRENGTH OF CURRENT USED. Make. Break. Make. Break. Very weak. . ... Yes No No No Weak Yes No Yes No ^Moderate Yes Yes Yes Yes Strong Yes No No Yes During the passage of a constant current through a nerve and immediately after its cessation, there is a change in the conductivity as well as of the irri- tability of the nerve at the anode and cathode, respectively. During the pas- sage of the current, the conductivity is increased at the cathode and decreased at the anode. After the passage of the current, the effect is reversed. With strong currents the area of decreased conductivity may be sufficient to act as a block, preventing the passage of impulses over it. EFFECT OF BATTERY CURRENTS ON DEEP-SEATED NERVES 473 The foregoing statements concerning the changes produced in a nerve by the passage of a constant current may be briefly summarized as follows: I. A nerve is more irritable to the closing of a constant current than it is to the opening of a constant current. II. During the passage of the current through the nerve, both its irrita- bility and conductivity are increased at the cathode and decreased at the anode. III. After the passage of the current, the irritability and conductivity are both decreased at the cathode and increased at the anode. The Effect of Battery Currents on Deep-Seated Nerves. The follow- ing account is condensed from Lombard in "An American Text-book of Physiology." As an electric current cannot be applied to living human nerves directly, it is applied to the skin along the course of the nerve. The current passes from the anode or positive pole through the skin, and spreads out in the tissues much as the bristles of a brush; it then gradually concentrates and leaves the skin at the cathode or negative pole. In addition to the physical anode and cathode of the battery, there are what are called physiological anodes and cathodes. There is a physiological anode at every point where the current enters a nerve, and a physiological cathode at every point where it leaves it. Generally when the current is applied to nerves through the skin, only part of it flows longitudinally along the nerves; most of it passes diagonally through Shin FIG. 335 A. — Diagram of Skin and Subjacent Nerve. A, the positive electrode or physical anode; B, the negative electrode or physical cathode. Signs, + physiological anodes; signs- physiological cathodes. (After Waller.) them to the tissues below. Thus it happens that in that part of the nerve beneath either the physical anode or cathode, groups of physiological anodes and cathodes are found. The contraction which occurs when the current is closed (closing con- traction) represents irritation at the physiological cathode, while the opening contraction represents irritation at the physiological anode. Since there are physiological anodes and cathodes beneath each electrode, one or more of four conditions may arise: i. Anodic closing contraction, i.e., the effect of the change developed at the physiological cathode, beneath the physical anode (positive pole). 474 MUSCLE-NERVE PHYSIOLOGY 2. Anodic opening contraction, i.e., the effect of the change developed at the physiological anode, beneath the physical anode (positive pole). 3. Cathodic closing contraction, i.e., the effect of the change developed at the physiological cathode, beneath the physical cathode (negative pole). 4. Cathodic opening contraction, i.e., the effect of the change developed at the physiological anode, beneath the physical cathode (negative pole). The following abbreviations of these contractions are used: ACC, AOC, KCC, KOC. The closing contractions, KCC and ACC, are stronger than the opening contractions, KOC and AOC. Of the closing contractions, KCC is strong- er than ACC. Of the opening contractions, AOC is stronger than KOC. These facts are also shown in a table of the effects of gradually increasing the strength of the current. Weak Currents. KCC Medium Currents. KCC ACC AOC Strong Currents. KCC ACC AOC KOC Sometimes AOC is stronger than ACC. In diseases which cause degeneration of the nerves going to a muscle, stimulation causes results different from the above, and we get what is known as the reaction of degeneration. r. nervl med. m. pron. tereti. m. palmaris longus m. ulnarls Int. n. ulnaris r. vol. prof. n. ulnar. m. palmar brevis m. abduc. dig. min. m. flex. dig. min. m. oppon. dig. min. mm, Uimbr. II.,III.,IV. m. radial. Intern, m. flex. dig. prof. m. flex. dig. sublim. m. flex. poll. long, m. medianus •- -S^ m. abduc. poll. brey. .7 L'. „ .A m. oppon. poll. m. flex. poll. brev. m. adduc. poll. - m. lumbric. I. FIG. 336. — Figure Showing Motor Points in the Forearm. LOCOMOTION 475 The intensity of the anodic or cathodic effects is increased by using small electrodes, and decreased by electrodes of large surface. In fact in practice it is usual to apply the indifferent electrode to an extended surface, thus re- ducing its effect below the stimulating intensity. This gives only one active stimulating electrode and is known as the method of unipolar stimulation. SOME SPECIAL COORDINATED MOTOR ACTIVITIES. I. LOCOMOTION. The greater number of the more important muscular actions of the human body, those, namely, which are arranged harmoniously so as to subserve some definite purpose in the animal economy, are described in various parts of this work in the sections which treat of the physiology of the processes by which these muscular actions are resisted or carried out. There are, however, some very important and somewhat complicated muscular acts which may be best described in this place. Walking. The coordinated movements of the body are carried out by the skeletal muscles acting on the skeletal elements as a system of levers. Even the bones of the skull are levers in so far as their relations to muscles are concerned. Examples of the three orders of levers in the Human Body. All levers have been divided into three kinds, according to the relative position of the power, the weight to be moved, and the axis oj motion or fulcrum. In a lever of the first kind the power is at one extremity of the lever, the weight at the other, and the fulcrum between the two. If the initial letters only of the power, weight, and fulcrum be used, the arrangement will stand thus: P. F. W. A poker as ordinarily used, or the bar in figure 337, may be cited as an example of this variety of lever; while, as an instance in which the bones of the human FIG. 337. skeleton are used as a lever of the same kind, may be mentioned the act of raising the body from the stooping posture by means of the hamstring muscles attached to the tuberosity of the ischium or of the triceps which extends the forearm by action at the elbow, figure 337. 476 MUSCLE-NERVE PHYSIOLOGY In a lever of the second kind, the arrangement is thus: P. W. F.; and this leverage is employed in the act of raising the handles of a wheelbarrow, or in stretching an elastic band, as in figure 338. In the human body the act of opening the mouth by depressing the lower jaw is an example of the same kind — the tension of the muscles which close the jaw representing the weight, figure 338. In a lever of the third kind the arrangement is, F. P. W., and the act of raising a pole, as in figure 339, is an example. In the human body there are numerous examples of the FIG. 338. employment of this kind of leverage. The act of bending the forearm may be mentioned as an instance, figure 339. The act of biting is another example. At the ankle we have examples of all three kinds of lever, ist kind — Extending the foot. 3d kind — Flexing the foot. In both these cases the foot represents the weight: the ankle joint the fulcrum, the power being the calf muscles in the first case and the tibialis anticus in the second case, ad kind — When the body is raised on tiptoe. Here F 3? FIG. 339- the tip of the toe is the fulcrum, the weight of the body acting at the ankle joint the weight, and the calf muscles the power. In the human body, levers are most frequently used at a disadvantage as regards power, the latter being sacrificed for the sake of a greater range of motion. Thus in the diagrams of the first and third kinds it is evident that the power is so close to the fulcrum that great force must be exercised in order to produce motion. It is also evident, however, from the same diagrams, that by the closeness of the power to the fulcrum a great range of move- ment can be obtained by means of a comparatively slight shortening of the muscular fibers. In the act of walking, almost every voluntary muscle in the body is brought into play, either directly for purposes of progression, or indirectly for the proper balancing of the head and trunk. The muscles of the arms are LOCOMOTION 477 least concerned; but even these are for the most part instinctively in action to some extent. Among the chief muscles engaged directly in the act of walking are those of the calf, which, by pulling up the heel, pull up also the astragalus, and with it, of course, the whole body, the weight of which is transmitted through the tibia to this bone, figure 340. When starting to walk, say with the left leg, this raising of the body is not entirely dependent on the muscles of the left calf, but the trunk is thrown forward in such a way that it would fall prostrate were it not that the right foot is brought forward and planted on the ground to support it. Thus the muscles of the left calf are assisted in their action by those muscles on the front of the trunk and legs which, by their contraction, pull the body forward; and, of course, if the trunk form a slanting line, with the inclination forward, it is plain that when the heel is raised by the calf muscles, the whole body will be raised, and pushed obliquely forward and FIG. 340. upward. The successive acts in taking the first step in walking are repre- sented in figure 340, i, 2, 3, etc. Now it is evident that by the time the body has assumed the position No. 3, it is time that the right leg should be brought forward to support it and prevent it from falling prostrate. This advance of the right leg is effected partly by its mechanically swinging forward, pendulum- wise, and partly by muscular action; the muscles used being — i, those on the front of the thigh, which bend the thigh forward on the pelvis, especially the rectus femoris, with the psoas and the iliacus; 2, the hamstring muscles, which slightly bend the leg on the thigh; and, 3, the muscles on the front of the leg, which raise the front of the foot and toes, and so prevent the latter in swinging forward from striking the ground. The second part of the act of walking, which has been just described, is shown in the diagram, 4, figure 340. When the right foot has reached the ground the action of the left leg has not ceased. The calf muscles of the latter continue to act, and, by pulling up the heel, throw the body still more forward over the right leg, now bearing nearly the whole weight, until the time when the left leg should again swing forward, and the left foot be planted on the ground to prevent the body from falling 478 MUSCLE-NERVE PHYSIOLOGY prostrate. As at first, while the calf muscles of one leg and foot are preparing, so to speak, to push the body forward and upward from behind by raising the heel, the muscles on the front of the trunk and the same leg (and of the other leg, except when it is swinging forward (are helping the act by pulling the legs and trunk, so as to made them incline forward, the rotation in the inclining occur- ring mainly at the ankle joint. Two main kinds of leverage, are, therefore, employed in the act of walking, and if this idea be firmly grasped, the details will be understood with comparative ease. One kind of leverage employed in walking is essentially the same with that employed in pulling forward the pole, as in figure 339. And the other, less exactly, is that employed in raising the handles of a wheelbarrow. Now, supposing the lower end of the pole to be FIG. 341. placed in the barrow, we should have a very rough and inelegant, but not altogether bad representation of the two main levers employed in the act of walking. The body is pulled forward by the muscles in front, much in the same way that the pole might be by the force applied at p, while the raising of the heel and pushing forward of the trunk by the calf muscles are roughly represented on raising the handles of the barrow. The manner in which these actions are performed alternately by each leg, so that one after the other is swung forward to support the trunk, which is at the same time pushed and pulled forward by the muscles of the other, may be gathered from the previous description. There is one more thing to be especially noticed in the act of walking. In- asmuch as the body is being constantly supported and balanced on each leg alternately, and therefore on only one at the same moment, it is evident that there must be some provision made for throwing the center of gravity over the RUNNING 479 line of support formed by the bones of each leg, as, in its turn, it supports the weight of the body. This may be done in various ways, and the manner in which it is effected is one element in the differences which exist in the walk- ing of different people. Thus it may be done by an instinctive slight rotation of the pelvis on the head of each femur in turn, in such a manner that the cen- ter of gravity of the body shall fall over the foot of this side. Thus when the body is pushed onward and upward by the raising, say, of the right heel, as in figure 340, 3, the pelvis is instinctively by various muscles made to rotate on the head of the left femur at the acetabulum, to the left side, so that the weight may fall over the line of support formed by the left leg at the time that the right leg is swinging forward, and leaving all the work of support to fall on its fellow. -Such a "rocking" movement of the trunk and pelvis, however, is accompanied by a movement of the whole trunk and leg over the foot which is being planted on the ground, figure 341 , the action being accompanied with a compensatory outward movement at the hip, more easily appreciated by looking at the figure (in which this movement is shown exaggerated) than from the description. Thus the body in walking is continually rising and swaying alternately from one side to the other, as its center of gravity has to be brought alternately over one or the other leg; and the curvatures of the spine are altered in corre- spondence with the varying position of the weight which it has to support. The extent to which the body is raised or swayed differs much in different people. In walking, one foot or the other is always on the ground. The act of leap- ing or jumping consists in so sudden a raising of the heels by the sharp and strong contraction of the calf muscles that the body is jerked off the ground. At the same time the effect is much increased by first bending the thighs on the pelvis, and the legs on the thighs, and then suddenly straightening out the angles thus formed. The share which this action has in producing the effect may be easily known by attempting to leap in the upright posture, with the legs quite straight. Running. Running is performed by a series of rapid low jumps pro- duced by each leg alternately; so that, during each complete muscular act concerned, there is a moment when both feet are off the ground. In all these cases, however, the description of the manner in which any given effect is produced, can give but a very imperfect idea of the infinite number of combined and harmoniously arranged muscular contractions which are necessary for even the simplest acts of locomotion. II. THE PRODUCTION OF THE VOICE. Before commencing the consideration of the Nervous System and the special Senses it will be convenient to consider first speech, the production of the human voice, and the physiology of the larynx as a muscular apparatus. 480 MUSCLE-NERVE PHYSIOLOGY The Larynx. In nearly all air-breathing vertebrate animals there are arrangements for the production of sound, or voice, in some parts of the respiratory apparatus. In many animals, the sound admits of being variously modified and altered during and after its production; and, in man, one such modification occurring in obedience to dictates of the cerebrum, is speech. It has been proven by observations on living subjects, by means of the laryngoscope, as well as by experiments on the larynx taken from the dead body, that the sound of the human voice is the result of the vibration of the inferior laryngeal ligaments, or the true vocal cords which bound the glottis, caused by currents of expired air impelled over their edges. If a free opening exists in the trachea, the sound of the voice ceases, but it returns if the opening is closed. An opening into the air-passages above the glottis, on the con- trary, does not prevent the voice being produced. By forcing a current of air through the larynx in the dead subject, clear vocal sounds are elicited, though the epiglottis, the upper ligaments of the larynx or false vocal cords, the ventricles between the upper ligaments and the inferior ligaments, and the upper part of the arytenoid cartilages, be all removed. But the true vocal cords must remain entire with their points of attachment, and be kept tense and so approximated that the fissure of the glottis may be narrow. The vocal ligaments or cords, therefore, are regarded as the proper organs for the production of vocal sounds. The modifications of these sounds are effected, as will be presently explained, by other parts, viz., by the tongue, teeth, lips, etc. The structure of the vocal cords is adapted to enable them to vibrate like tense membranes, for they are essentially composed of elastic tissue; and they are so attached to the cartilaginous parts of the larynx that their position and tension can be variously altered by the contraction of the muscles which act on these parts. Thus it will be seen that the larynx is the organ of voice. It may be said to consist essentially of the two vocal cords and the various cartilaginous, muscular, and other apparatus by means of which not only can the aperture of the larynx (rima glottidis) be closed against the entrance and exit of air to or from the lungs, but also by means of which the cords themselves can be stretched or relaxed, brought together and separated in accordance with the conditions that may be necessary for the air in passing over them to set them vibrating to produce the various sounds. Their action in respiration has been already referred to. Anatomy of the Larynx. The principal parts entering into the formation of the larynx, figures 342 and 343, are — the thyroid cartilage; the cricoid cartilage; the two arytenoid cartilages; and the two true vocal cords. The epiglottis, figure 343, has but little to do with the voice, and is chiefly useful in protecting the upper part of the larynx from the entrance of food and drink in deglutition. The false vocal cords and the ventricle of the larynx, which is a space between the false and the true cord of either side, need be only referred to. Cartilages, a, The thyroid cartilage, figure 342, i to 4, does not form a complete ring ANATOMY OF THE LARYNX 481 around the larynx, but only covers the front portion, b, The cricoid cartilage, figure 342, 5, 6, on the other hand, is a complete ring; the back part of the ring being much broader than the front. On the top of this broad portion of the cricoid are, c, the arytenoid car- tilages, figure 342, 7, the connection between the cricoid below and arytenoid cartilages FIG. 342. — Cartilages of the Larynx Seen from the Front, i to 4, Thyroid cartilage; T, verti- cal ridge or pomum Adami; 2, right al&; 3, superior, and 4, inferior cornu of the right side; 5, 6, cricoid cartilage; 5, inside of the posterior part; 6, anterior narrow part of the ring; 7, arytenoid cartilages. Xf. above being a joint with synovial membrane and ligaments, the latter permitting tolerably free motion between them. Joints and Ligaments. The thyroid cartilage is also connected with the cricoid, not only by ligaments, but also by joints with synovial membranes; the lower cornua of the thyroid clasping the cricoid between them, yet not so tightly but that the thyroid can re- Caife "Wriabergii Cart, Santorint Cart, aryten. ICroc. itrasciil. „_ Eigs crico-aryten. Corntcin&E. — — Cartviracnero membra*. FIG, 3 43 . — The Larynx as Seen From Behind after Removal of the Muscles. The cartilages and ligaments only remain. (Stoerk.) volve, within a certain range, around an axis passing transversely through the two joints. The vocal cords are attached behind to the front portion of the base of the arytenoid car- tilages, and in front to the re-entering angle at the back part of "the thyroid; it is evident, therefore, that all movements of either of these cartilages must produce an effect on them of some kind or other. Inasmuch, too, as the arytenoid cartilages rest on the top of the back portion of the cricoid cartilage, and are connected with it by capsular and other liga- ments, all movements of the cricoid cartilage must move the arytenoid cartilages, and also produce an effect on the vocal cords. 31 482 MUSCLE-NERVE PHYSIOLOGY Intrinsic Muscles. The intrinsic muscles of the larynx are so connected with the laryngeal cartilages that by their contraction alterations in the condition of the vocal cords and glottis are produced. They are usually divided into four classes according to their action, viz., into abductors, adductors, sphincters, and tensors. The Abductors, the crico- arytenoidei, widen the glottis, by separating the cords; the Adductors, consisting of the thyro-ary-epiglottici, the arytenoideus posticus seu transversus, the thyro-arytenoidei externi, FIG. 344. — The Cartilages and Ligaments of the Larynx, Viewed from the Front, a, Epiglottis; b, hyoid bone; c, cartilage tritica; d, thyro-hyoid membrane; e, superior cornu of thyroid cartilage- j, thyroid notch; g, pomum Adami; h, crico-thyroid membrane; i, inferior cornu of thyroid cartilage; /, cricoid cartilage. (Cunningham.) the crico-arytenoidei later ales, and the thyro-arytenoidei interni, approximate the vocal cords, diminish the rima glottidis, and act generally as sphincters and supporters of the glottis. Finally, the tensors of the cords put the cords on the stretch, with or without elongating them; the tensors are the crico-thyroidei and the thyro-arytenoidei interni. The attachments and the action of the muscles will be readily understood from the following table. All the muscles are in pairs except the arytenoideus posticus. TABLE or THE SEVERAL GROUPS OF THE INTRINSIC MUSCLES OF THE LARYNX AND THEIR ATTACHMENTS. GROUP. MUSCLE. ATTACHMENTS. ACTION. L Abductors. Crico-aryte- This pair of muscles arises, on either Draw inward and noidei pos- side, from the posterior surface of the backward the out- tici. corresponding half of the cricoid car- er angle of ary- tilage. From this depression their tenoid cartilages, fibers converge on either side upward and so rotate out- and outward to be inserted into the ward the processus outer angle of the base of the ary- vocalis and widen tenoid cartilages behind the crico- the glottis. arytenoidei laterales. ANATOMY OF THE LARYNX 483 GROUP. MUSCLE. ATTACHMENTS. ACTION. II. and III. Adductors and Sphincters. D. Middle layer. i. A r y t e n o i d e u s posticus. ii. Thyro- ary tenoi- dei ex - terni. n three lay- ers: Outer layer, Thy- r o - a r y - epiglot- tici. iii. Crico- arytenoi del late rales. c. Inner most layer Thyro-ar y tenoidei in terni. pair of muscles. Flat and narrow, which arise on either side from the processus muscularis of the arytenoid cartilage, then passing upward and in- ward cross one another in the middle line to be inserted into the upper half of the lateral border of the opposite arytenoid cartilage and the posterior border of the cartilage of Santorini. The lower fibers run forward and downward to be inserted into the thyroid cartilage near the commissure. The fibers attached to the cartilage of Santorini are continued forward and upward into the ary-epiglottic fold. single muscle. Half-quadrilateral, attached to the borders of the ary- tenoid cartilages, its fibers running horizontally between the two. A pair of muscles. Each of which con- sists of three chief portions. The lower and principal fibers arise from the lower half of the internal surface of the thyroid cartilage, close to the angle, and from the fibrous expansion of the crico-thyroid ligament, and are inserted into the lateral border of the arytenoid cartilage. The inner fibers to the lower half of this border, anc the outer fibers into the upper half some pass to the cartilage of Wrisberg and the ary-epiglottic fold. A pair of muscles. They arise on eithe: side from the middle third of the up per border of the cricoid cartilage anc are inserted into the whole anterio: margin of the base of the arytenok cartilage. Some of their fibers join the thyroid -ary-epiglottici. A pair of muscles. They arise on eithe side, internally from the angle of the thyroid cartilage, internal to the las described muscle, b. iii., and running parallel to and in the substance of the vocal cords are attached posteriorly to the processus vocalis and to the oute surface of the arytenoid cartilages. lelp to narrow or close the rima glottidis. Oraws together the arytenoid carti- lages and also de- presses them. When the mus- cle is paralyzed, the inter-carti- laginous part of the cords cannot come together. Approximate the vocal cords by drawing the processus muscu- laris of the ary- tenoid cartilages forward and downward and so rotate the pro- cessus vocalis in- ward. Render the vocal cords tense and rotate the aryte- noid cartilages and approximate the processus vo- calis. 484 MUSCLE-NERVE PHYSIOLOGY GROUP. MUSCLE. ATTACHMENTS. ACTION. IV. Tensors. Crico -thy- A pair of fan-shaped muscles attached The thyroid carti- roidei. on either side to the cricoid cartilage lage being fixed below; from the mesial line in front by its extrinsic for nearly one-half of its lateral cir- muscles, the cumference backward the fibers pass front of the cri- upward and outward to be attached to coid cartilage is the lower border of the thyroid carti- drawn upward, lage and to the front border of its lower and its back, cornea. with the aryte- noids attached, Thyro - ary- The most posterior part is almost a dis- is drawn down. tenoidei tinct muscle and its fibers are all but Hence the vocal interni. horizontal: sometimes this muscle is cords are elon- described as consisting of two layers, gated a n t e r o - superficial with cortical fibers, deep posteriorly and with oblique fibers, described under put upon the Group III. stretch. Paral- ysis of these muscles causes an inability to produce high notes. Nerve Supply. The sensory filaments of the superior laryngeal branch of the vagus supply the epithelial lining of the larynx, giving it that acute sensibility by which the glottis is guarded against the ingress of foreign bodies, or of irrespirable gases. The contact of these stimulates the nerve endings; and the sensory nerve impulse conveyed to the medulla oblongata, whether accompanied by sensation or not, arouses motor impulses through the filaments of the recurrent or inferior laryngeal branch, which excite contraction of the muscles that close the glottis. Both these branches of the vagi cooperate also in the pro- Lig. ary-epiglott. Cart. Wrisbergii Cart. Santorini mm. Aryten. obliqu. m. Crico-arytenoid. post. Cornu inferior Lig. cerato-cric. Pars. post. inf. membrani Pars, cartilag. FIG. 345. — The Larynx as Seen from Behind. To show the intrinsic muscles posteriorly. (Stoerk.) ANATOMY OF THE LARYNX 485 duction and regulation of the voice. The inferior laryngeal determines the degree of contraction of the muscles that vary the tension of the vocal cords, and the superior laryn- geal conveys to the brain the sensation which indicates the state of contraction of these muscles. Both the branches co-operate also in the actions of the larynx in the ordinary slight dilatation and contraction of the glottis in the acts of expiration and inspiration, more evidently in the acts of coughing and other forcible respiratory movements. The Laryngoscope. This is an instrument employed in investigating the condition of the pharynx, larynx, and trachea. It consists of a large concave mirror with perforated center and of a smaller mirror fixed in a long handle. In use the patient is placed in a chair, a good light (argand burner, or lamp) is arranged on one side of, and a little above his head. The operator fixes the concave mirror round his head in such a manner that FIG. 346.— The Parts of the Laryngoscope. he looks through the central aperture with one eye. He then seats himself opposite the patient, and so adjusts the position of the mirror, which is for this purpose provided with a ball and socket joint, that a beam of light is reflected on the lips of the patient. The patient is now directed to throw his head slightly backward, and to open his mouth ; the reflection from the mirror lights up the cavity of the mouth, and by a little alteration of the distance between the operator and the patient the point at which the greatest amount of light is reflected by the mirror — in other words its focal length — is readily discovered. The small mirror fixed in the handle is then warmed, either by holding it over the lamp, or by putting it into a vessel of warm water; this is necessary to prevent the condensation of breath upon its surface. The degree of heat is regulated by applying the back of the mirror to the hand or cheek, when it should feel warm without being painful. After these preliminaries the patient is directed to put out his tongue, which is held by the left hand of the operator gently but firmly against the lower teeth by means of a handkerchief. The warm mirror is passed to the back of the mouth, until it rests upon and slightly raises the base of the uvula, and at the same time the light is directed upon it: an inverted image of the larynx and trachea will be seen in the mirror. If the dorsum of the tongue be alone seen, the handle of the mirror must be slightly lowered until the larynx comes into view; care should be taken, however, not to move the mirror upon the 486 MUSCLE-NERVE PHYSIOLOGY uvula, as it excites retching. The observation should not be prolonged, but should rather be repeated at short intervals. The structures seen will vary somewhat according to the condition of the parts as to inspiration, expiration, phonation, etc. They are the following: first, and apparently at the posterior part, the base of the tongue, immediately below which is the accurate out- line of the epiglottis, with its cushion or tubercle, figure 348. Then are seen in the central line the true vocal cords, white and shining in their normal condition. In the inverted image the cords are closer together posteriorly. Between them is left an open slit, narrow while a high note is being sounded, wide during a deep inspiration. On each side of the true vocal cords, and on a higher level, are the false vocal cords. Still more externally than the false vocal cords is the aryteno-epiglottidean fold, in which are situated upon each side FIG. 347. — To Show the Position of the Operator and Patient when Using the Laryngoscope. three small elevations; of these the most external is the cartilage of Wrisberg, the interme- diate is the cartilage of Santorini, while in front and somewhat below the preceding is the summit of the arytenoid cartilage seen only during deep inspiration. The rings of the trachea, and even the bifurcation of the trachea itself, if the patient be directed to draw a deep breath, may be occasionally seen. Movements of the Vocal Cords. The position of the vocal cords in ordi- nary tranquil breathing is so adapted by the muscles that the opening of the glottis is wide and triangular, figure 348, B, becoming a little wider at each inspiration, and a little narrower at each expiration. On making a rapid and deep inspiration the opening of the glottis is widely dilated, figure 348, C, and somewhat lozenge-shaped. In Vocalization. At the moment of the emission of a note the opening is narrowed, the margins of the arytenoid cartilages being brought into contact and the edges of the vocal cords approximated and made parallel at the same time that their tension is much increased. The higher the note produced, the tenser do the cords become, figure 348, A; and the range of a voice depends, of course, in the main, on the extent to which the degree of tension of the vocal cords can be thus altered. In the production of a high note the vocal cords are brought well within sight, so as to be plainly visible with the help of the laryngoscope. In the utterance of low tones, on the other hand, the epiglottis MOVEMENTS OF THE VOCAL CORDS 487 is depressed and brought over the vocal cords, figure 349. The epiglottis, by being somewhat pressed down so as to cover the superior cavity of the lar- ynx, serves to render the notes deeper in tone and at the same time somewhat duller, just as covering the end of a short tube placed in front of caoutchouc tongues lowers the tone. In no other respect does the epiglottis appear to have any effect in modifying the vocal sounds. The degree of approximation of the vocal cords also usually corresponds with the height of the note produced; but probably not always, for the width FIG. 48. — Three Laryngoscopic Views of the Superior Aperture of the Larynx and Surrounding , in easy and quiet inhalation r IG. 348. — Three i^aryngoscopic Views ot tne superior Aperture or t) Parts. A, The glottis during the emission of a high note in singing; B, i of air; C, in the state of the widest possible dilatation, as in inhaling a very deep breath. The diagrams A', B' , and C , show in horizontal sections of the glottis the position of the vocal ligaments and arytenoid cartilages in the three several states represented in the other figures. In all the figures, so far as marked, the letters indicate the parts as follows, viz.: /, the base of the tongue; e, the upper free part of the epiglottis; , proportional to the refractive indices of the media. A line drawn through a on the principal vertical and b on the nodal vertical will cut the optical axis at the posterior principal focus, and vice versa. FIG. 453. — Diagram of a Simple Optical System. (Foster.) The curved surface, bd, is sup- posed to separate a less refractive medium toward the left from a more refractive medium toward the right. If a luminous point outside the anterior principal focus is considered, it is obvious that rays from it will be so refracted when they enter the convex surface that they will become converging and will ultimately meet again in a point or focus. Two such points form conjugate foci, figure 454. If the anterior focus of a conjugate is moved away from the anterior principal focus, then the posterior conjugate will move toward the posterior principal focus, and the converse. If one conjugate is known, the other can be found as FIG. 454.— Diagram to Show the Relations of Conjugate Foci, cd. Refracting surface; AB and ba, conjugate foci; o, nodal point; F", posterior principal focus. follows: From a point in the plane of the known conjugate, but outside the principal axis, draw two rays, one perpendicular to the refracting surface which will pass through the nodal point, the other parallel to the principal axis. The latter will be refracted through the posterior principal focus and when prolonged will meet the first ray in the plane of the second conjugate, figure 454, a. This relationship between conjugate foci is played upon in the focussing of a camera. IMAGE FORMATION 641 It is quite obvious that the eye, even considering only the three surfaces above indicated, is a much more complicated optical apparatus than the one described in the figure. It is, however, possible to reduce the refractive surfaces and media to a simpler form when the refractive indices of the dif- ferent media and the curvature of each surface are known. All of these data have been very carefully collected. They are as follows : Index of refraction of aqueous and vitreous, .... " " " " the lens, ....'.. Radius of curvature of cornea, " anterior surface of lens, " " " posterior " " ... Distance from anterior surface of cornea and anterior surface of lens Distance from posterior surface of cornea and posterior surface of lens I-336S I-4371 7.829 mm. 10. o 6.0 3-6 7-2 With these data it has been found comparatively easy by mathematical calculation to reduce the different refractive surfaces of the different curva- tures into one mean curved surface of known curvature, and the differently refracting media into one mean medium the refractive power of which is known. The simplified or so-called schematic eye, formed upon this principle, suggested by Listing as the reduced eye, has the following dimensions: From the anterior surface of the cornea to the principal point, . = 2.3448 mm From the nodal point to the posterior surface of lens, . . . = 0.4764 " Posterior chief focus lies behind cornea, . . . . . = 22.8237 *' Anterior chief focus in front of cornea, . . . . . = 12.8326 ' Radius of curvature of ideal surface, . . . . . . = 5.1248 ' In this reduced or simplified eye the principal posterior focus, about 23 mm. behind the spherical surface, would correspond to the position of the retina behind the anterior surface of the cornea. The refracting surface would be situated about midway between the posterior surface of the cornea and the anterior surface of the lens. The optical axis of the eye is a line drawn through the centers of curva- ture of the cornea and lens, and when prolonged backward it cuts the retina between the optic disc and the fovea centralis. This differs somewhat from the visual axis which passes through the nodal point of the reduced eye to the fovea centralis, and forms an angle of five degrees with the optical axis. The visual or optical angle is the angle included between the lines drawn from the borders of any object through the nodal point. It has been shown by Helmholtz that the smallest angular distance between two points which can be appreciated is fifty seconds, the size of the retinal image being 3.65 /*; this practically corresponds to the diameter of the cones at the fovea centralis which is 3 /*, the distance between the centers of two adjacent cones being 4 /*. The image of an object formed upon the retina may be considered as a series of points, from each of which a pencil of light diverges to the eye, and 41 642 THE SENSES this pencil has for its center or axis a ray which impinging upon the refrac- tive surface perpendicularly to the surface is not refracted, but passes through the nodal point and is prolonged backward to the retina, whereas the diverging rays are also made to converge to a principal posterior focus behind the lens, FIG. 455. — Diagram of the Method of the Formation of an Inverted Image Exactly Focussed upon the Retina. The dotted line is the ideal surface of curvature. or the chief axis of the pencil of light proceeding from the point in question, and this focus, if the image is to be clear, should fall on the retina. Thus from each point of an object a corresponding image is formed on the retina, so that an image of the distant object is produced. It is an inverted image. Whether the image is blurred or not depends upon the refractive power of the media, and upon the distance of the anterior surface of the cornea from the retina. If the refractive media are too powerful, or the eye too long, the image is formed in front of the retina, figure 456 ; if the reverse, the image FIG. 456. — Diagram of the Course of a Ray of Light, to Show how a Blurred or Indistinct Image is Formed if the Object be not Exactly Focussed upon Retina. The surface CC should be supposed to represent the ideal curvature. The nodal point should be nearer the posterior surface of lens as in figure 455. is formed behind the retina, and in both cases an indistinct and blurred image is the result. Accommodation. The distinctness of the image formed upon the retina is mainly dependent on the perfection with which the rays emitted by each luminous point of the object are brought to a focus upon the retina. ACCOMMODATION 643 If this focus occurs at a point either in front of or behind the retina, indis- tinctness of vision ensues, in the way we have just described, with the pro- duction of a halo. The focal distance, i.e., the distance of the point at which the luminous rays are collected from a lens, besides being regulated by the degree of convexity and density of the lens, varies with the distance of the object from the lens, being greater as this is shorter, and vice versa. In other words, the luminous points on the object and the focal points on the retina are conjugate foci. Hence, since objects placed at various distances from the eye can within certain limits be seen with almost equal distinctness, there must be some provision by which the eye is enabled to adapt itself, so that, at whatever distance the luminous object may be, the focal point may always fall exactly upon the retina. Accommodation is the act of adapting the eye to vision at different distances. It is obvious that the effect might be produced in either of two ways, viz., i, by altering the convexity, and thus the re- fracting powrer, either of the cornea or of the lens; or 2, by changing the position of the lens relative to the retina, as in the focussing of a camera, so that whether the object be near or distant, the focal points to which the rays are converged by the lens may always fall exactly on the retina. The amount of either of these changes which is required in even the widest range of vision is ex- tremely small, for from the refractive powers of the media of the eye the difference be- °{J^-ot tween the focal distances of the images *£?$?& of an object at a distance and of one at four inches is only about 3.5 mm. On this calculation the change in the distance of the retina from the lens re- quired for vision at all distances, supposing the cornea and lens to remain the same, would not be more than about one line. Beer has shown that the second method is indeed the type of accommodative apparatus in fishes. But in man and the higher animals accommodation occurs by the first method, i.e., by changing the convexity of the refracting surface. The accommodation of the human eye for objects at different distances is primarily due to a varying shape of the lens, its front surface becoming more or less convex, according as the distance of the object looked at is near or far. The nearer the object, the more convex the front surface of the lens, up to a certain limit, and vice versa ; the back surface takes little or no share in accommodation. The following simple experiment illustrates this point: If a lighted candle be held a little to one side of a person's eye, an observer looking at the eye from the other side sees three distinct images of the flame, 644 THE SENSES figure 457. The first and brightest is, i, a small erect image formed by the anterior convex surface of the cornea; the second, 2, is also erect, but larger and less distinct than the preceding, and is formed at the anterior convex surface of the lens; the third, 3, is smaller, inverted, and indistinct; it is formed at the posterior surface of the lens, which is concave forward, and FIG. 459. FIG. 458. — Diagram of Sanson's Images. A, When the eyes are focussed for far objects, and B, when they are focussed for near objects. The figure to the right in A and B is the inverted image from the posterior surface of the lens. FIG. 459. — Phakoscope of Helmholtz. At B, B', are two prisms, by which the light of a candle is concentrated on the eye of the person experimented with at C. A is the aperture for the eye of the observer. The observer notices three double images, as in figures 457 and 458, reflected from the eye under examination when the eye is fixed upon a distant object; the position of the images having been noticed, the observed eye is then focussed on a near object, such as a reed pushed up by C; the images from the anterior surface of the lens will be observed to move toward each other, in consequence of the lens becoming more convex. therefore, like all concave mirrors, gives an inverted image. If now the eye under observation be made to look at a near object, the second image be- comes smaller, clearer, and approaches the first. If the eye be now adjusted for a far point, the second image enlarges again, becomes less distinct, and recedes from the first. In both cases alike the first and third images remain unaltered in size, distinctness, and relative position. This proves that during accommodation for near objects the curvature of the cornea, and that of the posterior surface of the lens, remain unaltered, while the anterior surface of the lens becomes more convex and approaches the cornea. The experiment, figure 458, is more striking when the two prisms of the phakoscope which form two images of the candle are used. The pair of images of the candle from the front surface of the lens not only approach those from the cornea during accommodation, but also approach one another, and become somewhat smaller, Sanson's images. THE MECHANISM OF ACCOMMODATION 645 The Mechanism of Accommodation. The mechanism of accommo- dation depends primarily upon the inherent tendency of the lens to approxi- mate the shape of a sphere. When the eye is at rest the intra -ocular tension is such as to put stress on the suspensory ligament around its equator, which compresses the elastic lens in its antero-posterior dimension. The elasticity of the lens can make itself apparent when the tension of the suspensory liga- ment is relaxed. This takes place completely after a division of the fibers of the zonula. When we remove the lens from the eye of a young person, we see it assume the spherical shape immediately upon the division of its connections. In life this slackening of the tension of the suspensory liga- ment of the lens is brought about by the contraction of the fibers of the ciliary body. This allows the anterior surface of the lens to become more convex, by its own elastic powers, thus focussing entering rays of light from a near object upon the retina, figure 460. It therefore appears that when the eye is at rest it is focussed for distant objects, inasmuch as the suspensory liga- ment is taut and the anterior surface of the lens more flattened. The normal eye is passive when in focus for distant objects. It is the active contraction of the muscles of accommodation that focusses for near objects. The iris acts in coordination with the accommodative contractions of the ciliary mus- cles. In viewing near objects the pupil contracts, and upon viewing distant ones it dilates. Range of Distinct Vision. Near-point. In every eye there is a limit to the power of accommodation. If a book be brought nearer and nearer to the FIG. 460.— Diagram Representing by Dotted Lines the Alteration in the Shape of the Lens on Accommodation for Near Objects. (E. Landolt.) eye, the type at last becomes indistinct, and cannot be brought into focus by any effort of accommodation, however strong. This limit, which is termed the near-point, can be determined by the experiment of Scheiner. Two small holes not more than 2 mm. apart are pricked in a card with a pin; at any rate their distance from each other must not exceed the diameter of the pupil. The card is held close in front of the eye, and a small needle viewed 646 THE SENSES through the pin-holes. At a moderate distance it can be. clearly focussed, but when brought nearer, beyond a certain point, the image appears double and more or less blurred. This point where the needle ceases to appear single is the near-point of vision. Its distance from the eye can of course be readily FIG. 461. — Diagram of Experiment to Ascertain the Minimum Distance of Distinct Vision. measured. It is usually about five or six inches, 12 to 15 cm. In the accom- panying figure, 461, the lensfr represents the eye; «,/, the two pin-holes in the card, nn the retina ; a represents the position of the needle. When the needle is at a moderate distance, the two pencils of light coming from e and / are focussed at a single point on the retina nn. If the needle be brought nearer FIG. 462. — Diagram of the Axes of Rotation of the Eye. The thin lines indicate axes of rotation, the thick the position of muscular attachment. than the near-point, the strongest effort of accommodation is not sufficient to focus the two pencils, they meet at a point behind the retina. The effect is the same as if the retina were shifted forward to mm. Two images h, g, are formed, one from each hole. It is interesting to note that when in this way REFLEXES OF THE PUPIL 647 two images are produced, the lower one g really appears in the position Q, while the upper one appears in the position P. This may be readily verified by covering the holes in succession. During accommodation two other changes take place in the eyes. The eyes converge by the action of the extra-ocular muscles, chiefly by the internal and inferior recti or internal and superior recti. The pupils contract. Movements of the Eye. The eyeball possesses movement around three axes indicated in figure 462, viz., an antero-posterior, a vertical, and a transverse, passing through a center of rotation a little behind the centre of the optic axis. The movements are ac- complished by pairs of muscles. Direction of Movement. Inward, .... Outward, .... Upward, Downward, .... Inward and upward, Inward and downward, . Outward and upward, Outward and downward, By what muscles accomplished. Internal rectus. External rectus. ( Superior rectus. | Inferior oblique. j Inferior rectus. / Superior oblique. Internal and superior rectus. Inferior oblique. j Internal and inferior rectus. ( Superior oblique, j External and superior rectus. \ Inferior oblique, j External and inferior rectus. ( Superior oblique. The contraction of all of the muscles during the act of accommodation, viz., of the ciliary muscle, of the recti muscles, and of the sphincter pupillae, is under the control of the fibers of the third nerve. But the superior oblique may also be employed, in which case the fourth nerve is concerned. Reflexes of the Pupil. Contraction of the iris may occur under the following circumstances: i, On exposure of the eye to a bright light; 2, On the local application of eserine (active principle of Calabar bean); 3, On the administration internally of opium, aconite, and in the early stages of chloro- form and alcohol poisoning; 4, On division of the cervical sympathetic or of stimulation of the third nerve. Dilatation of the pupil occurs, i, in a dim light; 2, when the eye is focussed for distant objects; 3, on the local applica- tion of atropine and its allied alkaloids; 4, on the internal administration of atropine and its allies; 5, in the later stages of poisoning by chloroform, opium, and other drugs; 6, on paralysis of the third nerve; 7, on stimulation of the cervical sympathetic, or of its center in the floor of the front of the aqueduct of Sylvius. The contraction of the pupil is under the control of a center in the floor of the aqueduct beneath the anterior corpora quadri- gemina. This center is reflexly stimulated by a bright light, and the dilata- tion when the center is not in action is due to the stimulation of the radial fibers of the iris by sympathet* nerves. In addition, it appears that both 648 THE SENSES contraction and dilatation may be produced by a local action of certain drugs which is independent of and probably often antagonistic to the action of the central apparatus of the third and sympathetic nerves. The close coordination between the two eyes is nowhere better shown than by the condition of the pupil. If one eye be shaded by the hand its pupil will of course dilate; the pupil of the other eye will also dilate, though unshaded, due to crossed reflex action. Defects in the Optical Apparatus. Under this head we may con- sider the defects known as: i, Spherical Aberration; 2, Chromatic Aberra- tion; 3, Astigmatism; 4, Myopia; 5, Hypermetropia. The normal or emmetropic eye is so perfect that parallel rays are brought exactly to a focus on the retina without any effort of accommodation, figure 466. Hence all objects except near ones (in practice all objects at a distance of twenty feet or more) are seen without any effort of accommodation; in other words, the far-point of the normal eye at rest is at an infinite distance. In viewing near objects we are conscious of the effort (the contraction of the ciliary muscle) by which the anterior surface of the lens is rendered more convex, and rays which would otherwise be focussed behind the retina are converged upon the retina. Spherical Aberration. The rays of a cone of light from an object situated in the field of vision do not all meet in the same point, owing to the greater refraction of the rays which pass through the circumference of a lens than that of those traversing its central portion. This defect is known as spherical aberration. In the camera, telescope, microscope, and other optical instru- ments it is remedied by the interposition of a screen with a circular aperture in the path of the rays of light, cutting off all the marginal rays and allow- ing the passage only of those near the center. Such correction is effected in the eye by the iris, which forms a diaphragm to cover the circumference of the lens, and prevents the rays from passing through any part of the lens but its center, which corresponds to the pupil. The iris is pigmented to pre- vent the passage of rays of light through its substance. The image of an object will be most defined and distinct when the pupil is small, if the light is abundant; so that, while a sufficient number of rays are admitted, the narrowness of the pupil may prevent the production of indistinctness of the image by spherical aberration. But even the image formed by the rays passing through the circumference of the lens, when the pupil is much dilated, as in the dark, or in a feeble light, may, under certain circumstances, be well defined. Distinctness of vision is further secured by the pigment of the outer sur- face of the retina and of the posterior surface of the iris and the ciliary proc- esses, which absorbs any rays of light that may be reflected within the eye, and prevents their being thrown again upon the retina so as to interfere with the images formed there. The pigment of the retina is especially im- portant in this respect; for with the exception of its outer layer the retina is DEFECTS IN THE OPTICAL APPARATUS 649 very transparent; and if the surface behind it were not of a dark color, but capable of reflecting the light, the luminous rays which had already acted on the retina would be reflected again and would fall upon other parts of the same membrane, producing indistinctness of the images. Chromatic Aberration. In the passage of light through the periphery of an ordinary convex lens, decomposition of each ray into its elementary colored parts commonly ensues, and a colored margin appears around the image, owing to the unequal refraction which the elementary colors undergo. This is termed chromatic aberration. It is corrected by the use of lenses constructed of alternate layers of glass of different refractive indices so ground that they produce chromatic dispersion in opposite directions and thus mutually correct any chromatic aberration which may have resulted. The human eye has considerable chromatic aberration, as may readily be demonstrated, experi- ment 13, page 673. An ordinary ray of white light in passing through a prism has its con- stituent rays refracted in unequal degrees, and therefore appears as colored bands fading off into each other, known as the spectrum. The colors of the spectrum are arranged as follows: red, orange, yellow, green, blue, indigo, violet; of these the red ray is the least, and the violet the most, refracted. Hence, as Helmholtz has shown, the rays from a white point cannot be ac- curately focussed on the retina, for if we focus for the red rays, the violet are out of focus, and vice versa: such objects, if not exactly focussed, are often seen surrounded by a pale yellowish or bluish fringe. For similar reasons a red surface looks nearer than a blue one at an equal distance, because, the red rays being less refrangible, a stronger effort of accommodation is necessary to focus them, and the eye is adjusted as if for a nearer object, and therefore the red surface appears nearer, experiment 13. Astigmatism. This defect, which was first discovered by Airy, is due to a greater curvature of the refractive surfaces of the eye in certain meridians than in others. Thus vertical and horizontal lines crossing each other can- not both be focussed on one plane; one set stands out clearly, and the others are blurred and indistinct. This defect, which is generally present in a slight degree in all eyes, is usually seated in the cornea, but occasionally in the lens as well. The plane of greatest curvature in the cornea is usually in the vertical meridian, a fact which doubtless comes from the pressure of the eyelids during development. If one looks at figure 463, A or B, with one eye, the three lines in the radii of the figure will be seen with unequal distinctness. Certain sets will stand out sharp and black and others dim and with indistinct out- lines, and if the astigmatism is great enough the three lines may not be dis- tinguished. Figures C and D of this series enable one to detect minute traces of astigmatism with great accuracy. It is somewhat difficult to picture the rays from a luminous point in their 650 THE SENSES courses through eyes which have this defect, but an examination of figure 464 will show their refraction. In this figure four rays coming from the point L in the arrows are represented as striking on the refractive surface of the eye atA,B, C, D, and being converged toward a focus. The rays A, C, separated by vertical line on the refractive surface, are focussed at flt while the lines A, B, separated by the horizontal distance on the refractive surface, are ABC FIG. 463. — Astigmatic Charts. brought to a focus at /2. The point L, therefore, has two apparent focal points, one point composed of the rays that strike in a horizontal plane, /2, the other of rays that strike in a vertical plane, /r If the retina of the eye be placed at /! it will see an image of a point with indistinct horizontal rays. If placed at the position /2 it will see a luminous point with indistinct rays in the vertical plane* If the series of points in the arrow MN be considered, it is evident that at the position fl the rays which fall in the vertical plane will form distinct foci, while those that fall in the horizontal plane will form overlapping diffuse images in that plane. Since they are overlapping, they will not appear separate except at the ends of the image of the arrow, and the arrow will therefore be seen distinctly. If the position /2 is considered where the rays of the horizontal plane are focussed, then it is evident that FIG. 464. — The Unequal Refraction of Rays in an Astigmatic Eye. (John Green.) the points in the arrow MN will present a series cf rays or halos in the vertical plane, thus rendering its outline very dim or indistinct. The condi- tion with the arrow OP is exactly the reverse. Hence, in the astigmatic eye the images of the horizontal arrow MN will be distinct at the focus }ly while the image of the vertical arrow OP will be distinct in the focus /2, and the eye cannot see the two lines distinctly at the same time. This condition is DEFECTS IN THE OPTICAL APPARATUS 651 further illustrated in figure 465 which represents the position /t shown in figure 464. Myopia. This is that refractive condition of the eye in which parallel rays are brought to a focus in front of the retina, 4, figure 466. It is due either to an abnormal elongation of the eyeball, antero-posteriorly, or to an increase in the convexity of the refracting surfaces, or to both of these con- ditions. Parallel rays are focussed in front of the retina, and, crossing, form circles on the retina. Thus, the images of distant objects are blurred and indistinct. The eye is, as it were, permanently adjusted for a near point. Rays from a point near the eye are exactly focussed on the retina. But those which issue from any object beyond a slight distance, the myopic jar-point, which is less than twenty feet, cannot be distinctly focussed. This defect is corrected by concave glasses, which cause parallel rays entering the eye FIG. 465. — Diagram of Character of Retinal Images in Astigmatism. (John Green.) to diverge. Such glasses of course are needed only to give a clear vision of distant objects. For near objects they are not required. Hypermetropia. This is that refractive condition of the eye in which parallel rays are brought to a focus behind the retina, 3, figure 466. It is the opposite of myopia, and is due either to an abnormal shortening of the eye- ball, antero-posteriorly, or to a decrease in the convexity of the refracting surfaces, or both. Parallel rays entering the eye at rest are focussed behind the retina. An effort of accommodation is therefore required to focus parallel rays on the retina. When the rays are sharply divergent, as in viewing a very near object, the accommodation is insufficient to focus them. Thus, both ne2r and distant objects require an effort of accommodation, and the eye is under a constant strain which produces in the end various nervous, as well as ocular, disorders. This defect is obviated by the use of convex glasses, which render the pencils of light more convergent. Such glasses are espe- cially needed for near objects, as in reading, etc. They are also required for distant vision to rest the eye by relieving the ciliary muscle from constant work. Presbyopia. Presbyopia is a condition of diminished range of accom- modation. It takes place with considerable uniformity from youth to old age. 652 THE SENSES It is not a disease, but a physiological process which every eye undergoes as its owner grows older. It is due to a gradual diminution of elasticity of the lens by a sort of sclerosis from the center toward the periphery. It begins even in childhood, but advances so slowly that it is not until the age of twenty-five or so that a distinct, though small, nucleus is present. With advancing years the process goes on until finally the lens becomes inelastic FIG. 466. — Diagram Showing: i, Normal or emmetropic eye bringing parallel rays exactly to a focus on the retina; 2, normal eye at rest, showing that light from a near point is focussed behind the retina, but by increasing the curvature of the anterior surface of the lens (shown by dotted lines) the rays are focussed on the retina; 3, hypermetropic eye. In this case the axis of the eye is shorter, and the lens normal (or the lens may be flatter than normal and the eyeball normal); parallel rays are focussed behind the retina; 4, myopic eye. In this case the lens is too convex (or the axis of the eye is abnormally long) ; parallel rays are focussed in front of the retina. and is unable to assume a shape convex enough to focus rays from a near object upon the retina, as in reading. The defect is remedied by the use of convex lenses equivalent to the loss in accommodation. Visual Sensations, from Excitation of the Retina. Light is the normal agent in the excitation of the retina. The only portion of the retina capable of reacting to the stimulus is the rod and cone layer. The proofs of this statement may be summed up thus: i. The point of entrance of the optic VISUAL SENSATIONS, FROM EXCITATION OF THE RETINA 653 nerve into the retina, where the rods and cones are absent, is insensitive to light and is called the blind spot. The phenomenon itself is very readily demonstrated. If we close one eye, and direct the other upon a point at such a distance to the side of any object that the image of the latter must fall upon the retina at the point of entrance of the optic nerve, its image is lost. If, for example, we close the left eye, and direct the axis of the right eye steadily toward the circular spot in figure 467, while the page is held at a distance of about six inches from the eye, both dot and cross are visible. On gradually increasing the distance between the eye and the object, by removing the book farther and farther from the face, keeping the right eye steadily on the dot, it will be found that suddenly the cross disappears from view, while on removing the book still farther it suddenly comes into view again. The cause of this phenomenon is simply that the portion of retina which is occupied by the entrance of the optic nerve is quite blind; and there- fore that when it alone occupies the field of vision objects cease to be visible. • -I- FIG. 467. — Diagram for Demonstrating the Blind Spot- 2. In the fovea centralis and macula lutea, which contain rods and cones but no optic-nerve fibers, light produces the greatest effect. In the latter, cones occur in large numbers, and in the former cones without rods are found, whereas in the rest of the retina, which is not so sensitive to light, there are fewer cones than rods. We may conclude, therefore, that cones are even more important to vision than rods. 3. If a small lighted candle be moved to and fro at the side of and close to one eye in a dark room while the eyes look steadily forward into the darkness, a remarkable branching figure, Purkinje's figures, is seen floating before the eye, consisting of dark lines on a reddish ground. As the candle moves, the figure moves in the opposite direction, and from its whole appearance there can be no doubt that it is a reversed picture of the retinal vessels projected before the eye. The two large branching arteries passing up and down from the optic disc are clearly visible, together with their minutest branches. A little to one side of the disc, in a part free from vessels, is seen the yellow spot in the form of a slight de- pression. This remarkable appearance is due to shadows of the retinal vessels cast by the candle. The branches of these vessels are chiefly dis- tributed in the nerve fibers and ganglionic layers; and since the light of the candle falls on the retinal vessels from in front, the shadow is cast behind them, and hence those elements of the retina which perceive the shadows must also lie behind the vessels. Here, then, we have a clear proof that the light-perceiving elements of the retina are not the fibers of the optic nerve forming the innermost layer of the retina, but the external layers of the retina, the rods and cones. 654 THE SENSES When light falls on the rods and cones it produces changes which develop nerve impulses that are transmitted by the chain of neurones extending through the retina, the optic nerve and chiasma, the geniculate bodies, etc., to the cerebral cortex of the occipital lobe, which is the sensorium for visual sensations. We have already seen that the eye possesses a wonderful me- chanical perfection for receiving and focussing light on definite parts of the retina. A comparison of visual sensations shows that there are corresponding qualities in the sensation, as, for example, its intensity, duration, localiza- tion, complexity, etc. Duration of Visual Sensations. The duration of the sensation pro- duced by a luminous impression on the retina is always greater than that of the stimulus which produces it. However brief the luminous impression, the effect on the retina always lasts for about one-twentieth of a second. Thus, suppose an object in motion, say a horse, to be revealed on a dark night by a flash of lightning, the image remaining on the retina during the time of the flash. The object is really revealed for such an extremely short period (a flash of lightning being almost instantaneous) that no appreciable movement could have taken place in the period during which the stimulus was produced on the retina of the observer. The horse would appear stand- ing in the position of motion for about a twentieth of a second, though he would not be seen to make any motions. And the same fact is proved in a reverse way. The spokes of a rapidly revolving wheel are not seen as dis- tinct objects, because at every point of the field of vision over which the re- volving spokes pass, a given impression has not faded before another comes to replace it. Thus every part of the interior of the wheel appears filled. The duration of the ajter-sensation produced by an object is greater in a ratio proportionate to the duration of the impression which caused it. Hence, the image of a bright object, as of the light of a window, may be perceived in the retina for a brief period, the positive after-image. If, however, the primary stimulation is sharp and intense there will follow presently an appearance of the window in which all the contrasted lights are reversed, the negative after- image. Intensity of Visual Sensations. It is quite evident that the more luminous a body the more intense is the stimulus it produces. But the in- tensity of the sensation is not directly proportional to the intensity of the luminosity of the object. It is necessary for light to have a certain intensity before it can excite the retina, but it is impossible to fix an arbitrary limit to the power of excitability. As in other sensations, so also in visual sensa- tions, a stimulus may be too feeble to produce a sensation. If it be increased in amount sufficiently, it reaches a point that is intense enough to produce an effect; this is a minimal or threshold stimulus. The amount of increase in the stimulus that produces a perceptible change in the sensation is at first very slight, but later quite great. It dees not depend on the absolute INTENSITY OF VISUAL SENSATIONS 655 change of intensity of the stimulus, but is proportional to the intensity of the stimulus already acting, Weber's law. This law, which is true only within certain limits, may be best under- stood by an example. When the retina has been stimulated by the light of one candle, the light of two candles will produce a difference in sensation which can be easily and distinctly felt. If, however, the first stimulus is that of an electric arc -light, the addition of the light of a candle will make no dif- ference in the sensation. So, generally, for an additional stimulus to be felt, it may be proportionately small if the original stimulus is small, and must be greater if the original stimulus is great. The stimulus increases as the numbers expressing its strength, while the sensation increases as the logarithms. Every one is familiar with the fact that it is quite impossible to see the jundus or back of another person's eye by simply looking into it. The interior of the eye forms a perfectly black background to the pupil. The same FIG. 468. — Diagram to Illustrate the Action of the Ophthalmoscope when a Plane Concave Glass is Used, c, Observer's eye. The light reflected from any point, d, on retina of a, would naturally be focussed at e; if the lens b is used it would be focussed at i, in other words, at back of c. The image would be enlarged, as though of g, and would be inverted. (After McGregor Rob- ertson.) remark applies to an ordinary photographic camera, and may be illustrated by the difficulty we experience in seeing into a room from the street through the window, unless the room be lighted from within. In the case of the eye this fact is partly due to the feebleness of the light reflected from the retina, most of it being absorbed by the retinal pigment. But the difficulty is due more to the fact that every such ray is reflected back to the source of light and cannot be seen by the unaided eye without intercepting the in- cident light as well as the reflected rays from the retina. This difficulty is surmounted by the use of the ophthalmoscope. The ophthalmoscope, brought into use by Helmholtz, consists in its simplest form of a concave mirror with a hole in it. The one described is one of the less intricate of the modern instruments. It consists of, a, a slightly concave mirror of metal or silvered glass perforated in the center, and fixed into a handle; and 6, a biconvex lens of 6 to 8 cm. focal length. Two methods of examining the eye with this instrument are in common use — the direct and the indirect : both methods of investigation should be employed. A nor- mal eye should be examined. A drop of a solution of atropine (two grains to the ounce) or of homatropine hydrobromate should be dropped into the right eye only about twenty minutes before the examination is commenced; the ciliary muscle is thereby paralyzed, 656 THE SENSES the power of accommodation is abolished, and the pupil is dilated. This will materially facilitate the examination; but it is quite possible to observe all the details to be presently described without the use of this drug. The room being now darkened, the observer seats himself in front of the person whose eye he is about to examine, placing himself upon a FIG. 469. — Diagram to Illustrate Action of Ophthalmoscope when a Biconvex Glass is Used. The figure d on retina of a is under ordinary conditions focussed at / and inverted. If the lens b be placed between eyes, the image h is seen by the eye c as an enlarged image. (After Mc- Gregor Robertson.) somewhat higher level. A subdued but steady light is placed close to the left ear of the patient in the examination of the right eye. Guiding the mirror in his right hand, and looking through the central hole, the operator directs a beam of light into the eye of the patient. A red glare, called in practice the reflex, due to the illumination of the retina, is seen. The patient is then told to look at the little finger of the observer's right hand as he holds the mirror; to effect this the eye is rotated somewhat inward, and at the same time the reflex changes from red to a lighter color, owing to the reflection from the optic disc. The observer now approximates the mirror, and with it his eye to the eye of the patient, taking care to keep the light fixed upon the pupil, so as not to lose the reflex. At a certain dis- tance, which varies with the refractive power in different eyes, but is usually an interval of about two or three inches between the observed and the observing eye, the vessels of the retina will become visible as lines running in different directions. The smaller and brighter red arteries can be distinguished from the larger and darker colored veins. An examination of the fundus of the eye reveals the optic disc and the entrance of the blood-vessels, the macula lutea, and the fovea centralis. No blood-vessels are seen in the fovea. This constitutes the direct method of examination, figure 468; by it the various details of the fundus are seen as they really exist, and it is this method which should be adopted for ordinary use. If the observer is ametropic, i.e., is myopic or hyper- metropic, he will be unable to employ the direct method of examination until he has remedied his defective vision by the use of proper glasses. In the indirect method, figure 469, the patient is placed as before, and the operator holds the mirror in his right hand at a distance of 30 to 40 cm. from the patient's right eye. At the same time he rests his left little finger lightly upon the patient's right temple, and holding the lens between his thumb and forefinger, two or three inches in front of the patient's eye, directs the light through the lens into the eye. The red reflex, and subsequently the white one, having been gained, the operator slowly moves his mirror, and with it his eye, toward or away from the face of the patient, until the outline of one of the retinal vessels becomes visible, when very slight movements on the part of the operator will suffice to bring into FIG. 470. — The Ophthalmo- scope. The small upper mir- ror is for direct, the larger for indirect, illumination. THE FIELD OF VISION 657 view the details of the fundus above described, but the image will be much smaller and in- verted. The lens should be kept at a fixed distance of two or three inches, the mirror being alone moved until the disc becomes visible: should the image of the mirror obscure the disc, the lens may be slightly tilted. The Field of Vision. The field of vision of an eye is that part of the external world which can be seen by it when the eye is fixed. Under such circumstances objects near the axis of vision stimulate points in the retina near the fovea or on it, while objects at an angle of 60° to 90° from the axis 105 60* 180 10, S10 225 21*0 255 FIG. 471. — Perimeter Chart, Showing Extent of Field of Vision for White Light and to the .Colors Red, Green, Yellow, and Blue. (Krapart.) of vision stimulate regions of the opposite side o"f the retinal cup, i.e., the retinal field is inverted. The perimeter is an instrument for measuring the field of vision in terms of angular measure. When a field is charted by means of the perimeter it is revealed that objects can be seen further out in the field in some directions than in others. For example, objects in the temporal field can be seen at an angle of 90° to 100°, while on the nasal side they are seefi only 60° to 70°. If the head is turned to the right or the left while keeping the eye fixed, it is found that objects are seen at a greater angle. This shows that the limita- tions are due to the facial boundaries of the eye preventing the light from entering the eye and not from lack of sensitiveness of the retina. In fact the retina is sensitive to light out to the ora serrata. Localization in the Retina. Careful exploration of the retina with the perimeter gives a measure not only of the extent of the visual field but of 42 658 THE SENSES its acuteness and localization in different areas toward the periphery. Con- sidering the minimal distance apart which two luminous points must be to be distinguished as two, it is found that when the image falls on the fovea the two points may be very near together, as little as one minute or even less. Two stars can be seen only at a somewhat greater angular distance, two to three minutes. One minute angular measure covers an area on the retina of a trifle over 4 /*. The diameter of the cones is about 2 /*, so that the stimuli in the fovea fall on at least two separate cones. The inference seems reasonable that the retina in its most sensitive part can localize stimuli that fall on ad- jacent cones. The area of the fovea centralis is small, from 0.5 to 1.5 mm. Outside of its area the acuteness of vision quickly falls off. The fact is roughly estimated by fixing the vision on a letter in the printed line in the book before the reader and then determining the number of letters to either side that can be identified. The height of these letters is 1.5 mm. ; by measuring the distance of the page from the eye one can quickly calculate the area of distinct vision on the retina. Test types are printed on the basis of an angle of five minutes. In the outer limits of the retina the power of localizing stimuli is very slight; in fact, in the extreme borders of the field it is difficult to determine other than general form. Visual Purple. The method by which a ray of light is able to stimulate the endings of the optic nerve in the retina is not yet understood. It is supposed that the change effected by the agency of the light which falls upon the retina is in fact a chemical alteration in the protoplasm, and that this change initiates a nerve impulse that is transferred to the optic nerve endings. The discovery of a certain temporary reddish-purple pigmenta- tion of the outer limbs of the retinal rods in certain animals, e.g., frogs, which had been killed in the dark, forming the so-called rhodopsin or visual purple, appeared likely to offer some explanation of the matter, especially as it was also found that the pigmentation disappeared when the retina was exposed to light, and reappeared when the light was removed, and that it underwent distinct changes of color when other than white light was used. It was also found that if the operation were performed quickly enough and in the dark, the image of an object, optogram, might be fixed in the pigment on the retina by soaking the retina of an animal in alum solution. The visual purple cannot, however, be absolutely essential to the due pro- duction of visual sensations, as it is absent from the retinal cones, and from the macula lutea and fovea centralis of the human retina, and does not appear to exist at all in the retinae of some animals, e.g., bat, dove, and hen, which are, nevertheless, possessed of good vision. However, the fact remains that light falling upon the retina bleaches the visual purple, and this must be considered as one of its effects. It has been found that certain pigments, also sensitive to light, are contained in the inner VISUAL PURPLE 659 segments of the cones. These colored bodies are said to be oil globules of various colors — red, green, and yellow — called chromophanes, and are found only in the retinae of animals other than mammals. The rhodopsin at any rate appears to be derived in some way from the retinal pigment, since the color is not renewed after bleaching if the retina be detached from its pig- ment layer. The second change produced by the action of light upon the retina is the movement of the pigment cells. On the stimulation by light the granules of pigment in the cells which overlie the outer part of the rod and cone layer of the retina become diffused into the parts of the cells be- tween the rods and cones, the melanin granules, as they are called, passing FIG. 472. — Sections of Frog's Retina Showing the Action of Light upon the Pigment Cells and upon the Rods and Cones, (von Gendesen-Stort.) A, From a frog which had been kept in the dark for some hours before death; B, from a frog which had been exposed to light just before being killed. Three pigment cells are shown in each section. In A the pigment is collected toward the nucleated part of the cell, in B it extends nearly to the basis of the rods. In A the rods, outer segments, were colored red (the detached one green) ; in B they had become bleached. In A the cones, which in the frog are much smaller than the rods, are mostly elongated ; in B they are all con- tracted. down into tne processes of the pigment cells. A movement of the cones and possibly of the rods is also said to occur, as has been already incidentally mentioned. Under the influence of the stimulus of light the outer parts of the cones, which in an eye protected from light extend to the pigment layer, are retracted. It is even thought by some that the contraction is under the control of the nervous system. Finally, according to the careful researches of Dewar and McKendrick, and of Holmgren, it appears that the stimulus of light is able to produce an action current in the retina. McKendrick believes that this is the electrical expression of those chemical changes in the retina of which we have already spoken. Color Sensations. When a ray of sunlight enters the eye it pro- 660 THE SENSES duces a sensation of white light. But if the ray first passes through a prism, then it produces sensations corresponding to the colors of the spectrum. As is well known, white light is produced by vibrations of the luminiferous ether through a wide range of vibration rates. When a beam of white light is passed through a dispersing prism those vibration rates of low frequency are refracted less than those of higher frequency, giving rise to the spectrum. Vibrations of the luminiferous ether of rates just outside of the spectral rates exist, those which have a lower rate giving rise to heat rays, and those of higher rate to the so-called actinic or chemical rays, because they exert a powerful chemical action. Those spectral colors which stimu- late the retina to produce sensations of color presumably affect the retinal elements through chemical changes which they produce there. But this matter will be discussed under theories of color vision. The examination of color sensations reveals certain correspondences be- tween the physical color of the stimulus and the resulting color perception. If a pure spectral color be allowed to fall on the retina, a corresponding simple sensation is produced. If two colors fall on the same portion of the retina at the same time, a sensation is produced that is different from that which occurs when either color alone stimulates. The same fact holds true for three colors or more. In fact, three spectral colors can be selected which by proper combination can be used to produce sensations of all the colors of the spectrum. Such colors are called the fundamental colors, and while the choice is more or less arbitrary, red, green, and violet are the colors usu- ally considered. Extent of the Visual Field for Color. The retina is most sensitive to color in the region of the macula lutea. If by means of the perimeter one explores the retina to spectral red, for example, it is found that the color can be identified only at a distance of from 30° to 50° from the macula; the limits extending out somewhat farther on the nasal side of the retina, that is, the part corresponding to the temporal visual field. In the same way yel- low can be identified for from 40° to 70°, blue from 40° to 50°. The visual field for green is quite restricted, usually extending only from 20° to 30°. The extent of the color visual field varies greatly in different individuals. Complemental Colors, and After-images of Color. Certain colors, when allowed to stimulate the retina at the same time, tend to neutralize each other. That is, they produce sensations approaching white, usually some shade of gray, which will have a tinge of one or the other primary colors according to the proportion of stimulation. These pairs of colors are called complemental colors. Each spectral color has its complemental color, a fact that is represented in figure 473. The complemental colors of greatest physi- cal significance are red and green (greenish blue), yellow and deep blue (indigo blue), green (greenish yellow), and violet. Positive after-images of color exist for a brief moment, but the greatest COLOR-BLINDNESS 661 significance attaches to the negative after-images. The negative after-images of color following the stimulus of colored light upon the .retina are not the sensation of color produced by the color of an object, but are the opposite or complemental color. The after-image of red is, therefore, green, and that of green, red; that of violet, yellow and of yellow, violet, etc. The same relation holds with the other colors. A condition for the development of a strong after-image is that the primary image shall have continued to a certain degree of fatigue. The colors which reciprocally excite each other Green MMM FIG. 473. — Geometrical Color Table for Determining the Complemental Colors. in the retina are those placed at opposite points in the color table, figure 473. The after-images of color are most intense in the axis of the visual field and are not always present in the periphery of the retina, as can readily be seen by examining the chart, figure 471. Color sensations may also be produced by contrast. Thus, a very small dull gray strip of paper, lying upon an extensive surface of any bright color, does not appear gray, but has a faint tint of the color which is the comple- ment of that of the surrounding surface. A strip of gray paper upon a green field, for example, appears to have a tint of red, and when lying upon a red surface, a greenish tint; it has an orange-colored tint upon a bright blue surface, and a bluish tint upon an orange-colored surface; a yellowish color upon a bright violet, and a violet tint upon a bright yellow surface. The color excited thus must arise as an opposite or antagonistic condition of the retina, and the opposite conditions of which it thus becomes the subject, would seem to balance each other by their reciprocal reaction. A necessary condition for the production of the contrast colors is that the part of the retina in which the new color is to be excited shall be in a state of compara- tive repose; hence the small object itself must be gray. A second condition is that the color of the surrounding surface shall be very bright. Color-Blindness. Many persons are unable to distinguish one or more of the fundamental colors, and therefore have different perceptions THE SENSES of the color combination from that of the normal individual. It is said that from 4 to 5 per cent of men and about E per cent of women are defective in color vision. This defect is called color-blindness. In very rare cases complete color-blindness exists. Such individuals distinguish lights and shades only, that is, form. A more common defect, however, is the absence of one or more of the fundamental color sensations, the most common of all being the red-blind, or the red-green blind. The red- green blind individual cannot distinguish red and green colored yarns from each other or from shades of gray which reflect light with the same intensity. When they are given the color test by the Holmgren yarns, they indiscrim- inately mix the reds, greens, and grays. Cases have been described in which the individual was red-blind alone, or green-blind alone. A less common color defect is the inability to distinguish yellows and blues, yellow-blue blindness. Color-blindness may occasionally arise from disease or accident, but it is usually congenital. The individual often does not discover his defect until examined especially for his color vision. He may have learned to apply the terms green and red to surrounding objects, such as the grass, bricks, etc., but he distinguishes these objects by slight differences in intensity of lumi- nation, form, etc., and not by the sensations of color which the normal individual experiences. Theories of Color Vision. We have no way of determining the method by which the colors stimulate the retina other than our inferences from indirect evidence. It is probable that the energy of light vibration is transformed in the retinal structures into either physical or chemical change, perhaps the latter. Those interested in the phenomena of color vision gener- ally accept one of two theories, or their modifications, in explanation of the facts. The Young-Helmholtz Theory of Color Vision. This theory assumes that there are three fundamental sensory elements in the retina which cor- respond to and are stimulated primarily by the three primary colors — red, green, and violet. The theory in its present form further assumes that each color-perceiving element is slightly stimulated by others of the spectral rays, as shown in figure 474. When red rays fall upon the retina, they stimulate the red-perceiving elements strongly and the green and violet very feebly. The resulting sensation is that of red. So also is it with green and violet rays. When the retina is stimulated by both red and green rays, the two correspond- ing color-perceiving elements are strongly stimulated. The resulting color perception, however, is a combination of the two sensations and corresponds to some region of the spectrum between the red and green, according to the relative intensity of the two stimuli. When all three color-perceiving ele- ments are stimulated at the same time, this theory assumes that white light will be perceived. In a similar manner all the various color sensations are arrived at. THEORIES OF COLOR VISION 663 Bering's Theory of Color Vision. This theory is based on the assump- tion that there are chemical substances in the retina, photogenic substances, which are stimulated by the colors of the spectrum. It assumes three photo- genic substances which are called the red-green, the yellow-blue, and the FIG. 474. — Diagram to Illustrate the Stimulating Effects of the Three Primary Colors. (Young- Helmholtz theory.) i is the red; 2, green, and 3, violet, primary color sensations. The lettering indicates the colors of the spectrum. The diagram indicates by the height of the curve to what extent the several primary sensations ef color are excited by vibrations of different wave lengths. (Helmholtz.) white-black substances. By the theory, when the red-green substance is stimulated by red or green light, respectively, the former produces destruc- tive or catabolic changes, the latter constructive or anabolic changes, in the substance. When red light falls upon the retina, it produces catabolism in the red-green substance, which in turn develops a nerve impulse that arouses FIG. 475.— Diagram to Illustrate the Reactions of the Three Photogenic Substances, according to Hering's Theory. (Foster.) the sensation of red. When green light, on the other hand, stimulates the retina, it produces anabolism of the red-green substance and the sensation of green. The same rule holds with the other two substances. It will be noticed that this theory is based on the complemental colors. THE SENSES ^hen we apply the theories mentioned above to the phenomena of color- contrast and color-blindness, we find that each is defective in some point. By the Young-Helmholtz theory it is difficult to understand the perception of the sensation black, for by the theory black could be perceived only as the absence of all colors, and it is generally granted that there is a distinct black sensation other than and different from mere darkness. This theory explains those cases of blindness to one color, as red-blindness, for example. The Hering theory, on the other hand, gives us a rational explanation for positive black sensation, and is particularly applicable to the observed facts of color-contrast and negative color after-images. Color after-images, as for instance the after-images of green following stimulation by red light, are readily explained by Bering's theory, since the strong catabolism in the red-green substance will be followed immediately by anabolism to bring this substance up to its normal in the eye, thus pro- ducing the after-image. This phenomenon can be explained by the Young- Helmholtz theory only by assuming that following the stimulation by red light and the consequent fatigue of red-perceiving elements there is sufficient light entering the eye to stimulate the relatively sensitive green and violet perceiving elements, thus producing an after-image. Strong after-images are perceived in the dark room, so that the Hering theory is most applicable in the explanation of these cases. Binocular Vision. When one looks at an object with a single eye, the eye is so adjusted that the axis of vision is directed toward the object investigated. This is called ocular fixation. The ocular fixation is accom- plished by the coordinated contractions of the six pairs of ocular muscles. Its purpose is to bring the image of the object examined in the external visual field as nearly as possible upon the macula lutea. In binocular vision both eyes are fixed on the same pofnt in the visual field. A projection of the visual axis of each eye will pierce the point of fixation in the external object. It is evident that objects to either side of the point of fixation will give off rays which will enter the eyes, stimulating fields in the retina on the opposite side of the visual axis. An examination of figure 476 will show that each point in the visual field, A, B, C, D, stimulates corresponding points, a, b, c, d, a', b', c', d', in the retinas of the two eyes, a, b, c, d, and a', V, c', d', are corre- sponding points in the two retinas. When a and a' are stimulated at one and the same time, the resulting sensation is attributed to one object in the visual field, A, and these are corresponding points. This can be shown by pressing one eye out of its normal fixation so that the axes of the two eyes are not directed toward the same point. If one eye is pressed lightly by the thumb while examining a given object, as soon as, the pressure is applied two objects will appear. This phenomenon is known as diplopia. Diplopia is due to the fact that the images of visual objects do not fall on correspond- ing points in the two retinae. BINOCULAR VISION 665 The parts of the retinae in the two eyes which thus correspond to each other in the property of referring the images which affect them simulta- neously to the same spot in the field of vision, are, in man, just those parts which would correspond to each other if one retina were placed exactly in front of and over the other, as in figure 477. Thus, as we have noticed in speaking of the distribution of the optic nerve fibers, the temporal portion of one eye corresponds to or is identical with the nasal portion of the other eye. The upper part of one retina is also identical with the upper part of FIG. 476. — Diagram Showing the Symmetrical Correspondence of the Retinal Fields. N, Nodal point; F, fovea cen trails. The observer is supposed to be looking down upon the optical apparatus from above. Note that the line CD, which is on the lower side of the object, is the upper side of the image; and that the line BD, which is the right side of the object, is the left side of the image, which brings it at the inner segment of the right retina and the outer segment of the left retina. the other; and the lower parts of the two eyes are identical with each other. The distribution of the optic nerve fibers corresponds with the distribution of the identical points. The identical points on the upper and lower parts of the retinae may also be shown by the following simple experiment. Pressure upon any part of the ball of the eye, so as to affect the retina, produces a luminous circle, seen at the opposite side of the field of vision to that on which the pressure is made. If, now, in a dark room, we press with the finger at the upper part of one eye, and at the lower part of the other, two luminous circles are seen, one above the other; so, also, two figures are 666 THE SENSES seen when pressure is made simultaneously on the outer or the inner sides of both eyes. But if pressure be made with the fingers upon both eyes simultaneously at their lower part, one luminous ring is seen at the middle of the upper part of the field of vision. If the pressure be applied to the upper part of both eyes, a single luminous circle is seen in the middle of the field of vision below. So, also, if we press upon the outer side of one eye and upon the inner side of the other eye, a single luminous spot is produced, and is appar- A jb FIG. 478. FIG. 477. — Diagram to Show the Corresponding Parts of the Retinae. FIG. 478. — Diagram to Show the Simultaneous Action of the Eyes in Viewing Objects in Dif- ferent Directions. ent at the extreme right of the field of vision. The hemispheres of the two retinae may, therefore, be regarded as lying one over the other, as in C, figure 477; so that the left portion of one eye lies over the identical left portion of the other eye, the right portion of one eye over the identical right portion of the other eye; and with the upper and lower portions of the two eyes, a lies over a', b over b', and c over c'. The points of the one retina intermediate between a and c are again identical with the corresponding points of the other retina between a' and c'; those between b and c of the one retina, with those between V and c' of the other. If the axes of the eyes, A and B, figure 478, be so directed that they meet at a, an object at a will be seen singly, for the point a of the one retina and a' of the other are identical. So, also, if the object ft be so situated that its image falls in both eyes at the same distance from the central point of the retina— namely, at b in the one eye and at b' in the other— ft will be seen single, for it affects identical parts of the two retinae. The same will apply to the object y. The reason why the impressions on the identical points of the two retinae give rise to but one sensation, and the perception of but a single image, must either lie in the structural organization of the deeper or cerebral por- tions of the visual apparatus, or it must be the result of a mental operation; VISUAL JUDGMENTS 667 for in no other case is it the property of corresponding nerves of the two sides of the body to refer their sensations to one spot. Many attempts have been made to explain this remarkable relation be- tween the eyes, by referring it to anatomical relation between the optic nerves. The circumstance of the inner portion of the fibers of the two optic nerves decussating at the commissure, and passing to the eye of the opposite side, while the outer portion of the fibers continue their course to the eye of the same side, so that the left side of both retinae is formed from one root of the nerves, and the right side from the other root, naturally led to an attempt to explain the phenomenon by this distribution of the fibers of the nerves. And this explanation is favored by cases in which the entire half of one side of the retina sometimes becomes insensible. Visual Judgments. Form and Solidity. The estimation of the form of bodies by sight is the result partly of the visual sensation and partly of the association of ideas. The form of the image perceived by the retina depends wholly on the outline of the part of the retina affected; the sensa- tion alone is adequate only to the distinction of superficial forms from each other which lie in one plane, as of a square from a circle. But the idea of a solid body, as a sphere, or a body of three or more surfaces, e.g., a cube, can be attained only by the action of the mind in constructing it from the dif- ferent superficial images seen in different positions of the eye with regard to the object, and (as shown by Wheatstone and illustrated in the stereoscope), from two different perspective projections of the body being presented simul- taneously to the mind by the two eyes. Hence, when, in adult age, sight is suddenly restored to persons blind from infancy, all objects in the field of vision appear at first as if painted flat on one surface; and no idea of solidity is formed until after long exercise of the sense of vision combined with that of touch. The clearness with which an object is perceived, irrespective of accommodation, would appear to depend largely on the definiteness of stimu- lation of the rods and cones which its retinal image covers. Hence, the nearer an object is to the eye, within the limits of vision, the more clearly are all its details seen. Moreover, if we want carefully to examine any object, we always direct the eyes straight toward it, so that its image shall fall on the yellow spot, which has already been shown to be the area of most acute vision. In binocular vision the images of an object, while they fall in approxi- mately corresponding points on the two retinae, are never absolutely the same. When an object is placed so near the eyes that to view it the optic axes must converge, a different perspective projection of it is seen by each eye, these perspectives being more dissimilar as the convergence of the optic axes becomes greater. Thus, if any figure of three dimensions, an outline cube, for example, be held at a moderate distance before the eyes, and viewed with each eye successively while the head is kept perfectly steady, A, figure 479> will be the picture presented to the right eye, and B that seen by the left eye. 668 THE SENSES Wheatstone has shown that on this circumstance depends in a great measure our conviction of the solidity of an object, or of its projection in relief. If different perspective drawings of a solid body, one representing the image seen by the right eye, the other that seen by the left, for example, the drawing of a cube, A, B, figure 479, be presented to corresponding parts of the two retinae, as may readily be done by means of the stereoscope, the mind will perceive not merely a single representation of the object, but a body pro- jecting in relief, the exact counterpart of that from which the drawings were made. Size and Distance. The estimation of the size of an object and its distance away from the observer is based in part upon the visual image and in part upon judgments due to past experience. The two elements are inseparable and mutually dependent. Thus, a lofty mountain many miles away may subtend the same visual angle as a small hill near at hand. While the size \ FIG. 479. — Diagrams to Illustrate how a Judgment of a Figure of Three Dimensions is Obtained. and shape of the two images may be identical, yet the image of the hill near at hand is more distinct, its details are perceived, and its outlines are sharper than in the image of the mountain. If the atmosphere be charged with moisture or with dust, the image of the mountain will be still more indistinct and dim. From previous experiences we have learned that the dimness and indistinctness of the one and the definiteness of the other are associated with distance. If two objects are very near at hand then there will be a difference in the convergence of the two eyes in binocular vision. It is now well known that the ocular muscles are possessed of a very delicate muscle sense. This muscle sense leaves the impression which enables us to judge that the one object is nearer and the other farther. In the common and familiar objects about us we have from long experience and intimate contact learned their actual size and the character of the retinal image formed at definite, but known distances. When such an object forms an image of the common size and usual distinctness on the retina, the judgment as to its distance is quickly made. In the case of unknown objects which are associated with known ob- jects, the judgment of the size and distance, of the latter is used in forming LABORATORY EXPERIMENTS ON THE SENSE ORGANS 669 a judgment of the size and distance of the former by comparison. Many visual deceptions are based on these comparisons, a fact that is often taken advantage of by photographers. It is also well known that people living in a moist, hazy climate are utterly unable accurately to estimate distances when suddenly transferred to a clear mountain climate. LABORATORY DIRECTIONS FOR EXPERIMENTS ON THE SENSE ORGANS. i. Touch. Use the small compasses with rounded tips provided for the purpose, and determine the power of localization of the sense of touch as follows: Have the person observed close his eyes, then touch different parts of the skin, of the hand, arm, face, neck, etc., and let the observed one announce the exact point touched. The localization can also be determined by touching two points 6n the skin with the points of the compasses separated by varying distances. Ex- amine especially the skin on the forearm, on the back of the hand, on the palm of the hand, the tips of the fingers, and at different points on the face, including the lips and tip of the tongue. Touch these regions of the skin FIG. 480. — Aristotle's Experiment. with either one or with two points of the compasses, and allow the person observed to announce results, drawing your conclusions according to the principle of trial and error. Make a table showing the power of local dis- crimination in the different regions. 2. Aristotle's Touch Experiment. Roll the tips of the middle and index fingers over a marble and note that the sensation from the two fingers is interpreted as that of a single object. Now cross the fingers and repeat the experiment. This time there is the sensation of touching two spheres. 3. Temperature Sensations. It is a common experience that the hand brought in the neighborhood of a warm or a cold object develops the 670 THE SENSES sensation of warmth or cold. Examine a given small area of the back of the hand with the thermoesthesiometer. Certain points will give stronger sensation of heat than others. Map these out carefully. Examine the same area for the cold. A large number of cold spots will be found and they will not coincide with the warm spots, figure 421. The stimulation for the hot and cold spots does not depend upon the absolute temperature, but on the relative temperature. Insert the hand in fp. FIG. 481. — Localization of Taste. Bitter ; acid ....; salt, ; sweet ; T, tonsils; FC, foramen cecum; CF, circumvallate papillae; FP, fungiform papillae. (Hall.) water that feels lukewarm. Place the same hand in a cup of quite warm water for a moment, then reinsert it in the lukewarm water. This will now feel cold. 4. Sensations of Taste. The distribution of taste organs in the tongue is shown in figure 481. Examine your own tongue for organs of sweet, acid, saline, and bitter, using solutions of i to 2 per cent salt, 10 per cent sugar, 2 to 5 per cent acid, 5 per cent acetic acid, and o.i per cent quinine. Wipe the tongue dry and apply the solution named from the tip of a glass rod. The best form of rod is about 15 cm. long by 0.5 cm. in diameter, and has one end drawn out to a slender pencil-shaped tip and of a size which will suspend a very small drop. Too large a drop diffuses over too great an area of the tongue. Occasionally small crystals of sugar, salt, etc., give more satisfactory results. Perform the experiments on yourself before a mirror and map the re- sults as shown in figure 481. If the experiments are done with care certain papillae will be found which give one or two of the taste sensations, but not all. 5. Sensations of Smell. Quantitative experiments on the sense THE LIMITS OF THE SENSE OF HEARING 671 of smell are difficult to determine. Inhale vapor of ammonia so dilute that it can just be detected. Note that the sensation is strongest at the moment of drawing the vapor into the nostril. Fill the nostrils with the diluted vapor and close the external opening; the sensation quickly disappears. Keeping the nostrils closed, walk into the open air, then inhale fresh air. At the moment of the inhalation of fresh air the ammonia is again per-eptible. Repeat with bergamot, rose water, etc. 6. The Limits of the Sense of Hearing. Use a set of tuning forks for the purpose, and determine the lowest vibration per second which can be perceived as sound. Determine the highest limits in the same way. 7. Acuteness of the Sense of Hearing. Listen to the vibrations, of a tuning fork, or, better, to the ticking of a watch which is moved back and forth from the ear. Measure the distance at which it can just be distinguished. This experiment should be performed with the person blindfolded, and ex- traneous noise should, of course, be suppressed. 8. Refraction. Light passes out from a luminous point in straight lines so long as the line of propagation is in a medium of uniform density. If the rays pass form a transparent medium of one density into a second medium of different density, they will usually be turned out of their course, or refracted. If the rays enter the second medium at right angles to its surface, they will continue in straight lines, but if they enter at any other angle they will be refracted. If the second medium is denser than the first, the rays will be refracted toward the perpendicular; if it is less dense, away from the per- pendicular. Use a Hall's refraction-measuring apparatus (constructed of a carpenter's try square). Adjust it in a water-pan, and fill to the exact level with clear water. Clamp a rule to the vertical limb of the apparatus at an angle with the axial point of the instrument. Read the horizontal scale of the instrument along the edge of the clamped rule. Remove the instrument from the pan, using care not to disturb the adjustment of the ruler, and construct the angle of refrac- tion on coordinate paper. Determine the relation of the angle of incidence and of refraction, and compute the refractive index of the water, the air having a refractive index of one. Repeat the determination using a block of glass. 9. To Determine the Refractive Power of a Convex Lens. Use a meter stick which is provided with a movable diaphragm or screen, and a holder for a lens. Measure the focal distance of lens number i as furnished from the optical set. Put the lens in its holder and focus the image of the sun or. of an electric bulb on the screen, moving the screen back and forth until the sharp focus is determined. If the lens is accurately ground, the focus will be at a distance of one meter, which is the refractive power of a one-diopter lens, by definition. In the same way determine the refractive power of Jenses numbers 2, 3, and 4. THE SENSES Construct the path of the light in the formation of the image in these cases. If the measurement in the above case is made through two parallel open- ings or diaphragms about 5 mm. in diameter each, and separated by 4 or 5 mm., the point of focus can be more accurately determined (see Schemer's experiment, No. 14.) Construct the mathematical figure showing the course of both cones of rays in this test. 10. Determination of Near and Far Limits of Vision. Support a meter stick in a horizontal position at a comfortable level for the eye. Mount a needle in a cork and set it on the meter stick about 25 cm. in front of the eye. Make two pin-holes in a card at a distance of about 2 mm. from each other. Hold this card with the pin-holes close in front of one eye, and bring the eye up to the end of the meter stick; cover the other eye. Observe that when the needle is brought nearer and nearer to the eye, at a certain distance it becomes double. Determine this distance very accurately. It is the near- point of accommodation for the right eve. Make the same determination for the left eye. Hold the punctured card in front of the right eye, and move the needle (it is better to use something larger) farther and farther away until it becomes FIG. 482. — Diagram of Experiment to Ascertain the Minimum Distance of Distinct Vision. again double, if it does so. This is the far-point of accommodation. In normal eyes there is no far limit. In practice an eye that has no far limit under twenty feet is considered normal. This test should be made on each eye. 11. Inverted Image on the Retina. Dissect off a segment of the sclerotic of a fresh ox eye, or use a fresh eye from an albino rabbit. Make a tube of black paper of the size of the eye, and insert the eye in one end, with the cornea directed into the tube. In the dark room examine the image of the candle flame as formed on the retina of the eye in the tube. In a favorable experiment, a clear inverted image of the candle can be seen on the retina through the semi-transparent membranes of the eye. The same experiment can be demonstrated with the camera, or with a small lens, using a ground-glass plate to make the image more apparent. 12. Spherical Aberration. In physical optics it is found that it is difficult to grind lenses so that they will refract equally in the center or CHROMATIC ABERRATION 673 optical axis and in the periphery. Unequal refraction of these two regions is called spherical aberration. It is corrected in optics by diaphragms which shut out the light, either from the borders of the lens or from its center. The former method is used in the eye. To demonstrate Spherical Aberration, look at an object two meters from the eye, such as part of the window. Pass a card across the eye until the light enters only at the margin of the pupil, i.e., the borders of the lens. It will be found that the object is no longer in focus and the outlines are dim and diffused. Normal eyes are near-sighted for the rays that are refracted by the borders of the lens. 13. Chromatic Aberration. Look toward the borders between the sash and the bright light of an open window, at a distance of twenty feet or more. Use the right eye only. Bring a card across the pupil approaching from the side of the light until the eye is almost covered with the card. The window sash will seem to have a blue-violet fringe. If the card is brought across from the opposite side, the sash will have a reddish-yellow fringe. Make a cross of two strips of Bradley's pure color paper, one red and the other blue, on a black surface. When held at the proper distance the red appears nearer than the blue. This phenomenon is brought out more strongly by covering the colored papers with very thin white tissue paper. The judgment of distance is based on the effort of accommodation which is greater for the red than for the blue and violet rays. 14. Schemer's Experiment. Use two needles on corks, the method described in experiment i, placing one at a distance of 20 cm., and the other about 60 cm. from the eye. Use only the right eye, look through two pin- holes in a card at the far needle. The near needle will appear double, but the images will be somewhat blurred. While looking at the far needle, bring a cardboard across the right hole, note that the left image of the near needle disappears, and vice versa. If one accommodates for the near needle, the far needle appears double, and upon covering the right hole with the card the right image of the far needle disappears. This is known as Scheiner's Ex- periment. Construct a diagram to explain these phenomena. 15. Purkinje-Sanson's Images. Examine the eye of another person in a dark room as follows : With the observing eye focus for a far object, let the observer hold a candle slightly to one side of the axis of vision and about one foot from the eye. If the observer looks into the other eye from the side opposite the candle, he will be able to see three reflected images, figures 457 and 458. One, from the anterior surface of the cornea, is bright and dis- tinct, and of medium size and erect. In the middle of the pupil there will be a second image, larger and quite dim. This is a reflection from the front of the lens. The third image, reflected from the posterior surface of the lens, will seem to be farther back in the eye, quite small and inverted. These images can all three be seen at once with careful adjustment of the relative 43 674 THE SENSES positions of the candle and the observer, with reference to the axis of vision of the eye observed. If the observer protects his own eye from the direct light of the candle by a blackened cardboard between his eye and the candle, and asks the observed person to accommodate now for near objects, now for far, keeping the axis of vision constant, he will be able to note that the middle image, i,e., the one from the anterior surface of the lens, changes in size and in relative position with reference to the other two, which are essentially constant. With near accommodation this image becomes smaller and seems to move toward the image from the cornea; with far accommodation it becomes larger and appears to move to the image reflected from the posterior surface of the lens. This shows that the act of accommodation consists in a change in the con- vexity of the front of the lens. 1 6. The Phakoscope of Helmholtz. This classical instrument was invented by Helmholtz to demonstrate the act of accommodation, as out- FIG. 483. — Disc of Concentric Lines for the Astigmatic Test. lined in the second paragraph of the preceding experiment. Repeat the preceding experiment, using this instrument in a dark room. 17. Astigmatism. Astigmatism is a term used to describe the con- dition of unequal curvature of the refracting surfaces of the eye in the different meridia. The cornea is the surface which usually shows the greatest astigmatism. This defect is demonstrated by numerous forms of astigmatic charts, the most serviceable of which are the barred-letter test type, the clock dial, or the dials shown in figure 463 or 483. Hang an astigmatic dial at a distance of six meters and test the right and left eyes separately, as follows: When the vision is focussed on the center of the dial, if the eye is normal, the three bars in each radius of the clock dial will be seen with equal distinct- ness and have sharp black lines. In an astigmatic eye one or more of these radii will appear sharp and distinct, while the other will appear dim and THE BLIND SPOT 675 indistinct, the relative difference depending upon the degree of astigmatism. Note the meridian of astigmatism in the right and left eyes separately. Use the test set, and find the cylinder necessary to correct the astigmatism in each eye and determine its meridian. Astigmatism is commonly shown by the presence of radii when one looks at the stars at night, or by the ragged outline of a pin-hole in a card, when held at arm's length against a white sky. In extreme cases outlines like FIG. 484. — Diagram for Demonstrating the Blind Spot. the bars in the window sash or checks in clothing may be distorted, or some of the lines may not even be seen. 1 8. The Blind Spot. Look with the right eye at the spot in the ac- companying figure at a distance of about 20 to 25 cm., covering the left eye. Hold the spot in the line of direct vision and move the book to and from the eye; in some cases it is necessary to rotate the book slightly. It will be found that the cross to the right will, at a certain position, completely disappear. This happens when its image falls on the retina directly over the entrance of the optic nerve, which has no visual cells, and is, therefore, the blind spot. FIG. 485. — The Blind Spot with the Eye 30 cm. from the Paper. This area is large enough to cause a man completely to disappear at a dis- tance of about one hundred meters. Place a sheet of white paper at a distance of 30 cm. in front of the eye, holding the head in a fixed position by some support; look with the right eye at the top of the cross made on the left of the sheet of paper. Covering the sharpened portion of a lead pencil with white paper, leaving the black tip exposed, move this pencil across the paper from the visual center to the right. At a certain distance the black lead will suddenly disappear. 676 THE SENSES Mark this point. Continue to move the pencil until the lead reappears. Mark this point. These two points represent the limits of the blind spot in the horizontal plane, as magnified by the conditions of the experiment. Mark the limits in the other meridians in the same manner. Compute from the figures obtained the exact size of the blind spot in your right eye, figure 485. Repeat on the left eye. Usually these areas are not symmetrical. The com- putation may be based on the following proportion: a, the diameter of the mapped blind spot is to the distance of the map from the nodal point of the eye, x, as c, the distance from the nodal point to the retina, which is 1.5 cm., is to x, the diameter of the actual blind spot in the retina, x varies from 1.5 to 3 or more mm. a : b : : c : x. 19. Relations of the Size of the Retinal Image to Distance. Com- pute the size of the retinal images of familiar objects by the equation given in the last experiment. Compute the size of the image formed on the,, retina by a man six feet tall at a distance of 100 feet. Compute the size of the image formed by a tower 125 feet tall at a distance of 575 feet. 20. Purkinje's Shadows. Stand in front of a blackened wall in the dark room. While looking toward the wall with the right eye accom- modated for distant objects, move a lighted candle back and forth about 10 to 20 cm. to the right of the eye and a little below its level. Presently many branching shadows will be seen as though they stood in space in front of the individual. These are the shadows of the blood-vessels cast upon the retina. A careful examination will show that these shadows seem to con- verge to a point to the right of the center of vision of the right eye. By moving the candle up and down or from side to side, the shadows seem also to move slightly. Many persons can readily see Purkinje's figures by looking through the narrow spaces between the fingers of the hand moved close in front of the eye, when the vision is directed toward a bright sky. One can demonstrate by this means that the macula is free from blood-vessels, since the pattern of the blood-vessels around the borders of the macula is very readily de- termined. This is especially true if there is slight retinal congestion. 21. Duration of the Retinal Image. When a beam of light falls upon the retina for an instant it produces a stimulus which endures for a time after the stimulus is removed. This interval can be measured by the proper mechanical device. Place on the color wheel a disc, which has a small seg- ment cut out at one point on the periphery. Put a printed page behind the segment with the observer standing in front. Rotate the segment faster and faster until the printed page is seen continuously. At this point the visual image made at one revolution of the disc lasts until the next impression on the same spot. The speed of the revolution of the color wheel can be measured by attaching an electric contact key and signal magnet to the disc wheel and measuring the rate of interruptions against the known vibrations of a tuning fork. The same phenomenon may be determined by placing on the disc LIMITS OF THE FIELD OF VISION 677 two complemental colors and judging the speed of revolution required for complete fusion. 22. Limits of the Field of Vision. The limits of the visual field are determined by direct measurement with the perimeter. Set the person whose retina is to be measured in a comfortable erect position, with one eye at the center of the arc of the perimeter and the other covered by an eye-shade. The observed eye must be fixed on the center of the field of vision, and care must be used to prevent obstruction of the field. The examination is made with greatest accuracy by bringing an object into the field of vision from behind the person observed. When the individual examined first detects the presence of the object, he announces it and the angle is read off from the arc of the perimeter and recorded on the chart for the purpose. These readings should be made in about twelve radii. They should be made for each eye. 23. Limits for the Field of Vision for Color. To measure the limits of the field of vision for colors one should proceed as in the preceding experi- ment, except that small squares of colored papers are brought into the field from the rear. The retina should be mapped for red, green, yellow, and blue. Use Bradley's pure color papers. Take four penholders and mount on the end of one a centimeter square of red paper, on the others green, yellow, and blue. To make a determination bring the color up from behind and, as soon as it is certainly detected and announced, remove it from the field of vision. Examine the eye for all four colors at one sitting, mixing them indeterminately in the individual tests. Occasionally an eye will be found which exhibits a well-marked restriction of the color field, though the individual himself may not be completely color-blind. 24. Color-Blindness. Make an examination for color-blindness, using Holmgren's colored yarns. Spread the yarns out on a table in the best of light. Place the three confusion skeins in front of the individual to be ex- amined and ask him to match them quickly from the skeins on the table, paying no attention to lights and shades of the same color. A color-blind individual will confuse colored skeins, most usually the reds, greens, and grays. 25. Color Mixing. Use Bradley's color wheel and test the effect of simultaneous stimulation of the retina with two or more colors, by placing on the wheel two or more colored discs, rotating the wheel at a speed sufficient to cause complete fusion. The sensation produced by two colors applied simultaneously will be entirely different from that produced by either alone. Red and green (or greenish blue), when mixed in the proper proportion, pro- duce a sensation of gray. The same effect may be had from yellow and blue, orange and violet, or any of the complementary colors chosen according to the geometrical color table, figure 473. By mixing three colors, red, green, and violet, in the proper proportion one can produce a sensation almost the same as that produced by white light. 26. Color After-images. Color after-images can be demonstrated 678 THE SENSES by looking continuously at the center of one of the primary colors of Bradley's color charts against a white or gray wall until there is apparent fatigue, then suddenly removing the chart. An after-image of approximately the complementary color will appear in the course of a few seconds. Occasionally these images are very vivid. The experiments are brilliant if performed in the dark room, using colored gelatin screens through which an intense light shines. When the light is turned off, a brilliant after-image of the comple- mentary color appears. 27. Retinoscopy. Use the ordinary small ophthalmoscope and ex- amine the retina of the eye of a cat or rabbit. Dilate the eye by the use of atropine. Place the animal whose eye is to be examined on a support in front of a bright but uniform light (an Argand burner). Reflect the light from the mirror of the ophthalmoscope through the pupil into the retinal cup of the animal. Usually the ophthalmoscope has to be focussed for a cat's retina. When a good light is secured, the retinal cup will appear as a bril- liantly colored disc, with the branching blood-vessels, and usually with some brilliant bluish-green pigment in the lower portions of the retinal disc. After some practice on the cat or the rabbit, the student should examine the retina of one of his mates, preferably an eye that has an unusually wide pupil. In some cases a light dosage of homatropine may be used on one eye. This will dilate the pupil and the examination will be much easier. Students are not recommended to use atropine unless under conditions which permit the eye to rest for two or three days following. 28. Visual Acuity. The visual acuity of the eye should be tested first for the right eye, then for the left. Hang a test chart at a distance of twenty feet, so that its disc is well illuminated, and allow the individual tested to read off the letters on the chart, beginning with the larger ones at the top. The letters on this chart are constructed on the basis of a visual angle of five degrees. When the letters marked "twenty feet" or "six meters " represent the limit of accurate identification, the visual acuity is said to be i, or normal. If the line marked "thirty feet" is the limit, then the acuity is one and a half; if "fifteen feet," then the visual acuity is three-fourths, etc. If the eyes tested are astigmatic, or have other optical defects, these must first be corrected before testing for visual acuity. 29. The Test Set. The student is recommended to close the ex- periments on the eye by fitting glasses for himself and at least two others. He should correct for the defects that have been revealed in the preceding experiments, especially for astigmatism; myopia, or hypermetropia ; and presbyopia. Of course each eye must be tested and fitted separately. CHAPTER XVI THE REPRODUCTIVE ORGANS THE REPRODUCTIVE ORGANS OF THE MALE. THE male reproductive organs comprise the Testes, the Vas Deferens, the Vesicula Seminalis, the Prostate Gland, and the Penis. The Testes. The testes consist of two parts, i, the testicle, which is covered by the tunica vaginalis and secretes the germinal cells, and 2, the conducting tubules, which compose the epididymis and vas deferens. The testicle is divided by connective-tissue septa into lobules, the tubuli semi ni jeri. Each tubule is limited by a membrana propria on which rests the germinal epithelium. On the approach of sexual maturity the process of spermatogenesis begins. \ FIG. 486. FIG. 487. FIG. 486.— Plan of a Vertical Section of the Testicle, Showing the Arrangement of the Ducts. The true length and diameter of the ducts have been disregarded, a, a, Tubuli seminiferi coiled up in the separate lobes; b, tubuli recti or vasa recta; c, rete testis; d, vasa deferentia ending in the coni vasculosi; /, e, g, convoluted canal of the epididymis; h, vas deferens; /, section of the back part of the tunica albuginea; i, i, fibrous processes running between the lobes; s, me- diastinum. FIG. 487.— Vertical Section through the Wall of the Tubules of Epididymis. X 700 (Kol- liker.) b, Connective tissue and smooth muscle cells; e, basal layer of epithelial cells; f, high columnar cells; p, pigment granules in columnar cells; c, cuticula; h, cilia. The germinal cells multiply rapidly, and, by a complex series of mi totic divisions or stages, form ultimately the male reproductive cells, or sperm cells. The important stages in order are: archispermiocyte, spermatogonia, primary and secondary spermatocytes, spermatids, and spermatozoa. The spermatogonia stage is the stage of rapid multiplication; the spermatocyte, that of maturation, comparable to the maturation stage of the ovum. 679 680 THE REPRODUCTIVE ORGANS The sperm cells are the essential male reproductive cells. Each sperma- tozoan consists of a minute oval head, a middle piece, and a tail. The head is 4 /* by 2.5 P. The middle piece and tail are about 50 to 60 M long. Sperm cells possess the power of flagellate movement. The Vas Deferens. This is the single duct proceeding from each testicle to join its fellow at the base of the bladder. Each has an ampulla or spc.i FIG. 488. — Later Stages in Spermatogenesis of the Bull, spg.r, Reserve spermatogonium; spg, spermatogonium; spc.g, spermatocyte in late synapsis stage; spc.i, spermacyte in stage just preceding the maturation divisions; spd, spermatids in advanced stage of histogenesis, with heads deeply embedded in Sertoli cell. Highly magnified. (After Schoenfeld.) enlargement just before it unites with its fellow. The vas deferens has muscu- lar walls and is lined with ciliated epithelial cells. The Vesiculae Seminales. The seminal vesicles have the appear- ance of outgrowths from the base of the vasa deferentia. Each vas deferens, just before it enters the prostate gland, through part of which it passes to terminate in the urethra, gives off a side branch which bends back from it at an acute angle. This branch, dilating, variously branching, and pursuing in THE PENIS 681 both itself and its branches a tortuous course, forms the vesicula seminalis. Each vesicula is a single-branching convoluted and sacculated tube. The structure resembles closely that of the vasa deferentia. The Penis. The penis is attached to the symphysis pubis by its root. It is composed of three long, more or less cylindrical masses enclosed PIG. 489. — Section of a Tubule of the Testicle of a Rat, to Show the Formation of the Sperma- tozoa, a, Spermatozoa; b, seminal cells; c, spermatoblasts, to which the spermatozoa are still adherent; d, aaembrana propria; e, fibro-plastic elements of the connective tissue. (Cadiat.) FIG. 400 — Dissection of the Base of the Bladder and Prostate Gland, Showing the Vesiculae Seminales and Vasa Deferentia. a, Lower surface of the bladder at the place of reflection of the peritoneum; b, the part above covered by the peritoneum; i, left vas deferens, ending in e, the ejaculatory duct; the vas deferens has been divided near i, and all except the vesical portion has been taken away; s, left vesicula seminalis joining the same duct; s,s, the right vas deferens and right vesicula seminalis. which has been unraveled; p, under side or the prostate gland; m, part of the urethra; u, u, the ureters (cut short), the right one turned aside. (Waller.) 682 THE REPRODUCTIVE ORGANS in remarkably firm fibrous sheaths. Two, the corpora cavernosa, are alike and are firmly joined together. They receive below and between them the third part, or corpus spongiosum. The urethra passes through the corpus spongiosum. The enlarged extremity, or glans penis, is continuous with the corpus spongiosum. Cowpcr's glands are at its base, and their ducts open into the base of the urethra. The Prostate Gland. The prostate is situated at the neck of the urinary bladder, and encloses the base of the urethra. The prostate is made up of small compound tubular glands embedded in an abundance of mus- FIG. 491. — Human Spermatozoa (after Retzius). A, Side view; B, front view. cular fibers and connective tissue. The glandular substance consists of numerous small saccules, opening into elongated ducts, which unite into a smaller number of excretory ducts. The acini of the upper part of the prostate are small and hemispherical, in the middle and lower parts the tubes are longer and more convoluted. The ducts, twelve to twenty in number, open into the urethra. They are lined by a layer of columnar cells, beneath which is a layer of small polyhedral cells. The muscular tissue of the prostate not only forms the chief part of the stroma of the gland, but also forms a continuous layer inside the fibrous sheath, as well as a layer surrounding the urethra continuous with the sphincter of the bladder. The Seminal Fluid. The sperm cells of the testes are joined on their way to the exterior by the fluids secreted by the mucous lining of the various tubules and glands. Of the fluids the chief ones are the secretions of the THE REPRODUCTIVE ORGANS OF THE FEMALE 683 seminal vesicles, of the prostate gland, and of Cowper's glands. The sperm cells and the secretions together constitute the seminal fluid. After the period of puberty the seminal fluid is secreted constantly but slowly, except under sexual excitement. It is ordinarily received into the seminal vesicles, whence it is expelled at the time of coitus. In celibates the seminal fluid may at times escape in small quantity into the urethra to be washed away by the urine, or periodic reflex emissions may occur. The seminal vesicles contribute a secretion, as well as a vesicle to receive the sperm. The secretion of the seminal vesicles and that of the prostate gland are in some way concerned in maintaining the activity and prolonging the life of the spermatozoa. These cells remain alive in the fluid for as much as forty- eight hours after removal from the body, and remain alive quite indefinitely in the vesicles in the body. The secretions have been proven necessary to the life and function of the spermatozoa by the results of operations in which the seminal vesicles and the prostate were removed, whereby the animal be- came sterile. THE REPRODUCTIVE ORGANS OF THE FEMALE. The female genital organs consist of the ovaries, the Fallopian tubes, the uterus, and the vagina. The Ovaries. The ovaries are paired bodies, situated in the cav- FIG 492.— Diagrammatic View of the Uterus and Its Appendages, .as Seen from Behind. The uterus and upper part of the vagina have been laid open by removing the posterior wall; the Fallopian tube, round liagment, and ovarian ligament have been cut short, and the broad liga- ment removed on the left side. «, The upper part of the uterus; c, the cervix opposite the os m- SSSTtte triangular shape of the uterine cavity is shown, and the dilatation of the cervical cavity with the rug* termed arbor vite; v, upper part of the vagina; od Fallopian tube -or ovi- duct • the narrow communication of its cavity with that of the cornu of the uterus on each side is seen- /, round ligament; lo, ligament of the ovary; o, ovary; «, wide outer part of the right Fal- lopian tube; fi, its fimbriated extremity; po, parovarium; h. one of the hydatids frequently found connected with the broad ligament, i. (Allen Thomson.) ity of the pelvis, and adherent to the posterior surface of the broad ligament. The border of the ovary is called the hilum, and it is at this point that the 684 THE REPRODUCTIVE ORGANS blood-vessels and nerves enter it. Each ovary is about 4 cm. long, 2 cm. wide, and 1.25 cm. thick. It is supported by the suspensory ligament. The internal structure of the ovary consists of a peculiar soft fibrous con- nective tissue, stroma, abundantly supplied with blood-vessels. The surface of the ovary is covered with cubical epithelium. Embedded in the stroma in various stages of development are numerous minute follicles cr vesicles, the Graafian follicles, containing the ova, figure 494. They are small and numer- ous near the surface of the ovary, either arranged as a continuous layer, as in the cat or rabbit, or in groups, as in the human ovary. Nearer the center are large and fully developed follicles. Each follicle has an external membranous envelope, or membrana propria, which is lined with a layer of nucleated cells, forming a kind of epithelium FIG. 493 . — Diagrammatic Section of the Ovary, Showing its Cortical or Ovigenous Layer, Formed of Ovisacs in Various Stages of Evolution. (Duval.) A, A, A, Primordial ovisacs; B, B, B, ovisacs further developed; C, ovisac approaching maturity; D, ripe ovisac with its proligerous disc (DP) containing the ovum; MG, membrana granulosa; H, hilum of ovary. or internal tunic, and named the membrana granulosa. The cavity of the follicle contains the ovum enclosed in a very delicate membrane. The large spherical nucleus contains one or more nucleoli. The nucleus is known as the germinal vesicle, and the nucleolus as the germinal spot. The human ovum measures about 0.2 mm. in diameter. Its external investment, or the zona pellucida, or vitelline membrane, is a transparent membrane, about 10 ^ in thickness, which under the microscope appears as a bright ring, figure 495. The ovum itself has the characteristic structure of the typical cell, with the exception that its cytoplasm is filled with numerous yolk granules. The larger granules cr globules, which have the aspect of fat-globules, are in greatest number at the periphery of the yolk. The nucleus, or germinal vesicle, is about 0.05 mm. in diameter. The vesicle is of greatest relative size in the smallest ova. The Graafian follicles are formed in the following manner: The em- THE OVARIES 685 bryonic ovary is covered with short columnar cells, or the so-called germinal epithelium. The cells of this layer undergo proliferation so as to form several strata, and grow into the ovarian stroma as longer or shorter columns or tubes. By degrees these tubes become cut off from the surface epithelium, and form cell nests, small if near the surface, larger if in the depth of the stroma. The nests increase in size from multiplication of their cells. , Certain cells of the germinal epithelium enlarge, and form ova; and the formation of ova takes place in the nests within the stroma. The small cells of a nest surround the ova, and form their membrana granulosa, and the stroma growing up separates the surrounded ova into so many Graafian follicles. The smallest follicles are formed at the surface, and make up the cortical Downgrowths of epith^Hum Germinal epithelium Ovum with its investing cells Stratum grajmlosom epithelial cells Ovarian strorna Graafian follicle Ovum uorfolliculi Discus proligerus FIG. 494. — A, Diagrammatic Representation of the Manner in which the Graafian Follicles Arise During the Development of the Ovary. B, Diagram Illustrating the Structure of a Ripe Graafian Follicle. (Cunningham.) layer. It is said by some that the superficial follicles as they ripen become more deeply placed in the ovarian stroma; and, again, that as they increase in size, they make their way toward the surface. When the Graafian follicles mature, they form little prominences on the exterior of the ovary covered only by a thin layer of condensed fibrous tissue and epithelium. From the earliest infancy, and through the whole fruitful period of life, there appears to be a constant formation, development, and maturation of Graafian vesicles, with their contained ova. Until the period of puberty, however, the process is comparatively inactive. But, coincident with the other changes which occur in the body at the time of puberty, the ovaries enlarge and become very vascular, the formation of Graafian vesicles is more abundant, the size and degree of development attained by them are greater, and the ova are capable of being fertilized. THE REPRODUCTIVE ORGANS The Fallopian Tubes, or Oviducts. The Fallopian tubes are about 10 cm. in length and extend between the ovaries and the upper angles of the uterus. At the point of attachment to the uterus, each tube is very narrow; but in its course to the ovary it increases to about 3 mm. in thickness. At its distal extremity, which is free and floating, it bears a number of fimbria, one of which is longer than the rest and is attached to the ovary. The canal FIG. 495. — Diagrammatic Representation of a Human Ovum and Its Coverings. (Cunning- ham.) The corona radiata, which completely surrounds the ovum, is represented only in the lower part of the figure. 1, Corona radiata; 5, vi tell us or yolk; 2, granular layer; 6, germinal vesicle (nucleus); 3, vitelline membrane; 7, germinal spot (nucleolus); 4, zona pellucida (oolemma) ; 8, nuclear membrane. of the tube is narrow, especially at its point of entrance into the uterus. Its other extremity is wider and opens into the cavity of the abdomen by the fimbriae. The Fallopian tube is invested with peritoneum, and its canal is lined with ciliated epithelium. The Uterus. The uterus, u, c, figure 492, is a somewhat pyriform organ, and is about 7.5 cm. in length, 5 cm. in breadth at its upper part or fundus, but at the neck or cervix only about 1.25 cm. The part be- tween the fundus and neck is termed the body of the uterus; it is about 2.5 cm. in thickness. The uterus is constructed of three principal layers, or coats: serous, fibrous and muscular, and mucous. The serous coat, which has the same general structure as the peritoneum, covers the organ except the front surface of the neck. The middle coat is a thick mass of unstriped muscle. The muscle fibers become enormously developed during pregnancy. The arteries THE VAGINA 687 and veins are found in large numbers in the outer part so as to form almost a special vascular coat. The mucous membrane of the uterus is composed of col- umnar ciliated epithelium, which extends also to the interior of the tubular glands, of which the mucous membrane is largely made up. In the cervix of the uterus the mucous membrane is arranged in permanent longitudinal folds, palma plicatce. The glands of this part branch repeatedly, and extend deeply into the substance of the cervix. The body has numerous simpler tubular glands. The glands are also lined with ciliated epithelium. They secrete a thick glairy mucus, resembling white of egg. The Vagina. The vagina is a membranous canal 8 to 10 cm. long, extending obliquely downward and forward from the neck of the uterus, which it embraces, to the external organs of generation. It is lined with mucous membrane, covered with stratified squamous epithelium, which in the ordinary contracted state of the canal is thrown into transverse folds. External to the mucous membrane, the walls of the vagina are constructed of unstriped muscle and fibrous tissue, within which in the submucosa, especially around the lower part of the tube, is a layer of erectile tissue. The lower extremity of the vagina is embraced by an orbicular muscle, the sphincter vagina. The external organs of generation are the clitoris, the labia interna or nymphce; and, the labia externa or pudenda, formed of the external integu- ment, and lined internally by mucous membrane. Numerous mucous follicles are scattered beneath the mucous membrane of the external organs of genera- tion; and two larger lobulated glands, the glands of Bartholin, analogous to Cowper's glands in the male, are located at the sides of the lower part of the vagina. The ducts of these glands are about 1 2 mm. long and open immediately external to the hymen at the mid-point of the lateral wall of the vaginal orifice. Ovulation and Menstruation. In the process of development in the ovary, the individual Graafian follicle increases in size and gradually ap- proaches the surface of the ovary. When fully ripe or mature, it forms a little projection on the exterior. Coincident with the increase in size, which is caused by the augmentation of its liquid contents, the external envelope of the distended vesicle becomes very thin and eventually bursts. The ovum and fluid contents of the vesicle escape on the exterior of the ovary, whence they pass into the Fallopian tube. In man and mammals ovulation apparently occurs only at certain periods. These periods seem to precede or occur during the changes in the woman that constitute the phenomenon of menstruation, or, in the lower mammals, of heat. That ovulation and discharge occur periodically, and only during the phenomenon of heat, in the lower mammalia, is made probable by the facts that, in all instances in which Graafian vesicles have been found presenting the appearance of recent rupture, the animals were at the time or had recently been in heat. There are few authentic and detailed accounts of Graafian 688 THE REPRODUCTIVE ORGANS vesicles being found ruptured in the intervals of heat; and females do not ad- mit the males, and never become impregnated, except at those periods. Al- though conception is not confined to the periods of menstruation, yet it is more likely to occur about a menstrual epoch than at other times. The exact relation between the discharge of ova and menstruation is not very clear. It was formerly believed that menstruation was the result of a congestion of the uterus arising in association with the enlargement and rupture of a Graafian follicle; but though a Graafian follicle is, as a rule, ruptured at each menstrual epoch, yet instances are recorded in which men- struation has occurred where no Graafian follicle can have been ruptured, and FIG. 496. FIG. 497- FIG. 498. FIG. 496. — Diagram of Uterus just Before Menstruation. The shaded portion represents the thickened mucous membrane. FIG. 497. — Diagram of Uterus when Menstruation has just Ceased, Showing the Cavity of the Uterus Deprived of Mucous Membrane. FIG. 498.— Diagram of Uterus a Week After the Menstrual Flux has Ceased. The shaded por- tion represents renewed mucous membrane. (J. Williams.) cases where ova have been discharged in amenorrheic women. It must therefore be admitted that menstruation is not dependent on the matura- tion and discharge of ova. Observations made after death, and facts obtained by clinical investiga- tion, support the view that rupture of a Graafian follicle does not happen on the same day of the monthly period in all women. In the minority of cases it may occur toward the close or soon after the cessation of a flow. On the other hand, in almost all subjects examined after death, of which there is record, rupture of the follicle appears to have taken place before the com- mencement of the menstrual flow. SOURCE AND CHARACTER OF MENSTRUAL CHANGES However, the presence of the ovaries seems necessary for the performance of the menstrual function; for women do not menstruate when both ovaries have been removed by operation. (See page 432 for a discussion of the functional effects of removal of the ovary.) Source and Character of Menstrual Changes. The menstrual periods usually occur at intervals of a lunar month, the duration of each being from three to six days. In some women the intervals are so short as three weeks or even less; while in others they are longer than a month. The periodical return is usually attended by pains in the loins, a sense of fatigue in the lower limbs, and other symptoms, which vary extremely in different individuals. The menstrual discharge is a thin sanguineous fluid, and consists of blood, epithelium, and mucus from the uterus and vagina. The menstrual flow is preceded by a general engorgement of all the pelvic organs with blood. The cervix and vagina become darker in color and softer in texture, and the quantity of mucus secreted by the glands of the cervix and body is increased. The uterine mucous membrane is swollen and the glands are enlarged. The dis- charge of blood, the source of which is the mucous membrane of the body of the uterus, is probably associated with uterine contractions. There is great difference of opinion as to whether or not any of the uterine mucous membrane is normally shed during the process of menstruation. John Williams believes that the whole of the mucous membrane of the body of the uterus is thrown off at each monthly period, forming a true decidua men- strualis, figure 496, while Moricke and others believe that the mucous mem- brane remains intact. Leopold believes that red blood-corpuscles escape from the congested capillaries and undermine the superficial epithelium, and that in this way the superficial layer of the mucous membrane is eroded and subsequently regenerated. There is a period of regeneration followed by a period of rest before the next repetition. Minot distributes the variations in time as follows : Tumefaction 5 da7s Menstrual discharge 4 Restoration of mucosa 7 Period of rest 12 The menstrual period is often accompanied by profound disturbances in other parts of the body, especially of the vascular and of the nervous systems and of the nutritive processes. Corpus Luteum. Immediately before, as well as subsequent to, the rupture of a Graafian follicle and the escape of its ovum, changes ensue in the interior of the follicle, which result in the production of a yellowish mass, termed a Corpus luteum. When fully formed, the corpus luteum of mammals is a roundish solid body, of a yellowish or orange color, and composed of a number of lobules, 44 gg0 THE REPRODUCTIVE ORGANS which surround, sometimes a small cavity, but more frequently a small stelli- form mass of substance, from which delicate processes pass as septa between the several lobules. The processes gradually change till they nearly fill the cavity of the follicle, and even protrude from the orifice in the external cover- ing of the ovary. Subsequently this orifice closes, but the fleshy growth within still increases during the earlier period of pregnancy, the color of the substance gradually changing to yellow, and its consistence becoming firmer. After the orifice of the follicle has closed, the growth of the yellow substance con- tinues during the first half of pregnancy, till the cavity is reduced to a com- paratively small size or is obliterated; in the latter case, merely a white stelli- form cicatrix remains in the center of the corpus luteum. The first changes of the internal coat of the Graafian follicle in the proc- ess of formation of a corpus luteum seem to occur in every case in which an ovum escapes. If the ovum is impregnated, the growth of the yellow sub- stance continues during nearly the whole period of gestation and forms the large corpus luteum commonly described as a characteristic mark of impreg- nation. The significance of the corpus luteum is found in the belief that it is the portion of the ovary especially concerned in the production of an internal secretion that affects the uterus, especially stimulating it at and before the menstrual period. Menstrual Life. The occurrence of a menstrual discharge is one of the most prominent indications of the commencement of puberty^ in the female sex; though its absence even for several years is not necessarily at- tended with arrest of the other characters of this period of life or incapability of impregnation. The average time of its first appearance in females of this country and others of about the same latitude is from fourteen to fifteen: but it is much influenced by the kind of life to which girls are subjected, being accelerated by habits of luxury and indolence, and retarded by contrary con- ditions. Its appearance may be slightly earlier in persons dwelling in warm climates than in those inhabiting colder latitudes. The menstrual functions continue through the whole fruitful period of a woman's life, and usually cease between the forty-fifth and fiftieth years, which time is known as the climacteric. Menstruation does not usually occur in pregnant women. CHAPTER XVII DEVELOPMENT Changes Which Occur in the Ovum Prior to Impregnation. The ovum when ripe and detached from the ovary is a single cell enclosed within the zona pellucida, and containing the germinal vesicle and germinal spot. The ovum undergoes a series of changes preparatory to fertilization, known as maturation, the general effect of which is to reduce the chromatin in anticipa- FIG. 499. — The Maturation of the Ovum; Extrusion of the "Polar Bodies." (Diagrammatic.) A, An ovum at the commencement of the process; B, after the formation of the spindle. The chromosomes are gathered at the equator of the spindle. C, One apex of the spindle has pro- jecteJ into a bud on the surface, and half of the divided dyads have passed to each pole; D, the separation of the first polar body; E, the commencement of the second polar body; F, the comple- tion of the second polar body. (Cunningham.) tion of the added chromatin from the sperm nucleus. The primary change observed in the ovum consists in the migration of the germinal vesicle or nucleus to the surface, and the disappearance of its nuclear membrane, with a con- sequent indistinctness of its outline. Its protoplasm becomes to a consider- able extent confounded with the yolk substance, and its germinal spot dis- appears. The next step in the process is the appearance in the yolk of two 691 692 DEVELOPMENT centrosomes in a clear space near the poles of the elongated vesicle, and the formation of a nuclear spindle, with the aster at either end lying near the sur- face of the yolk. The nucleus now divides into two parts, and that nearer the surface is extruded from the ovum enveloped in a very small amount of protoplasm. This forms the first polar body. The nucleus again divides by mitosis, one-half of the chromatin is extruded from the ovum, forming a second polar cell; the chro- matin that remains behind constitutes the female pronucleus. The centrosome has disappeared and the ovum undergoes no further changes unless fertilized by the sperm. Changes Following Impregnation. The process of impregnation of the ovum has been observed most accurately in the lower types. The process is as follows: The head of a single spermatozoon joins with an elevation of the yolk substance, the tail remaining motionless and then disap- pearing. The head enveloped in the proto- plasm then sinks into the yolk and becomes a nucleus, from which the yolk substance is arranged in radiating lines. This is the male pronucleus. The middle piece of the sperm is believed to furnish a new centro- some to the ovum. The centrosome now divides and moves to either side the two pronuclei, a segmentation spindle is formed, and the egg undergoes its first segmen- tation. The process of segmentation begins almost immediately in each half of the yolk, and cuts it also in two. The process is repeated until at last by continued cleav- ages the whole yolk is changed into a mul- berry-like mass, still enclosed by the zona pellucida, figure 500. Fertilization prob- ably takes place in the Fallopian tubes, and segmentation of the fertilized ovum occurs on its passage to the uterus. PIG. 500. — Conversion of the Mo- rula to the Blastula. Formation of Blastodermic Vesicle and Membrane. A, Appearance of segmentation cavity and attachment of inner cell- mass to ectoderm at upper pole of ovum; B1, extension and flattening of inner cell- mass as it oc urs in rabbits and some other mammals; B2, extension of en- toderm as it occurs in insectivora, monkeys, apes, and man; C, comple- tion of bilaminar blastodermic vesi- cle; BC, blastodermic cavity; EC, ectoderm; EE, embryonic ectoderm; EN, entoderm; 7, inner cell-mass; SC, segmentation cavity; ZP, zona pellucida. (Cunningham.) CHANGES FOLLOWING IMPREGNATION The passage of the ovum from the ovary to the uterus occupies probably eight or ten days in the human. The peripheral cells, which are formed first, arrange themselves at the sur- face of the yolk into a membrane, the ectoderm. The deeper cells of the in- terior pass gradually toward the surface, thus increasing the thickness of the membrane already formed by a second, or entoderm, layer of cells, while the central part of the yolk, the blastoderm cavity, remains filled only with a clear fluid. By this means the yolk is shortly converted into a kind of secondary vesicle, the walls of which are composed externally of the original vitelline membrane, and within by the newly formed cellular layer, the blastoderm or germinal membrane, as it is called. Important changes occur in the structure of the mucous membrane of the uterus. The epithelium and subepithelial connective tissue, together with the tubular glands, increase rapidly, and there is a greatly increased vascularity of the whole mucous membrane, while a substance composed PIG. 501. — Section of the Lining Membrane of a Human Uterus at the Period of Commencing Pregnancy, Showing the Arrangement and Other Peculiarities of the Glands, d, d, d, with Their Orifices, a, a, a, on the Internal Surface of the Organ. Twice the natural size. chiefly of nucleated cells fills up the interfollicular spaces in which the blood- vessels are contained. The effect of these changes is an increased thickness, softness, and vascularity of the mucous membrane, the superficial part of which itself forms the membrana decidua. The object of this increased development is the production of nutritive materials for the ovum; for the cavity of the uterus shortly becomes filled with secreted fluid, consisting almost entirely of nucleated cells in which the chorion villi are embedded. When the ovum first enters the uterus it becomes embedded in the structure of the decidua, which is yet quite soft, and in which soon afterward three portions are distinguishable. These have been named the decidua vera, the decidua basalis, and the decidua capsularis. In connection with these villous processes of the chorion, there are de- veloped depressions or crypts in the decidua vera, which correspond in shape to the villi they are to lodge; and thus the chorionic villi become more or less embedded in the maternal structures. These uterine crypts, it is im- 694 DEVELOPMENT portant to note, are not, as was once supposed, merely the open mouths of the uterine follicles. The Placenta. During these changes the deeper part of the mucous membrane of the uterus, at and near the region where the placenta is placed, becomes hollowed out by sinuses, or cavernous spaces, which com- municate on the one hand with arteries and on the other with veins of the uterus. Into hese sinuses the villi of the chorion protrude, pushing the thin Pecidua basalis Unchanged layer Maternal vessel Stratum spongiosum Stratum compactum Placontal villus. Primitive streak Mesoderm Placental villus Cavity wind becomes cud on Decidua vera/ Decidua vera FIG. 502. — Diagram of the Early Stage of Human Embryo in Relation to the Uterus. (Cunningham.) walls of the sinuses before them, and so come into intimate relation with the blood contained in them. There is no direct communication between the blood- vessels of the mother and those of the fetus; but the layer or layers of membrane intervening between the blood of the one and of the other offer no obstacle to a free interchange of matters between them by diffusion and osmosis. Thus the villi of the chorion, containing fetal blood, are bathed or soaked in maternal blood contained in the uterine sinuses. The placenta, therefore, of the human subject is composed of a fetal part and a maternal part — the term placenta properly including all that entangle- ment of fetal villi and maternal sinuses, by means of which the blood of the fetus is enriched and purified after the fashion necessary for the proper growth and development of those parts which it is designed to nourish. The whole of this structure is not, as might be imagined, thrown off immediately after birth. The greater part, indeed, comes away at that time, as the after-birth; and the separation of this portion takes place by a rending CIRCULATION OF BLOOD IN THE FETUS 695 or crushing through of that part at which its cohesion is least strong, namely, where it is most burrowed and undermined by the cavernous spaces before referred to. In this way it is cast off with the fetal membrane. The remain- ing portion is either gradually absorbed, or thrown off in the uterine dis- charges which occur at this period. A new mucous membrane is of course gradually developed. Circulation of Blood in the Fetus. The circulation of blood in the fetus differs considerably from that of the adult. Returning from the placenta by the umbilical vein the blood is first con- veyed to the under surface of the liver, where the stream is divided— a part of the blood passing straight on to the inferior vena cava through a venous canal FIG. 503. — Diagrammatic View of a Vertical Transverse Section of the Uterus at the Seventh or Eighth Week of Pregnancy, c, c, c', Cavity of uterus, which becomes the cavity of the decidua, opening at c, c, the cornua, into the Fallopian tubes, and at cf into the cavity of the cervix, which is closed by a plug of mucus; dv, decidua vera; dr, decidua reflexa, with the sparser villi embedded in its substance; ds, decidua serotina, involving the more developed chorionic villi of the commenc- ing placenta. The fetus is seen lying in the amniotic sac. The umbilical cord and its vessels pass up from the umbilicus to the distribution of the blood-vessels in the villi of th chorion- and the pedicle of the yolk-sac the cavity between the amnion and chorion. (Allen Thomson.) called the ductus venosus, while the remainder passes into the portal vein and reaches the inferior vena cava only after circulating through the liver. It is carried by the vena cava to the right auricle of the heart, into which cavity the blood is also pouring that has circulated in the head and neck and arms, and has been brought to the auricle by the superior vena cava. It might be DEVELOPMENT naturally expected that the two streams of blood would be mingled in the right auricle, but such is the case only to a slight extent. The blood from the superior vena cava— the less pure fluid of the two— passes almost exclusively into the right ventricle, through the auriculo-ventricular opening, just as it does in the adult. The blood of the inferior vena cava is directed by a fold FIG. 504. — Diagram of the Fetal Circulation. of the lining membrane of the heart, called the Eustachian valve, through the foramen ovale into the left auricle and into the left ventricle, and out of this into the aorta, and thence to all the body, but chiefly to the head and neck. The blood of the right ventricle is sent out in small amount through the pul- monary artery to the lungs, and thence to the left auricle, as in the adult, but the greater part by far passes through a canal, the ductus arteriosus, lead- ing from the pulmonary artery into the aorta just below the origin of the three PARTURITION 697 great vessels which supply the upper parts of the body, and is distributed to the trunk and lower parts of the body. A large portion passes out by way of the two umbilical arteries to the placenta. From the placenta it is returned by the umbilical vein to the under surface of the liver, from which the de- scription started. After birth the foramen ovale, the ductus arteriosus, and ductus venosus all close, and the umbilical vessels are tied off, so that the two streams of blood which arrive at the right auricle by the superior and inferior vena cava, re- spectively, thenceforth mingle in this cavity of the heart, and pass into the FIG. 505. — Dissection of the Lower Half of the Female Mamma During the Period of Lactation, f. — In the left-hand side of the dissected part the glandular lobes are exposed and partially un- ravelled, and on the right-hand side the glandular substance has been removed to show the reticular loculi of the connective tissue in which the glandular lobules are placed, i , Upper part of the mammilla or nipple; 2, areola; 3, subcutaneous masses of fat; 4, reticular loculi of the con- nective tissue which support the glandular substance and contain the fatty masses; 5, one of three lactiferous ducts shown passing toward the mammilla, where they open; 6, one of the sinus lactei or reservoirs; 7, some of the glandular lobules which have been unravelled; 7', others massed together. (Luschka.) right ventricle, by way of the pulmonary artery to the lungs, and through these, after aeration, to the left auricle and ventricle, to be distributed over the body. Parturition. With the implantation of the embryo and the devel- opment of the placenta, the uterus grows rapidly until the end of preg- nancy. The muscles of its walls increase enormously in volume, appar- ently by an increase in the size of the fibers, and the whole structure may become thirty or forty times its size in the resting period. Many changes take place also in other parts of the body, changes which are dependent on the presence of the fetus. Full-term pregnancy occurs when the uterus is 698 DEVELOPMENT isolated from the nervous system, hence it has been inferred that there is some sort of special secretion, possibly of the embryo itself, that makes its way into the blood and influences the organs of the mother. At the end of the period of pregnancy the strong4jterine walls begin periodic contractions which ultimately result in the delivery of the fetus. These con- tractions are at first weak and at long intervals, but later become very strong and follow each other in rapid succession. The uterine contractions are sup- ported by reflex contractions of the abdominal and thoracic muscles. After the fetus is delivered the uterine contractions become milder, but still continue until the placenta is finally expelled. The initiation of the contractions of the uterus at delivery probably de- pends on the chemical stimulation of some substance or substances produced in the uterus itself or in the fetus; substances that react on the nervous mech- anism and on the uterine muscles themselves. This view cannot be said to be proven, but it is supported by certain observed facts and experiments. Lactation. There is a marked development of the mammary glands especially in the later part of the period of gestation. Upon delivery of the fetus the gland enlarges very sharply and an abundant secretion is formed. FIG. 506. FIG. 507. FIG. 506. — Section of Mammary Gland of Bitch, Showing Acini, Lined with Epithelial Ce-lls of a Polyhedral or Short Columnar Form. Xzoo. (V. D. Harris.) FIG. 507. — Globules and Molecules of Cow's Milk. X4oo. The secretion of the first few days is called the colostrum. It contains a larger per cent of solids, has the large granular colostral corpuscles, is more alkaline than ordinary milk, and has a specific gravity of 1040 to 1046. The mammary glands have been isolated from the nervous system to determine whether or not the association in time between their changes and the changes in the uterus were of a nervous nature. The isolated mammae develop and begin lactation at parturition as in the normal. It would seem that here, too, there is some special form of stimulation through the medium of the blood. Yet one must not draw the conclusion that the nervous system THE COMPOSITION OF MILK 699 exerts no influence on the mammary gland. Stimulation of the nerves to the gland produces vascular changes that increase or decrease the quantity of secretion. Many observations have been noted in women, which show that the secretion of milk is sharply influenced by, or even completely suppressed by, nervous states. The Composition of Milk. Milk has a specific gravity of 1028 to 1034. Its fat is held in emulsion. Under the microscope, it is found that the milk globules vary in size, the majority being from 2 to 3 p. in diameter. The old view that they have an investing membrane of albuminous mate- rial is now generally discarded. COMPOSITION OF COLOSTRUM (PFEIFFER). Proteids 5.71 Fat i 2 . 04 Sugar 3.74 Salts 0.28 Water 88.23 100.00 SALTS IN WOMAN'S MILK (ROTCH). Calcium phosphate 23.87 Calcium silicate 1.27 Calcium sulphate 2.25 Calcium carbonate 2 . 85 Magnesium carbonate 3-77 Potassium carbonate 23 .47 Potassium sulphate 8.33 Potassium chloride 12 .05 Sodium chloride 21 . 77 Iron oxide and alumina °-37 100. oo In addition to the oil or butter fat, milk contains certain proteids, milk- sugar, and several salts. Its percentage composition is given in the tables appended. CHEMICAL COMPOSITION OF MI-LK. (AFTER FOSTER, HARRINGTON, et a/.) Human. Cow. Mare. Bitch. Water 87.30 87 90 76 Solids 12.70 13 10 24 Fats 4-oo 4-0 2.0 10.0 Proteids i-S° 4-Q 2.5 10.0 Sugar 7-0° 4-3 5-° Salts.. o-20 °-7 °-5 °-5 INDEX ABDOMINAL viscera, vascular nerves for, 223 Abducens nerve, 554 Absorption, 361 conditions for, 362 methods of, 361, 364 places for, 362, 370 rapidity of, 362, 370 through the intestines, 363 the lungs, 370 the mouth, 362 the skin, 369 the stomach, 362 Accelerator centers for heart, 183 Accessory olives, 539 thyroids, 428 Accommodation of vision, 642, 645 Achromatic layer, 17 spindle, 19 Achromatin, 18 AchroSdextrin, 311 Acid albumin, 82 Acromegaly, 431 Activating ferments, 303 Adamkiewicz reaction, 196 Addison's disease, 429, 431 Adenoid tissue, 35 Adipose tissue, 37, 38 Adrenalin, 431 Adrenals, 428 After-birth, 694 -images, 654, 660, 677 -sensations, 602 Agglutinative substances, 129 Air cells, 250 changes in, during respiration, 263 composition of, 263 diffusion of, 267 pressure of, 267, 285 quantity breathed, 259, 284 volume breathed, 284 Albumin, acid, 82 alkali, 83 Albumin, egg, 81 native, 80, 8 1 serum, 81 Albuminates, 82 reactions of, 97 Albuminoids, 86 effect of diet of, 411 Albumins, 81 reactions of, 97 Albumoses, reactions of, 97 Alcohol as a food, 300 Alkali albumin, 83 Ameba, 3 Ameboid movement, 3 Amido-acids, 89 Amitosis, 10, 19 Ammonia, effect of breathing, 279 in the urine, 383 Ammonium carbamate, 412 Amylolytic ferments, 303 Amylopsin, 303, 334, 337 Anabolism, 6, 405 Anabolites, 405 Anacrotic limb, 206 wave, 207, 208 Anaphase, 20 Anelectrotonus, 471 Animal heat, 433 Animals differentiated from plants, 10 Anode, 471, 473 Ano-spinal center, 526 Anterior association center, 589 Antipeptone, 336 Antiperistalsis, 350 Apnea, 277, 289 Arborization, interepithelial, 72 Archispermiocyte, 679 Archoplasm, 18 Areolar tissue, 34 Aristotle's experiment, 669 Arterial flow, 196, 198 rhythmic, 198 velocity of, 199 701 702 INDEX Arterial pulse, 237 blood-pressure and nervous reg- ulation in, 239, 240 Arteries, 149 blood-pressure in, 187 nerves of, 151 Arterioles, 149 Articulate sounds, 490 Asphyxia, 278, 290 Assimilation, 6 Association centers of brain, 587 Aster, 19 Astigmatism, 649, 674 Atmosphere, composition of, 263 Attraction sphere, 18 Auditory center, 587 judgments, 626 nerve, 556 Auricles, action of, 155 Auriculo-ventricular valves, action of, 156 Autolytic substances, 129 Axis cylinder, 65 Axone, 64 BACTERIA in digestive tract, 347 Basement membrane, 22 Basket cells, 562 Basophile, 113 Bezold's ganglia, 175 Bidder's ganglia, 175 Bile, 340, 360 acids, 341, 360 capillaries, 340 coloring matter of, 341 chemical composition of, 341 discharge of, 343 functions of, 342 mode of discharge of, 343 mode of secretion of, 343 pigments of, 360 salts, 341, 360 Bilirubin, 90, 341 Biliverdin, 90, 341 Binaural sensations, 627 Binocular vision, 664 Bioplasm, 2 Biuret reaction, 96 Bladder, urinary, 377 Blastema, 2 Blastoderm, 14 Blind spot, 653, 675 Blood, 10 1 arterial flow, 196 buffy coat, 103 capillary flow, 199 carbon dioxide of, 271 chemical composition of, 115 circulation of, 141, 186 experiments on, 226 in fetus, 695 coagulation of, 102, 137 calcium in, 106 conditions affecting, 106 fibrin in, 103 theories of, 105 corpuscles of, 107 chemical composition of, 139 colorless, 112 ameboid movement of, 113, 201 chemical composition of, 117 number of, 112 phagocytosis, 134 varieties of, 113 enumeration of, 134 percentage of, 135 red, 107 action of reagents on, 133 characters of, 108 chemical composition of, 118 development of, no number of, 108 origin of, 1 10 varieties of, no defibrination of, 104 differences between arterial and venous, 127 elimination of carbon dioxide by, 271 examination of, 132 ferments in, 117 flow, arterial, 196 capillary, 199 regulation of, 209 velocity of, 203 in arteries, 199 in capillaries, 201 in veins, 203 venous, 202 INDEX 703 Blood, gases of, 267 hemoglobin, 118 isotonicity of, 136 laboratory experiments on, 132 laking of, 128 microscopical examination of, 132 morphology of, 107 oxygen of, 269 plasma, 101 chemistry of, 139 composition of, 115 percentage of, 135 reaction of, 136 plates, 115 portal, 127 pressure, 186 arterial, 187, 234, 239, 240 capillary, 195, 238 in man, 192 model, 236 respiratory undulations of, 191 variations in, 195 venous, 195 production of heat by the, 434 quantity of, 101 influence on secretion, 295 respiratory changes in, 267 serum, 102 chemistry of, 139 composition of, 117 globulicidal properties of , 128 specific gravity of, 136 uses of, 10 1 variations in composition of, 126 velocity of flow, 203 venous flow, 202 whipped, 138 Blushing, 215 Body, chemical composition of, 78 energy requirements of, 425 experiments on the chemistry of, 95 Bone, 41 blood-vessels of, 42 canaliculi of, 43 cells, 44 development of, 45 growth of, 50 Haversian canals of, 44 lacunae of, 43, 44 Bone, lamellae of, 43, 44 marrow, 41 microscopic structure of, 43 ossification in cartilage, 46 in membrane, 46 periosteum of, 42 Bowman's sarcous elements, 60 theory of urinary secretion, 386 Brain, 531 after-, 533 arrangement of different parts, 531 association centers of, 587 distinctive characters of human, 532. 574 fore-, 532 gray matter in, 568 hind-, 533 inner-, 532 mid-, 533 motor areas of, 577, 582 of human, 581 tracts in, 583 Rolandic area of, 583 sensory areas of, 584 stem, 531, 532 vascular nerve-supply cf, 220 weight of* 574 Bronchi, 245 Buffy coat, 103 Bulb, the, 534, and see Medulla centers in, 540 connections with cerebrum and cerebellum, 539 functions of, 540 Bundle of Vicq d'Azyr, 547 Burdach, column of, 514 CAJAL, cells of, 570 Calcification, 47, 50 Calcium salts in the body, 94 in coagulation of the blood, 106 tests for, 99 Calorimeter, 290, 426 Calorimetry, 290 Canaliculi, 43 Cane sugar, 92 Capillaries, 151 blood -pressure in, 195 structure of, 152 704 INDEX Capillary circulation, 238 flow, 199 velocity of, 20 1 Carbohydrates, 91 absorption of, by intestines, 367 as foods, 297, 300 chemical reactions of, 98 metabolism of, 416 Carbon, amount excreted, 407 dioxide, determination of, 286, 287 elimination of, 263, 264, 271, 396 monoxide, effect of breathing, 279 hemoglobin, 140 Carbonates, 94 Carboxy hemoglobin, 121 Cardiac action, force of, 169 contractions, automatic, 231 experiments on, 227, 228 maximal, 174 cycle, 155, 1 68 impulse, 160 muscle, 61, 465, 500 action of, 465 compared with other muscles, 466, 500 automatic contractions of, 231 development of, 63 properties of, 170 refractory phase, 465 nerves, 232 Cardio-accelerator centers, 183, 543 Cardiogram, 161, 226, 228 Cardiograph, 161 Cardio-inhibitory centers, 181, 543 Cartilage, 38 development of, 41 elastic, 41 hyaline, 38 temporary, 40 white fibro-, 41 Casein, 85 Caseinogen, 85 Catabolism, 6, 405 Catabolites, 405 Catacrotic limb, 206 wave, 207 Catelectrotonus, 471 Cathode, 471, 473 Caudate nucleus, 548 Cell, i, 8, 17, 18 body, 17 difference between plant and ani- mal, 10 differentiation, 14, 17 division of, 10, 18 functions of, 1 1 , 14 growth, 7, 10 multiplication, 18 nucleus of, 9, 17 reticulum of, 8 structure of, 8, 17 Cells, decay and death of, 22 derived elements of, 22 modes of connection, 21 origin of, 2 1 shapes of, 21 types of, 21 Cellulose, 13, 91 Center for muscle tone, 525 Centers, motor, 577, 581 sensory, 584 spinal, 526 Centrosome, 18 Cerebellar cortex, paths through, 564 Cerebellum, 561 connection with bulb, 539 functions of, 564 general structure of, 562 Cerebral cortex, fibers from, 572 structure of, 568 Cerebrum, 567 arrangement of parts, 568 connection with bulb, 509 effects of removal of, 575 functions of, 575 motor areas of cortex, 577, 582 sensory areas of, 584 weight of, 574 Cerumen, 394 Ceruminous glands, 394 Chemical composition of the body, 78 elements in the body, 78 Chemistry of the body, experiments on, 95 Chest, changes in diameter of, during respiration, 284 Cheyne-Stokes breathing, 278 Chlorides in the body, 94 in the urine, 385 INDEX 705 Chlorides, tests for, 99 Chlorine, effect of breathing, 279 Chlorophyll, 12 Chondrigen, 87 Chondrin, 87 Chorda tympani, 306, 352, 355 Chordae tendineae, 148 Chromatic aberration, 649, 673 Chromatin, 18 Chromophanes, 659 Chromoplasm, 17 Chromo-proteids, 84 Chromosome, 19 Chyme, 329 Cilia, 30 Ciliary apparatus, 632 contraction, 468, 502 epithelium, 502 motion, 468 Circulation, coronary, 183 during sleep, 590 effect of respiration on, 280 in brain, 220 in erectile structures, 224 laboratory experiments on, 226 local peculiarities of, 220 of blood, 141 regulation of flow, 209 time of, 236 through blood-vessels, 186 velocity of, 203 vegetable, 4 Coagulated proteids, 83 Coagulating ferments, 303 Coagulation of blood, 102, 137 calcium salts, in 106 conditions affecting, 106, 138 theories of, 105 Cochlea, 619 Cohnheim's areas, 61 Cold, influence of extreme, 436 Collagen, 86 Collaterals, 68 Colloids, 129 Color, after-images, 654, 660, 677 -blindness, 66 1, 677 complemental, 660 extent of visual field for, 660 Bering's theory of, 663 limits of field of vision for, 677 -mixing, 677 Color, sensations of, 659, 66 1 Young's and Helmholtz's theory of, 662 Colorless corpuscles, 112 Colostrum, 698 Column of Burdach, 514 of Goll, 514 Columnae carneae, 145, 148 Comma tract, 516 Common sensations, 595 Complemental air, 259, 285 Compound proteids, 81, 84 Conductivity of muscle, 447 Conjunctiva, 630 Connective tissues, 31 adenoid, 35 adipose, 37 areolar, 34, 36 cells of, 31 development of, 36 fibrous, 36 gelatinous, 34 general structure of, 31 intercellular substance of, 32 lymphoid, 35 retiform, 35 varieties of, 32 white fibrous, 33, 36 yellow elastic, 33, 36 Consonants, 490 Contractility of muscle, 442 Contraction phase of muscle, 449 Contracture, 460 Convoluted tubule, 372 Cooking, effects of, 301 Cornea, 631 Corona radiata, 545, 546 Coronary circulation, 183 Corpora cavernosa, 224 geniculata, 546 quadrigemina, 546 striata, 548 Corpus Arantii, 148 dentatum, 562 luteum, 689 spongiosum, 224 Corpuscles, blood, 107 Malpighian, 372 of Bowman, 372 of Golgi, 76 of Krause, 74 706 INDEX Corpuscles of Meissner, 74 of Pacini, 73 Coughing, center for, 542 Cranial nerves, 548 Crassamentum, 102 Creatinin, 383, 402, 413, 414 Crura cerebri, 545 Crusta, 545 petrosa, 52 phlogistica, 103 Crystalloids, 129 Cutis vera, 393 Cystin in urine, 385 Cytolysis, 128 Cytoplasm, 17 DEATH, 7 Decay, 7 Decidua basalis, 693 capsularis, 693 menstrualis, 689 vera, 693 Decussation of the pyramids, 535 Defecation, 351 center for, 526 Degeneration in spinal cord, 515 reaction of, 474 Wallerian, 506 Deglutition, 313 center for, 316, 542 nervous mechanism of, 315 time occupied in, 315 Demarcation currents, 451, 452 Dendrites, 64 Dental papilla, 55 Dentine, 52 Depressor nerve, 215 Dermis, 393 Development, 691 Dextrin, 92 tests for, 98 Dextrose, 92 tests for, 98 Diabetes mellitus, 418 Dialysis, 129 Diapedesis, 201 Diaphragm in respiration, 254, 256 Diaster, 20 Diastole of heart, 154, 156 Dicrotic notch, 207 pulse, 208 Dicrotic wave, 207, 208 Diet, normal, requisites of, 405, 442 tables, 423 Diffusion, 129 Digestion, 297, 301 enzymes in, 301, 303 experiments in, 351 in intestines, 331, 345, 346 in mouth, 303, 353, 354 in stomach, 316 Digestive ferments, 303 Diphasic current, 453 Diplopia, 550, 664 Disassimilation, 6 Distance, estimation of, 668 Diuretics, action of, 389 Dogiel's cells, 175 Dreams, 591 Du Bois-Reymond's induction coil, 445 key, 444 Ductless glands, influence on metabo- lism, 427 Ductus arteriosus, 696 venosus, 695 Dyspnea, 278, 290 EAR, cochlea of, 619 external, 614 function of, 622 internal, 617 function of, 625 membranous labyrinth, 618 middle, 615 function of, 622 organ of Corti, 619 ossicles of, 616 tympanum, 615 Eck's fistula, 412 Edestine, 82 Egg albumin, 81 Eggs, composition of, 299 Eighth nerve, 556 Elasticity of muscle, 442 Elastin, 87 Electrodes, 445 Elect rotonus, 471 Elements, chemical, in body, 78 Eleventh nerve, 560 Emission of semen center, 526 Emulsification, 99, 337, 342 Enamel, 53 INDEX 707 Enamel cap, 56 germ, 55 organ, 55 papilla, 55 End -brushes, 68 -bulbs, 74 -plates, 62 Endocardiac pressure, 162 Endocardium, 143 Endomysium 59 Endoneurium, 68 Endothelium, 24 Energy, income and output of, 426 requirements for body, 425 Enterokinase, 303, -345, 360 Enzymes, 301 action of, on pancreatic juice, 359 activating, 303 amylolytic, 303 classification of, 302 coagulating, 303 t digestive, 303 lipolytic, 303 proteolytic, 303 Eosinophile, 100, 113 Epiblast, 14 Epidermis, 391 Epiglottis, 245 Epinephrin, 431 Epineurium, 68 Epithelial tissues, 22 Epithelium, 22 ciliated, 29, 31 classification of, 23 columnar, 23, 24, 28 cubical, 23 functions of, 24, 31 glandular, 29 simple, 23 situations of, 23, 31 specialized, 29 squamous, 23, 27 stratified, 23, 27 transitional, 28 Equilibrium, sense of, 628 Erectile tissue, 224 Erection center, 526 Erepsin, 303, 345 Ergograph, 461 Erythroblasts, 112 Erythrocytes, 107 Erythrodextrin, 311 Eustachian tube, 615, 624 valve, 143, 696 Excreta, analysis of, 406, 407 channels of elimination of, 407 quantity of, 406 Excretion, 291, 371, 398 during starvation, 422 from skin, 395 laboratory experiments in, 398 Expiration, forced, 256 muscles of, force of, 262 quiet, 256 relative time of, 258 Expired air, oarbon dioxide of, 263, 286, 287 changes in, 263 External genitals, vascular nerves for, 224 Eye, 630 anatomy of, 630 astigmatism, 649, 674 chromatic aberration of, 649, 673 image formation, 639 movements of, 647 muscles concerned in, 647 optical apparatus, 638 axis, 641 refractive surfaces and media, 639 schematic, 641 spherical aberration of, 648, 672 Eyeball, 630 blood-vessels of, 637 ciliary apparatus, 632 cornea, 631 iris, 632 lens, 632 retina, 633 Eyelids, 630 FACIAL nerve, 554 function of, 555 paralysis of, 555 relation to taste, 555 secretory, 555 Fallopian tubes, 686 Falsetto voice, 489 Far-point, 672 Fasciculus cuneatus, 534 gracilis,. 534 of Rolando, 535 708 INDEX Fasciculus solitarius. 556 Fasting, 420, 421 metabolism during, 414 Fatigue, effect on muscular contrac- tion, 497, 49 8 Fats, 90, 98 absorption of, by intestines, 367 as food, 297, 300 chemical reactions of, 98 digestion of, 337, 338 emulsification of, 99, 337, 342 energy value of, 414 metabolism of, 414 saponification of, 99, 337 source of, in body, 415 Fatty acids, 91 tests for, 99 Feces, 347 composition of, 348 excretion by, 407 Fermentation in intestine, 347 Ferments, 97 chemical reactions of, 97 in the blood, 117 unorganized, 301, and see En- zymes Fetus, circulation of blood in, 695 Fibers of Remak, 66 Fibrin, 83 . ferment, 105 Fibrinogen, 82, 105 Fictitious feeding, 321 Fifth nerve, 551 -Fillet, 544 Filtration, 361 Finger, vasomotor changes in, 241 Fish, composition of, 299 Fission, 7 Food, and digestion, 297 effects of deprivation of, 420 mastication of, 303 -principles, 297 salts of, 300 Foods, 297 carbohydrates, 297, 300 classification of, 297 effect of cooking, 301 fats, 297, 300 heat production from, 426, 437 income and output of. energy, 406 inorganic, 297, 300 Foods, liquid, 300 mineral, 297, 300 nitrogenous, 297 percentage composition of, 298 proteids, 297 salts, 300 water, 297 Forced movements, 567 Fore-brain, 532 Form, estimation of, 667 Fossa ovalis, 143 Fourth nerve, 550 Fovea centralis, 633 Frontal association center, 589 GALACTOSE, 93 Gall-bladder, 340 Galvanic currents, 443 Ganglia, 508 spinal, functions of, 523 Gases in alimentary canal, 348 Gastric digestion, 316, 355 changes in food in, 327 circumstances influencing, 327 cleavage products of, 356 products of, 326 time of, 327 juice, 321, 355 acid of, 323 'action on milk, 327 on proteids, 326 artificial, 356 chemical composition of, 323, 355 digestive action of, 356 enzyme action of, 356 fictitious meals, action on, 321 hydrochloric acid in, 324 pepsin in, 325 psychic secretion of, 355 quantity of, 323 secretion of, 320, 355 secretion, changes in glands dur- ing, 320 nervous mechanism of, 322 Gelatin, 86 Gelatinous tissue, 34 Gemmation, 7 Genito-spinal center, 526 INDEX 709 Germinal epithelium, 685 matter, 9 spot, 684 vesicle, 684 Giant cells, 42 Glands, cardiac, 317 ceruminous, 394 gastric, 316 mammary, 698 pyloric, 318 reproductive, relation to metabo- lism, 432 salivary, 304 sebaceous, 395 secreting, 293 sudoriferous, 393 types of, 293 Globulin, serum, 82 Globulins, 81 reactions of, 97 Globus pallidus, 548 Glomerulus, 374 Glosso-pharyngeal nerve, 556 in respiration, 274 Glottis, respiratory movements of, 257 Glucoproteids, 85 Glucose, 92 Glycin, 341 Glycogen, 92, 417 destination of, 418 formation of, 416 relation to metabolism, 416 sources of, 417 tests for, 98 Glycogenesis, 416 Glycoproteids, 85 Glycosuria, 418 Goblet cells, 26 Golgi, corpuscles of, 76 Goll, column of, 514 Gowers' tract, 516 Graafian follicles, 684 Granulose, 91 HAVERSIAN canals, 44 Head, vascular nerve supply of, 220 Hearing, acuteness of, 671 limits of, 671 physiology of, 620 Heart, 142 action of, 154 Heart, anatomy of, 142 automaticity of, 178 -beat, 1 60 rate of, 226, 227 sequence, 227 theories of, 174 -block, 176 capacity of, 146 chambers of, 143 character of contraction, 170, 174 coronary circulation of , 183; cycle of, 155, 1 68 depressor nerve of, 215 development of, 146 endocardiac pressure, 162 excised, experiments on, 228, 229 force of action, 169 frequency of action, 154, 185 ganglia of, 175 impulse of, 160 influence of accelerator nerve on, 182, 543 of coronary circulation on, 1 83 of drugs on, 185 of inhibitory nerves on, 179, 543 of mechanical tension on, 184 of nervous system on, 179 of nutrient fluids on, 229 of sympathetic system on, 211 of temperature on, 184 of vagus on, 179 irritability of, 172 isolated, 230 metabolism oft 178 methods of investigating beat, 226 muscle, 61, 500 properties of, 170 nerves of, 179 production of heat by, 434 regulation of force and frequency of contraction, 179 relation of rhythm to nutrition, 178 rhythmic contraction of, 1 70, 1 78 size of, 146 sounds of, 158 causes of, 159 structure of, 146 tonicity of, 172 710 INDEX Heart, valves of, 148 action of, 156 volume of, 229 weight of, 146 work per diem, 426 Heat, animal, 433 dissipation of, 434 from lungs, 436 from skin, 434 influence of extreme, 436 of nervous system on pro- duction of, 438 produced in muscular contrac- tion, 453 -producing tissues, 433 production of body-, 425, 433, 437 regulation of body-, 434, 438 centers for, 439 -rigor, 462 variations in loss of, 434 in production of, 437 Heidenhain's experiments on urine secretion, 386 Hemachromogen, 124 Hemacytometer, 135 Hematin, 124, 125 Hematoblasts, no Hematoidin, 125 Hematoporphyrin, 124 Hemianopsia, 585 Hemin, 125 Hemiopia, 585 Hemoglobin, 118, 140, 269 action on gases, 121 combining power with oxygen, 269 derivatives of, 124, 140 estimation of , 122, 136 reduced, 121 Hemoglobinometer, 122, 136 Hemolysis, 128 Hemometer, 136 Henle's membrane, 150 loop, 373 Hepatolytic sera, 128 Hind -brain, 533 Hippuric acid, 383 formation of, 383, 413 Histons, 84 Hyaline cartilage, 38 cells, 113 leucocytes, 113 Hyaloplasm, 8, 17 Hydrochloric acid, 324, 325 combined, 324 digestive action of, 325 test for free, 324 Hydrogen, amount excreted, 407 effect of breathing, 279 Hyperisotonic solutions, 130 Hypermetropia, 651 Hyperpnea, 278, 289 Hypertonic solutions, 130 Hypoblast, 14 Hypoglossal nerve, 560 Hypoisotonic solutions, 130 Hypotonic solutions, 130 INCOME of energy, 425 Indol, 360 % Induced currents, 445 Induction coil, 445 Infundibulum, 144 Inhibition, function of nerve centers in, 527 Inogen, 464 Inorganic foods, 300 principles, 93 Inosite, 93 Insalivation, 304 Inspiration, 253 forced, 256 muscles of, 253 force of, 262 quiet, 253 relative time of, 258 Inspired air, 263, 286 Intercellular substance, 21, 32 Interepithelial arborizations, 72 Internal capsule, 545 secretions, 291, 427, 431 Intestinal digestion, 331 r61e of bile in, 342 gases, 348 juices, 344, 360 secretion, 344 functions of, 345 Intestines, absorption in, 363 action of microorganisms in, 346 defecation, 351 digestion in, 331 feces in, 347 fermentation in, 347 INDEX 711 Intestines, gases in, 348 large, summary of digestive changes in, 346 movements of, 349 influence of nervous system on, 350 putrefaction in, 347 small, summary of digestive changes in, 345 vascular nerves for, 224 Intonation, 491 Invertase, 303 Involuntary muscle, 501 lodothyrin, 428 Iris, 632 contraction of, 647 Iron, 94 tests for, 99 Irritability, 5 of heart-muscle, 172 of muscle, 442 Islands of Langerhans, 332 Isotonic solutions, 130 Isotonicity of blood, 136 Ivory, 52 JUDGMENT of form and size of bodies, 604 of form and solidity, 667 of size and distance, 668 Jumping, 479 KARYOKINESIS, 10. 19 Karyolymph, 17 Karyoplasm, 17 Karyosomes, 18 Keratin, 87 Kidneys, 371 action of diuretics on, 389 blood supply of, 374 effect of blood pressure on, 398 factors affecting secretion from 386 function of, 371 glomeruli of, 374 Malpighian bodies of, 372 nerves of, 376, 387 structure of, 371 tubuli uriniferi of, 372 vasa efferentia of, 375 recta of, 375 Kidneys, vascular nerves of, 224 volume of, 387 Krause, corpuscles of, 74 membrane of, 60 Kronecker-Meltzer theory of deglu- tition, 313 Kymograph, 188 LABYRINTH, 618 Lachrymal apparatus, 630 Lactalbumin, 81 Lactase, 303 Lactation, 698 Laekeals, 364 Lactic acid, test for, 324 Lactose, 92 Lacunae, 43 Laky blood, 128 Langerhans, islands of, 332 Large intestine, summary of digestive changes in, 346 Laryngoscope, 485 Larynx, 245, 480 Latent period of muscle, 448, 495 Leaping, 479 Legumes, composition of, 299 Lens of eye, 632 Lenticular nucleus, 548 Leucocytes, 112 Leucolytic sera, 128 Levers, action of, in the body, 475 Levulose, 93 Life, phenomena of, i Limbs, vascular nerves for, 225 Linin, 18 Lipase, 303, 337 Lipochromes, 90 Lipolytic ferments, 303 Liquid foods, 300 Liquor sanguinis, 101 Lissauer, tract of, 516 Liver, 338 glycogenic function of, 416 secretions of, 338 structure of, 339 urea formation in, 411 vascular nerves for, 224 Localization, cerebral, 577, 584 Locomotion, 475 Locus ceruleus, 544 Lud wig's theory ot urine secretion, 386 712 INDEX Lungs, 248 absorption from, 370 blood supply of, 252 excretion by, 407 interchange of gases in, 272 loss of heat from, 436 lymphatics of, 252 nerves of, 252 structure of, 249 Luxus consumption, 409 Lymph, 131 chemical composition of, 131 flow, 132 formation of, 131 Lymphatic sheaths, peri vascular, 154 spaces, in blood-vessels, 154 Lymphocyte, 100, 113 Lymphoid tissue, 35 Lytic substances, 128 MAGNESIUM salts in the body, 94 Malpighian bodies, 372 Maltase, 303, 311, 334 Maltose, 92, 312 Mammary glands, 698 Manometer, 188 Marrow, bone, 41 Mastication, 303 muscles of, 303 nervous mechanism of, 304 Maximal stimulus, 454 Meat, composition of, 298 Meconium, 343 Medulla oblongata, 534, 537, and see Bulb as a conducting path, 540 functions of, 540 reflex centers of, 540 section of, 531 Medullary sheath, 65 Meissner's corpuscles, 74 Melanin, 90 Membrana decidua, 693 tympani, 616 ' Membranous labyrinth, 618 Menstrual discharge, 689 life, 690 Menstruation, 687 Mesoblast, 14 Mesothelium, 24 Metabolism, 6, 405 Metabolism, constructive, 6 destructive, 6 during fasting, 414 endogenous, 410 exogenous, 410 influence of ductless glands on, 427 reproductive glands on, 432 intermediate, 410 nutrition and diet, 405 tissue, 410 Metaphase, 19 Metaplasm, 17 Methemoglobin, 122 Microcytes, no Micro-organisms, action of, in intes- tine*,^ 46 Microsomes, 8 Micturition, 390 center for, 526 Mid-brain, 545 Milk, composition of, 299, 699 Millon's reaction, 96 Mineral foods, 300, 419 absorption of, in intestines, 368 Minimal stimulus, 454 Mitosis, 10, 19 Monaster, 19 Motor activities, coordinated, 475 areas of cortex, 577, 582 of human brain, 581 end-plates, 62 impressions, 530 -oculi nerve, 549 tracts in human brain, 583 Mouth, absorption in, 362 digestion in, 303 in speech, 491 Movement, ameboid, 3 gliding, 4 streaming, 4 Movements, circus, 567 forced, 567 Mucigen, 309 Mucin, 85, 309 Mucous membranes, 292 Mucus in urine, 384 Murexide test, 402 Muscle, blood supply of, 62 cardiac, 61, 465, 500 chemical changes of, 451 INDEX 713 Muscle, chemical composition of, 440, 441 clot, 440 coagulation of, 440 conditions affecting irritability of, 454 conductivity of, 447 contractility of, 442 contraction of, 443, 467 contracture, 460 currents, demonstration of, 452 development of, 62 effect of blood supply on, 458 of drugs on, 459 of nerve supply, 458 of single induction shocks on, 446 of temperature on, 456 of use on, 458 elasticity of, 442 electrical phenomena of, 451 end-plates, 62 experiments in, 492 ferments, 441 heart, 61, 465, 500 in rigor mortis, 461 involuntary, 57, 466, 501 compared with skeletal and cardiac, 466 irritability of, 442, 493 -nerve preparation, 492 nerve supply of, 62 non-striated, 57 plain, 57 plasma, 440 properties of, 442 record of contraction of, 443 serum, 440, 441 skeletal, 59 stimuli, 442, 496 striated, 58 tetanus, 459 -tone, center of, 525 voluntary, 58 Muscular action as heat producer, 433 activity, 464 center for tone of, 525 contraction, 443, 465 action currents, 452 apparatus for producing and recording, 443 Muscular contraction, changes in shape during, 449 characteristics of single, 448 chemical changes during, 451 conditions affecting character of, 454 co-ordinated, 460 differences between volun- tary and involuntary, 466 effect of blood supply on, 458 of drugs on, 459 of fatigue on, 497, 498 of load on, 499 of nerve supply on, 458 of rate of stimulation on, 459 of repeated activity on, 455 of strength of stimulus on, 454, 496 of temperature on, 456, 498, 499 of use on, 458 electrical changes during, 451 energy liberated during, 454 heat produced during, 453 latent period of, 448, 495 metabolism during, 463 preparation for, 446 record of, 443, 447 recording, 446 refractory phase of, 465 response to stimuli in volun- tary and involuntary, 466 simple, 448, 494 single twitch, 448 summation of contractions, 459 tetanic, 459, 499 voluntary, 459 co-ordination, 460, 629 energy, 464 tissue, 56 Musculi pectinati, 144 Mydriasis, 550 Myelin sheath, 65 Myelocyte, 100, 113 Myeloplaxes, 42 Myoalbumin, 441 Myoalbumose, 441 Myoglobulin, 44- 714 INDEX Myogram, 448 Myograph, pendulum, 448 Myohematin, 441 Myopia, 651 Myosin, 82, 44.1, 464 ferment, 441 Myosinogen, 441, 465 Myxedema, 428 NASAL region, smell, 610 Near-point, 645, 672 Nephrolytic sera, 128 Nerve cells, 70, 503 arrangement of, in spinal cord, 511 body, 70 characteristic of individual, 5°4 functions of, 503, 504 neurone theory, 504 nutritive influence of, 506 transmission of impulses through, 507 types of, 508 centers, 508 functions of, 508 collaterals, 68 end-brushes, 68 fibers, 64, 72 effect of battery current on, 471, 473 fatigue of, 470 functions of, 469 medullated, 64 non-medullated, 66 impulses, 469 cellulifugal, 507 cellulipetal, 507 character of, 469 specific energy of, 507 transmission through cells, 507 velocity of, 470 stimuli, 442, 469, 492 terminations, 72 tissue, 64, 66 trunks, 67 Nerves, cardiac, 232 cranial, 548 functions of, 548 depressor, 215 Nerves, effect of currents on human, 471. 473 experiments on, 492 irritability of, 492 spinal, 516 vasomotor, 211, 213, 217, 219 Nervous system, 503 functions of, 504 influence on secretion, 295 sympathetic, 591 tissues, 64, 66 axones of, 64, 507 dendrites of, 64, 507 ganglia of, 508 neuroglia of, 64, 77 Pacinian corpuscles, 73 Neuraxone, 64 Neurilemma, 64 Neuroglia, 64, 77 Neurokeratin, 87 Neurone, 64, 503 theory, 504 varieties, 508 Neutrophile, 100, 113 Ninth nerve, 556 Nitrogen in proteids, 88 Nitrogenous bodies, 79 equilibrium, 408 foods, 297 output, 409 Nitrous oxide, effect of breathing, 279 Nodes of Ranvier, 65 Nceud vital, 272 Nostrils, respiratory movements of , 2 5 7 Nuclear matrix, 1 7 Nuclei of optic thalamus, 546 Nucleic acid, 85 Nucleins, 85 Nucleoli, 1 8 Nucleoplasm, 17 Nucleoproteids, 84, 85 Nucleus, 9, 17 ambiguus, 556 ruber, 546 structure of, 17 OBESITY, 416 Ocular fixation, 664 Odontoblasts,.52, 55 Oils, 90 as food, 300 INDEX 715 Olein, 90 Olfactory apparatus, 609 bulb, 611 center, 585 glomeruli, 586 membrane, 613 nerve, 586 tract, 587 Olivary bodies, 536, 538 Olive, accessory, 539 superior, 544 Onkograph, 388 Onkometer, 388 Ophthalmoscope, 655 Optic center, 585 nerve, 633 thalami, 546 Optical apparatus, 638 defects in, 648 Organ of Corti, 619 Organized ferments, 346 Osmosis, 129 Osmotic pressure, 130 Ossein, 86 Osseous labyrinth, 618 Ossicles of ear, 616 Ossification, 45 center of, 46 in cartilage, 46 in membrane, 46 Osteoblasts, 46 Osteoclasts, 48 Osteogenetic fibers, 46 Output of energy, 426 Ovaries, 683 relation to metabolism, 432 Oviducts, 686 Ovulation, 687 Ovum, 684, 686 changes in, following impregna- tion, 692 prior to impregnation, 691 Oxalic acid in urine, 385 Oxygen, amount excreted, 40 / in expired air, 265 in tissues, 270 determination of, in air, 286 Oxyphile, 113 PACINIAN corpuscles, 73 Pain, sense of, 602 Pancreas, 332 enzymes of, 334 extirpation of, 431 extract of, 334 internal secretion of, 43 1 islands of Langerhans in, 332 secretion of, 333 structure of, 332 Pancreatic digestion, 358 cleavage products of, 359 fistula, 333 juice, 333, 358 artificial, 358 chemical characters of, 358 composition of, 334 conditions influencing action of, 338 enzymes of, 334, 358 action of, 335, 338, 359 secretion of, 358 action of nerves on, 334 action of secretin on, 334, 358, Papillae of skin, 392 of tongue, 606 Paralytic secretion of saliva, 306 Paranucleoproteids, 84 Parathyroid glands, 428 Parietal association center, 589 Parotid gland, 304 nerves of, 308 Parturition, 697 center, 527 Pelvic viscera, vascular nerves for, 224 Penis, 68 1 Pepsin, 303 action of, 325 in gastric juice, 325 Pepsinogen, 325 Peptone plasma, 107 Peptones, 84, 325 characteristics of, 326 reactions of, 97 Perforating fibers of Sharpey, 45 Pericardium, 142 Perichondrium, 38, 46 Perimysium, 59 Perineurium, 68 Periosteum, 42 Peripheral resistance, 186, 210 Peristalsis, intestinal, 349 716 INDEX Peristalsis, reversed, 350 Peri vascular lymphatic sheaths, 154 Perspiration, 395 Pfliiger's law of contractions, 472 Phagocytes, 134 Phagocytosis, 134 Phakoscope of Helmholtz, 674 Phenomena of life, i Phenomenon of treppe, 497 Phosphates, 94 tests for, 90 Phosphoric acid in urine, 384 Phosphorus in foods, 420 Phrenic nerve, influence on respira- tion, 289 Physiological material, source of, 1 5 utilization of, 15 Physiology, i Pigment cells, 32 Pigments, 90 bile, 360 Pituitary body, 431 Placenta, 694 Plants differentiated from animals, 10 Plasma, 101, 115 chemistry of, 139 composition of, 115 percentage of, in blood, 135 reaction of, 136 Plasmosomes, 18 Plethysmogram, 241 Pleurae, 248 Pneumogastric nerve, 558, and see Vagus Pneumograph, 258 Pons Varolii, 543 Postdicrotic wave, 207 Posterior longitudinal bundle, 544 marginal zone, 516 pyramids, 534 roots of spinal nerves, 518, 523 Potassium salts in the body, 94 Poultry, composition of, 299 Precipitins, 129 Predicrotic wave, 207 Presbyopia, 651 Pressor nerves, 216 Pressure, endocardiac, 162 Prickle cells, 27 Pronucleus, female, 692 male, 692 Prophase, 19 Prostate gland, 682 Protamin, 84, 89 Proteids, 79 absorption of, from intestines, 365 action of trypsin on, 336 as fat formers, 410 as glycogen formers, 410 circulating, 409 coagulated, 83, 97 color reactions of, 96 compound, 81, 84 classes of, 80 decomposition products, 87 digestion of, 325 floating, 409 metabolism of, 408, 409 morphotic, 409 nitrogen in, 88 precipitations, 96 properties of, 79" reactions of, 95 simple, 80, 8 1 sulphur in, 89 tissue, 409 Proteolytic ferments, 303 Proteoses, 84, 325 Prothrombin, 106 Protoplasm, i, 2 chemistry of, 3 definition of, 2 effect of stimuli on, 5 growth of, 7 irritability of, 5 movement of, 3 physiological characteristics of, 3 properties of, 2 reproduction of, 7 structure of, 8 Pseudo-nucleoproteids, 84 Ptosis, 550 Ptyalin, 303, 310 action of, 303, 311, 354 Pulse, 2t>4 arterial, 237 dicrotic, 208 variations in rate of, 185 -wave, rate of propagation of, 237 Pulvinar, 547 Pupil, 632 contraction of, 647 INDEX 717 Pupil, dilatation of, 647 center for, 542 reflexes, 647 Purkinje's cells, 562 figures, 653 shadows, 676 Purkinje-Sanson's images, 673 Putamen, 548 Putrefaction in intestines, 347 Pyramids, 534 decussation of, 535 RACEMOSE glands, 294 Ranvier, nodes of, 65 Reaction of degeneration, 474 Red corpuscles, 107 action of reagents on, 133 chemical composition of, 118 , development of , no origin of, no varieties of, no nucleus, 546 Reflex action, 519 time of, 523 arc, 519 centers in medulla, 540 Reflexes, complex, 521 cutaneous, 528 inhibition of, 527 morbid, 527 muscle, 528 simple, 520 special centers for, 526 spinal, 524 tendon, 528 Refraction, 671 Refractory period, 172 phase, 465 Relaxation phase of muscle, 449 Remak's fibers, 66 ganglia, 175 Rennin, 303, 334 action of, 327, 337, 357 reproductive organs, 679 of female, 683 of male, 679 Reserve air, 260, 285 Residual air, 260 Respiration, 243 changes in diameter of chest, during, 284 Respiration, effect of altitude on, 280 of, on circulation, 280 of various gases on, 279 of vitiated air on, 279 expiration, 256 influence of cutaneous nerves on, 288 of general sensory nerves on, 274, 288 of glosso-pharyngeal on, 274 of phrenic on, 289 of superior laryngeal on, 274 of vagus on, 273, 289 inspiration, 253 internal, 244 laboratory experiments in, 283 mechanism of, 253 nervous apparatus of, 272, 288 rhythm of, 258 special types of, 277 tissue, 244 volume of air breathed, 284 Respirations, number of, 262, 283 Respiratory apparatus, 244 elimination of carbon diox- ide by, 271 nervous regulation of, 272 capacity, 260, 285 circumstances affecting, 261 center, 272, 542 automatic action of, 275 stimulation of, 275 changes in air breathed, 263 in the blood, 267 in the tissues, 270 interchange, 290 movements, 253 character of, 283 establishment of, at birth, 277 nervous mechanism of, 288 rate and character of, 287 recording of, 257, 283 relative time of, 258 of nostrils and glottis, 257 murmur, 259 muscles, force of, 262 pressure, 267, 285 quotient, 266 rate, 262, 283 rhythm, 258 718 INDEX Respiratory rhythm, action of stimuli on, 273 terms for quantity of air breathed, 259 Rete mucosum, 392 Reticular formation in medulla, 538 Reticulum, 8, 17 Retiform tissue, 35 Retina, 633 cones of, 636 inverted image on, 672 layers of, 634 localization in, 657 movement of pigment cells, 659 rods of, 636 Retinal image, duration of, 676 relation of size to distance, 676 Retinoscopy, 678 Rheoscopic frog, 470 Rhodopsin, 658 Rhythmical contractility, 170 Rhythmicity of arterial flow, 198 Ribs, movement of, in respiration, 255 Rigor mortis, 461 cause of, 461 heat, 462 order of occurrence, 462 water, 462 Rima glottidis, 245 Rolandic area, 583 Running, 479 SACCHAROSE, 92 Sacculus, 6 1 8, 629 Saliva, 309 action of, on starch, 311, 312, 353 chemical compositipn of, 310, 352 function of, 310 properties of, 310 ptyalinin, 303, 310, 311 quantity of, 310 secretion of, center for, 305 mechanism of, 305 rate of, 310 Salivary digestion in stomach, 313 influence of acids and alkalies on, 354 of temperature on, 353 glands, 304 Salivary glands, changes in, during secretion, 308, 352 nerves of, 351 structure of, 304 secretion, 308 reflex, 351 Salts, absorption of, by intestines, 368 as foods, 300 bile, 341, 360 in the body, 93 tests for, 99 Sanson's images, 644 Saponification, 99, 337 Sarcode, 2 Sarcolemma, 59 Sarcoplasm, 61 Sarcostyles, 59 Sarcous elements of Bowman, 60 ScKeiner's experiment, 673 Schwann, sheath of, 65 Sebaceous glands, 394 Secretin, 334, 345 influence on pancreatic secretion, 334, 358 Secreting glands, 293 production of heat by, 434 types of, 293 organs, types of, 292 Secretion, 291 circumstances influencing, 295 discharge of, 295 external, 291 internal, 291, 427, 431 organs and tissues of, 292 process of, 294 psychic, 355 true, 291 Segmentation, 692 Semicircular canals, 619, 628 Semilunar valves, 148 action of, 157 Seminal fluid, 682 Sensations, binaural, 627 common, 595 objective, 596 of color, 659 special, 596 subjective, 596 Sense, hearing, 614 muscular, 595, 603 of equilibrium, 628 INDEX 719 Sense of pain, 602 of sight, 630 of smell, 609 of taste, 604 of temperature, 600 of touch, 597 organs, directions for experiments on, 669 perceptions, 597 Senses, the 595 special, 597 Sensorium, 596 Sensory areas of brain, 584 illusions, 596 impressions, 529 Serous membranes, 292 Serum, 102 agglutinative substances, 129 albumin, 81 blood, 102, 117 chemistry of, 139 composition of, 117 globulicidal action of, 128 globulin, 82 hemolytic action of, 128 precipitins of, 129 Seventh nerve, 554 Sharpey's fibers, 45 Sight, 630 Silicon, 94 Sixth nerve, 554 Size, estimation of, 668 Skein, 19 Skin, absorption from, 369 amount of carbon dioxide ex- haled by, 396 excretion by, 407 excretory functions of, 391, 395 exhalation from, 396 functions of, 391, 397 glands of, 393 loss of heat from, 434 papillae of, 392 respiratory functions of, 396 structure of, 391 Sleep, 590 Small intestine, digestion in, 345 mucosa of, 364 villi of, 364 Smell, center for, 585 sensation of, 670 Smell, sense of, 609 Soaps, 91 Sodium salts in the body, 94 Solidity, judgment of, 667 Somesthetic area of brain, 584 Somnambulism, 591 Sound, 622 Sounds, articulate, 488, 490 localization of, 626 of the heart, 158 pitch of, 625 Special centers in bulb, 540 sensations, 596 Speech, 480, 490 action of tongue in, 491 mouth in, 491 Spermatids, 679 Spermatocytes, 679 Spermatogonia, 679 Spermatozoa, 679, 680, 682 Spermin, 432 Spherical aberration, 648, 672 Sphygmogram, 206 Sphygmograph, 205 Sphygmomanometer, 194 Sphygmometer, 206 Spinal accessory nerve, 1 560 bulb, 534 centers, 525, 526 cord, 510 antero-lateral ascending tract; 5i6 descending tract, 516 arrangement of nerve cells in, 5ii ascending degeneration of, 5i6 columns of, 514 comma tract of, 516 conduction in, 528 course of motor impulses in, 53<> of sensory impulses in, 529 crossed pyramidal tract, 515 descending degeneration of, 5*5 direct cerebellar tract, 516 pyramidal tract, 515 functions of, 510, 513 Gowers' tract, 516 720 INDEX Spinal cord, hemisection of, 531 intrinsic cells in, 513 irradiation of impulses in, 521 Lissauer's tract, 516 peculiarities of different re- gions, 519 postero-lateral column, 516 postero-marginal zone, 516 postero-median column, 516 reflex action in, 519, 524 reticular formation, 513 tracts of, 514 weight of, 574 nerve-roots, functions of, 523 nerves, 516 anterior roots, 517, 523 course of fibers, 517 posterior roots, 518, 523 reflexes, 524 Spirem, 19 Spleen, vascular nerves for, 224* Spongioplasm, 8, 17 Staircase contractions, 455 Stammering, 491 Starch, 91 action of amylopsin on, 337 of ptyalin on, 311, 312, 353 chemical reactions of, 98 hydrolysis of, 98 Starvation, 420 death from, 420 effect on body temperature, 421 symptoms of, 420, 421 Steapsin, 303, 334, 337 Stercobilin, 90, 342 Stereoscope, 667 Stethograph, 258 Stethometer, 257 Stimuli, forms of, 442 maximal, 454 minimal, 454 Stokes' fluid, 121 Stomach, 316 absorption from, 362 action of pylorus, 328 blood-vessels of, 319 changes in glands during secre- tion, 320 digestion in, 313, 316 gases in, 349 Stomach, glands of, 316 lymphatics of, 319 movements of, 327 nerves of, 316 nervous control of movements of, 329 secretion in, 320 structure of, 316 vascular nerves for, 224 Stomata, 25 Strabismus, 550 Stratum granulosum, 392 lucidum, 392 Malpighii, 392 Striated muscle, 58 development of, 62 Submaxillary gland, action of atro- pine on, 306 paralytic secretion of, 306 secretion of, 306 Substantia nigra, 545, 546 Succus eritericus, 344 Sucking, center for, 542 Sudoriferous glands, 393 Sugar, test for, in urine, 403 Sulphates, 94 tests for, 94 Sulphur in proteids, 89 Sulphuretted hydrogen, effect of breathing, 279 Sulphuric acid in urine, 384 Sulphurous acid, effect of breathing, 279 Summation, 459 of stimuli, 521 Superior laryngeal nerve in respira- tion, 274 Supplemental air, 260 Suprarenal capsules, 428 active principle of, 430 functions of, 428 internal secretion, 431 nerves of, 428 relation to Addison's dis- ease, 429, 431 extract, 430 Swallowing, 313 Sweat, 395 centers, 543 chemical composition of, 395 glands, 393 INDEX 721 Sweat, influence of nervous system on secretion of, 397, 399 Sympathetic ganglia, functions and structure, 591, 594 nervous system, 591 functions, 594 organization and distribu- tion, 591 Synapsis, 520 Synovial membranes, 292 Systole of heart, 154, 156 TACTILE corpuscles, 74, 599 of Meissner, 74 menisques, 75 Taste, 604 after-, 608 buds, 605 center, 587 influence of fifth nerve on, 553 seat of, 604, 607 sensation of, 670 varieties of, 607 Taurin, 341 Teeth, 50 dentine of, 52 development of, 54 enamel of, 53 ivory of, 52 permanent, 51 structure of, 51 temporary, 50 Tegmentum, 544, 545, 546 Telophase, 20 Temperature, body, 433 dissipation of, 435 influence of extreme heat and cold on, 436 regulation of, 434 sense of, 600, 669 variations in, 433 influence of, on muscular con- tractic.i, 456 Tenth nerve, 558 Testes, 679 relation to metabolism, 432 Tetanometer, 499 Tetanus, 459, 499 Thermogenic centers, 439 Third nerve, 549 46 Thoracic viscera, vascular nerves for, 222 Thorax, respiratory changes in diam- eter, 284 Thrombin, 105 , Thrombocytes, 115 Thrombogen, 106 Thrombokinase, 106, 139 Thyroid gland, 427 accessory, 428 functions of, 428 Tidal air, 259, 285 Tissues, connective, 31 elementary, 22 epithelial, 22 interchange of gases in, 272 muscular, 56 nervous, 64 Tone, of artery, 212 of muscle, 172, 525 Tongue, 604 action of, in speech, 491 papillae of, 606 Tonicity of heart muscle, 172 Tooth-pulp, 51 Touch corpuscles, 599 sense of, 597, 669 acuteness of, 599 Tract of Gowers, 516 of Lissauer, 516 Traube-Hering curves, 216 Treppe, phenomenon of, 497 Trigeminus nerve, 551 functions of, 552 Triolein, 90 Tripalmitin, 90 Tristearin, 90 Trochlearis nerve, 550 Trommer's test, 403 Trunk, vascular nerves for, 225 Trypsin, 303, 335 action of, 336 Tubular glands, 293 Tubuli seminiferi, 679 uriniferi, 372 Twelfth nerve, 560 Tympanum, 615 UNORGANIZED ferments, 301, and see Enzymes Unstriped muscle. 57 722 INDEX Urea, 380 amount in tissues of body, 381 antecedents of, 412 determination of, 402 formation of, 381, 411 preparation of, 401 properties of, 380 quantity excreted, 382 Ureters, 377 Uric acid, 382, 402 condition of, in urine, 382 formation of, 413 properties of, 382 tests for, 402 Urinary bladder, 377 Urine, 377 abnormal constituents of, 403 albumin in, 385, 403 ammonia in, 383 analysis of, 399 average daily quantity of con- stituents, 379 chlorides in, 385, 400 creatinin in, 383, 402 cystin in, 385 dextrose in, 385, 403, 404 discharge of, 390 diuretics, action of, 389 excretion by, 407 of, experiments on, 386 factors affecting secretion of, 386 nitration theory of secretion, 386 general properties of, 377 hippuric acid in, 383, 413 method of excretion of, 386 mucus in, 384 nitrogenous substances in, 380 occasional constituents of, 385 oxalic acid in, 385 phosphates in, 384, 401 pigments in, 383, 402 • quantity of , 377, 399 reaction of, 378, 399 relation of blood pressure to secre- tion of, 398 saline matter in, 384 secretion of, theories of, 386 solids of, 400 specific gravity of, 379, 399 sugar in, 403, 404 sulphates in, 384, 400 Urine, urea in, 380, 401 uric acid in, 382, 402 variations in quantity of con- stituents, 379 in specific gravity, 379 Uriniferous tubules, 372 Urobilin, 90, 342, 383, 402 Urochrome, 90, 383 Uroerythrin, 90, 384 Uromelanin, 384 Uterus, 686 Utriculus, 6 1 8, 629 VAGINA, 687 Vagus nerve, 558 effects of section, 560 functions of, 560 relation to deglutition, 315 to gastric secretion, 321 to heart's action, 179 to respiration, 273, 289 Valves of heart, 148 action of, 156 of veins, 154 Vas deferens, 680 Vasoconstrictor ac.tivity, 219 center, 214 nerves, 213, 219, 226 reflexes, 215 Vasodilator activity, 219 center, 218 nerves, 217, 219 reflexes, 218 Vasomotor centers, 543 changes, 241 nerves, 211, 220 tone, 214 Veins, 152 blood pressure in, 195 . . structure of, 152 valves of, 154 vasoconstrictor nerves in, 226 Venous flow, 202 velocity of, 203 Ventilation, 279 Ventricles of heart, action of, 155 Vesico-spinal center, 526 Vesiculae seminales, 680 Vesicular breathing, 259- Vicq d'Azyr,* bundle of, 547 Villi, 361 INDEX 723 Visceral sensations, 529 Vision, accommodation of, 642, 645 binocular, 664 field of, 657 limits of, 660, 672, 677 localization of, 657 ' mechanism of accommodation, 645 range of distinct, 645 Visual acuity, 678 center, 585 judgments, 667 purple, 658 sensations, 652 after-images, 654 intensity of, 654 sense, 630 Vital capacity, 260, 285 phenomena, i Vitellin, 86 Vitiated air, effects of, 279 Vocal cords, 245, 480 movements of, 486 Voice, 480 • difference between male and fe- male, 488, 489 in singing and speaking, 488 production of, 479 quality of, 489 Voice, vocal range of, 488 Vomiting, 330 action of abdominal muscles, 330 of diaphragm, 330 of pylorus, 330 center for, 331 nervous mechanism of, 331 Vowels, 490 WALKING, 475 Wallerian degeneration, 506, 515 Water, 95 absorption of, in intestines, 368 amount excreted, 396, 407 in expired air, 266 in the body, 95 as food, 300 rigor, 462 Weyl's reaction, 402 White fibrous tissue, 33 development of, 36 Wreath, 19 XANTHO-PROTEIC reaction, 96 YELLOW elastic tissue, 33 development of, 36 ZYMOGENS, 302 Handbok of physi. erican rev!