COLUMBIA LIBRARIES OFFSITE HEALTH SCIENCFS STANDARD HX64087662 Q P34 . F59 A textbook of physio RECAP ii!iifi?i!.ii!;;ii;rf;ii.'ii:)i!!!!;jt)ii)iNiiii!; iiiiiiiiiiiiiii ill illitiljilliljjlJIJIJIiJiil!! TIITTTniTTITITiilTTiTTiJ iFpartm^nt of pti^siologg A TEXTHOOK OF rilVSlOLOGV Digitized by the Internet Archive in 2010 with funding from Columbia University Libraries http://www.archive.org/details/textbookofphysioOOflac A TEXTBOOK OF PHYSIOLOGY BY MARTIN FLACK C.B.E., M.B., B.Ch.(Oxon.) RESEARCH STAFF, DEPARTMENT OF APPLIED PHYSIOLOGY, MEDICAL RESEARCH COMMITTEE ; LATE LECTURER IN PHYSIOLOGY AND CHEMICAL PATHOLOGY LONDON HOSPITAL MEDICAL COLLEGE ; AND LEONARD HILL M.B., F.R.S. DIRECTOR OF APPLIED PHYSIOLOGY DEPARTMENT MEDICAL RESEARCH COMMITTEE LATE PROFESSOR IN PHYSIOLOGY (LONDON UNIVERSITY) LONDON HOSPITAL MEDICAL COLLEGE ILLUSTRATED NEW YORK LONGMANS, GREEN & CO. LONDON: EDWARD ARNOLD 1919 [.4// ri^/its resefve1E(HANISM I.XXII. THE SPINAL (OLD . . . . . I.XXIII. THE HIiAJN ...... LXXIV. SLEEP ....... LXXV. SOUND PRODUCTION AND SPEEt H LXXVI. THE AUTONO.MIC NERVOUS SYSTEM ;•)()!) 57!) 58.5 593 59!) ()4;5 (i.-4 (5(52 685 735 73!t 74S BOOK XIII.— REPRODUCTION LXXVII. OROWTH AND REPRODUCTION - INDEX .----- 755 785 A TEXTBOOK OF PHYSIOLOGY BOOK I GENERAL PHYSIOLOGY CHAPTER I BIOLOGICAL INTRODUCTION Living in the stagnant water of most ditches is the tiny animalcule known as the Amoeba (Fig. 1). If a drop of water containing this little •organism be placed on a slide beneath the lens of a microscope, exami- lU.V, ' 6' .'^■'.''o ■::&>.'/ ■.•v..°'v'';.-'(5'*'.-i-.- i "•X©. ''■.■?• i-:-' ; ;*.--. ... o", *••; "J ?yr n. c.v. Fig. 1. — Amceba Proteus, an Organism consisting of a Single Naked Cell. X 280. (Redrawn after Sedgwick and Wilson.) iV, Nucleus; v).v., water- vacuoles; c.v., contractile vacuole; /.),■., food vacuole. nation shows that the tiny animal consists of a mass of semi-fluid material known as protoplasm. Scattered in this semi-fluid mass HV810LO(iY structure, the nucleus. 01)servation shows that the ania-ha gradually moves about in the fluid — here thrusting out one little foot-like mass, or pseudopodium, there retracting another, and thus ju-ogressing. If it be touched in an}- way, the pseudojiodia are withdrawn. The organism thus responds to a stimulus, and possesses what is termed irritability. Should there, perchance, be any food material present, such as algse, it may be seen how, by means of the pseudopodia, the food is surrounded and gradually absorbed into the ])rotoi)lasmic mass. This food is gi-adually broken down, digested, and assimilated, any indigestiljle or waste material being latet extruded from the surface. From time to time the vacuole contracts, voiding by this process waste products of the animal's activity. Finally, under favourable circumstances, the little animal may be seen to grow, and eventually divide into two organisms, thereby reproducing itself (Fig. 2). ^;i^j K_y Fig. 2. — Successive C'hais(ges exhibited by an Amceba. (Vcrvvorn from "Quain's * Anatomy.") The amoeba is a type of what is known as a unicellular organism; it consists of but one unit or cell. That one cell performs all the life-processes. All organisms, however, are not so simjDle in structure; the higher forms of life consist of a great number of cells, and are therefore termed multicelli lar. The multicellular organisms have been evolved from the simpler unicellular one — in some cases through an almost infinite number of stages. Past history, or phylogeny, as shown by fossil remains, indicates that, as the ages passed, animals gradually became more and more complex in structure. Some of the simpler forms have continued to exist, others have become lost. So, too, of the evolved multicellular forms — many continue with us, but some have passed away. The abilit}" of an organism to maintain its life depends upon its power to adapt itself to existing conditions — upon its being efticient. The multicellular organism developed its efficiency over the unicellular organism along two lines: BIOLOGICAL INTRODUCTION 3 first, b}' forming a colony of individuals; secondly, by instituting a differentiation of cells, with a division of labour. In the first method, the formation of a colony of similar cells, the cells, like the amoeba, still carry out all the life-functions indi- vidually; each cell lives alone. The number of cells in such a colon}' is not limited; it is but a group of individuals, not one individual. Certain protozoa and protophyta exist as colonies. An example is Carchesium (Fig. 3). In a little more advanced order of colonization the number of members of the colony is limited and kept constant, death of a member being followed b}- replacement. Such a colony is generally ensheathed by a wall, so that the cells have no independent movement. With these limitations, each cell of the colony performs its vital functions independently- . An example of such a colony is Gonium (Fig. 4). Fig. 3. — A Colony of Individuals of Carchesium, ATT.iCHED by a Common Branch- ing Stalk, showing /, the Contractile Stalk of One Individual. ' (Reray, I'cdrivvn after Dahlgron and Kepner.) In the second method a differentiation of cells, with a division of labour, takes place. Here the colony becomes the individual not a group of individuals. The members of this group range from a simple multicellular organism to man. Volvox globator (Ficr. 5) represents the beginning of this type of organization. In it certain cells become differentiated for the main function of life — reproduction — each of the other cells performing all the other functions. In the higher organizations certain cells become segregated and form a tissue— that is, a group of cells performing more or less one definite function. Later the differentiated tissues become grouped into organs, each having some particular function. Nevertheless, each cell remains a separate living unit, having its own share of work to perform. The developmental history — ontogeny — of the multicellular organ- A TEXTBOOK Ol' PHYSIOLOOY 1 u; 4. — GoNiirM Pectokale, showiisx, the Individuals. (From Tahlgren and Kepnor, after Stern.) Fig. 5. — Volvox Globatoe, a Colony of Cells in which All the Cells aee con- EINED TO THE SuEFACE OF THE SpHEEE, LEAVING A CaVITY InTEEIOELY. (From Dahlgren and Kepner, after J. H. Emerton.) The cells are united by protoplasmic strands radiating from each cell. The dif- ferentiated cells, or ova, are shaded dark. BIOLOGICAL INTRODUCTION 5 isms confirms the evidence of the past history, or phytogeny. Each multicelhilar organism develops from a single fertilized egg, or oosperm. The fertilized cell at first divides, and divides again to form many similar cells. These cells then become differentiated into various tissues, which eventually become grouped to form different organs (p. 773). In the course of development a three-layer blastoderm is formed. From the outer laj'er — ectoderm — chiefl}^ the epithelial protective and nervous tissues are developed; from the middle layer— mesoderm — the supporting and muscular tissues; from the inner — endoderm — the respiratory and alimentary tissues. By the name of epithelium is designated the tissue lining the outer and inner surfaces of the body. Occupying this position, its main function is that of transferring material from the surfaces to the tissues within. It also plays a part in protecting the underlying organs, and in receiving stimuli and transforming these into sensory nerve impulses. From it, also, the glandular structures of the body are developed — e.g., salivary glands, glands of stomach, intestine, etc. The supporting and connective tissues are developed to give rigidity and tensile strength to protoplasm, and thus enable the mul- ticellular organism to preserve a definite form. For these purposes fibres, plates, and such massive structures as the bones, are formed. The ligamentum nuchse of the ox affords an excellent example of tensile strength, while the shells of molluscs and cartilaginous and bony structures testify to the great rigidity which may be developed. Cells of like origin may also act as a storehouse of food material — ■ e.g., fat. The muscular tissue has become developed, not only to move the organism from place to place, but also to assist in the internal opera- tions of the stationary organism — for example, the heart, cilia, etc. Its essential property is the power of contraction. By a combination of thes3 three tissues, epithelial, connective, and muscular, the outer covaring parts, or integument, of the body is formed. One of the chief functions of this integumsnt i^ to protect the expovsed outer parts of the body from dangers to which it is sub- jected, whether the animal live in the water or in the air. This it can do both mechanically and by the production of means of defence — e.g., poison. The integument possesses also lubricating and cleans- ing powers. Sometimes, too, it has the power to produce attractive or repulsive odours, to prepare adhesive material, or to spin. Examples of mechanical protection are seen in the stiff fibres developed by many lower animals — e.g., the turbellarian worms, to protect against undue pressure ; the cuticle of the earthworm ; the carapace of the lobster and the shell of the tortoise; the scales of fishes and of birds' legs; the feathers of birds and the hair of animals; the outer covering of the human skin generally, and in particular the thickened areas of the palms of the hands and soles of the feet. Various examples of offensive protection may also be given. Formed within the cell are the trichocyst of paramoecium, the rhabdites or C A TEXTBOOK OF PHYSIOLOGY stylets of the turbellarian worms, the stings of the nettle colls of hydra. Built by ((lis are the stings of bees and wasps, the poison hairs in the larva? of some moths, the ])()ison glands of some spiders, the stinging spine of the weaver-fish and of the whip-ray, the weak poison of the ]tectoral fin of the cat-fish, the spine of the porcupine, the claws of the higher animals, and the nail of man. The integument may provide lubricating material either all over the body surface or onl}' in special areas. The lubricant material may at the same time serve additional functions-^for examjile, as a preservative from water, as a cleanser, or as a food-gatherer, and so forth. The lubricating material may be slimy (mucus), oily, or watery, in nature. The mucus provided by certain of the clams serves the purpose of lubricating, and also of removing dust and aiding the collection of food. The slime produced by the earthworm serves the double purpose of lubricating the animal and of preparing its dwelling-place. The mucus of the salivary glands of the mammal and of the mucous cells lining the alimentary tract is both lubricant and protective. The second form of lubricating material, that of an oily nature, is found in the higher animals (birds and mammals). It is a protec- tion against both the drying of the skin and the wetting of the feathers, hair, or skin. Such a material is formed in the oil glands, b}' which birds oil their feathers, and in the sebaceous glands, by which the hairs and skin of mammals are kept greased. Sometimes these oils possess a distinctive scent, either repulsive or agreeable; such is the case, for example, in the musk rat, musk ox, and the skunk. The watery (serous) form of secretion is comparatively rare. Possibly the lachrymal glands moistening the eyes of mammals, and the sweat glands moistening the skin, may be grouped here, as well as the secretion which lubricates surfaces of joints, the synovial fluid. By the evaporation of sweat the body is cooled. Among the lower animals an extremely adhesive fluid is sometimes l^rodviced, which enables them with the aid of a sucker or pad to stick to surfaces — e.g., that of the head of the leech and the legs of beetles. In other cases the adhesive fliiid hardens into a thread; thus the cocoons are formed by the spinning glands of the larvse of moths (silkworm). Many of the lower animals also possess odour-producing glands — e.g., the skunk; a well known example also is the so-called stink-pot turtle. Other reptiles — for example, the American toad (Bufo) — produce an extremely offensive fluid. The secretion of Bufo is partly mucous, partly serous, and it is said to be poisonous. But it is among the invertebrates that this power of producing offensive and attractive odours, as judged by man, has been reduced to a fine art. Various butterflies produce distinctly j)leasant odours. Such odoriferous glands are situated in various parts of the body or wings. But besides rendering themselves efficient in this direction, the multicellular organisms have developed other systems of tissues, well adapted to meet the conditions under which the animals live. With BIOLOGICAL INTRODUCTION 7 the division of labour there is elaborated [a) an alimentary system, by which the necessary foodstuffs are taken into the organism and reduced to a proper state for absorption; (6) a respiratory system, by which the oxygen necessary for the cell processes is introduced, -and the carbon dioxide produced by these processes eliminated; (c) a transport and circulatory s^^stem, b}' which these necessaries are conveyed to all the body cells to supply their needs, and the laroducts of cell activity conveyed away for excretion either by the respiratory mechanism or by (d) a specially developed excretory .system. Finally there remain two special systems — the nervous and the reproductive. The nervous sj^stem serves to put the organism into communication and correlation with outer chemical, physical, and mechanical conditions. It does this by its receptor, conductor, and effector functions. It is irritable, and receives a stimulus either directly or indirectly, conducts the stimulus as a nerve impulse, dis- charges it on some other cell or cells, and the e produces its effect. The system is primarily intended for communication between parts of the body more or less widely separated; in the higher animals it becomes an extremely complicated system, and according to its degree of comj)lexity and the manifold functions it perfo:-ms, so is the organism classed by man in the ladder of life. Man, placed by himself at the top of the ladder, has the most complicated and most highly developed nervous system. To the reproductive system is assigned the highly important function of maintaining the particular species of the organism. In the multicellular organism, the cells other than the reproductive cells perish after a longer or shorter period of exist- ence. But the reproductive cells, under appropriate conditions, give rise to fresh individuals, thereby perpetuating an unbroken chain of living cells. Physiology is the science which treats of the normal functions of these various systems. CHAPTER II THE CELL During the latter part of the seventeenth century the simple micro- scopes of the day demonstrated that plants were composed of small box-like spaces surrounded with a distinct wall, and filled with lic^uid. The name of cell was given to these. In 1839 Schwann put forward the theory that the animal body was built of cells. The identity of ];)rotoplasm in all forms of life, plant and animal, was established, and the cell defined as a nucleated mass of protoplasm. The cell may be regarded as a working unit of protoplasm. The body of a cell consists of a substance called protoplasm or cyto- plasm (Fig. 6). In the young living egg cell (such as echinoderm ova), the structure appears homogeneous, like egg white; while in older cells it appears alveolar or reticular. To bring structures into view,^ and to enable thin sections of organs to be cut, fixing and staining reagents are used. The reagents which are used to fix and harden tissues for microscopical examination, such as alcohol, a saturated solution of mercuric chloride, etc., coagulate protoplasm and j)roduce thread-like and granular precipitates in cells — artefacts — which often produce appearances of structure not existing in the living cells. Svich granules and fibres apjDcar in homogeneous solutions of egg white or peptone when treated with hardening reagents. We must not draw conclusions as to cell structure without comparing the fixed with the living cell. The same method of hardening — i.e., the same chemical process — can, however, be justly used to compare the structure of normal with that of abnormal organs. Reagents can also be used to investigate the chemistry of the cells ; to identify in them by different staining reactions fat, glycogen, iron, potassium, etc. This is a valuable method of microscopical studj\ The essential structure of a living cell appears to be a homogeneous fluid material studded with a large number of minute granules (Fig. 7). Between these two phases, granule and fluid, physico-chemical changes take place which manifest themselves in the life of the cell. The foam structure of protoplasm can be closely imitated by rubbing up oil with potash or sugar into a very finely divided paste. A drop of this is jDut into a drop of wat^r on a microscopic slide. The water is attracted h\ the osmotic pressure of the potash or sugar and produces the foam. Radium bromide powder dropped into a gelatin and broth medium produces cell -like structures which increase in size and divide, multiiDlying, apparently, like a living organism. The radium gives off an emanation, the product of its. 8 THE CELL 9 atomic energy, and this is accompanied by heat. The emanation coagulates the protein and decomposes water into oxygen and hydrogen producing the " cells," really bubbles of gas surrounded by a coagulum. As the gaseous emanation continues to form, " cells " grow — i.e., the bubbles bulge out, burst, and form new bubbles. There is no production of life in these phenomena. They are of interest as show- ing ways in which an alveolar structure may be formed in colloidal solutions. The atomic energy made evident to us by radium may ncl. yk . a/.i _ Fig. 0. — Ovum of a Cat Just Before Matueitv. (Redrawn from Dahlgren and' Kepner. ) Cm., Cell membrane; n.m., nuclear membrane; nd., nucleolus; mics., microsomes; yk. al., yolk alveoli. possibly be a form of energy of fundamental importance in living matter, although the elements into which livmg matter is decomposed are, as far as we can see, stable. If an unstable mixture be made of two sterile colloidal solvitions of opposite electrical sign., such as fsrric hydrate ( + ve) and silicic acid ( — ve), and be left standing, growth-like structures appear, simulating in outward appearance simple Hving protoplasmic forms. The granules so frequently lodged in the cell may be fat, pigment, glycogen, or protein. The last may stain either with a dye possessing 10 A TEXTBOOK OF PHYSl()LO(iY an active acid radicle — e.g., prtassium chroma' e — or one with an active basic radicle — e.g., rosanilin acetate. The graniile.-i with affinity for acid radicles are basic, those for basic are acidic in nature;' still other granules are neutral and stain with both radicles: the names given for these are respectively oxyphil, basophil, and neutrophil granules. The first and last are most common. A constant element of the cell is the nucleus. It consists of nuclear plasma and nuclear network. The form of the nucleus varies, but corresponds in general to the shape of the cell — large and round in nerve cells, long and oval in involuntary muscle fibres, irregular neck- lace-shaped in leucocytes. Especially large nuclei are found in young ova and nerve cells. The nuclear reticulum consists of granules of nuclein, which stain deeply with basic dyes, and is thus called chro- matin bv histo'ogists. The basic affinitv of nuclein is due to the Fig. 7. -Yeast Cells photographed by Ultraviolet Light iHRouiiu Quartz LENSE.S. (Barnard.) nucleic acid it contains. This substance is rich in phosphorus, as may be shown by sjoecial staining methods. The nuclein granules are embedded in a less stainable network — the linin. Embedded in the nucleoplasm are one or two larger granules which do not behave to chemical reagents in the same way as the nuclein ; these are called nucleoli. Surrounding the resting nuclevis is a perforated nuclear membrane, through which cell protoplasm and nucleoplasm are in continuity. The nucleus seems to be the mainspring of the cell's activity. Wherever in a cell growth is active, there seemingly is placed the nucleus (Fig. 8). It controls the cell metabolism and its reproduction. In the case of the protozoa, when the nucleus is separated off with one part of the ceil, that part grows; the remainder ceases to grow, and dies. THE CELL 11 The complicated structure of protoplasm, and the fact that it is constantly in a state of flux and change, prevent its existence in large masses It must be intimately bathed Avith the fluids that feed and cleanse it. Hsnce the cellular structure, and the evolution of circu- latory mechanisms in the higher multiceJluJar animals. Protoplasm, in order to live, must protect itself from extremes of temperature, and from other active physical or chemical changes which split up its Fig. 8. — To show the Migration of the Nucleus to the Point of Growth in Plants. (Redrawn after Haberlandt, from Wilson's " The Cell," etc.) A, Young epidermal cell of Luziila, with central nucleus before thickening of the membrane ; B, three epidermal cells of Monstera during thickening of outer wall; (7, cell from seed coat of ScopuUna during thickening of the inner wall; D, E, position of the nuclei during the formation of branches in the root -hairs of the pea. molecules into simpler (dead) compounds. It must have the food necessary to keep up its cycle of change served to it in proper form. Protoplasm, therefore, moves, not onl}' to find food, but to avoid injurious influences. Protoplasm moves by effecting a redistribution of its substance, and certain parts are especially set apart, so situated as to produce definite changes in the shape of the living organism, and so differentiated in structure as to ]ierform rapid movements — cilia, muscles. It is well to remember that movement in response to ex- 12 A TEXTJiOOK OF PHYSIOLUCY citation is by no means confined to the living world. Heat and mag- netism cause movements in inanimate matter, and the response of living matter to certain foims of excitation appears to be as inevitable as the lengthening of an iron bar when heated. The unicellular animals move either by flowing out in one or other direction, a part forming a pseudopodium, and the rest following, or by means of vibratile lashes, the cilia, which are set round the circumference of the cell body or at one or othei' pole. A pseudo]X)dium may be imitated by a capillary tube filled with mastic varnish. This will extend a pseudopodium towards and eventually engulf a glass fibre wet with alcohol. A glass fibre covered with shellac is taken up by a chloroform drop (Figs. 9a and 9b). Movement is excited by the various chemical and physical forms of energy, and may be toward the source of energy or against it — positive or negative. The slime fiuigus, Myxomycetes plasmodium, Fig. 9a. — A Glass Fibre Wet with Alcohol BEiKG Engulfed by a Pseudopodium of Mastic Vaknish. (After Ehumblcr.) Fig. 9b. — A Glass Fibre Coated with Shellac, taken up by a Drop of Chloro- form. (After Rhumbler.) forms, by the union of many amoeba-like cells, a sheet of protoplasm which spreads for many inches, over rotten woods. The plasmodium shows marvellous veins in which granular p)rotoplasm streams, with extraordinary rhythm, first in one and then in the reverse direction. The Plasmodium flows towards and over its suitable food, digesting and absorbmg as it goes. It is attracted by certain chemical sub- stances— positive chemiotaxis. It is repelled by others, e.g., a trace of Cjuinine, or too concentrated a solution of salts, etc. — negative chemiotaxis. Similarly, paramoecia or opalinse gather round a drop of dilute acid, and are repelled bj^ dilute alkali. H - ions exert a positive and HO + ions a negative chemiotaxis. Paramoecia exhibit positive galvanotaxis to the negative pole of a constant current. They gather round this pole when the current is passed through the drop of water containing them. Tadpoles turn their heads toward the anode. The}' avoid one end of a trough if this be heated to 25°-30° C, and seek the cooler end — negative thermotaxis. They seek red light and avoid the blue — phototaxis. Worms, earwigs, etc., placed in a box with a THE CELL 13 cover half blue and half red, and exposed to sunlight, are disturbed by blue light, and actively move till they finalty come to rest under the red. This exciting effect of blue light acts on the skin and produces its effect even in blind animals. It is the most refrangible rays of the spectrum, the so-called viltra-violet raj^s, which have the marked effect on living matter. These rays produce in us sunburn, followed by a protective pigmentation of the skin. They act as a bactericide, e.g., the tubercle bacillus is killed by light and the powerful arc light (the Finsen light) is emploj^ed to cure lupns. The exclusion of all but red and yellow rays from the sick-room is said to prevent the sup- puration of the eruption in small-pox The black man is protected from the ultra-violet rays by his pigment. Similar but more ]iowerful effects are produced by mercury vapour lamps enclosed in quartz. The light from these lamps is particularly rich in ultra-violet rays, since the •spectrum of mercury vapour contains many bright lines in the ultra-violet region of the spectrum, and quartz, unlike glass, is easily transparent to the rays (Fig. 10). As a rule cells are small in size, some few thousandths of a millimetre in diameter. Occa- sionally—for example, the egg of a bird — the cell is macroscopic in size, owing to the large amount of vegetative or nutritive cytoplasm present. The shape varies more than the size. In the various tissues it becomes modified to almost any shape — flat discs, cubes, hexagons, ' rods, or branching forms. There is an individuality of the cells of the multicellular organism. Their power to survive removal from the body is very great; thus, the sperm of the drone is received by the queen bee in her nuptial flight, and remains active for the rest of her life in the receptaculum seminis. In the cloacal sac of the female salamander the sperm is retained active for two years after copulation. The bat is Aved in autumn, and be- comes pregnant after her winter sleep. Living spermatozoa have been found eleven days after excision in the excised testicles of guinea- pigs kept at 0° C. Living human spermatozoa have been found in the uterus eight and a half days after cohabitation. The leucocA'tes of the frog showed amoeboid movements after being kept tliree weeks in a moist chamber. Dog's blood kept ten days on ice has been successfully transferred into a dog. Movement of ciliated cells has been observed in a tumour eighteen days after its removal from the nose. Pieces of the mucous membrane of the frog's mouth ])\\t in the dorsal :^:^ Fig. 10. — Lesions produced by the Ultra - Violet Rays acting upon the Rabbit's Ear screened by a Piece of Black Cardbo.^rd, from which THE Design AND Letters were Cut Out. (After V. Henri.) 14 A TEXTBOOK OF PHYSIOLOGY lymph sac of the same animal showed active cilia after five months Pieces of hmnan skin kept in ascitic fluid for at least one week have grown on trans])lantation. The cornea of a hare kept at 0° C. has survived nine to twelve days, and l)een successfullj^ transplanted. The excised heart of a three-months-old child has been made to beat twenty hours after death. In the last few years the survival of tissue Fig. U. — Camera Lucida Drawixc; of Cells from the Heart of Rabbit's Embryo (Sevek to Eight Days Old) growing in Culture Medium. (N. C. Lake, from Journal of Physiology.) A. Main mass of tissue; B, degenerate cells; C, inner columnar cell; D, liquefied medium; A', protoplasmic thread; F, outer spindle cell; G, fibrin network with blood platelets at nodes; H, nucleus showing chromatin; /, tendency to striation. cells has been extensively studied, and the question arises as to whether true cultures are obtained. The growth of nerve cells has been studied in pieces of the frog embryo j^laced in clotted frog's lymph. By repeatedly alternating the life of the tissue, first putting it in a culture medium and warmth and then in Ringer's solution and cold, pulsating pieces of heart muscle have baen kept for three months. Cell move- THE CELL 15 luent in cxplanted tissue has been kinematographically studied. Such cells use the threads of fibrin of the plasma medium as guides in their wanderings. While the cells of explanted tissues live and multiply, it is doubtful how far they show the characteristics of the particular tissue.^ It is said the new-formed cells take on an indifferent character, and never show the characteristic formation of the mother organ. If true cultures of the cells' organs could be obtained, the method would lend itself admirably to the stud}' of histogenesis, metabolic processes, age and death phenomena of cells. It has, however, been claimed recently that contractile cells which must be considered muscular have been obtained by culture of the cells of the heart of the embryo ra1)bit (Fig. 11). The phenomena of movement, irritability, the digestion and ab- sorption of food, its assimilation and dissimilation, the excretion of waste materials, growth and reproduction, are essentiall}^ those of living matter. Phj^siology is the study of such life processes. These processes in part conform to the laws of physics and chemistry which have been found to govern matter generally. Of much, how- ever, at present the explanation is not clear, and to expess the reactions of living matter terms such as " biological force," '"vital force," and " biotic energy," are often employed. The use of such terms does not, or should not, indicate that there is any deep and unfathomable mystery about life phenomena other than that hitherto insoluble mystery which enwraps the universe, and conceals from us the ultimate origin and the nature of what we choose to term matter and energy; rather, it means that the phj-sico-chemical laws governing matter have not yst been sufficiently found out to render clear the interpretation of living processes. With each fresh advance in natural science the phenomena of life are being correlated with phenomena of non-living matter, and there can be no doubt that with a fuller knowledge of chemical and physical laws manj^ of the processes now labelled '' vital " will be capable of being grouped under these laws. To say this does not lessen the dignitj^ of the conception of life; rather, it exalts, by unifying, our general conception of the universe. A certain arrange- ment of matter acts as a transformer through which the phenomena of life become manifest. The universal source of energy, whatever it may be, becomes transformed into the various manifestations of energy which we call life, including the workings of Mind. In dead matter the transformations of energy are otherwise in character, but the play of energy is no less ceaseless in character, no less beyond final explanation, no less worthy of veneration. Nothing is common or simple to him who has really probed into the secrets of Nature. The following has been put forward as a tentative sj^eculation on the origin of life : The whole world of living plants and animals depends for its present continuance upon the synthesis of organic compounds from inorganic by the green colouring matter of the plant acting as a transformer of light energy into chemical energy. This present stats of affairs must have been evolved from something more simple existing at the com- 13 A TEXTBOOK OF PHYSIOLOGY mencement. For chloroijliyll, which now acts as the transformer, is itself one of the most complex of known organic substances, and could not have been the first organic substance to be evolved from inorganic matter. In considering the origin of life, therefore, the start must be made in a purely inorganic Avorld without a trace of organic matter, either plant or animal. Recently it has been shown that, when dilute solutions of colloidal ferric hydroxide, or the corresjionding uranium compound, are exposed to strong sunlight, or to the ultra-violet Ta,ys of .a quartz mercury arc, there are synthesized the same organic compounds which are at present formed as the first stage in the process of organic synthesis bj^ the green plant — namel}', formaldehyde and formic acid. Taking the ^ iew that the earth arose from a gaseous nebula, it may be assumed that at first, as the planet cooled down, only elements were present, at a lower temj)erature binary compounds formed, next simple crystalloidal salts arose. Then, by the union of single molecules into grouj)s of fifty or sixty, large molecular colloidal aggregates ap2:)eared. As these non- diffusible or colloidal aggregates increased in complexity, they also became more delicately balanced in structure and labile — that is to say, they were easily destroyed by sudden changes in environment, but, within certain limits, were peculiarly sensitive to energy changes, and could take up energy in one form and transform it into another. These labile colloids took up water and carbon dioxide, and, activated by the sunlight, produced the pimj^lest organic structures. Next these simpler organic structures, reacting with themselves, and with nitro- genous inorganic matter, continued the process, and built up more and more complex, and also more labile, organic colloids, until finally these acquired the property of transforming light energy into chemical energy. By the continued action of this " law of molecular complexity " life originated. Such an origin of life was no fortuitous accident, and the same processes are still guiding life onwards to higher evolution in a progressive creation. CHAPTER III PHYSICO-CHEMICAL INTRODUCTION The cells of the boch' are bathed in solutions containing Ijoth col- loids and crystalloids. The phenomena exhibited by substances in solutions are closely related to those exhibited by gases, concerning which the basic facts are better known. The fundamental gas laAvs, proven by experiment, may be grouped, two as physical, and one as ■chemical, in nature. The first law is that the volume occupied by a given mass of gas varies inversely as th" jjressure to which it is subjected, provided the temperature is kept constant (Boyle's law). Experimental work has shown that for ■ordinary gases under ordinary conditions Bojle's law may be taken as accurate. The second law is that the volume occupied by a given mass of gas, kept under constant pressure, increases as its temperature is raised, and the relative expansion is approximately the same for all gases (Gay- Lussac's law). It is found that the volume of a gas increases by ^U, of the volume it occupies at 0^ C. for a rise of 1° C, always provided the jjressure remains the same. From these two laws it can be shown that the pressure exerted by a given mass of gas kept at constant volume increases with rising tem- perature in the same proportion as the volume increases at constant pressure. The third law is also associated with the name of Gay-Lvissac. It is the law of volumes. It states that, when tivo gases combine with each other to form, a third gas, the volumes of the reacting gases are in simple ratios to one another and O the volume of the gaseous product, all being measured at the same temperature and pressure — for example, one volume of hydrogen combines with one volume of chlorine to form two volumes of hydrochloric acid. On one hypothesis (Avogadros) regard- ing the nature of gases, it is supposed that equal volumes of different gases measured at the same temperature and pressure contain the same number of molecules or ultimate particles. The molecules are rot the same thing as the atoms of an element; a molecule may contain one, two, or more atoms, and the element is univalent, divalent, trivalent, according to the number of atoms its molecule contains. Diffusion. — A characteristic feature of a gas is its ability to occupy with great rapidity any space afforded it. If two vessels containing different gases at the same pressure be put in communication with each other, the gases gradually mingle, each moving from places of high concentration to places of low concentration until the partial pressure 17 2 18 A TEXTBOOK OF PtnSJOLOOY of each gas is the same tliiougl.out and cquilibiiiun is attained. This is termed the process of diffusion of gases; it is a molecular process, and takes place independently of any movement of gas as a whole by stirring. Diffusion is a relativel}^ slow process, and the mixture of gases is very greatly accelerated by stirring — e.g., in the lungs. Ex- perimentally it was found by Gr-aham that the velocity of " effusion," as he termed it, of a given volume of any gas is inversely proportional to the square root of its density. His experiments consisted in determining the times taken for a given volume of various gases, kept Fig. 12.— Kydkcgen Generated from a Kipp"s Apparatus is liberated in the Neighbourhood of the Porous Pot. The Hydrogen diffuses into the Pot Quicker than the Air diffuses out, so that Water is forced up the Tube out of the Woulffe's Bottle. at CQUStant pressvire, to pass through a minute hole in a metal plate into a receiver, which he kept constantly evacuated. This law, governing the rate of diffusion of gases, is well shown by the experi- ment illustrated in Fig. 12. Experiments have been made in which the diffusion of a gas is observed through a tube, when the concentration of the gas at one end is kept at zero or at a constant low value. For example, when caustic potash is kept at the bottom of a tall cylinder full of carton dioxide, there is a constant flow of carbon dioxide to the potash at the bottom of the cylinder; the flow is inversel}' proportional to the PHYSICO-CHEMICAL INTRODUCTION 19 length of the diffusion cohimn. The same holds good for the diffusion of water vapour into strong sul})huric acid. If a diaphragm be placed at the free end of the diffusion column, it is found that the amount of gas which diffuses is proportional to the diameter of the ajierture, and not to its area. Another remarkable fact is that, if in the diffusion tube a diaphragm be pkiced containing many minute perforations, the diffusion flow is checked but little or nil, each aperture in a multi- perforate diaphragm acting independently of the others. It has been found that the assimilation of CO., by the leaf of a plant is due to a similar process of diffusion. If the stomata or pores of the leaf be blocked, no assimilation of CO.^ takes place. The amount of CO., entering the leaf depends on the concentration of CO^ inside the leaf and the linear dimensions of the stomata. It is found experi- mentally Avith leaves of Helianthus that the amomit of CO^ taken in is but a fraction of the amount calculated for the leaf as a mult iperf orate septum. This is because the gas, having sntered the stomata, has to pass into solution in the leaf fluid —a relatively slow process as compared with gaseous diffusion. This brings us to the next point — the passage of gases into solution in water. The power of v\ater to dissolve a gas varies markedly with the nature of the gas : the solubility of the same gas in the water also varies with the temjieratiu'e and the pressure at which the absorption is taking place, and with the concentration of other substances in solution in the water. In regard to temi^erature, the solubility di- minishes as the temperature rises. The solution of the gases of the atmosphere in fat, on the othov hand , is independent of the temperature. In regard to pressure, it is found that the quantity of gas dissolved, either by weight or A'olume, at normal temperature and pressure (N T.P.) in a given volume of water at a given temperature is directty proportional to the pressure; thus, by doubling the pressure twice as much gas passes into solution (Henry's law). The definite relationship between the gas and the absorbing fluid is sometimes termed the " absorption coefficient " — that is, the volume of gas reduced to N.T.P. which is taken up b}' that volume of the fluid under the normal pressiue of one atmosphere. In the following table the absorption coefficients are given for oxygen, nitrogen, and CO.,, in v/ater. "emp. Oxi/jen. X itro'jiii. Carbon Diox\de. {\° 0-0 iS9 0 0230 1-713 10= 0-0380 o-oior. 1-101 20" ()-0310 0-01(34 0-S7S 30^ ()-02(i2 0 0138 0-G65 40" 0UJ31 0-01 IS 0-520 The table shows that the absorption coefficient of nitrogen in water at 30° is 0 0138 — that is to say, one c.c. of water at 30° C. absorbs at atmospheric pressure 00138 c.c. of nitrogen measured at N.T.P. It also shows that oxygen is more soluble than nitrogen, and CO., more soluble than either. Fat dissolves between five and six times as much of these gases as water. 20 A TEXTBOOK OF PHY,SrOL()(;Y Diffusion oJ Gas through a Liquid Film. — The solululitv of a gas is important iu (U-tt'iiiiiiiing the })a.ssage of a gas through a watery fihn. It is found that the velocity of its diffusion is directly ])ro- portional to the absorption coefficient of a gas in water. It is also found that, other things being equal, the amount of gas passing from the ])lace of high ])ressure through a Avatery film to the ]ilace of low pressure is proportional to the difference in pressure of the gas on the two sides of the film. The importance of the first factor may be demonstrated as follows: A piece of pig s bladder is tied over one end of a short wide tube. The other end of the tube'is closed by a rubber cork through which is passed a narrow glass tube, which passes to a manometer containing coloured water or to some other mechanism for recording change in pressure. The membrane is now impregnated with water; it is important to note that membrarics dried in air are almost if not quite impermeable to such gases as carbon dioxide and oxygen. A beaker containing a gas is then inverted over the tube carrying the membrane. If the gas be hydrogen, no movement of fluid is recorded bj" the manometer. On the other hand, with a very soluble gas such as ammonia, a rise of pressure is shown in a short time. The exchange of oxygen and carbon dioxide in aquatic plants depends upon the power of the water to dissolve these gases, and on the diffusion of the dissolved gases through the membrane of the plant, which is impregnated with water. If the medium in which the plant lives be freed from air, the plant dies. The process of the diffusion through the walls of submerged plants has been shown to follow the laws cited aljove; the gaseous interchange is therefore a slow process. On this account the oxygen and carbon dioxide liber- ated in the assimilatory and respirator}' processes of the plant are stored in intercellular sjoaces and kept for future use. This is particu- larly the case in the parts of aquatic plants Avhich are embedded in the mud at the bottom of the water. Fiwther, since oxygen and carbon dioxide are more soluble in water at low temperatures, the facilities for gaseous interchange are greater at these temperatures, and it is known that marine plants such as algae flourish more abundantly in the Arctic than in warmer waters. In dealing with the gaseous interchange in the process of respiration, we shall have to discuss whether this takes place according to the principles regulating the diffusion of gases across a liquid film. Solubility of Gases in Salt Solutions. — In general, the more con- centrated a salt solution, the less soluble a gas in it. Thus, while 1 c.c. of pure water at 25° C. dissolves 0 0308 c.c. of oxygen, 1 c.c. of a ?? sohition of NaCl dissolves but 0-0262 c.c. of this gas, a N solution* 00223 c.c. a 2 N sohition 00158 c.c. We shall see that the absorption of oxygen by the blood, which contains salts in solution, is not a physical j)rocess; for. instead of taking * A normal solution (N solution) is made by dissolving the molecular weight in N . , . grammes of NaCl in 1 litre of water. ^ denotes a halt' norm."!l solution, 2 N a twice normal soluiion, and so on. PHYSICO-CHEMICAL IXTRODUCTION 21 --b u]_) a lessened amount of oxygen compared with water, it is capable laced in the tube, which is then immersed in potassium ferrocyanide. By this means a brown film of copper ferrocyanide becomes deposited in the almost colourless gelatin, and a membrane is obtained which is good for demon- stration purposes. The membrane of cop]:;er ferrocyanide has been found to be impermeable to substances such as cane-sugar and dex- trosCj but permeable to water. It is therefore semi-];erme.ible in regard to water and such substances in solution. - This can be demon- strated by filling the vessel bearing the mciubrane with cane-sugar solution, and cementing into it a rubber cork carrying a long glass tube. On immersing the pot in a vessel of water, liquid is seen to rise in the glass tube, and it attains a considerable height if the membrane be sufficiently well made and strong. Eventually the height of the column balances the pressure, which is tending to force the water in, thereb}'' giving a measure of the driving force, which, although opposite to it in direction, is equivalent to the osmotic pressure of the substance in solution. In the animal and plant world we meet A\'ith many such semi- permeable membranes. Such a one is that covering peas, beans, or barley grains. If the last be placed in an aqueous solution of sul- phuric acid, the water penetrates the grain, which swells in consequence and increases 76 per cent, of its weight. Sulphuric acid does not penetrate, as is shown by the fact that the blue pigment in the aleurone granules inside the grain is not changed red, as it would be if the acid penetrated the grain. When the covering of the grain is broken, the change cf colour at once takes place. Instead of the acid, a salt such as sodium chloride might be used. The amount of water absorbed by the seeds wall then depend upon the concentration of the salt in the water, since there is noAv competi- tion between the seed and the salt for the water. Thus, the increase of weight of the seeds with a 2 per cent, solution of sodium chloride is aboiit 40 per cent. ; with a saturated solution it is but 14 per cent. The phenomenon is, however, not one of osmosis only, the process known as imbibition also comes into play. This comparative im- permeability of the outer coat of seeds is recognized by agriculturists; otherwise such poisons as copper sulphate could not be used to destroy fungus spores upon the seeds Avithout killing the seeds themselves. Much study has been devoted to the phenomena of osmosis. It has already been stated that, if the force of attraction between solvent and solution be measured, the osmotic pressure of the solution is measured at the same time. The exact nature of this force is not yet completely understood, but it has been shown that it is governed by certain fundamental laws closelj^ allied to those already given for gases. Thus, it is found that the osmotic 'pressure exerted by a given quantity of the dissolved substance is inversely jnoportional to the volume of the solution [e.g., Boyle's law). In other words, the osmotic pressure of a solution is proportional to the concentration of the dissolved sub- PHYSICO-CHEMICAL INTRODUCTION 23 «t?.nce. In regard to temperature, it appears to be true, allowing for ex)Derinieti.tal difficulties, that the osmotic pressure of a solution is pro- portional to the absolute temperature {e.g., Gay-Lussac's law for gases). Also it is true for dilute solutions {e.g., of sugar) that the osmotic x>res- si'.re is e^ual to the pressure ivhich the molecular concentration of the substance would exert if it were in the gaseous state at the same tempera- ture, and occ^^pied the same volume as the solution. If two solutions of different osmotic pressure be separated by a semi-permeable membrane, osmotic exchange of water will take place until the pressures are equal on the two sides of the membrane, the water passing from the solution with the smaller osmotic pressure to that with the greater. This can be well shown by the following pretty experiment, the success of which depends upon choosing the right strengths of solution: A little potassium ferrooyanide (nearly saturated) is slowly run from a narrow glass tube the end of which dips below a solution of copper sulphate (a gramme-molecular solution)* contained in a tall glass jar. As the ferrocyanide runs out, a filmy bag of copper ferrocyanide is formed at the end of the tube. When the bag is about 1 to 2 cm. in diameter, a slight jerk will disengage it, and it will sink slowly to the bottom of the vessel. Its rontent having a greater osmotic pressure, water will entor the bag and gradual^ distend it. The density of the bag is thus gradually diminished, and eventualh^ becomes less than that of the surrounding copper sulphate solution, when the bag rises spontaneously to the top of the jar. The experiment may be varied by fitting the top of the narrow glass tube, containing the ferrocyanide solution, with a piece of rubber tubing, and pushing a drop of ferrocyanide out by closing this tubing with a chp- When the glass tube is now lowered into the copper sulphate, a hanging membrane is formed at its bottom. Water passes into the ferrocj^anide, and the copper sulphate, concentrating in the immediate neighbourhood of the membra,ne, becomes denser than the rest of the solution and sinks. This can be easily seen by the naked eye, owing to the difference in refractive power of the denser solution. If the experiment be reversed, and dilute feiro?yanide, in a tube with an upturned end, be placed in strong copper sulphate solution, the copper sulphate in the neighbourhood of the membrane is diluted, and a steady ascending stream of the diluted liquid can be seen. Interesting experiments on osmosis have been done Avith plants. For example, in the epidermis of the leaf of the plant Tradcscantia discolor the fluid coloured contents of the cells are normally in close contact with the rigid cell wall, which behaves as a semi -permeable membrane (Fig. l-', ^). If it be immersed in a solution containing 0-22 of a gramme-molecule of cane-sugar per litre, the coloured contents detach themselves from the wall at one or more places. '" Plas- molysis," ao it is termed, has taken place (Fig. 14, B). Owing to the withdrawal of water, there has been a decrease in the bulk of the cell * The molecular weight in grammas dissolved in 1 litre. 24 A TEXTBOOK OF PHYSIOLOGY contents. The solutidii of cane-sugar has ther(>forc a greater osmotic- pressure than the cell saj); it is termed a hypertonic solution. If. instead of sugar, another substance, such as potassium nitrate (I gramme-molecule per litre), be used, the solution formed is so strongly hypertonic that the plasmolysis is very marked (Fig. 14, C). Plasmolysis may also be readily demonstrated by taking shavings fVoui a beetroot, carefully washing these and immersing them for a time in 5 per cent, sodium chloride. The appearance under the microscope before and after is very characteristic. The red corpuscles of the blood behave in a similar manner. The delicate membrane surrounding the corpuscle is j^ermeable to water, but impermeable to many dissolved substances. In this case, however, there is no rigid cell wall foi mii-g the outer membrane. If, therefore, water passes into such a cell, it A\ill first swell up, and then burst, thus allowing the contained red pigment to escape, a process known as the laking of Fiu. 14. — To .SHOW THK Effect of Plasmolysis in Tradesca.vtia Dlscolor. (After Dc Vries.) h. Cell wall; /,-. nucleus; r(. plastids; .s. stream lines in protojilasni; y;, ])iot()]ilast. blood, or haemolysis. A solution fiom which water passes into the corpuscles is known as hypotonic. A solution from which water passes in and out of the corpuscle in equal amounts is known as isotonic. The concentration of sodium chloride required to form a sohition isotonic with nearly all mammalian bloods is 0-9 per cent.; a solution of this concentrat.'on is terjned '" physiological saline '" or " physiological salt '" solution. Hypertonic solutions diminish the volume of the corpuscle owing to water passing out of them. It is suggested that this passing out of fluid from living cells as the result of the action of hypertonic solu- tions may affect the activity of such cells. Thus, it is possible that in many plant cells the formation of stai-ch from sugar onl}' takes, place when the sugar concentration reaches a certain limit. Indeed, it is found that with cells having a sugar concentration short of this limit the formation of starch can be induced by i)roducing i^las- molysis with a solution of potassium nitrate; thi- by withdrawing physic()-che:mical introduction 25 Avatci raises the concentration in the cell to the minimum necessary for starch production. It has also been shown that unfertilized eggs of the sea-urchin (Strongylocentrotus purpuratiis) m^,}' be made to develop parthe- nogenetically by the use of h^-^jertonic solutions. The unfertilized egg of the frog develops if its membrane is pricked with a needle, and its osmotic relation to the surrounding water thus disturbed . C=^ The Mode of Action of a Semi-Permeable Mem- brane.— .Since osmosis plays an important part in the maintenance of equilibrium between plant and animal cells and their surroundings, it is highly important to know how semi-permeable mem- branes act. From the study of precipitation membranes, it appears to be the size of the molecular interstices which enables such a mem- brane to differentiate between various substances. It was at first thought to act merely like a sieve, but that is not the sole factor. For example, if a glass tube with a length of rubber tubing and ?. clamp at the end be filled with carbon dioxide, the rubber then clamped, and the glass tube cpiickly placed in a vertical position in a beaker of water, the carbon dioxide will gradu- ally diffuse out through the rubber and the water rise in the glass tube (Fig. 15). Rubber is per- meable to carbon dioxide but not to oxygen and nitrogen. Further, when methyl alcohol and ether are separated b}' a membrane of pig's bladder, th re is an osmotic flow from the alcohol to the ether. If, however, the two fluids be separated by vul- canized rubber, osmosis takes place in the opposite -^^ carbon dioxide .lirection. This is because the pig's bl.ckler TniZltS:t absorbs ten times as much alcohol as ether, whereas rubber absorbs one hundred times as much ether as alcohol. Therefore the compara- tive permeability or imperin^abilit}' to different substances of a non-living semi-jiermeable mem- brane depends, also, on its power to dissolve or absorb them. Experiments on living membranes, made chiefl}^ on plants, tend to show that it is a selective absorption on the part of the membrane which determines the ability or inability' of a sub- stance lo enter the cell. The permeable substances have been found by experiment to be generally soluble in fatty oils; the plasmatic membrane of the cells, therefore, probably consists of some such substance; indeed, it is claimed that cell walls are rich in lecithin and cholesterin — both bodies of a lipoid nature. xAs evidence of this it is found that the basic aniline dyes, which readily permeate Fig. 15. — To show THE PeIXCIPLE OF THE Semi-Perme- able Membrane. the top, water rises from the beaker, owing to ability of diffuse in the rubber. the in- air to through 26 A TEXTBOOK OF PHVSrOLOGY the cell, are dissolved by solutions of cholesterin aiul of lecithin, whereas sulphone dyes, to which the cells are impermeable, are but sparingly soluble in these media. This hypothesis of the lipoid nature of cell membranes is widely accepted at the present day, but it is not altogether satisfactory, and has been subjected to adverse criticism. It fails, for instance, to cx])lain reasonably wh}' cells arc so readily permeable to water. It is also stated that there are dyes readily soluble in these lipoids which are quite incapable of penetrating into the living cell; while there are also dyes insoluble in cholesterin which readily pass through the plasmatic membrane of the cell. Moreover, certain inorganic salts insoluble in fat penetrate into the cell. The sap in the plant, for instance, supjjlies salts by some means to the cells. From a physiological point of view, then, a purely physical theory of permeability is not altogether adequate. The red corpuscle is rich in potassimn and phosphate, yet the medium (plasma) in which it floats is j^oor in these substances, but rich in sodium and chlo- ride, in which the corpuscle is poor. Yet, as the cell receives its nutriment from the plasma, the membrane of the corpuscle cannot be wholty impermeable to potassium salts. If this be so, their retention in the cell is opposed to osmotic force. Apparently there is some specific intervention of the membrane or some special affinity of the cell substance for potassium salts. So, too, in the case of the bodily secretions. We shall see that it is difHcult to understand, for instance, how urea can be passed by purely osmotic agency from the blood, in which it is in weak concentration, to the urine, where its concen- tration is much greater. There appears, therefore, to be a physio- logical as well as a physical permeability of the cell. This is further shown by the following interesting experiments : If tadpoles be im- mersed in a 5 to 6 per cent, solution of cane-sugar they are unaffected. If they be transferred to an 8 per cent sohition, they shrink, owing to loss of water. But immersion in a solution less than 6 jDer cent, (hypotonic) is not followed by an intake of water and swelling of the tadpoles, as might be expected. Therefore the epithelial membranes of the tadj)ole are apparently permeable to water in one direction only. A bag made of toad's lung, if placed in effervescing soda water, rapidly fills with gas and floats. If, however, the lung be titrncd inside out, it does not fill with gas. The experiment succeeds no less if the lung in each case is filled with water. Each cell must be regarded as the seat of active chemical action, where concentrations of dissolved substances are con^itantl}^ altering. Other phenomena, e.g., imbibi- tion, T)lay an iinportant part. The direct determination of the osmotic pressure of a solution is a matter of difficulty. Therefore it is usual to ascertain it by some indirect method — by other properties of solutions quantitatively related to osmosic pressure — such as the lowering of the vapour pressure of the solvent when the dissolved substance is non-volatile, or the raising of the boiling-point of the solvent. The method, however, most generally employed for physiological solutions is the lowering PHYSICO-CHEMICAL INTRODUCTION 27 of the freezing-point of the solvent. The extent to which the freezing- point of a solution is lower than that of the solvent is proportional to the concentration of the dissolved substance. —The appar- Beckniann's V Determination of the Lowering of the Freezing-Point atus generall}^ emplo3'cd for this purpose is known xw (Fig. 16). It consists of a tube, A , placed in a jacket, B, provided with a special thermom- eter, D, and a platinum or nickel wire stirrer. The jacket B fits into a metal plate which covers a thick glass jar, C, also provided with a stirrer. When the experiment is to be made, this jar is filled with a freezing mixture, Avhich will give a temperature about 2-3° below the F.P. of the solvent. A known weight (10-20 c.c.) of the solvent is placed in A, and its cork carrying the thermometer and stirrer inserted. The temperature of A is first low^- ered by placing it in the freezing mixture; but as the freezing-point is approached it is fitted into the jacket B and stirred regularl}^ so that a steady fall of temperature is assured. The thermometer is carefully- watched; after p. time the merciu^y ceases to fall, then suddenly rises and remains stationary for a moment before starting to fall again. The point risen to gives the F.P. of the solvent for pure v'ater, 0° C. A known weight (1-2 gms.) of the solute (the body to be dissolved) is noAv introduced through the side-tube, and after it has dissolved the F.P is again determined in a similar manner. It is well not to cool too rapidly or too much; the thermometer should not rise more than 0-4° to 0-5° C. to its final position, otherwise the operation must be repeated. Excessive supercooling causes the separation of a con- siderable quantity of the solid solvent when freezing occurs, and this makes an appreci- able increase in the concentration- of the solution. The freezing-point method has been extensively used in studN^ng the osmotic pressure of the blood in different the urine in patho- man. It has been shown tliat the F.P. of invertebrate marine animals is the same as which they liv3; they are incapable of preserv- ing any difference of osmotic pressure; if the osmotic pressure of the w^ater be varied, that of the bod}' fluids varies also. But in the Fig. 10. — Beckmann's Ap- paratus FOR DETERJirS- iNG THE Depression of Freezing-Point. animals, and also logical conditions in the bod}^ fluids of that of tlie water in 28 A TEXTBOOK OF PHY8IOLO(;^• case of many aquatic vertebrates this i.s not the case, the blood luider ordinary conditions has a different osmotic pressure to the medium in which the animal lives, and is but shghtly altered by variations in the medium. This is true, for instance, of the tclecstean fishes; the blood <^»f the clasmobranchs. on the other hand, varies in osmotic pressure with that of the surrounding sea-water. It was stated above that the lowering of the osmotic jiressure of a solution is proportional to the concentration of the dissolved sub- stance. Although this is true, it is found that there are very many substances, such as sodimn chloride, for example, which yield, by the method of the lowering of the F.P.. a molecular weight quite incon- sistent with the formula? accepted for them. The osmotic activity of these bodies points to an abnormally large number of dissolved units in their solutions. This is explained b^' the view that acids, bases, and salts, in aqueous solution become dissociated to a greater or less extent into j^ositively and negatively charged particles or ions. These ions increase the number of nnits present in the solution, and endow it with an enhanced osmotic activity. Sodium chloride, for example, when dissolved in Avater splits to a large extent into positively' charged sodium ions, Na, and into negatively charged chlorine ions, CI. Hydrochloric acid splits into H and C"l. caustic j^otash into K and OH, potassium nitrate into K and NO.,. One molecule, it Avill be seen, produces but two ions. The "" ionic '"" hypothesis furnishes an adequate explanation of the abnormal osmotic influence exerted by such bodies 'n aqueouj solution. It also explains intel- ligibh" the behaviour of various solutions to the passage of an electric current. It is known that the solutions of the bodies which give an abnormal effect in lo^^ering the F.P. of water ako conduct an electric current: they are electrolytes. When two electrodes, one charged j^ositively and the other negatively, are placed in such fjolu- tions, according to this hy};othesis an attractive force is exerted upon the ions of opposite signs. Thus, the positively charged ions move towards the negative electrode, and the negatively charged to the positive electrode : the undissociated neutral molecules, remaining unaffected and exhibiting no tendency to move in either direction, play no part in the transport of electi'icity through ^he solution. The efficiency, therefore, of a given quantit}' of a salt to conduct an electric current depends upon the extent of dissociation of that salt. It is found by experiment that the amount of dissociation, and there- fore the condu.ctivity. increases as the .solutions of the salts become less concentrated. In the body fluids there are some substrnccs in solution which are electrolytes, and will therefore conduct electricit}- ; others which are non-electrolytes, and will not conduct electricit3\ The fluids conduct according to the amount of the electrolytes present. Thus, blood- serum has a conductivity of about the same as that of a 0-8 per cent, sodium chloride solution. When the non-conducting corpuscles PHYSICO-CHEMICAL INTRODUCTION 21) of the blood are present, as in Avhippeil blood, the conductivity is reduced to about half. We shall see how various ions are supposed to play important parts ill the body functions. For example, the excised muscles remain contrac- tile and the heart beats when bathed with a solution containing a certain concentration of sodium, potassium, and calcium ions. The hydrogen (H) and the hydroxyl (OH) ions also are important. These when com- bined yield a molecule of water. The free H ion in aqueous solution possesses the ])roperty of endowing a substance with acidity — e.g., 4- HCl (H and CI): the OH ion, on the other hand, gives alkalinity — e.g., caustic potash (K and OH). Various reactions will only take place when a free H ion is present — for example, the splitting of cane-sugar into dextrose and levulose — and it is found that the rate of this change depends upon the concentration of the H ions. So, too, it is suggested that the free H ion in the blood plays a part in exciting the respiratory centre and determining inspiration. The immunizing properties of the blood are closeh' connected with the concentration of H ions. Crystalloids and Colloids. — Thus far attention has been jjaid only to such characteristics as the osmotic activity and the conduction of the electric current by various bodies. Another distinction between substances may now be ]3ointed out — that is. the readiness with which they crystallize ^"^''- 17. —To show from water; and those which crystallize readily — e.g., sodium chloride, sugar — also diffuse readily through animal membranes, and are known as crystalloids. Those which crystallize with diffi- culty, or not at all, are characterized by low diffusive power or absolute inability to pass through animal or vegetable membranes. Such bodies are termed colloids, from the gummy nature of many bodies belonging to the group — e.g.. gums, starches, etc. This difference may be demonstrated by placing a mixture of a colloid and crystalloid in a tube of ])arehment, and ]ilacing the tube in distilled water — e.g., a solution containing the red ])igment of blood (haemoglobin) and sodium chloride. The litemoglobin does not pass through the membrane, and the water outside remains uncoloured. But a test for chloride shows the presence of this in the water after a short time (Fig. 17). Some crystalloids are electrolytes and ionize; others are non- electrolytes and do not ionize. All, however, form true solutions in water. In contradistinction to the last property of these bodies, we have a group of substances which are quite insoluble in water when in bulk, but which, if finely divided by mechanical means, can be TALLOID, BUT XOT OF .4. Colloid. The hiBiiioglobin in the parchment tube does not diffuse out, the chloride does. 30 A TEXTBOOK OF PHYSIOLOGY suspended in Widcr in such a manner a.s to l)e evenly distributed throughout the Ihiid with but little tendency to settle out or aggre- gate together. 8uch sul)stances form suspensions or emulsions. They are non-diffusible, refract light, exert no osmotic pressure, do not conduct electricity, and contain particles visible under the microscope. Between these two extremes comes the group of bodies classed at the present time as colloids, some a])pr(v;\chiiig more nearl}^ the crystalloids, some more nearly the suspensions. But for the most part colloids possess characteristics which clearly differentiate them from crystal- loids. These characteristics may be enumerated as follows: They are generally amorphous in form; some, however, can be made to crystallize luider appropriate conditions. Although giving a homogeneous solution when seen beneath the microscope with ordinary illumination, yet if a beam of light be passed through the solution particles become visible, or, rather, halos surrounding these, owing to the dispersion of light waves from the surfaces of the particles suspended in the solution, just the same as a ray of light becomerj visible on passing into a dusty room. This is known as " Tyndall's phenomenon." The particles arc too small, but the halos surrounding them are large enough, to be seen under the microscope. Since colloids are not far removed from suspensions, relatively slight changes suffice to aggregate the particles and throw them out of solution. If the colloid, thus thrown out, can again be dissolved in the solvent, it is said to be precipitated; often, however, it cannot be rediseolved, and it is then said to be coagulated. Agencies which produce aggregation or agglutination are a rise of temperature, and the adding of large quantities of neutral salts, a process known as " salting out." The suspenrjion of the colloid particles in the solvent depends on the particles carrying an electrical charge and their mutual repulsion. Any factor which reduces this charge tends to aggregate the particles. Colloidal suspensions, like those of colloidal gold, are at once thrown out by the electrical discharge of the particles — labile colloids. In the case of colloidal emulsions there is a relation between the molecules and the solvent, and the particles are less easily thrown out — stabile colloids. In colloidal solutions the size of the particles, roughly, is between the limits of microscopical vision (0-1 fi) and ultra-microscopical vision (0-001 ju)- Above the limit we have suspensions, and below it we approach the true molecular solutions. The :;u.rfc.cc of the particles plays a great ])art in the chemistry of the colloids. The minute sub- division causes an enormous increase in surface. Supi:ose a cubic centimetre of gold be subdivided into particles with a side of 0 001 ^t the little cubes (10^^ in number) Avoidd have a total surface of 600 square metres, roughly equal to a surface measuring 25 yards by 25 yards. All surfaces have the jiower of adsorption — e.g., charcoal adsorbs gases, colouring matters; fire-clay adsorbs coal-gas in such a way that intense incandescence with very perfect combustion is brought about in the surface of the brick when coal-gas is forced through it and lighted; platinum black adsorbs and brings about the PHYSICO-CHEMICAL INTRODUCTION 31 union of hydrogen and oxj'gen. The adsorptive power of colloids is very great owing to their fine particulate condition and enormous surface, and this plays a great part in the chemistry and physics of living cells. Most colloids are held back bj' very fine filters. Thus, the colloids of blood-plasma can be separated by the use of a porcelain filter candle which has Ijeen soaked in a solution of gelatin. The water and salts can be pressed through such a filter. Colloids are indiffusible through animal or vegetable membranes. The membranes themselves are colloids, and, since colloids do not readily dissolve in colloids, it is clear they will diffuse but little through each other. Crystalloids, on the other hand, as we have seen, diffuse readily; they are generally soluble in colloids. This difference in property can be well demon- strated by placing a stick of agar jelly (colloid) in some ammoniated copper sulphate .solution (crystalloid), and another in some Prussian blue solution (colloid). It will be found that the blue copper solution penetrates readily, the Prussian blue not at all. Colloids also appear to influence physico-chemical processes but little. Crystalloids will diffuse almost as readily from colloids as from water. So, too, chemical processes take place in colloidal solution almost as if colloids were absent. Advantage is taken of these properties in the body. A crystalloid, when not linked or adsorbed to a colloid, will wander freely and diffuse away from a cell; a colloid will remain where it is formed. Thus, we find that the crystalloid dextrose is con- verted in the liver hito the colloid glycogen for storage j^urposes, but to escape from the liver cell the glycogen is converted again to the crystalloid dextrose. The osmotic pressure exerted by colloids is very small or nil. It is believed that when absolutely pure and free from traces of crystalloids colloids exert no osmotic pressure. Also they depress the freezing-point of a solution but little. Increasing the amoimt of egg albumin in water from 14 to 44 per cent, causes l)ut an alteration of freezing-point from 0-02" to 0-06° C. Since, also, lolloids ionize Init little, they conduct electricity but little. On the passage of an electric current through a colloidal solution, however, the particles of most colloidal solutions tend to move in the electric field ; cataphoresis, as the phenomenon is termed. This j^robably depends upon the existence of a high surface tension in colloids. Surface tension may be described as the force with which a fluid strives to reduce its free surface to a minimiim. When, therefore, we sjaeak of the lowering of the surface tension of a fluid, we mean that the force tending to reduce its free .surface is weakened, so that the free surface increases. The formation of emulsions is due to such a lowering of the surface tension. Water and oil will not mix, the oil floating on the surface of the water, owing to the high sm-face tension of the oil. If, how- ever, some sf)a]) he added to the water, the big oil drop is seen to break down gradually into a number of smaller. Imbibition, — Most of the organic colloids exhibit the proj^erty of taking up fluid without chemical change. This is the phenomenon of imbibition. For example, dry gelatin brought in contact with 32 A TEXTBOOK OF PHY8lOLO(;Y Avater swells greatly and becomes a jelly, liuhihition j)lays a great part in the vital phenomena of cells. Each cell has a normal water content, which, however, may vary within certain limits according to the tissue. Withdrawal of water below the normal limits impairs the cell processes, which are either suspended for the time being, as in the case of the spores of bacteria, or altogether destroyed. With- drawal of 15 jjcr cent, of water ra]iidly from a frog, or of 33 per cent, slowly, stops all its cell activities. If, however, the amount of water in a cell rises above its normal upper limit, its activities are also im- paired; it becomes water-laden and boggy, ^r, to use the scientific term, " oedematous." The power of a cell to regulate its water con- tent is largely due to the iihenomenon of '' ini])ibilion." Tn this phenomenon, perhaps the electrical charge, and repulsion of the particles, of the colloids of the cells are chiefly concerned, and exert the pull which draws the water into the cell. The process is different from osmosis, since the addition of certain salts to the colloid, instead of aiding the passage of water, tends to hinder it. Electrolj'tes, which favour the aggregation of a colloid, oppose the imbibition of water by it, and vice versa. The cells — e.g., secreting cells of glands — are confined b}" more or less rigid membranes, and the force of imbibi- tion may be used to do work such as secretion. When a tissue becomes oedematous, the normal imbibition power of the tissues is altered; for example, owing to an alteration of the reaction of the tissues in an acid direction, the proteins of the cell exert increased imbibitory power, and thus become "oedematous" or "water-logged." Thus, the dead eye of an ox placed in faintly acid water becomes tensely swollen. Such swelling is hindered by the addition of sodium citrate. So, too, if the hind-leg of a frog be ligatured so that the blood-supply is cut off, and the animal placed in water, the ligatured hind-limb swells up to three or four times the normal size. If placed in a dry vessel, the limb decreases in size, almost drying u]) If removed from the body and placed in water, it swells up again to a great size. The muscles of a frog swell when exj^osed to a pressure of water over 350 atmospheres, and lose their contractile power. This may return if the excess of water is at once dried off. Exposure to such pressures kills all terrestrial and shallow-Avater life, except that of spore-bearing bacteria, by a kind of water coagulation. The bacteria are protected by their tough membrane. The deep sea fishes which live at depths of two miles or more must be immune to such water- pressures. CHAPTER IV THE CHEMICAL COMPOSITION OF THE BODY A CONSIDEBA-BLE iminljcr of the elements have been detected on anaI3^sis of the dead bodies of the various forms of hfe found on the earth, but the number com])osing the bodily structure of the higher animals is strikingl}' few. The chief of these are carbon (C), hydrogen (H), nitrogen (N), oxygen (O), phosphorus (P), sulphur (S), chlorine (CI) so:]ium (Na), potassium (K), calcium (Ca), magnesium (Mg), and iron (Fe). Others, such as iodine, boron, and fluorine, are found in minute traces. The elements contained in the above list occur chiefly in combination; some, however, such as nitrogen and oxygen, are dissolved in the body fluids. The chief chemical compounds which are obtained on dissociation of the bod}^ may be grouped as (1) water, (2) inorganic compounds, (3) organic compounds. Water is a constituent part of all tissues of the animal body, the water content varying according to the nature and function of the tissue from 50 to 90 per cent. The chief exceptions are the enamel and cement of the teeth, which contain 0-2 per cent, and 10 j)er cent, respectively'. Adipose tissue contains 29 to 30 per cent, water, the brain 90 per cent., skin 72 per cent., muscles 76 per cent., lungs 79 per cent., heart 79-5 per cent., and the lens of the eye 98-7 per cent. The percentage in the body fluids ranges from 79 per cent, in blood to 99-5 per cent, in sweat and .saliva. Inorganic Compounds. — These are chlorides, phosphates, carbon- ates, and sulphates. The chlorides are found chiefly as sodium chloride. This salt may be extracted from all tissues and fluids. More rarely found are the chlorides of potassium and r.mmonium. The phosphates are also ^^'idel3' distributed, calcium and mag- nesium phosphate occurring particularly in .bone, of which the ash contains respectively 85 to 90 of the former and 1-5 to 1-9 per cent, of the latter sal;. Soluble phosphates are also found in nearly all the tissues and body fluid.;. The soluble carbonates and bicarbonates of the alkalies, sodium and potassium, occur chiefly in the body fluids, helping to confer uj)on these a slightly alkaline reaction to litmu.-i. Insoluble car- bonates occur in bone. 33 3 34 A TEXTBOOK OF PHYSIOLOGY The sulphates do not occur in any large quantity, but the alkaline sulphates are regular constituents of the chief body fluids. A little fluorine occurs combined as calcium fluoride in the teeth ;uk1 bones. Among the inorganic bodies must also be classed hydrochloric acid, which occurs in the secretion of the stomach, and carbon dioxide, present in the blood and body fluids as well as in the expired air. Organic Compounds. — These are compounds of carbon with hydro- gen, oxygen, and in some cases nitrogen. Phosphorus, sulphur, iron, chlorine, iodine, may also enter into the composition of the various organic compounds, of which there are three chief grouj)s, proteins, fats and lipoids, and carbohydrates. In addition there are the pro- ducts of the breaking down of these bodies within the organism. The carbon atom is tetravalent-^that is to say, it can combine with four atoms of another element (for example, hydrogen) to form such a body as CH^, which is methane, or marsh-gas. Another fundamental proj^erty of the carbon atom is that it can unite with other carbon atoms to form a chain or a ring, thus giving rise to the possibility of a large number of very complicated bodies, the molecides of which are imited together through the carbon atoms contained in them. There arc- also rings composed of carbon and nitrogen. 1. Starting from methane, CH^, by the addition of one atom of oxygen, H H H OH C +0= c H H H H IMcthano Methyl alcohol we obtain an alcohol, methyl alcohol, HCH^OH, which, as it contains the group CHgOH, is termed a primary alcohol. If we start from propane, CHgCH.jCH^, the compound two above methane in the chain. CH3 I CH, I CH3 Propane the f ormula5 show that it is possible to obtain two monatomic alcohols (alcohols containing one OH group) : one the primary alcohol (primary propyl alcohol, as it is termed), containing the group CH^OH; the other with the group CHOH characteristic of a so-called secondary i Icohol — secondary propyl alcohol. CH,,OH CH, CH, 1 CHOH 1 CH3 CH3 •imary propyl alcohol Secondary propyl alcohol THE CHEMICAL COMPOSITION OF THE BODY 35 But it is possible to obtain (if the carbon chain be long enough) diatomic, triatoraic, hexatomic alcohols. For example, from propane: CH3 I CH, I CH3 Propane CH2OH 1 CHOH CH3 A diatomic alcohol CH2OH CHOH CHoOH Triatomic alcohol (glycerine) 2. If, instead of one atom of oxj^gen, two atoms are linked on to methane, H OH H OH \ C / H OH C H lOH H \ C -O H Formaldehyde water sj^hts off, leaving a body containing the group = CO which is designated as the carbonyl group. Thus, from propane it is possible to obtain by oxidation: CH, CH., I " CH> Propane 0 c I ^ CH, CH3 Propaldehyde CH. C = 0 CH3 Acetone Bodies containing the characteristic grouping CHO are known as aldehydes ; those Avith the grouj)ing C = 0 are termed ketones. Generally aldehj'des and ketones are obtained bj' oxidation of alcohols, primary alcohols yielding aldehydes, secondary alcohols yielding ketones. Thus: 0 CH20H c CHoOH H CHOH CHOH 1 C=0 CH2OH Glycerine ( Glyce (0 :^H20H rine aldehyde vcyaldehydo) ( Die (0 :^H20H xyacetone ^yketone) 30 A TEXTBOOK OF PHYSIOLOGY 3. If three molecules of oxygen be introduced into methane, water iigain splits off: HO OH OH \ , / C -^H-C orH.COOH : \. H OH , 0 Formic acid A body containing the characteristic gTQup COOH is obtained. This is called the carboxyl group ; its possession confers acid properties CHs'. upon the bodies containing it. From ethane, | it is possible to CH3 obtain either one or two carboxjd groups bj' oxidation : CH3 CH3 COOH CH3 COOH COOH . Ethane Acetic acid Oxalic acid (a monocarboxylic (a dicarboxylic acid ) acid ) A body containing one COOH, such as acetic acid above, is known as a monocarboxylic acid; a body containing two such groups, like oxalic acid, is known as a dicarboxylic acid. In general acids are obtained by the oxidation of alcohols, aldehydes, ketones: CH3.CH2.OH +00= CH3.COOH + H2O Ethyl alcohol Acetic acid 2CH3.CH,.CHO +0^= 2CH3.CH0.COOH Pro})aldehyde Propionic acid CH3.CO.CH3 + 2O0 = CH3COOH + CO., + H2O Acetone Acetic acid In the group of bodies known as amino-acids, one of the valencies of the carbon atom is satisfied h\ the amino group NHg, instead of with hydrogen: CH3 CH,NH2 I ■ I " COOH COOH Acetic acid Monamino-acetic acid (glycin) Just as there exist many acids of which acetic acid is the first of the chain, so there exist many amino-acids of which glycin is the simplest. By introducing two amino groups into the acid molecule, bodies known as diamino-acids are obtained. 4. If four molecules of oxygen be introduced into methane, tAvo THE CHEMICAL COMPOSITION OF THE BODY 37 molecules of water split off, leaving carbon dioxide, COg, the end product of oxidation of carbon compounds in the body. HO IHO / CI OIH. ;0H = 2H,0+COo The tendency of the carbon molecule to form rings has been men- tioned ; the chief of these is the so-called benzene or carbocyclic ring,, which is represented as six carbon atoms hnked together thus : or Benzene itself is CgH,., an atom of hydrogen being linked on "to each carbon atom. Starting from benzene, it is possible to obtain a large nmnber of compounds, so-called aromatic compounds, a few of which, such as phenylalanin and tyrosin, enter into the construction of some of the body compoiuids. Or carbon may be linked with nitrogen to form a ring thus : C- C C c or N H N I H Four carbon atoms linked to an=:NH or imino group give the pyirhol ring. In other bodies the benzene and pyrrhol rings are found combined together, yielding a compound ring found in such bodies as tryptophan, indol, and skatol. The ring may be represented thus: H H KH 38 A TEXTBOOK OF PHYSIOLOCJY A combination of four carbon atoms vvitii two nitrogen atoms yields a ring known as the pyrimidin ring: N CH I I HC CH II I' N— CH Another ring which occurs is — HC— NH i CH HC N known as the iminazol ring. This is found in the body histidin. A combination of the pyrimidin Avith the iminazol ring yields the important nucleus or ring known as the purin ring. The different positions in this nucleus have been numbered, and it may be repre- sented thus: N, - C, C2 5C-N, '^ ': . C, N3-C4-N, Each of these rings will be referred to A\heu dealing with com- pounds or groups of bodies containing them. CHAPTER V THE PROTEINS Section I. The proteins form a group which i.s to be regarded as the most im- portant of all orgajiic compounds. They are obtained from all dead cells, and are intimately connected with the life of the cell, for without them as foo:lstuffs the cells cannot live. Tiiey are bodies of biological origin; so far no effort to make them in the laboratory has been suc- cessful. Most of the members of this group are amor23hous bodies of high molecular weight. The protein molecule is made up of the elements carbon, h3'drogen, nitrogen, oxygen, and sulphur. The amounts of these elements vary considerably in different proteins, as can be seen from the following table: Prolein. G. H. N. O. S. 1-25 FibrinD^en .. .52-93 .. 090 .. Ilr66 .. •22-06 Serum albumin .. .>2-()8 .. 7-10 .. 15-93 .. 21-96 Serum trlobulin . . .-)2-71 . . 7-01 . . 15-85 . . 23-32 Keratin .. .. 50-G5 .. &'M .. 17-14 .. -20-85 Elastin .. .. 54-32 .. (v99 .. 16-75 .. 21-94 y the action of a ferment, tyrosinase. Kresol and ])hen()l are formed out of ])henyl alanin and tyrosin in the colon by bacterial decomposition, and are excreted as *' ethereal sul])hates " in the urine. Tryptophan, ^uHj.^NgO^, is /-indol-amino-pro])ionic acid; it con tains a heterocyclic ring formed of the fusion of the benzene and pyrrhol rings. Its formula is — C.CH.C H(NH,)COOH "cH NH It is the mother-substance of indol and skatol. It is responsible foi" the giyoxyhc reaction (see later). Prolin is ^a-pyrrolidin carboxylic acid, C^HgNO.,, or graphically: H,C CH., I 1 H,C CH.COOH NH It has been found in both animal and vegetable proteins. Oxyproline is oxy-pyrrolidin carboxylic acid, and was first obtained by the hydrolysis of casein and gelatin. Arginin, lysin, and histidin, each contain six molecules of carbon, and being of a basic nature, were formerly classified together as the "■ hexone bases." Lysin is a-diamino-caproic acid; leucin is monamino-caproic acid. The formula of lysin is CH,(NHJ.(CH,)3CH<^^^^jj By putrefaction of Ij^sin i^entamethylendiamin (cadaverin) is produced, while tctramethylendiamin (putrescin) is formed from ornithin. Arginin is a guanidine derivative of ornithin, which is u-S-di- amino-valerianic acid, C4H_(NHJ^C00H. It has basic properties, and reacts strongly to litmus. Its formula is — (NH)C—NH.(CH2)3— CH.COOH I I NH^ NH^ Histidin is not a true diamino-acid ; it is a diazine derivative. It is amino-imidazol-propionic acid, and has the formula THE PROTEINS 43 CH— NH CH / C N' I CHo I CH(NH,) COOH From the fact that these three bodies (especially argnin) occur largely in the simplest proteins known (protamines), and appear to be among the very last bodies split off by hydrolysis from more complex proteins, it has been thought that they form the central nucleus of protein. Cystin is notable for the amount of sulphur which it contains. It is di-amino-di-thio-lactylic acid : CH.,S SCH, I " 1 " CHNH., CHNHo I " 1 " COOH COOH It is found largely in the keratin of Jiair, horn, nails, and hoofs. It crystallizes in colourless hexagonal plates. The pyrimidin and pur in bases are obtained chiefly from the group of proteins known as nucleoproteins, and are more fully discussed later When protein is subjected to hydrolysis by the digestive juices, it is parti}' converted by the action of the acid or alkali present into ?. derivative of protein known as metaprotein. A considerable amount of ammonia is also split off. The hydrolysis of protein may be repre- sented as follows : Protein ^ Metaprotein ' Proteoses Peptones Polypeptides -4/ Amino acids 1 Group 7. A Group /.B 4^ xl- Group II. A Group II.b (Monamino Monocar- box ylic ) Glycin Alanin (ilonamino dicarboxylic) Aspartic acid Glutamic acid (Bonzene ring) (Other rings) Phenyl alanin Prolin Tyrosin Oxyprolin Tryptophan Histidin Serin Valin L^uoin Group HI (I)iamino acids) Lysin Arginin C3^stin (Other con- stituents Pyrimidin bases Purin bodies Carbohydrate, etc. 44 A TEXTBOOK OF J'HV.SIOLOGY 111 the following table will be seen the varying yields of the different amino aeids obtained from 1(10 jn^rts of varions jjroteins, after complete hydrolysis with iiych-oehloric or snl])huric acid. Tyrosin and cystin are separated by crystallization, after neutralizing and concentrating the liquid. The diamino acids — arginin, lysin, and the allied body histidin — are separated from the rest of the products by being pre- cipitated by phosphotungstic acid in acid solution. Try])tophan is separated by })reci])itation by mercuric sulphate in the presence of 5 per cent, sulphuric acid after ti-yptic digestion. The othei- amintt acids are separated after hydrol3'sis of protein by hydrochloric acid by fiactional distillation of their ethereal salts under greatly reduced pressure. It will be noticed that the figures given do not by anj^ means add up to 100 per cent. This is due to the occurrence of some in- evitable loss in the method of separation, and to the fact that, doubt- lees, all the components of protein have not yet been isolated. Globulin Caseiuo- Glob in ! Gliadin ! 1 Keratin Edestin (Jrom i H cmp- { Seed). ' Fibroin I'Jnd Products. (Horse gen (Cow's 31 ilk). of [from ' (Sheep' s- 1 [from \Seruni). Horse. Wheat). Wool). j Silk). Group I. a: ' Glycin 3() — — 0-8 0-G 3-8 i 3G-0 Alanin 2-1 !•(» 4-2 2-() 4-4 3-G 24-0 Serin 0-4 (:)-4 0-G 0-1 1 0-1 0-2 , 1-6 Valin — 1-0 — — . 1 2-8 1-0 Leucin j 18-0 10-2 30-0 G-0 ! 11-4 21-0 1-6 Group I.b: j Aspartic acid 1 2-G 1-2 4-4 1-2 2-4 4-6 0-2 Glutamic acic ij 9-0 11-0 1-8 3G-() 13-0 14-0 — Group II. a: I Phenyl alanir 11 3-8 3-2 4-2 2-G . 2-4 l-G Tyrosin 1 2-2 4-4 1-G 2-G — 2-1 ll-« Group II. b: Prolin , 2-8 3-2 2-0 9-0 2-0 2-0 Oxyprolin ; — — — Tryptophan 1-4 — 1-0 1-4 Histidin i 2-1 2-6 12-0 — 0-6 0-G O-l Group III. : Lysin i '^' ^ 5-8 4-4 1-0 Arginin i 4-8 ?yi 3-4 14-0 1-0 Cystin 0-8 0-1 0-3 0-4 Ammonia .'j-l; Large 7-2 0-2 Absence Yields Large Absence Large Largo of also amount amount of of phenyl! amount amounts arginin j diamino - of glutamic alanin of leucin. of glycin, Character- trioxy- leucin. acid. and glutamic alanin. istics dodecamic ' histidin, ammonia ; tyrosin ; ' acid, and icid 0-75; lysin absence large arginin tyrosin absence of of lysin amount ' glycin; and ' )f cystin; large histidin smaU amount j amount ; ^ of lysin c )f glyc'n ' THE PROTEINS 45 As a result of this hydro lytic method of procedure, we now know that the proteins differ greatly in composition; for example, the protein of the spleen is different from that of the thymus or of the pancreas. Further, the protein of the same tissue differs in animals of different species — e.g., the serum albumin of the blood of one animal has a different constitution to the serum albumin of an animal of another species; the same is true of the chief protein (caseinogen) of milk. We can understand, therefore, why it is that the proteins of the food have to be broken down into such numerous end products in the digestive tract; of these end products those are selected which are of value in building up the animal's own particular forms of protein, forms which differ in various parts of the body and differ from the protein ingested. It is only by a yevy complete hydro- lysis that the particular valuable end products can be obtained free from products of lesser value (see also under Digestion). The results of the second procedure, the synthetic, have been highly interesting. Starting with a simple end product such as glycm, two of its molecules have been combined together, forming a dipeptide, glycyl-glycin, with the elimination of water, thus: OH 1 H NH,CH2C0 I NHCH^COOH =-- NHaCHaCO.NHCH.^COOH + H^O Glycin 4- Glycin Glycyl-glycin + Water Tlie addition of another molecide forms a tripeptide, and so on until polypeptides are formed. Penta-glycl-glycin, for example, is — NH2CH2CO(NHCH3CO) 4NHCH2COOH Not only has gtycin been combined with glycin ; other end products, such as alanin, leucin. tyrosin, have been combined together. An example of such is the polypeptide (do-dekapeptide) leucyl-deka- glycyl-glycin: (NHCH.,CO)io I NHCH.COOH Glvcyl (Hycin C,H9CH(NH2)CO Lcucjd By many such operations polypeptides have been obtained, which, if not actually having the same composition, have many resemblances to peptones. Section II. The Physical and Chemical Properties of Proteins. The proteins possess certain well-marked physical and chemical properties. 1. All proteins, with the exception of a few vegetable proteins, are insoluble in alcohol and ether. They vary as to theh solubility in water, the more common proteins (albumins and globulins) being either soluble in water (albumins) or soluble in weak saline solutions (globulins). 46 A TKXTBOOK OF PHYSIOLOGY 2. The solution given by them, however, is colloid;',!, and therefore will not diffuse through animal membranes or parchment paper. In this they are xnilike crystalloids, such as inorganic salts, which readily diffuse through such membranes. 3. Most of the so-called native proteins (al})umins and globulins) coagulate when their solutions are heated, different proteins coagu- lating at different temperatures, varying usually from SO"" C. to 78'' ('. A faint degree of acidity and the presence of much neutral salt aids this process. Heat coagulation is probably brought about first by the interacli.n of protein and water : a hydrolytic product, metaprotein, is produced (dcnaturation); secondly by agglutination and separation. A certain increase of acidity or alkalinity favours denaturation, but opi)oses agglutination. The reverse is true for neutral salts. Protein does not form a true solution; its particles are suspended in the solvent, and carry an electrical charge. Any factor which reduces this charge tends to bring about agglutination, cither precipitation, which is reversible on dialyzing away the reagent, or coagulation. The particles are no longer electrically repelled, and run together under the influence of gi'avity. In the case of proteins, which have amphoteric properties, the charge of the particle is positive when the fluid is acid, and negative when the fluid is alkaline. When a neutral salt is added, the agglutinating ion is that which carries a charge opposite in sign to that of the par- ticle. The agglutinating power increases with the valency. Thus an acid solution of protein is precipitated by negative ions, for the particles of protein have positive oharges; the potassium salt of citric acid (trivalent) is much more effective than the potassium salt of sulphuric acid (divalent), and this more than the potassium salt of hydrochloric acid (univalent). An alkaline solution of protein is agglutinated by positive io; s; cerium chloride (trivalent) is more efficient than barium chloride (divalent), and this Tiiore than sodium chloride (monovalent). 4. Most proteins are uncrystallizable. Some j^roteins, however, can be fairly easily crystallized, especially certain vegetable proteins, such as those of hemp-seed (edestin) or of the Brazil nut (excelsin). 5. Almost all proteins turn polarized light to the left. Haemo- globin is an exception. 6. Certain well-marked colour reactions are given by the majority of proteins, all of which give valuable information as to the constitu- tion of the protein molecule. One such reaction — namely, the biuret — is characteristic ; a body that does not give this is not classed as a protein. The most important of these reactions are — {a) The biuret. A violet or rose-pink colour with copper sulphate and caustic potash denotes the presence of two or more CO — NH — linkages. All proteins give this reaction. (b) The xanthoproteic. With nitric acid a white curd turning yellow on heating, and orange on addition of ammonia, denotes the presence of the benzene ring in the protein molecule. Proteins yielding the ringed amino-acids give this reaction. (c) Millon's — with a mixture of mercuric and mercurous nitrates, a white precipitate turning brick red on heating — signifies the presence of a benzene ring with m\ hydroxyl group attached — in other words, the phenolic group. Proteins containing tyrosin give this test. {d) Hopkins's modification of Adamkiewicz's reaction. The reaction signifies the presence of tryptophan in the protein molecule. Acetic acid, containing glyoxylic acid as an impurity, is THE PROTEINS 47 added to protein, and then a little strong sulphuric acid carefully; a violet ring is developed at the jiniction of the fluids. (e) Proteins containing a carbohydrate moiety yield Molisch's test. A purple colour over green is developed when a-naphthol and sulphuric acid are added to the protein. (/) Proteins containing loosely combined sulphur yield with lead acetate and caustic alkali a black precipitate of lead sulphide. (g) Many proteins are jjrecipitated (" salted out ") from solution by the addition of neutral salts, such as ammonium sulphate, magnesium sulphate, sodium chloride, in varjang concentrations. Such precipi- tates are again soluble in the original solvents. (h) Proteins are coagulated — that is, thrown down as a precipitate no longer soluble in the original solvent — b.y mechanical agitation, addition of the salts of heavy metals, mineral acids and many other acids, such as tannic, picric, etc. All proteins do not necessarily give all the above reactions. It is perhaps somewhat difficult to define a protein. Most of them may be defined as bodies of biological origin insoluble in alcohol and giving the biuret test. (All these properties should be studied in connection with the experiments given in Practical Physiology). Section III. The Classification of Proteins. The following classification has been adopted; it is based partly upon the results of chemical investigation, and f)artly upon such physical properties as solubility, salting out, etc. It cannot be regarded as complete. 1. Protamines. . 2. Histones. 3. Albumins. 4. (iJlobulins. 5. Phosphoproteins. 6. Scleroproteins. 7. Compound proteins. The protamines are held to be the simplest proteins known. They occur combined with nucleic acid in the spermatozoa of certain fishes such as the salmon, sturgeon, mackerel, and herring. Sturin, from the sturgeon, has the formula C.^^H^gNj^O. ; salmin (salmon) and clupein (herring) have the formula Cg^H^.N^-Og. They are difficult to obtain in a state of purity. Upon hydrolysis they yield large amounts of the hexone bases, arginin, lysin, and histidin, esjiecially arginin. The histones occur mainly in combination. They are more com- plex than the protamines, and are coagulable by heat, soluble in dilute acid, and precipitated from water}' solution by ammonia. The best known is globin split off from the heemoglobin of the blood ."=\'^ 48 A TEXTBOOK OF PHYSIOLOGY The albumins, of which serum al])unun, lactalbiimin, and egg albumin, uie examples, are soluble in distilled water and in saline, but not in saturated solutions of ammonium sulphate and anhydrous Rcdium sul])hate. The globulins, on the other hand, are insolu})le in distilled water and in saturated solutions of all neutral salts. Furthermore, they are insoluble in half-saturated solutions of ammonium sulphate and anhj'drous sodium sulphate. They are soluble in weak saline solutions. The most important are serimi globulins, egg globulin, the myosinogen of muscle, and the fibrinogen of blood. The phosphoproteins derive their name from the large amount of l^hosphorus which they contain. Phosphorus is easily split off by prolonged treatment with 1 per cent, caustic soda at 37° C, a fact which distinguishes the phosphoproteins from nucleoproteins. They differ, too, from the latter in containing no purin bodies. They resemble the globulins in many of their properties, but the}^ are not coagulable by heat. The chief members of the groups are the case- inogen of milk and the vitellin of egg yolk. The scleroproteins com2:)rise a heterogeneous group of proteins formerly known as the albuminoids. They are obtained mainly from the " hard " or supporting structures of the body. Among the better known are collagen, from white fibrous tissue, and its hydride gelatin. Gelatin is remarkable in yielding little or no aromatic bodies on de- composition. Keratin, charactcrizxl bj' containing a large amount of sulphur, occurs in the skin and its appendages, such as hair and horn. Elastin is found in elastic tissue, ossein in bone. The compound proteins consist of proteins to which groups other than protein are united to form a complex molecule. The groujjs usually classified are — (1) chromoproteins, (2) glucoproteins, (3) nucleo- proteins. Some authorities add lecitho-protein.s — that is, compounds of lecithin and protein (see Lecithin). The chromoproteins, as their name signifies, are the coloured proteins, the chief member being haemoglobin, a compound of a globin, and an iron-containing portion, heematin. The glucoprotains contain a carbohydrate nucleus attached to the protein. Several proteins not contained in this class, such as egg albumin and nucleoprotein, contain carbohydrate, but not in such large amoixnts. The chief members of this class are the mucins. The carbohydrate in them is usually glucosamine, of which there is often as much as 30 per cent. When glucoprotein is treated Avith dilute mineral acid, a sugar is split off which gives the " reducing " tests for sugar, but will not ferment with yeast. The nucleoproteins form the chief constituent of the nuclei of cells. They consist of protein in combination with nuclein, itself a compound of protein with nucleic acid. There are several nucleic acids. The simplest (so-called guanylic acid), found in the pancreas, yields, on decomposition, phosphoric acid, guanin, and a pentose; nucleic acid proper yields the purin bodies, guanin and adenin, a hexose, and THE PROTEINS 49 pyrimidin bases, especially cytosin. The following scheme shows the relationship of nuclein: Nucleoprotein (digested with pepsin) Nuclein (brown sediment decomposed ~ ~~ by acid alcohol) 4/ Peptone (goes into solution) Acid melfiprofi.in (in solution) Nucleic acid (white precipitate) heated in clo'-'cd tube with HCl \lr \1/ \U Purin bodies Garhohjdrate Phosphoric acid adenin, guanin) (pentose or hexose) Pyrimidin bases (especially eytosia) The chief of the pyi'imidin bases is cytosin — amino-oxyiDyrimidin CjH^N^O, graphically expressed : HN— CNH II II OC CH N=CH Uracil is diox3rpyrimidin, C^H^NoO.,, HN— CO I I OC CH I II HN— CH Thymin is methyl uracil, CsHgNgO^, HN— CO I I OC C.CH3 I II HN— CH The Purin Bases are perhaps the most important cleav^age products of nucleoprotein, distinguishing it from phosphoprotcin, which does not contain them. They are all compounds of the hypo- thetical purin ring (see p. 3!- ), The two immediate products of hydrolysis are adenin and guanin. These are in close relationship with the bases hypoxanthin and xanthin and with uric acid. 50 A TEXTBOOK OF PHYSIOLOGY Adeniii is 6-amiiio-purin, CjHyN^NH^, the amino grouping ])oing ill the () position of the purin ring. (jlr<'])hically expressed it is N=C.NH., ^CH HC C— NH. II II N_C— N- Oiianin, C-H3N4O.,, is 2-amino-6-oxypurin, or HN— CO NH, CH H2N.C C— NH N— C— N^ Besides being fonnd as a product of hydrolysis of nucleoprotein, it is found in small quantity in muscles and also in the scales of fishes Hypoxanthin, C^H^N^O, is 6-oxypurin, or HN CO I 1 HC C— NH II II t'H N C— N It is obtained from adenin by " deaminization," the replacement of the NH., group by an atom of oxygen. This takes place in the body as the result of the action of an enzyme known as adenase : C5H3N4NH2 + H.O = C5H4N4O + NH3. Hypoxanthin is also found in the muscles. It is abundant in the sperm of certain fishes, such as the salmon and the carp. It also occurs in snuxll quantities in bone marrow, in milk, and in urine. Xanthin, C^H^N^O^, is 2, 6, dioxypurin, or HN— CO I I OC C— NH I II CH NH— C— N It bears the same relationship to guanin as hypoxanthin does to adenin. In the body the enzyme guanase converts guanin into xanthin. Oxidizing enzymes also possess the power of converting hypoxanthin to xanthin by adding on an atom of oxygen. Uric acid is trioxypurin; its chemical relationshij3s are discussed fully later (see p. 458). Derived Proteins : Acid and Alkali Metaprotein may be pre- pared by treating a solution of egg A\'hite with a little dilute acid (10 per cent. HCl) or dilute alkali at body temperature for five minutes, and then heating uj^ to the boiling-point. The metaprotein thus formed differs from the original egg albumin in not being coagulated by heat while in the acid or alkaline solution, and in being precipitated (salted out) by half-saturation with ammonium sulphate (see table THE PROTEINS 51 below). Acid metaprotein may be changed into alkali metaprotein, but the reverse change cannot take place, since the alkali splits off some of the loosely combined nitrogen and siili)hur. If alkali meta- protein be prepared by the action of strong alkali on egg white, a substance known as '" Lieberkuhn's jelly " is formed. Acid meta- protein is formed in peptic, alkali metaprotein in tryptic, digestion. Proteoses and Peptones. — These occur in the first stages of protein cleavage (see table I xlo\\), and are more fully dealt with under Diges- tion (p. 386). The proteoses are usueJl}' divided into i^rimary and secondary. They are not coagulated by heat, are very slightly diffusible, give a pink colour with the biuret test, and a white j^recipitate with salicyl-sulphonic acid, which disap23ears on heating and reappears on cooling. Primary proteoses (except a form known as hetero- protecse) are salted out by half-saturation with ammonium sulphate, secondary proteoses by full saturation (see table bcljw, also p. 3h'6). Peptones are characterized by their read}^ diffusibility through parchment membranes. They also give a characteristic pink colour with the biuret test. They are not coagulated by heat, and are not precipitated by nitric or salicyl-sul])honic acid. They are preci])itated by alcohol and picric acid. Protein. Solii- hility. Diffusi- bility. Action of Heat. Biuret Test. 11 Is' Salting out with + MgSOJull Satu- ration. Globulin Saline Nil Coagu- Violet Half lated Albumin Water Nil Coagu- lated Violet Full - Primary Water Slight Not Pink Half -1- proteoses coagu- lated Secondary Water Slight Not Pink Full _ proteoses coagu- lated Peptones Water Consider- able Not coagu- lated Pink Not ' Acid Acid Not Half -1- metaprotein coagu- lated Alkali AlkaU Not Half + metaprotein coagu- lated Caseinogen Weak a kali Nil Not coagu- lated Violet Half -h Nitric or Sal icy I Sill pho- nic Acids. Action of Alcohol. Pp. insol. Ppt'd, then on coagu- hcating lated Pp. insol. Ppt'd, then on heating Pp. sol. on heating Pp. sol. on heating No pp. coagu- lated Ppt'd Ppt'd Not ppt'd Ppt'c 52 A TEXTBOOK OF PHYSIOLOGY CoLOiTK Tests for Proteins. Name. Biuret (Rose's or Piotrowski's tost). Xanthoproteic Millon's Adamliiewicz's or Hopkins's (glyoxylic) Lead sulphide test Molisch's test Procedure- Result. KOHandCuSO^ Add HN0:5 Add mixture of mercuric and mercurous nitrates Glacial acetic and H2SO4 Lead acetate + KOH a-Naphthol and H2SO4 Violet or pink colour White pp., yellow on heating, orange with ammonia White pp., brick red on heating Violet ring Black colour on heating, due to formation of lead sulphide Purple ring Significance. Two CONH groups linked toofether Presence of benzene ring Presence of hydroxybenzene ring Presence of tryptophan Presence of sulphur Presence of carbohydrate group attached to protein CHAPTER VI FATS AND LIPOIDS Section I. Neutral Fats and Fatty Acids. — Fats occur widely distributed in the plant and animal kingdom. In the former they occur in seeds, roots, and fruits; in the latter in varying quantities in all tissues, but particularly in the adijjose tissue, bone marrow, and milk. Neutral fats are compounds of the fatty acids with the triatomic alcohol, glycerine. They are generally j^ellowish in colour or colourless, and when pure have neither odour nor smell. They have the general formula : CH2— O— CO— R I CH— 0— CO— R I CH.— 0— CO— R — where R, the fatty acid radical, usually stands for palmitic, stearic, or oleic acid. Of these, palmitic and stearic are saturated acids, and have the general formula CnHg^ ^^COOH, n being 17 in stearic acid, CJ-H35COOH, and 15 in palmitic acid, C15H33COOH. Oleic acid, C1.H33COOH, is unsaturated, and therefore possesses the power of decolorizing dilute bromine-water and of combining with iodine. This latter propertj^ is used to determine the amount of olein present in the ordinary fats, which are mixtures of varying proportions of olein, stearin, and palmitin. The melting-point of fat also varies according to the relative amounts of these fats present. Olein is fluid at ordinary temperature, melting at -5° C; whereas palmitin melts at 45° C, and stearin at about 56° C. The Huid nature of fat at body tempera- ture is therefore due to the amount of olein which it contains. Butyrin occurs in the fat of milk. When a liquid fat is shaken with soap, mucilage, or egg albumin, it becomes finely divided, or " emulsified." Rancid fat emulsifies on addition of alkali far more easily than neutral fat, because soap is formed from the alkali, free fatty acid being present, and the soap renders emulsification easier. Hence the fact that fat is rendered faintl}^ rancid in the stomach is of importance. Emulsification is a physical change; the minute subdivision hastens the chemical change of fat. By hydrolysis of fat, glycerine and fatty acid are produced. This process is known as saponification, and can be brought about by such agencies as superheated steam, boiling with alkali, long-continued 53 54 A TEXTBOOK OF PHYSIOLOGY contact with air (oxygen is taken up and rancid oil produced), the action of fat-sphtting enzymes or Hpases. The reaction can be represented thus: C3H,(OCj,H3,CO)3 + 3H.0 = C3H3(OH)3 + 3Cj,H3,COOH Palmitin GlyccMinc i'almitic acid In true saponification the fatty acid formed combines with the alkali present to form a soap : t^isHs^COOH +NaHO= Ci^HgiCGONa + H2O Soap Fats from different species of animals vary in composition, and fats from different parts of the same animal have \'arying composition depending upon the combination of individual fats which form the mixed fat of any part. From the liver, for example, fatty acids, more unsaturated than oleic and belonging to the linolic and linolenic series, have been isolated. Milk fat is characterized by its yield of butyric, caproic, caprylic, and other volatile fatty acids. From kidney fat an acid known as carnaubic acid has been isolated. Stearin, CH20Ci8H3,0 CH0Ci8H350 CH,0C,A50 occurs generally in animal fat, but is found also in certain vegetable fats. It is the hardest and most insoluble of the three common fats. Its melting-point when pure is 55° C, but as obtained from the tissues about 63° C. Stearic acid, the acid of stearin, crystallizes in long rhombic plates, and crystals of it may sometimes be seen in a melted rancid fat after it has solidified. Palmitin, CIl.,OC^Ji^^O CHbCieH.^iO CH,OCi,H,iO occurs largely in human fat. Its melting-point is about 50° C. Palmitic acid crystallizes as fine needles. Olein, CH2OC18H33O CH0Ci,H3,0 CH,OCi8H3,0 is verj^ widespread, being found in most animal and vegetable fats. At ordinary temioeraturc it is liquid, solidifying at - G° C, and acts as a solvent for the stearin and palmitin of ordinary fat. The melting-point of a fat, its iodine value, and staining properties with osmic acid, depend upon the amount of oleic acid present. The fatty acids may be obtained from neutral fats by treating with dilute mineral acid, when the fatty acid will collect as an oily FATS AND LIPOIDS 55 scum upon the top of the fluid. Fatty acids in appearance closely resemble neutral fats, being generally almost colourless. Fatty acids may be distinguished from neutral fats — . 1. By their reaction. This is usually tested as follows: Some alcoholic phenolphthalein solution is added to alcohol, and one drop of weak alkali (1 per cent, sodium carbonate) added. The addition of neutral fats will not discharge the red colour thus produced, fatty acids will. 2. Fatty acids dissolve in cold sodium carbonate to form a soap; neutral fat is insoluble in cold sodium carbonate. 3. The acrolein test. The acrolein is derived from glycerine. Neutral fats therefore give this test, fatty acids do not. To ]ierform the test, the substance is mixed with acid potassium suli^hate (KHSOJ by grinding in a mortar. Upon heating the mixture acrolein is evolved, if the test is positive, and may be recognized by its acrid smell and by the fact that it blackens a })iece of paper dipped in an ammoniacal solution of silver nitrate. It is important to be able to distinguish different forms of fat. The chief chemical methods emplo3'cd are — 1. Melting-point. This varies with different animals. Mutton fat, 44° to 51° C, is generally higher than pig fat, 36° to 46° C. 2. Specific gravity. Some melted fats will float in alcohol at room temperature; others will not. For example, margarine, which often contains light vegetable oils, will float, pure butter will sink. 3. Acid value. The amount of free fatty acid contained in the fat. 4. Iodine value. The percentage amount of iodine absorbed by a weighed, quantity of fat. This depends upon the amount of un- saturated fatty acids present, such as olein. 5. The amount of volatile fatty acids present (Reichert-Meissl value). Obtained by saponifying the melted fat with alcoholic potash, and treating the soap thus obtained with sxdphuric acid. Volatile fatty acids will distil off. These are collected in standard ^^^ alkali, and their amount determined by titration. Pure butter has a much higher value in volatile acids than has margarine. Soaps are the compounds of fatty acid and a base. When the base is sodium, ordinary washing soap is obtained : when it is ])otassiinn. " soft " soap is produced. Those are soluble in water, f. 'ming a " soapy " colloidal solution. They are "' salted out '" b\- full satura- tion with ammonium sulphate. With solutions of calcium or mag- nesium salts they yield a dense white 2)recipitate ; this accounts for the dithculty, familiar to everyone, of washing with a "" hcird " water. When boiled with a mineral acid (20 per cent. sul})huric), the fatty acid is displaced from combination, and collects at the top as a Avhitc scum or oily fluid. If lead acetate be added to a soap solution, a white ]n-ecipitatc of lead soap (lead plaster) is obtained. 56 A TEXTBOOK OF PHYSIOLOGY Section II. Lipoids. — Uudcr this uanie are grouped a number of fat-like (lijjoid) bodies, rebciubliiig fat mainly in their common sohibiHty in certain solvents. They occur in the protoplasm of all cells, and are probably bodies of wide biological significance. They are particularly abundant in nervous tissue. They may be classified as follows : I. The Phosphatides — bodies containing carbon, hydrogen, oxygen, nitrogen, and phosphorus. II. The Galactosides — bodies containing carbon, hydrogen, oxygen and nitrogen. III. The Cholesterols — bodies containing carbon, hjalrogen, and oxygen. I. The PoHriPitATiDEs are all compounds of the triatomic alcohol glycerine, to which a fatty acid, phosphoric acid, and a nitrogenous base are attached. The chief members of this group are the lecithins. The members may be classified according to the proportion of nitrogen to phosphorus in their molecule : Monamino-monophosphatides : lecithins, cephalin. IN IP Monaniino-diphosphatides : cuorin. IN 2P Diamino-monoj^hosphatides : sphingomyelin, jecorin. 2N IP Diamino-diphosphatides, etc. 2N 2P, etc. Triamino-monophosphatides : carnaubin, obtained from kidney fat, belongs to this group, but yields no phosphoric acid. The action of narcotics and of chloroform and ether has been attributed to the solubility of these substances in the phosphatides of the nerve cells. In the reactions of specific cell poisons, toxins such as snake poison, and ha^molysins, lecithin may take an active part. So, too, in the action of ferments. Cholesterol, on the other hand, may act as an antibody, precipitating ferments, and neutralizing the action of snake venom. The Lecithins. The lecithins are the most important members of this group of phosphatides, and also, perhaps, the most important of lipoids. They are present in all the cells of the body, and are particularly plentiful in the envelope of red blood -corpuscles, in nervous tissue, bone marrow, liver, and bile. The lecithins probably play an important part in the metabolism of the cells, forming easily dissociable compounds with sugars, pro- teins, etc., and helping in the transport of these substances in the body fluids. The fact that each tissue has its specific lipoid helps to endow that tissue with it;i specific function. In the nervous tissues these substances arc of paramount importance, and on extensive degenera- tion of nervous tissue the body becomes poorer in kcithhis. FATS AND LIPOIDS 57 Lecithins differ from fats in containing nitrogen and phosphorus. Two of the hydroxyl groups of the glycerine radical are combined with fatt}^ acids, the remaining one being linked to phosphoric acid in conjunction with an ammonium base, chohn. The structural formula of lecithin is, therefore — / CH,OCi,H35CO| CHOC17H35CO f Stearic acid Glycerine OH [ CR^— 0— P— 0 ^ 0-N= (CH3)3 Phosphoric \ Acid CH.,— CH.OH Cholin Pure lecithin has a waxy appearance; it is soluble in alcohol and chloroform, less soluble in ether. When mixed with water and viewed under the microscope, it gives out peculiar processes which remind one of the pseudopodia of an amoeba. There are various lecithins, which differ according to the fatty acid combined with the molecule. Like the fats, the lecithins can be hydrolyzed. When saponified they yield fatty acid, glycerophosphoric acid, and cholin: C4iH9oNP09 + 3H20 = = 2{C,sR,,0,) +c,}i,-po,+c,ii,,m, Lecithin Stearic Glycero- Cholin acid phosphoric acid Lecithin is split up by cell ferments, and phosphatides may be rebuilt in the laboratory of the cell. Cholin — trimethyloxyethylammonium hydrate — OH (CH3)3N- CH2.CH2OH — is closely related to the alkaloid muscarin. Methylamines are among the products of bacterial decomposition of lecithins. Neurln, which contains one molecule of Avater less than cholin, is a very poisonous product, and may be the cause of "ptomain" poisoning. ChoUn pro- duces a marked fall of blood-pressure when injected into the blood. It is said that cholin occurs in the blood and spinal fluid when nervous tissue is undergoing degeneration, and can be isolated as yellow octahedral crystals by adding platinum chloride to an alcoholic extract of the fluids. These crystals differ from similar ones obtained by the inter- action of potassium chloride (also present in b'ooi) with platinum chloride, in that thej^ become changed when treated with a strong solu- tion of potassium iodide to dark brown plates. The claim that choHn can be demonstrated in these fluids has not met with general acceptance. II. The GALACT031DE5. — These bodies occur largely in the body known as protagon, obtained from the brain tissue. They are so 58 A TEXTBOOK OF PHYSIOLOGY (•all(!(l hecaii.so ii])on hydrolysis they yield the reducing sugar galactose, ill addition they also yield a base known as sphingosiii, and an acid of a fatty acid nature. The two chief members of this group are cerebrin, or ])hrenosin. and kerasin. TTT. The Cholesterols. — Cholesterol, C^.H,.OH, chemically s])eak- ing belongs to quite a different series of t)odies. It contains neither nitrogen nor phosphorus, and is prol)ably a monatomic alcohol of the terpcne series. Bodies of this series are common in plants, examples being camphor and turpentine. The following formula has been suggested : (CH,)^ - OH— CH^— CH^— Ci.H., — CH = CH, CH, CH, CH(OH) It occurs in all the cells and fluids of the body in small quantities, but particularly in nervous tissue and in the envelope of the red blood- corpuscles. It is also present in the bile, from which in catarrhal states of the bile-ducts it may sometimes separate, forming biliary calcvdi. Cholesterol is probably not merely a waste product as it was once deemed to be. As stated above, it hinders the action of ferments and also that of certain poisons, such as snake venom and saponin, upon the red blood-corpuscles. It is sometimes found as an ester in the liver and plasma in com- bination with a fatty acid such as oleic, palmitic, or stearic. It occurs also in the suprarenal capsules in this form. Cholesterol is soluble in ether, chloroform, and warm alcohol. Its solutions are dextrorotatory. From these it crystallizes in charac- teristic colourless transparent plates, each with a small piece knocked out of the corner. It is insoluble in water, dilute acids, or alkalies. The most general tests for cholesterol are— 1. A red coloiu' results when concentrated sidphuric acid is added to a chloroform solution of cholesterol. (Salkowski's test.) 2. A play of colours, red, blue, green, is obtained when the same acid is added to a solution of cholesterol in acetic anhydride. (Liebermann's test.) Isocholesterol, a body similar to cholesterol in most respects, is found in sebum. It differs from cholesterol in not giving Salkowski's test, and in being levorotatory in solution. Phytocholesterol is the special name ajiplicd to the cholesterols of plants, from ^hich animal cholesterols are probably derived. Cephalin is found largely in both the Avhite and grey matter of nervous t issues. It is soluble in ether and chloroform, but not in alcohol . Sphingomyelin is found in protagon, and also in the suprarenal capsules. Jecorin is found in the liver. It is probably a combination of a phosjjhatide and a sugar. CHAPTER VII THE CARBOHYDRATES These important foodstuffs occur abundantly in the vegetable kingdom, and are also found in small quantities in the animal kingdom, either in the free state or combined with proteins. As a group the carbohydrates form one of the chief energy-producers or foods. As their name implies, they are composed of carbon, hydrogen, and oxygen, the latter elements being j^resent in the proportion found in water (2 : 1). Their general formula is C^^^H.^ifin- It was at one time thought that carbohydrates were bodies containing six atoms of carbon or some multiple thereof. This is now known not to be the case; indeed, the most recent classification of the simplest members of the group is according to the number of carbon atoms contained in the molecule; those, for example, containing three atoms being termed trioses, those with five atoms pentoses, those with six atoms hexoses, and so on. It must not be thought that all bodies containing C, H, 0, with the hydrogen and oxygen in the proportion of water, are contained in the group of carbohydrates; for example, C.^H^Oa is the empirical formula for acetic acid, CgHgOg that of lactic acid. Nevertheless, the definition holds for the most part, and the best- known members of the series do contain six molecides of carbon or some multiple of six. These are generally grouped as follows: 1. The monosaccharides — CV.HjoOr, 2. The disaccharides— Ci.Ho.O,"'! 3. The polysaccharides — (CpHjoOg)^ Section I The Monosaccharides. — The chief monosaccharides of physio- logical importance arc the hexoses, dextrose, levulose, and galactose. Each has the em})irical formula C,.Hi._,0,,. Dextrose is the aldehyde of the hexatomic alcohol sorbite; levulose is the ketone of the hexatomic alcohol mannite; galactose is the aldehyde of another hexatomic; alcohol, dulcite. Each alcohol has the formula C,.H^(OH)|.. The structural formula of these sugars mav be represented as given on p. 60. Levulose differs from the other t^o in being a ketone; dextrose and galactose differ from each other and from their many isomers in the position of the so-called as} inmetric carbon atoms. All bodies 59 CO A TEXTBOOK OF PHYSIOLOGY like the above, which rotate the phiiie of pohirized hght, contain one or more asymmetric atoms. COH I HCOH HOCH I HCOH 1 HCOH CH2OH Dextrose CH.OH CO I HCOH I HOCH 1 HOCH CH2OH Lovulosc COH I HCOH I HOCH I HOCH HCOH CH2OH Galactose The waves of light, moving onwards, vibrate in every plane. When they pass through a quartz plate they are plane polarized, and vibrate only in one plane. A .stretched string can be plucked and made to A'ibrate from side to side, or from above down, or in any other plane. If the string passes through a vertical slit, it can onlj' be made to vibrate in the above-down direction; it is, so to speak, jjlane polarized. The quartz plate has a similar effect on light. If two quartz plates are arranged so that the light must pass through both, then the light polarized by the first plate can pass through the second if this be placed with its optical axis in the same relation as that of the first plate. If the second plate is turned at right angles to the first plate, the light polarized by the first plate cannot pass the second. If a solution which rotates polarized light is placed in a tube between the two quanz plates, its efiect on the rotation of the second quartz plate can be determined. Special instruments called polarimc '^ers are contrived for measuring the effect of solutions on the rotation of polarized light, and so arriving at the strength of the solutions, e.g., of sugar. The various groups may be arranged in a figure round an asymmetric carbon atom so that one arrangement corresponds to dextrorotation, another to levorotation. The two figures cannot be superimposed so that the same two groups coincide. In this respect it is interesting to note that Pasteur found that racemic acid, which has holohedral crystals, and is neutral in its action to polarized light, could be decomposed into dextrorotatory and levorotatory tartaric acids with hemihedral crystals. Of these crystals, those which were right-sided gave dextrorotation, those which were left- sided gave levorotation. By growing Penicillium glaucum upon racemic acid, the dextrorotatory portion of ordinary tartaric acid is destroyed and the levorotatorj^ acid is left. The monosaccharides are colourless cr3'stalline bodies (with a sweetish taste) readily soluble in water, with difficulty soluble in alcohol, and insoluble in ether. They possess the property of depositing metallic silver from ammoniacal silver solutions, cuprous oxide from alkaline coj)per solutions, and bismuth suboxide from alkaline bismuth solutions. This property is of especial value as a test. The chief tests are the following : 1. Moore's test. Upon heating with one quarter of its volume of strong caustic potash or soda, the solution becomes yellow, then brown, THE CARBOHYDRATES 61 due to the formation of caramel and levulinic acid; a faint odour of caramel is also produced. 2. Trommer's test. A mixture of weak copper sulphate and potassium hydrate yields, on heating with the sugar solution, a red precipitate of cuprous oxide. At first cupric hydrate is formed by the interaction of the alkali and the copper sulphate; this hydrate is then reduced to cuprous hydrate, with the formation of acid. The cuprous hydrate on further heating loses water, forming cuprous oxide. 1 . CuSO^ + 2K0H = Cu(OH)., + K0SO4 Copper Caustic Cupric Potassium siilpliato potash hydrate sulj)hate 2 . 2Cu(OH)2 + RCHO = Cu2(OH)2 + R.COOH + H2O Cupric Aldehyde Cuprous Acid and water hydrate lij^drato 3. Cu,(OH)+H20 = Cu20 The above only takes place when the amount of copper solution is neither too little nor too much. Excess of copper salt leads to the formation of brown cupric hydrate, which spoils the test. 3. Fehling's test. For this reason the excess of copper salt is generally held in solution by the addition of Rochelle salt (sodium potassium tartrate) in definite proportion to the alkali and copper salt. This is known as Fehling's solution.* When freshly prepared it is unaltered by boiling. It is reduced by all the sugars except cane-sugar. Unfortunately, it is also reduced by other bodies, such as uric acid, creatinin, glycuronic acid, etc. 4. Nylander's test. This disadvantage does not pertain so much to the salts of bismuth. The solution most generally employed is Nylander's solution. f Upon boiling for a few minutes with a sugar, the solution goes yellowish-brown to black, and finally deposits a precipitate of metallic bismuth. Glycuronic acid gives this test; uric acid and creatinin do not. 5. Barfoed's test. An acid solution of cupric acetate gives a red precipitate with the monosaccharides. 6. Phenylhydrazine test. This test consists in heating about 10 c.c. of the sugar solution in a test-tube on a water-bath with phenyl- hydrazine hydrochloride and sodium acetate — as much as will cover a threepenny-piece of the former, and a sixpenny-piece of the latter. After about thirty minutes a yellow crystalline precipitate settles out which looks like yellow sheaves under the microscope. The osazones yielded by dextrose and levulose are the same; that of galactose is the same in appearance, but differs in melting-point (see table, p. 04). Of the disaccharides, cane-sugar does not yield an osazone; until * Fehling's solution = Copper sulphate 3-l*30 grammes, NaOH 50-60, Rochelle salt 173 grammes, per litre of water. t Nylander's solution == Bismuth subnitra to 20 grammes, Rochelle salt 40 grammes, dissolved in 1,000 c.e. of 8 per cent. NaOH. , 62 A TEXTBOOK OF PHYSIOLOGY it becomes inverted; lactose yields distinctive crystalline rosettes, which are better obtained if a little free acetic acid be also added to the sugar solution; maltose yields an osazone, so soluble that it does not appear until the solution is cooled. 7. Molisch's test. All carbohydrates yield with a-naphthol and sulphuric acid a purple colour. The greenish colour which is also present forms no part of the test. The test is ver}^ sensitive; carbo- hydrates linked to proteins yield it. 8. The Fermentation test. This is a very useful test for aiding in distinguishing the different sugars. The sugar- solution is introduced with a small piece of brewer's yeast into a Southall's urometer (see p. 4r)8), and placed in an incubator at 37" C. The production of carbon dioxide gas indicates fermentation. A control tube of 3^east and water should yield no gas. 9. The Polarimetric test. This consists in determining the rotation power of a solution of known strength of the sugar. In the case of disaccharides the rotatory power is determined before and after inversion with acid. Each disaccharide behaves differently on hydro- lysis (see table, p. 64). Dextrose (also termed glucose and grape-sugar) occurs abundantly as such in the grape, in other sweet fruits, seeds and roots, and honey ; it is more often found in conjunction with levulose. It is formed by boiling starches and dextrins with dilute sulphuric acid, the syrupy sugar thus formed being largely em])loyed in beer, jam, and sweet making. Occasionally arsenical impurities in the common sulphuric acid (oil of vitriol) used in this process have led to cases of arsenical poisoning. It is also produced from starch by hydrolytic changes in the alimentary tract. Dextrose is the sugar found in the blood and muscles (1 per 1,000 parts), being an important source of energy to the latter. Under normal conditions only the merest trace occurs in the urine. In the body it is converted into and stored as animal starch or glycogen. The specific power of rotation of glucose is + 52-6. Levulose (fructose) occurs widely in conjunction with dextrose in fruits, and also in hone}'. It is generally obtained as the result of the splitting up of cane-sugar. It may occur in the urine. It is readily soluble in water, but not in cold alcohol. Its levorotatory power is about — 93. It gives the usual reducing tests, and ferments readily with yeast. Its osazone is similar to that of dextrose, the melting-point being 204° C. The characteristic test for levulose is known as Seliwanoff's test. When one part of HCl in two parts of water, in which a few crystals of resorcin have been dissolved, is added to levulose, a deep cherry-red colour results. Galactose is obtained by the splitting of lactose (milk-sugar). It is also obtained when certain lipoids (galactosides) are split by weak mineral acids. It is less soluble in water than dextrose. It gives the reducing tests. Its osazone melts at 196° to 197° C. It turns the plane of polarized light to the right, its rotatory power being -f 81. With yeast it ferments but slowly. Upon oxidation with nitric acid THE CARBOHYDRATES 63 it 3uekls first galactonic and then mucic acid; the latter, being in- soluble, separates out as crystals. The Pentoses, CgH^^Og, occur as the complex carbohj'drates of the vegetable world, known as pentosans. They also occur in the constitution of certain nucleoproteins of the animal kingdom (see p. 49). They are of interest as occurring in human urine in the rare anomaly of metabolism known as pentosuria. Glyeuronic acid, C,.HjqO., CHO (CH0H)4 I COOH, is a derivative of dextrose. It is found as a combined acid in the blood, bile, and urine. It gives the same reduction tests as dextrose, and also the special pentose reactions (q.v.). The osazone, which resembles glucosazone, is difficult to obtain. With bromphenylhy- drazine hydrochloride a gh'curonate is formed characterized by its insolubilit}^ in alcohol. Glj'curonic acid itseH is dextrorotator}', but its compounds are levorotatory. Glucosamine, CgHjgNOj, CH,OH 1 ■ (CH0H)3 CHNH, 1 COH, also called chitosamine, is most readily prepared from ehitin {e.g., decalcified lobster shells) by the action of strong hydrochloric acid. It is an amino sugar, and has been obtained from glucoproteins (mucins) and other proteins. Glucosamine has reducing properties similar to dextrose, yields the same osazone, but is not fermentable. Sectiok II. The Disaccharides (Ci-iHooO^^). — The disaccharides cane-sugar, maltose, and lactose, are to be regarded as the combination of two molecules of monosaccharides with the elimination of a molecule of C12II22O11 + H3O = CgHioOg + CgHi^Ofi Cane-sugar -f- water = dextrose-H levulose Maltose -|- water=dextrose-l- dextrose Lactose -h water = dextrose + galactose Each disaccharide is readily split by boiling with Aveak mineral acid into its component monosaccharides. Cane-sugar may also be 04 A TEXTBOOK OE rHYSIOLiXlY split by weak organic acids such as citric and tartaric. This process, one of hydrolysis, is sometimes termed inversion owing to the fact that cane-sugar before hydrotysis is dextrorotatory, but after hydrolysis is levorotatory. In the case of maltose and lactose the term is also employed, but no inversion of polarized light takes place on hydrolysis ; maltose gives a considerable fall, lactose a slight rise, in rotating power after " inversion." None of the disaccharides yields Barfoed's test. Cane-sugar, or saccharose, occurs widely in the plant world, very abundantly in the sugar-cane and the sugar-beet. It jDossesses a distinctly sweet taste, is easily soluble in water, but with difficulty in alcohol. Its rotator}^ power is 60-5 before, and - 20 after, inversion. In other resjaects it gives few positive tests. It does not give Moore's test nor the ordinary reducing tests. It gives no osazone. It does not ferment with yeast mitil inverted. The Reactions op Monosaccharides and Disaccharides. Dextrose. Levidose. Galactose. Maltose. Lactose. ; Cane- Sugar. Moore's test (KOH) + + + -t- -f- - Trommer's test (CUSO4+ KOH) + -1- -1- -Fve 33% weaker than D. -Fve 26-50/, weaker than D. Fehling's test (CuS04+K0H-f- Rochelle salt) -1- + -1- + + — Nylander's test (bismuth sub- nitratt + KOH-t- Rochelle salt) + + + -1- i -1- Barfoed's test (acid cupric acetate) -f- + -f - - - Phenylhydrazine test (Osazone crystals formed) Long thin needles M.P. 204 Long thin needles M.P. 204 Long thin needles M.P. 186 Short thick needles ;M.P. 206 YeUow rosettes M.P, 201 Rotary power on polarized light -1-52-7 -93 -1-81 + 137 -t-52-5 + 66-5 Effect of hydro- lysis on rotary power — — — Marked fall Slight rise Inverted to 20 to the left Yeast fermentation test Marked Marked Very little Marked Nil Marked after inversion Solubility in alco- hol; cane-sugar =1 — + — 1 Insol. 1 THE CARBOHYDRATES 65 Maltose is produced as the result of hydrolytic changes either by the action of acids or of enzymes upon starch. It is readily soluble in water, and fairly soluble in alcohol. Its solutions are dextro- rotatory: [ajjj = 137-139. It ferments readily with yeast. It gives the same reduction tests as dextrose, with the exception of Barfoed's. The osazone is difficult to prepare, requiring warming for as long as one and a half hours. The crystals are characteristic in shape, being coarser than those of dextrososazone. Their melting-point is 205°. Lactose is the characteristic animal sugar, being found only in milk, and occasionally in the urine of pregnant women. It dissolves fairly readily in water, has a faint sweetish taste, and is insoluble in alcohol. Its solutions are dextrorotatory, and [aj^ = 52-5. With the exception of Barfoed's it gives all the reduction tests. Its osazone forms characteristic rosettes, and has a melting-point of 201° C. With nitric acid it yields mucic acid crystals. It is not fermentable with pure j^east, but it undergoes alcoholic fermentation with the " kephir"' fungus. With this fiingus an alcoholic drink is prepared chiefly from mare's and camel's milk. Section III. The Polysaccharides. — This group includes the more complex ■carbohydrates, such as the dextrins and vegetable gums, starches and celluloses. They are characterized by the large size of their molecule, being tlierefore colloidal in nature. The Celluloses (C^H^qO.)??-. — Plant cellulose is in reality a mixture of celluloses. These bodies are insoluble in hot or cold water, alcohol, ether, and dilute acids or alkalies. They are soluble, Jiowever, in ammoniacal copper oxide solution (Schweitzer's re- agent), from which they are precipitated by acids. When acted upon with strong sulphuric acid, cellulose yields a substance known as amyloid, which gives a blue colour with iodine solution; by pro- longed treatment dextrose is produced. By the action of strong nitric acid, explosives (nitro-celluloses) such as gun-cotton are produced. In the intestinal tract, particularly of herbivora, the enzyme known as cytase partially decomposes cellulose. The Starches (C^-Hj^oO^)/?- are a reserve food of wide distil bution in the vegetable kingdom, being stored as grains shaped in various forms in seeds (the cereals), tubers (potatoes), etc. As a commercial product starch is a white amorphous powder without taste or smell, insoluble in cold water, but jdelding an emulsion with hot water. A starch emulsion is best made by mixing starch to a paste in the cold, and gradually stirring this into boiling water, a well- known domestic process. By the action of the boiling water the starch grains are made to swell up and break, and the starch i« eon verted m A TEXTliOOK OF PflYSTOLOCY from the variety known as in.solii))le starch into sohible starch. The sohition yields a characteristic bhie colour with iodine solution, which, if sufficient starch be present, disappears on heating, and reappears on cooling. 2-5 to 4-G j^er cent, solutions exhibit a rotatory power of about +202. Starch gives neither Moore's nor Trommer's test, and none of the other reduction tests. It does not ferment with yeast. Upon boiling witli dilute acid, or under the action of the grouji of enzymes known as diastases, it is split first into dextrins and then into sugars, maltose being formed as the result of enzyme action, dextrose by the action of the acids. Starches are " salted out " by half-saturation with ammonium sulphate. They are also precipitated from their solutions by 50 to 55 jier cent, alcohol. In some plants, such as the tubers of the dahlia, a special variety of starch known as inulin occurs. It forms an amorphous white powder, differing from ordinary starch in giving a yellow colour with iodine solution, and yielding levulose on h3^drolysis with acid. Diastatic enzjmies have little or no effect on this body. Glycogen, or animal starch, found chiefly in the liver of animals, is obtained as a white amorphous powder soluble to an opalescent solu- tion in water. It gives a mahogany brown colour with iodine, is pre- cipitated from solution by 60 per cent, alcohol and basic lead acetate. Characterlstic Reactions of Polysaccharides. Starch. Glycogen. Eryihrodextrin. Achroodextrin. Moore's test - - Reduction fests: Trommer, etc. ~ — - - Ditto after hydrolysis + + + + S olubility in water Opalescent ; sol. in hot water Opalescent solution in cold Clear solution in cold Clear solution in cold Solubility in alcohol Insol. Precipitated by 60% Precipitated by 80%-85% Precipitated by 90% Iodine solution Blue Mahogany brown Red No colour Salting out with Am^SOi Half- saturation Full Full Not salted out Basic lead acetate Precipitated Precipitated Not precipitated Not precipitated Dextrins (C'^HjqO-)?^. — These are the first products of the hydro- lysis of starches produced by the action of weak acids or of starch- THE CARBOHYDRATES 07 splitting enzymes. Commercial dextrin is a sweetish, sticky amorphous powder. It probably consists of many dextrins, of which two may be mentioned — erythrodextrin and achroodextrin. It often contains some reducing sugar. Erythrodextrin, or "red dextrin," as its name imi^lies, is so called because it yields a port-wine colour with iodine solution. It is regarded as the first product of the hydrolysis of soluble starch. It is distinguished from glycogen by giving a clear solution in hot water, and requiring 80 to 85 per cent, alcohol to precipitate it from solution. It is also not precipitated by basic lead acetate solutions. It requires full saturation with ammonium suljjhate to salt it out (see table, p. 00). Achroodextrin, or '' colourless " dextrin, gets its name because it giv^es no colour with iodine solution. It occurs at a later stage in the hydrolysis of starch; being of smaller molecular weight, 90 })er cent, alcohol is required to precipitate it from solution. The dextrins when pure do not give Moore's test, Trommer's, or other reduction tests; these are only given after hydrolysis to sugars has taken place. CHAPTER VllI ENZYMES OR FERMENTS The chemist recognizes a class of bodies of far-reaching action called catalysts. A catalyst is a substance which by its presence hastens a chemical reaction. A catalyst cannot start a reaction. Chemical eqviilibrivim depends on the laws of chemical dynamics, on the nature of the reacting substances, their active mass or concenti'ation, and external conditions such as temperature, pressure, etc. A catalyst cannot alter the equilibrium of forces, or the final transformation of energy due to a reaction. It can only, so to speak, oil the wheels of the machine. When dry hydrogen and oxygen gas are mixed, they combine to form water, but with such slowness that the reaction 2H2 + 02^21120 escapes observation. Finely divided platinum acts as a catalyst, and enormouslj^ accelerates this reaction. The catalysts may accelerate a reversible reaction in either direction. Thus, in the common type of reaction. Acid and alcohol ;^ ester and water, the acid ester in the presence of a great excess of water can almost wholly be split into acid and alcohol, while in strong concentration most of the acid and alcohol goes to form the ester. The same catalyst can accelerate this reaction in either direction according to the condi- tions. Enzymes (ev (vfjiyj, in yeast) or ferments, are bodies which act like catalysts, and have the power of accelerating the rate of hydrolysis of certain substances or substrates. Probably all the reactions which take place within living cells, or are produced in digests by the secretions of the cells, are aceelerated b}' enzymes. It is the accelera- tion of any reaction which makes it manifest and effectual, for the transformation of energy produced by the reaction is concentrated in a short space of time. It was from the action of yeast that the term " fermentation " arose. The yeast sets the must in a fer- ment; it froths and bubbles. When the action of digestive juiees came to be studied, it was seen to be of the same ferment nature, and a distinction came to be made between "organized" and "unor- ganized " ferments. An organized ferment was the living cell, such as yeast, which brought about fermentation by the metabolism involved in its growth and multiplication. The unorganized ferment was contained in the juice secreted from a cell, and acted on a substrate at a distance from that cell — e.g., saliva acting on starch in the momtk and stomach. 68 ENZYMES OR FERMENTS 69 It was thought that onty the living yeast organism could bring about this characteristic fermentation; after many attempts, how- ever, a juice was expressed from the yeast cell which fermented no less well than the hving organism; thus the distinction between the two kinds of ferments disappeared, and the term " organized ferment " became unnecessary. When the action of enzj^mes, like those of yeast, is normally effected within the cell, the enzymes are grouped as "intracellular'' enzymes, or endoenzymes; those which act when discharged from the cell are classed as " extracellular " enzymes, or exoenzymes. Under this latter group are placed the enzymes concerned in the processes of digestion. There are granules of a precursor, or zymogen, stored within the cells of the secreting glands of the stomach, pancreas, etc., and these are discharged in response to certain definite stimuli. The precursors when discharged require to be " activated " — i.e., turned into the active enzyme by the presence of some other body. Prob- ably all enzymes require the presence of a " co -enzyme " before they manifest their full activitj". Thus yeast juice can be squeezed through a porcelain filter candle impregnated with gelatin by a pressure of 300 atmosiDheres ; the expressed juice is found to have no enzymic action until mixed with phosphates, and some other substance that is diffusible and not destroyed by boiling, which is left behind in the cell residues on the filter. These act as co-enzyme to the expressed juice. The " intracellular " enzymes are concerned intimately with processes of metabolism. If a piece of liver be kept under aseptic conditions, it will be found that the longer it is kept the less nitrogen it contains in the form of protein, the more in the form of products of protein disintegration. Thus, of the nitrogenous substances in some fresh liver, 90-4 per cent, were found to be in- soluble and 9-6 per cent, soluble in water. After keeping mider aseptic conditions for twenty days, 39-4 per cent, of the nitrogenous compounds were found to be insoluble, and 60-6 soluble. Similar results have been obtained on keeping other organs, such as the spleen, th^'mus, kidney. The products of tliis self-digestion, or '■ autolysis," appear to be the same as those of ordinary intestinal digestion, but the different stages have not yet been worked ovit. Autoh'sis takes place in an}^ part of the living organism Avhen the blood-supply is shut off from it. Thus, if an artery be blocked by a thrombus, and the blood-supply cut off fiom part of the brain, it is found that the central part softens and undergoes autolysis. The same occurs in a part of the liver if the circulation be cut off from it. The chief circumstance favouring this change appears to be the in- creased acidity of the cell juice produced by want of oxygen. The peripheral parts do not undergo the same degree of autolysis, owing to the diffusion into them of oxygen and alkaline fluid from the neigh- bouring cells. Such changes take place anj^where in the bod}' as the result of thrombosis or infarction. Autolysis also occurs in the living organism in acute yellow atrophy of the liver, in phosphorus-poisoning, and in certain acute fevers. The products of this digestion can in 70 A TEXTBOOK OF PHYSIOLOGY such cases be detected in the urine. It is sn|)])osed that there are intracellular enzymes normally contained within the tissues; these enzymes, under the varying conditions of life, build up and break down the tissues according to the need of that tissue and of the body as a whole. Under adverse circumstances, such as the shutting off of the blood-supply or the presence of toxins and poisons, the action jnay ]iroceed mainly in the direction of disintegration. Besides the enzyme concerned with the cell proteins, we have evidence of enzymes acting upon carbohydrates and fats. A striking example is the enzyme glycogenase, which forms glycogen from the dextrose brought to the liver cells, and as occasion needs reconverts this glycogen into dextrose. There are intracellular enzymes con- cerned in the formation of urea, uric acid, etc. From the liver alone at least fifteen enzymes have been isolated, which shows the great importance of the intracellular enzymes in the metabolic processes of the body. Whether enzymes be extracellular or intracellular, they have the following well-marked properties : 1. Enzymes perform their action best at an ojotimum temperature. For the enzymes of our body this is 37° C, the body temiDerature. Cold inihibits their action, but does not kill them, even when they are subjected (as has been the case with some unicellular organisms) to the great cold produced by evaporation of liquid air. Warming above the temperature of the body tends to inhibit, while temperatures varying from 55° C. to 70° C. destroy their action altogether. 2. They have an optinnnn medium in which they act. This is usually faintly alkaline (to litmus), and corresponds in the case of intracellular enzymes to the reaction of the body tissue fluids. The pepsin contamed in gastric juice acts best in an acid medium; others apparently work best in a neutral medium. The enzymes of some micro-organisms work best in the absence of free oxygen, and are termed " anaerobic," in contradistinction to the enzymes reqviiring free oxygen for their activity, which are called "'aerobic." 3. They are specific in action. Enzymes are classified according to the substrate upon which they act. There are, for example, pro- teolytic (protein-splitting), lipolj'tic (fat-splitting), amylolytic (starch- splitting), sucrolytic (sugar-sjilitting) enzymes, as well as several others. It is found that the proteolytic act only on protein, the starch-splitting only upon starch, and so forth. Nevertheless, the active powers of some enzymes, which are secreted together, correspond so closely (for examj^le, j^epsin and rennin) that the double action may be manifestations of one parent substance. We may regard the parent substance as having different groups of '' side- chains " attached to it, one group of side-chains acting as jiepsin, the other as rennin. This idea is even more applicable where the sphere of action of some of them appears to be so limited that it is difficult to conceive of the existence of a separate enzyme for each action. Proteolytic (Protein-splitting) are pepsin, trypsin, and erepsin. Pepsin is the active proteol3?tic enzyme of the stomach, tryj)sin ENZYMES OR FERMENTS 71 •of the ]}aiicreas. Erepsin occurs in the succns entericus, in the intestinal mucous membrane, and in the tissues generally. The main action of these enz^'mes (explained more full}' later) may be ^ynopsized thus: Pepsin Trypsin Erepsin _ • • Protein • -^ Proteoses Peptones ' Polypeptides I \\^ Amino acids Erepsin (V) Lipolytic (Fat-splitting) lipase or steapsin occur particularly in the gastric juice, pancreatic juice, and the bloocl: Neutral fat 1/ ::j Fatty acid Glycerine Amylolytic (Starch-splitting) — sometimes known as the diastases. The chief are the ptyalin of the saliva, which acts on boiled or soluble starch, and amylopsin of the pancreatic juice, which can act on un- boiled starch. Amj'lopsin Starch « Ptyalin \j/ • Soluble starch Erythrodextrin Achroodextrin ^ Maltose The glycogenase of the liver ma}^ iDerhajDS be included in this group; it converts glycogen through similar stages to maltose. Sucrolytic (Sugar-splitting). — These enzymes split the disaccharide sugar into monosaccharides. They occur chiefly in the succus enteri- • cus; their action may be expressed graphically as follows: Maltase Lactase Invertase Maltose Lactose Cane-sugar \l/ \lr \!/ \U 4/ "nI/ Dextrose Dextrose Dextrose Galactose Dextrose Levulose 72 A TEXTBOOK OF PHYSIOLOGY De-aminizing. — A grou}) of euzyincs which remove the NH.^ group- from bodies, substituting therefor an OH grou]) and forming ammonia. —e.g. : (1) CH3CH.NH.,.C00H + H^O = CH3CHOH.COOH + NH3 Alanin Water Lactic acid Ammonia (2) C5H3N4.NH, + H,() -- C.H^NjO + NH., Ack'iiin Hypoxaiithiii Ammonia Coagulative. — In this grou]) are included '" rennin," which helps to bring about the clotting of milk, and '" thrombin,'" \\'hich is believed to play a part in the coagulation of the blood. These actions are by no means identical; for whereas the product of the rennin action is still soluble, that of the thrombin action is insoluble: Rennin Thrombin Caseinogen I'ibrinogen 1 Soluble casein 1 Fibrin (insoluble) 4. The action of enzymes is inhibited by the accumulation of the products of activity. This is best seen in test-tube experi- ments. In the body such products are constantly being removed by absorption. 5. They are reversible in action. This has been shown to be true for a great number of enzymes, not yet for all. Reversible action wa& first shown with the sugar-splitting enzyme maltase. This enzyme usually splits maltose into two molecules of dextrose. In a test-tube experiment only a certain amount of maltose is converted into dex- trose, the accumulating dextrose tending to stop the action. A point of equilibrium is therefore reached when there is present as the result of the enzymic action a certain amount of maltose and a certain amount of dextrose. If more maltose be added, the action goes on until the same proportion is reached. If dextrose be added, the enzyme reconverts some of the dextrose to maltose until the same point of equilibrium is again reached. Another example is the enzyme (lipase) which, according to the conditions, breaks ethyl butyrate down into ethyl alcohol and butyric acid, or builds up ethyl butyrate from these bodies. C3H-COOC2H,= C3H,C00H +G,H50H Ethyl butyrate Butyric acid Ethyl alcohol <- — ^ This reversible action is particularlj^ important in the case of intra- cellular enzymes ; with varying conditions of the blood and tissue fluids the cells of the body may at one time act in a building-up (anabolic), and at another time act in a breaking-down (katabolic), direction. ENZYMES OR FERMENTS 75 6. They are inhibited by the action of antiseptics and disuifectants and kindred bodies. This statement is true for the enzymes found in the body, but not for all enzymes. 7. They are carried do\\ii from solution by flocculent precipitates. For this reason it is difficult to say whether enzymes are protein in nature or only carried down by the precipitated protein. Most enzymes are apparently closely associated with protein, although it is claimed that some have been prepared which do not give the protein tests. They are colloidal in nature and indiffusible, and readih' taken up by finely divided substances, such as kaolin, alumin, etc. In general they are soluble in dilute glycerine, sodium chloride solution, and dilute alcohol and water. 8. (a) They are precipitated from solution by alcohol and am- monium sulphate. (6) The precipitate on redissolving in water again manifests enzymic characteristics. These facts (6, 7, 8) show the intimate relationship that enzymes bear to other products of cell activity — e.g., bacterial toxins, h9emol3'sins, and such bodies. 9. By the presence of an enzj'me a chemical action is accelerated without the enzyme itself being used up in the final reaction. One part of invertase can hydrolyze 100,000 parts of cane-sugar; one part of rennin acts on 200,000 parts of caseinogen. It is not possible to saj^ whether an enzyme combines in any intermediate stage of the reaction. This is sometimes the case in other forms of catalytic action. 10. It was originally believed that the rate of action of enzymic activit}' was proportional to the square root of the amount of enzyme present. Recent investigations with more delicate methods tend to show that for most enzymes the intensity- of action is almost directly proportional to the concentration of enzyme ])resent. 11. The action of an enzyme may be hindered or stopped by the presence of a body known as an anti-enzyme. The exact manner in which these work is not sufficiently well known. Anti-rennin may be produced in the blood by the injection of rennin. The alimentarj^ tract is believed to contain anti-enzymes which prevent the digestive enz3'me from attacking it. Intestinal worms also contain anti- enzymes for the usual ferments of the digestive tract. Administra- tion of an enzyme for which the worms {e.g., tape-worms) have no anti-enzyme {e.g., papain) brings about, their partial diges- tion, so that their removal from the body by a purge then becomes eas}'. All the above-mentioned enzymes belong to a class the mode of action of which is hydrolytic. Besides these there exists in the body a group of enzymes, " the oxidases," which plays a great part in the oxidative processes of the body. These are generally divided into two groups: the primary, or direct oxidases, which can transfer oxygen directh' to other bodies; the indirect, or peroxidases, which transfer oxygen only in the presence of a peroxide, from which they set the 74 A TEXTBOOK OF PHYSIOLOGY oxygen free and then transfer it to the body to be oxidized. An example of oxidizing action occurring in the body is the following: C5H4N4O + 0 - C5H4N4O0 + O = C5H4N4O3 Hypoxaiithin Xanthin Uric acid The oxidases give a blue colour with tincture of guaiacuni alone, the peroxidases with tincture of guaiacum in the j^resence of peroxides. According to recent investigations, it is claimed that oxidases are in reality a mixture of ox^'genases, bodies containing iron and manganese, and peroxidases. The oxygenase in the process of oxidation is believed to take up molecular oxygen and become converted into peroxide. This peroxide is then activated by the peroxidases, and has a great oxidizing power. It is i^ossible that certain of the reductions taking jilace in the body may be ascribed to the i^resence of enzymes known as " re- ductases." More light is required on this subject; some of the eductions in the body are apparently not of an enzymic nature. BOOK II CHAPTER IX THE BLOOD All the cells of a multicellular organism are engaged in building-up (anabolic) and breaking-down (katabolic) processes. In the unicellular these processes are performed by a direct interchange between the single cell and the surrounding medium, but in the higher organiza- tions special fluid tissues — the blood and the lymph — have been evolved, which circulate in order to supply the requisite conditions for these metabolic processes. The functions of the blood may be summarized as follows: 1. To act as the medium of absorption and exchange between the alimentary canal, the lungs, and the tissues, and to supj^ly the sources of energy (food, oxygen) to the tissues for metabolic purposes. 2. To supply to the tissues a medium consisting of water, colloids and electrolytes (inorganic salts) of a concentration and osmotic pressure kept constant within narrow limits, in which they are able to carry oiit their vital processes. 3. To convey from one organ to another the internal secretions and the hormones (chemical messengers), which regulate the activity of the organs. 4. To convey the products of katabolism from the tissues to the organs of excretion, the lungs and kidneys. 5. To endow the body with a mechanism protective against harmful micro-organisms. 6. In the higher animals to distribute and help to regulate the heat of the body. 7. By its power of clotting to seal up wounds and prevent serious loss of blood or tissue lymph. The blood is a thick, viscous liquid, with a saltish taste and a peculiar faint odour. When viewed under the microscope it is seen to consist of a transparent liquid, the l>lood-plasma, in which float a number of formed bodies, the red and pale corpuscles of the blood. According to some authorities, there is a third solid component — the blood-platelets. 75 76 A TEXTBOOK OF PHYSIOLOGY The Colour of vertebrate blood varies from a bright red in the blood of the arteries to a deep purple-red in the veins. It is due to a pigment — haemoglobin — which is contained within the red corpuscles of the blood and acts as the carrier of oxygen. The blood of inverte- brates and coidatcs may be either colourless or possess one of a variety of colours. Haemoglobin occurs in solution in the plasma of many o.f the worms and lower Crustacea. The echinoderms also possess a red pigment in their blood (echinochrom). Some Crustacea have a blue pigment — haemocyanin — which contains copper and is in solution in the blood. It is blue in the arterial blood, when combined with oxygen, and colourless in venous blood — i.e., when deoxygenated. Its combining power for oxj'gen is only about one-fourth that of haemoglobin. Some worms contain a green pigment (chlorocruorin) ; others a red pigment (haemoerythrin). Certain molluscs and tunicates possess colourless blood and yet have substances in it capable of com- bining with oxygen and transporting it to the tissues (achroglobin). The Specific Gravity of the blood of man varies between 1055 and 1060. The red corpuscles have a specific gravity of 1 080 and the plasma one of 1030. The specific gravity is usually obtained by the fol- lowing method. By means of a pipette a drop of blood is placed in the middle of a mixture of benzol (sp. gr. 0-88) and chloroform (sp. gr. 1-485). The mixture has a specific gravity approaching that of blood. If the blood-drop falls, more chloroform is added; if it rises, more benzol — until a condition is obtained when the corpuscle remains suspended in the mixture. The specific gravity of the mixture is now taken with the hydrometer. The operation must be quickly performed (1 to 2 minutes), otherwise the specific gravity of the blood alters owing to diffusion taking place between the blood and the liquids. The specific gravity is infiuenced by the number of corpuscles and the amount of haemoglobin. It is high in the new-born (1066). It sinks in starvation, after haemorrhage, in anaemias, and in diseases of the kidney, etc. Specific Gravity of Blood. Man 1056-1061 Rabbit 1042-1062 Woman 1053-1061 Of serum 1030-1042 Dog 1060 Of red corpuscles .. .. 1080-1085 The specific gravity varies with the age and sex; it is diminished after eating and increased by exercise. It gradually falls during the day and rises during the night. Reaction. — The reaction of a fluid depends upon the number of free hydrogen (H) ions in it, which give an acid reaction relative to the number of free hydroxyl (OH) ions, which give a basic or alkaline reaction. Blood is almost neutral in reaction as determined by the electrical method. Its reaction to litmus is slightly alkaline. This is because litmus acts as a weak acid, and, displacing carbonic acid gas from its combination in the blood (carbonate), combines with the base and turns THE BLOOD 77 blue — the alkaline reaction. To phenolphthalein blood is neutral, for this reagent cannot decompose the carbonates. Blood can take up a certain amount of acid before it begins to react acid. This is because it contains carbonates (" buffer salts ") and proteins which combine with the acid. It is for this reason that it is difficult to ascer- tain the reaction of the blood by chemical means. Titrating with acid, fhe amount of neutralizable alkalinity is obtained, alkali being liberated in the process from the proteins and by dissociation of the carbonates (NagCOg, NaHCOg) and the phosphates (NagHPOJ. This neutrahzable alkali usually equals 350 to 400 milligrammes NaHO per 100 c.c. But the real alkalinity, as measiired by the electrical method, is due to free OH ions, and these are usually present in a concentration little greater than in water. Na^COg in aqueous solution is dissociated, + = more or less, into the ions 2Na and CO3. 8ome of the CO3 ions com- + _ - - bine with H ions of the dissociated water, forming HCO^, and HO ions are thus set free to produce the alkaline reaction. On adding acid these HO ions are removed, and, the equilibrium being disturbed, more Na.^COg is dissociated, and this goes on until all the Na.^COg is dissociated. The alkali existing as salts, carbonates, and phosphates, is knoAvn as diffusible alkali; that combined with protein is termed non-diffusible alkali. As the corpuscles are richer in diffusible alkali than the plasma, the number of corpuscles modifies the amount of neutralizable alkali. On passing carbon dioxide gas through blood, the loose combination between alkali and protein of both the plasma and corpuscles is split up, and sodium carbonate partly formed. CO3 ions pass from the corpuscles into the plasma, and CI ions from the plasma into the corpuscles, and as the sodium carbonate in the plasma is increased, so is the neutralizable alkalinity. It is very difficult to affect the reaction of the blood by swallowing acids. Two drachms of official hydrochloric acid taken with food have no effect upon the reaction of the blood, because the acid com- bines with the ])roteins of the food, etc.; two drachms of tartaric acid, on the other hand, may diminish the neutralizable alkahnity. These acids combine with the bases and form salts which are little disso- ciated. Acids entering the blood are neutralized by combination with ammonia, a product of protein katabolism, or by union with bases of the carbonates, carbonic acid being expired. Alkalies are neutralized b}^ the carbonic acid produced in the body. The blood is thus kept neutral while the amount of acid or alkali passing into it varies considerably. Muscular exertion diminishes the titration alkalinity owing to the production of lactic acid. The concentration of the H ions in the blood regulates the activity of the respiratory centrsf; lactic acid and carbonic acid are both produced on exertion, and their eumulative effect produces dyspnoea. The '" buffer salts "' help to regulate this. 7S A TEXTBOOK OF PHYSIOLOGY The Amount of Blood. — This varies according to the method by which it is determined and for different animals. The following table gives some of the results which have been obtained : ■iv-is of body-weight Dog . . jV of body-weight Pig .. Guinea-pig . . A- Bird Rabbit '.'■ "^ ',', Frog Cat . . ^i^ Man Horse Tr. »> New-born child It is stated in man to vary from 3| to 4 litres. The old method (that of Welcker) of obtaining the amount of blood of an animal was (1) to bleed the animal into a weighed flask, (2) remove all traces of blood by perfusing the vessels thoroughly with water, (3) chopping up the body with the exception of the in- testines and washing the choppings in water.- The washings are measured and the amount of blood in them gauged by determining the amount of haemoglobin — by finding how much the blood must be diluted to correspond in depth of tint to that of the washings. This method is not very exact, since during the death from haemorrhage the tissue fluids pass into the blood, giving too high a result. In man the amount has been ascertained by the carbon monoxide method. In this method the subject breathes, through a tin of soda lime to absorb exhaled CO,, in and out of a bag containing a known volume of carbon monoxide mixed with a sufficiency of oxygen. Carbon monoxide has a strong affinity for haemoglobin, and combine? with this, displacing oxygen. After sufficient time for the whole of the CO to be absorbed a sample of the subject's l)lood is taken and the percentage saturation of the blood with carbon monoxide determined. The carbon monoxide gives the blood, suit- ably diluted, a pink colour, and the determination is effected by comparing the tint of (1) the sample, with (2) a sample of the subject's normal blood, (3) a sample of the subject's blood saturated with CO, all three samples being diluted 1 in 200. A standard carmine solution is added to (1) and (2) till the tint of each equals that of (3). Suppose twice as much carmine has to be added to (2) as to (1), then (1) is half saturated with CO. The amovnit of O, or CO which can combine with 100 c.c. of the subject's blood is found by the use of the Haldane-Gowers hsemoglobinometer. The amount of CO absorbed is known, and thus, if it be found that blood is 25 per cent, saturated and the person has absorbed 150 e.c. of CO, it is obvious that all the blood will require 600 c.c. of CO to saturate it. If it is found that 100 c.c. of the blood are satiirated by 20 c.c. of carbon monoxide or oxygen, the total volume of the blood is -- =3,000 c.c, etc. , j& ' 20 By this method the amount of blood in man is reckoned to be about -L of the l)ody weight (^L for fat men). Generally speaking, this method gives a lower value than the other, and there has been a considerable amount of discussion recently as to the accuracy of the CO method. CO is taken nj) by the haemoglobin in* the muscles; the 'THE BLOOD 79 amount of this seems to increase with age, even equalhng 5 or 6 per cent, of the whole Hb content of the bod3^ This is a som'ce of error. The more muscular animals with darker flesh have more Hb in their •muscles — e.g., hare more than rabbit, duck than fowl. It is claimed by authorities who have made careful experiments by the "bleeding method that this is really the more exact, and that the quantity of blood in an animal bears a definite relationship to the amount of the bod}^ surface. Thes-e observers used oxygenated Locke's fluid to wash out the circulator}^ system, and so avoided the transference of tissue fluid into the blood. B = W«/j. — ^where B is the blood- volume in cubic centimetres, W the weight of the body in grammes, nO-10-0-12, and h a constant (calculated from experiments) determined for each species of animal. The body surface is usually calculated from the body weight by the formula S=A-.Wf (0-70 -0-72 is more accurate 6 3. 6 9 12 is 18 21Z4 27'36'-'--'-'---'-0"V ^ ^ 12 15 18 Atcent T.O.C.= Total Oxygen Capacity. ^^^^ Fig. 18. — Effect of High Altitude (.in Blood. (Dreyer and Walker.) than ^). The smaller and lighter animals, which have a relatively greater body surface than the heavier ones, have also a relatively greater blood-volume. This agrees with their relative rates of body heat loss and metabolism, and also with the sectional areas of their tracheae and aortae and weight of heart muscle. A wild-rabbit con- tains 25 per cent, less blood and 25 per cent, more haemoglobin in its blood than a tame rabbit of the same weight. A wild-hare contains double the blood-volume, 30 per cent, more haemoglobin, and three times more heart muscle than a wild-rabbit of the same weight. No doubt the same kind of difference exists between an athlete and sedentary worker. In travellers to high altitudes the blood becomes concentrated and the oxygen capacit}^ increased (Fig. 18). The concentration happens in the first day or two, and is due to withdrawal of plasma. After some weeks the number of corpuscles and the total amount of 80 A TEXTBOOK OF PHYSIOLOGY haemoglobin are found increased by the new formation of corpuscles in the red marrow. In rabbits taken from Basle (740 millimetres barometric pressure) to St. Moritz (620 millimetres) the total haemo- globin increased 12 per cent, and the blood-volume decreased 11 per cent. The increase in the percentage of haemoglobin Avas 12 per cent. Thus the body compensated for the attenuation of the air and lowered partial pressure of oxygen. Cooling or bandaging a limb concentrates the blood therein. The breathing of an excess of COg and the taking of amyl nitrite dilutes, of chloral hydrate concentrates, the blood. The Osmotic Pressure. — The osmotic pressure of the whole blood is measured by the depression of the freezing-point. Generally /\ = -0-56° C. for human blood, but varies from -0-51° C. to — 0-62° C. with, the diet and amount of fluid ingested. If the products of metabolism increase in the blood, owing to the fact that they are not properly eliminated by the kidneys, ^ may be increased. According to some observers, if /^ constantly equals or exceeds —0-58° C. it is a sign that both kidneys are diseased. The Electrical Conductivity o£ the Blood. — As the blood-plasma contains inorganic salts (electrolytes) in solution, it has the jDroperty of conducting an electric current. Defibrinated blood is generally employed for this measurement. The conductivity varies with the relative proportion of corpuscles and serum — being low with many corpuscles and less serum, high with relatively few corpuscles and much serum. In cases of anaemia the conductivity is greatly increased. The corpuscles, owing to their colloid nature, lessen the conductivity. Viscosity. — Blood compared to water is relatively a viscous fluid. Its viscosity maj^ be determined by allowing blood to flow under a definite pressure through a capillary tube of known dimensions, and measuring the outflow in a given time Taking the viscosity of water as 1, that of the blood of man is 5-1 ; that of dog, 4-7 ; that of the cat, 4-2. Viscosity generally varies in the same direction as the specific gravity. Sweating increases it; increased temperature, on the other hand, diminishes it. In the condition known as polycythaemia the viscosity may become 9 or 10 times that of water. In this condition the red blood- corpuscles are greatl}^ increased in number in proportion to the plasma, reaching as many as 11,000.000 per c. mm. On the other hand, in the form of anaemia known as chlorosis or "" green sickness," because of the greenish look of the patient, the plasma is greatl}' increased in amount, so that the corpuscles are relatively diminished, and the viscosity of the blood is also nu;ch diminished, often to just over 2. The flow of the blood is so controlled by the va so -mot or system that slight altera- tions in viscosity are of little if any account. Analysis. — The most accurate analyses of the blood have been . erythrocyte uasoform. cell — '■ — *'*#^— -^:ir>~vW (5) '/S^ , , , , L, X ->w ----^^-,^^}^^^ii^z/^ — blood ues. hypoblast ^^^00^^"^^^^: Fig. 20. — Section across Yolk Sac showing Bloodvessels and Nucleated Red Blood -Corpuscles forming in its Mesoblastic Layer. (Keith, after Selenka.) The cells (angioblasts) in the region where a capillary is to be formed unite together to form a syncytium (a fusion of cells). Their nuclei divide at some places faster than others, so that an accumula- tion of colourless cells (primitive hsemoblasts) is formed at certain points. These cells become coloured by the formation of haemoglobin within them, and form the primitive coloured cells of the blood — ^the so-called primitive erythroblasts. A hoUowing-out process now takes place at the enlargements, and the newly formed corpuscles float in a clear fluid in the cavities thus made, the whole forming so-called * Hayem's solution consists of: Mercuric chloride, 0-5 gramme; sodium sulphate^. 5 grammes; sodium chloride, 1 gramme; distilled water, 200 c.c. t Toison's solution is: Methyl violet, 0-025 gramme; sodium chloride, 1 gramriae;. sodium sulphate, 8 grammes; glycerine, 30 c.c. ; distilled water, IfiO c.c. Sherrington's fluid is: Methylene blue, 0-1 gramme; sodium chloride, 1-2 grammes; neutral potassium oxalate, 1'2 grammes; distilled water, 800 c.c. THE CORPUSCLES OF THE BLOOD 89 blood-islands. The spaces between the blood-islands is next exca- vated, some of the angioblasts becoming converted into blood-cor- puscles, others forming the cells of the capillary wall. This process goes on until the circulation is established and capillary formation is complete. The blood-cells thus formed multiply within the vessels. Later on, when the circulation is established, large blood-cells (megalo- blasts), derived from the primitive hsemoblasts, also make their appearance in the blood. From the megaloblasts are derived smaller normoblasts, which lose their nuclei and become converted into the erythrocji^es similar to those of the adult. By some authorities it is held that hsemoblast cells also give rise to lymj)hoblasts, from which lymphocj'tes are developed, and possibly leucocytes; also to myeloblasts, from which myelocytes and leucocj'tes are develoiDcd. All the first blood-corpuscles according to this scheme have a common mesoblastic parent cell, the hsemoblast. HiEMOBLAST Primitive Megaloblast Lymphoblast Myeloblast Erythroblast | | " | Normoblast Lymphocyte Eosinophil Neutrophil Basophil I (large and small) myelocyte myelocyte myelocyte Primitive Erythroblast Leucocyte ? Eosinophil Neutrophil Basophil Erythrocyte | (neutrophil) leucocyte leucocyte leucocyte "^ , ' Erythrocyte — -,. ^ , — — ■' Mesoderm ^ , — - Lymph Red marrow of foetus Red marrow glands The red corpuscles are formed in mid-fcetal life to a certain extent, and in late foetal life to a large extent, in the liver, spleen, connective tissue, and red bone marrow; but in the last few weeks of foetal life the red bone marrow becomes almost the sole source. The cells arising from the bone marrow are non-nucleated. In the human embryo at the fourth week only nucleated cells are present; in the fourth month they form about 25 per cent, of the whole, while at full time but few nucleated corpuscles are found. 2. After birth the red bone marrow is the sole source of the red blood-corpuscles. Here nucleated erythroblasts are always to be found, derived from mega'oblasts and normoblasts. When extensive destruction of the corpuscles is taking place, this erythroblastic tissue shows signs of great activity, and in times of great need the nucleated red cells of the marrow may pass into the blood. Generall}^ however, the erythroblasts multiply by cell division; these cells then exclude or absorb their nucleus, and pass into the circulation as non-nucleated er}i:hroc3'tes. Function. — The great function of the red corpuscles is to carry oxygen to the tissues. This it does by virtue of the haematin portion of its haemoglobin. This function is destroyed on taking blood from an animal, defibrinating it, and heating it to 56° C. On injecting into the animal the blood which has been thus warmed, the corpuscles <)J A TEXTBOOK OF PHYSIOLOGY are immediately dissolved. On the other hand, blood kept at 0° for several days (three to four) can be reinjected into an animal and still functionate. Haemoglobin plays a considerable part in the transport of carbon dioxide from the tissues to the lungs. It has a specifir capacity for absorloing Cavbou dioxide. The Fate of the Red Blood-Corpuscles. — It is not po.ssible to say how long the red corpuscle circulates before it is destroyed, j^ossibly three to four weeks. After some such time the corpuscle is probably destroyed in the spleen, the liberated hsemoglobin passing to the liver to be disintegrated there. From it the iron-free bile-pigments bilirubin and biliverdin are formed, the. iron being stored in the liver. This iron can be stained blue by treating sections of the liver with potassium ferrocyanide and hydrochloric acid, or black by a pure solution of haematoxylin. The iron in the liver is greatly increased in conditions in which a large destruction of red corpuscles takes place. It has been suggested that the spleen regulates the iron metabolism of the body; and it is possible that some of the destruction of red corjjuscles takes place there, accompanied by the formation of pigment and the storage of iron in the sjDlenic cells. It is sujjposed that the stored iron is again used to form haemoglobin. Chemistry of the Red Corpuscle. — The framework, or stroma, consists of protein and lipoids, ^\•ithin which are the salts, notably salts of potassium, and the haemoglobin (see table, p. 81). The pigment hsemoglobin forms 90 per cent, of the corpuscle. It is one of the compound proteins, a chromoprotein consisting of an iron-containing portion (hsematin) and a protein portion (globin); the latter is a histone. Haemoglobin, as other proteins, varies in composition in different animals. C. 1 H. \ 7-25 1 .V. .S'. 0-447 Fe. 0-400 0. Ox 54-66 17-70 19-54 Horse . . 51-15 6-76 17-94 0-390 0-335 23-43 Dog .. 54-57 7-22 16-38 O-.'idS 0-336 20-93 Pig .. 34-71 7-38 17-43 0-479 0-399 19-60 Its percentage composition is approximately — C 54-71; H 7-.38; N 17-43; S 0-79; Fe 0-399; 0 19-602. Hsemoglobin is readily soluble in water; coagidated by heat to a brown coagulum; dextrorotatory to polarized light. It can be obtained in crystalline form, but more readily from some bloods than others. It is easily obtained from the blood of the rat after the addition of distilled water. In the guinea-pig's blood haemolysis is first produced by the addition of chloroform or ether. Upon THE CORPUSCLES OF THE BLOOD 91 evaporation the chloroform or ether extract deposits crystals of oxy haemoglobin. Crystals are readily obtained from the blood of the squirrel, rabbit, and also from the mouse and rodents generally ; less readily from man, horse, cat, birds, and fishes. It is a more difficult matter to obtain crj'stals from the blood of the sheep, ox, and pig. The crj'stals vary in size and shape according to the animal from which they are prepared (Fig. 21). Those from the rat are needle- shaped, resembling those from human blood; from the guinea-pig they are quadrilateral prisms; from the squirrel, hexagonal plates. The rosy colour and plump look of health is due to a plentiful supph' of well-oxj^genated blood in the face. The great function of the red corpuscle is to carry oxygen, and the most characteristic property of the pigment liijemogiobin is its power to form a loose chemical combination with oxygen. The body thus formed is termed Fi5. 21. — Crystals of Oxyh.5:jio:!Lobix fro:.i Horse's Elood. oxyhgemoglobin, and it is to this body that the bright red colour of arterial blood is due. If arterial blood, diluted, let us say, with water to 1 in 500, is examined with the spectroscope, two absorption bands are seen in the yellow and the green between the lines D and E (Fig. 22). The addition of a reducing substance, such as ammonium sulphide, to this solution displaces the oxygen from the oxy haemoglobin. The solution, now changed to a purplish colour, gives the spectrum of hsemoglobin; one broad but less dark band is seen between D and E (Fig. 22). Carboxyhsemoglobin. — Blood exposed to coal-gas or carbon mon- oxide gives a spectrum resembling OHb, but the solution of COHb is markedly pinker in colour, and is not reduced by the addition of ammonium sulphide. This serves to distinguish the two. When a solution of carboxyhsemoglobin is greatly diluted, it remains pink, while that of oxyhaemoglobin diluted to the same extent becomes yellowish-green . 92 A TEXTBOOK OF PHYSIOLOGY The presence of CO in coal-gas and in after-damp in mines is a frcqiicnt cause of death. CO has about 150 times as great an affinitj'^ for Hb as O^, and thus it comes about that, if a man breathes long euoiighan atmosphere containing 0-1 percent. CO, half the oxygen will be displaced from his V)lood. The haemoglobin of the blood becomes combined to form COHb, insufficient oxygen is now carried to the tissues, and death from oxygen want ensues. It is therefore dangerous to breathe an atmosphere containing more than 0-05 per cent. CO is without colour or smell, and its presence cannot be sensed. The want of oxj'gen gives little warning, and a man breathing CO may lose consciousness unwitting of his danger. A small vertebrate, such as a bird or mouse, is affected much sooner than a man, and it is a wise precaution to send a cage bird with an exploring party into a mine where " after-damp " exists. Ordinary illuminating gas contains about 5 per cent, of carbon monoxide, and water-gas, used in some towns, as much as 30 to 40 per cent. CO poisoning in such towns has accounted for even 1 per cent, of all the deaths. Seventy-five per cent, saturation of the haemoglobin with CO causes dizziness and palpitation on exertion; the heart fails to keep up the extra circula- tion required then. Brain-power is greatly diminished although the subjects do not know it. In deaths from house on fire the people are as a rule rendered unconscious by CO poisoning before they arc burnt. The bodies of men killed by CO poisoning have a pink colour, due to the COHb formed. Nitroxyhsempglobin (NOHb) also has a spectrum resembling the above, but the two bands, although in approximately the same posi- tion, are not by any means so clear-cut; the shading appears " woolly." NOHb is not reduced bj^ ammonium sulphide. It is prepared bj' adding a solution of ammonia to the blood, and then passing nitric oxide gas through the solution. It is formed in the blood by the action of the nitrites — e.g., amyl nitrite or such bodies as nitro-benzol. Methsemoglobin is first formed, and afterwards nitroxyhaimoglobin. For cases of partial j^ioisoning by carbon monoxide or nitrites the correct treatment is to place the j)atient in an atmosphere of oxygen, preferably under pressure, so that the Hb which is uncombined may have an ample supply of oxygen to draAv upon, and more oxygen may become dissolved in the plasma of the blood owing to its increased partial pressure. At a pressure of oxygen of two atmospheres about 2-5 per cent, of oxygen is dissolved in the plasma, and this is enough to maintain life in the presence of any percentage of CO. A mouse poisoned by CO, and rendered moribund, revives in two atmospheres of oxygen, and tumbles over again when the pressure is lowered to atmospheric pressure. The resuscitation and swooning of the mouse maj^ be repeated. NOHb is even more stable than COHb. It can be distinguished from COHb by giving a bright red coagulum on boiling, whereas COHb gives a brownish one. The difference in colour is approximately that between the outer red ring of salt beef and the inner brown zone. In this case the haemoglobin in the muscle has formed NOHb owins: THE CORPUSCLES OF THE BLOOD 93 to bacterial decomposition in the presence of the sahpetre used in the process of preservation. Metheemoglobin (MetHb). — Oxj-haemoglobin is frequently repre- sented by the formula HbC ; methaemoglobin by the formula Hb^ , although the correctness of the latter has been questioned. It is formed in the stale blood, and may be prepared by adding to a solution of Hb a few drops of a fresh-made solution of potassium Osyhaimoglobin Hiemoglobin (reduced) Carboxyhitmo- glubin Acid hiematin Alkaline hsematin Reduced alkaline h»niatin or h;i- mochroiuogen Methfemoglobic Acid Haem itop or- phj-iia Wave kngths in Fig. 22. — Ilood hPECTEv. (Waller.) ferric3-anide. The loosely combined oxygen of the OHb is turned out, and the Hb then combines in a more stable form with an equal amount of oxygen taken up from the decomposition of bicarbonates in the blood, a chemical reaction taking place in which the ferric^anide is reduced to ferroc3'anide. 0 ^ 0 Hb I -F4Xa3{reCy,.)-h4NaHC03=02+Hb' O 0 + 4Na,(FeCy6) +4C0., -f-2HoO 94 A TEXTBOOK OF PHYSIOLOGY Oil this reaction depends the chemical method of determining the amount of loosely combined oxgyen in the blood. The solution of MetHb is greenish-brown in colour. The spectrum of this solution suitably" diluted shows, in addition to the two bands characteristic of OHb, another band in the red near the line C. These three bands are well marked and of almost equal intensity. The O^ in methajmoglobin is not yielded to the vacuum pump, and is not available for respiratory jDurposes. By treatment, however, with ammonium sulphide MetHb can be easily reduced to Hb, which in turn can be converted again to OHb by shaking well in air. MetHb is sometimes passed in the urine after the administration of excessive doses of potassium chlorate, and antipyretics such as phenacetin, antifibrin, etc. It is formed when the red corpuscles are hsemolyzed and a considerable amount of Hb is set free in the blood-stream. The condition is known as methaemoglobinuria. The deep brown colour gives the urine a peculiar look. The spectroscopic test serves to identify it. Haemoglobin is split into globin and haematin by the action of heat, acids and alkalies, etc., and there are a number of derivatives of hsematin which give characteristic spectra. Chief of these are acid haematin, alkaline hsematin, reduced alkaline hsematin (hsemochromogen), and hsematoporphyrin (iron-free hsematin). Acid Hsematin is readily prepared by shaking up a small amount of defibrinated blood with a few drops of 20 per cent, acetic acid, and then suitably diluting the mixture with 60 per cent, alcohol. It forms a brownish solution, giving a well-marked absorption band in the red near the line C, nearer than the similar band of MetHb. Sometimes two bands are seen between D and E, but they are feeble, and not of the same intensity as the band in the red. Acid hsematin cannot be reduced to Hb by the action of ammonium sulphide. This serves to distinguish acid hsematin from methsemoglobin. Alkaline Haematin is prepared similarly by shaking up a small amount of defibrinated blood with 20 per cent, potash and diluting with weak alcohol. It gives one broad absorption band between C and T>, which is in contrast to the band of Hb between D and E. Reduced Alkaline Hsematin (Hsemochromogen). — This gives an extremely characteristic spectrum in suitable dilutions ; one very dark band between D and E and another less dark band between E and b. It is only the spectrum which has a band in this postion. Hsemo- chromogen is prejoared by adding potash to the solution of blood, or dissolving an old dried blood-stain in potash, and reducing it by ammonium sulphide. As it can be prepared from old blood-stains, it affords us a test for blood of great medico-legal value. A solution of hsemochromogen and globin, if mixed and allowed to stand, will reunite and form hsemoglobin. Acid Hsematoporphyrin. — By the addition of acid to hsemo- chromogen the iron is spUt off from the compound with the production THE CORPUSCLES OF THE BLOOD 95 of acid hsematoporphyrin. It can be prepared by treating a drop of defibrinated blood with a small amount of strong suli^huric acid, shaking well, and diluting the resultant mixture with more concentrated acid until the mixture is suflficiently diluted to be viewed through the spectroscope. The spectrum presents two bands: one narrow, just to the red side of the line D; another broader, between D and E. The sulphuric acid splits haemoglobin into its constituents hsematin and globin; the hsematin is then deprived of its iron with the formation of hsematoporphj^rin. Alkaline hsematoporphj'rin is produced in a similar manner to the acid, but very strong alkali is used. Alkaline hsematin is first formed, but this is subsequently broken down to iron-free alkaline hsematin or alkaline hsematoporphyrin. The spectrum of this body presents four bands — a narrow band between C and D, two between D and E, and a broad band between E and F. Hsematoporphyrin may occur in the urine after such drugs as svilphonal have been taken, and is usually of the alkaline variety. The formula for hsematoporphyrin is CigH^gXoOg. It is closely related to the pigment bilirubin ,of the bile, which has the same empirical formula. If a solution of a copper salt in ammonia be added to hsematopor- ph^Tin, turacin is formed — a pigment found in the red feathers of certain birds (plantain-eaters). The important pigment of plants, chlorophjdl, is a near ally. If treated with caustic jootash at 190° C, it yields a body phylloporph3'rin, CigH^gNjO. Both hsematoporphyrin and iDhylloporphjTin yield on reduction a bod}' called hsemopjrrol. It has been suggested that hsemoglobin is synthesized out of the chloro- phjdl eaten in the food. From hsematin, bj' the action of acids, hsematoporphjrin and a body termed mesoporphyrin are obtained. B3' reduction of haema toporphj*rin, hsemopyrrol (CgH^gN) is obtained, and by oxidation and treatment with caustic potash methylethylmaleic acid anhydride (CgHgOj). Both these bodies can also be obtained by the splitting of chlorophyll. Oxyhaeraoglobin Haematin Haematoporphyrin Mesoporphyrin Hsemopyrrol (CgHjgN) Methylethylmaleic acid anhydride (C^HgOs) The pigments of the bile (bilirubin and biliverdin), the pigments of the fseces (stercobilin), one of the pigments of the urine (urobilin), are derivatives of hsematin, and, like hsematoporphyrin, contain no iron. 96 A TEXTBOOK OF PHYSIOLOGY In old blood-clots, flat, lozciige-shaped crystals, of a bright red colour, are often found. This is an iron-free derivative of hsemoglobin, isomeric with bilirubin, and called hsematoidin. Besides the derivatives which have been studied with the spectro- scope, there is another derivative of haematin — haeniin, which is identi- fied by the rhombic form and Inown colour of its crystals. Haemin is the hydrochloride of hsematin, and is prepared by heating blood with glacial acetic acid. The Estimation of Hsemoglobin. — By estimating the haemoglobin in the blood we can measure the oxygen-carrying power, and make comparative tests of the blood in cases of anaemia, etc. The measure- ment is made by the use of an instrument known as the haemoglobin- ometer. In this country, apparatus shown in Fig. 23 is chiefly employed. This contains a sealed tube (D) containing coal-gas and Fig. 23. — Haldane-Gowers' H^emoglobinometer. a standard solution of human blood (1 in 200); the haemoglobin, being combined with CO, makes the solution a stable one. A small quantity (up to mark 20 or so) of distilled water (carried in a bottle (^4) furnished with a pij^ette stopper) is placed in the graduated tube C. Blood is taken from the patient, either from the finger-tip or the lobe of the ear, and sucked up into the pipette B to the mark 20, and then carefully added to the water in the graduated tube. The distilled water lakes the blood, and a solution of oxyheemoglobin is formed. This is converted into COHb b}^ passing coal-gas into the tube and shaking it with the solution. Or the distilled water in the bottle A may be previously saturated with CO by bubbling coal-gas through it. All that now remains is to dilute carefully the solution of COHb with water until it is of the same tint as the standard tube when compared against a white background. The percentage of Hb is registered by the graduations in the tube. The standard is THE CORPUSCLES OF THE BLOOD 97 made from ox-blood which had the power to combine with 18^ vohimes of oxygen when shaken with air. Blood of the same strength as this can coml)ine with the same amount of oxygen. ■ Taking the percentage of haMiioglobin in man as 100, woman nor- mally has 90 per cent., children 85 per cent. The new-born infant has a high percentage, 140 per cent., which quickly decreases in the first few months of life to just bolow normal. The effect of altitude has been mentioned. The Pale Corpuscles. — The pale corpuscles of the blood have been variously classified. At present the best classification appears to be that based upon their supposed origin and their staining properties. According to the origin, the pale corpuscles may be divided into leuco- cytes (amoeboid cells), arising in the bone marrow and passing primarily into the blood — essentially, therefore, blood-corpuscles; lymphocytes, probably non-amoeboid or but faintly amoeboid cells, arising in lymphoid tissue and passing primarily into the lymph — essentially lymph-corpuscles. By staining reactions the leucocytes are classified under three headings : Neutrophil. Eosinophil, or acidophil. Basophil. The lymphocytes are divided into two groups — the large and the small. The various staining properties can be seen in a well-made blood-film, which can be prepared as follows: Two clean slides are taken with well-cut edges. The slide upon which the film is to be made is gently rubbed with fine emery-paper to give it a very slightly roughened surface. The edge of the other slide is applied to a small drop of blood obtained by pricking the finger; this edge is applied to the roughened slide at an angle of 45 degrees, and by a sweeping movement the blood is lightly and evenly spread over the roughened surface. To this film Leishman's stain is added ; it consists of equimolecular weights of methylene blue and eosin dissolved in methyl alcohol, and is a fixing agent by virtue of the methyl alcohol. After fixing for thirty seconds the stain is diluted with water, 1 : 2, when it assumes a pinkish tint and acts as a stain. The film is stained for about five minutes, and is then washed with distilled water. It is finally dried wdth blotting-paper. The methylene blue acts as a basic dye because the base in this salt is the active group, and it reacts with nucleic acid in the nucleo-protein of the cell. Eosin is an acid dj^e because the acid in this salt is the active group, and it reacts with the basic substances of the cell. Stained in this way the neutrophil corpuscles appear two and a half times as wide as a red corpuscle, with a fragmented nucleus stained blue and the fragments joined together with faintly stained pieces of chromatin. For this reason it is called polymorphonuclear. With the magnification of a '. objective small pinkish granules may be just visible; these are well seen with an oil-immersion (J,) lens. 7 98 A TEXTBOOK OF PHYSIOLOGY The eosinophil corpuscles are also polymorphomiclear, ))ut their big I'ed granules are easily seen under the ,1 objective. The rare basophil cell (sometimes called a mast cell) has large blue granules. In numbers the pale corpuscles vary from 5,000 to S, ()()() ])er cubic millimetre. If they are much above this number, the condition of leucocytosis is said to exist; below that, of leucoj^enia. A differential blood-count of the pale corpuscles {i.e., the relative percentage of each corpuscle) of a film shows that there is in normal blood visually 75 per cent, leucocytes and 25 per cent, lymphocytes. The leucocytes are divided as follows: Neutrophils 71 to 73 per cent., eosinophils 2 to 4 per cent., basophils 0-5 per cent, or less. Morbid conditions which cause large numbers of basophils to appear in the blood are extremely serious, and for this reason they have been termed " the harbingers of death." Of the 25 per cent, of lymphocytes, normally 23 per cent, are small, 2 per cent, large ; these numbers vary slightly, but any large variation is regarded as pathological. In the horse the nimiber of leucocytes per cubic millimetre of blood is 8,000 to 11,000; in the ox, 7,000"to 9,000; goat, 9,000 to 12,000; sheep, 9,000; pig, 16,000. The proportion of leucocytes to lymphocytes also differs, lympho- cytes forming 30 per cent, of the total in the j)ig, 30 to 40 per cent, in the horse, 25 to 35 per cent, in the ox. The Origin oJ the Pale Corpuscles. — Although, as stated above, it is generally held that the leucocytes and lymphocytes have a separate origin, especially in adult life, the leucocytes arising from myelocytes in the bone marrow, and the lymphoc3rtes from lymphatic tissue, there are some authorities who believe that in foetal life the haemo- blast affords an origin for all the other forms of corpuscles (see table, p. 89). The Functions of the Pale Corpuscles. — The leucocytes by virtue of their amoeboid or pseudopodial movements can surround particles of foreign material and take them into their substance. For this reason they are termed phagocytes. By virtue of their phago- cytic action the leucocytes play a great part in defending the bod}^ from the onslaught of invading microbes, emigrating from the vessels for the purpose (Fig. 24). They also probably play a part in forming the protective substances of the plasma, such as antigen, complement, and opsonin (see p. 109). When blood is shed, these corpuscles help to produce the clotting of blood. The lymphocytes play a part in the absorption of fat, and possibly in uric acid metabolism. Enumeration of White Corpuscles. — The pale corpuscles may be counted by the Thoma-Zeiss instrument. In this case the pipette giving the smaller dilution 1 in 10 (labelled 11) is used. The usual diluting fluid contains 0-3 per cent, acetic acid tinted with methyl green. The weak acid destroys the red corpuscles, and the methyl THE CORPUSCLES OF THE BLOOD 99 green tints the nuclei of the pale corpuscles, rendering counting easier. The process of effecting the required dilution and placing it on the slide is the same as that described for the red corpuscle. The pale may be counted at the same time as the red corpuscles if Toison's or Sherrington's fluid is used. Leucocytosis. — An increase in the number of pale corpuscles occurs physiologically during digestion, especially after meals rich in proteins and fat ; after muscular exercise ; in pregnant and parturient women ; and in the new-born child. The neutrophil cells are increased in a number of pathological conditions, in acute infections such as supj^u- ration, pneumonia, diphtheria, erysipelas, etc. In the condition known as leuksemia, either the levxcocytes or the lymphocytes may be greatly increased, according as the marrow or lymph glands are the seat of disease. Sometimes, although the total number is not much increased, Fig. 21. — Emigration of Leucocytks. (From Waller's "Human Physiology.") Vc;Sjls of the inferior surface of the frog's tongue as they appear after the escape of the corpuscles, filled with stationary blood, deformecl and indented at the points of escape, near which the corpuscles are generally found. (After Waller, Phil. Mag., 1840, "Microscopic Observations on the Perforation of the Capillaries by the Corpuscles of the Blood.") the proportion of eosinophil corpuscles is increased. This occurs in cases infected with the parasites trichina or anchylostomum, in asthma, and certain skin diseases. Leucopenia occurs after exposure to X rays and injections of cholin. In certain infections such as typhoid the pale corpuscles are said to be diminished. Blood-Platelets. — The so-called blood-platelets, or thi'ombocytes, are bodies of doubtful origin. Opinions vary as to their character and nature. According to one group of observers thej' are to be A TEXTBOOK OF PHYSIOLOGY looked upon as a third kind of l^lood-corpuscle; according to the others they are but artefacts. A great diversity of opinion exists among the supporters of the view that they are a true corpuscle. They are variously stated to be amceboid and non-amoeboid ; nucleated and non-nucleated. Their diameter is 2-3 ^^. They are best seen if a drop of blood is received on to a block of paraffin wax and placed in a rrmist chamber. The blood does not coagidate when thus received on wax. At the end of twenty minutes most of the red cor])UScles have sunk to the bottom of the drop. The platelets, being lightest, remain at the top of the drop, and, if this be gently removed, large numbers of platelets will be seen. Platelets increase in number after the blood is shed. In a well- made blood-film few or no platelets are seen. If, however, the blood is allowed to stay on the slide some time before being drawn into a film, it will be found that many bodies which might be termed blood- platelets are visible. It seems probable that they are to Ije looked upon as artefacts, and may be grouped into four categories: 1. Platelets containing haemoglobin. 2. Platelets containing no haemoglobin. 3. Platelets with an inner body. 4. Platelets without an inner body. In normal blood there exist few, if any, platelets, and such as exist are generally clumped together. They separate from the plasma owing to contact with foreign bodies, and in part owing to the lowering of temperature. The addition of so-called fixing and indifferent fluids may produce enormous numbers of them, the number varying for different fluids. On adding a metaphosphate solution to blocd the platelets appear suddenly, and belong to the amoeboid tyj)e; when a solution of potassium oxalate is used, they are at first of this type, but afterwards appear as pin-like and tailed bodies; subse- quently small bodies are extruded from the red corpuscles. These bodies stain differently, and resemble bodies which form in coagulating blood after the administration of certain poisons. It is possible that a few platelets of this type may exist in normal blood. The exact source of origin is not known; they may arise from the fragmentation of red corpuscles, possibly the fragmentation of jDale corpuscles, but generally are regarded as fine deposits of the blood-proteins. When first discovered they were regarded as young red corpuscles, after- wards they were thought to be young white corpuscles; both views are now known to be wrong. Recently a compromise between the divergent views has been suggested, and the platelets grouped into " platelets " — true cori:»uscles, which are believed to play some part in the coagulation of the blood, and "blood-dust" protein granules of about 1^, known as hsemoconea. " Blood-dust " is insoluble in alcohol or ether, and is not blackened by osmic acid. Some regard it as formed of the extruded granules of the i)ale corpuscles. CHAPTER XII THE CLOTTING OF BLOOD If the blood be allowed to flow freely from a wound, the flow gradually lessens as the blood becomes more viscid, and at length ceases, a clot, or coagulum, being formed at the site of injury. , As a rule the blood coming from clean-cut wounds clots less readily than that from jagged wounds. Washing and cleaning a wound prolongs the bleeding; on the other hand, contact of the wound with a foreign body such as a piece of rag or of cotton-wool quickens its arrest. The clot serves a double purpose — it plugs the bleeding-points, and so prevents the loss of precious blood, and it forms a protection against the entry of harmful organisms into the blood-stream. If the blood be received as it is shed into a perfectly clean vessel and put aside to clot in a quiet place, it will be found that the jelly-like coagulum is at first so solid that the vessel can be turned upside clown, and considerable force is required to disengage the clot from the vessel. The clot gradually shrinks in size and squeezes out drops of a clear, almost colourless, fluid known as the serum. The shrinkage slowly continues until at last there remains a shrunken dark red clot at the bottom of the vessel and a quantit}^ of clear straw-coloured serum above it. If the blood be horse's or cat's blood, an upper yellowish layer is also formed, known as the " buffy coat." This consists of the pale corpuscles which are lighter and romain on top, the heavier red corpuscles quickly settling down to the bottom in the blood of these animals. Coagulation of the blood may be retarded in various ways. The best-known methods are the following: (i.) Cold, by receiving blood into a vessel placed on ice. (ii.) Contact with the wall of the bloodvesjcl. If a large vein — for example, the jugular vein of the horse — be ligatured in two places, and the tube of blood thus formed be excised and hung up, the cor- puscles will sink to the bottom, leaving the unclotted plasma above. (iii.) Receiving the blood into a smooth vessel smeared with oil. (iv.) Addition to the blood of neutral salts such as magnesium or sodium sulphate. (v.) Addition to the blood of a soluble oxalate, citrate, or fluoride. (vi.) Addition of a body (hirudin) obtained b}' extracting the heads of leeches. Certain snake poisons and bacterial toxins also stop coagulation. 101 102 A TEXTBOOK 01^^ PHYSIOLOGY (vii.) By injecting into an animal before killing it certain substances such as commercial peptone, soap solution, or, very slowly, a weak alkaline solution of nucleoprotein. (viii.) The addition of acids, alkalies, ammonia sugar solution, glycerine, or much Avater. Clotting may be facilitated, on the other hand — (i.) By keeping the temperature that of the body, (ii.) By injuring the wall of the containing bloodvessel, (iii.) By receiving on to a rough surface to which the blood adheres; by beating it with twigs or shaking it with glass beads. The addition of finely powdered carbon or platinum black also quickens coagulation, (iv.) By adding serum or blood-clot. (v.) By adding saline extract of lymphatic glands and other tissues, (vi.) Possibly by the addition of soluble calcium salts. The explanation of all the above facts in regard to the clotting of blood is a matter of great difficulty. Opinions strongly at variance are held in regard to the exact processes which take place. The following seem to be the certain facts about the clotting of blood, whatever may be the interpretation of the same : (i.) When blood clots the protein of the plasma known as fibrinogen is involved and becomes converted either partially or wholly into a solid body known as fibrin. This is shown by the experiment that fibrinogen may be precipitated from plasma, redissolved in saline, and clotted at 37° C, by the addition of a trace of blood-serum or a watery extract of serum proteins coagulated by alcohol. (ii.) Calcium ions are necessary for the process. Thus, the addition to blood, as it is shed, of a soluble oxalate or fluoride which precipitates the calcium ions, or of a soluble citrate which prevents their dissocia- tion, stops the coagulation of the blood. (iii.) Calcium ions take part in an intermediate and not in the final process, since a calcium-free solution of fibrinogen may be clotted by the addition of calcium-free blood-serum — i.e., blood which has already clotted. (iv.) Tissue juice has the property of greatly accelerating the process of clotting. Bird's blood straight from the vessel does not clot; if tissue extract be added, the blood clots almost at once. The addition of lymph from a blister accelerates the clotting of human blood. (v.) Adhesion between the blood and a foreign substance gives an impidse towards coagulation, while lack of such adhesion prevents the blood from clotting. The explanation given of the above facts is that blood, flowing from a wound, becomes mixed with the tissue fluids in the cut, and the blood with the tissue fluid in the presence of calcium ions forms an enzyme known as thrombin from a forerunner present in the blood, known as thrombogen or prothrombin, which is probably derived from the white corpuscles and blood-platelets. It is only when tissue juices and calcium ions are present that this enzyme formation takes I lace. This explains why a jagged wound clots more readily than THE CLOTTING OF BLOOD 103 a clean cut, and why, when calcium ions arc withdra^Mi from the blood b}^ the addition of a solul^le oxalate or citrate, the blood will not clot. The enzyme thrombin thus formed then acts upon the fibrinogen of the plasma and transforms it into so.id fibrin, which entangles the red corpuscles and forms the blood -c'ot. The process may be represented as follows : Thrombokinase (from Free Ca ion Prothrombin or thrombogen tissue fluid, possiblj^ (I'r^m plasma] (from white corpuscles, blood-platelets) also white corpuscles) ^ _^— -^ Thrombin Fibrixogen (enzyme) (soluble protein of j)lasma) -I Fibrin (insoluble protein or clot entangling red corpuscles) In accordance with the above view of enzymic action it is supposed that oxalate, fluoride, and citrate, prevent the formation of the enzyme b}' withdrawing calcium ions, and that fluoride also destroys throm- bokinase. Hirudin is believed to be an antithrombin. Cobra poison is held somehow to interfere with the action of thrombokinase. Roughened surfaces, etc., break down white corpuscles and provide •points d'appui from which the enzyme can act. Cold inhibits enzymic activity; on the other hand body temperature hastens it. Oil and smooth surfaces deprive the enzyme of points for action. Coagulation Time, tested in a Glass Vessel at Room Temperature. Man 2 to 6 minutes Ox 8 to 10 minutes Dog 1 to 8 „ Pig 10 to 15 Sheep ., .. 4 to 8 „ Horse .. .. 15 to 30 ,, According to the above view the tissue extract has only an indirect action on clotting; other authorities believe that the tissue juices have a direct clotting action. Recently it has been suggested that thrombin results from the interaction of two substances, cytozyme and serozyme. The former is said to be present in tissue cells and blood-platelets, and is not destroyed by heating to 100° C, while the latter is present in serum and is destroyed by heat at 56° C. Vt-ry little serozyme is srid to be in plasma, and its origin is unknown. According to another view of clotting, thrombin and its antibod}', antithrombin, are present in the blood. When blood is shed the tissue fluid combines with the anti-thrombin, leaving the thrombin free to convert fibrinogen into fibrin. According to still another view, thrombin does not bring about clotting, but is a body produced as the result of clotting. Upon this view the bodies which take part in the clotting are fibrinogen, thrombogen, thrombokinase (sometimes called thrombozyme), and calcium salts. When blood is shed the three colloids — fibrinogen, 104 A TEXTBOOK OF PHY8IOLO0Y lluomliooc-n and lluoinliokiiiiisc — become in a state of unstable e(|uilibrhnn, and unite together to form fibrin and thrombin. The presence of calcium ions is necessary for this to take place. The projiortion of fibrin produced, compared to thrombin, varies according to the proportion of the three colloids taking part in the process. The exciting cause of this unstable equilibrium may be any of the j)hysical or chemical agents known to facilitate clotting, such as contact with the walls of a glass vessel, tissue extracts, and so forth. Haemophilia. — This is a disease characterized'by the great tendency to severe bleedings in those afflicted with it; hence these are known as " bleeders." The characteristic bleedings are into joints, and subcutaneous haemorrhages following slight injuries or strains. It is an hereditary disease, confined to the male sex; women transmit the disease, bvit never suffer from it. The cause of the condition is not known; it has been wrongly attributed to abnormal thinness or brittle- ness. of the vessel wall. The most generally accepted view is that some agent (thrombokinase) is missing from the tissue fluids, so that these do not cause the blood to clot. This view accords with the fact that certain tissues of a bleeder mav' bleed, and not others; and that tissues may bleed at certain times, and not at other times. The condition is very rare. Genealogical trees, showing male bleeders and tranauission through females, have been constructed from records going back to many generations. CHAPTER XIII HiEMOLYSIS AND IMMUNITY Haemolysis. — If small amounts of blood be taken in two test- tubes and diluted with physiological saline (0-8 per cent. NaCl solution) and with distilled water respectively, it will be seen that there is a marked difference betAveen the red fluid contained in the two tubes. The blood diluted w^ith physiological saline is red and opaque; that distilled with distilled water is red and clear. The blood has become " laked," or haemolyzed, by the water. By means of the change to a clear red solution it is easy to say when haemolysis has taken place. Very slight traces of haemolysis may be detected in the upper layers of the tube when the corpuscles have sunk to the bottom. By haemolysis is understood the process in which a red corpuscle is damaged so that the haemoglobin contained within passes into the surrounding fluid. Heemolj'sis or laking is always due to injury of the stroma or envelope of the red corpuscle, and may be induced b}' a number of means: (a) Physical. (6) Chemical. (c) Foreign sera. (d) Bacterial toxins. (e) Vegetable poisons. (/) Animal poisons such as snake venoms. Physical. — Tlie addition of phj'siological saline to blood does not cause laking because it contains salt (NaCl) in about the same concen- tration as that of the salts in the plasma. There is therefore no great interchange of Avater between the added fi^iid and the red corpuscles. The addition of distilled water causes laking because it contains no salts in solution. The red corpuscles of the blood contain inorganic salts in the ionized state. When the distilled water is added to the blood, water passes into the red corpuscles, until there is produced an ec[ual concentration of ions on either side of the cor2)uscular en- velope. The water passing in greatly distends the corpuscle and eventually ruptures the envelope. The pigment contained in the corpuscle then passes into the surrounding medium, and. becoming dissolved in it, forms the clear red solution characteristic of haemoh'sis. The membrane of the corpuscle forms a semi-permeable membrane which is easily permeated by the Avater but does not alloAv the salts to pass out. Alternate freezing and thawing also damage the envelope 105 J Of) A TEXTBOOK OF PHVSTOLOCIY owing to water being separated as ice in the process of freezing. Electrical currents of high potential may also disintegrate the corpuscles. Chemical.^Many chemical bodies, such as arseniuretted hydrogen, nitro-benzol, nitro-glycerine, nitrites, guaiacol, saj)onin, jjyrogallol, acetanilide, and ammoniinn salts, produce laking. Others, such as sugar and sodiuni chloride, do not; these cannot permeate the corpus- cular envelope. While urea and ammonium chloride permeate the corpuscles readily, a solution of urea in isotonic solution of sodium chloride does not lake the corpuscles, although ammonium chloride does. A solution of ether in distilled water produces laking. It is suggested that the permeability of the corpuscles is controlled by the cholesterin and lecithin in the stroma as solvents of lecithin and cholesterin i^roduce laking — for example, chloroform, ether, bile salts, and amyl alcohol; but the majority of hajmolytic agents, both inor- ganic and organic, are not solvents of these lipoids. Haemolysis by Foreign Sera. — If a few drops of the blood of a man be mixed with the serum of a rabbit in a test-tube, it will be found that the solution, red and opaque to begin with, becomes after a time transj^arent, showing that haemolysis has taken place. This property is increased by immunizing the rabbit against the foreign red corpuscles. The injection of a very small dose of foreign corpuscles is sufficient to raise the haemolytic power of the serum. For example, 0-125 gramme of ox blood, injected intravenously in the rabbit, produces a hsemo- lysin which specifically acts on ox corpuscles, so that rapid laking takes place when the rabbit's serum is mixed with ox corpuscles but not when mixed with any other animal's corpuscles. The explanation given for this phenomenon is the same as for bacteriolysis (see p. 109). Sera, and especially imunized sera, have po^er to destroy bacteria. There are concerned two substances in the serum: (1) an amboceptor, which is increased by immunization, and (2) a complement, which is present in fresh normal serum and is destroyed by heating to 55° C. Very little is known as to the chemical properties or mode of action of these bodies. The action takes place quickest at a little above body temperature. If the ox corpuscles and rabbit's serum are mixed at 0° C, there is no haemolytic action, because the complement cannot act at this temperature, but the amboceptor combines with the corpuscles and can be removed with these from the serum. After separation by the centrifuge the corijuscles can be washed in isotonic salt solution, to remove all traces of the rabbit's serum, separated by the centrifuge again, and then mixed with normal serum and warmed to body temperature. Laking then takes place because the complement alone is wanted to complete the reaction, and this is present in any fresh normal serum. Haemagglutinins, similar to the agglutinins which are produced to antagonize bacteria, can also be obtained by the injection of foreign blood into an animal. These cause the red corpuscles to run together, or agglutinate. Some sera contain no hsemo- lysins, only agglutinins; others contain hsemolysins and no agglutinins. The two bodies, however, usually exist side Ijy side, sometimes the action of one being more marked, sometimes the action of the other. In agglutination the surface tension is altered; the lecithin and cholesterin constituents of the stroma are supposed to take a part. The haemolytic action of eel's serum is exceptional. If as little as O'l c.c. of eel's serum per kilo of body weight is injected into a rabbit, it dies in two or three minutes. This serum differs from other sera insomuch as heating to 54° C. destroys its action, which is not restored by the addition of complement. H.^MOLYSTS AND IIVCVIUNITY 107 Bacterial Hsemolysins. — Certain pathogenic bacteria — e.g.. Bacillus pyocyaneus and staphylococcus (the organism of boils) — produce agglutinins for human corpuscles. Sometimes these play a part in the formation of emboli. The corpuscles may bo clumped together, mixed with the infecting bacteria, and carried by the circulation 'to another part and so spread the mischief. Haemolysis occurs in the blood during an attack of blood-poisoning (septicsemia). The best-known bacterial hsemolysins are those produced bj- the bacteria of tetanus (lockjaw) and of typhoid, and the staphj^- lococcus and streptococcus. They are known as totano-lysin, typho-lysin, etc. Their action is due to direct combination with the cell without the aid of an inter- mediary (amboceptor). They are therefore comparable to toxins, which unite directly with the red corpuscles and destroj' them. Hsemolysis produced by Vegetable Poisons. — Some vegetable poisons, crotin (croton-oil seed) and plialein (Pltallu-i impitdictis, a fungus), have a very marked haemolytic action, and others, ricin (castor-oil bean) and abrin (jequirity bean), agglu- tinate,' but produce little hannolysis. Immunity can be established against these bodies and antibodies produced. Against another group of vegetable poisons no antibodies are produced. In this are included saponin, cyclanin from cyclamen, solanin from the green potato, helveUic acid from a species of mushroom {Helrdla esctdenta). Saponin produces hsemolysis in 1 : 100,000. These poisons differ alto- gether from bacterial toxins, being resistant to heat, and having no resemblance to proteins. They are related to glucosides. The action of saponin is prevented by the presence of an excess of cholesterin in the blood ; haemolysis is probably caused by the cholesterin portion of the stroma linking the poison to the corpuscles. The toxicity of these substances is not in anj^ way proportional to their hsemotytic powers', their chief effect being paralysis of the heart and injury to the central nervous system. Haemolysis by Snake Venoms. — The salivary secretion of certain snakes — cobra, rattlesnake, copperhead — causes agglutination of the red corpuscles, and in some cases also induces hsemolysis. The snakes secrete in their saliva an amboceptor, and the person bitten provides the complement. An animal can be immunized agamst snake venom so that it comes to withstand many times the lethal dose. An " anti- venin " is produced which, bj- linking on to the amboceptor in the snake venom, pre- vents its union with the red corpuscle. The hsemolj-sins can be dried at a cool temperature without losing potency, are destroj^ed by acids and alkalies, and inhibited in their action by salts. Introduced by the stomach they have no action. In health but little haemolysis takes place apart from the destruction of effete corpuscles. In fevers haeiliolysis may be produced by bacterial toxins. It is suggested that certain anaemias may be due to haemolysins formed by parasitic inhabitants of the alimentary tract. If more than a small amount of haemoglobin is set free in solution in the plasma, it escapes in the urine, giving rise to the condition known as haemoglobinuria. In some rare cases haemoglobinuria foUows exposure to cold — e.g., it occurs in some persons after putting the hands in iced water. Immunity. — Besides the substances which can be isolated by chemical means, weighed, and anatyzed, there are manj^ and subtle properties possessed by the plasma, such as its immunizing powers, which can only be detected by the newly-discovered biological tests. These tests depend on the reaction of living substances, and are of the most extraordinary delicacy. On these properties of the plasma depend the immunity of the organism against infective diseases and certain toxins of animal or vegetable origin. The immunizing sub- stances are quite specific for each bacterium or toxin. It is known that man is immune to certain infective diseases which affect other animals. For example, he is immune to swine fever. This is termed natural immunity. It is also known that a second attack of whooping- cough, measles, smallpox, etc., is rare. He who has suffered once has an acquired immunity. Such acquired immunity may be estab- K)S A TEXTBOOK OF PHYSIOLOGY lislu'd agaitisl xarious ioi'Dis of poisons, vcgetabk' or animal, hnt in ])articular against bacteria and tlie ])oisons they elaborat{\ which are known as toxins. Two forms of ijnnninity, then, may be acquired — one, which is the better understood, deals with the toxins, the second deals with the bacteria themselves. In dealing with toxins the body has the ])()wer to elaborate a group of substances which are known as antitoxins. If at appropriate intervals and in ap])ropriate doses an aninud's body be injected either (1) with one of the poisons or toxins, p.oduced in nutrient media by the growth of such bacteria as the bacilli of diphtheria, tetanus (lockjaw), or (2) withr vegetable proteins of a poisonous nature, such as abrin (jecj[uirity bean) and ricin (castor- oil bean), or (3) Avith an animal poison, such as the venoms of different forms of snakes, scorpions, bees, wasps, and spiders, a sj)ecific antitoxin negativing the action of each of these poisons is produced in the blood. It his been postulated that the living protoplasm consists of a central living nucleus and numerous side chains, or receptors, w liich are attached to this. To each of these one or other function is allotted — above all, the absorption of nourishment. The side chains, or receptors, form complexes of atoms in the molecules of the protoplasm which, owing to their chemical structure, are able to combine or link up with other substances — for example, nutritive material, or toxit s. The receptors combine with certain groups of atoms of these substances which, owing to their combining powers, ^are termed haptophoric groupa, or h:)p';ophors. The combination between these haptoi^hors of the nutritive material, or of the toxins with the rcceiators of the cells, which have an affinity for them, is necessary before either the nutriment or the toxin can have its effect on the cell. If when a toxin gains entrance within the organism it finds no receptors of a structural substance to link with it, it can exert no poisonous effect, and the organism is naturally immune to that toxin. Besides the haptophoric group the toxin possesses a grou]) which has the poisonous effect. This is the toxi- phoric groui^, or tjxoplior. We may sujijiose that a nutritive group linking itself to the central chemical nucleus of the cell help? to maintain the lability of the mole- cular complex which manifests the phenonuna of life, while a toxic group either arrests the lability or shatters the molecular structure of this nucleus. The toxophor is harmless unless anchored on to the cell by the haptophor. Just as a lock cannot be opened unless the person, the active agent, has the key. Evidence has been obtainecl which makes it likely that these two groups do exist, and that the toxin may lose its poisonous properties without losing its power of uniting to the cells; thus, in the case of tetanus toxin it has been ,'hown that treatment with carbon disulphide destroj'S the poisonous property of the toxin, but not its power to evoke the production of antitoxin. The haptophoric group remain; linked with the body tissue cells, and produce; antitoxins by stimulating the production of re- ceptors. Such a modified toxin is called a toxoid. Antitoxin; are cell-receptors which combine with the haptophorous grouji of the toxin and render it harmless. These cell-receptors are produced in great numbers, and set free in the blood by the action of a toxoid, or by repeated small and non-lethal injections of a toxin. The union of the haptophoric groups with the cell-receptors stimulates an increased pro- duction of these cell-receptors which are secreted into the blood. Anti oxic sera are thus produced by the injection of toxoids or non-lethal doses of toxins. It is suggested that the linkage of a chemical group with a particular side chain of a cell evokes the production of other side chains of a similar configuration, and the jDroduction of these may be stimulated to such an extent that they escape from the cell into the blood and endow this with antitoxic power. The receptors (antitoxin) Uberated by any mammal immunized against a given toxin are apparently the same; thus, the antidiphtheritic toxic serum of horse, sheep, or goat will, if injected, neutralize the diphtheria toxin in another animal — as, for example, the guinea-pig or man. But each antitoxin is specific and will neutralize the toxin which produces it and no other; antidiphtheritic serum, for example, would be of no use if employed as the curative agent for the toxin of tetanus. Every lock, so to speak, must have its own key, and if the man has not the right key he cannot open the door. In this comparison the man HEMOLYSIS AND IMMUNITY 109 is the toxin, the key the haptoph(n-, tlie lock the receptor. If the man happened to have left his key fitted in a loose lock he would not be able to open his door on reaching home. So the toxins meeting the loose receptors in the blood (antitoxin) become bound to these and cannot attack the cells. The neutralization of the toxin by' the antitoxin can be demonstrated in vitro. It is stated to be a chemical process taking place in definite proportions with the liberation of a small amount of heat. Neither toxin nor antitoxin is destroyed in the process; they are simply linked to- gether, and in some cases, at any rate, can be separated again by appropriate means. The reaction is accelerated by warmth, slowed by cold, and occurs more rapidly in strong than in weak solutions. The chemical nature of the antitoxin is unknown. It is closely related to serum globulin, being carried down when this is precipitated, but is not necessarily pi'otein, although its general pro])erties are those of a colloid. Unlike an enzyme, it is not carried down by an indifferent precipitatj. A toxin seems to be a simpler body than an antitoxin, for in the case of the haemolysis produced by the Megatherium bacillus, the toxin can be pressed through a porcelain filter impregnated with gelatin, while the antitoxin cannot pass it. Toxic effects are sometimes produced by the injection of antitoxic sera. These effects must not be ascribed to the antitoxins, but to other bodies contained in the foreign serum which is injected. There are many bacteria which do not liberate soluble toxins into the plasma, but have endotoxins which accumulate within them, and only become liberated when the bacteria are disintegrated. The body elaborates no antitoxins for such as these. Under this class come cholera and typhoid bacilli. If an animal be injected with appropriate doses of typhoid bacilli, alive or dead (the bacterial vaccines prepared for man are sterilized by heat), the blood acquires bactericidal j)roperties which are specific for the typhoid bacillus. It is then found to contain an agglutinin which causes the bacilli to stick together or agglutinate, and, if motile, to become motionless. This is seen to take place when a drop of serum is mixed with a drop of culture fluid containing living typhoid bacilli. Further, it contains an opsonin which renders the bacilli more "tasty," so that they are eaten or destroyed by the white leucocytes, known as phagocytes. In some cases the plasma also acquires anti-enzymes which counteract the action of the enzymes contained in the bacteria. The plasma natui'ally contains anti-enzymes which neutralize the enzymes in the body, such as thrombin, pepsin, etc. Lastly, by virtue of precipitins it obtains the power of precipitating the bacterial proteins. All these reactions arc specific against the bacteria injected, and are quite distinct from each other. The mode of action of bactericidal serum is different to that of antitoxic serum. If a bactericidal serum — for example, a serum taken from an animal which has re- ceived repeated injections of non-lethal doses of cholera vibrios — be heated to 55'^ C. for fifteen minutes, it is found to have lost its power of destroying these bacteria. Vet if now inactive normal serum be added to this inactivated heated serum, it again becomes bactericidal. By the process of immunization the blood has obtained some new substance not destroyed by heating to 55' C, which is unable by itself to kill bacteria, but is able to do so when associated with another body, which is contained in normal serum and is destroyed by heating to 55° C. Just as is the case with hsemo- lytic sera, there are two bodies concerned in this process of bacterial immunity — the one devolop:nl during immunization and not destroyed by 55° C, the immune body, or amboc:p'.or, the other present in normal serum and susceptible to heat — the complemsiit. Any protein which provokes the production of an haemolj-sin, antitoxin, antivenin, precipitin, immune body, etc., is called an UTlt'gDi?. The action of the immune body and complement is explained on the supposition that the immune body is a haptophor which unites the bacteria to the complement. The complement takes on the role of toxin (toxic to the bacteria). The immune body differs from antitoxin in having two affinities — one for the bacteria and one for the complement; for this reason the immune body is termed amb coptor. There are some sera which naturally possess amboceptors apart from any process of immunization. The term immune body is reserved for amboceptors produced by immunization. The Immune Sody. — The immune bodj' is apparently formed in all the tissizes of the body, particularly the connective tissues. It is not destroyed by temperatures which are fatal to the complement Thus, twenty hours' heating at (iO" C. scarcely injures it, but at lU(t ('. it is destroyed almost at once. It is resistant to putrefaction, and has been ke])t for as long as eight years. It seems to be closely associated with, or absorbed to, the serum globulins, and on this account is not dialyzable. 110 A TEXTBOOK OF PHYSIOLOGY The Complement is believed to be tlie actual destroying agent. It is not increased in tlic blood during the process of immunization, and thus it comes about in some cases that there is not sufficient comjjlcment for all the immune substances whose action it is sought to demonstrate. A sufficiency can be provided by the addition t)f normal serum. The origin of the complement is not known. The leucocytes and the tissues may each play a part in providing it. The complement is easily destroyed by heating to 5(5° C. While its chemical nature is quite unknown, it is worth noting that in the ease of snake venom the phosphorized fat, lecitliin, plays the part of, or is associated with, the complement. The Deviation of the Complement. — When serum containing a specific immune body is inactivated (has its complement destroyed) by heat and mixed with the antigen used in its ])roduction, a combination takes plajoe between the two, and the antigen is then said to be sensitized. However, no visible effect is apparent until complement contained in fresh serum, usually that of a guinea-pig, is added. The complement combines with the sensitized antigen, and may produce a visible effect (e.g., haemolysis). It should be noted that an antigen can only be sensitized by its specific immune body, and that complement can only combine with the antigen when linked to the specific immune body; thus, the combination, or fixation, of the com- plement can be made a test for the presence of a specific immune body. The test is very delicate and of great diagnostic value, and is carried out in the following way : A rabbit is immunized against sheep's blood-corpuscles. Its serum is obtained, heated to 56° C, and kept in sealed capsules. This serum will hajmolyze sheep's corpuscles if a certain minimal amount of normal serum of a guinea-pig is added. The minimal amount is determined by experiment. All is now ready for testing the blood, say, of a man susi^ected to be infected with typhoid bacilli. Serum is obtained from this man and heated to 56° C. to destroy the complement in it. It is then mixed with typhoid bacilli and the minimal amount of normal guinea-pig serum added. The mixture is kept at body temperature, and time enough allowed for the specific immune body (if present) to fix the complement and antigen (the typhoid bacilli). It is then added to a mixture of sheep's corpuscles and the heated rabbit's serum. Haemolysis will not take place if the complement has been fixed in the first stage of the test, since none will be left to combine with the sensitized sheep's corpuscles; and in such a case it is clear that the suspected serum did in fact contain typhoid immune bodies. If haemolysis does take place, the complement could not have been fixed in the first stage, and thus the suspected serum was not from a case of typhoid. Opsonins. — -These are specific substances in the serum which act on bacteria in such a way as to make the phagocytes ingest them. Their presence is demonstrated thus : Blood is collected and allowed to clot. The white corpuscles are separated from the serum by means of the centrifuge. The serum is pij^etted off, and the corpuscles mixed with physiological salt solution, and again separated by the centrifuge. This procedure washes the corpuscles free from serum. Bacteria are mixed with the washed corpuscles and the mixture kept at body temperature for ten minutes. A film is then made, stained, and the average number of bacteria ingested by the phago- cytes counted. A similar experiment is performed, only in this case the serum is allowed to act on the bacteria. The phagocytes ingest many bacteria which have been first acted on by the serum, and very few of those which have not been so treated. Thus, the serum contains opsonin which prej^ares the dish for the leucocytes to ingest. Opsonins exist in the normal blood of many animals, and aie increased in amount by the process of immunization — by vaccination with dead bacteria. The opsonins in the serum of one animal are able to act on the bacteria, so that they are ingested by the phagocytes taken from another animal. Their chemical nature is not known. They are of the utmost importance in furthering the defence of the body by the phagocytes. Agglutinins, — These are bodies possessing the property of clumping bacteria. The bacteria themselves are not greatly damaged by the process, but it tends to pre- vent the dissemination of the organisms, and it may in some way favour phagocytosis. The nature of the change thus brought about in the bacteria is not well known, but their colloidal nature is probably altered by changes in surface tension. Agglutinins can be prepared against almost all bacteria. Their place of formation is not known. They have been demonstrated in the blood and to a less extent in the milk. Attached in some way to the globulin in the plasma, they cannot be separated from it. They are destroyed by heat; the temperature of destructidh varies for different agglutinins. As in all processes of a like nature the concentration of the electrolytes in solution affects their action. HAEMOLYSIS AND IMMUNITY 111 Precipitins. — These bodies are present in the blood of an immunized animal, and produce a precipitation of the soluble bacterial proteins if added to a filtrate of the culture used for immunizing the animal. Their action is specific. Precipitins can be produced bj' the injection of any protein, provided that the protein is foreign. It is useless to try and immunize a rabbit against rabbit's serum, and it is better not to employ closely related specie?, such as rabbit and guinea-pig. As the result of the injection of horse's serum into a rabbit a precipitin is obtained in tlie rabbit's serum which precipitates the proteins in the serum of the horse and of no other animal. Similarly, as the result of the injection of cow's milk a precipitin is obtained which precipitates only the proteins of cow's milk and not those of the milk of any other animal. The specific action of precipitins shows us that the structure of the homologous proteins varies in different animals. Only by the injection of foreign proteins can precipitins be produced, and the power of the proteins to produce precipitins is lost when they become split up into peptones. Fats and carbohj^irates cannot produce precipitins. The precipitation test can only be made outside the body. If serum containing precipitins be injected intravenously, it does not cause precipitation, but provokes an increase in the number of leucocytes. The material obtained from a mummy five thousand j^ears old gave the j^recipitin reaction for man. The action of precipitms is modified by the concenti-ation of electrolytes. A precipitin has two linkages: one the haptophor, which links on to the protein, and another linkage (destroyed by heating to 60° C), which induces the change bringing about the precipitation of the protein. The precipitin appears in the blood about six days after the first injection of protein has been made. Following each subsequent injection it disappears for a time, and then appears again. When the injections are finished, the precipitin quickly disappears from the blood, its fate is not known, and it cannot be detected in the urine. The source of precipitins is not known. As an increased number of leucocytes (leucocytosis) follows each injection, it has been thought that these produce the precipitins. The precipitins are attaclied to the globulins in the plasma and cannot be separated from them. Cytotoxins. — By the injection of animals' cells, bodies called cytotoxins are pro- duced in the blood. These are capable of destroying the foreign cells injected. Red corpuscles, leucocytes, spermatozoa, kidnej- substance, stomach, thyroid, and nervous tissues, have all yielded specific cytotoxms, and so-called erythrolytic, nephrolytic, and other " lytic " sera have been produced. Small gastric ulcers have been caused by injecting the blood of one animal immunized against the injections of the mucous membrane of the stomach of another species of animal. The red corjjuscles afford the best material for stud3dng this phenomenon (c/. Haemolysis, p. 105). Hypersusceptibility, Anaphylaxis. — Some peojile are extraordinarily sensitive to the ingestion of certain nutritive material such as crab flesh, strawberries, egg white. They are made sick by eating one or other of these things, or suffer from the eruption of a nettle-rash, the result of a disturbance of the equilibrium between the osmotic pressure of the tissues and tissue lymph, whicli in its turn is due to the toxic effect whicli the ingested material has on the tissue metabolism. Similarily, sensitivity may be produced by injection of a small dose of a foreign protein — e.g., of horse serum; the sensitivity is so increased that a second dose of the same serum, containing perhaps little more than a millionth of a gramme of protein, may produce the severest sj^mptoms of intoxication and even death. The hypersusceptibility or hypersensitivity thus induced is termed anaphylaxis. The initial cause of the symptoms seems to be con- striction of the bronchial tubes and obstruction of the airway and a great fall in the blood-pressure, accompanied by congestion and even haemorrhages in the mucous membranes of the bowels. Convulsions, follow the consequent anaemia of the brain. If the animal recover, it is immune to further injections of this serum. The sensi- tivity lasts a very long time. Anaphylaxis has been the cause of alarming symptoms in man in certain eases where a second dose of antitoxic serum has been given after an interval of time. (In some 10 per cent, of normal individuals a single injection of antitoxic serum is followed by similar though less severe symptoms.) Anaphy- laxis may be regarded as the opposite to immunity. OH AFTER XIV THE TESTS FOR BLOOD t'ROM what has gone before we may now grou]) the chief tests for blood. These may be divided into ( 1 ) microscopical, (2) spectroscopical, (3) chemical, (4) biological. Microscopical. — By the use of the microscope the size and shape Oi the corpviscles can be ascertained (see p. EG). Reptilian, birds', or camel's blood can be distinguished from that of the domestic animals or man. The method is of no service in distnginshing between the com m oner ma mmals . Spectroscopical. — The preparation of spectra of hsemochromogen, hsematoporphyrin, and acid hsematin, are useful in indicating the presence of blood (see p. 94). In old blood-stains the haemoglobin is broken down to hsematin. Chemical. — Under this heading we may include {a) the preparation of hsemin crystals, (6) the guaiacum test for blood. Preparat:c7i of Hoemin Crystals. — Some of the suspected deposit is taken and placed upon a slide with a crystal of common salt or sodium iodide. Acetic acid is added sufihciently to float the cover-slip. Warmth is then applied until bubbles begin to rise beneath the cover- slip. The slide is then removed from the flame to cool, and the pro- cess is repeated three or four times. Great heat must not be used. Upon examination beneath the microscope, chocolate rhombic crystals of hsemin (hsematin chloride or haematin iodide) will be seen (Fig. 25). The Cuaiacum Test for Blood is usually employed in testing for blood in urine, stomach contents, and other body fluids. If to the boiled suspected solution a drop of tincture of guaiacum be added, then a few drops of ozonic ether, and the reddish guaiacum turns to a blue colour, it signifies blood. The ro:.ct:on depends on the iron combined in the haemoglobin. The enzymes known as oxidases give the test, and therefore a positive result is sometimes obtained with such body fluids as milk and saliva, and with the juices of vegetables, apple, pineapple, potato, which sometimes leave a brown stain re- sembling stale blood. As the oxidases are destroyed by heat a solu- tion suspected to contain blood should be boiled before it is tested. If this condition is complied wdth, a positive reaction may be taken to indicate blood. If the test is negative, blood is certainly absent. Instead of ozonic ether, hydrogen joeroxide or old oil of turpentine can be used. Various tests have been devised using bodies other than guaiacum resin. Such bodies are — aloin, bcnzidin, and the leuco 112 THE TESTS FOR BLOOD 113 base of malachite green and of phenolphthalein. The last-named body is stated to be extremely sensitive. Fi ;. 2.:\— H i:MiN Crystals, x 1,500. Biological. — The biological te?t depends upon the fact that the serum of an animal injected with foreign corpuscles develops the power of precipitating, aggkitinating, and dissolving corpuscles similar to those injected, but not those of other species of animals. A rabbit is injected with 2 to 3 c.c. of human serum at intervals during four days, until 10 to 15 c.c. have been injected. After one to two weeks the animal is bled, the serum collected and placed in sterile tubes, and used as needed. This serum is mixed with the suspected blood, which is dissolved or suspended in isotonic salt solution in the proportion of 1 : 100; the mixture is placed at 37° C. If the blood be human, a turbidity is produced, changing within three hoiirs to a flocculent precipitate. The blood of closely allied species, such as the other Primat'CS — e.g., chimpanzee — may give a slight precipitate. The test has been used to detect human blood in medico-legal cases, and to con- firm the supposed consanguinity of different species of animals. It shows the near relation of man to the gorilla, the ourang, and the chimpanzee. 8 BOOK III THE CIRCULATION OF THE BODY FLUIDS CHAPTER XV THE MECHANISM OF TRANSPORT The unicellular organism floating in a nutritive water}' fluid lives by exchange between its body and the surrounding medium. In the multicellular organism the deeper parts become too far removed from the siu-face for a rapid exchange of material to take place, and devices such as infolding are evolved, which lead the medium into the inner recesses of the bod}'. With the higher organization brought about by evolution, a limit soon became set to such infolding, which interfered with the differenti- ation of structure and division of labour necessary to render the organism efficient in the struggle for existence. Hence, there came about the development of a body cavity, or coelom, filled with an internal medium, which, as blood or lymph, was at first made tO' circulate by the general movements of the bodj-. Later was evolved a special pump — the heart, or several hearts — and a system of vascular tubes, at first partly and then conipletel}- closed. By the aid of these the internal medium could be driven with greater swiftness and insure the better nourishment of every part. The internal tissue of a Turbellarian worm, for example, is a loose aggregate of cells, differ- entiated to a slight extent in structure and no doubt in function, comiected by strands of protoj^lasm. Between the cells are inter- cellular clefts, which are connected with larger channels which extend through the body, and act as circulatory channels. These clefts and channels are filled with a fluid which carries the food and oxygen supply to, and the waste products from the internal tissues, and in every way acts as a simple blood. A to-and-fro movement takes place as a result of the movements of the animal. The meso- dermal ceUs in contact with the primitive channels become differ- entiated in part into tissues, which form waUs to these spaces. The primary circulation spaces become specialized into continuous channels which run the length of the body. The blood is driven to and fro in this body cavity, or coelom, by the movements of the muscles of the body, and, so propelled, bathes the respiratory tissues, the wall of the gut, the nephridia and other structures. 115 IIG A TEXTBOOK OF PHYSIOLOGY In the mollusca we find definite blood-channels, the larger of which, in the cephalopods, have well-developed muscular walls, and act as ])umiDs driving by Avavc-like contractions the contained fluid before them. In the lobster there is developed a heart. It is endowed with a rhythmic activity of its own, and forces the blood through a sj^stem of larger vessels — the arteries — to smaller frailer vessels — the capil- laries^ — and thence to open spaces between the masses of connective tissue — the lacunse. From these lacunse the blood is returned to the heart by another system of channels — the veins. In insects the circulatory mechanism is simple. A dorsal pump — the heart^forces the blood through a vessel which runs in the median line from one end of the body to the other into large sinuses and spaces; from these it is returned to the heart. In the limbs are placed accessory hearts, which force the blood to their extremities. In the vertebrates the evolution of the circulatory system is carried to the highest point. Blood is pumped from a well-differentiated strong muscular heart, by means of an arterial system with well- marked muscular and clastic walls, into a capillary system the walls of which are formed by a single layer of endothelium. The lacunar system still persists in part, for in certain organs, such as the spleen, the capillaries are not closed vessels, but open into the tissue spaces. From the capillaries the blood is returned by Itirger channels — thi.; veins — to the heart. In Amphioxus the blood vascular sj'stem is still of the primitive lacunar type This lowest vertebrate possesses two hearts — a dorsal heart, driving arterial blood to the system, and a ventral one, which is termed the "' respiratory heart,"' sending blood to the gills. In fishes the heart is single, and essentially respiratory in function, propelling blood to the giUs, thence to the aorta and to the system generally, and back again to the heart. In the amphibia there are two auricles and one ventricle ; in reptiles two auricles and a partial separation of the ventricle into two. It is only in the birds and mammalia that the two systems become quite distinct — two auricles and two ventricles — the right auricle and ventricle forming the respiratory system, the left auricle and ventricle the systemic. This evolution has, however, been carried out on quite a different plan in the two hearts, the bird's heart differing in many points from the mammalian. In man the heart is about equal in size to a closed fist, measuring about 5 inches long, 3-| inches wide, and weighing in the adult about 300 grammes, or 0-46 per cent, of the body weight. In the new-born baby it weighs about 24 grammes, 0-76 per cent, of the body weight. The average weight of the male and female heart is almost the same. The volume is estimated by filling the cavities with wax, to be 100 to 130 c.c. for each auricle, and 150 to 200 c.c. for each ventricle. The auricles have much thinner walls than the ventricles. The muscle of the auricles consists of a circular layer common to both, THE MECHANISM OF TRANSPORT 117 and a deeper layer separate for each chamber. The auric ulo- ventri- cular ring consists of connective tissue separating the muscle of the auricles from that of ventricles except at one spot on the septiim (see p. 121, the A.-V. bundle), and possibly at the right lateral external margni. The right auricle is more or less quadrilateral in shape, being prolonged in the upper corner to an ear-like process — the right auricular appendix. Into it the superior and inferior vense cavse open. At the junction of the superior vena cava and auricle is situated a small mass of tissue known as the " sinu-auricular node." The right ventricle forms the chief part of the anterior surface of the heart. It communicates with the right auricle and with the pulmonary artery. At the entrance from auricle to ventricle are 'st arch 2ncl arch uentral aorta conus arteriosus prim, uentriciei . / \prim. auricle sinus uenosus vit vein^^'''^ ^"^uit ueir, Fig. 26. — ^The Primitive Divisions of the Embryonic Heart. (Keith.) situated the tricuspid valves, while the entrance to the pulmonary artery is guarded by thin watch-pocket-like valves — ^the semilunar valves. The left auricle is situated posteriorly. It likewise possesses an appendix. Into it the four pulmonary veins open. The left auricle communicates with the left ventricle, the orifice being guarded by the two flapped bicuspid or mitral valves. The left ventricle forms the chief part of the posterior surface, and also the apex of the heart. It forms the chief muscular mass of the heart, the wall being in places i inch in thickness. It com- municates with the left auricle and with the aorta. At the orifice of the aorta are situated delicate semilunar or watch-pocket valves. Opposite the cusps are bulgings of the aortic wall — the sinuses of Valsalva. From the anterior one arises the right coronary artery, US A TEXTBOOK OF PHYSIOLOGY and from the left posterior the left coronary artery. These vessels supply the heart muscle. Various accounts are given of the arrangement of the musculature of the ventricles. Internally, the muscular fibres are thrown into columns — the colunnue carna? and the papillary muscles. The super- ficial fibres take origin from the auriculo-ventricular ring, and wind .spirally about the heart, to end in the papillary muscles, or pass up in the septum to the ring again on the inner surface of the heart. The middle layers, which form the bulk of the tissue, consist of bundles of fibres running more or less circularly round the ventricles. Fig. 27. — Generalized Tvpe of Vertebrate Heart. (Keith.) a, Sinus venosus and veins; b, auricular canal; c, auricle; d, ventricle; e, bulbus cordis; /, aorta; 1-1, sinu-auricular junction and venous valves; 2-2, canalo-auricular junction; 3-3, auricular ]iart of auricle; 4-4, invaginated part of auricle; 5, balbo-ventricular junction. By the study of the primitive type of vertebrate heart a clear concej)t has been gained not only of anatomical arrangement, but of the function of certain parts in the more highly developed mam- malian heart. The heart develops as a tul:)e (Fig. 26), and the auricle is regarded as a dorsal expansion of this tube, and the ventricle as a ventral expansion. The diagram (Fig. 27) represents the general type of a primitive vertebrate heart. The cardiac tube begins at {a) and ends at (/). Dorsally is placed the expansion (c), the auricle, while {d) represents the ventricular outgrowth. Such a heart may be said to consist of five chambers. At the venous end (a) the sinus venosus is formed by THE MECHANISM OF TRANSPORT 110 the junction of the two great veins. The blood enters the heart, and the wave of contraction begins here. Chamber (6) represents the original cardiac tube from which the auricle has grown out dorsally. It is known as the " auricular canal," and may be subdivided into three parts: {A) the part of the cardiac tube antecedent to, and opposite, the outgrowth of the auricle (2-2) — generally termed the " basal part "; {B) the part which comes after the outgrowth of the auricle and before the downgrowth of the ven- tricle (3-3) — the ■■ auricular ring "; {€■) a part (4-4) which has become invaginated into the ventricle. The ventricle is represented by (d), while (e) at the arterial end of the cardiac tubs represents the chamber known as the " bulbus cordis." Fig. 28. — Right Auricle seen from thk Side. (Keith a-.id Flack.) it, Su]ierior vena cava; b, appendix; S.-A., sinu-auricular node; c, vestibule of left auricle; /, union in sulcus terminalis of two branch arteries arising from right coronary artery; HV8I0L0GY make the same number of beats as visual in a given time, in sjiite of the induction of extra systoles. The length of the compensatory paiise is due to the refractory period; the im])ulse (;ausing the normal contraction reaches the ventricle at a tim(i when it is in a state of systole induced by the artificial stimulus. It is therefore refractory, and the normal impulse has no effect. The ventricle is not stimu- lated again until the next normal impulse arrives, and thus the pause is produced. In the case of the frog's heart, a compensatory pause does not follow extra contractions ijiduced by stimidatibns of the sinus. Extra systoles, followed l>y the compensatory pause, are produced by a stimulus applied to some other part of the heart — e.g., auricle or ventricle. It is assumed, therefore, that the normal stimulus actually arises in the sinus. This is also true for the mammalian heart. Electrical stimulation of the sinu-auricular node does not induce an irregularity of rhythm, but either a slowing or a weakening of the whole heart, according to the intensity of the stimulus. immmmmmmmmmmmm Pjq. 41. — Normal Electro-Cardiogram. (W. T. Ritchie, from Cowan's "Diseases of the Heart.") Normal cardiac muscle cannot be tetanized (Fig. 40), as it is impossible to bring about a true summation of stimuli in the normal heart. In Fig. 38 it is seen that a second stimulus applied towards the end of systole can only produce a small amount of summation, because it does not act sufficiently soon after the first stimulus owing to the refractory period. The cardiac muscles of certain invertebrates — for example, of the horseshoe crab, Limulus — do not possess the characteristic properties of the vertebrate heart-tissue. It possesses no refractory period, gives submaximal contractions, and can be tetanized. Like other forms of muscle, the heart-muscle possesses the property of tonicity. The heart may be tonically contracted or dilated, and by its systole expel the blood from a larger or a smaller cavity. The mammalian heart can be placed in an instrument called the " cardio- meter " (Fig. 68), and its volume recorded and the alterations of tonicity measured. The tonicity is influenced by the cardiac nerves. If the frog's ventricle be placed in a weak solution of caustic soda (1 in 20,000 of normal saline), it relaxes less and less between the beats, THE PHYSIOLOGY OF THE HEART 133 and eventually stands still in systole ; in lactic acid (1 in 10,000 normal saline) the contractions become less and less, and finally the ventricle stops in a state of complete relaxation. The drugs digitalis and veratrine yield results similar to alkalies, muscarin similar to that of acids. Chloroform lessens, and adrenalin increases, the tonicity of the heart. After death from chloroform, the heart is dilated and the muscle flabby. The heart possesses the properties of rhythmic automaticity, of starting a stimulus. It also possesses the property of conduction fmm t^'-^ifsHmnH ^tsrmi^itm \f^Am»^ ^/Wi^ww^ ^ii^)mim \ Fig. 42. — Electro-Cardiogkam from a Case of Complete Heartblock. (W. T. Ritchie, from Cowan's " Diseases of the Heart.") The auricular rate is 97, the ventricular rate 38, per minute. of an impulse. It is a vexed question whether these properties reside in the heart-muscle itself, or in the nervous tissue abounding there, or in the intermediate nodal tissue. The electrolytes in solution in the tissue lymph are essential factors in the maintenance both of rhythmic automaticity and tonicity*. The Electrical Change of the Heart. — The contraction of the heart, like that of other muscle, is accompanied by an electrical change. The part in contraction is at different potential to the part at rest. pM^ Fig. 43. — Electro-Cardiogram shovving Regularly Recurring Ventricular Extra Systoles. (W. T. Ritchie, from Cowan's " Diseases of the Heart.") Thus, an electrical wave accomx^anies the wave of contraction. This is studied by means of either the capillary electrometer or the string galvanometer. The principle of the string galvanometer is that a movable conductor, a very fine silvered glass thread or a quartz fibre, suspended between the poles of a powerful electro-magnet at right angles to the lines of force of the magnetic field, tends to be deflected to one or other side according to the direction of the current. The degree of deflection is directly proportional to the intensity of the current and to the strength of the magnetic field, and inversely proportional to the weight and tension of the fibre. The changes of 134 A TEXTBOOK OF PHYSIOLOGY potential attending the contraction of the heart cause the lil)re to oscillate; these oscillations are rcc(,](l((l on a niovinf^ ])hotogra|)hic plate. The photographic records (electro-cardiograms) obtained with these instruments afford a most beautiful method of recording the rhythm of normal and abnormal hearts in man; they can be obtained by connecting right and left hands, the right hand and left foot, or the left hand and left foot, of a patient with the instrument by means of baths of salt solution into which the wires dip. The second varia- tion or " derivation ■' (right hand and left foot) is mo.st commcmly em- ployed. The heart is placed obli<[uely across the body, and the wave of contraction and accompanying electrical wave begins in the base, passes to the apex, and thence to the base again. The right hand or mouth is favovrably placed as a lead for indicating the electrical condition of the base, and the left hand or either foot for that of the apex. By recording the electrical variation, and using in turn different leads, favourable and unfavouraljle — e.(j., mouth and left hand, and mouth and right hand — the axis of the electrical current, and so of the heart in the body, can be determined. By making use of the telephone-wires, there have been recorded the electrical changes of the hearts of patients comfortably seated or in bed in a hospital a mile away. The normal electro-cardiogram is seen in Fig. 41. P is the deflection due to auricular systole; Q R 8T are deflections of ventricular origin, R representing ventricular systole. Fig. 42 represents the condition of heartblock; the ventricles are seen to be beating at a slower rate than the auricles, and quite independent of them. Fig. 43 is an electro- cardiogram showing in the big upward deflection the occurrence at regular intervals of a ventricvdar extra systole. Tissue of Origin and Mode of Conduction of the Excitatory Wave. — A long controversy has raged around the question as to the actual tissue in w^hich the excitatory wave of the heart arises and by which it is conducted. It is to be borne in mind that the two questions are really distinct. They are frequently confused. Experiments which bear on the site of origin — i.e., the tissue in w^hich the excitatory wave arises— have been quoted as evidence of the mode of conduction of this wave, and vice versa. It must be granted that, if the excitatory wave be found to arise in one form of tissue, it is highly probable that it will also be conducted by that tissue, but it is not necessarily the case. It is quite conceivable that the excitatory wave may arise in nerve and be conducted b}^ muscle, or arise in muscle and be con- ducted by nerve, or, arising how it maj^ the excitatory wave may be conducted both by muscle and by nerve in order that the proper sequence of contraction may be assured. The structure of the nodal tissues suggests that nerve structure there fuses into that of muscle. It is only recently that the claims of the nodal tissue have been ad- vanced as the site of origin of the excitatory wave. For several years a controversy has waged between those who uphold the neuro- genic and myogenic theories. According to the neurogenic theory, nerve is thought to be the supreme tissue, and it is supposed that the THE PHYSIOLOGY OF THE HEART 135 excitatory Avave of the heart arises in nervous tissue within the heart, and is conducted by that tissue. Those holding the myogenic doctrine state that the wave has its origin in heart muscle itself, and is pro- pagated by muscle. In the end, it seems likely to be shown that the pacemaker of the heart is a kind of tissue half nerve, half muscle. Of the two views, the neurogenic is the older. As the heart beats in the bod}^ after all the nerves passing to the heart are cut, or outside the body when properly fed, it was clear to the older observers that the nervous centre originating the heart impulse could not be in the brain, and therefore it was supposed to be in the ganglion cells of the heart. The fact that a ligature tied tightly round the sinu-auricular groove brings the auricles and ventricles of the frog's heart to a stand- still was thought to indicate that the chief grouj) of ganglion cells concerned in the origin of the excitatory wave was situated in that region. A second ligature applied to the A.-V. groove (the second Stannius' ligature) causes the ventricle to beat again, and the neuro- genist ascribed this to the fact that the ganglia in this region are stimulated by such a ligature. Why one ligature should destroy the action of ganglion cells and a second similar ligature excite their action is not apparent; but it is said that, if the A.-V. ganglia be ex- tirpated, this second ligature is ineffective in starting the ventricle. Other evidence cited as supporting the neurogenic theory is the ex- periment of thrusting a needle into the interventricular septum of the mammalian heart. It is said, that, if the needle be inserted on the left side of the lower end of the ujDper third of the septum, it .produces, instead of a beat of the ventricles, a condition known as '■ fibrillation." Recent experiments upon the heart of the horseshoe crab, L'mulus, afford clear evidence of the neurogenic origin of the excitatory Avave' in this invertebrate heart. The heart consists of a tube 10 to 15 centimetres long, divided into segments by the successive origin of the arteries. When the heart beats, all the segments appear to contract simultaneously, although probably a rapid wave of con- traction passes. There are three nervous strands — one median and two lateral — which run along the outer surface of the heart and anastomose freely. The median strand contains ganglion cells, and one especially large ganglion. It is easy to separate this strand from the heart without injury to the muscle. Its entire removal causes cessation of the whole heart-beat, while removal of a portion causes stoppage in the corresponding segment of the heart. As regards the nervous conduction of the excitatory wave, the •chief points advocated in its favour are these: 1. It has been asserted that a different rhythm in aiu'icles and ventricles (allorh\thmia) can be set up by cutting a nerve running from auricle to ventricle. This is unconfirmed. 2. For a long time no muscular connection was known to exist between auricles and ventricles in the mammalian heart, This piece ■of evidence is negatived by the discovery of the A.-V. bundle, but 136 A TEXTBOOK OF PHYSIOLOGY it cannot be denied that this connection contains nerve fibres — a point insisted upon by the upholders of the neurogenic theory. 3. If in the heart of the Lhni lus a section of the median nervous strand be made, it immediately abolishes the synchronism of the different segments. The parts on either side of the section continue to beat, but no longer with the same rhythm. If a section be made of the muscle of this heart, it produces no effect. In estimating the value of the experiments on Limulvs it must be remembered that it is an invertelirate evolved in the epochs of geological tinu', and that the muscle of its heart seems more akin to mammalian smooth muscle. The m\'ogenic theory is based upon the following points : I. The different chambers of the heart beat with a different rhythm when separated from each other. There is no differentiation of any nervous tissue of origin and conduction in these chambers, so far as is known, while there is a marked difference in the histological appear- ance of the muscle of the different heart chambers. Fig. 44.— Kabbit's Heart, A.-V. Bundle Cut, showing Effect of Stimulation of Right Vagus Nerve. (W. Cullis and E. M. Tribe.) The indejendcnt rhythm of aiiricles and ventricles is scon at the beginning, but particularly well at the end of the tracing. The nerve acts upon th? auricles but not ujon ih? ventricles. 2. The experiment in regard to the A,-V. ganglia is incorrect. Excitation of the ganglion cells of this group causes *no contrac- tion. It is the excitation of the muscidature of the auricular ring which evokes contraction. 3. Isolated parts of the great veins of cold-blooded hearts con- taining no ganglion cells beat automatically. Thus, a jDiece of the- sinus of the frog beats for four days, and no less than 17,0CO con- tractions were recorded. 4. The apex of the mammalian heart, said to have no nerve ganglia, Avhen suitably fed exhibits slow rhythmic contractions. 5. The embryonic heart pulses before muscle and nerve have become differentiated in it. 6. It is possible to cause hearts to beat again several hours after death. The heart of a boy, dead of pneumonia, was resuscitated rf , (M'lvrrriTY THE PHYSIOLOGY OF THE HEART 137 ^ l/C 006^ -00/8 OO^^ J) &:l Figs. 4:5a and 45b. — A, Outline (Three-quarters Natural Size) to Scale of THE Right Surface of a Dog's Heart, giving Time-Readings of Intrinsic Deflections of the String Galvanometer taken at a Number of Points. B, Ditto of Left Surface. (Lewis and Rothschild.) 138 A TEXTBOOK OF PHYSIOLOGY twenty-eight hours after death, the heart of a eat after freezmg and thawing. Nervous tissue dies quickly. 7. Certain molluscs, arthropods, and tunicates, have automatic hearts containing no ganglion cells. For muscular conduction of the excitatory wave there is also a considerable array of evidence : 1. With the discovery of the A.-V. bundle there is now no histo- logical reason against it; in fact, experiments upon this bundle show that its destruction by cutting, ligaturing, or clamping, produce allorhythmia — a different rhythm in auricles and ventricles, the Fig. 46. — Figure showing T^, the Point of Peimary Negativity, as studied BY the String Galvanometer, to Various Leads from Other Parts of the Heart. The Excitatory Wave therefore starts from T^. T are Leads FROM T.5;nia, S prom Sinus, A from Auricle. (T. Lewis.) auricles beating considerably quicker than the ventricles (Fig. 44). By gradual compression of the bundle, varying degrees of arhythmia can be produced before this allorhythmia is brought about. Recent work Avith the string galvanometer has showTi that the excitatory wave follows the course of the A.-V. bundle. The impulse reaches the inside of the ventricular wall where the A.-V. bundle arborizes before it reaches the outer surface. It also reaches the outer surface in the neighbourhood of the moderator band before it reaches parts of the ventricular wall nearer the A.-V. groove (Fig. 45). Clinically, disease of the A.-V. bundle leads to an allorhythmia — Stokes-Adams' disease or heartblock (Fig. 42). Whether allo- rhythmia induced by absolute destruction of the A.-V. bundle ever THE PHYSIOLOGY OF THE HEART 139 passes off, and the ventricles again come to follow the lead of the auricles, is a point requiring further investigation. 2. The auricular and ventricular muscle can be cut in zigzag fashion, and yet the muscular impulse still passes, provided the muscular bridges are of sufficient breadth. Fig. -17. — Showing (A) Effect of Cold on the Dog's Sinu-Aukicular Node (Cold applied at F) and (B) on the Axtricle. (M. F.) 3. No disturbance of rhythm is brought about by cutting or stimulating the nerves connecting auricle and ventricle. Fig. 48. — Showing Effect of Clamping Sinu-Auricular Nude at A in Dog's Heart. No Stoppage, but Slight Slowing of Rhythm. (M. F.) Tiiiu" in seconds, 4. In perfused hearts, conduction may occur when the nervous elements are presumably degenerated. 5. The conduction of the excitatory wave can pass in all directions. Reverse conduction from ventricle to auricle can also occur. Thus, 140 A TEXTBOOK OF PHYSIOLOGY with a quick stimulatioti of the ventricles, these may beat first, fol- lowed by the auricles. The rate of conduction of the excitatory wave is said to be in favour of muscular comhiction. It is certain that the excitatory wave arises in the region of the [^"■iG. 49. — Showing Effect of Excision of Sinu-Auriculak Node and Part of THE Superior Vena Cava and Right Auricle at A in Rabbit's Heart. No Stoppage of Heart. (M. F.) great veins, and under normal conditions passes through the auricles and thence to the ventricles. With the discovery of the sinu-auricular node at the junction of the superior vena cava with the auricle there was a tendency to regard this nodal tissue as the automatic tissue of the heart. Experimental evidence has shown that the nodal tissue Fig. 50.— Showing the Effect (B) of Ligature of the Muscular Connection between Auricles and Ventricles in the Heart of the Chicken. Heart- block is induced. (M. F.) yl = Normal rhythm before ligature. Time in seconds. possesses a high degree of automaticit}-. The string galvanometer shows that it is in the sinu-auricular node that the normal excitatory wave of the heart arises (Fig. 46). Here alone can the normal rhythm of the mammalian heart be modified — e.g., by cold, which lessens the frequency of the heart (Fig. 47), or by mechanical or electrical stimidation. But elam^nng or excision of the sinu-amicular node docs not stop THE PHYSIOLOGY OF THE HEART 141 the normally beating heart (Figs. 48, 49). In the dog it causes a slight slowing, in the rabbit it has no effect. Under these circum- stances, the electro-cardiogram shows that the excitatory wave now arises in the A.-V. node. But excision of the A.-V. node in the well-nourished normal heart, beating in situ, does not stop either auricles or ventricles. The auricles beat as before, and the ventricles with a slow independent rhythm of their own. The nodal tissue, therefore, cannot be regarded as the sole re- pository of the automaticity of the heart. It is apparently longer lived than the other parts; so that under conditions of malnutrition the excision of the tissue may cause cessation of the heart-beat. It is in the areas of the nodes that the dying heart beats last, and beats first when restored by perfusion. Further, the bird's heart, which possesses a very high degree of automaticity, possesses no nodal tissue. In the bird's heart, heartblock may be induced by the ligature of the muscular connection between auricles and ventricles (Fig. 50). This connection does not run in the position of the A.-V. bundle, but posteriorly in the outer wall of the right side of the heart. It is possible that there is also a connection between auricles and ventricles in the mammalian heart in this region, but if there be, it is not the path of the normal excitatory wave of the heart. To sum up, it appears that the evidence at present available supports the view that the excitatory wave of the mammalian heart arises normally in the sinu-aurici;lar node, and spreads over the auricular muscle, and thence to the ventricles by the musculature of the A.-V. bundle. The retardation which takes place in the A.-V. bundle causes the ventricle to beat at the projjer period after the auricle. The A.-V. bundle normally conducts the excitatory wave to the different parts of the ventricles, so that these parts contract co-ordinately, and wring the blood out of the heart. Although the property of rhythmic automaticitj^ is highly developed in the nodal tissue, this tissue is not to be regarded as the only tissue of the heart possessing automaticity. The ordinary musculature of the auricles is also endowed with this property, and that of the ven- tricles to a less degree. CHAPTER XVIT THE COURSE OF THE CIRCULATION IN MAMMALS The heart is to be regarded as a double organ, each half consisting of an auricle and a ventricle. The right half contains dark venous blood which has been returned from the body, and is sent to the lungs; the left heart contains the bright oxygenated blood which has been returned from the lungs, and is distributed to the body. There are thus two circulations — the one, the pulmonary, from the right side of the heart by the pulmonary artery to the capillaries of the lungs, and back to the left heart by the pulmo- nary veins; the other, the systemic, from the left side of the heart by the aorta to the arteries and capillaries of the body tissues and organs, whence the blood returns by the veins to the right side of the heart. A schematic representation is given of the circulatory system in the accompanying diagram (Fig. 51). The venous blood flows into the right auricle (R.A.) from the superior and inferior venae cavae, and from the right auricle into the right ventricle through the right auriculo -ventricular orifice. The right ventricle (R.V.) driv^es through the pulmonary artery the blood received from the right auricle. The right auriculo-ventricular valve, or tricuspid, and the pulmo- nary semilunar valve, are represented directing flow of blood in this direction. From the pulmonary capillaries the blood returns by the pulmonary veins (P.V.) into the left auricle (L.A.), and so through the left auriculo-ventricular orifice, guarded by the mitral valve, into the left ventricle (L.V.). By the left ventricle the blood is driven through the aortic orifice, guarded by the semilunar valves, and is distributed to the systemic arteries, and so to the capillaries of the various organs and back to the veins. The muscular wall of the auricles, and that of the right ventricle, 142 'vc. \ nv. Fig. 51. — Diagram of Heart tu SHOW THE Course of the Blood. (M. S. Pcmbrey.) S.V.G., Superior vena cava; /. F.C, inferior vena cava; R.A., right auricle; T., tricuspid valves; R.V., right ventricle; P., pulmo- nary valves; P. A., pulmonary artery; P.V., pulmonary vein; L.A., left auricle; M., mitral valves; L.V., left ventricle; a, aortic valves; A., aorta. COURSE OF CIRCULATION IN MAMMALS 143 are much thinner than that of the left ventricle. This is so because the energy required of the left ventricle must exceed that of the right %-cntricle, inasmuch as the resistance in the systemic system exceeds that in the pulmonary circuit. The Cardiac Cycle. — The changes in form of the heart can be studied in an animal the heart of which has been exposed by opening the thorax under an ansesthetic, artificial respiration being meanwhile maintained, the movements being recorded by levers writing on the kymograph ; or the mammalian heart may be removed and fed with warm oxygenated nutritive fluid (see p. 159); or the circulation may be short-circuited by what is known as the heart-lung preparation, the blood still being sent through the lungs of the animal to keep it oxygenated (see p. 163). When the heart is watched beating in full vigour and rapidity, it is an impossible task to unravel by the eye alone the sequence of events. Harvey, the discoverer of the circulation of the blood, felt and described this difficulty in his wTitings: '" When first I gave my attention to vivisections, as a means of discovering the movements and uses of the heart, and sought to discover these from actual inspection, and not from the Avritings of others, I found the task so truly arduous, so full of difficulties, that I was almost tempted to think (with Fracastorius) that the movement of the heart was only to be comprehended by God; for I could neither rightl}^ perceive at first when the systole and when the diastole took place, nor when and where dilatation occurred, by reason of the rapidity of the movements, which in many animals is accomplished in the twinkling of the eye, coming and going like a flash of lightning: so that the systole presented itself to me, now from this point, now from that, the diastole the same; and then everything was reversed, the movements occurring, as it seemed, variously and confiLsedly together. " When the heart begins to flag, to move more slowly, and, as it were, to die, the movements then become slower and rarer, the pauses longer, by which it is made much more easy to perceive and unravel what the movements really are, and how they are performed. '■ In the pause," Harvey sslys, "as in death, the heart is soft, flaccid, exhausted, lying, as it were, at rest. In the movement and* interval in which this is accomplished, three principal circumstances are to be noted : " 1. That the heart is excited, and rises upward, so that at this time it strikes against the breast, and the pulse is felt externally. " 2. That it is everywhere contracted, but more especially towards the sides, so that it looks narrower, relatively longer, and more drawn together. " 3. The heart, being grasped in the hand, is felt to become harder during its action. Now this hardness proceeds from tension, precisely as, when the forearm is grasped, its tendons are perceived to become tense, and resilient when the fingers are moved. 144 A TEXTBOOK OF PHYSIOLOGY ■• 4. Jt may further be observed in fishes and the colder-blooded -animals, such as frogs, serjients, etc., that the heart, when it moves, becomes of a j)aler colour; when quiescent, of a deeper red colour. ■• There is also to be noticed in the heart a certain obscure un- dulation and lateral inclination in the direction of the axis of the ri^'ht ventricle, as if twisting itself shghtly in jDcrforming its work." Analyzing the movements of the chambers of the heart, Harvey •determined that: •' First of all the auricle contracts, and in the course of its contrac- tion forces the blood (which it contains in ample quantity as the head of the veins, the storehouse, and^cistern of the blood) into the ventricle, Avhich being filled, the heart raises itself straightway, makes all its I 1 1 1 . ■f^. ' 'T^ Kk I •^B ^i^V JiK ' : ". '. — 1 t ^li Fie. 52. — Serial Photogeaphs of the Perfused Heart of the Frog, from a Cinematograph Film; Fifteen Images per Second. (G. R. Mines.) fibres tense, contracts the ventricles, and performs a beat, by which » beat it immediately sends the blood sujiplied to it by the auricle into the arteries." A cinematograph record of the movements of a frog's heart is seen in Fig. 52. Movements oJ the Heart. — The movements of the heart consist of a period of contraction, which is called the systole, and a period of relaxation, the diastole. The two auricles contract at the same time, followed by the synchronous contraction of the ventricles. Finally, there is a period when the whole heart is in a state of relaxation. This sequence of events is known as the cardiac cycle. Taking seventy-five as the average number of heart-beats per minute, each cardiac cycle will occupy 0-8 second. COURSE OF CIRCULATION IN MAMMALS U5 -By some it is believed that the right auricle contracts very shortly before the left auricle, and the left ventricle before the right ventricle. Of this period of 0-8 second — Auricular S3'stole occupies about 0-1 second. ,, diastole ,, ,, 0'7 „ Ventricular systole „ ,, 0*3 „ ,, diastole ,, „ O-o „ The sequence and duration of the events happening in the heart, and the pressure inside the heart — the endocardiac pressure — are studied by means of an instrument termed the " cardiac sound." The sound — a two-way tube — is pushed down the jugular vem until 1 1 1 j 17. [ r\ 1\ 1 ^ ^ It 1 \ / l\ i! / ?// J \ i 1 c } 0 7 • r ^ >s_- / v.- . — [ C Til ^^r' 1 1 1 1 1 -fi s' 1 d r^ ; i 1 A>^ ,r <^ \ I 1 "yj u '-^ \ r 1 1 \ 1 \\ 1 1 vi 1 / \ 7c' } A 1 \,/- ' 1 y / '-, _ X sJ ■<^ ^N J, !.v -^ \ -^\ j 4L 1 1 ? ^ jr- ft t" e'' 1 f> IT :i 1 r /\ Jt ' / rr J A V 1 g'\ 1 V >\ 'X. ^., 1 -/^ r \ _J / ^f\ i ^i^T \^ 1 \^ '' 1 I j.>-, 1 Fig. 53. — Tracings from the Heart of a Horse, by Chauveatj and Marey. The upper tracing is from the right auricle, the middle from the right ventricle, and the lowest from the apex of the heart. The horizontal lines represent time, and the vertical amount of pressure. The vertical dotted lines mark coincident points in the three movements. The breadth of one of the small squares repre- sents one-tenth of a second. The auricular contraction is less sudden than the ventricular, and lasts only a very short time, as indicated by the line a h. The ventricle, on the other hand, contracts suddenly and forcibly and remains contracted a considerable time, as shown by the line c' d' and by the flat top to the curve which succeeds d' . the orifice of one tube lies in the right ventricle, and of the other in the right auricle. The cardiac orifices of the tubes are covered with rubber membrane, beneath which are wire springs set to resist com- pression. The tubes are connected with recording tambours, which AVTite on a moving drum covered with smoked paper. Another tambour may be used to record the cardiac impulse. The aortic pulse curve may also be recorded in other experiments simultane- ously with the left intraventricular pressure. This is effected by pushing the sound down the carotid, so that one tube opened into the aorta and the other into the left ventricle. The tracings so obtained 10 140 A TEXTBOOK OF PHV.SIOl.OOY (Fig. ~)2) teach us the following facts: (1) The auricular contraction is less siuklcn than the ventricular, and lasts only a v^ery short time, The ventricle, on the other hand, contracts suddenly and forcibly, and remains contracted a considerable time, as shown respectiv^ely by the ascent of the curve and the flat top of the curve which succeeds. (2) The aiiricular movement precedes the ventricular, and the latter coincides with the impulse of the apex against the wall of the chest. (3) The contraction of the auricle influences the pressure in the ven- tricle, as shown by the small rise a' b', and that of the ventricle influ- ences the pressure in the auricle somewhat, as shown by the wave c' d'. A tracing of aortic and intraventriculFjr pressure curves is given in Fig. 54. The beginning of the aortic pulse curve (I) obviously marks the opening of the semilunar valves, the dicrotic notch (4) follows their closure. The moment of closure (3) can be ascertained by listening to the second sound of the heart, which occurs immediately after the closure, and is produced by the sudden tension of the closed valves. It Fig. 54. — Aortic and Intraventricular Pressure Curves. (Hiirthle.) Time trace= j-J^^ sec; O'l, period of rising tension; 1-4, period of output; 4, dicrotic notch. can also be determined by connecting the two-way sound to a differential manometer, and recording the difference of pressure in the ventricle and aorta. The valves open at the moment when the ventricular pressure exceeds the aortic, and close when the aortic exceeds the ventricular pressure. If the differential manometer be used, with, one sound opening in the right auricle and the other in the right ventricle, the tracing indicates the moment when the auriculo-ven- tricular valves close and open. The absence of a mechanism for preventing regurgitation of blood from the auricles of birds and mammals is remarkable, for in fishes,, amphibia, and reptiles, this is effected by valves guarding the sinu- aurictilar junction (Fig. 2(3). In the warm-blooded vertebrates, with the appearance of the diaphragm and the fusion of the sinus vcnosus with the right auricle, the venous cistern formed b}^ the sviperior and inferior vense cavse, the innominate, iliac, hepatic, and renal veins takes the place of the sinus. Six pairs of valves prevent regurgitation from this. COURSE OF CIRCULATION IX MAMMALS 147 cistern — viz., those placed in the common femoral, the subclavian, and jugular veins (Fig. 55). The cistern, when filled, may hold some 400 c.c. of blood. In the liver there may be some 500 c.c. of blood. This can be expressed into the cistern by abdominal pressure. In the i^ortal venous system, when distended, may be held another If- oiniiich f^r-l IthO Fig. 5o. — Diagram of the Venous Cistern from which the Heart is Filled (Keith.) The abdommal or infra-diaphragmatic part of the cistern is indicated in black; the thoracic or supra-diaphragmatic is stippled. The heart is compressed upwards and backwards against its attachments. 500 c.c, which can be expressed through the portal veins and the liver into the cistern. There is thus a large volume of blood for the heart to draw upon during diastole, and this may be of particular value during the performance of a great muscular effort. Respiration bj^ the aspirating action of the thorax sucks this blood into the heart, while the inspiratory descent of the diaphragm squeezes the abdominaf 14S A TEXTBOOK OF PHVSIO.LOOY contents and forces blood from the liver and cistern into the heart. These forces take the place of the sinus venosus, and are far more efficient. The intra-abdominal pressure may be raised considerably on bending or straining. Under such conditions, the pericardium protects the right side of the heart from being over-distended with venous blood. With these facts in view, we can now describe the complete course of a cardiac cycle (Fig. 56). We Avill start at the moment when both chambers of the heart are in diastole. The blood pours from the vena cava and pulmonary veins into the two auricles. These are relaxed, and their cavities open into the ventricles by the funnel-shaped apertures formed by the dependent segments of the tricuspid and mitral valves. The blood passes freely through these apertures into the ventricles. The small positive pressure which is always present in the venous cistern (aided by the respiratory forces) is at this time filling both chambers of the right heart, while the positive pressure in the pul- monary veins is filling those of the left heart. The auricular systole now takes place. Their circular muscle bands compress the blood out of the auricles into the ventricles, while the longitudinal bands aid in this, and also pull up the base of the ventricles to meet the load of blood (Fig. 58). As the contraction starts from the mouths of the vena cava, and sweeps towards the ventricles, little or no regurgita- tion of blood occurs into the venous cistern under normal conditions, but the cessation of flow into the auricle during its systole does produce a slight rise of pressure in the cistern, which is shown by the wave a in tracings taken from the jugular pulse (see Fig. 116). The function of the auricles is to rapidly complete the filling of the ventricles, and thereby slightly distend its walls. Within normal limits, the greater the distension the more forcible the contraction. The auriculo-ventricular valves are floated up and brought into apposition by eddies set up in the blood which streams into the ven- tricles, and close without noise or jar at the moment when the intra- ventricular pressure in the least exceeds that in the auricles. The thin, moist, film-like edges of the tricuspid and mitral valves of the heart come into perfect apposition, and prevent all leakage, while the fibrous parts give strength and support. Then follows ventricular systole {A, Fig. 56). The contraction of the ventricular musciilature around these orifices limits the size of the auriculo-ventricular orifices, and maintains the competency of the valves. By contracting synchron- ously with the muscular wall of the ventricles, the papillary muscles, with the aid of the chordae tendinese, pull down the diaphragm formed by the closed auriculo-ventricular valves. As these form the floor of the auricles, their cavities are thereby expanded. At the same time, the papillary muscles shorten the longitudinal diameter of the ventricles, and enable the valvular and muscular parts of the ventricles to approach together and squeeze out the blood from the ventricles. By the attachment of the chordae tendinese to the auriculo-ventricular valves, and the action of the papillary muscles, the membranous diaphragm formed by the valves is made to act as part of the muscular wall of COURSE OF CIRCULATION IN MAMMALS 149 each ventricle, and thus the cavity of each comes to be equivalent to a sphere surrounded by muscle. When the intraventricular pressure rises the least bit above that in the pulmonary artery and aorta respectively, the semilunar valves O.Ssec. Fig. 56. — The Time Relations of the Impulse, Intra-Aueicular and Ventric- ular, AND Arterial Pressure Curves. (Modified from Hiirthle; L.H., from AUc bin's "Manual of Medicine.") A, The beginning of ventricular systole; B, tbe oiDening of tbe semilunar valves j J-J5, period of rising tension; (7, the closure of the semilunar valves; A-C, period of output (systole); D, the beginning of the dicrotic wave on the pulse curve; C-E, period of diastole ; E, the beginning of the next cardiac cycle. The dura- tion of the first and second sound of the heart is marked below the intra-auric- ular pressure curve. The pressures arc given in mm. Hg. The waves on the plateau of the ventricular curve are due to elastic vibrations and are partly instrumental; the first fall in the curve of auricular pressure is produced by the systolic output of blood ; the second auricular fall is due to ventricular diastole. The high-pressure pulse is anacrotic. quietly open {B, Fig. 56) and the blood is expelled. The elastic vessels are in their turn expanded by the expulsive force of the heart, so as to receive the blood. The outflow of blood from the ventricles is rapid at first. It becomes slower as the arteries become distended and the pressure of 150 A TEXTBOOK OF PHYSIOLOGY blood rises within them, and ceases when the arterial pressure becomes equal to that iii the ventricles. As the outflow diminishes, the semi- lunar pockets are filled by eddies of blood, and their thin, delicate «dges are biought nearer and nearer, until finally they come into apposition. This closure, which effectually iDrevents regurgitation, is effected without jar or noise at the moment when the outflow ceases and the ventricles begin to expand. The heart, as a good ]iuni]) should, works with the least possible jar. During the contraction of the ventricles, blood has been pouring from the veins into the auricles; and directly the ventricular systolS ceases, the auriculo- ventricular valves open, and the blood begins to fill the expanding ventricular cavities. For a brief moment the ventricles remain dilated and at rest, then the auricles contract again, and the cycle of changes once more is repeated. During the first period of ventricular systole — the period of rising tension (A-B, Fig. 56), or " presphygmic A B Tig. 57. — Diagram of Right Side of Heaet, showing A, Systole- AiTRif:uLo- Ventrictjlar Valves Shut, Chords Tendine.^ drawn Tattt, Semilunar Valves of Pulmonary Artery Open. B, Diastole- Auriculo-Ventric- ular Valves Open, Blood entering from Auricle to Ventricle, Semi- lunar Valves of Pulmonary Artery Shut. interval," as it is called — all the valves are closed, and the ventricle is getting up pressure. This period has been measured, and has been found to occupy about 0-02 to ()-04 second. The second period is that of the systolic output (B-(\ Fig. 56), and lasts about 0-2 second— that is, from the moment when the semilunar valves open to the moment when they close. These periods can be measured on man by taking simultaneous records of the pulse in the carotid artery and of the cardiac impulse and sounds. The ujjstroke of the pulse-curve recorded from the carotid artery can be taken as marking the moment when the semilunar valves open, while the dicrotic notch on the pulse-curve marks their closure. The second sound of the heart occurs immediately after their closure, fnd, by listening to it, one can note the time of this event on the impulse-curve, the upstroke of which marks the beginning of ven- tricular systole. Thus, the presphj'gmic interval extends from the COURSE OF CIRCULATION IN MAMMALS 151 beginning of the upstroke of the impulse-curve to the beginning of the upstroke of the carotid pulse-curve. The first sound of the heart is synchronous with the upstroke of the impulse-curve. A small cor- rection must be made for the delay in the transmission of the pulss to the carotid artery. The period of sj^stolic output extends from the beginning of the upstroke of the 2:)ulse-curve to the dicrotic notch, and the diastolic period from this notch to the beginning of the next upstroke. The relation of the auricular systole to the ventricular can be determined by simidtaneously recording the pulse in the jugular vein and carotid artery. The c wave in the jugular pulse is synchronous with the upstroke in the carotid pulse, and the a wave, which precedes the c wave, marks the auricular systole (see Fig. 116). The intraventricular pressure rises or falls during the output period according to the state of the peripheral resistancie. The maximal systolic pressure exerted by the heart varies with the internal tension — that is, with the degree of diastolic filling and obstruction SUP: VEN.-CAV /'•.RT:ME.SOCARD PERlCARO sinus transv v£ncus mesocaro inf:ve:n.cav Fi:;. 58. — Heart pulled Forwards to show its Attachment bv Arterial (di) AND Venous (ce) Mesccardii. (Keith.) to outflow. The heart-muscle responds to increased tension by a greater output of energy, and this it does with little loss in rapidity of action. By its reserve power the heart may throw out during hard exercise ten times the volume of the normal output per minute, and may maintain its output when the aortic pressure is even twice its normal value. The Movements of the Heart in Situ. — The normal fulcra for the movements of the heart in the closed thorax are afforded through the pericardium (Fig. 58). The pericardium is reflected on to the wall of the heart at the point where the vena cava and aorta leave the pericardial sac. This part of the pericardium gives a fixation point to the auricles, being attached to the roots of the lungs, and thereby to the thoracic wall, to the diaphragm, and to the structures at the root of the neck. On opening the chest, the normal fulcra for the movements of the auricles are lost, and this renders it difficult to record the exact move- ments of the heart. The longitudinal and circular muscle fibres of 152 A TEXTBOOK OF PHYSIOLOGY the ventricles are antagonists. The circular fibres, by their con- traction, tend to lengthen the apex-base diameter. The longitudinal fibres resist this, and the two together wring the blood out of the heart. The apex is maintained as a fixed point by this antagonistic action, and thus the longitudinal fibres are enabled to expand the auricles by ]oulling down the floor of these chambers. This action is important, as it contributes to the filling of the auricles simultaneously with the emptying of the ventricles. Tracings of the jiigular pulse give evidence of such action. In the case of the auricles, the longitudinal musculi pectinati not only help the circular fibres to expel the blood, but draw up the base of the ventricle to meet its load of blood. Thus, the A.-V. groove is "^_' ^- FiG. 59. — To SHOW THE Antagonistic Action of the Musculatuees of the Eight Auricle and Ventricle. (Keith.) .4, position of A,-V. groove at end of auricular systole; B, at end of ventricular systole. l^ulled up during auricular systole, and down during ventricular systole {A, B, Fig. 59). The posterior and upper borders of the left auricle lie against the unyielding structures of the posterior medi- astinum, the pidmonary artery, and bronchi, the floor and anterior part being in contact with the base of the ventricle and ascending aorta respectively. The latter parts alone are free to move during systole. Thus, the left ventricular base is drawn up and the aorta back on auricular systole. Modes of Examining the Living Heart. — The physiologist or physi- cian has many means at his disposal of examining the heart's action. Its efficiency may be tested by noting how much its COURSE OF CIRCULATION IN MAMMALS 153 rate of beat is increased b}' taking exercise and also how quickly the normal rate of beat is resumed after such exercise. By palpa- tion, with the hand over the region of the heart, its stroke, the cardiac impulse, can be felt; b}^ percussion, the anatomical limits of the organ can be defined; by auscultation with the ear directly, or with use of the stethoscope, the sounds of the heart can be heard. The cardiac impulse can be recorded by the tambour method of registration; the heart -sounds by means of the microphone and string galvanometer; while the volume and movements of the heart can be studied with the help of the Rontgen rays. Mitral Tricuspid ~ Fig. 00. — Diagram showing Surface Relations of Lungs, Heart, and Cardiac Valves. (Cowan.) The Cardiac Impulse. — The impulse is caused b}' the sudden harden- ing of the muscular mass of the ventricles against the chest wall. It coincides with the beginning of systole. The position at which the impulse is felt varies with the position of the bod}'. Normally, with the bod}^ in the supine position, the impulse is visible in the fourth or fifth intercostal space 2 inches below the nipple and 3i inches from the mid- sternal line (Fig. 60). In rising to the standing posture, the impulse shifts its position downwards and to the left for 4 to 1 inch. When a man rolls over on to his right side, the impulse may shift from 3 to 4 inches to the right, and disappear beneath the sternum. Similarly, on rolling on to the left side, the impulse shifts to the left of the nipple line. I"i4 A TEXTBOOK OF PHYSIOLOGY The shifting is due to the effeet of gravity on the lieart. In each position a different part of the heart is brought in close contact with the chest wall. The chest wall is driven out by the systole only where the heart -muscle touches it; at other places it is slightly drawn in. This indrawing is believed to be due to the expulsion of the blood from the thorax by the left ventricle. The thorax being a closed cavity, negative pressure is produced by each systole when the blood passes out by the. arteries of the head, limbs, and abdomen. This vacuum is filled by (1) the drawing of air into the lungs; hence the cardio-pnevnnatic movement, which may be detected by connecting a water manometer with one nostril, and closing the other nostril; (2) the drawing of venous blood into the great veins and right auricle ; (3) the slight indrawing of the chest wall. The impulse may be re- corded by placing a small cup or receiving tambour over the spot where it is most evident, and connecting the inside of the cup by a tube to the recording tambour. The cup need not be closed by a rubber dam, for an air-tight junction can be effected by pressing it upon the skin. The stroke of the heart is transmitted as a wave of comiDression to the air within the system of tambours. The recording tambour writes on a drum moved by clockwork, and covered with a smoked paj^er. From the record so obtained we can obtain informa- tion as to the time-relations of the heart-beat, but no accurate in- formation as to its energy or amount of contraction. The Sounds of the Heart. — When the ear is apjilied over the cardiac region of the chest, or a stethoscope is employed, two sounds are hoard. The first, heard most intensely near the apex, is a didler and longer sound than the second, which is shorter and shar-jDer, and is heard best over the base of the heart. The syllables lilb, dnjip, express fairly well the characters of the two sounds, and the accent is on lub when the stethescope is over the apex — thus, h'lb-dvj^jJ, Inb-dujjp, lib-duj)}) — and on the second sound when over the base — thus, lub- d/'ij)]^. lub-d'pj), lub-ditpij. The first sound is caused by the sudden tension (1) of the cardiac muscle; (2) of the diaphragms formed by the closed auriculo-ventricular valves; (3) of the papillary muscles and chordae tendinese. This sound is heard in an excised mammalian heart empty of blood ; there- fore it is largely muscular in origin. It is not heard in a turtle's heart, because this contracts too slowly. When the sounds and the contraction are recorded together, the record shows that the first sound begins about 0-01 second before the cardiogram marks the beginning of the systole, and for the first 0-06 second of its duration this sound is heard only over the apex (Fig. 61). Over the base of the heart the first sound is heard just at the time when the semilunar valves open and the output begins. The first ft,ound ceases before the ventricular contraction is over, for it is the sudden tension, not the continiiance, of contraction that causes it. The beginning of the second* sound marks the sudden tension of the semilunar valves, which immediately follows their closure. For clinical purposes it is important to bear in mind what is COURSE OF CIRCULATION IN MAMMALS 155 happening in the heart whilst one hstens to its sounds. During the first sound we have (1) contraction of the ventricles, closure of the auriculo -ventricular valves, and impulse of the apex against the m Via. <>1. — Electro-Cakdiosram, Carotid Pjlss CuitvE, amd Heart Sounds of A Dog. (T. ].o.vis.) Tho sounds are recorded ))y a microphone titted to a stethoscope connected with a second st'ino- sjalvanonioter. Fia. ()2. — Electro-Cardiogram and Rough Aortic Murmu.i in Man. (T. Lewis.) chest; (2) rushing of the blood into the aortic and pulmonary artery, and filling of the auricles. With the second sound we have closure of the semilunar valves from the elastic recoil of the aorta and pul- !,-)() A TEXTBOOK OF PHYSIOLOGY monary artery, relaxation of the ventricular walls, opening of the a\n-icnlo-ventricular valves so as to allow the passage of blood from ^ auricle to ventricle, and diminished pressure of ajDex against chest wall. During the long pause there are taking place (1) gradual re- filling of the ventricle from the auricle ; (2) contraction of the auricle COURSE OF CIRCULATION IN MAMMALS 157 so as to entirely fill the ventricle. The sound of the tricuspid valve is heard loudest at the junction of the fourth right costal cartilage with the sternum, that of the mitral over the apex beat, that of the aortic semilunar valves in the direction of the aorta, where it comes nearest to the surface at the second right costal cartilage — the pul- monary— to the left and external to the margin of the sternum. The sounds are changed in character by valvular lesion (Figs. 62 and 63) or muscular weakness of the heart, and afford important signs to the physician. Murmiu-s are produced by eddies setting some part of the mem- branous walls or valve flaps in vibration. Thus, if a fine instrument provided Avith a hook be passed down the carotid into the aorta, and the aortic valves are torn and rendered incompetent, a murmur results. Inflammation, shrinkage, and incompetence of the valves results from rheumatic and other infections. If a stethoscope be placed over a large artery, a murmur will be heard, caused b}" the blood rushing through the vessel narrowed by the pressure of the instrument. The fluid escapes into a wider portion of the vessel beyond the point of pressure, and the sound is caused by the eddies set up there throwing the membranous wall of the vessel into vibration. Such a sound is heard over an aneurism. The placental bruit heard during pregnancy is a sound of this kind, arising from pressure on the uterine arteries. In cases of insufficient aortic valves a double blowing murmur may be heard, the first being due to the rush of blood into the vessel, and the second by the regurgitation of the blood back into the ventricle. These murmurs are produced by eddies of blood setting the membranous parts into vibration. Occasionally a murmur seems to be produced by the displacement of air in the bronchial vessels by the beat of the heart, and may simulate the murmur of aortic incompetence. By placing a stethoscope over the jugular vein on the right side, and above the collar-bone, a murmur is heard — the bruit de diable — particularly if the subject turn his head to the left. This is held to be due to the vibration of the blood in the jugular vein rushing from the dilated to the contracted part. It is more marked during auricular diastole and during inspiration. CHAPTER XVIII THE NUTRITION OF THE HEART In the lower vertebrates, such as the frog, the heart is directly nourished by the blood which fills the cavities in its sponge-like struc- ture. In the warm-blooded vertebrates, there is a special arrange- ment of coronar\- vessels. The two coronary arteries (right and left) originate at the root of the aorta from bulgings of the aortic walls — the sinuses of Valsalva. The sinuses are three in number, corre- sponding to the number of cusps of the semilunar valves. The right coronary artery arises from the anterior sinus, the left coronary artery from the left posterior sinus. Their branches penetrate the muscular substance, and end in a rich plexus of capillaries. From these arise the radicles of the coronary veins, which open into the right auricle by the coronary sinus and other small veins. These openings are valved by remnants of the primitive sinus venosus. The heart, in contracting, exerts a greater pressure than that of the coronary arteries, and so arrests the flow in these during the height of systole, and squeezes the blood within the coronary capillaries and veins on into the right auricle. On diastole, the coronary system fills again. 8udden occlusion — e.g., by the injection of paraffin — of any large part of the coronary arteries produces irregular and inco- ordinate contractions — " fibrillation," as it is called — followed by death of the heart. Degeneration of the coronary arteries in advanced life is associated with a distressing form of cardiac illness known as " angina pectoris."' The great anatomist John Hunter, who died after a heated debate, was found by Jenner to have calcified coronary arteries. It has long been known that the heart of the frog or tortoise can be kept beating normally for hours after removal from the body, particularly if it is provided with a suitable solution of salts. Ringer worked out the necessary ingredients of this solution to be : sodium chloride, 0-7 per cent.; potassium chloride, 0-03 per cent.; calcium chloride, 0-02") per cent. The excised mammalian heart can be kept beating in the same way, provided the nutritive fluid is oxygenated and the heart kej)t at body temperature. A solution containing one-third defibrinated blood and two-thirds Ringer's salt solution is especially suitable. The beat of the heart of a child was restored thereby twenty hours after death from pneumonia; the excised heart of a cat was kept beating for four days; the heart of a monkey was restored after 158 THE NUTRITION OF THE HEART 159 freezing the aniinal. The nex-ves of the excised heart retain their action for some time if the nutritive flvxid is immediately circulated through the coronary arteries. Thus, the heart's action can be con- veniently studied when taken from the body of a mammal. By using defibrinated blood mixed with the perfusion fluid food material is brought to the heart. By some it is considered that the serum albumin is the essential substance. In Locke's fluid* dextrose is added to the above salts, and this forms an admirable perfusion fluid. But the heart will beat when supplied with oxygenated Ringer's solution only : neither the serum albumin nor the dextrose appfear to be necessary. The important factors are the free ions of sodium, potas- sium, and calcium, and certain concentrations of these appear to be absolutely necessary for the rhythmic automaticity and efficient working of the heart. With increase of the contents of the calcium, ions the heart contracts more powerfully (Fig. 64). If the amount of calcium be large the heart relaxes less and less completely, and eventually stops in a state of tonic contraction. Fig. ()1. — Isolated Rabbit's Heart perfused with Locke's Solutiox. (Dixon.) At the arrow 5 mgrm. of calcium chloride were given. Time in seconds. Excess of the potassium ions has an oj^ijosite effect (Fig. 65). The beat of the heart becomes more and more feeble, and it ceases to beat in a state of complete relaxation (diastole). Excess of the sodium ion causes the beat of the heart to become weaker and weaker, and eventually fail altogether (also in diastole). There is therefore an antagonism between the calcium ions and those of sodium and potassium. The origin of the excitatory wave is intimately dependent upon interaction between these ions and the colloids of the heart muscle, those of calcium playing a prominent part in the contraction of the heart, those of potassium in its relaxation. If the heart is treated with lactic acid until it is brought to a standstill in diastole, it can be j^artly restored by increasing the con- centration of calcium in the Ringer's solution, and completely restored * Locke's fluid is distilled water, 100 c.c. ; sodium chloride, 0-9 gramme; potassium chloride, 0-042 gramme; calcium chloride, 0-04S gramme; sodium bicarbonate, 0-0'? gramme; dextrose, 0''2 gramme. . .. 160 A TEXTBOOK OF PHYSIOLOGY by then perfusing with a high concentration of iwtassiuni sahs, sub- sequently washed out by physiological saline. Potassium itself may restore the heart from a lactic acid diastole, but not so completely as the combination of calcium and potassnim. The fact that the heart can be restored from diastole induced by lactic acid by a high concentration of ])otassium, which is jxjisonous Fig. 65. — Isolated Rabbit's Heart perfused with Ringer's Solution. (Dixon.) In I., 0*2 per cent, potassium chloride .added to the fluid. 11. shows gradual recovery when KCl withdrawn. to, and induces complete relaxation in, the normal heart, shows how far we are from understanding the true part played by these ions in relation to the antomaticity of the heart. The Diastolic Filling of the Heart.— In the excised heart no evidence of any suction power has been observed; indeed, the heart will only fill when supplied with blood under a positive pressure. THE NUTRITION OF THE HEART K3I Similarly, when the thorax is opened, the heart cannot fill itself unless aided by a positive pressure in the veins. If the pressure in the vense cavse were not positive, then negative pressure occurring in the heart cavities would lead to a collapse of the thin- walled venae cavae, and not to suction of blood from the veins. In hydraulic engineering, the efforts of engineers are directed towaids making the water enter the system without shock. If the negative pressure had any sudden and decided action, there would be shock and consequent loss of energy. The driving force of the heart is sufficient by itself to maintain, at any rate for a time, and in the horizontal position of the animal, a circulation when the thorax is opened, artificial respiration established, and the muscles paralyzed by injection of curari. Under these con- ditions, the circulation may fail altogether in the vertical posture when gravity opposes the return (see later, the effect of posture, p. 11)4). Normally, the filling of the heart is largely under the control of the respiratory pump. In the closed thorax, the pressure is less than that of the atmosphere by that amount which is required to overcome the pulmonary elasticity and expand the lungs to the size of the thoracic cavity. In ordinary inspiration, this pressure is equivalent to 9 mm. Hg; in the position of the deepest inspiration, it may sink to 30 mm. Hg. On the one hand, the extrathoracic veins are under a pressure made jjositive by the compressive action of the skeletal muscles, contraction of muscular walls of viscera, and the respiratory pump; on the other hand, the intrathoracic veins and the heart are under a slight negative pressure, which in inspiration may become 9 to 30 mm. Hg. The venous blood is thus pressed and aspirated into the heart from the venous cistern. Each descent of the diaphragm compresses the abdominal organs, and if in sequence to, or synchronously with, the inspiratory movements of the thorax the abdominal muscles be thrown into contraction, then the resijira- tory muscles act powerfully on the venous cistern, not only as a suction but also as a force pump. To prevent overdistension of the right heart, the breath is always held when the abdominal muscles are forcibly contracted — e.g., on straining at stool, or when the abdomen is compressed. The pericardium, too, supports the heart and limits its distension. The venous cistern in its turn is filled by the force of the heart-beat (the vis a tergo), but in particular by the muscular jnovements of the limbs and viscera aided by the valvular action of the veins. During any violent exercise, such as running, the skeletal muscles alternately contract and expand, and a full tide of blood flows through the locomotor organs. The stroke of the heart is then both more energetic and more frequent, and the blood circulates with in- creased velocity. Under these conditions, the filling of the heart is maintained by the pumping action of the skeletal and respiratory muscles. The abdominal wall is contracted, and the reserve of blood is driven from the splanchnic vessels to fill the dilated vessels of the lo 3omotor organs. At each respiration the pressure within the thoracic cavity becomes less than that of the atmosj)here, and the blood is 11 162 A TEXTBOOK OF PHYSIOLOGY aspirated from the veins into the right side of the heart and lungs ^ conversely, at each expiration the thoracic pressure increases, and the blood is expressed from the lungs into the left side of the heart. While the respiratory pump at all times renders important aid to the cir- culation of the blood, its action becomes of supreme importance during such an exercise as running. The runner pants for breath, and this not onl}' increases the intake of oxygen, but maintains the diastolic filling of the heart. It is of importance to grasp the fact that the circulation of the blood depends not only on the heart, but on the vigour of the respiration and the activity of the skeletal muscles. Muscular exercise is for this reason a sine qua non for the maintenance of vigorous mental and bodily health. An experiment which throws light on the filling of the heart is the following: A pressure-bottle filled with oil is connected by a T-piece with (1) an oil manometer, (2) a tube tied into the pericardial sac. So soon as the jaressure of the oil is raised to 60 to 70 mm. oil, the arterial pressure falls by 20 to 30 mm. Hg, while the vena cava pressure rises to about 5 mm. Hg. By a pressure of at most 240 to 300 mm. oil, the arterial pressure is brought to zero. By no possible means in the anajsthetized animal can the vena cava pressure rise beyond this pressure, and thus the heart is unable to fill. The quantity of blood thrown into the aorta by each contrac- tion of the left ventricle must correspond to that entering the right ventricle during diastole, otherwise the blood will become congested in the veins, and the circulation quickly come to an end. In the dog, either the vena cava superior, or the vena cava inferior below the liver may be completely occluded, and yet no change of pressure in arterial pressure is indicated by the arterial manometer. If on the other hand the vena cava inferior between the liver and the heart be compressed, there occurs an immediate and marked descent of the arterial pressure. Thus a rabbit, in which the portal vein has been ligatured, perishes within a few minutes, owing to the rapid accumulation of the blood in the portal tributaries. The capacity of these is so great that they are sufficient to hold all the blood; the plasmia, too, rapidly leaks out of the capillaries when the circulation is thus arrested. The filling of the heart is thus enormously diminished while the aorta continues to empty itself by its elastic reaction into these veins. On occluding the jnilmonary artery of an animal the left heart empties, and the arterial pressure falls towards zero. The pressure in the vense cavse rises, but only by a very few millimetres of Hg. If one vena cava be half occluded, the venous pressure rises distal to the obstruction, but only by a few millimetres of Hg, and for a short while. A few hours after the pressure in the veins is found to be normal. It is important to note that the oedema, or dropsy, which follows such obstruction, or occurs in heart disease, is not caused by transudation due to a rise of venous pressure, but by nutritive changes in the tissues which follow the obstructed flow. If the thorax of a dog or cat be compressed, the arterial pressure THE NUTRITION OF THE HEART 1G3 falls towards zero, owing to the increased intrathoracic pressure obstructing the filling of the heart, while the vena cava pressure rises a few millimetres of Hg (Fig. 6G). The extent of the effect depends greatly on the rigidity of the thorax and resisting-power of the animal. In man, compression of the chest produces the same result; loss of consciousness may be induced and convulsive spasms owing to the production of acute cerebral anaemia. In the fatal crushes of panic-stricken crowds, death is produced by compression of the thorax and circulator}^ failure. The women and children with collapsible chests are the first to die, while the men with most rigid chests escape. When a person is strangled, or the lar3aix is blocked bj' some hard, impacted mass of food too hastily swallowed, death is hastened by the violent expiratory spasms, which drive the blood out of the abdominal veins into the heart and engorge the face with venous blood. To sum up, the heart is filled in diastole by- 1. The contraction of the heart produc- ing a positive pressure in the veins (the vis a tergo). 2. The action of the respiratory pump creating a negative pressure in the thorax and a positive pressure in the abdomen. 3. The contraction of the muscles of the bod}' generally impelling the blood onward toward the heart. 4. Change of posture and the action of gravity. Fig. 66. — -Compression of THE Thorax {A-B). (Hill and Barnard.) Compensitory effect of poweifiil inspirations, alternating with forced expiratory efforts (glot- tis closed). Aorta mm. Hg, vena cava mm. water. The Systolic Output and the Work of the Heart. — To estimate the work of the heart, it is necessary to know the mean pressure (H), the velocity of blood in the aorta (V), and the volume of sj'stolic output (Q). The velocity of blood in the aorta may be obtained by one of the methods given later (p. 203). Having obtained the velocity (V), the output can be reckoned if the sectional area of the aorta (A) and the time of the cardiac cycle (T) be known. To calculate half the diameter of the aorta, thus 2"^ getting the radius (r). The sectional area (A) = :?/•- (77== "'); 60 (From Schiifer's "Physiology.") divided by the number of heart-beats per minute gives T in seconds Then Q = AVT. The output of the heart may be determined by means of the heart- lung preparation (Fig. 67). Under an anaesthetic, and after injection of hirudin to prevent the clotting of the blood, artificial respiration is established, and the common carotid artery, the descending aorta and 1G4 A TEXTBOOK OF PHYSIOLOGY the interior vena cava are ligatured. A cannula, connected with a manometer, M, is placed in the innominate artery. From this the blood is led past the air cushion B, which represents the elasticity of the arteries, to a rubber tube, R, in a tube, T. This can be compressed by the pump 8 and jjressure bottle A, and corresponds to the perijoheral resistance. Thence the blood passes to a vessel, N, where it is aerated and thence siphoned to one where it is warmed, and from there to the .superior vena cava through a cannula containing a thermometer. Fig. G7. — Diagram of Apparatus (described in Text) used in the Heart-Lung Preparation. (Knowlton and Starling.) The output of the ventricle for a given time may be estimated by measuring the flow from the bypass to the vessel N. If the rate of beat be known, the output per beat is easily calculated. The volume of output may be estimated indirectly by deter- mining (1) how much oxygen is absorbed from the inspired air per minute; (2) the difference in the oxygen content of the arterial and venous blood; (3) the number of heart-beats. If 1,000 c.c. of oxygen are absorbed from the air breathed in a minute, and the arterial blood contains 10 per cent, more oxygen than the venous, and the heart beats 100 times per minute, then, since 10 c.c. of oxygen are carried away by each 100 c.c. of THE NUTRITION OF THE HEART 165 blood, the amount of blood necessary to carry away 1,000 c.c. is — ^- — =10,000. If this be divided by the beats per minute (100), then the output for each beat would be 100 c.c. In man, the output volume can be determined by breathing in a deep breath of air mixetl with nitrous oxide — a very soluble gas — holding the breath and find- ing how much of this gas is carried away by the blood dviring a given time, about thirty seconds. A sample of the alveolar air is taken at the beginning and at the end of holding the breath, and the amount of air in the lungs at the beginning and at the end of this period is determined. From the amounts of nitrovs oxide in the samples the amount of nitrous oxide present in the lungs at the beginning and at the end of the experiment is known. This gives the amount absorbed from the lung in the time. Then, knowing the solubiHty of the gas (1 c.c. of blood absorbs 0-43 c.c. of the gas), the amount of blood necessary to absorb the known amount from the mean percentage of gas present can be calculated. This divided by the length of time of the experiment and the heart-beats i)er minute gives the output for each beat. The output for man is calculated to be 60 to 100 c.c. It is ten times as great or more during hard exercise. The work of the heart may be calculated from the following formula : W=QH + ^^\ where M = the weight of the mass of blood moved, and ^=the acceler- ating force due to gravity, this = 9-8. Q x H represents the work of each heart-beat in overcoming the peripheral resistance. =the energy of the velocitv of the blood ejected. These two must be added together. We may take the output of the left ventricle as 100 grammes; the mean pressure of the aorta as 110 mm. Hg. Since mercury is about 13-5 times heavier than blood, this = 110 millimetres x 13-5, or 0-110 metre x 13-5. We have therefore in gramme-metres of work : W= 100 X 0-110 X 13-5 + ^^^ 2 X 9-8 = 148-5+1-26.3 = 149-765, or, approximately, 150 gramme-metres of work for each contraction of the left ventricle. It is clear that almost all the work of the heart is spent in overcoming resistance, and it suffices, for roughh" calcu- lating the work, to multiply the output by the arterial pressure. We can say that the work of the left ventricle is equivalent to 166 A TEXTBOOK OF PHYSIOLOGY throwing uji a 5-ouiice ball a yard high seventy times a minute. The right ventricle, since it contracts against considerably less pressure, has less work to do. It is generally considered as doing about one- third the work of the left. Taking into consideration the variations in pressure and f)utput, the hunum heart is estimated to perform about 12,000 to 20,000 kilo- gramme-metres of work per day — that is to say, it performs sufficient work to raise the body weight through 200 to 300 metres above sea- level — say up a hill of 1,000 feet. Twenty thousand kilogramme-metres would be equivalent to 50 calories out of the total 3,000 calories which a man takes in as food. A labourer does about 150,000 kilogramme-metres of external work a day. The work of the heart is increased two or three times by muscular labour, and even ten times by great exertion. When the heart does work it also produces heat, and probably five times as much heat as work. It has lieen estimated that the heart requires per diem, to Recorder Via. tiS. — The Cakdiometek. maintain its energy, an amount of solid food (water-free) equal to the weight of solids in the heart itself — i.e., about 60 grammes of sugar or protein. A relatively high jiroportion of blood must be circulated per minute through the coronary arteries to maintain the vigour of the heart, and its use of oxygen per gramme of weight per minute is high. Thus, for the whole body of the dog there was used 0-017 c.c. per gramme of tissue per minute; for the heart, 0*045 to 0-083; and for the active secretory glands, 0-07 to 1-0. The volume of the output of the heart may be recorded by means of the cardiometer. Various forms have been devised. The most convenient consists of a large thistle funnel covered with a rubber membrane in which a round hole of appropriate size has been made with a heated soldering- iron (Fig. 68). After the establishment of artificial resjiiration, the thorax of the animal is opened and its heart inserted through the rubber membrane so that this fits snugly to the base of the ventricles. The tube of the funnel is connected with a piston recorder. A cannula THE NUTRITION OF THE HEART 167 is placed in the carotid artery, and connected to a mercury valve, whereby the blood-pressure can be regulated by raising or sinking a tube in mercury, and in which the blood is also kept warm until it is returned to the animal by the jugular vein. The circulation is' CUEARIZED. (L. H.) At A the artificial respiration was stopped. The large oscillations are Traube- Hering curves. D-.:ration in hundredths of a second ]0n 60 70 Pulse-frequencj- \ 50 per minute ) FiQ. 71. Duration of Systole and of Diastole with Different Pulse- Frequencies. (Waller.) THE NUTRITION OF THE HEART im such as the si^lanchnic, is thrown into constriction, and the blood is propelled from the constricting vessels into the veins, and thus the diastolic filling of the heart is increased; at the same time, the velocity of flow through the locomotor organs is accelerated, owing to a compen- ! (Rate of Fiilse : prSssuri of pulse) 1 1 0,- Cons ur.fpt'ion 1 J 1 1 1 1 ! ' 1 pressure \r)f p-J/sc 1 numoer of pulse beak 1 i i 1 1 1 ' 1 1 1 Time in periods of 20 minutec Fig. 72. — Diagkam showing the Relationship of Oxygen Consumption to the Rate of the Pulse and the Arterial Pressure. (Barcroft.) satory dilatation of the vessels in these organs.- The heart accelerates, the systolic output increases, and the arterial pressure rises (Fig. 70). In the second stage the vagal centre of the spuial bulb is excited by the high arterial pressure, the heart freci[uency is lessened, and the Fig. 73.— Contraction of Frog's Heart, showing Accelerator Effect of Weak Stimulation of Vago-Sympathetic. (Pembrey and Phillips.) Tlierc is increased tone in the after-effect. output diminished. Further, so soon as the arterial pressure reaches a certain point, the heart becomes unequal to the strain of emptying itself against the resistance; the output then becomes imperfect, the residual blood increases, the left aiu'icular pressure rises, and the blood is congested in the lungs and within the venous system. 170 A TEXTBOOK OF PHYSIOLOGY The amount of work done by the heart varies with the pulse frequency per niimite (Fig. 71). Tahlk siiowiNri Duration of Systhle to Diastolic, ktc, with Different Pulse-Frequencies. Puhe.- Duration of Duration of Frequency per Minute. Systole in Hun- Diastole in Hun- Ratio of Systole to Hours of Work dredths of a dredths of a Cardiac Cycle. per Diem. Second. Second. 50 37 83 •31 1-5 60 34 m ■34 8^2 70 32 54 •37 8^9 §0 30 45 •40 9^6 90 28 38 •42 10^2 100 27 33 .45 10-8 In Fig. 71 jDulse-frequencies per minute are indicated along the abscissa. Durations of systole and of diastole are given in hundredths of a second. Their respective curves show that the systole shortens by about y^^ second for each increase of ten beats per minute, and that the diastole shortens by about j\% second. Fig. 74. — Excitation of Vago-Sympathetic. (L. H.) Note the after-effect: a staircase augmentation of the heart-beat. The stars indicate the beginning and end of stimulation. The downstroke represents contraction. The time is marked in seconds. The shaded and unshaded portions represent resjoective time of work and time of rest at various pulse-frequencies. The rate of beat and the arterial pressure also influence the amount of oxygen consumption by the heart muscle. This is well seen in the diagram (Fig. 72). CHAPTER XIX THE CARDIAC NERVES The vagus nerve, when excited, slows or even arrests the action of the heart (Fig. 44). The cardio-inhibitory nerves, as they are called, have been found in all classes of vertebrates and in many inverte- brates. The existence of nerve fibres which, when excited, augment and accelerate the beat of the heart has also been demonstrated. These belong to the sympathetic nervous system. In the frog, the two nerves run in one triuik — the vago- sympathetic nerve — a variable response to stimulation is therefore obtained (Figs. 73, 74). In the Fig. 75. — Cardiac Nerves of Frog. frog, the symjDathetic fibres come off the ganglion of the third spinal nerve (first post-brachial), and pass along the sympathetic trunk to join the vagus nerve where its ganglion lies at the base of the skull (Fig. 75). In mammals, the accelerator nerves arise from the first to the fifth thoracic anterior spinal nerve roots, the preganglionic fibres having their "cell .stations" in the first thoracic and inferior cervical ganglia, whence they pass to the heart partly in company with the cardiac branches of the vagus, and partly as separate twigs (Fig. 76). The vagus cardiac fibres belong to the cerebral 171 172 A TEXTBOOK OF PHYSIOLOGY autonomic system. They arise from a centre in the medulla oblongata by the middle of the lowermost group of vagus roots, and the pre- ganglionic fibres have their cell-stations in the ganglion cells of the heart. These ganglion cells lie chiefly in the subpericardial tissue, in the posterior wall of the auricles between and around the orifices of the venae cava^ and j^ulmonary veins, and between the aorta and pulmonary artery. The right nerve goes particularly to the^anglion cells in the neighbourhooti of the sinu-ain-icular node, through Fig. 7G. — C'akdiac Nervks of Dog. (Foster.) which certain of the post-ganglionic fibres act. The inhibitory fibres run chiefl}^ in this nerve. The centre is in tonic action, and constantly bridles the heart's action, and this when the vagi are divided, the frequency of the heart increases and the blood-pressure rises. During stimulation of the peripheral end of the vagus the arterial pressure falls and the vena cava pressure rises (Fig. 77). The vagus centre is reflexly excited by the inhalation of chloroform, ammonia, or other vapour irritant to the air-passages; also by the want of oxygen in the blood, as in asphyxia. It may be THE CARDIAC NERVES 173 excited refiexly by irritation of the abdominal nerves — e.g., a blow in the abdomen — and by increased pressure in the cerebral vessels. The accelerator and augmenting fibres likewise have their centre in the spinal bulb, and this is in tonic action, antagonizing more or less the action of the vagal centre. The vagus nerve, by its action, pro- duces changes Avhich result in a dejDression of the excitabilitj% the conductivity, the force, and the frequency of the heart. By some authorities these are believed to be separate influences, so that the vagus nerves are said to contain bathmotropic, dromotropic, inotropic, ,NMNN^ Fig. 77. — The Effect of Excitation of the Peripheral End of the Vagus Nerve upon the Blood-Pressure in the Aorta (Top Curve) and the Vena Cava (Second Curve) in mm. Hg of a Curarized Animal with Artificial Respiration. (L. H.) Note the inhibition of the heart; the great fall of aortic and the insignificant rise of vena cava pressure; the escape of the heart from the vagus action and the after- effect on the aortic pressure. The time is marked in seconds, and the signal line shows the duration of vagus stimulation. and chronotropic fibres, influencing through their nerve endings the above-mentioned properties in the order named. Possibly, also, the tonicity of the heart muscle is affected. The chronotropic action, slowing the frequency of the beat, is the most characteristic action. The heart becomes dilated and engorged with blood, stopping in diastole. The right vagus, in which chronotropic fibres chiefly run, probably manifests its action upon the auricles through the sinu- auricular node. The left vagus is held by those authorities who believe in the different kinds of fibre to contain chiefly fibres other 174 A TEXTBOOK OF PHYSIOLOGY (i) (ii) r r I I I r I M M I I M I M M f I I M ( I M N M M I M I i%l%(^TftTfl'^ w¥^IMriM% r I f M I 1 1 I M I I n I n n N M 1 1 ( M I N I ( r I f M ( M r (iii) 1, 'ii.lMl'l ' ■W"i'»Mll llii *' 'ill if iiiiii ■!> 'i I I I) I I I I I I I I M M I I M I I I ( I I M I Fig. 78. — Tracings (i.) to show and (ii.) the Abolition of Effect^ of^ Right ACCELERATOE IN THE DOG, FREEZING THE S.-A. NODE. THE ACCELERATOR Nerve was stimulated between the Strokes, (iii.) The Action of Right Nerve beforehand — the Action also returned after the Effects ^of THE Cold had passed off. (M. F.) If ilill m 'I'lf 'I'll 'I' rTTTTTTl'f I r I I I [)( f M'l ? n If / I f '1 [ N I f f I f f I 11 M I I Fig. 79. — To show the Action of the Left Accelerator in the Dog even after FREEZING OF S.-A. NODE. (M. F.) The nerve stimulated from A'-A" ; freezing started at Z'and continued all the time. THE CARDIAC NERVES 175 --^^^---'^^^MU^jmwjm/MM^ i^''ff'^mm^'yni"rr"ni \\\.'VfW^ ^MfMmmiwmimMi iJ'uUlI'dUUiJU Fig. 80. — Shows Effect uf Stimulation of Vagus (A) and of Accelerator Nerves (B) in Cat's Heart with A.-V. Bundle Cut. (W. Cullis and E. M. Tribe.) The vagus effect is abolished, but the action of the accelerators persists, especially the augmentor effect. Tvi. 81. — Shows the Effect of a Small Injection of Muscarine upon the Dog's Heart (Ventricle Upp3h, Auricle Lower Tracing). (Dixon.) The auricle was completely inhibited in diastole. At B atropine was injected into a vein, r.nd tlu' inhibitory effects passed off. 176 A TEXTBOOK OF PHYSIOLOGY than chronotropic. Its chronotropic fibres generally do not pass to the sinu-auriciilar node; perhaps they may pass to the A.-V. node. The left nerve has been said to act directly on the ventricles; it is })robable, however, that the vagus nerves only manifest their action indirectly through action upon the auricle (Figs. 44 and 80). We need not suppose different kinds of nerve endings; it is probable that the different results are obtained through varying intensity of stimulation action upon the same endings. After vagal arrest, the heart beats more forcibly, owing, perhaps, to the greater accumula- tion of contractile material dviring the period of rest. The converse of all these effects occurs on stimulation of the accelerator nerves (Figs. 78 and 79). During stimulation of these Li 1.0, sth..|v;'j. Jmm Fig. 82. — Dissection^ of the Vagus, the Depressor, and Cervical Sympathetic Nerves in the Rabbit, (Cyon.) nerves the heart beats more quickly and forcibly, excitability and conductivity being also increased. Excitation of these nerves may excite to renewed efforts an excised heart which has just ceased to beat owing to a withdrawal of the supply of nutritive solution ; hence it is thought by some that the accelerator nerves tonically exert a sustaining influence on the heart. The accelerator nerves act directly upon both auricl s and ventricles (Figs. 79 and 80). The alkaloid atropine paralyzes the vagal nerve endings in the heart, while nicotine paralyzes the endings of the preganglionic fibres in the THE CARDIAC NERVES 177 ganglion cells. In a frog, these differences can be easily shown. -Stimulation of the sinu-auricular groove will produce an action both before and after the application of nicotine, but not after atropine. Both drugs prevent the effect of stimulating the vagus. In mammals, a local application of the drugs to the sinu-auricular node abolishes the mhibitory action of the vagus. Muscarin, obtained from poisonous fungi, slows and finally arrests the heart probably by acting upon the vagus nerve endings; atropine antagonizes this action (Fig. 81). A great many of the cardiac vagal fibres convey impulses to the spmal bulb (centripetal), and reflexly influence the heart-frequency, the breathing, and the tonus of the bloodvessels. In particular, certain fibres, termed depressor, cause dilatation of the arterioles, and a fall of arterial pressure, by inhibiting the tonic action of the vaso- motor centre in the spinal bulb. The depressor fibres arise from the root of the aorta, and overdistension of this part excites them, as Fig. 83. — Aoktic Pkessuee. Excitation of Depkessor. (BayKss.) The drum was stopped in the middle of the curve, and the excitation maintained for seventeen minutes. evidenced not only by the above effect, but also by the electrical variation (action current) which has been observed passing uj) the depressor nerve. In some animals, such as the rabbit, it is found in the neck as a slender nerve running close to the sympathetic. It can be recognized in the rabbit by the fact that it joins the vagus and its superior laryngeal branch, dividing into two shortly before its junction with these (see Fig. 82). Stimulation of its peripheral end has no effect. The fall of blood-pressure (Fig. 83) induced by excitation of the depressor results chiefly from vaso-dilatation in the splanchnic area. After section of the splanchnics, this fall of blood-pressure naturally is not marked. Its action is increased by the secretion of the thyroid gland, induced by stimulation of the superior laryngeal nerves, or by the injection of thyroid extract. In the vagus nerve there are also sensory fibres which when excited cause reflexly through the vasomotor centre a rise of pressure (Fig. 84). 12 178 A TEXTBOOK OF PHYSIOLOGY Sensory impressions originating in the heart do not as a rule enter into consciousness. Carried by the cardiac nerves to the sympathetic gangha, and thence to the upper thoracic region of the spinal cord, they come into relation there with the senf-ory nerves from the pectoral region, u])])cr limb, shoulder, neck, and head. The impressions are not felt in the heart, but referred to these sensory cutaneous nerves (Fig. 38'} ). Thus, cardiac pain is felt in the chest wall and upper limbs, and par- ticularly on the left side. The function of the cardiac nerves is ta vw.v.,Vvv^^^^^ Vu*.y "%\M/'' iiniiiiiiiiiiiilmiui iiniiiiil iiiiiiii.iiiiii I III mil I iiiimiiiiiiii Fig. 84. — Aortic Blood-Pressuke. (L. H.) A, Effect of exciting the central end of vagus. The effect was depressor. B, On shifting up the electrodes to a fresh unexposed part of the nerve the effect changed to pressor. The time is marked in seconds. co-ordinate the beat of the heart with the needs of the body, and to co-ordinate the functions of other organs with the needs of the heart. For example, an undue rise of arterial pressure, induced, let us say, by compression of the abdomen, excites the centre of the vagus, and produces slowing of the heart and a consequent lowering of arterial pressure. The heart of a mammal continues to functionate after a section of all the branches of the cardiac plexus has been made, so that the nervous control and co-ordination of the heart are not abso- lutely essential to the continuance of life. CHAPTER XX THE PHYSICAL FACTORS OF THE CIRCULATION Some of the phj-sical laws which govern the circulation may be ilhistrated ])y means of schemata made of rigid cyHndrical tubes. Flow of Fluid in Cylindrical Tubes. — In a cylindrical tube, the fluid particles, flowing" under constant pressure, move parallel with the axis, but with varying velocity. In the axial layer the velocity is at its greatest; at the wall it is almost nil. The wall is wet with the fluid, and there is friction between the moving particles of fluid. The fluid may be considered as consisting of an infinite number of concentric cylindrical surfaces, which glide over one another, and move the more rapidly the smaller their radius. The velocity, which is reckoned from the outflow per second per sectional area of the tube, yields us the mean velocity of all these cylinders of fluid. Poiseuille has laid down the law that the mean velocity is directly proportional to the sectional area of the tube and pressure gradient. We can find the mean velocity by the product of three factors — sectional area, pressure gradient, and a constant coefficient, which depends on the viscosity or physico-chemical nature of the fluid in the conditions of experiment. This coefficient can be defined as that mean velocity which a current would have with a unit pressure gradient in a tube of unit sectional area. The coefficient at one and the same temperature varies for different fluids, and is found to be smaller in proportion to the viscosity of the fluid. The viscosity of blood is found to be three and a half to five times that of distilled Avater. A mixture of blood and water is less viscous than blood. Thus, the velocity of the circulation is increased by the injection of Ringer's solution. The viscosity of the blood is increased when there is great loss of water — e.g., in cholera. Alterations in viscosity can be compensated for by the vaso -motor system, which regulates the peripheral resistance, and are therefore of minor im- portance. By experiments upon the flow of distilled water in capillary glass tubes, 0-65 to 0-15 millimetre in diameter, Poiseuille reached the following conclusions : 1. That the amount of OTitflow is proportional to the head of pressure. . 2. That the time spent in the outflow of a certain volume of flmd 179 180 A TEXTBOOK OF PHYSIOLOGY at a constant i)ressure, if the diameter be constant, is diiectly pro- portional to tlu^ length of the tube. 3. That with the same head of pressure the time spent in the outflow of a certain volume of fluid through equally long tubes is inversely |)roi)orti()nal 1o the fourth power of the diameter. The Flow in a Tube of Varying Diameter. — Since fluid is hicom- pressible, an equal amount must flow in the unit of time through every section of the tube, and thus the velocity in any part of a tube which varies in diameter stands in inverse proportion to the sectional area. In such a tube the pressure gradient is steepest in the narrowest section, for there the velocity and the friction is greatest. In two sections of equal tliameter the pressure gradient is the same. Where a wide section follows ujDon a narrower, the lateral pressure may either Fig. 85.— Schema to show the Velocity and Resistance Heads. B, Pressure bottle ; A, tube with piezometers; E F, Pitot tubes. sink, remain unaltered, or even rise. How this can be so is seen by the following considerations: At any point of the tube the whole pressure head (H) equals the sum of the velocity head (h^) and the resistance head (h^). Now H decreases uniformly along the tube, and since, where the tube widens, the velocity becomes less, and H^ suddenly diminishes, it follows that /r increases, and it is conceivable that h} in the wide section may become higher than h'^ in the narrow section. In other words, since more of H is spent in maintaining the velocity in the narrow section, the lateral pressure may be lower here than in the succeeding wide section. The Flow in Branching Tubes.— When a tube branches into a number of smaller branches, and these connect again into one tube, we have two opposing factors to consider: PHYSICAL FACTORS OF THE CIRCULATION 181 1. The increase of sectional area. The velocity is inversely pro- portional to the whole sectional area of the branches. 2. The increase of resistance, due to the great extent of surface contact between the moving fluid and the fluid that wets the walls of the tubes. The resistance is proportional to the surface area, nearly proportional to the square of the velocity, and inversely pro- portional to the sectional area. The formula used by engineers for what they cafl "skin fraction" is R = ^S^;^ where R = resistance ; 1c, a constant; S, surface area; v, velocity. If water flows from a head of pressure through a tube on which stand a number of vertical side tubes, it is found that, according to Fig. 86. — Schema to show Effect of introducing Resistance. the degree that the outflow from the tube is obstructed, so will the water rise in the side tubes ; the nearer the side tube to the head of pressure, the higher the fluid rises in it (Fig. 86). This is because water flowing through a tube from a constant head of pressure encounters a resistance occasioned by the friction of the moving water particles against each other and against the stationary layer that wets the wall of the tube. Part of the potential energy of the head of pressure is spent in endowing the fluid with kinetic energy, part in overcoming this resistance. The latter and greater part is rubbed dowai into heat. The narrower the tube is made, the greater the friction, until finally the flow ceases, the total energy being then insufficient to overcome the resistance. This is well exemplified by the modified schema (Fig. 86). W is a bottle containing coloured water connected to the rigid tube X, on which 182 A TEXTBOOK OF PHYSIOLOGY stand the vertical side tubes A to E. R is a resistance introduced by means of a wide tube filled with f-mall glass marbles. Y is a rubber tube of equal calibre to A' leading to the rigid tube Z, similar to X. The amount of fluid flowing to the tube can be regulated by the clami? K. Further, the fluid can flow from the tube X to the tube Z either by Y when the clamp L is shut and clamp L^ open, or by the tube R when the clamp L^ is shut and clamp L is open. When there is a free flow from W (K open), and free communica- tion b}^ }' from X to Z {L closed, L^ ojien), it will be seen, according to the resistance introduced by clamp M, the coloured fluid rises in all the side tubes to a nearly equal extent, gradually decreasing irom A to J. When the clamp L^ is slightly closed, the fluid rises higher in tubes A to E than before, and faUs in tubes F to J. The same thing is seen if the fluid, instead of passing by 7, is sent through i?, which better exemplifies the circulation. Fig. 87. — Schema to show the Flow in Rigid and Elastic Tubes. (Marey.) The compressor should compress the single tube not the double tube, as figured. In this schema the flow has been through rigid tubes. The same laws which have been discussed in connection with rigid tubes obtain in elastic tubes if the flow of fluid be continuous. If the inflow be intermittent, in the case of the rigid tube, the whole column of fluid is driven on, atep by step, by each stroke of the pump, and the outflow is intermittent. In an elastic tube, on the other hand, if the resistance to the output has been made great, as by constricting the orifice, the elastic wall of the tube is extended by the input, of the pump, and the elasticity of the wall comes into play, and con- tinues the output after the stroke of the pump has ceased, so that the flow becomes continuous. This is shown by the schema (Fig. 87). Here the coloured water flows from a head of pressure through two tubes 1 metre long, and of the same bore; but one tube is rigid, the other elastic. The outflow orifices are also of the same size. PHYSICAL FACTORS OF THE CIRCULATION 183 On rhythmical^ shutting and opening the compressor, it will be found that the outflow from the elastic tube is continuous, from the rigid it is intermittent. The increased and continuous flow is due to the potential energy stored up in the stretched wall of the elastic tube. The elastij tube also delivers more fluid per minute than the former. In the circulator}^ sj^stem we are concerned with a system of elastic tubes. The conditions appertaining in the circulation can best be repre- sented, therefore, by a schema having elastic tubes, such as Fig. 88. Here H, the bulb of a Higginson syringe, represents the head of pressure^the heart. Two valves, representing the mitral and aortic valves, regulate the flow in one direction only. Coming away from the syringe is a rubber tube (about i inch diameter), which divides into two .channels the arteries, leading (1) to two lamp glasses filled Co-pillarics Fig. 88. — Artificial Schema. with chopped rubber sponge (the capillaries), and (2) to a rubber tube «hut with a clamp (the short circuit). This clamp represents the muscle wall of the arterioles. These are connected with the inner tube of a bicycle tyre, representing the capacious venous system, and this in turn to the Higginson syringe again. Inserted in the circuit are manometers connected by T-pieces to the artery and to the vein. The whole system is filled with water, air being removed by tilting the board to which the schema is fixed and working the pump, but only so far that the vein is not distended, and there is no positive pressure in the system when at rest. When the screw clip (the arterioles) is widely open, there is little resistance to flow. The outflow from the artery into the vein then ceases during diastole, the conditions being the same as if the artery were a rigid tube. The variations of pressure are great both in artery and veins, and both 184 A TEXTBOOK OF PHYSIOLOGY manometers are affected to almost a like extent. On screwing up the clip (increasing the resistance in the arterioles), the flow becomes less and less intermittent as the resistance increases, and eventually becomes contiivuous. The pressure rises in the arteries, the systolic and diastolic variations in pressure becoming greath' reduced. The variations in pressure disappear from the veins. This represents what takes place in the vascular system. The Elasticity oi Arteries. — An artery possesses great lability, that is, it is easily distended; it has great elasticity, recovering its shape after the distending force is removed. The curves of extensibility and elasticity may be worked out on excised arteries either by weighing and unweighing a strip of vessel wall, or by recording the expansion of a short length of artery when submitted to a pressure of water. Such curves vary according as the artery is relaxed or contracted. The muscle in its wfll alters the lability by its contraction or relaxa- tion (Figs. 89, i;0). The breaking strain of a healthy artery is very great. In some experi- ments the caret d of a goat f.r.ccc^;;;- fully withstood a pressure of 2.250 mm. Hg — that i.;, about fourteen times the normal blood-pressure. It takes an internal pressure of 3,000 to 8,500 mm. Hg to rupture the carotid artery of a dog. In the ease of the human carotid the smallest rupturing pressure was found to be 1,290 mm. Hg. The larger arteries rupture more easily than the smaller, and thus the aorta breaks asunder at a lower tension than the radial. In the vascular sj^stem, an area of vessels of capillary size is placed between the large arteries and veins. This area opposes a great resistance to flow. The effect of the peripheral resistance, as it is called, is to raise the pressure on the arterial side and lower it on the venous. The resistance to flow is situated chiefly, not in the capil- laries, but in the small arteries, where the velocity is high. " Skin friction " — that is, the friction of the moving concentric layers of blood against one another and against the la^^er which wets the wall of these bloodvessels — is f)roportional to the surface area and to the viscosity of the blood; is nearly proportional to the square of the Fig. 89. — Elongation of Con- tracted Aktery, with Rise OF Internal Pressure (0 to 300 Mm. Hg). Length = Hi Mm. (Mac William.) Fig. 90. — Elongation OF Relaxed Artery, with Rise of Inter- na l Pressure. L e N g.t h 2 1 Mm. (MacWilliam.) PHYSICAL FACTORS OF THE CIRCULATION 185 velocity of flow; and is inversely proportional to the sectional area of the vessels. Owing to the resistance to the capillary outflow, the large arteries are expanded by each systolic output of the heart, and the elasticity of their walls comes into play, causing the outflow to continue during the succeeding diastole of the heart. The conditions are such that the intermittent flow from the heart is converted mto a continuous flow through the capillaries. If the arteries were rigid tubes, it ^\-ould be necessary for the heart to force on the whole column of blood at one and the same time; but, owing to the elasticity of these vessels, the heart is saved from such a prolonged and jarrmg strain, and can pass into diastolic rest, leaving the elasticity of the distended arteries to maintain the flow. Besides the saving of heart-strain, there is the advantage of a greater outflow through elastic than through rigid tubes. As a result of disease, the elastic tissue may degenerate and the arteries become more rigid. The four chief factors which co-operate in producing the conditions of pressure and velocity in the vascular system are — (1) The heart-beat; (2) The peripheral resistance ; (3) The elasticity of the arteries; (4) The quantity of blood in the system. Suppose the body to be in a horizontal position, and the vascular system to be brought to rest by, say, arrest of the heart. A sufficiency of blood to distend it collects within the venous cistern. The arterial system, owing to its elasticity and contractility, empties. If the heart now begin to beat, blood is taken from the venous system, and is driven into the arterial system. The arteries receive more blood than escapes through the capillary vessels, and the arterial side of the system becomes fllled until equilibrium is reached, when as much blood escapes from the arterial into the venous side per unit of time as is delivered into it by the heart. The flow in the capillaries and veins now becomes a constant one, and if the side-pressure be measured, it will be found to fall from the arteries to the capillaries, and from the capillaries to the vense cavse. In the large arteries there is a large side-pressure which rises and falls with the pulses of the heart. The pulse-waves spread out over a wider and wider area as the arteries branch. They finally die away in the arterioles. An increase or decrease in the energy of the heart-beat will increase or decrease respectively the velocity of flow and pressure of the blood. An increase or decrease in the total width of the arterioles respectively will lessen or raise the resistance, increase or decrease the velocity, lower or raise the blood-pressure. A loss of blood, other conditions remaining the same, would cause a decrease in pres- sure and velocity. As a matter of fact, even a considerable loss is compensated for by the adjustability of the vascular system. Tissue lymph passes from the tissues into the blood, and the bloodvessels of the limbs and abdomen constrict, and thus the pressure is kept up, and an efficient circulation maintained through the brain, lungs, and coronary vessels of the heart. CHAPTER XXI THE ARTERIAL PRESSURE The term " blood-}Dressiire " is somewhat loosely used. Generally, it signifies the arterial pressure, but it can be equally well applied to the pressure of blood in the capillaries or in the veins. For the sake of accuracy, it is better to speak of the arterial blood-pressure or arterial pressure, the capillary pressure, and the venous pressure. The Blood-Pressure. — It has long been known that the blood is under different jiressure in the various parts of the system. From a divided artery the blood flows out in forcible spurts, from a vein it flows out continuously and with little force. It takes very little pressure of the flngers to blanch the capillaries of the skin or nail-bed, to stop the blood-flow in the superficial veins, but an appreciable amount of pressure to obliterate the radial artery. Fig. 91. — Arterial Cannula. Measurement of Arterial Pressure. — Stephen Hales (1733) was the first to measure the blood-pressure. He fastened a long glass tube held vertically to the femoral artery of a horse, using a brass cannula and a goose's trachea as a flexible tube for making connection. He saw the arterial blood rise some 6 feet high in the tube, and oscillate there with each pulse-beat and respiration. Later the mercurial manometer was adapted to the same purpose. This consists of a U-shaped tube containing mercury, which, being 13-5 times heavier than blood, allows the manometer to be brought to a convenient height. On the top of the mer;ury rides a float provided with a writing style (see Fig. !t2). The 186 THE ARTERIAL PRESSURE 187 introduction of rubber tubing for the connections made the method of inquiry comparatively simple. The method of procedure now usually employed is as follows: The artery of an anaesthetized animal is exposed and ligatured. A clamp is pla:ed upon the artery nearer the heart, and the special- shaped cannula (Fig. 91) introduced between the ligatiu-e and the clamp. The cannula and tubing are filled with a suitable fluid,* to prevent coagulation, from a reservoir (R, Fig. 92), raised to a height sufficient to introduce a pressure about equal to the antici- pated arterial pressure of the animal. This prevents more than a trace of blood entering the connections. The clamp is now removed from the arterj^ and the ])ressure is transmitted to the manometer, the style of which can be brought to Fig. 92. -Arrangement of Cannula, Pressure Bottle, and Mercurial Manometer, for Recording Blood-Pressure. C, Cannula; p, p^, clips; F, float; S, writing style. write on a drum covered with smo':ed paper, and driven slowly round by clockwork or electric motor. By this means tracings (»f the arterial blood-pressure are obtained, and the influence upon the blood-pressure of various agents recorded and studied. For the veins, a manometer filled with salt solution is used, as mercury is too heavy a fluid to record the far slighter changes of venous pressure. The manometer may be connected with a recording tambour. The arterial blood-pressure record obtained with the mercurial manometer exhibits cardiac and respiratory oscillations. The method gives us a fairly accurate record of the mean pressure, l)ut the mass of the mercury causes such inertia that the instrument is quite * Saturated magnesium sulphate may be employed for t he dog and rabbit, but not for the cat. For this animal, saturated sodium sulphate should be used. A 10 per cent, sodium citrate or 0-4 per cent, potassium oxalate solution may also be employed for all animals. 188 A TEXTBOOK OF PHYSIOLOCiY unable to record faithfully the actual systolic and diastolic varia- tions of pressure. To effect this record, delicate spring manometers of rapid action and small inertia have been invented (Fig. 93). The sphygmoscope consists of the finger of a rubber glove drawn loosely Fiu. 93. — Kurthle'.s Spring Manomt." lr. 'iit ailN' Fig. 94. — Sphygmoscope. so as to leave an air-space over the end of a rubber cork and enclosed in a glass tube. The finger stall acts as a spring and the tube is connected with a recording tambour (Fig. 94). A mercury manometer Fig. 95. — The Armlet Sphygmometer. (Leonard Hill.) The arm is slipped through the armlet, and the latter fixed round the upper arm by- drawing the straps tight. The armlet should be placed at the same level as the heart. The syringe bulb is then rhythmically compressed, while the radial pulse is felt. The height of the mercurial column is noted at which the pulse just fails to meet the wrist. The screw valve attached to the syringe bulb is opened, and the pressure allowed to fall gradually, a reading being taken at the moment when the pulse again reaches the wrist. provided with maximum and minimum valves has also been employed to indicate the maximal systolic and minimal diastolic pressure. For determining the arterial pressure in man, the apparatus used is known as a " sphygmometer," or " sphygmomanometer." This con- THE ARTERIAL PRESSURE 189 sists of an armlet, a rubber bag encased in soft leather, connected bj tubing and T-piece to a syringe bidb for raising the pressure, and a mercury manometer or spring gauge for registering the same (Fig. 95). After the armlet is buckled on, the pressure is gradua,lly raised in the armlet b}' means of the syringe. A reading is taken when the pulse in the artery is obliterated below the armlet (the systolic pressure). The disappearance and reappearance of the j)ulse may be felt with the fingers, or heard by placing a stethoscope over the artery at the elbow. When, as the pressure i.s relaxed, the i^ulse comes throiigh under the armlet, a loud sound is heard sj'nchronous with each systolic wave. As the pressure is further relaxed, the sound undergoes variation in tone, but at a certain point suddenly diminishes or dis- appears. If the pressure be read at this point, it denotes the diastolic pressure. It has been proved by experiments on animals that the sj'stolic and diastolic jwessures, so measured, agree with measurements made directly by connecting the artery- with a spring manometer. The pocket sphj'gmometer shown in Fig. 06 consists of a rubber J, J. HICKS SOLE MAKER LONDON. PATENT. Fig. 96. — Leonard Hill Pocket Sphygmometer. bag covered with silk, which is tilled v\'ith air, and connected by a short length of tube to a manometer. This manometer consists of a gradu- ated glass tube open at one end. A small hole is in the side of the tube near this end. A meniscus of coloured t Ikalinc water is introduced up to the side hole — the zero mark on the scale — by placing the open end of the tube in water. The bag is now connected to the gauge, so that the side hole is closed by the rubber tube. To take the arterifc.l pres- sure the rubber bag is covered with the hand, and pressed on the radial artery until the pulse (felt beyond) is obliterated, the height to which the meniscus rises in the manometer being read. This gives the systolic pressure in the artery. The air above the meniscus acts as a spring, converting the instrument into a spring manometer. It is graduated empirically in millimetres of mercury.*- The systolic pressure of young men, taken in the radial artery with the arm at the same level as the heart, may be taken to be about 100 to 110 mm. of Hg. In men of forty to sixty years the systolic pressure is often about 140 millimetres, but in some robust men it is no higher than in youth. It is very necessary to remember that the blood-pressures, taken * The graduation is at sea-level. A correction would be necessary for high altitude:). 19D A TEXTBOOK OF PHYSIOLOGY in different vessels and postures, vary with the hydrostatic pressure of the eohnnn of blood which lies above the point of measurement. In the horizontal ])osture the pressure is practically the same in all the big arteries. In the standing position the arterial pressure in the 'A O C5 a<*^ Si) rj CO -g 'tS ? o S ^ . r, ^ Q^ r!* c3 _£2 ^ -tiW S .-; «^ 5 2 ^ S - '^ {- It: C C 5^ Si a -> S^ P- * o ?i c fi c 5 * • 3 S cS ^ ^ = " ^ S * ^ CD w 1J ^ S :2 a ;s5 arteries of the leg is higher than in the arm by the height of the column of blood separating the two points of measurement (see p. 200). A difference between arm and leg pressures in the horizontal position can be brought about in the nornipJ person by violent exercise, for this increases the height of the systolic wave. The leg arteries, THE ARTERIAL PRESSURE 191 under, the above conditions, are less labile, and conduct the big crest of the wave better than the arm arteries. There are other possible factors at work which cannot be discussed here. In cases of aortic regurgitation there is present a well marked and diagnostic difference of pressure between arm and leg in the horizontal position. When the bag of the sphygmometer is applied to an arterj- (such as the dorsalis pedis) which lies upon bone unsupported by tissues, a far lower jDressure (30-35 mm. Hg) than that in the artery suffices to obliterate the pulse. Under these conditions, the artery is easily deformed from the round to the oval shape. This change in shape occasions an in- creased resistance to the passage of the pulse-wave, and the force of k ^j-j^MrU.y^-mu^^' A. ABDOMEN. B. CHEST. C.ABOOMEN. "^nsp. BP.Lme D. CHEST. Fig. 98. — Influexce of Chest axd Abdumi>"al Beeathixg ()>• the Pulse. (Lewis.) the pulse in consequence becomes spent in the labile arterial system above the point of deformation. Where the arter}' is surrounded by tissues full of circidating blood, it cannot become deformed until the blood-pressure in the vessels of the surrounding tissues is overcome. The pressure of the bag first obliterates the veins; the pressure then rises in the capillaries and approximates to the arterial pressure as the compression is increased. Finalh\. the arterial pressure is overtoj)ped, and then the compression comes to act upon the main artery, and this being deformed, the pulse ceases to come through. This is ex- emplified in Fig. 97. In A, with the artery laying in a tube surrounded by tiuid, corresponding to the tissues, the pressure recj^uireel to drmp 192 A TEXTBOOK OF PHYSIOLOGY down the pulse; just overto])})e(l the arterial pressure. When exposed on a watchglass, as in B, the lumen became deforinod and the pulse damped at a much lower pressure. If the armlet be placed upon the arm, and kept at a pressure a little below that of the arterial supply to the arm, the limb gradually becomes congested and the superficial veins engorged with blood. Measurement of the pressure in these superficial veins reveals a pressure approximately equal to that registered by the manometer measuring the arterial joressure. The capillaries of the arm, under these condi- tions, become more and more congested; those that were previously empty gradually fill. An aching feeling comes on, which terminates the experiment. The experiment shows how many capillaries arc cmj^ty under normal conditions. In active life we are continually moving our position, so as to prevent continuous jjressure on any ]:)art and further the circulation. Circumstances affecting the Arterial Pressure. — The arterial pres- sure is raised during exertion by the more forcible beat of the heart — e.g., pressures of 140 to 190 mm. Hg have been observed immediately after running upstairs. It rapidly sinks to a lower level than usual after the exertion is over — e.g., 90 mm. Hg — owing to the quieter action of the heart and the persistence of the cutaneous dilatation of the bloodvessels which is evoked by the rise of body temperature. In athletes, after a long race, rectal temperatures of 102° to 105° F. have been observed. Mental occupation and excitement raises the arterial pressure. People engaged in brain work have in general a higher pressure than people engaged in purely manual labour working in the same atmospheric conditions. After meals there is a rise in l^ressure. The ordinary statement that insj)iration raises and expiration lowers the blood-pressure is only true for an animal under experi- mental conditions. The effect of respiration on the blood-pressure is very complex. A deep intercostal breath, if not too prolonged, yields a fall, a deep diaphragmatic inspiration, a rise, of pressure. Forced breathing ceaises a fall, while Valsalva's experiment, a deep expiration with the mouth and nose shut, causes a marked rise in the arterial pressure. The effects on the pressure of different tj'pes of breathing in a trained subject were as folloAvs: Type of Ereathinj. i Inspiration. Suspended Inspiration. Expiration. Suspended Expiration. Thoracic . . - Abdominal . . 4 + + ■Jr- Records of the pulse obtained by the suspension method (p. 211) show these results (Fig. 98). In such records a rise in the tracing indicates a rise of pressure, a fall in the tracing, a fall of pressure. Increase in the amount of fluid by transfusion cannot raise the THE ARTERIAL PRESSURE 193 pressure alxive what can be obtained with a normal amount of blood. Similarly, bleeding to the extent of 2 to 3 per cent, of the body weight causes little or no fall of arterial pressure. The taking of alcohol lowers the arterial pressure. During chloro- form anaesthesia the pressure falls (Fig. 104). During deep sleep the pressure is lower, but not lower than in the waking state when the body is recumbent and at rest. Immersion in a hot bath lowers, in a cold bath raises, the pressure. The arterial pressiu-e is considerably higher in warm than in cold blooded animals — at least three times greater. The pressure is inde- pendent of the size of the animal, and thus may be as great in the cat as in the horse. It will thus be seen that the maintenance of a mean arterial pressure of constant height is the function of the circulatory mechanism. On the one hand, we are convinced that this object is attained during life; on the other hand, we know that countless and ceaseless variations. are occurring in all parts of the circulatory system. The whole system, is, therefore, so craftily built and so delicately balanced that every variation in one part is compensated by a simultaneous and contrary variation in another part, and thus, throughout the wear and tear of life, the aortic pressure is kept at a constant mean height. 15 CHAPTER XX IT THE EFFECT OF CHANGE OF POSTURE ON THE CIRCULATION Thk circulation is «o contrived that it remains constant and efficient, not only in the horizontal position, but also when the living animal is ceaselessly shifting the position of his body. The hydro- static influence of gravity must have had a most imj)ortant bearing on the evolution of the mechanisms which control the circulation. This is well demonstrated by the following model ; Suppose a closed and rigid tube filled with water and fixed to a board. When the board is placed in the horizontal joosition, the pressure in all parts of the tube will be the same. If the board be turned into the vertical position, then the pressure p, I ^ — v^. I y. at the top end will become higher than the pressure lrn|f\Jl^']( \\i at the bottom end by the height of the column of fluid. The fluid will still equally pervade the tube in all its parts. This must be so, because the fluid is incompressible, and the tube is rigid and unyield- ing in structure. If the rigid tube be now replaced by an elastic tube, and this at the j)oints A and B be made to expand into thin-walled elastic bags, then the con- ditions become markedly different (Fig. 99). On placing such a model in the vertical position, the bag {B) expands under atmospheric pressure plus the pressure of the column of fluid [A, B); and while the water flows into B, A empties and shrinks luider the atmospheric pressure. If a pump, P, which can work with uniformity and maintain a constant circiilation, })e placed in such a model ; if the outflow tubes or arteries be made of small capacity, and labile — that is, possessing considerable extensibility, and elasticity — and the inflow tubes or veins be valved, and be made of considerable capacity and slight extensibility and elasticity ; and if a sponge be inserted as a resistance in the bags {A and B), then many of the conditions of the systemic circulation are closely represented in the model. A is now equivalent to the capillary area of the head, B to the splanchnic area of capillar'es. When the model is placed in the vertical position with the puni]) 194 Fig. 99. — Artifi- cial Schema to SHOW Effect of Gravity on the Circulation. THE EFFECT OF CHANGE OF POSTURE 195- at work, owing to the great disteusibility of the splanchnic capillaries, and veins {B), the fluid will collect in B, and A will cnipt}-. But it B is compressed by the hand so as to raise the fluid in the vein u]> to the pump, then the circulation Avill recommence. The blood, owing to its weight, continually presses downwards, and under the influence of gravity would sink if the veins and capil- laries of the lower parts were sufficientlj' extensile to contain it. Such is actually' the case in the snake or eel, for the heart empties so soon as one of these animals is immobilized in the vertical posture. This does not occur in an eel or snake immersed in water, for the hydro- static pressure of the column of water outside balances that of the blood within. During the evolution of man there have been developed special mechanisms bj' Avhicli the determination of the blood to the lower parts is prevented, and the assumption of the erect posture rendered j)ossible. The pericardium, by its attachments, prevents displacement of the heart as a whole, and also supports the right heart Avhen the weight of a long column of venous blood suddenly bears upon it — as, for example, when a man stands on his head. The ab- dominal viscera are slung upwards to the spine; below they are sup- ported bj'' the pelvic basin and the wall of the abdomen, the muscles of which are arranged so as to act as a natural waistband. If tame hutch rabbits, with large patulous abdomens, be suspended and immobilized in the erect posture, death may result in from fifteen to thirty minutes, for the circulation through the brain ceases and the heart soon becomes emptied of blood. If, however, the capacious veins of the abdomen l^e confined by an abdominal bandage, no such result occurs. In a man 6 feet high the hydrostatic pressure of a column of blood reaching from the vertex of the head to the sole of the foot is equal to 140 mm. Hg. But man is naturally provided v\'ith an efficient- abdominal belt, although this is often weakened by neglect of exercise and by gross indolent living. The splanchnic arterioles are maintained in tonic contraction by the vaso-motor centre, and thus the floAv of blood to the abdominal viscera is confined within due limits. The veins of the limbs are broken into short segments by valves, and these support the weight of the blood in the erect posture. The brain is confined M'ithin the rigkl wall of the skull, and by this wall are the cerebral vessels supported and confined when the pressure is increased by the head-down posture. Every contraction of the skeletal muscles compresses the veins of the body and limbs, for these are confined beneath the taut and elastic skin. The pressure •of the body agamst external objects has a like result. Guided by the valves of the veins, the blood is b}^ such means continually driven upwards into the vense cava?. If the reader hangs one arm motionless until the veins at the back of the hand become congested, and then either elevates the limb or forcibly clenches the fist, he will recognize the enormous influence which muscular exercise and continual change of posture has on the return of blood to the heart. It becomes weari- some and i^oon impossible for a man to stand motionless. When a J9() A TEXTBOOK OF PHVS10L0(JY man is crucified — that is to say. iiiiinobiii/.ed in the erect posture — the blood slowly sinks to the most dependent parts, oedema and thirst result, and finally death from cerebral anaemia ensues. In man, standing erect, the heart is situated above its chief reservoir— the abdominal veins. The blood is raised by the action of the respiratory movements, which act both as a suction and as a force pump; for the blood is not only aspirated into the right ventricle by the expansion Fig. 100. — To show Effect of Gravity upon the Circulation : Carotid and Superior Vena Cava Pressures of Dog. (L. H.) FD, Animal turned into feet-down position with cannulse in axis of rotation. The arterial pressure fell in fifty minutes from 110 mm. Hg to 42 mm. Hg. From C to EX animal was immersed in a bath which was deepened to chin at D. Note increased effect of respiration on venous pressure after FD, and again after bath. Note also fall of pressures at FD. and compensatory rise of arterial pressure, which gradually weakens. of the thoracic cavity, but is expressed from the abdomen by the descent of the diaphragm. When a man faints from fear, his miiscular system is relaxed and respiration inhibited. The blood, in conse- quence, sinks into the abdomen, the face blanches, and the heart fails to fill. He is resuscitated either by compression of the abdomen or by being placed in a head-down posture. To prevent faintness and drive the blood-stream to his brain and muscles, a soldier tightens THE EFFECT OF CHANGE OF POSTURE 197 his belt before entering into action. Similarly, men and women with lax abdominal wall and toneless muscles take refuge in the wearing of abdominal belts. To maintain a vigorous circulation and digestion, it is necessary to exercise the muscles daily, particularly those of the abdomen. . The question may be studied experimentally by passing cannuls& •down the external jugular vein and carotid artery into respectively the superior vena cava and aorta of a dog, ana?sthetized, and placed upon a specially constructed animal table, which is made to tm-n romid an axis j^assing through the body at the level of the cannulas. Upon turning the table, any alteration in the level of fluid in the manometer tubing is thus avoided. The effect of changes of posture are then truly recorded. On placing the animal in the feet-down posture, the arterial and venous j^ressures immediately fall. The venous pressure remains down luitil the horizontal posture is once more assumed. The arterial pressure raj^idly rises again to normal Fig. 101. — Aortic Press-re. (L. H.) A, Vertical feet-down position ; B, C, effect of abdominal compression; D, hDrizontal position. {FD: Fig. 100), and often it may be found to rise above normal. The respiratory undulations are frequently intensified while the animal is in the feet -down posture. If left long in the feet-down position, the compensatory mechanism graduallv fails and the arterial pres- sure falls (Fig. 100). If the spinal cord be divided at the level of the first dorsal vertebra, the infiuence of the bidbar centres on the parts below the section is removed. Abdominal and intercostal respiration is paralyzed, and the breathing becomes purely diaphragmatic. The tone of the great splanchnic area of arterioles is lost, the tone of the abdominal A\all is abolished, and thus the capacity of the abdominal vessels is greatly increased. The. total effect on the animal, when lying in the horizontal posture, is a considerable fall of arterial pressiu-e, and a marked diminution of the respiratory undulations of pressure. If the animal be now droiDjied into the vertical feet-down posture, the arterial pressure falls rapidh^ and may reach zero; the circidation is then at an end. This is so because the great abdominal veins sag •out midcr the hj'^drostatic pressure. In them the whole of the blood 1U8 A TEXTBOOK OF PHYSIOLOGY collects, for it can ])ass rapidly through the dilated arteiioles; there is no mechanism left for filling the heart. Thus the heart, empty of blood, continues to beat to no purpose. If the abdommal wall be compressed with the hand (B, (\ Fig. lOl). the capacity of the veins and si)lanchnic area is reduced, the right heart is once more filled with blood, the arterial pressure rises, and the circulation is renewed. On taking off the hand, the heart once more empties, the arterial pressure falls, and the circulation ceases. When the animal is returned to the horizontal position, the influence of gravity is abolished, and the circulation immediately becomes re-established. The effect of compression of the abdomen in the horizontal position is also evident (/?, C, Fig. 102) but slight. In the feet-up position the aortic pressure rises under the influence of gravity, returning to normal if compensation takes place or when the horizontal posi- tion is resumed (Fig. 102). Such experiments prove that in the anaesthetized animal there are two chief compensatory mechanisms by which the hydrostatic effect of gravity is overcome — namely, the vaso-motor mechanism of the arterioles and the respiratory ];ump. Fig. 102. — Aortic Pbessuee. (L. H.) A, Horizontal position; B, C, abdomen compressed; D. vertical fect-iip position; £", i^, abdomen compressed; G, horizontal. It is necessary to examine these separately, and estimate the relative power of each. The vaso-motor tone of the great splanchnic area can be easily abolished, without affection of the respiratory mechanism, by section of the sjilanchnic nerves — that is to say, if these nerves are reached by a lumbar incision, and all interference with the thorax or abdominal wall is avoided. As the result of section of the splanchnic nerves in the vertical feet- down posture, the arterial pressure falls very considerably; but, nevertheless, the circulation may remain efficient, on account of the action of the respiratory pump. A form of respiration may be evoked whicli consists of thoracic inspiratory aspirations, combined with powerful abdominal compressions. Thereby the diastolic filling of the heart is maintained, and the velocity of flow through the splanchnic capillaries checked. On dividing the abdominal wall by a crucial incision, the support of the abdominal muscles is withdrawn, the splanchnic vessels dilate, and the pressure falls to a further extent. Finally, on suddenly opening the thorax, the j)ressure falls to zero,. THE EFFECT OF CHANGE OF POSTURE 199 and the circulation ceases (Fig. 103). By compression of the abdomen, or by a return to the horizontal posture, the circulation can be onoe more renewed. This experiment shows that the respiratory pump can compensate for the influence of gravity when the vaso-motor mechanism is paralyzed. The respiratory pump can be paralyzed by itself and without damage to the vaso-motor meohan'sm by the inject'on of curari. The power of the heart miy then be sufficient by itself to maintain the circulation in the feet-down position, so long as the capacity of the abdominal vessels is kept under control bj' the vaso- motor nerves. The effect on the circulation of rendering the intrathoracic pressure Fig. 103. — Aortic Pressuee : Morphixized Dog. (L. H.) .4, Vertical feet -duwn position, .>planchnic nerves divided ; B, effect of compressing abdomen ; C, abdominal wall divided ; D, thorax opened. positive — e.g., by compression of the thorax — is that the blood stag- nates in the abdomen, and the circulation ceases, whenever, by any means, the thoracic pressure is rendered sufficiently positive to over- come the venous pressure produced by the driving power of the heart and the compressive action of the abdominal wall. Owing to the influence of gravity, this state of affairs is brought about more easily in the vertical feet-down position than in the horizontal posture. Compensation for the positive intrathoracic pressure is supplied by firm compression of the abdomen: the heart then fills, and the arterial pressure regains its normal level. Measurements of arterial pressure likewise reveal the effect of gravity upon the circulation in man. In a normal man standing up- 200 A TEXTBOOK OF PHYSlOLOdY right the pressure in the post-tibial artery in the leg is higher than the pressure in the brachial artery by the height of the column of blood which reaches from one artery to the other, about 70 mm. Hg. In the horizontal posture the ])ressures are the same. With the body in an L-^haped ])osition, or in the head-down posture, there is also a difTercnce in jiressure between arm and leg. These differences are well exemplified in the following figures. It will be noticed that it is the leg pressure which alters, not the brachial to any great extent: Posture. Horizontal .Standing L-posture, legs up Vertical, head down Brachial Artery, Pressure in Mm. Hg. 106 110 115 115 Posterior Tibial A rtery. Pressure in Mm. Hg. 106 165 85 50 Difference in Mm. Hg. 30 65 Difference calculated Height of Colnmti, JromHeig/it of Column separating Armlets, in Mm. Hg. in Cm. 0 0 58 75-4 .S3 44 63 82 In changes of posture, then, the pressure in the brachial artery — that is, in the root of the aorta — is maintained at practically a con- stant height by the tone of the splanchnic arterioles and action of the respiratory pump. If the splanchnic arterioles are in an efficient state of tone, and if the abdominal veins are supported by the tone of the abdominal wall, then the splanchnic vessels will not dilate under the hydrostatic stress of gravity. The nervous mechanism involved is probably of the simplest nature, for if the arterial pressure sud- denly rise or fall at the moment of change in posture, the bulbar centres are thereby either directly or reflexly excited to increased or decreased activit3^ A sudden fall of arterial pressure provokes acceleration of the heart, amplified respiration, and increased vaso- constriction. A sudden rise of pressure, on the other hand, provokes a slow heart, shallow respiration, and vaso -dilatation. When the compensatory mechanism is abolished by destruction, exhaustion, or inhibition of the bulbar centres, the circulation fails, and becomes inadequate to maintain life in the vertical feet-down posture. The blood passes into the capacious reservoirs of the tone- less abdominal veins, the heart empties, and the cerebral circulation ceases. There can be no doubt that the control of this compensatory mechanism is one of the most important and necessary functions of the group of bulbar centres — a function which must have been evolved to its highest point as man in his evolution assumed the erect posture. During the course of each daj' the compensatory mechanism becomes exhausted ; especially is this so after severe muscular exertion. By sleep the compensatory power is restored. In condi- tions of neurasthenia, weakness and exhaustion after disease, shock after severe injury or haemorrhage, this i)ower may be almost entirely lost. In this connection we must bear in mind the supply of ad- THE EFFECT OF CHANGE OF POSrURE 201 Fig. 104. — The Effect t>F Aujiini.stkatiun ijf Chlukofurm upon the Heart Volume (Cardiometer) and Arterial Pressure of a Decerebrate Dog : Time in Seconds. (Dixon.) 3 to 4 per cent. Chloroform administered during period A. Systole (downstroke) becomes progressively weaker and cardiac tonus is diminished, so that the heart becomes distended with blood, only a small proportion of which is expelled during systole. The fall in blood-pressure is due to this effect; as the cardiac systole improves the blood-pressure rises. Fig. IOo. — Sa.me as Fig. 104, but nearly Pure Ether administered. (Dixon. The systolic contractions are weakened, but the effect is less serious than with chloro- form, and the fall in blood -pressure less. 202 A TEXTBOOK OF PHYSIOLOGY renalin furnished by the a(h-eiial «i;laiMls. Ath-enah'n maintains the tone of the syni))athetic S3'stem. By su(I(l(ui fright in the standing posture the respiration is often arrested, th(; vaso-motor tone inhibited, and syncope induced by the blood sinking into the abdomen. Recovery from syncope is brought al:out by the assumption of the horizontal position or compression of the belly. When the compensatory mechanism is entirely lost, the circulation is only possible in the recumbent position, and life is at its lowest ebb. Among the anaesthetics in common use, chlorofoj-ni stands jDrepotent as a drug which has the power to abolish the com- pensatory mechanism. Chloroform causes cardiac dilatation (Fig. 104), weakens the respiration, and makes flaccid the abdominal muscles. The effects of ether are not so serious (Fig. 105). A useful clinical guide to the condition of the compensatory mechanism in man is afforded not only by the pressure in the brachigl artery, but by the rate of the pulse on change of posture. If the heart greatly accelerates on rising from the horizontal to the vertical position, the mechanism is deficient. CHAPTER XXiri THE VELOCITY OF BLOOD-FLOW The velocit^'of the blood at an}' point in a vessel may be defined as the length of the column of blood flowing by that point in a second. In the case of a tube siipplied by a constant head of pressure, we can divide the tube and measure the outflow per second: knowing the volume of this, and the cross area of the artery, v.'e can determine the length of the column. This kind of experiment cannot be done ■ >n the living animal, because the opening of the vessel alters the resistance to flow, and the loss of blood also changes the physiological conditions. To determine the velo- city, other means must be devised. One form of instrument is called the " stromuhr " (stream-clock), (Fig. 106) consisting of two bulbs mounted on a rotating platform pierced with two holes. One bulb is tilled with oil, the other with blood. The bulbs are connected together by a tube at their upper end, and the lower end of the one full of oil is brought over one hole in the rotating platform. The central end of the arter}' is connected to the same hole and the peripheral end to the other, over which stands the bulb full of blood. The blood, being allowed to flow, displaces the oil out of the one bull) into the other. Directly this happens, the bulbs are rotated, and the one full of oil is again brought over the central end of the artery. The number of rotations per minute is counted, and the volume of the bulb being known, we obtain the volume of blood that passes through the instrument per minute. An improved form of the instrument is seen in Fig. 107. In using this instrument, the tube {y^) is placed in connection with the central end, and the tube (^/.,) in connection with th& 203 Fig. 106. — Thk Stromuhr. 204 A TEXTBOOK OF PHYSIOLOGY peripheral cud of the artery which is under investigation. The whole instrument is washed out with oil to prevent clotting, and filled with defibrinated blood. 80 soon as the blood is allowed to flow from the artery, the metal ball {b) is driven over by the current till it reaches the end of the cylinder (a). The instrument is then rapidly rotated Fig. 107. — Stromuhr. (Tigcrstedt.) on the drum (k), so that the position of the entering and exit tubes is le versed. The metal ball is now once more driven by the current to the opposite end of the cylinder. This jDrocedure is repeated several times, and the number of revolutions during the period of observation is noted. The capacity of the cylinder Fig. 108. — ChAUVEAU's H.^MODliuMUilETER. (a), minus the volume of the ball (6), multiplied by the number'of Tevolutions, gives the volume of blood which has passed during the period of observation ; and this volume, divided by the time and the sectional area of the artery, gives the mean velocity per second. In using the stromuhr, the mean velocity in an artery is found to vary greatly. This, for the most part, is owin^ to the variations of resist- THE VELOCITY OF BLOOD-FLOW 205 ance in the peripheral arterioles. During the operative procedure,, the blood-How must for a time be cut off, and this causes a temporary parah'sis of the arterioles, which, passing off as the circulation is restored, causes variations in resistance. In another instrument, the hsemodromometer (Fig. 108), a T-tube is inserted into the artery, in which hangs a small pendulum, the stem, of the pendulum pasing through a rubber dam, which closes the vertical limb of the tube. The pendulum is deflected b}^ the How, and the greater the velocity, the greater the deflection. The deflection can be recorded by connecting the free end of the pendulum to a tambour arrangement. By this instrument the variations of velocity during systole and diastole of the heart can be recorded and measured, biit it can only be used in the vessels of large animals. If in a schema similar to that given in Fig. 85 two |i— - shaped tubes, a and b (Pitot's tubes), be inserted, one with the elbow opposing the stream, the other with the elbow in the direction of the stream, the fluid will rise higher in a than in an ordinary side tube, and lower than this in b. This is because the flowing stream exerts a push on a and a pull on b. The amount of this push and pull varies with the velocity of the stream, so that from the difference in the height of the two tubes the velocity can be calculated. In an instrument known as the photohaematochometer (Fig. 109) the difference in height is recorded by photography. The velocity may also be calcidated b}' the electrical method, estimating the time taken for the blood to pass between two points of an artery when salt solution is injected into the circulation (see Circulation-time, j^. 209). In man, the quantity of blood which passes through the hand or foot has been measured by plethysmographic Fig. 109. — means (Fig. 110) and also deduced from the quantity pnOTo'^ri of heat which the part gives off to a water calorimeter matocho- in which it is immersed. The flow in grammes meter. XT 1 per minute is obtained from the formula, Q= - ,^~^, ' where Q m(I-i^) s is the quantity of blood, H the number of small calories given off in tn miniates, T the temperature of the blood entering the hand, T^ that of the blood leaving the hand, and s the specific heat of the blood (0-9°). T may be taken as 0-5° lower than the rectal temperature, and T^ the same as that of the tepid water in the calorimeter. The general relations of the velocity of the blood in the arteries, capillaries, and veins, is expressed bj' the curv^e shown in Fig. 111. The velocity in the large arteries may reach 500 millimetres per second in s^^stole, and fall to 150 millimetres in diastole. The smaller the artery the less is this difference, and the more uniform the rate of flow. The velocity and pressure of the blood in the aorta are dependent 200 A TEXTBOOK OF PHYSIOLOGY u])()n the energy of the heart and ii])on the ])eri|)h by that in the systemic circuit. In animals of the same species 14 210 A TEXTBOOK OF PHYSIOLOGY the circulation time increases rather in proportion with the surface- than the Aveight. That some of the blood takes a very long time to return to the heart is shown by the long time it takes to wash the vascular system free of blood by the injection of salt solution. The circulation -time is shortest for the heart and the retina. The circnilation-time for the stomach is relatively short — equal generally to about that of the lungs. It is relativeh" long in the kidney, spleen, and liver, being much more variable in these organs than it is in the lungs, more easily affected by changes of external temperature — diminished by warmth, increased by cold. Circulation Tevies. Doo- Time Weight. in Seconds. 2-0 kilos 4-05 (pulmonary) 11-8 „ 8-70 18-2 ., . . 10-40 13-3 „ 8-40 13-3 „ 10-95 (spleen) 13-3 , 1.3-30 (kidney) CHAPTER XXIV THE PULSE By the expulsion of the blood at each systole the walls of the aorta are suddenly distended. From the aorta a wave of distension passes down the walls of the arteries. This wave of distension is called the " pulse." As the pulse is distributed over an ever -widening field its energy is expended in dilating the elastic arteries, and disappears tinally in the arterioles. From a wounded artery the blood spurts in pulses, from a wounded vein it flows continuously. By Fig. 113. — The SrsPE>fsiON Method of using the Dudgeon Sphygmogeaph, (Lewis.) feeling two pulses, or, better, by placing tambours on, say, Uie carotid and radial arteries, and recording the two pulses synchro- nously, it has been found that the pulse occurs later the farther the seat of observation is away from the heart. The velocity with which the pulse-wave travels dowii the arteries has been determined thus. It is about 7 to 8 metres per second — twenty to thirty times as fast as the blood flow. The wave-length of the pulse is obtained by multiplying the duration of the inflow of blood into the aorta by the velocity of the pulse-wave. It is about 3 metres. ^ 211 212 A TEXTBOOK OF PHYSIOLOGY The examination of the ])nlsc is of great importance to the physician. It yields him information as to the state of the heart, the static of the arteries, the amount and variations of the arterial pressnre. The pulse may be investigated either directly by the finger or, by the aid of instruments known as sphygmographs (Fig. 113). The pulse is generally felt in the radial at the wrist. i)r(iferably on both sides. With the linger the jjoints noted may be grouped into (a) those which give information concerning the heart — e.g., the frequency, generally seventy to seventy-five per minute in man, regularity or irregularity, equality or inequality of the beats; (6) those which yield knowledge Fig. 114. — Mackukzie's PoLYCUAru. The parts of the polygraph may be described as follows: The body A, containing the paper-rolling and time-marker movements; the writing tambours BB, with supporting tjar, Bl ; wrist tambour, C, with attachment, CI, for strapping on to wrist; paper roll bracket, D; paper roll, Dl ; cup receiver, E; pens, FFF. about the vessel — e.g., its size and the' condition of its wall; (c) those which yield combined information of the two — the volume, force, and tension of the pulse. B}' volume is meant the amovnit of movement in the pulse during the passage of the pulse-wave; by force is understood the maximum pressure as felt by the finger in the vessel during the beat; by tension the pressure between the beats. These last data can only be accurately measined by means of the sphygmometers already described, for the finger begins to flatten the artery and stop the passage of the pulse-wave when exerting a pressure much less than that within the artery. In a normal healthy pulse the beats are regular and of equal strength. The vessel is soft and pliant, not tortuous, rigid, or thick- ened. The force and tension are moderate — that is, they are best felt when a moderate degree of pressure is applied. THE PULSE 213 For recording the j^ulse, an instrument such as that shown in Fig. 113 may be used. The disadvantages are that the tracings are but of short length and that in the ordinary form, which is strapped round the wTist, the pulse tracing is modified by the effect of pressure upon the venae comites of the army. For this reason it is better to employ the suspension method illustrated in the figure, in which the pressure of the lever is exerted directly over the radial artery. Of greater service is the instrument knowai as the polygraph (Fig. 114). With this mstrument it is possible to take two tracings at the same time, and that of a time-marker. The usual combina- tion is a tracing of the radial and venous pulses. Fig. 115. — Diagram showing the Average Position of the Jugular Bulb. (Keith.) a. The jugular point, 25 nun. from the sternal end of the clavicle (c); h, jugular bulb, behind sternal head of sterno -mastoid and in front of first stage of subclavian artery ; rf, subclavian vein ; e, sternal head of sterno-mastoid ;/, superior vena cava ; (J, manubrium sterni . Such simultaneous graphic curves are valuable, since they record information of the time relations and the nature of the contraction of the separate heart chambers. The Venous Pulse in man is best recorded by applying a small metal receiver (3-4 centimetres diameter, 1 centimetre deep) between the two heads of origin of the relaxed sterno-mastoid muscle (Fig. 115), and transmitting the pulsations by air to a delicate recording tambour. By this means a tracing of the Jugular bulb is obtained, where it lies a little above, and about 25 millimetres external to, the inner end of the clavicle. The bulb is so called because in the internal jugular vein at this point is a pair of valves, and here a bulging of the vessel takes place in cases of impeded flow to, or of regurgitation from, the auricles. The venous pulse shows three main elevations (o. c, v). The exact interpretation of some of these factors is still a matter of doubt. 214 A TEXTBOOK OF PHYSIOL()(.Y The a wave is due to the contraction of the right auricle. It disappears Avhen this chamber is not beatmg. and is sometimes re- placed by a series of oscillations when the auricle is fibrillating. Its exact mode of origin and propagation is not known, but it is certainly synchronous with, and an indication of, auricular contraction. Comparison of the records in Fig. 1 10 shows that p precedes a. Allow- ance must be made for time of propagation. The c wave owes its origin to the ventricular systole, since it dis- appears when the ventricle ceases to beat. It has been supposed to be due to the pulsation of the neighbouring artery, and in many instances this is undoubtedly the case; but it occurs also in curves taken when the arterial influence has been removed, and also iw the curves of interauricular pressure. It is possibly due to the bulging I I 1 I Fig. 116. — Simultaneotts Records showing the Time Relations of Waves of Jugular Pulse and Electrocardiogram. (AV. T. Ritchie, from Cowan's " Diseases of the Heart." ) P Precedes a, B precedes c. into the auricle of the closed tricuspid valve at the onset of ventricular systole. The mode of origin is under discussion — both factors may con- tribute— \\h\\e for clinical purposes it may be reckoned as synchronous with the primary wave of the arterial jiulse in the neck. In Fig. 116 it is seen that the wave R of the electrocardiogram precedes the wave c. Various divergent views are held about the origin of the v wave. The two views generally held are — (1) that it is due to the filling of the auricles during ventricular sj-stole; (2) that it is due to the move- ment of the auriculo-ventricular groove at the beginning of diastole (Fig. off) Probably both factors contribute. The depressions on either side of the c wave, sometimes called X and x', are really one depression broken by the c wave. They are probably due to (1) the auricular relaxation dependent upon the inspirator}^ diminution of intrapleural pressure; (2) the expansion of the auricular walls which results from ventricular systole, by the de- pression of the diaphragm formed at the floor of the auricle by the closed auriculo-ventricular valves. The first factor is active only during inspiration. THE PULSE 215 The depression after v, sometimes termed the // dcpre^r-ioii, is usually attribiited to the opening of the A.-V. valves, and the passage of blood from auricles to ventricles at the beginning of .•.■mmon diastole. The Arterial Pulse Curve.— In the arterial record, or sphygmograph, the upstrol^e corresponds to the systolic output of the left ventricle, marking the openhig of the aortic valves and the pouring of the blood into the arteries. The downstroke represents the time during which the valves are shut and the blood is flowing out of the arteries into the capillaries. There are subsi- diary waves on the downstroke. The chief of these is called the " dicrotic wave," the notch preceding which marks the closure of the semilunar valves (c, Fig. 117). The dicrotic notch is caused by the swing back of the blood towards the heart when the outflow ceases, and the elastic rebound of the blood from the closed semilunar valves and root of the aorta causes the dicrotic wave. If the aortic valves move back 1 centimetre and the diameter of the orifice of the aorta is 2-6 centimetres, then 1-8 centimetres of blood move back towards the heart. It is most manifest when the systole is short and sharp, and the output of l)lood from the arterioles rapid; in other words, when the heart- beat is strong, the systolic pressure high, and the diastolic pressure low. Its central origin is proved b}' the fact that it appears in the carotid or brachial at the same interval of time after the primary wave as in the radial artery. A smaller wave, predicrotic, ])receding this occxu's during the period of output. and sometimes is placed on the ascend- ing limb of the pulse-curve. This occurs when the peripheral resistance is great, and the pulse is then termed anacrotic. It usually occurs when the outflow from the heart is impeded — as, for example, by stenosis of the aortic valves. By compression of the abdominal aorta the carotid pulse can easily be made to exhibit an anacrotic wave. The post-dicrotic waves are due to secondary elastic swings of i:he big arteries followins the dicrotic swinsf. The form of these waves ;ij ^ 21G A TEX'rP>()()K OF PHYSIOLOGY is modified !)>>■ the prestsure of ap])lication of the sphygmograph and by instrumental errors. The pulse may be recorded by allowing an artery to spurt upon a moving paper (Fig. 118). As already said, the pulse wave occurs later, the farther the place of observation is from the heart. This is well seen in Fig. 119. We have no scale by which we can measure the blood-pressure in sphygmograph tracings. When the arterioles are dilated, or Avhen the capillaries are only filled at each systole, the pulse may pass through the arterioles and reach the capillaries, as may be seen in the pink of the nail when the arm is held above the head in cases of aortio regurgitation. IB The normal average pulse-rate is ijB 72 per minute, in woman about 80. Tall men usually have a slower rate than MB^ short men. Individual variations from I W 40 to 100 have been observed consistent ^ * ' with health. Napoleon, a short man, had a pulse-rate of 40. In the new-born, the pulse beats on the average 130 to- 140 times a minute ; in a one-year-old child, 120 to 130; three years, 110; ten years, 90; fifteen years, 80 to 85. Active muscular exercise may increase the pulse- rate to 130. Nervous excitement, extreme debility, and rise of body temperature, also increase it markedly. The pulse is^ more frequent when one stands than when one sits or lies down. In 100 young men of twenty-seven years the average was : 78-9 standing, 70-1 sitting, 66-6 lying. In states of debility this difference be- tween horizontal and erect postures may increase to 30 to 50 per minute. The taking of food, especially hot food, increases the frequency; so does smoking cigarettes. The average pulse-rates for different ages is given in the following; table • Fig. 118.— HiEMAUTOGEAM. (Landois and Stirling.) Age, in Years. Foetus 0-1 1-12 3-4 5-9 9-10 12-13 16-17 19-20 ilea Women Pulse-Bate, per Minute. 135-140 134 117 108 98 91 88 80 72 80 THE PULSE 217 At the third month the infant's pulse may be faster than at birth, owing to the increase of muscular activity. Large animals have a slower rate than small. The elephant. has a frequency of 25 to 30, the ox 36 to 40, the sheep 60 to 80, the dog Femoral Radial Foot (plctliysm.) Time in i„ second Fig. ll!>.— The Pulse Wave ix the Arterial SYSXEii, (Waller.) 100 to 120. the rabbit about 150, small birds and mice over 600. Li the last the rate is recorded by means of the electrical variation of the heart. CHAPTER XXV THE CAPILLARY CIRCULATION The blood is brought into contact with tlie tissues through the? endothelial wall of the capillaries; this is therefore of the greatest- tenuity. Here takes place that exchange of material which maintains the combustion of the body — the lire of life. The aim of the circu- lation is attained when the arterialized blood laden with food material and oxygen is driven into the capillaries of the bod}'. In size, the capillaries vary in different organs. In the biain the length has been estimated to be 0-7(J9 millimetre (pons) and 042 milli- metre (optic thalanuis); in the mucosa of the stomach 0-6 millimetre; and in the liver 0-5 to 1 -1 millimetres. The diameter of the capillaries varies from (j-007 to 0-013 millimetre. Malpighi (1661) first observed the capillary circulation under the microscoj^e. He examined the lung, the mesentery, and bladder of the frog. It has since been seen in many other transparent or translucent parts of animals. The Microscopical Examination of the Circulation. — By usi)ig a low power it is possible to examine simultaneously arteries, capillaries, and veins in the same tield. The first thing which strikes the obserxer is the different direction of the stream in the arteries and in the veins. On account of the reticular arrangement of the capillaries, the direc- tion of the stream through them is by no means constant. There may l)e a complete cessation of the flow for a period in a capillary channel, or the direction of the current may even be reversed for a longer or shorter time. The flow through the arteries is by far the most rapid. In the veins, also, the stream is so rapid that it is diffi- cult to catch the contour of the corpuscles. The stream is slower in the small veins, and in the capillaries the movement is, as a rule, so tardy that the individual corpuscles can be determined without any difiicultv'. The inconstancy of the caj)illary stream is generally ap- parent. If a group of capillaries be kept for some time under observa- tion, the blood is occasionally seen to hurry suddenly through a number of these with increased rapidity. This continues for a while, aiid then the stream becomes again sloAver and slower, till after an interval it resumes the quiet rate of flow which has been maintained A^ithout interruption in the neighbouring capillaries. These variations depend on alterations in the lumen of the afferent arteries. The arterial stream is pulsative, and each systole may be recognized even in very small arteries by the rhythmical acceleration and re- 218 THE CAPILLARY CIRCULATION 219 tardation of the blood-stream. Such a rhythmical movement is absent from the capillaries and veins in a normal condition; the stream is continuous in both. In the arteries the core of red corpuscles does not completely fill the lumen, but moves along the axis of the stream. To the outside there lies a clear layer of plasma, in which, when the stream moves slowly, white corpuscles roll. In the veins there is also a similar peripheral plasmatic layer, in which the white corpuscles roll slowlj- along, sticking noAV and again to the wall of the vessels in their course. In the smallest cai^illaries the plasma layer cannot be distinguished, the red corpuscles march in single file, and often become distorted and bent as they pass. These capillaries are invisible to the eye so soon as corpuscles cease to pass tlu^ough them. Thus, in the course of an observation, capillaries may be seen to appear and vanish from view. In the angles of the capillary network, red corpuscles may be seen to stick and hang in the balance, bent round the angle, half in one branch and half in another, until finally swept on into the rush and hurry of the stream. The white corpuscles progress with a sIom" rolling motion in the plasmatic layer. The axial stream travels with the greatest velocity, and thus the side of the leucocyte which lies at any moment nearer the axis is driven on with the greater speed; hence the rolling move- ment. The white corpuscles travel in the peripheral layer, the red in the axial layer, for the latter are the heavier. It is not, as has been supposed, that the white are lighter and the red corpuscles heavier than the plasma. Both forms are of a higher density than the plasma. If particles of graphite and carmine be circulated through glass capillaries, the lighter carmine particles travel in the peripheral layer. When resin is substituted for graphite, the carmine travels in the axis. If pus corpuscles and milk globules are circulated, the cor- puscles occupy the axial stream. If the resistance in the arterioles be lowered to a certain point, the capillar}^ circulation remains no longer pulseless. Tiius, when the chorda tympani nerve is stimulated, the blood may issue in pulses from the vein of the submaxillary gland. By plunging the hand in very hot water, the pulse may be seen to reach even the turgid veins on the back of the hand. In ca.ses of aortic insufficiency, a capillar}^ pulse is readily obtained in any area of congestion which is produced by scratching the skin. The effect of vaso-dilatation can be observed under the microscope — e.g., in the tongue of a curarized frog. On bnishing the tongue an appearance of intense redness shows that arterial congestion has set in. All the vessels, arteries, capillaries, and veins, are wide and strongly distended with blood. Innumerable capillaries are perceptible at a glance, where previous^ a few red-coloured threads were toil- somely sought for ; and in all these vessels, small and large, the blood rushes on with the greatest rapidity — so rapidty that even in the capillaries the ej-e in vain strives to catch the outline of a single corpuscle. 220 A TEXTBOOK OF PHYSIOLOGY By the application of a piece of ice- to the tongue of a frog, vaso- dilatation can be converted into constriction. The arteries become narrow, the tongue pale. The eye has difficulty in finding any except the larger vessels. Few capillaries ap])ear to contain blood, and where a considerable quantity of blood is still present, as in the arteries and veins, the flow is tardy, and even in the arteries the individual corpuscles can now generally be recognized. In a warm-blooded animal, the results of exjiosure to an irritant are much more rapidly established. After exposure of a rabbit's ear to water at 55^ 0., the blood is altogether unable to penetrate the arteries. A change has taken jilace in the relations between the blood and the vessel wall as regards friction and adhesiveness, and thus complete stasis of the circulation arises. If the change be less intense, the porosity of the vessel is affected, and a quantitative and qualitative change in the transudation from the capillaries ensues. The rabbit's ear may be entirely separated from the body, with excep- tion of the central artery and vein. After section of all the vaso- motor nerves by this means, vascular dilatation is greatly increased by rubbing the ear, and all the phenomena of inflammation occur after the application of an irritant. We have here to deal, not with a nervous mechanism, but with a change of the vessel wall. The circu- lation through the capillaries is possible only so long as the vessel wall is in the normal physico-chemical condition which characterizes the living state. The corpuscles continue to move through the capillaries for some seconds, or even minutes in a few of the capillaries, after the bulbus arteriosus has been ligated ; they run faster on pressing or moving the leg. Observations of this kind show how immeasurably slight a difference of pressure is required to produce a flow in the capillaries. On clenching the fist the cajjillaries of the hand blanch. By the ceaseless muscular movements and changes of posture of the living mobile animal the capillary pressure is kept in the skin approximately the same as the atmosphere, for whenever the blood is thus pressed out of them into the veins the pressure does not become positive in the capillaries till they fill agahi. In the intestinal wall the blood is similarly expressed by the muscular contractions of the gut. In encapsulated organs, such as the glands, on the other hand, the capillary pressure may rise with the secretory pressure up towards the arterial pressure. This is the case in the salivary gland when the secretion is made to take place against pressure. Secreting cells are confined by limiting membranes, membranae proprise, tough and homogeneous, but of great tenuity. These membranes, Avhile allowing the protoplasm of gland cells or muscle plasma to imbibe fluid from the capillaries, limit the expansion produced by intracellular forces. Thus the salivary glands may secrete saliva at a pressure greater than arterial pressure, and the blood continue to flow through the gland. The expansion of the alveoli is limited, so that it narrows and does not shut up the veins (see Fig. llPc). The result is THE CAPILLARY CIRCULATION 221 a rapid tiow of blood through dilated arteries, and almost rigid vessels, arteries, capillaries, and veins, all at the fnll or nearlj'^ full arterial pressure. Similarly, in an inflamed area, by the inhibition of fluid in the damaged tissue cells which are confined by connective tissue, the veins are compressed and narroAved, and the arteries being dilated, the capillary pressure rises, and the whole part throbs Avith the pulse and receives a rapid flow of blood. If the swelling is too great, strangulation of the circulation occurs, and the surgeon's knife is reqviired to relieve tension and promote flow. Rate of Flow. — The velocity of a blood-cor]^uscle in the capillai'ies of a frog's muscle has been reckoned to be 0-28 mm. per second. The method most conveniently used is to employ an ocular micrometer, and follow the course of a corpuscle d\iring a ]^eiiod of time given by a clock beating one-fifth seconds. The velocity has thus been found by various observers to be 0-25 to 0-57 millimetre per second in cold- blooded animals. B}^ the entoj^tic method the velocity in the retinal capillaries has been calculated to be 0-75 millimetre per second. With suitable illumination of the eye the corpuscles are seen by the subject on a ground-glass screen held 11 to 16 centimetres from the eye. A corpuscle can be followed 20 to 30 millimetres on the screen. Knowing the distance of the screen from the anterior nodal point of the eye (A), the distance of the retina from the posterior nodal point (B), and the distance travelled by the corpuscle on the screen (C), the real distance x travelled in a given time can be cal- culated. BC "= A • As the red corpuscles travel in the axial part of the stream, and as the mean velocity in any tube equals one-half the axial velocity, the true mean velocity of flow is less than the above. It can be taken to be about 15 to 3') millim3tre3 per minute, and in the smallest capil- laries, where the flow is often obstructed, it is still less. Since the v'elocity stands in inverse proportion to the sectional area at any point in a system of tubes, the proportional relationship of the total .sectional area of the capillaries to that of the aorta can be reckoned if we know the mean velocity in the capillaries and in the aorta. Thus, if the mean velocity be taken as 500 millimetres per second in the aorta, and 0-5 millimetre par second in the capillaries, the reUtioa is 1 =1,000. In man the sectional area of the aorta is 4-4 square centi- metres. The total sectional area of the capillaries filled with blood at the thw. is thus equal to 4,400 square centimetres. This result is, of course, only'ai)proximate. The Capillary Blood-Pressure. — The measurement of the capillary pressure has been attempted by placing a glass plate 2-5 to 5 square millimetres in size on the skin in a suitable place, such as on the last jomt of the finger. From this glass plate hangs a small scale-pan. 222 A TEXTBOOK OF PHYSIOLOGY On Ihi.s weights are i)lace(l until t\u' pressure is reached at which the skin is blanched and the capillaries comi)ressed. In another inethod a small rubber bag with a hole in the centie is placed on the skin. Both bag and skin are moistened with glycerine, and the whole is covered with a glass plate so held as to make an air- tight junction. By means of a side tube air is then blown into the bag until the skin blanches, the pressure being indicated on a man- ometer. These methotls are inaccurate, for the horny layer of the skin resists the compression. The web or mesentery of a frog, being laitl on a glass jDlate, can be compressed, while under the microscope, by a thin transparent membrane, which forms the base of a glass capsule. The latter is filled with water, and connected with a pressure-bottle and manometer. By this means it was found that pressure of 100 to loO mm. H._,0 is suflficient to stop the circulation in the capillaries and veins of the frogs web; in the arteries 200 to 250 mm. K^O. In periods of a few- minutes the pressure may vary 20 to 30 mm. H^O. On producing vagus inhibition of the heart by striking the abdomen, the pressure sank to 0, and then rose again in the veins to 70 to 100 mm. H.^0, owing to venous congestion. Temporary anaemia of the web caused dilatation of the vessels, and this produced in its turn a higher capillary pressure. Such methods necessitate the fixation of the jjart, and cannot be quickly performed. They obstruct the flow and therefore do not give the capillary pressure laider normal conditions. If the upper arm be constricted, so as to block the venous exits, the pressure in the cutaneous veins of the arms rises fairly rapidly to the static arterial pressure. It takes a long time for the cajiillaries to all become flistended with blood. The veins fill through the wider channels. If we .«queeze the fist luider these conditions, the capillaries are emptied into the veins and momentarily blanched, and we see that it is possible to have then a high pressure in both arteries and veins, and a low pressure in the capillaries. The distension of the capillaries vessels causes aching pain, and this d'scomfort prevents our keeping our limbs motionless in a dependent posture, and causes us to move the parts of the body, to fidget, and so relieve congestion. In the brain, the capillar}' venous pressure can be estimated by finding the tension which is sufficient to just compress the brain as it bulges into the trephine hole. This j^ressure in the horizontal position of the animal is usually about 10 mm. Hg. The capillary pressure varies widely with changes in the general venous and arterial pressures, and with the position of the animal. Thus, iu the brain, the pressure may fall below zero in the vertical feet-down jjosition (the fontanelle of an infant suffering from diarrhoea may become depressed), and rise to almost 50 mm. Hg during the height of strychnine convulsions. The intracranial pressure (cerebro -spinal fluid pressure), and the cerebral venous pressure, are one and the same. So, too, in the eyeball the intra-ocular pressure (aqueous fluid 2:»ressure), and the pressure of the veins within the eyeball, are the THE C.M'ILLAUY CIKCIJLATION 223 cixp Fig. 119a. — Schema of Kidney. Thi' renal L-apsulc (c) encloses the whole, including arteries («), capillaries (cap),^'and veins («), with surrounding Ijniph sj)ace {Is). The menihrana propria (//)/>), confines the secreting cells (.sc). The pelvis [p) and ureter, membrana propria and capsule, are inextensile beyond a certain degree. Fig. 119b. — Schema of Eyeball. The rigid coat (c) confines the whole. The secreting cells (.sc) are set on a membrana propria (w/>), and secrete the aqueous {nq). There is adjustment of capillarv- venous to secreting pressure by latter acting on venous outlet (c). The flow of blood through capillaries icap) stops when aqueovs pressure is raised just about arterial pressure in ya). Fig. 119c. — Schema of Salivary Glaxd. The alveolus, with secreting cells (.sc) and duct, ars surrounded by a membrana propria {mi)), inextensile beyond a certain degree. The capsule of the gland (c) is also inextensile beyond a certain degree. The secretorj- cells (.sc) raise the pressure of saliva, and the membrana propria {mji) prevent strangulation of the circula- tion through capillaries [cap) by limiting the expansion of the alveolus. A certain am.ount of expansion is permitted, which, acting on the vein (v) just before its exit through capsule, raises the capillary-venous pressure. The capillaries and vein- then become a more rigid system of tubes, and the flow of blood from a to v is accelerated. 224 A TEXTBOOK OJ-^ PHYSIOLOGY same. Tissue iluid pressure and capillary pressure constantly balance each other. The capillary pressure stands in far closer relationship to the venous pressure than to the arterial pressure. Between an artery and its capillaries lies the unknown and varying resistance of the arterioles; between the capillaries and veins there is no such resistance. Although often put forward, the view is erroneous, that fluid filters through the cai)illary wall under the influence of the capillary blood -pressure. No measurable difference in pressure normally exists between the capillary pressure and that of the tissue fluids, such as the aqueous or cerebro-spinal fluid. The wet films of the protoplasm which form the walls of capillaries cannot act as rigid sieve-like struc- tures. The tissue cells are bj- their colloidal structure endowed with the power of linking np or setting free the crystalloids l)rought to them in solution. They are the seat of play of complex physical forces, such as imbibition and osmosis, as well as of chemical reaction, selective in character, and dependent on the enzymic contents of the cells. The cells control the passage of fluid in one of the other directions in just the same way as do the unicellular organisms, in which, as regards the secretory processes, there can be no question of filtration. This vicAv is illustrated in Figs 1 KIa, IUIb, llOc Apart from other experiments which tell against the filtration hypothesis, and quoted m their respective sections, there remains the outstanding fact that in the brain and eye, where measure- ments have been made, the capillarj^-venous pressure and the tissue- fluid pressure are not measurably different. Moreover, the membrante propiise are arranged to allow the tissue cells to produce osmotic and secretory pressures, not to support the capillaries as rigid filtering membranes. Leakage occurs when the skin, or capsule fan oi-gan, is wounded, because capillary pressure is then no longer balanced by tissue fluid pressure. The organs rhythmically pulse full Avith systole and shrink with diastole, and the pulse furthers the flow of tissue lymph as well as the circulation. Every muscular movement, by compressive action and the action of valves in veins and lymphatics, aids the circulation. The membranse proprise, by limiting expansion, allow secretory cells to raise the pressure of the tissiie fluid and produce, for example, the intra-ocular pressure. The capillary-venous pressure within the eye- ball adjusts itself to this secretory pressure, for the pressure must just exceed the intra-ocular pressure for the circulation to continue. CHAPTER XXVI THE PRESSURE AND VELOCITY OF THE BLOOD IN THE VEINS The most striking difference between the structure of an artery and its vense comites is a decrease of elastic tissue in the veins, together with an increase of white connective tissue. The veins are tubes with muscular walls, which not only fall together, but contract when empty, and under slight pressure expand to their full capacity. Beyond this point, the walls, on account of the quantity of connective tissue entering into their structm'e can extend but little. The resistance to a breaking-strain on the part of the veins is very great. It requires a higher pressure to rupture a vein than the cor- responding artery. If by external compression the various outlets be blocked, the pressure rises in the vein to the full pressure in the artery. For this reason the veins must be strong enough to bear any such increased strain. There is, however, another need for strength of veins, and that is that they may be able to bear the strain which may arise from external violence. The superficial veins are endowed with more muscular and elastic tissue than those deeper, while those veins which run in the muscles and in the bones, and are protected from violence and supported by firm structures, possess no muscular elements. When exposed, a superficial vein contracts on mechanical stimu- lation and on cooling, while it may be made to dilate on applying warmth. Pressure in the Venous System. — -In the active animal the venous pressure varies according to the hydrostatic pressure of the column of blood above the point of measurement and with the action of the muscles which express the blood onwards towards the heart. In the horizontal position, when these factors are almost elimin- ated, the pressure in the large veins is found to be equal to a few centimetres of blood, or about 5 mm. Hg. When a cannula is pushed down the jugular vein past the valve till its opening lies in the vena cava superior, the lateral pressure of this vein is ob- tained. It may become negative during inspiration. The negative pressure which occurs in the right auricle on each cardiac oscillation is estimated at — 2 to — 3 mm. Hg, and may become — 5 to - 8 mm. Hg during inspiration. In the sheep, with the animal in the horizontal posture and ini- 22") 15 226 A TEXTBOOK OF P>^^^SJ()LOGY mobile, during normal quiet resijiration tlio following venous j^ressures have been found: Mm. llg. Mm. JJg. Left innominate . . — 0-1 External facial . + 3-(» Right jugular .. + 0-2 Rrachial . + 4-1 Right subchivian . . — 0-1 Rranch of the brachial . . + y-o Left jugular . . — 0-1 Crural . + 11-1 Left subclavian . . - 0-G It must be clearly understood that these venous pressures are only true for the animal in the horizontal posture. They vary greatly with the posture and movement of the body. The negative pressure in the central veins is due to the action of the heart and the suction of the thoracic cavity produced by the elastic pull of the lungs. Owing to this negative pressure, when a large vein is opened in the neighbourhood of the thorax, air may be sucked into the circulation. Air that has thus obtained an entry has been observed to pass right through the pulmonary circulation and to enter the arteries. The danger of air thus entering during surgical operations has been recognized. A large amount of air can be slowly injected into a vein without killing an animal. A rapid injection, such as would be caused by blowing air into the venous cannula, kills by causing frothing in the heart and embolism in the lungs and coronary arteries. The danger of embolism from the entry of air is much greater in a small than in a large animal, for the smaller the heart the less the amount of air required to hinder its action by frothing. In man, the venous pressure has been measured by finding the pressure just required to prevent a cutaneous vein refilling after it has been emptied beyond a valve. The armlet, or bag, of the sjihyg- mometer is j^ressed upon a suitable vein, with the limb placed at the heart level, and the vein emptied by stroking the blood on past the next valve. The pressure of the armlet, or bag, is then relaxed till the vein just refills, and the pressure read. On immobilizing the part to take such a measurement, the venous pressure rises; how quickh' depends on the state of dilatation of the arterioles in the limb. It is not possible thus to measure the pres.sure in the normal conditions. Rate of Flow in the Veins. — Turning to the question of the velocity of the venous flow, it is obvious that the average input of the heart must equal the average output per second in- order that the circulation may continue. If the veins that enter the heart were of the same sectional area as the arteries that leave it, then the velocity would be the same in these A^eins as in the arteries. When the vense cavse are filled with blood, the total sectional area is found to be con- siderably greater than that of the aorta. But, as normally these veins are not filled to their capacity, it is probable that the velocity of the flow in them is approximately equal to that of the aorta. The velocities in the carotid artery and the jugular vein, or in the umbilical artery and the vein of sheep's embrA'o, have been measvtred with the stromuhr, and have been found to be almost the same. PRESSURE AXD VELOCITY OF BLOOD I^; VEINS 227 The valves in the veins allow the blood to be forced only towards the heart. The pumping action of walking can be observed on the veins of the back of the foot. After standing still for a time, the veins become prominent. The pressure is considerable, as can be ganged from the feel. After taking a few stej^s, they are emptied, squeezed between the .skin and muscle. Numerous anastomoses exist between the veins, so that, if the floAv^ of blood be obstructed in one direction, it readily finds a passage in another. The venous circulation is imj)eded by (1) a lessening of the heart power; (2) cardiac valvular effects, such as incompetence or narrowing of the valvular orifices; (3) obstruction to the filling of the heart, as in cases of pericardial effusion; (4) obstruction of the pulmonary circulation, as by coughing and by pleuritic effusion. The results of venous congestion are less efficient circulation, a duskj^ appearance of the skin, a fall of cutaneous temperature, and an effusion of the fluid into the tissue .spaces, producing oedema or drop.sy. This last effect is not due, as has been supposed, to increased capillary pres- sure producing increased transudation, for no such increase in venous and capillary pressure is found under the conditions. It is due to the altered nutrition of the tissues, which results from the deficient circulation. The products of katabolism which collect within them increase the osmotic properties of the tissues. If for any reason the left ventricle fail to maintain its full systolic output, it ceases to receive the full auricular input, and in consequence the i3ulmonary vessels congest. This tells back on the right heart, and the right ventricle is unable to emptj^ itself into the congested pulmonary vessels, and this in its turn leads to venous congestion. The final result of any obstruction thus is a pooling of the blood in the venous cistern. D^'spnoea results from cardiac insufficiency. It is excited by the increa.sed venosity of the blood acting on the respira- tory centre. Both the excess of carbon dioxide and deficiency of oxygen increase the acidity of the blood, and this excites the centre. The increased respiratory movements aid the circulation. The vascular system is so constructed that considerable changes of pressure may be brought about on the arterial side without any (or scarcely any) alteration of the pressures in the venous or pulmonary sections of the circulatory system. A high-pressure main (the arteries) runs to all the organs, and this is supplied with taps; for by means of the vaso-motor nerves, which control the diameter of the arterioles, the stream can be turned on here or there and any part flushed A^ith the blood, while the supply to the remaining parts is kept luider control. Normally, the sum of the resistances which at any moment oppose the oiitflow through the capillaries is maintained at the same value, for the vascular S3^stem is so co-ordinated by the nervous system that the dilatation of the arterioles in any one organ is compensated for by constriction in another. Thus the arterial pressure remains con- stant, except at times of great muscular activity. The great splanchnic .system of arterioles acts as " the re^is^ance 228 A TEXTBOOK OF PHYSIOLOGY box " of the arterial system. By the constriction of these arterioles during mental or muscular activity, the blood-current through the abdominal organs is diminished, and increased through the brain and muscles; while by dilatation during rest and digestion the contrary effect is produced. The constriction of the splanchnic vessels does not sensibly diminish the capacity of the total vascular system, for the veins relax. Thus big variations of arterial pressure, brought about by constriction or dilatation of the arterial system, produce little or no effect on the pressure in the great veins or pulmonary circuit. On the other hand, the contraction of the abdominal muscles, as we have seen, intluences the diastolic or filling pressure of the heart. Hsemorrhage and Transfusion. — The circulation may be aided by the transfusion of salt solution (0-8 per cent.) or blood after severe haemorrhage, or in states of surgical shock. Only the blood of man must be used. The direct giving of blood by connecting the radial artery of a relation to the median vein of a patient has been used as a means of effecting restoration. Blood may be withdrawn from the system slowly to the extent of 4 per cent., rapidly to the extent of 2 per cent., of the body weight without lowering the arterial pressure, owing to the compensatory contraction of the anerioles and the rapid absorption from the tissues into the blood. The beneficial effects of the old treatment by bleeding were probably due to this latter effect. The immune properties of the blood may be increased by the passage of tissue juices into it. The withdrawal of the tissue lymph excites extreme thirst and a great need for water after severe haemor- rhage. About 75 per cent, by weight of the tissues, excluding fat and bone, consists of water. The volume of tissue lymj^h is unknown, but it must be considerable — perhaps greater than that of the blood. The lymphatics drain off the excess of fluid which transudes from the capillaries, and finally return it to the vascular system. The interchange between tissue, blood, and lymph, depends upon the forces of the living cells, which are as yet far from complete elucidation. The vascular system confines the red corpuscles to its channels, but cannot be regarded as a closed system ; for the fluid of the blood- plasma transudes through the capillary wall into the tissue spaces, and enters the lymphatics. Thus, if large quantities of Ringer's solution be transfused into the circulatory system, it not only collects in the capacious reservoirs of the veins and capillaries, especially in the lungs, liver, and abdominal organs, but in the tissue spaces. Hence the pressure in the vascular system cannot be raised b}^ the injection of enormous quantities of fluid. If the fluid part of blood be increased, capillary transudation becomes greater, and the excess of fluid is excreted from the kidneys and glands of the alimentary canal. If the fluid part of the blood diminish, then fluid passes from the tissue spaces into the blood, and the sensation of thirst arises, and more drink is taken. CHAPTER XXVII THE VASO-MOTOR NERVES The bloodvessels are supplied with constrictor and dilator nerve fibres which regulate the size of the vascular bed and the distribution of the blood to the various organs. The arteries may be compared to a high -pressure main supplying a town. By means of the vaso- motor nerves the arterioles (the house taps) can be opened or closed, and the current turned on to or off any organ according to its func- tional needs. If all the arterioles be dilated at one and the same time, the aortic pressure falls, and the blood, taking the pathways of least resistance, gravitates to the most dependent parts of the vascular system; just as, if all the taps in the town were opened at once, the pressure in the main would fail, and only the taps in the lower parts of the town would receive a supply. The discovery of the vaso-motor nerves is due to Claude Bernard (1851). He dis- covered that b}' section of the cervical sympathetic nerve he could make the ear of a rabbit flush, while by stimulation of this nerve he could make it blanch. He almost made the further discovery that stimulation of certain nerves, such as the chorda tympani supplying the salivary gland, produces an active dilatation of the bloodvessels. The vaso -constrictor fibres issue in the anterior spinal roots (the white rami), from. the second thoracic to the second lumbar root, and pass to the sympathetic chain of ganglia. The fibres are of small diameter, and probabl}" arise from cells situated in the lateral horn of the grey matter of the spinal cord. They each have a cell station in one or other ganghon, and proceed as post-ganglionic fibres to the cervical sympathetic, to the mesenteric nerves, and back as the grey rami to join the nerves of the limbs (Fig. 457). Nicotine paralyzes ganglion cell synapses, and by ap];)lying this test to the various ganglia the cell stations of the vaso-constrictor fibres supplying each organ have been mapped out. The vaso-dilator fibres have not so restricted an origin, for they issue in the efferent roots in all parts of the neural axis. The two kinds of nerves, although antag- onistic in action, end in the same terminal plexus which surrounds the vessels. The presence of vaso-dilator fibres in the common nerve trunks is masked, on excitation, by the overpoAvering action of the vaso-con- strictor nerves. The latter are, hoMever, more rapidly fatigued than the former, and by this and other means the presence of vaso-dilator fibres can be demonstrated in almost all parts of the body. The nervi erigentes to the penis and the chorda tympani supplying the salivary glands are the most striking examples of vaso-dilator nerves. 229 230 A TEXTI3()()K OF PHYSIOLOGY The vaso-dilator nerves for the hmbs issue in the jwsterior spinal roots. The posterior roots contain the afferent nerves (touch, pain, etc.). The same fibres serve as vaso-dilator fibres. The impulses Fig. 120. — Diagram of a Plethvsmograph axd Piston PvEcordek. The rubVjer bands fasten the glass lid in position. which produce vaso-dilatation are termed '" antidromic " (against the stream). We know that nerve fibres conduct impulses indifferently in either direction, and that the synai3sis and nerve endings control the result of such impulses. Fig. 121. — Pithed Cat: Carotid Blood-Pressuke. (H. H. Tale.) Upper curve shows effect of 0025 uiilligrammc of adrenalin before, lower curve of 0-1 milligramme of adrenalin after, 10 milligrammes of crgotoxine. Excitation of these posterior roots causes reflexly a rise of blood - pressure, and directly a vaso-dilatation in the part the nerves supply. Thus it is assured that the irritated or injured part receives immedi- lately a greater supply of blood. THE \'ASO-MOTOR NERVES 231 The vaso-iuotor centre exerts a tonic influence over the caUbre both of the arterial and portal systems. Much work has been done to determine the origin and exact distribution of the vaso-motor nerves to the various organs, and the reflex conditions under which they come normally into action^ and our knowledge, the fruits of these inquiries, has come to a con- dition of considerable exactness. This knowledge is of great practical importance to the physician, and it has been obtained entirely by experiment on living anaesthetized animals. No dissections of the dead animal could have informed us of the vaso-motor nerves. Vaso- C.C. Fig. 122. F, Depressor; R, pressor afferent impulses affecting the arteriole muscle through CC, vaso -constrictor centre, and through DC, vaso-dilator centre. Effect shown by + and — signs. (Bayliss.) motor effects can be studied by (1) observing the flushing or blanching of an organ: (2) measuring the temperature of a part or organ; (3) measuring the venoi;s outflow ; (4) recording the pressure in the artery going to and the vein leaving the organ; (5) observations on the volume of an organ. To make these last observations, the organ is enclosed in a suitable air-tight box, or plethysmograph, an opening being contrived for the vessels of the organ to pass through so that the circulation may continue. The box is filled with air or water, and is connected with a recording tambour (Fig. 120). The chief effects of vaso-constriction are an increased resistance 232 A TEXTBOOK OF PHYSIOLOGY and lessened How through an organ, diminished volume and tension of the organ; the venous blood issues fiom it very slowly and is darker in colour, and the temperature of the organ sinks. If a large area be constrieted, the general arterial pressure rises. The vaso -motor centre is situated in the spinal bulb beneath the middle of the floor of the fourth ventricle. The tone of the vascular system is not disturbed when the great brain and mid-brain is destroyed as far as the region of the pons, but as soon as the spinal bulb is injured or destroyed the arterial pressure falls very greatly, and the animal passes into a condition of j^ surgical shock if kept alive by artificial respiration. Painting the floor of the fourth ventricle with a local anaesthetic — e.g., cocaine — has the same lowering effect on the blood-pressure. Division of the cervical spinal cord or of the splanchnic nerves lowers the blood- pressure greatly. The one lesion cuts off the whole body, the other the abdominal organs, from the tonic in-- ///^ fluence of the centre. The fall of " ' pressure is due almost entirely to the pooling of the blood in the portal veins and vena cava inferior. On the other hand, electrical excitation of the lower end of the divided cord or splanchnic nerves raises the pressure by restoring the vascular tone. If an animal be kept alive after division of the spinal cord in the lower cervical region, which is possible, since the phrenics, the chief C, Constrictor; Z>, dilator neurones; ^otor nerves of respiration, come off ^, muscle cell of arteriole in body; above this region, it is found that the K, muscle t-ell of arteriole of vascular tone after a time becomes kidney; E, anercnt nerve oi the . . i ,i t, • r i i kidney influencing the body restored and the condition of shock arteriole through the bulbar passes awav. By iio second section centres and the kidney arteriole ^f ^jje spinal cord can the general locally through the spinal centres. ,.,. e ^ ,, -, ii. Effect on centres shown by + and Condition of shock be reproduced, but - signs. (Bayliss.) a total destruction of the cord once more causes a general loss of the vascular tone. From the experimental result so obtained, it is argued that subsidiary vaso-motor centres exist in the spinal cord, and there is evidence to show that these centres may be excited re- flexly. After the lumbar cord has been destroyed, the tone of the Fin. 123. THE VASOMOTOR NERVES 233 vessels of the lower limbs is recovered in the course of a few days. In this case the recovery is attributed to the ganglionic and nervous structures which are intercalated between the spinal cord and the muscular walls of the bloodvessels. There are thus three mechanisms of control: the bulbar centre, influenced particularly by the visual, auditory, and vestibular nerves ; the spinal centres ; and the peripheral ganglionic structures. The vaso-motor centre is reflexly excited by the afferent nerves, and its ever-varj^ing tonic action is made up of the balance of the Fig. 124. — Showing the Effect of a Pleasant Taste (+ ) and of an Unpleasant Taste (-) upon (1) the Volume of the Abdominal Organs, (2) the Volume of the Arm, (3) the RESPiR^TiaN. pressor and depressor influences which thus reach it, and from the quality of the blood which circulates through it. Pressor effects — i.e., those causing increased constriction and rise of arterial pressure — may be produced by stimulating the central end of almost any afferent nerve, and especially that of a cutaneous nerve (see Fig. £4). Depressor effects are always obtained by stimulating the depressor nerve (Fig. S3), and may be obtained by stimulating the afferent nerves under special conditions. There seems to be good evidence that, after division of the vaso-constrictor nerves, dilatation of a limb can be brought about reflexly by stimulating the depressor nerve, and 234 A TEXTBOOK OF PHYHIOLOOY in this case the effect must be brought about by active excitation of the vaso-dilator nerves. It is probable that there are vaso-dilator fibres in symj)athetic nerves. Thus adrenalin, which normally causes a rise of arterial pressure, after a dose of ergotoxine causes a fall (Fig. 121). The best explanation of this result is that vaso-dilator fibres are now stimulated. It seems probable that with depressor reflexes there is, along with the inhibition of tone in the vaso-constrictor centre, an excitation of the vaso-dilator centre; and with pressor reflexes an excitation of the vaso-constrictor centre and an inhibition of the vaso-dilator centre (Fig. 122). When an afferent nerve from Fig. 125. ^The Effect of the Suggestion to a Hypnotized Subject of his Execution (- to -i- ) upon (1) the Volume of the Abdominal Organs, (2) the Volume of the Arm, (3) the Respir.4.tion. any particular organ — e.g., the kidney (Fig. 123) — excites the usual pressor reflex on the general blood-pressure, a vaso-dilatation is pro- duced through spinal centres in the organ itself, thus ensuring a maximal blood supply to the active organ. In these local reflexes there is excitation of constrictors and inhibition of vaso-dilators (Fig. 123). That these reflex vaso-motor effects frequently occur is shown hy the blush of shame, the blanching of the face by fear, the blanching of the skin by cold, and the flushing which is produced by heat. The rabbit's ear blanches if its feet are put into cold water. In Fig. 124 are shown the effects of pleasant r.nd unpleasant tastes THE VASO-MOTOR NERVES 235 upon the volume of the abdominal organs, the volume of the ai'm, and the respiration. In like manner the effects of the suggestion of his execution to a hypnotized subject are recorded in Fig. 125. The vaso-motor mechanism is one of the most important of those mechanisms which control the body heat. Stimulation of the nasal iliucous membrane causes flushing of the vessels of the head, constric- tion elsewhere, and a rise of arterial pressure. Food in the mouth, or even the sight or smell of food, causes dilatation of the vessels of the salivary gland. The mucous membrane of the air-passages flush and secrete more actively when a draught of cold air strikes the skin. Ice placed on the abdomen constricts not only the vessels in the skin, but those in the kidney. Many other examples might be given of the control which the vaso-motor system exerts, but the above are suffi- cient to suggest the influence which the physician can bring to bear on the blood-su]3ply of the various organs. CHAPTER XXVIII CIRCULATION IN SPECIAL PARTS The Pulmonary Circulation. — The pulmonary artery, carrying venous blood, divides and subdivides, and the smallest branches end in a plexus of capillaries on the walls of the air cells of the lung. From this plexus the blood is drained by the radicles of the four pulmonary veins which open into the left auricle. The pressure in the pulmonary artery has been found to be 12 to 30 mm. Hg — that is, from one-third to one-sixth of the aortic pressure; the blood also takes only one-third of the time to complete the pulmonary circuit that it takes to make the systemic. The four chief factors which influence the pulmonary circulation are — (1) the force and output of the right ventricle; (2) the diastolic filling action of the left auricle and ventricle; (3) the diameter of the pulmonary capillaries, which varies with the respiratory expansion of the lungs; (4) the intra- thoracic pressure. In inspiration, the lungs are distended in consequence of the greater positive pressure on the inner surfaces being greater than the negative pressure on their outer pleural surfaces. The negative pressure in the intrathoracic cavity results from the enlargement of the thorax by the inspiratory muscles. When the elastic lungs are distended by a full inspiration, they exert an elastic traction amounting to about 15 mm. Hg. The heart and vessels within the thorax are submitted to this traction — that is, to the pressure of the atmosphere minus 15 mm. Hg — while the vascular system of the rest of the body bears the full atmospheric pressure. The thin-Avalled aiu'icles and veins yield more to this elastic traction than the thick-walled ventricles and arteries. Thus, inspiration exerts a suction action which furthers the filling of the veins and auricles. This action is assisted by the positive pressure exerted by the descending diaj)hragm on the con- tents of the abdomen. Blood is thus both pushed and sucked into the heart in increased amount during inspiration. Experiment has shown that the bloodvessels of the lungs when distended are wider than those of collapsed lungs. Suppose an elastic bag having minute tubes in its walls be dilated by blowing into it, the lumina of the tubes will be lessened, and the same occurs in the lungs if they are artificially inflated with air ; but if the bag be placed in a glass bottle, and the jDressure on its outer surface be diminished by removing air from the space between the bag and the side of the bottle, the bag will distend and the lumina of the tubes be increased. Thus, it seems that inspiration, by increasing the calibre of the pul- monary vessels, draws blood into the lungs, and the movements of the lungs become an effective force in carrying on the pulmonary 236 CIRCULATION IN SPECIAL PARTS 237 circulation. It has been estimated that there is about one-twelfth of the whole blood quantum in the lungs during inspiration, and one- fifteenth during expiration. The great degree of distensibility of the pulmonar}' vessels allows of frequent adjustments being made, so that within wide limits as much blood in a given time will pass through the puhnonary as through the systemic system. The limits of their adjustment may, however, be exceeded during violent muscular exertion. The compressive action of the skeletal muscles returns the blood to the venous cistern, and if more arrives than can be trans- mitted through the lungs and oxygenated in a given time, the right heart becomes engorged, breathlessness occurs, and signs of venous congestion appear in the flushed face and turgid veins. The w^eaker the musculature of the heart, the more likely is this to occur, hence the breathlessness on exertion which characterizes cardiac affections. Any oedema of the lung resulting from its congestion also impedes the passage in of oxygen. Hence the benefit of oxj-gen inhalation in strenuous exercise. The training of an athlete consists largely in developing and adjustmg his heart to meet this strain. Similarly, the weak heart may be trained and improved by carefully adjusted exercise. Rhythmic compression of the thorax is the method of resuscita- tion from suffocation, for this not only aerates the lungs, but produces a circulation of blood. B}" compressmg the abdomen to fill the heart, and then compressing the thorax to empty it, the valves meanwhile directing the flow, a pressure of blood can be maintained in the aorta even when the heart has ceased to beat, and this if patiently continued may lead to renewal of the heart-beat. As regards the effect of breathing upon the arterial blood-pressure, the resvilts are complex. It is generally stated that inspiration at first causes a fall and then a rise of blood-pressure, and that expiration causes flrst a rise and then a fall. The rate of the heart-beat is also affected during these times, being, when the vagi are intact, slower in expiration and quickened by inspiration. In animals under deep ansesthesia the inspiratory rise is due to lessened pressure in the pericardium, and the consequent increased filling of the heart. It is abohshed b}' allowing free access of air to the pericardial sac. In man sphygmographic tracings, taken by the suspension method (Fig. 98), show that the effect on the arterial pressure varies with the type of breathing (see p. 191). A deep breath generally produces a fall, often accompanied by the so-called pulsus paradoxus, an alteration in rhythm often considered to have a pathological import, but normal in sleeping dogs, and of occasional occurrence in boys at the time of adolescence. The pulmonarj' circuit may be shut off to a large extent in animals under artificial respiration, with little or no effect upon the arterial blood-pressure. Ligation of the vessels of the left lung produced in eighteen cases no noticeable effect on the output of the heart per second. Of the other thirteen, in eleven the pressure was decreased 238 A TEXTBOOK OF PHYSIOLOGY 6 to 10 per cent., in two 18 to 20 per cent. The lungs and their circulation in men are arranged to meet a demand ten times that of the resting condition. A rise of arterial blood -pressure is obtained in Valsalva's experiment — a deep expiration with the nose shut — and is due to the greatly increased abdominal pressure. In this condition and in coughing this pressure as measured per rectum may rise as high as 94 mm. Hg. In deep abdominal breathing it may rise to 30 mm. Hg, showing a respiratory variation of 20 mm. Hg. The evidence that the pulmonary arteries are controlled by vaso- motor nerves is conflicting. In the intact animal it is diflicult to determine whether a rise of pressure in the pulmonary artery is pro- duced really by constriction of the j)ulmonary system or by changes in the output of the heart; hence different observers have reached conflicting conclusions. When the lungs have been sujiplied with an artificial circulation and a constant head of pressure, to eliminate the action of the heart, no diminution in outflow has been observed on exciting the branches of the vagus or sympathetic nerves which supply the lungs. The use of adrenalin, which causes vaso-constriction when perfused through organs possessing vaso-constrictor nerves, has given con- flicting results. This is apparently due to the fact that different joreparations and compounds of adrenalin have been used. With adrenalin itself there is evidence of vaso-constriction; with adrenalin chloride there is no evidence of such. The vaso-constriction when produced is, however, not of a very marked character. Weighing the evidence, it would appear that the pulmonary vessels may possess vaso-constrictor nerves, but that the action of these is far less marked than that of the nerves to other organs. The Coronary Circulation. — The heart is supplied with blood from the two coronary arteries, which arise from the aorta just above the semilunar valves. The arteries supply both auricles and ventricles, and their terminal ramifications run deep into the muscle. The heart becomes fliished and supplied with blood during each diastole ; with each systole the heart pales and the blood is expressed into the right auricle through the coronarj^ sinus. To determine the existence of coronary vaso-constrictor and of vaso-dilator fibres is a complex matter, since stimulation of the effector nerves, the vagus and the sympathetic, also affect the heart miiscle. During stimvdation of the vagus with the heart in situ, it is claimed that a marked vasodilatation of the smaller arteries can be seen with the aid of a hand lens. On the isolated perfused heart, stimulation of the vagus, according to some observers, jaelds a diminished outflow from the coronary veins, evidence of vaso-constriction; stimulation of the sympathetic, an increased outflow, evidence of vaso-dilatation. In i^erhaps the most trustworthy of those experiments performed on the perfused heart, neither vagus nor sympathetic gave evidence of any effect whatsoever on the calibre of the coronary arteries. This is confirmed by the fact that adrenalin is also without apparent effect when perfused through the coronary vessels. CIRCULATION IN SPECIAL PARTS 239 The Cerebral Circulation. — The circulation of the brain is some- what peculiar, since this orgaii is enclosed in a rigid bony covering. The limbs, glands, and viscera, are enclosed in connective-tissue sheaths, but can exjsand when the blood-pressure rises ; the expansion of the brain, on the other hand, is confined. The circulation in the marrow of bones resembles that in the brain and spinal cord. In 1783, Alexander Monro the younger put forward the view that the quantity of blood within the cranium is almost invariable. " For being enclosed in a case of bone," he writes, " the blood must be continually flowing out of the veins, that room may be given to the blood which is entering by the arteries. For as the substance of the brain, like that of the other solids of our body, is nearty incompressible, the quantity of blood within the head must be the same at all times, whether in health or disease, in life or after death, those cases only excepted in which water or other matter is effused or secreted from the bloodvessels; for in these a quantity of blood equal m bulk to the effused matter will be pressed out of the cranium." These facts are confirmed by experiment. If a glass plate be screwed into a trephine hole, on compressing the innominate and subclavian arteries, the j)ial arteries can be seen to become less in size. The brain, however, does not collapse or retreat from the glass window. If the arteries empty, the veins fill. If, on the other hand, the glass window be faultily jilaced, and allow leakage into the cranial cavity, air passes within, and the brain collapses under atmospheric pressure. This experiment proves that the brain in the closed cranium can by no means completely empty itseK of blood, even though the arterial pressure should fall to zero. Similarly, if an animal be placed in the vertical feet-down position, and the skull be trephined, then, on opening the dura mater, the brain, which before was in close apposition with that membrane, can be seen collapsing, as it is emptied of blood by atmospheric joressure. The quantity of cerebro-spinal fluid which moistens the surface of the brain is not large, and the blood-content of the brain can vary suddenly only to a slight degree by displacement of the cerebro-spinal fluid. No sure evidence of the condition of the cerebral circulation can be drawn from examination of the brain after death, for in many different ways the relative volume of blood and the serous fluid within the cranium may be altered by post-mortem changes. By slow changes there can come about more blood and less tissue fluid and brain substance in the skull, or less blood and more brain sub- stance and fluid. In inflammatory states brain substance may undergo lysis, and be carried away by the blood-stream, and the bloodvessels dilate and hold more blood. The balance between volume of brain substance and blood must continually var}^ with the metabolism of this organ. The conditions affecting the cerebral circulation may be studied by simultaneously recording (1) the aortic pressure, (2) the vena cava pressure, (3) the intracranial pressure, (4) the cerebral venous pressure — the cranium being, as in the normal condition, a closed cavity. 240 A TEXTBOOK OF PHYSIOLOGY To effect this tlu^ intracranial pressure is measured by means of a brain-jn-essure gauge (Fig. 120), while the cerebral venous pressure is obtained by screwing a cannula into the torcular Herophili, a bony cavity within the occiput of the dog. The pressure of the cerebro- spinal fluid can be measured by ti'e])hining the atlas, opening the dura mater, screwing a tube into the trephine hole, and connecting this tube with a water manometer. By these means the following principles of the cerebral circulation have been determined : When the aortic pressure rises, the expansion of cerebral volume can take place only to a certain limited amount ; for as soon as all the cerebro-spinal fluid has been driven out of the cranium, the brain is everywhere in contact with the rigid wall of the skull. Any further exj)ansion of the arteries can only take place by an equivalent com- pression of veins, for the semi-fluid brain matter is incompressible. The reservoirs of blood in the veins will, therefore, be so far con- stricted, until the cerebral venous pressure rises to the pressure of the brain against these veins. Thus, as the arterial pressure rises, the whole circulatory system of the brain will assimilate itself more and fn r riu^Jwwiuii;cometek TKACI^■G (2) of Kidney Volume. (Bradford.) Between the points starred the tenth dorsal rcot was excited. The time is marked in seconds. preliminary constriction, followed by a dilatation. The usual effect, therefore, on the arterial pressure, of stimulating the peripheral end of the splanchnic, is a big rise followed by a fall of pressure. The spleen is supplied through the splanchnic nerves with con- strictor and inhibitory fibres. The existence of such has been demon- strated by oncometry. During digestion this organ shows rhythmic phases of expansion and contraction occurring at the rate of one per minute. In addition, as digestion proceeds, it gradually expands for several hours, and then returns slowly to its original size. The spleen therefore acts as a blood-reservoir in the portal circulation. The Renal Circulation. — The circulation in the kidney is studied with great ease by the plethysmographic method. A metal oncometer was first used for this purpose. A suitable box can be moulded with- 248 A TEXTBOOK OF PHYSIOLOGY out difficulty out of gutta-percha (Fig. IllO). The kichicy, having beeiv exposed by a lumbar incision, is drawn out of the wound and placed in the box. The pedicle of the kidney passes out through a groove in one side of the chamber. The box is closed by a glass cover, and this is made air-tight by a free application of thick vaseline. The altera- tions in the volume of the ki(hiey are recorded by means of a tambour. The tracing of renal volume follows exactly the curve of arterial pres- sure, and exhibits both the cardiac and respiratory oscillations. Excitation of the splanchnic nerves jDroduees constriction of the kidney. The renal vaso -motor fibres to the anterior roots arise from the sixth to the thirteenth thoracic nerves. Most of the renal vaso- motor fibres are found in the eleventh, twelfth, and thirteenth nerves. By reflex excitation it is more common to obtain contraction than expansion of the kidney, but expansion is frequently witnessed when the central ends of the eleventh, twelfth, and thirteenth posterior thoracic roots are stimulated. Vaso-dilator fibres in the anterior roots are evidenced by employing a slow rate of excitation (one per second). Injections of normal saline, or of a 2 to 3 per cent, solution of caffeine of soda, double the velocity of blood-flow in the renal artery, as measured by the stromuhr. This occurs after section of the renal nerves. Hence the diuretic action of these drugs. If urea be in- _ jected, it produces local dilatation of the kidney, while it excites the vaso -motor centre and causes general vaso -constriction. The Circulation in the Generative Organs. — Excitation of the first and second sacral nerves in the dog produces erection of the penis. The existence has been demonstrated of a centre in the lumbar region of the cord, by means of which erection can be reflexly excited. In the rabbit, monkey, and cat, the vaso-dilators run in the second and third anterior sacral roots. The outflow from the vena pudenda communis is increased as much as eight times on excitation of the nervi erigentes. The vaso-con- strictor fibres issue from the third, fourth, and fifth lumbar anterior roots. The internal generative organs are supplied with vaso -constrictor- nerves from the lumbar anterior roots. All the vaso-constrictor fibres to the generative organs pass through cells stationed in the inferior mesenteric and sacral ganglia of the sympathetic. The vaso-dilator nerves pass through cell stations in scattered ganglia situated near these organs. The Foetal Circulation.— In the mature foetus, the fluid brought from the placenta by the foetal umbihcal vein is partly conveyed at once to the vena cava ascendens by means of the ductus venosus, and partly flows through two trunks that unite with the portal vein,, returning the blood from the intestines into the substance of the liver,, thence to be carried back to the vena cava by the hepatic vein. Having thus been transmitted through the placenta and the liver, the blood CIRCULATION IN SPECIAL PARTS 249^ that enters the vena cava is purely arterial in character; but, being mixed in the vessels with the venous blood returned fi'om the trunk and lower extremities, it loses this character in some degree by the time it reaches the heart. In the right auricle, which it then enters, it would also be mixed Avith the venous l)lood brought down from the head and ui)j)er extremities by the descendmg vena cava, were it not that a provision exists to impede (if it does not entirely prevent) any further admixture. This consists in the arrangement of the Eustachian valve, which directs the arterial ciu-rent (that flows upwards through the ascendmg vena cava) into the left side of the heart, through the foramen ovale — an ojDening in the septum between the auricles — whilst it directs the venous current (that is beiiig retm-ned b}' the superior vena cava) into the right ventricle. Wiien the ventricles contract, the arterial blood contained in the left is propelled into the ascending aorta, and supplies the branches that proceed to the head ■and upper extremities before it undergoes any further admixture; while the venous blood contained in the right ventricle is forced into the pulmonary arter}-, and thus through the ductus arteriosus — branching off from the pulmonary artery before it passes to the two lungs — into the descending aorta, mingling with the arterial currents which that vessel previously conveyed, and thus supplying the trunk and lower extremities with a mixed fluid. A portion of this is con- vej^ed bv the umbilical arteries to the placenta, in which it undergoes the renovating influence of the maternal blood, and from which it is returned in a state of purity. In consequence of this arrangement the head and upper extremities are svipplied with pure blood returning from the placenta, whilst the rest of the body receives blood that is partly venous. This is probably the explanation of the fact that the head and upper extremities are most developed, and from their weight occupy the inferior position in the uterus. At birth the course of the circulation ixndergoes changes. As soon as the lungs are dis- tended by the first inspiration, a portion of the blood of the pulmonary artery is diverted into them and undergoes aeration; and, as this portion increases with the full activity of the hmgs, the ductus arteri- osus gradually shrinks, and its cavity finally becomes obliterated. At the same time the foramen ovale is closed by a valvular fold, and thus the direct communication between the two auricles is cut off. Wlien these changes have been accomplished, the circulation, which was before carried on upon the plan of that of the higher reptiles,, becomes that of the complete warm-blooded animal, all the blood which has been returned in a venous state to the right side of the heart being transmitted through the lungs before it can reach the left side or be propelled from its arterial trunks. After birth the umbilical arteries shrmk and close up, and become the lateral ligaments of the bladder, while their upper parts remain as the superior vesical arteries. The umbilical vein becomes the ligamentum teres. The ductus venosus also shrinks, and finally is closed. The foramen ovale is closed, and the ductus arteriosus shriveU and becomes the Ugamentum arteriosum. CHAPTER XXIX LYMPH By means of the circulatory system the blood is taken to the great network of capillaries which ramify in their myriads amid the various tissues of the body. Since, however, this blood capillar}' system is a closed one, blood itself does not come into actual contact with the tissue cells themselves.* These cells are bathed in a fluid — the tissue fluid, or lymph — and it is this fluid which finally takes to the tissues the substances necessary for their proper nutrition and adequate working, and takes from them the products of their activity. The lymphatic system is a most extensive one. It consists of the interstitial or lacunar spaces Avhich exist in almost all parts of the body; the delicate lymphatic capillaries; the larger lymphatic vessels, "which ultimately unite to form the thoracic duct or the right h'mphatic duct ; the lymphatic tissues of the body, such as the lymphatic glands ; and the lymphatic tissue incorporated in the spleen, thymus, etc. The large serous spaces, such as the peritoneum, pericardium, may also be included in this system. For many years past the exact relationship^ between the inter- stitial spaces and the lymphatic vessels has been the subject of con- siderable discussion. One view, formerly accorded almost general acceptation, is that the interstitial spaces, or lacunae, communicate directly with the delicate Ijanph capillaries, which in turn unite to form larger channels or lymphatics, and ultimately open into the venous system by the thoracic duct or the right lymphatic duct. According to this view, the tissue fluids bathing the cells and the lymph flowing from a lymphatic duct are one and the same fluid, since there is absolute continuity between the duct lumen and the tissue spaces. Another view, which has recently gained much support, is that the interstitial tissue spaces do not directly communicate with the lymph capillaries. The lymphatic system, according to this vie^ , is, as regards the tissue spaces, a closed system. It probably communi- cates by stomata with large serous spaces, such as the peritoneal space, and possibly also with the spaces of certain mucosae — e.g., the bronchial and nasal. On this h>])othesi; . the tissue fluid of the interstitial spaces is dis- tinct from the lymph of the lymphatic system. Little or nothing is known as to the exact composition of such tissue fluid ; it is assumed to be of much the same composition as the lymph. This bathes the * Except in the spleen and liver. Blood-capillaries, too, run into the giant ganglion cells which feed the electric organ in Malapterurus. 250 LYMPH 251 tissues with a suitable medium for thieir activities, and carries to them the food material necessar}^ for such activities and for repair ; carrying also bodies such as hormones or co-enzymes, which stimulate or aid tissue activity. From the tissues it carries away the products of their activity — either synthetic, such as internal secretions and hor- rnones, or the katabolic or waste products resulting from such activity. In regard to the digestive tract, the tissue fluid acts as a transport fluid for the absorbed products of digestion. Some of these, such as those of protem and carbohydrate digestion, pass into the blood of the portal vein. The products of fat digestion, on the other hand^ pass into the closed lymj^hatic vessel, or lacteal. They give to the lymph a milky appearance, from which the name of these particular lymph channels is derived. In other parts of the body, also, there is the same quick transference" of some bodies from the tissue fluid to the blood, and of others to the lymph. In discussing the processes of lymph formation (see later), this point must be borne in mind. For example, when a salivary gland is secreting, we must inquire what processes determine the bodies which pass (1) from the gland to the saliva, (2) into the tissue fluid, (3) from the tissue fluid to the venous blood, (4) from the tissue fluid into the lymph leaving the gland. The properties of lymph are generally studied by collecting the fluid as it flows from the thoracic duct of a small mammal, or from the main Ijanphatic channel of each of the varioixs organs of the larger domestic animals. For demonstration purposes, a cannula is usually placed in the thoracic duct of a fau'-sized fasting dog, and a good How of lymph insured by the intravenous injection of commercial peptone solution. Such lymph is a viscid, opalescent fluid, faintly alkaline in reaction, specific gravity 1010 to 1020. The first lymph which flows coagulates spontaneously, although less quickly than blood. After a time, however, owing to the effect of the peptone, it becomes incoagulable. Chemically, it contains the same constituents as blood- plasma, the diffei-ences being quantitative. It is poorer in proteins, and richer in Avater and salts. The lymph from different parts varies in quantitative composition. For example, that from the liver contains more solids than that from the limbs. The lymph flowing from the same organ also varies quan- titatively in composition according to the degree of activity of the organ. As a result of various analj'ses, the composition of lym^jh may be given somewhat as follows : Per Cent. Water 93-5- 9.5-8 Solids 4-2- {■)•.■■> Proteins . . . . . . . . . . . . 3- .5 — 4*3 Fats 'i ^o-'^P.^ I 0-4-0-9 Lipoids i Dextrose ) Salts (chiefly XaCl) 0-7— 0-8 0) . . . . . . . . . . • • • • traces CO., '.'. 37—5! vols. 252 A TEXTBOOK OF PHYSIOLOGY Lymph also contains white corpuscles similar to those in the blood, lymphocytes jjarticularly ioredominating. The amount of lymph flowing from the thoracic duct in twenty- four hours has been found in human patients to vary from 1,200 to 2,280 c.c. per day. Li a dog of 10 kilos, the amount was 640 c.c. We cannot take this as indicative of the normal flow, for the escape of lymph through a wound is unrestrained by the conditions which pertain in the closed l)ody. The Processes concerned in the Formation of Lymph. — Consider- able divergence of opinion is manifested as to these ; a vast amount of evidence has accumulated which is held to support the various views entertained b\' different authorities. From such experimental data one great fact emerges — namely, that lymph flow is the concomitant of tissue activity. For example — 1. When the liver is active, either as the result of an injection of peptone or during the processes of digestion, there is an increased flow of lymph from the liver. 2. When the salivary gland is made to secrete by stimulation of the chorda tympani nerve (see p. 374), there is a marked increase of lymph flow from the gland. 3. When the pancreas is made to secrete as the result of an injec- tion of secretin (see p. 307), there is similarly an increased flow of lymph from that organ. 4. From the resting limbs there is practically no flow of hanph; activity gives rise to a well-marked flow. The two chief views held in regard to lymph formation are the mechanical and the secretory. The mechanical view holds that lymph transudes from the blood-capillaries as the result of the processes of filtration and osmosis. A higher pressure is supposed to pertain in the capillaries and cause filtration. According to the secretory view, lymph is formed as the result of cell activity. The cells actively draw water, etc., from the blood-capillaries into the tissue spaces according to their functional needs. The experimental evidence in regard to filtration consists chiefly of experiments in which a rse of capillary pressure is induced as the result of partial or total blocking of the venous circulation. This does not occur under normal conditions. The result, also, is an in- creased flow of lymph, which differs considerably in composition from that flowing under normal circumstances. Such an experiment is the ligation of the veins of a limb, which causes an increased flow of lymph poorer in solids than normal and red-coloured, owing to the presence of red corj^uscles. Ligation of the portal vein ra ses the pressure in the capillaries of the intestinal area, and causes a marked increase of tymph. Occlusion of the inferior vena cava above the diaphragm causes an increased flow of lymph from the liver, due, according to this view, to the rise in pressure in the liver capillaries. Similarly, occlusion of the aorta causes an in- creased flow of lymph from the liver, the pressure in these circum- stances in the inferior cava being slightl}^ raised or remaining unaltered. LYMPH 253 It has never been shown that a rise m capillary pressure with a normal venous circulation produces an increased flow of lymph. On the contrary, experiments show that such a rise of capillary pressure may take place Avithout an increased flow of lymph necessarily- re- sulting. Reference, for example, has already been made to the fact that stimulation of the chorda tympani causes a great floA\' of saliva accompanied by a marked floAv of Ij^mph from the gland. When the endings of this secretory nerve are paralyzed by atrojiine, stimulation still produces a marked rise of capillary pressure, but no salivary secretion or increased lymph flow results. So, too, if the motor nerves to a limb be cut, and the blood-pressure raised by caiising a general vaso-constriction of the rest of the bodj^ the quantity of lymph flowing from the limb while performing passive rhythmical movements is not increased, but diminished. Differences in the constitution of lymph coming from different parts, or from the same part at different times, are attributed upon the filtration view to an altered permeability of the vessel wall. The exact reason for such alterations appears to be due rather to the different forms of activity in the various parts, and in the same parts at different times. Reasons for a disbelief in the possibility of a filtration mechan- ism within the body are adduced in dealing Avith the capillary pressure (see p. 223). Furthermore, it has been shown recently that Aenous stasis cause!>; lymph formation, not by A'irtue of filtration, but by changes in the tissues themselves, due primarily to lack of oxj^gen, causing the forma- tion of acid. With such acid formation, AA-ater passes by imbibition into the tissues, leading, if long continued, to oedema. Such a con- dition is pathological, not physiological. In regard to the part played by osmosis, it may quite Avell be that the interchange betAAeen blood and tissues is largely regulated by this process. For example, the lymph formation attending tissue activity maA' possibly be explained by the supposition that the products of cell actiAdty, being relatiA'ely of small molecular AA'eight, cause b}^ increased osmotic pressure a floAA' of fluid from the blood into the tissue spaces. The numerous experiments Avhich haA'e been made of injecting such crystalloid bodies as sodium chloride, dextrose, urea, so-called lymphagogues, tend to support the A'iew that osmosis plaj's a part in the formation of lymph. Certain recent experiments, hoAA^ever, shoA\' that the chloride content of the lymph may rise aboA^e that of the blood-serum. If this be the case, then osmosis cannot be the AA'hole story. It has also been pointed out that each tissue or organ obtains its •OAAii special products from the lymph, often in large quantities. TIk^ most -quoted example is the calcium content of milk. A coav may A'ield daily 25 litres of milk containing 42-5 grammes of Ca. As the lymph of the thoracic duct contains but 0-18 per cent., 236 litres of lymph would be needed to su])]ily this calcium to the milk, assuming that .all the calcium comes from the lymph. This is held greath' to sujjport 254 A TEXTBOOK OF PHYSIOLOGY the secretory view, that lymph and uiilk are formed by the special activity of the gland cells. The cells of each organ draw what they need from the blood. The fact that some bodies ajjpear to be quickly transferred from the tissue fluid to the venous blood, while others appear to be passed on into the lymphatics, has led to the view that the bodies passed into the lymphatics ai-e toxic, and are taken to the lymphatic glands to have this toxicity destroyed. It has been shown experimentally that tymph injected into the arterial system causes marked effects upon the arterial pressure and rate of heart-beat. The Movement oJ Lymph. — To what factors is due the flow of hanph ? In the amphibia and fishes there are special lymph hearts, but these are lacking in mammals. The lymphatics have valves to direct the flow, and these valves have special muscle fibres arranged about them which, it has been suggested, act as a pumping mechanism. Such a claim has not been substantiated. The vessels, however, appear to be innervated with constrictor and dilator nerves, and it is conceivable, although not proven, that alterations in the lumen may aid the flow. According to the ^neehanical view, the flow of lymph is maintained by the filtration pressure transmitted from the vis a tergo, the heart- This point has already been debated. The heart-beat plays an im- portant factor in pulsing organs full of blood with each heart-beat. This systolic filling squeezes on the lymph in the lymphatics. The chief factors in causing a flow of lymph are the activities of the tissues, muscular movement, and the resjiiratory pump. The various serous membranes of the body are moistened by fluids which more or less resemble lymph in composition. The amount of protein in these different fluids varies considerably, although imder normal circumstances the quantity of such fluids is in some cases so small that accurate analyses have not been made. The composi- tion of the fluids is altered when there is increased formation due to inflammatory disease, and it is such fluids which for the most part have been analyzed. The pericardial fluid is a somewhat sticky, lemon-coloured fluid, which contains about 96-1 per cent, of water and 3-9 per cent, of solids. The chief solids are proteins (2-8 per cent.) and salts, mostly sodium chloride (0-7 per cent.). Traces of fat, lecithin, and cholesterin, are also present. Pleural fluid is normally present in such small amounts that analysis of the healthj' fluid has not been made. The same is true of normal peritoneal fluid. The cerebro-spinal fluid is a thin, clear fluid, characterized by its low specific gravity (1007 or 1008) and its low protein content. The protein is of a globuhn nature. A small amount of cojojoer -reducing substance is also present, which is probably sugar. In disease, the constitution of the fluid may be altered in various Avays. The state- LYMPH 255 ment that choline is present in certain nervous diseases has not met with general acceptation. The fluid is secreted by the cells of the choroidal fringes of the brain, and absorbed into the cerebral veins, probably by way of the Pacchionian bodies. The aqueous humour of the eyeball is a clear fluid, alkaline in reaction, of low specific gravity (1005 to 1008), and containing normally but a trace of protein. It is secreted by the ciUary pro- cesses of the eyeball, and absorbed by the veins of the iris and those in the angle of the eye. BOOK IV CHAPTER XXX RESPIRATION One of the mo it rem.xrkable properties of living substance is its dependence on a supply- of ox^'gen. The vital processes in the cell substance by which energy is set free and food obtained depend on this, and carbon dioxide, the chief end product of these processes, must be got rid of, as well as a sufficiency of oxygen obtained. Many kinds of bacteria — g.gr., tetanus bacilli — and parasitic worms, which live in the intestine, are what are termed " obligate anaerobes." They secure their oxygen by decomposition of foodstuffs, and are poisoned by free oxygen. All other bacteria, the higher plants, and animals, are aerobes, and take up free oxygen from the atmosphere by a respiratory process. Plants both excrete carbon dioxide and assimi- late it. By the aid of chlorophyll energized by sunlight, plants synthesize water and carbon dioxide into formic aldehyde, which by molecular condensation is converted into an aldose; hence arise sugar and starch. At the same time as this remarkable synthesis goes on, the plant protoplasm uses up oxygen and produces carbon dioxide. From the nitrates and other salts absorbed by the rootlets and the aldose syn- thesized in the leaves the plant proteins are built. Sunlight forwards this synthesis, converting nitrates in watery solution into nitrites, An endDth3rmic reaction; the sugars and starch may also be converted into fat. The source of the energy of all these sjmtheses in the plant is the sun's rays. The chlorophyll absorbs the light rays, and trans- forms them into energy which is stored as potential energy in the proteins, carbohydrates, and fats, built by the plant. These form the foodstuffs of bacteria, moulds, and animals, by which they are broken down again into water, carbon dioxide, salts, and simple com- pounds of nitrogen — -the materials for fresh plant synthesis. So the cycle of life proceeds (Fig. 130). The bacteria form the final link in the chain; some decompose dead animal and plant matter (denitrify- ing bacteria), while other symbiotic bacteria help the rootlets of certain plants (legumes) to secure atmospheric nitrogen (nitrifying bacteria). If it were not for bacteria, the world would quickly become cumbe-re:! up as a charnel house. The circulation of nitrogen in nature is shown in Fig. 131. It has recently been found that when carbon dioxide gas is passed 257 17 258 A TEXTBOOK OF PHYSIOLOGY through very dilute solutions of inorganic colloids (uranic or ferric oxide) in the presence of sunlight, the synthesis of formic aldehyde and acid is obtained. It has been suggested that we have in this a possible first stage in the evolution of organic material and life pro- cesses from inorganic matter. »f The exchange of gases between the respiratory tissue and the outer medium is known as " external respiration." The process whereby the exchange of these gases takes place between the blood and the different jmrts of the body is known as " internal," or " tissue respiration," Cold-blooded animals can live for some hours in an atmosphere of nitrogen, and hibernating cold-blooded animals — e.g.y Products} of pla-nt lif,', H2O Proteid. ^tarch FsLt Pla.nt ucts of riaJ Decbm position moms. etc. IVATCR NITRATES & OTHER SALTS. Fig. 130, — ^To illustrate the Cycle of Plant, Animal and Bacterial Life, The arrows indicate the materials which each take up and give out to the'world. snails which shut themselves up for the winter — retain their existence for months without respiration. On the other hand, a very active respiration and rapid exchange of gases are necessary in the warm- blooded animal, because the rate of metabolism is very great, and within the body there is no means afforded for laying in a store of oxygen sufficient to last more than a minute. The carbon dioxide, too, which in normal concentrations plays an important part in regulating body processes, when present within the body in excess,, has a narcotic poisonous effect upon the organism. The blood is exposed to the air in the lungs over a verj^ extensive surface — perhaps as much as 100 square metres — in a film one corpuscle thick, and the whole blood circulates through the lungs about once a RESPIRATION 259 minute when resting, antl as often as ten times a minute during hard muscular work. According to the simplest hypothesis, and the one generally accej^ted, the venous blood, which enters the pulmonary capillaries, has a lower oxygen and higher carbon dioxide concentration or pressure than that in the pulmonary air. An exchange takes place between the blood and the pulmonary tissue lymph, and then be- tween this fluid and the pulmonary air, this exchange being in accordance with the physical laws which govern the solution and diffusion of gases. |NtTRATE-N.' lURINEl \ I FAECES I \^ /i_PL^ / a/ ;xx EA PUTRE- / IPUTRE- Y^ UREA I IPUTRE- I / FERMptTATIONl | FACTION | / • / / / . / I ^i^>^j»,■' / f ^ -t %J. 1 1 4 1^ - T / ^ ^ 1 =t IT --^ Z 1 ^ ^ '■lO \<.^ i 1 1 1 00 ^^ ^ -^ -I- ^ ^r -^ -^^- / A V ^ t I t'^J^ it H"" '^ I J ^ ^ 40 ' H 7 ^ ^ tl J ' 1 ; M 1 u i_j_ 31 t rr ^ 1 1 II 1^ 1 , / y III 1 1 ' 1 II 1 Mil on ,y]// M 1 1 M 1 1 i J 1! 1 1 1 1 1 30 7*nr^„ 1 1 1 1 1 1 1 M 1 1 II 1 II 1 i ^ / / /L v) '1 1 1 i 1 1 1 1 1 1 1 1 1 1 1 1 III 1 1 1 " ■■-■■-■ 1 1 1 1 || 1 1 1 1 1 1 1 1 1 1 M 1 1 II , It \ 1 1 ll 1 1 i 1 1 1 1 i 1 1 1 1 1 1 M nc . ' 1/ 1 |i M 1 1 1 1 1 1 1 1 1 1 1 20 ^jf- ■ ■ 1 r 1 1 1 1 1 I 1 1 1 i 1 1 1 I 1 i ;( '/ II 1 ! 1 1 1 1 i 1 II ' 1 M 11 1 1 /// 1 1 1 1 1 1 i 1 1 i M 1 ; 1 i 1 1 1 1 '// III 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 III ,n .''/ 1 1 1 1 ll 1 1 1 1 1 1 1 1 1 II III '0 /y 1 i 1 1 1 1 M 1 1 1 1 Ij 1 1 M 1 1 / 1 1 I 1 1 1 11 1 1 1 1 1 1 1 1 M ' M 1 /I 1 1 1 1 1 1 1 1 1 1 ll 1 1 1 M 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 i ! 1 1 ! 1 ! - 1 1 1 i i 1 1 1 1 1 1 1 Ill 1 M 1 ll 1 - 1 , 40 50 70 Fig. 139. — Effect of H.e.moglobin Solution and of Salts on Oxygen DISSOCLA.TION Curve. (Barcroft.) I. Dissociation curve of hsemoglobin dissolved in water. n. „ „ „ „ „ -T^o NaCl III. ,. „ „ „ „ -9% KCl Ordinate = percentage saturation of haemoglobin; abscissa = tension of oxygen in millimetres of mercury. Rectangle surrounding point = magnitude of experi- mental error. Temperature 37°-38° C. the protein jjortion (the globin) of the haemoglobin. Haemoglobin consists of 95 per cent, globin and 5 per cent, hsematin; the oxygen is attached to the latter, which contains the iron. Two in- teresting facts have been shown in regard to the chemical combina- tion of COg in the blood: first, that in spite of the presence of free alkali, blood — but not plasma — gives up almost all it-s CO., to the 2G8 A TEXTBOOK OF PHYSIOLOGY vacimm pump; and, secondly, that blood added to a soda solution sets free COg from it. The probable explanation is that the blood- proteins, especially the hsemoglobin and the serum globulin, by virtue ot their amphoteric reaction, can act as both acids and alkalies. The Ijiiilding-stones of proteins, the amino-acids, contain both NHg and COOH groups. When the partial pressure of CO2 is low, as in the lungs, these proteins act as weak acids, and turn out COg. On the other I \^ " ; ^__. — . . — : — 1 i " ^^"^^ / HI y^ ^ ^- - / / Vl^ ^ ^^ (/ / -- V ■^ \ // / / \\ / \\l / W / 1 / \ , 20 30 - 40 -\—l- 50 60 70 80 90 30 40 Fig. 140. 50 60 (Barcroft.) 100 Dissociation curves I., 11., III., IV., and V. correspond to 16°, 25°, 32°, 38°, and 4&°^C. respectively. Oxygen pressure plotted horizontally, perccnta£;e of reduced haemoglobin vertically downwards hand, when the CO2 pressure is high, as in the tissues, it seems probable that these proteins act as alkalies, and actually combine with the CO2 and aid in its transport away from the tissues. That the corpuscles help to expel the CO^ is shown by the fact that acid must be added to plasma in order to obtain all the CO2 combined with it, exj^osure to a vacuum not being sufficient by itself wholly to decompose the CO2 compounds in the plasma. RESPIRATION 2G9 The following was estimated to be the distribution of CO^ in 100 CO. of arterial blood, the pressure of CO2 being equal to 30 mm. Hg: Physically absorbed, 1-9 c.c. (0-7 c.c. in corpuscles); as bicarbonate, 12 c.c; as organic compounds in plasma, 11-8 c.c; in htjemoglobin, about 7-5 c.c; as bicarbonate in corpuscles, about 6-8 c.c— total. 40 c.c. The Pressure of the Gases in the Alveolar Air, Blood, and Tissues. — In order that we may discuss the processes by which the interchange of gases takes place between the alveolar air and the blood in the lungs, and between the blood in the capillaries and the tissue fluids, it is necessary that Ave know the pressure of the gases in these various parts. It is possible that such an interchange is a physical process following well-known physical laws ; on the other hand, it is possible that, owing to the incessant demand of the tissues for oxygen, and the need of freeing them from excess of CO2, that secretory processes, unexplainable by known physical laws, may play a part in this gaseous interchange. Such a process would be the passage of a gas from a region of lower concentration, through a layer of cells wet with tissue lymph, to a region of higher concentration. If this took place, it would be fair to assume that the intervening cells and the blood were in some way aiding the process by virtue of their own special vital metabolism. It might be said that the cells were actually secreting the gas into the region of higher concentration, just as the kidney secretes urea from the blood, where it may be 1 per 1,000, into the urine, where it may be 20 per 1,000. Both views have been advocated, and are still advocated, in regard to the processes of respiration. One school of thought believes that all the processes may be explained by known physical laws; another school holds that, under some circumstances at any rate, the pro- cesses of gaseous interchange are aided by active intervention on the part of the bod}^ cells, particularly those of the alveoli. To ascertain the merits of these conflicting views, it is necessary to know the partial pressure of the gases concerned in this interchange in the various parts of the body, and also to study the accuracy of the methods by which these pressures are calculated. Partial Pressure of Gases in the Blood. — Manj^ experiments have been made by various researchers to determine exactly the partial pressure of the gases in both arterial and venous blood. In general, the method employed has been to bring the circulating blood into contact with a gas mixture of known composition, and by analysis at the end of the experiment to ascertain the composition of this mixture. The blood, thoroughly shaken with the mixture, gets into equilibrium with it, and the blood gases then have th? same partial pressure as those found in the mixture. The instruments emploj^ed for this purpose are known as " aerotonometers." The microtonometer is the apparatus now most generally employed. In this apparatus (Fig. 141), a bubble of air (2) of 2 millimetres diameter is brought into contact with the blood coming from an arterj^ or vein. The blood enters by a fine point (1), and keeps the bubble in constant movement. 270 A TEXTBOOK OF PHYSIOLOGY so that the exchange between the air in the bubble and the gases of the blood is a ra]iid one. The bubble (2) can be drawn into the fine calibrated tube (3) by means of the screw piston (4), and measured therein. The wide part of this tube (1) is first filled with Ringer's solution, and the bubble introduced into it by means of a pipette. It is then drawn into (3), measured, and again returned to (1). The blood is now allowed to flow through (1) for a few minutes by way of (5) and (6). The bubble is once more measured in (3), and then (5) is filled with potash solution, the bubble returned to (5), then to (3), and again measured. Finally, (1) is filled with sodium pyrogallate solution, and the manoeuvre repeated. Thus the percentage of COj and O2 is obtained, for the potash absorbs the COg and the pyro- gallate Og. From the percentage measured at atmospheric pressure the partial pressures are calculated. Fio. 141. — Schematic Representation of Krogh's Mickotonometek. Description in text. The invasion coefficient is the amount of gas which enters 1 square centimetre of the surface in one minute at atmospheric pressure. This has been measured in the case of a bubble of air by means of the micro- aerotonometer. The film covering this bubble is comparable in tenuity to that of the pulmonary endothelium. A very rough calculation of the invasion coefficient sviggests that it demands a difference of pressure on the two sides of the lung surface of 1 nun. Hg for every 100 c.c. of oxygen absorbed by the lung per minute. RESPIRATION 271 The results obtained by the microtononieter support the view that the exchange of gases in the lungs is brought about by the process of diffusion, and not by active secretion. The oxygen passes from the alveolar air, where its pressure is higher, into the arterial blood, where its pressure is lower. The carbon dioxide passes from the venous blood, where its pressure is higher, into the alveolar air, where its pressure is lower; and the pressure of carbon dioxide in the arterial blood leaving the alveolus is higher, or at any rate not lower, than that in the alveolar air. There is nothing inherently improbable in the conception of the lung as a gas-secreting organ. Gas is secreted by several aquatic organ- FiG. 142. — Five Gas-Secreting Cells from the Gas Gland in the Svvim-Bladdek OF the Paradise Fish Macropodus V iridi-auratus. (Redrawn after Reis and Nusbaum from Dahlgren and Kepner. ) b, Tliickened distal border of cells on the lumen; vac, gas-vacuoles; ir., trophospougia, the organs concerned in the elaboration of gas from the materials of the cell ; bl. ca., blood capillary. isms for the purpose of flotation (Fig. 142). The swim-bladder of the fish is an organ developed, like the lung, as an outgrowth from the gut. Gas is secreted in it, so as to render the specific gravity of the fish equal to that of the surrounding water. In fish at great depths, the gas is compressed by even hvxndreds of atmospheres of pressure, due to the superincumbent water. The fish secrete oxygen gas against this enormous pressure, and the swim-bladder is immune to oxygen- poisoning. If the swim-bladder in a codfish is punctured, and the gas drawn off, the bladder fills again; but this does not take place if the vagus nerves be divided. Thus the secretion of the gas is con- trolled by these nerves. Some authorities have sought evidence that the gaseous exchange in the lungs is not only a process of secretion, but one controlled by the vagus nerves. The function of the swim- bladder is manifested by taking two goldfish, and fastening a piece of cork to the dorsal fin of one, and a piece of lead to the ventral fin of the other. Both are returned to a tall jar of water, and the one 272 A TEXTBOOK OF PHYSIOLOGY is drawn by the cork to the surface, and the other by the lead to the bottom. Next day they have adjusted their specific gravity by means of their swim-bladders, and are swimming about easily. On removing the lead, that fish irresistibly floats to the surface; on removing the cork, the other one sinks to the bottom. Thej^ have again to adjust their SAvim-bladdors. If goldfish in water are placed in a pressure chamber, and suddenly compressed, they sink to the bottom, owing to the shrinkage of the gas in the bladder. If a fish is hooked in deep Piii. 143. — Fish brought vp from a Considerable Depth with Swollen Swim- Bladder PROJECTING from Mouth. (After Regnard.) water, and started on the way up, the gas in the bladder exjjands, ■and the fish floats to the surface, and the bladder often bursts (Fig. 143). There is a glandular mechanism in the swim-bladder for secreting gas. and another mechanism for absorbing it. Against the theory of pulmonary secretion is the fact that the pulmonary endothelial cell is a flattened structure entirely unlike the granular secreting cells typical of glands. Evidence in favour of pulmonary secretion has been sought by a method quite different to that of the aerotonometer. If blood is shaken with air containing, say, 0-05 per cent, of carbon monoxide, the haemoglobin is shared between the oxygen and carbon monoxide RESPIRATION 273 in proportions depending on their relative pressures and chemical affinity. Carbon monoxide has an affinity about 150 times as great as oxygen. Blood saturated M'ith carbon monoxide, and diluted 1 in 200 times, has a pink colour; the extent of saturation with carbon monoxide can be estimated bj^ a method depending on the depth of this colour. If three samples of blood (diluted 1 in 200) are taken, and one is saturated with carbon monoxide (shaken with coal-gas), the second parth^ saturated, and the third not at all, the colours of the samples are obviously different. The normal sample is straw- coloured. A standard solution of carmine can be run in from a pipette, and the amounts found which will make Sample 2 and Sample 3 equal in pinkness to Sample 1 . From the relative amounts of carmine used the degree of saturation of Sample 2 is discovered. Fig. 144. — Haldane's AprARAxrs for determining Oo Tension in Human Blood. B, T, C, Apparatus for br- athing air containing CO at measured concentration; M, mouthpiece; T', valves made of pieces of intestine; B, air-bag for controlling pressure during expiiation; G, meter. Now, when air containing 0-05 per cent, carbon monoxide is breathed for a sufficient period to allow the w^hole blood to get into equilibrium, the saturation with carbon monoxide is found to be less than that when the blood is shaken with the same mixture outside the body; particularly is this the case under conditions of oxygen want — e.g., at high altitudes, partial asph}xia — when it is suggested there would be secretion of oxygen into the blood by the lung. The oxygen pressure in the arterial blood raised by secretion is supposed to antagonize the union of carbon monoxide with the haemoglobin. However, other explanations havb been given of this result. The technique of the method is as follows: 18 274 A TEXTBOOK OF PHYSIOLOGY The subject inspires through the mouthpiece 31, and expires through the meter (Fig. 144). Water is allowed to nm from R into C, which contains pure CO, and disphiccs this gas at such a rate as to give a known concentration of CO in the vohime of air, indicated by the meter, which is being breathed. The breathing is continued long enough for the blood to come into equilibrium with the partial pref - sure of CO and 0., which is being breathed (the partial pressure of O is that of the air). The finger is then pricked, and samples of blood taken, and the saturation determined by the carmme method given ^0 ' 19 . <- - •:.-.. _„--'- --l. i8 ■ 17 - ----- _— — — 3 16 "^ ^ 15 ■ 0^ 7 CO, 6 ■l~. r 5 //' '"^1 If \\^ / / 1 i 3 ~ ----_ V- . __^ \] 2 z^ 0,0 J 2,& 1 1 fi^^ , ■~-+— ^/^^96Ci>^/fiJf^ 220 30 W 60 3 20 30 ttO Fig. 145. 50 P.O 30 W Dotted line ^pressure in the air at bifurcation of trachea. Solid line = pressure in the blood. In the upper j)art of the figure are shown the pressures of oxygen, in the lower jiart the pressures of carbon dioxide. Ordinate pressure of oxygen expressed in per- centages of an atmosphere. Abscissa = time. (Krogh.) above. A sample is shaken with the air (contauaing the known per- centage of CO), which was breathed. If this sample is found to be more saturated with CO than that drawn from the finger durmg the breathing, the conclusion is drawn that the partial pre.ssure of oxygen in the blood in the pulmonary veins is higher than that in the air. The colorimetric method is liable to error ; moreover, a part of the carbon monoxide actually absorbed may leave the blood and com- ' bine with haemoglobin in the muscles. There is no evidence in favour of any of the carbon monoxide being destroyed in the body, error does not seem to arise from that cause. RESPIRATION 275 To sum up, the differences of pressure of carbon dioxide and of oxygen found by the microtonometer in the blood and at the bifurca- tion of the trachea support the view of diffusion (Fig. 145). It is estimated also that the process of diffusion can carry oxygen in amounts sufficient for hard work through the puhnonary endothelium. The rate of diffusion in the lung is probably accelerated by the chemical affinity of haemoglobin with oxj'gen: we need not therefore ascribe a secreting power to the pulmonary endothelium. But it is still a question whether diffusion can cover the oxygen needs at great altitudes — e.g., 24,000 feet, to which a few climbers have attained. Carbon dioxide is about twenty-five times as soluble in water as oxj^gen is, hence it passes through the alveolar wall far more easily than oxygen with a given difference of partial pressiu*e. A compara- tively slight increase in breathmg, hy ventilating the lungs, enormousty increases the small difference in diffusion pressvu'e on which the passage of COg depends, but only produces a slight proportional increase in the diffusion pressure which drives oxygen inwards. Hence, under certain conditions, grejTiess of the face, faintness, and danger from heart failure, the signs of oxygen-want, may arise when hypeipnoea and venous congestion, the signs of COg excess, are absent. CHAPTER XX XT THE MECHANISM OF RESPIRATION In the unicellular organism, oxygen is taken in from the surrounding medium, and the CO2 given out through the cell sur- face. In the more complex organisms, a special respiratory apparatus becomes evolved, and two kinds of respiration are distinguished: external respiration, by which oxygen is taken from the surrounding medium into the circulating transport fluid — the blood — and the COg given off from this fluid to the medium; internal respiration, by which a gaseous interchange takes place between the body fluids and the various body cells, oxygen being taken to the cells, and CO,^ removed from them. Internal respiration is probably the same process in all forms of animals. External respiration differs with the stage of develoiDment, and also with the habitat of the animal. The lower forms of invertebrates usually breathe through the skin; the higher forms, when living in the water, by a specially developed system of gills; when land dwellers, by a special system of branching tubes known as " tracheae," which carry the air diiect to the blood-spaces surrounding the individual cells. In low temperatures, the frog can breathe by its skin alone. In man, 1-5 per cent, of the respiratory exchange is reckoned to take place through the skin, and somewhat more on sweating. A small amount of respiratory exchange takes place through air which is swallowed: certain fishes breathe by this method. Among the vertebrates, fishes have a special system of gills, by which the gaseous interchange between the surrounding water and the blood is effected. Amphibians in the larval stage — e.g., the tadpole — also possess Fig. 147. Upper curve shows lung volume, lower arterial pressure of cat with right vagus cut. At indication mark 0*0075 gramme of i)ilocarpine nitrate injected. There is constriction of the bronchial muscles, which diminishes the amount of air entering and leaving the lungs. The blood-pressure falls. Both effects are due to stimu- lation of the vagus nerve-endings. (Brodic and Dixon.) Fig. 148. Upper curve represents the volume of small lobe of lung, amount of air entering and leaving lung shown respectively by up-and-down strokes. Lower curve, blood- pressure. At indicated marks two small doses of lobelia injected into a vein. There is almost immediate dilatation of the bronchioles; the rise in blood -pressure is a vaso-motor effect. (Brodie and Dixon.) resting man, 300 to 500 c.c. The amount of air which can be taken into the kings by forced inspiration after a normal qviiet inspiration is the complemental air, averaging 1,500 to 2,000 c.c; that which •can by forced effort be expelled from the lung after a quiet expiration 280 A TEXTBOOK OF PHYSIOLOGY is the supplemental air, also 1,500 to 2,000 c.c. in volume. three together give the vital capacity of an individual. These Tidal air . . Complcmental air Supplemental air 300-500 c.c. 1,500-2,000 c.c. 1,500-2,000 c.c. Vital capacity ■.. .. 3,300-4,500 c.c. The vital capacity can be measured by expiring to the greatest extent after the fullest possible inspiration mto a spirometer (Fig. 149)' — a form of gasometer. The vital capacity of an individual can be Fig. 149. — Spiuu-metek. T, Mouth-piece; M, manometer; Cp, counterpoise; R, scale. greaty increased by practice. Some athletes (swimmers) have a> capacity of 6i litres. The amount breathed out depends largely upon proper muscular co-ordination. It also varies' with posture, being, greatest when standing, and least when lying doAvn. The amount of air left in the lungs after the greatest expiration possible has been taken is termed the residual air, and measures 1,500 to 2,000 c.c. The expired tidal air comes from the trachea, bronchi, and alveoli. It is calculated, of 500 c.c. expired, 140 to- 160 c.c. comes from the trachea and bronchi, forming the " dead- THE MECHANISM OF RESPIRATIOX 281 space " air, and the remainder from the aveoH — true alveolar air. The dead-space air does not undergo a respirator}^ exchange. In the resting man, 350 c.c. of the total tidal air mixes with 3,000 to 4,000 c.c. in the lungs (supplemental and residual air), so that only about one-tenth of the air is changed at each breath; much less in shallow breathing. In deep breathing, the complemental air is added to the tidal, and 1,660 to 2,360 c.c. mixes with the air in the kmg^ about one-half is changed. A sample of alveolar air may be obtained by expiring deeply through a piece of rubber tubing of about 1 inch bore and 4 feet length (Fig. 150). The " dead-space " air is blown out of the tube, and the tube is filled with alveolar air. The end of the tube is closed with the tongue or with forceps, and through the T -piece a sample is drawn off into a suitable sampHng tube, which has been previous^ evacuated Mouth pi zee Wi SsLmpling Tube Fig. ' )0. — Apparattts for Collection of Sample of Alveolar Air. and Priestley.) (Haldane by means of a reservoir fitted with a rubber tube. The sample may be taken at the end of a normal expiration following an inspiration, or preferabh' two samples may be secured, the second immediately after expiration following normal inspiration. The mean of the analyses gives the normal alveolar air. Alveolar air contains 4-5 to 6 per cent. CO.,, 13-5 to 15 per cent. Og, 79 to 80 x>er cent. No. The CO., percentage in men (5 to 6 per cent.) is generally a little higher than in women and children (4 to 5 per cent.). The composition of ordinary inspired air at normal temperature and pressure — 0° C. and 760 millimetres — ma}^ be given as follows: Oxygen Carbon dioxide Nitrogen * . . Water vapour Temperature Expired an-: Oxygen Carbon dioxide Nitrogen * Water vapour Temperature 20- 9-2 volumes per cent. 0-03-0-04 . 79-03 \'ariablo Variable 16-00 per cent. •4-00 „ 80-00 „ Saturated 37° C. * Including 0-94 per cant, argon. 282 A TEXTBOOK OF PHYSIOLOGY Expired air is diminished about one-fiftieth in volume as com- pared with the inspired air. This is due to the oxygen combined with products of tissue oxidation which passes out of the body in the urine. To obtain expired air for analysis, the subject breathes M B Fig. 151. — Haldane's Gas Analysis ArrAKAXUS. through a mouth-piece, provided with inlet and outlet valves, inta a large rubber-lined canvas bag. The contents of the bag are squeezed through a meter, and thus the volume of expired air measured ; while a sample is secured for analysis by means of a T-piece into an evacuated sampling tube. If the subject breathe for, say. THE MECHANISM OF RESPIRATION 283 ten minutes, and the number of respirations be counted, the tidal air ean be calculated ; from the analysis the respiratory exchange can be estimated as well as the composition of the expired air (see later, p. 317). One of the best forms of apparatus for the estimation of the gases in inspired and expired air is shown in Fig. 151. The gas is measured in the graduated gas-burette .4, provided with a three-way tap. Surrounding the gas-burette is a water-jacket. The whole is supported b}' a clamp and retort stand. The gas-burette is connected b}' pressure tubing to the levelling tube B, which is held by a spring clamp attached to the retort stand. A and B contain mercury, and by raising or lowering B gas can lie expelled from or drawn into .4. One of the connections of the three-waj- tap is used for taking in the sample, the other connects the burette with an absorption apparatus arranged as in the figure. The bulb E, filled with 20 per cent, caustic potash, absorbs CO,. The bulb F, filled Avith alkaline pyrogallic acid solution, absorbs O.,. Alkali in G and H protects the p\To solution from the air. F is emptied and refilled through K. The tap on the absor])tion pipette places either E or F in connection with the gas-burette. There is a control tube by A\hich alterations in temperature or barometric pressure during the analj'sis can be compensated for. The sample of gas is taken into the burette from the sampling tube (Fig. 150), mercury being sucked into the tube to take the place of the gas entering the burette. After measuring the amount of the sample it is passed into E to absorb CO.^. When a constant reading is obtained, it is passed into F until all the oxygen is absorbed. To take an example : Suppose the amoimt of gas taken in was 20-12 c.c. After absorption of carbon dioxide in E the burette reading was 19-06; after absorption of oxvgen in F it was 16-01. Then in 20-12 parts of the sample there is 20-12- 1906 = 1-06 of CO^, in 100 parts therefore there are — 1-06x100 2().|2 — = 5"22 approx. Also in 20-12 parts of the sample there are 19-06- 16-01 -3-05 parts of 0-2 . In 100 parts therefore there are — 3-05 X 100 20-12 ^^"^'^^ approx. The percentage of sample, therefore, is 5-22 Ci).^; l"ill O2. CHAPTER XXXII THE MECHANICS OF BREATHING To facilitate gaseous interchange, the process of breathing or ventilation of the kings takes place. In the act of inspiration in mammals the chest is expanded, air is drawn into the lungs ; in the act of expiration the chest and lung capacity is diminished, and air forced out from the lungs. Anatomical Considerations. — To understand properly the move- ments concerned in the processes of inspiration and expiration, certain anatomical details in regard to the bony framework and the muscula- ture of the thorax have to be considered. The varying extensibility of different parts of the lung has also to be borne in mind. In the inspiratory movement, the thorax is expanded in three dimensions. In regard to the exact manner in which these move- ments take place there is still some uncertainty. The chief move- ments, ho\\ ever, may be grouped as — 1. The movements of the diaphragm. 2. The movements of the ribs and rib cartilages. Breathing of the abdominal type, such as occurs in man, is chiefly diaphragmatic; breathing of the thoracic t\^e, such as takes place in corsetted women, is mainly costal. Normally, breathing is a combination of the two t_\"pes — sometimes one, sometimes the other prevails. The Action and Movements of the Diaphragm. — Separating the thorax froiii the abdomen, the diaphragm, in its resting position, reaches up to aboiit the fifth intercostal space. The fleshy part of the muscle lies close to the ribs, the central dome-like part being mainly of a tendinous nature. There has been considerable speculation as to the exact nature of the movements performed by the diaphragm. The view commonh' expressed is that the muscle, by its contraction, in association with muscles which fix the throax, opens up the angle which it forms with the thoracic wall, thereby enabling the lung to expand in a downward direction. In such a movement the central tendinous portion is supposed not to participate. After contraction, it is assumed that the diaphragm passively returns to the position of rest. Recent study of the diaphragmatic movement by means of the X rays has shown, however, that there is a forward downward move- 28 i THE MECHANICS OF BREATHINC4 285 ment of the whole diaphragm, accompanied by a definite move- ment of the abdominal viscera. The diapln-agm may be regarded as. consisting of two parts: (1) The spinal, or crural, from the spinal column and arcuate ligaments to the back portion of the central tendon; (2) the costo-sternal, or anterior, attached to the front and sides of the central tendon, and arising by several digitations from the ribs. The arch of the diaphragm rests upon, and is supported equably by, the abdominal viscera, and is at the same time kept constantl}" applied at the circumference to the inner wall of the thorax by the negative intrathoracic pressm-e. Thus, when its two parts contract, it acts like a true piston, moving in a forward and downAvard direction. In quiet, normal breathing the amount of movement of the right dome is about i inch, that of the left dome and of the central tendon somewhat less. The Movement o£ the Ribs. — In general, two movements of the ribs are recognized as taking place in insjjiration : (1) Round an axis cor- responding to the spinal articulation, increasing the back-to-front diameter of the thorax; (2) round one corresponding to the spino- sternal articulation, increasing the diameter from side to side. Owing to the variation in size, shape, inclination, and articulation of the ribs, such an explanation, while essentially true in a general sense, is im- perfect. It is better to divide the ribs into two sets: (1) The upper, the second rib to the fifth; (2) the lower, the sixth rib to the tenth. These two sets differ in their musculature, in the nature of their articu- lation and ligaments, in their shape and arrangement, and in their movements. It is better not to regard the first rib as one of the costal series, but to associate it with the manubrium sterni, with which it performs a special movement of its own. The lowest two ribs, inasmuch as they are unattached in front^ — '" floating " — are essentially j^arts of the abdominal wall. Concerned in the resjiiratory movements, there- fore, are — 1. The first rib and manubrium sterni. 2. The upper costal series (2-5). 3. The lower costal series (6-10). 4. The floating ribs (11, 12). The First Rib and Manubrium Sterni. — The first pair of ribs and the manubrium sterni are intimately bound together, and form, Avith the manubrium, a lid or operculum to the thorax. Behind this lid is articulated with the spinal column, in front with the body of the sternum, the manubrio- sternal joint (Fig. 152). During inspiration there is a slight upward movement of the lid, allowed by the manubrio- sternal joint, which causes an expansion of the anterior part of the apex of the lungs. This movement is particularly marked in the thoracic tvqje of breathing. To demonstrate the movement at the manubrio -sternal joint small mirrors are fixed above and below this joint, and the movements of the reflected spots of light observed on a screen. During inspiration the spots diverge, during expii-atiou 286 A TEXTBOOK OF PHYSI0LO(;V they come together. In people ^ith ill-developed chests there is but little iiiovement here. The posterior part of the apex of the lung is but little affected by the movement of the operculum, its expansion being seciu'ed by diaphragmatic breathing. The Movement of the Upper Ribs. — It is on these that most of the observations upon rib movements and the action of the intercostal muscles have been made. During inspiration, both sets of intercostal muscles act together, and draw up the upi)er ribs towards the operculum, which acts as a fulcrum. During expiration, the lower set of ribs are fixed, and act as fulcrum, and the upper set are (h-awn down toward them by the intercostal muscles. This- view of the action of the intercostals is not accepted by everyone. There is some experi- mental evidence to show that the external intercostal muscles act during inspiration. The fibres slant from above downwards and for- 17/ Ce^y.'/eri:.' ^4 NecU of l^t F^'ib Apex oF Lung ^^^^^«^^^ ^"" ^'^ l^'Rib (inspir.) . ^-^^^^^^^^^^rd Manub.OnspirJ - ^ J^%g^ u^^^V^ "'^ Manub.ie.p.)-yL.^ '^^^-^ttS Fig. 152. — Diagram tu show Respiratory Movements of the First Pair or Ribs AND Manubrium Sterni and the Effect or these Movements on the Expan- sion OF THE Apex of the Lung. (Keith.) wards, and. shortening, raise the ribs. The fibres of the internal intercostals. on the other hand, slant from above downwards and backwards, and. shortening, lower the ribs. The Uvo, acting together, make rigid the thoracic wall. The intercartilaginous fibres act with the external intercostals. The Movement of the Lower Ribs. — The purpose of the miovement of the lower ribs is to expand the lower lobe of the lung. The dia- phragm is .the chief muscle concerned, aided by the ilio-costalis^ and the external intercostals, and the interchondral muscles. The an- tagonistic muscles are the external oblique, the internal oblique, and the trans versalis. During inspiration, owing to the mode of articulation of the ribs, the lateral and anterior part of each moves outwards more than the one above. At the same time, the lower ribs are raised, together with the sternum, so that the net result of the lower rib movement is to increase the transverse and back-to-front THE MECHANICS OF BREATHING 287 diameter of the lower thorax, and, with the diaphi-agm moving down- wards, the vertical diameter of the whole cavit>^ Inspiration is therefore a very complex act, "and it is owing to the complicated nature of the movements concerned that the lungs are divided into lobes. The upper ribs are chiefly concerned in the Lower Bord. (exp Louver Bord. Crus (inspir Crus (expir Fig. 153. — Mediastinal Aspect of Right Luxg to show Respiratory Movement OF the Root. (Keith.) The crus of the diaphragm is also indicated, and its attachment to the root of the lung thi-ough tlie pericardium. Arrows indicate direction of inspiratory move- ment of various parts of the lung. expansion of the upper lobes, the lower ribs in the expansion of the lower lobes, the diaphragm promoting the expansion of the M'hole In the act of inspiration it is also to be noted that, owing to the varjing degree of extensibilit}^ of the different structures of the luno-, the organ expands more in the manner of a Japanes3 fan — least in the neighbourhood of the great vessels and bronchi (the root of the lung), most in the outermost zone just beneath the pleurae (subplein-al zone). 288 A TEXTBOOK OF PHYSIOLOGY The infundibula also vary in size in these different zones of the lung, being largest in the subpleural zone, and smallest at the root of the lung (Fig. 153). The two surfaces which are most expanded are the diaphrag- matic and the sterno-costal, or ventro -lateral. In general, the apical surfaces remain almost stationary. It is only when the lungs are well ventilated that the parts most remote from these surfaces of direct expansion are brought properly into action. In peoj)le of sedentary habits, therefore, such parts of the lung fall into a condition of disuse, and receive a poor supply of blood, with its immunizing properties. This explains why phthisis so frequently attacks the apex of the lungs first. tT'! When inspiration becomes forced, accessory muscles, such as the scaleni, sterno-mastoid, trapezius, pectoral, rhomboid, and serratus anticus muscles are brought into play. The arms are fixed, so that the muscles passing from the thorax to the arms can come into play on the thorax. A patient suffering from dyspnoea sits up, and grasps the arms of a chair. In regard to expiration, it is often stated that quiet exinration is brought about by a passive collapse of the expanded liuig, the thorax following this recoil b}' virtue of its weight. It seems probable that such a process is aided and made to work smoothly, even in quiet expiration, by the contraction of the muscles antagonistic to those concerned in inspiration. Such muscles are those of the abdominal wall, and possibly the internal intercostals. In forced expiration many muscles are called into pla}^ such as the serratus posticus inferior and the rectus, obliquus, and trans- versus muscles of the abdominal wall. CHAPTER XXXIII THE REGULATION OF BREATHING The movements of respiration are regulated by a centre which has been localized in the medulla oblongata. This localization has been made by watching the effects upon respiration of removal of the brain from above downwards and from below upwards. By this means it is found that, when an area of grey matter in the floor of the fourth ventricle is damaged, all signs of respiratory movement completely cease. To this centre run afferent nervous paths from various parts of the body, and also from the higher nervous centres; from it pass Jmpu/sesC+and-) from cerebral cortex. Impulses (.-) from nostrils. Impulses(-or+)from skin. Impulses(-)from larynx. Impulses from bn^s limiting excessive inspiration ancK?) excessive expiration lo intercostals. To diaphragm. To accessory muscles m laboured breathing. Vui. 13-i. — Diagram illustrating Regulation !)<> Hyperpnoea, Dyspnoea. — By hyperpnoea, increased volunie of breathing is designated; dyspnoea, on the other hand, applies to dis- tressful breathing. Both may be induced by the agencies which excite the respiratory centre to increased action, such as excess of carbon dioxide, Avant of oxygen, diminished alkalinity of the blood, due to acid formation, and rise in the temperature of the blood (heat dyspnoea). The cardiac dyspnoea of heart disease is chiefly due to Avant of oxygen. Apnoea. — The condition of "' no breathing" is due to a lack of chemical stimulation of the respi- ratory centres. It occurs after forced breathing which washes out carbon dioxide from the blood (Fig. 164). It is claimed that there exists also a " vagus " apnoea, produced in animals by repeated rapid distension of the liuigs b}^ artificial means. By this means the inspiration-inhibiting fibres of the vagus are so stimulated that apnoea ensues. This apnoea may be due to washing carbon dioxide out of the l)lood, but it is more difficult to obtain when the vagi are cut; it is stated that if the ventilation of the lungs be made with an indifferent gas, such as hydrogen, it is jDossible to obtain apnoea, but not after the vagi arc cut (Figs 165, 166). It is very doubtful if vagus apnoea occurs in man, for it has been shown that apnoea cannot be produced if the alveolar air percentage of CO2 is not reduced below the normal CO., percentage. Periodic, Grouped, or Cheyne- JStokes Breathing. — Group ])reath- ing is natural in young children when asleep, and in hibernating (-i o ■A — < '1. s 6 1^ n '1 O o c5 g 300 A TEXTBOOK OF PHYSIOLOGY animals. Cheyne-Stokes breathing is a type of breathing characterized by a Avaxing and waning of the depth of the respiratory movements (Fig. 167). Starting from a state of apnoea, the respirations gradually Fig. 165. — Cat, Vagi Intact. Fig. 166. — Same Cat as Fig. 165. (F, H. Scott.) Vagi Divided. (F. H. Scott.) Upper tracing, thoracic respiration re- corded by means of tambours; lower tracing, carotid blood-pressure. Period of insufHation of lungs shown by rise iu line of respiratory tracing. , become more and more marked, reaching a maximum where the depth is considerably deeper than normal, and then gradually decline again, and cease, to be followed by another period of activity. This type of breathing occurs clinically in cases with defective circulation, renal Fig. 167. — Chevxe-Stokes Respiration. disease, etc., and is due to oxygen- want in the respiratory centre, which causes it to act in a periodic manner. Oxygen -want causes a hyperpnoea Avhich reduces the alveolar percentage of COj. Apnoea then results THE REGULATION OF BREATHING 301 until oxygen want again stimulates the centre. Group breathing may be abolished by the giving of ox^^gen, or breathing 2 to 3 per cent. CO.,. It frequently occurs at high altitudes, owing to the diminished partial pressure of oxygen in the rarefied atmosphere. It can be produced experiment all j' in most people by forced breathing for two to three minutes. After the subsequent apnoea, breathing returns for the lirst few minutes in a periodic fashion. If, however, the lungs are filled with oxygen instead of air at the end of the forced breathing, the apnoea is of much longer duration, and breathing returns in a perfectly regular manner. Under these circumstances, in addition to the ordinary respiratory oscillations, rhythmic variations of pressure frequentl}^ appear in the tracings of arterial pressure. These variations are known as Traube- Hering curves. They can be evoked by the injection of a little magnesium sulj)hate solution into the circulation of the dog (Fig. 168). During the asphyxial rise of arterial pressure in the curarized dog, Fi3. li)3. — Tkaube-Hering Cukves after Injection of Magnesium Sulphate. these curves occur, and also after injection of a large dose of morphia. In conditions of ansemia of the bulbar centres, produced either by tying the cerebral arteries, or compression of the brain, and after injection of chloroform into the cerebral arteries, Traube curves frequently become apparent. In periodic respiration of cerebral origin, the waxing and waning of the blood-pressure seems to be due to the effect of the venous blood on the vaso-motor centre, rather than on the heart. Oxygen -want stimulates the respiratory and vaso-motor centres at the same time. In the case of morphia, the respiratory centre injured by morphine does not react to the acid ions in the blood until these reach a con- centration which injiu'es the heart. The pieriodic fall of pressure in this case is due to an asphyxia of the heart. When the breathing starts, the heart recovers, and the blood-jiressure rises. The breathing ceases once more so soon as some of the carbon dioxide in the blool has been exhaled. CHAPTER XXXIV THE EFFECTS OF EXCESS OF CARBON DIOXIDE Breathe]) in very high percentages, 30 per cent, and upwards, CO., acts as an anaesthetic and narcotic. There is first induced a spasm of respiratioti . then consciousness is lost, the respiration becomes quiet, the heart-beat enfeebled, and death ensues owing to the direct action of COo upon the heart-muscle. In smaller percentages 00^ has an excitatory effect — at first upon the respiration, then upon the circulation also. A .small increase of COg in the air breathed in causes a marked increase in pulmonary ventilation. With an increase of 3 per cent, this becomes noticeable to the person breathing; with 5 per cent, the hyperpnoea is very marked, the respirations are quick- ened, the pulse becomes quicker and fuller; with 6 per cent, there begins to be a retention of CO.^ within the body, breathing is distressful, headache develops, ])rofuse sweating breaks out. The blood-pressure is greatly raised, and the pulse may be felt drumming in the ears. Later, the mind becomes confused, and loss of consciousness ensues. It is possible for a man, having filled his lungs with oxygen, and then holding his breath, to run himself into a state of unconsciousness. In such cases, as mtich as 11 per cent, of C'O., is found in the alveolar air. Athletes who run themseh'CS out are overcome by the excess of acid in the blooi ! . Most deaths attributed to excess of carbon dioxide are in reality due to oxygen-want. High percentages of COg sufficient to cause death cause spasm ^ »f the glottis and choking. Divers have often been over- come by an exc(^s,s owing to defective supply of air in deep water. At a pressure of, say, 4 atmospheres (100 feet) there is four times the volume of air in the helmet, and to ventilate it four times as much air must be pumped through it as at I atmosphere. It has not been recognized until recently that the deeper the diver goes, the more air must be given him. Effects of Deficiency of Carbon Dioxide. — If carbon dioxide be washed out of the body by forced breathing, the desire to breathe disappears for a time, and a condition of apnoea ensues, which may la.st as long as two to three minutes, and even longer (Fig. 164). If oxygen be forcibly breathed, the apnoea may last five to seven minutes, and even nine minutes. Forced breathing produces a curious condition of spasm of the hand, sensations of " pins and needles " in the hands and feet, with coldness and pallor, and a sensation of tight- 302 THE EFFECTS OF EXCESS OF CARBON DIOXIDE 303 ness round the head. The forced breathing of oxygen is unaccom- panied by such feelings. Probably a certain tension of CO., is required in the body fluids for the proper carrying out of many bodily processes. If this be lessened, such processes are impaired. Effects of Excess of Oxygen. — Breathing an excess of oxygen under normal conditions does not cause increased oxidation of the bod}-. The body cannot be fanned Uke a fire into rapid combustion. The nervous system sets the rate of activity of the tissues. When, however, hard ft Fii;. 169. — Section of Luxa showing Exudation in Bronchial Tube and Alveum OF Lung produced by Three Atmospheres of Oxygen. (Bulloch and Hill.) muscular ^^■ork is being performed, an excess of oxygen in the alveolar air enables more work to be done. This is because it prevents the formation of lactic acid in the muscles, and thus lessens the hyperpnoea, Avhieh renders work inelficient, and maintains the force of the heart. High percentages of O2 — e.g., 3 atmospheres — act as an irritant to the lungs, induce pneumonia (Fig. 169), lower the metabolism, and cause convulsions. Breathing of pure ox3'geii for several hours at ordinary atmospheric pressure does not have any harmful effect, but it causes pneumonia if breathed continuously for a dav or .304 A TEXTBOOK OF PH>'SlOLO(JY Iavo. An atniosphcro containing under 70 ])cr cent, of oxygen can he breathed witli impimily for any length of time. The Effects oi Want of Oxygen. — The s3nnptom.s produced vary greatly according to the rate at which such want is produced. When immediate, as on breathing into the lungs marsh-gas, nitrogen, or hydrogen, there is rapid loss of consciousness, followed by convul- sions (Fig. 170), with a slight rise of blood-j)ressure, followed by <;cssation of respiration, broken only by occasional inspiratory gasps, iall of blood-pressure, due to vagus inhibit 'ou. and death. l^iG. 170. Uj)))or tracing, respiration recorded by diaphragm .-lip: lower tracing, carotid blood- pressure. Time=t\vo f-cconds. During period indicated 5 per cent, oxygen in nitrogen was inhaled. (F. H. Scott.) A match or candle will not burn when there is less than 17 per cent, of oxygen in the atmosphere, but a man feels no inconvenience until the oxygen percentage falls below 14 per cent. Then there supervenes a hyperpnoea of gradual onset, Avith a slight rise of blood- pressure, increased pulse-rate, and marked cyanosis; and when about -6 per cent, is reached, lois of consciousness quickly takes place. At first, on breathing 14 to 10 per cent. O2, there is a slight exaltation. The person has tlie greatest confidence in himself, and is quite con- fident that he is '" all there.'' whereas, in reality, his mental capacity is greatly affected. The breathing is deepened, but no dyspnoea is present. Then, at about 8 per cent., without warning, or possibly THE EFFECTS OF EXCESS OF CARBON DIOXIDE 305 ^vith slight dyspnoea or air-hunger, consciousness may be lost, followed by i^aratysis, or in some cases the parah'sis of the muscles, particularly those of the limbs, may precede the loss of consciousness. Thus, in a balloon ascent, at 29.000 feet, Coxwell, although suddenly finding .himself jiaralyzed in his limbs, Avas able to pull M'ith his teeth the safet\'-valve rope of the balloon, and to save himself and Glaisher. In the case of the ascent of Croce-Spinelli, Sivel, and Tissandier, the aeronauts were all paralyzed suddenly before they could breathe from the oxygen bags with which they had provided themselves. Similar symptoms follow gradual poisoning by carbon monoxide or €oal-gas. Miners display the same lack of judgment when affected by carbon monoxide. Xormal respiration 1st stage (prolonged expiration) 2nd stajje (exj)iratjry eonvulsionsj 3rd si age (exhaustion ) Time iu seconds Fig. 171. — Asphyxia Tracing : Rabbit. (Waller. The line falls with inspiration, rises with expiration. In carbon monoxide jjoisoning, the lack of oxygen is brought about by the decreased oxygen-carrying capacity of the blood, due to the iormation of COHb. The symptoms begin to sho v themselves Avhen the blood is one-fourth saturated. With 50 per cent, saturation, thf mental sj-mptoms become mai-ked. and the slightest exertion is danger- ous, since it may bring on convulsions and death. It is dangerous to breathe air containing as little as 0-05 per cent. CO, for the affinity of CO for Hb is about 150 times that of 0.,. There is 5 to 6 per cent. CO in coal-gas, as much as 30 per cent, in water-gas, 3 per cent, or more in after-damp after explosions in mines. CO 03curs in con- •20 :o6 A TEXTBU(JK OF PHYSIOLOGY lined places where there is fuel burning with deficient oxygen-.su])ply.. To relieve CO poisoning, oxygen should be administered, and artificial respiration ])erfornied . The whole of the body is very susceptible to a deficiency of oxygen; it leads to acid formation and lessened alkalinity of the tissues. Oedema, cloudy swelling, and fatty degeneration, according to recent research, are associated with such diminished alkalinity. Lack of oxygen greatly affects the working capacitj' of the muscles, especially of the heart-muscle. Irritant gas poisons, by prtducing cede n: a of the lungs, cause oxygen-want. Recoveiy is very slow or may not occur after prolonged oxygen-want. Symptoms of oxygen-want may also he induced by poisons which form methaemoglobin. Such poisons are the chlorates of sodium and potassium, nitrites, and dinitrobenzene. EiG. 172. T, Tracing of tb-racic uiovemcnts; A, liacing of abdominal movements. In top tracing is sho-wn the respiratory movements and time (a — oj) during which hreath could be held in Turin. In lower tracing the same at Monte Rosa (l.')003 feet above sea-level). The increased depth of respiration and inability to hold the breath long is well seen. (Mosso.) Asphyxia is caused by interference with the ventilation of the lungs. It may be produced by breathing an irrespirable gas, as already described, but it may also be produced by such means as occlusion of the trachea or opening the chest cavity. When studied experiment- alty — as, for example, by clamping the trachea — asphyxia is di^•ided into three stages (Fig. 171): 1. The stage of increasing dyspnoea. 2. The convulsive stage. 3. The stage of exhaustion. When the trachea is clamped, the first stage lasts about a minute. The breathing is markedly increased in depth, expiration being pro- THE EFFECTS OF EXCESS OF CARBON DIOXIDE 307 Joiiged; the heart-beat is increased in force and frequenc}'; the blood- pressure rises; the tongue in the case of an animal, the lips and face also in the case of rnan, darken to a purplish hue. In the second stage, the respiration becomes violent and con- vulsive; the blood-pressure remains high, due to the vaso-constriction produced; the heart-beats show the sign of vagus inhibition; the duskiness of the mucous membranes increases. In the thh'd stage, the breathing and convulsions practically cease; the heart beats feebly and irregularly; the blood-j)ressure gradually falls, and the tracing shows marked undulations of pressure, known as the Traube-Hering Avaves (Fig. lOS). The pupils become Liens Arc -light Microscope Frog- Screen Compressed air cylinder Fig. 173. — Diagram of Apparatcs by which Eff:;ct of Compression and Decompression is stjdied upon Capillaries of Frog's Web. dilated, the mucous membranes become pale and anaemic, faeces and urine may be voided. Post mortem, the right side of the heart is found distended with blood, the left side contracted and empty. The great veins and the lungs are also engorged with blood. Effects of Diminished Atmospheric Pressure. — Another train of symptoms due to oxygen-want is that known as " mountain or alti- tude sickness." It effects aeronauts as well as mountain-climbers. In their case, the oxygen-want results from the d;min'shed atmo- sj)heric pressure, and consequent reduction in the partial pressure of the oxygen in the blood. The symptoms are headache, nausea, distress in breathing, especially upon exertion. Mountain sickness frequently begins at altitudes of 6,000 to 10,000 feet, particularly 308 A TEXTBOOK OF PHYSIOLOGY if the ascent has been fairly rapid b}^ railwaj^, so that no adapta- tion takes place during the journey. It is suggested that the oxygen- want leads the kidney to excrete more base than acid from the blood, and thus increasing the breathing, lessens the concentration of carbon dioxide in the blood and alveolar air. By lessening the concentration of CO, in the alveolar air, that of oxygen is increased. The effect of oxygen-want is well seen in the inability vohnitarily to hold the breath for any length of time (Fig. 172). Acclimatization takes place in about eight to ten days. This is due, in the first Fig. 174. — View of Chamber used for Study of Effects of Compression and Decompression on Man: Workman Inside. (Hill and Greenwood.) The chr^mber is fitted with electric belt, electric light, telephone, observation window, compression pipe from gas-engine, decompression tap. place, to a concentration of the blood-plasma, followed by an increased formation of blood-corpuscles and hsemoglobin (Fig. 18). Hence the oxygen-carrying power of the blood is increased ; an alteration in the acid concentration of the plasma compensates for the diminished jjartial pressure of carbon dioxide. On the strength of determinations of the partial pressure of oxygen in the blood, by the CO method (p. 273), it is asserted that compensation is brought about by secretory activity of the king epithelium, since the oxygen-pressure of the arterial blood has been THE EFFECTS OF EXCESS OF CARBON DIOXIDE cOO found to be 35 millimetres above the oxygen-pressure in the alveolar air. But there are doubts as to the validity- of this method. Airmen usuallj' suffer at altitudes from 15,000 to 20,000 feet. In their case there is no evidence of acclimatization to the effects of high altitudes. Administration of oxygen mitigates these ill effects. <*» Fig. 175. — Air Bubbles Set Free ix Vessels of Heart after Rafid Decompression, (v. Schrotter.) Increased Atmospheric Pressure — Caisson Diseass. — In contra- distinction to the effects of diminished barometric pressure, increased barometric pressure in itself produces no untoward symptoms. " Caisson Fi ;. 176. — To show Gas Bubbles in Arteries and Veins of Intestines after Rapid Decompression, (v. Schr6:ter.) disease " and " diver's palsy" result from the effects of decompression from a high atmospheric pressure, not from the compression. Caissons. 310 A TEXTBOOK OF PHYSIOLOGY are steel chaniljers filled with compressed air, and provided with air- locks, used for excavating tunnels and foundations of bridges under water. Divers are encased in a dress into which air is ] umped at a pressure just greater than that of the superincumbent water. A ^^'^....^^^ffo% A ^"•'■■:^^7 -'-->-'•- '*'.^^^-^- >/ ^ •A t,-"^' .t*^ •/.'' .,i't -"'^^i^-*' » It • • Fig. 177.— -4, Normal Kidney of Cat; i?, Kidney of Cat DEcoJMrr.issLD Rapidly FROM Eight Atmospheres prepared by' Same Method. At a pressure of 2 to 3 atmosi)hercs it becomes impossible to Avhistle or whisper, owing to the density of the air. There are no sensations, beyond this disability, to indicate the abnormal pressure. The pressure in the middle ear has to be equalized by opening the Eustachian tube during the rise of atmospheric pressure. This can be effected THE EFFECTS OF EXCESS OF CARBON DIOXIDE 311 I)y swallowing, or b}' an expiratory effort made with the mouth and nose shut. The symptoms of sickness range from small pains in the joints and muscles, known as '" bends," to sudden paralyses or death. The subject has been thoroughly studied experimentally (Figs. 173, 174) and the cause of the troiible is now clearly understood. At high pressures the blood and fat take up large quantities of nitrogen in simple physical soAition. When the pressure is reduced rapidly, the nitrogen becomes freed in the circulation, and, becoming lodged as bubbles of gas in various parts of the body, produces symptoms of varying severity according to the degree of damage and the site of injury (see Figs. 17.1-178). Rapid decompression is therefore the danger. The rate of decompression must be regulated according to the pressure and period of saturation of the body. A diver who has been for a short time at Pig. 178. — ^Xeirotic Areas (Pale) in Posterior Columns of Spinal Cord, frcm A Fatal Case of Compressed Air Illness, (v. Sehrotter.) a great depth may be relatively more quickly decompressed than a man who has been working several hours in a less pressure. The decompression is carried out in stages, for it is safe to allow a certain amount of supersaturation, as bubbles do not easily form in the blood — e.g., the diver ascends rapidly from a depth of 100 feet (4 atmos- pheres) to 33 feet (2 atmospheres), and pauses there for some time, meanwhile exercising his muscles to accelerate the circulation and ventilation of the lungs, and so wash the excess of dissolved nitrogen out of his bod}'. He then returns to the smface. For each atmos- phere of air the water of the body dissolves about 0-8 per cent, of nitrogen. As fat dissolves five to six times as much nitrogen as water, there is particular danger of bubbles forming in the nervous ti.ssues. All fat men are excluded from work in deep water. The solution of nitrogen in the body fluids durmg compression and the giving out of the excess of dissolved nitrogen dining decom- pression has b?en stuelied on subjects who drank a epiart or so of water just before entering the chamber, and collected samples of their mine at various stages of compression and decompression. The nitrogen dissolved in these samples was pumped out by means of the mercurj' gas pump and estimated. CHAPTER XXXV THE PRINCIPLES OF VENTILATION Our comfort or di.scouifort in crowded rooms and shut-up places depends on the chemical purity of the air only in so far ?.s it afiects the olfactory sense, but. to a vast degree, on the influence of the temperature, relative humidity, and the variations of these qualities of the air, which act on the great field of cutaneous sensibility. When it is stated that the chemical purity is of little account, the proviso is made that the air is only altered by the presence of healthy human beings, and is neither renclered poisonous by the escape of coal-gas, or other noxious trade product, nor deoxygenated by the oxidative pro- cesses of the soil, as it is in mines, reference l^eing made only to the discomfort and ill-health caused by the deficient ventilation of, or bad methods of heating, dwelling-houses, schools, factories, theatres, chapels, etc. The chemical purity of the air has to be considered from three points of view- — the concentration of carbon dioxide, the concen- tration of oxj^gen, the su]iposed presence of organic poison exhaled in the breath. It is commonly supposed that any excess of COo acts as a poison. The truth of the matter is quite otherwise; for, Avhat- ever the percentage of CO., in the atmosphere may be, that in the pulmonary air is kept constant, as we have seen, at about 5 per cent, of an atmosphere by the action of the respiratory centre. It is there- fore impossible that any excess of CO., should enter into our bodies when we breathe the air of the worst -ventilated room, in which the percentage of CO.^ assuredly does not rise above 0-5 per cent., or at the outside 1 per cent. The only result from breathing such an excess of COg is a slight and unnoticeable increase in the ventilation of the lungs. The increased ventilation is exactly adjusted so as to keep tl e concentration of CO., in the lungs at the normal 5 per cent, of an atmosphere. At each breath we re breathe into our lungs the air in the nose and large air-tubes (the dead-space air), and about one-third of the air which is inhaled into the lungs is " dead-space " air. Thus, no man breathes pure outside air into his lungs, but air contaminated perhaps by one-third or (on deep breathing) by one- tenth with expired air. When a child goes to sleep with its head partly buried under the bedclothes, or in a cradle with the air con- fined by curtains, he rebreathes the expired air to a still greater 312 THE PRINCIPLES OF VENTILATION 313 extent, as do all animals that snuggle together for warmth's sake. Not only the newborn babe sleeping against its mother's breast, but pigs in a stye, young rabbits, rats and mice clustered together in their nests, young chicks under the brooding hen, all alike may breathe a higher percentage than that legally allowed in spinning mills or Aveaving sheds. To rebreathe one's own breath is a natural and inevitable performance ; to breathe some of the air exhaled by another is the common lot of men who, like animals, have to crowd together and husband their heat in fighting the inclemency of the temperate and Arctic zones. By a series of observations made on rats confined in cages with small ill-ventilated sleeping chambers, it has been shown that the temperature and humidity of the air — not the carbonic acid and oxygen concentration of the air — determines whether the animals stay inside the sleeping-room or come outside. When the air is cold, thej^ hke to stay inside, even when the carbonic acid rises to 4 per cent, or 5 per cent, of an atmosphere; when the sleeping chamber is made too hot and moist, the}" come outside. In breweries, the men who tend the fermentation vats work for long hours in concentrations of CO^ of 0-5 to 1-5 per cent. Such men are no less healthy and long-hved than those engaged in other processes of the brewing trade. The ox\'gen in the worst-ventilated schoolroom, chapel, or theatre, is never lessened by more than 1 per cent, of an atmosphere. The ventilation through chink and cranny, chimney, door, and window, and the porous brick wall, suffices to prevent a greater diminution of the oxygen concentration. In all the noted health resorts of the Swiss mountains, such as St. Moritz, the concentration of oxygen is lessened considerably more than this. On the high plateaux of the Andes there are great cities: Potosi, with 100,000 inhabitants, is at 4,165 metres (barometric pressure about 440 mm. Hg). Railways and mines have been built even at altitudes of 14,000 to 15,000 feet. Owing to the nature of the chemical combination of oxj^gen with haemoglobin, man can adjust himself to verj' great variations in oxygen concentration. At Potosi, girls dance half the night, and toreadors display their skill in the bull-ring. All the evidence goes to show that it is only when oxygen is lowered below a pressure of 14 per cent, to 15 per cent, of an atmosphere that signs of oxygen- want arise. A diminution of 1 per cent, of an atmosphere has not the slightest effect on our health or comfort. A commonly accepted hypothesis is that organic chemical poisons are exhaled in the breath, and that the percentage of CO.2 is a valuable guide as to the concentration of these. It is believed necessary to keep the C0.> below 0-1 per thousand, so that the organic poisons may not collect to a harmful extent. The evil smell of crowded rooms is accepted bj' most as unequivocal evidence of the existence of organic chemical poison in the exhaled breath. This smell, however, is only sensed b}', and excites disgust in. one who comes to it from the outside air. He who is inside, and helps to make the " fugg." is whoUv unaware of the sp.me. and unaffected eo- 314 A TEXTBOOK OF PHYSIOLOGY by it. While wc naturally avoid any smell that excites disgust and jnits us off our appetite, yet the offensive quality of the smell does not prove its poisonous nature. On descending into a sewer, after the first ten minutes the nose ceases to smell the stench ; the air therein is usually found to be far freer from bacteria than the air in a school- room or tenement. If we turn to foodstuffs, we recognize that the smell of alcohol and of Stilton or Camembert cheese is horrible to a child or dog, while the smell of putrid fish — the meal of the Siberian native — excites no less disgust in an e])icure, who welcomes the cheese. Among the hardiest and healthiest of men are the North .Sea fishermen, who sleep in the cabins of trawlers reeking with fish and oil, and for the sake of warmth shut themselves up until the lamp may go out from want of oxygen. The stench of such surroundings may effectually put the sensitive, untrained brain-Avorker off his appetite, but the robust health of the fisherman proves that this effect is nervous in origin, and not due to a chemical organic poison in the air. The supposed existence of organic chemical poison in the expired air is based upon experiments in Avhich either the condensation water obtained from the breath, or water which was used several times over to wash out the trachea of dogs, was injected into guinea-pigs and rabbits. The water Avas injected subeutaneously and in large amounts, and produced signs of illness, collapse, and death. vSuch experiments have been repeated b}^ many others, and with negative results by those whose methods of work demand most respect. A few confirmatory results have been obtained by methods of experi- ment which are truly absurd in their conception: 1 to 2 c.c. of con- densation water (obtained by breathing for many hours through a cooled flask) have been injected into a mouse weighing 13 grammes or so. This is equivalent to injecting 5 litres of water into a man weighing 65 kilos. Who would not be made ill by the injection of about 9 pints of cold water beneath his skin ? It has been shoAvn that injections of pure water alone in doses of over 1 c.c. may make a mouse ill. In the washings of a dog's trachea, or the condensation fluid obtained from the breath, there is bound to be present traces of the proteins of the saliva. A second injection of such into the same animal might produce "anaphylactic shock" (see p. 111). Experiments have been published which seem to show that guinea-pigs can be sensitized by the injection of the condensation water of human breath, so that anaphy- laxis is produced in these pigs by a subsequent injection of a trace of human serum. Owing to the method employed, it seems certain that saliva must have contaminated the condensation water. The guinea- pigs therefore became sensitized to human protein by the injection of the condensation water containing traces of salivary protein. Such results, it is claimed, afford evidence in favour of the exhalation of a volatile protein — an organic chemical poison. If there were any- thing in these claims, we should expect to find rats, which dwell in the same confined cage and breathe each other's breath, sensitive to THE PRINCIPLES OF VENTILATION 315 the injection of a trace of each other's protein. According to those Avho study the phenomena of anaphylaxis, no such sensitivity can be shown. If rats and guinea-]iigs be confined together for one or two months under the worst possible conditions of ventilation, the gviinea- pigs subsequently show no signs of anaphylactic symptotus when injected with a smaJl dose of rats serum. It has been claimed that if rabbits be arranged in a series of chambers, with the air led from one chamber to another, so that each succeeding chamber received the vitiated air from the one before it, the animals in the end cage died ; but if the air received into this cage were passed through sulphuric acid the rabbits remained alive. These experiments also have been repeated with the greatest care by several workers. It has been proved conclusively that no harm results so long as a sufficient air-current is maintained to keep the carbonic acid below a poisonous amount. The animal in the last cage dies when the COg reaches 10 to 12 per cent. If the (-O^ is kept down, the animal in the last cage puts on Aveight and thrives as Avell as the animal in the first cage. Of course, it is necessary in such experiments to clean the chambers daily, and supply the animals with suitable food and bedding. A man can live many days in a closed chamber in comfort without damage to his health, having not the slightest cognizance of any defect in ventilation, when the ventilation is so reduced that the carbonic -acid accumulates in the chamber up to 1 per cent. — that is to say, so long as the air in the chamber is kept cool and dry. Eight students were enclosed in a small chamber holding about 3 cubic metres of air, and kept therein until the COo has reached 3 to 4 per cent., and the oxygen has fallen to 17 or 16 per cent. Unaware that the oxygen was insufficient to support comljustion they were puzzled to find they could not light a cigarette. The wet-bulb temperature rose meanwhile to about 85° F.. the dry-bulb a degree or two higher. Their discomfort became great, but this was relieved to an astonish- ing extent by putting on electric fans placed in the roof, whirling the air in the chamber, and so cooling their bodies. In a crowded room, the air confined between the bodies and clothes of the people is almost warmed up to body temperature and saturated with moisture, so that cooling of the bod}^ by radiation, convection by evaporation, becomes almost impossible. This leads to sweating, wetness, and flushing of the skin, and a rise of skin temperature. The blood is sent to the skin, and stagnates there instead of passing in ample volume through the brain and viscera. Hence arise the feelings of discomfort and fatigue. The fans in the experiment mentioned above whirled away the blanket of stationary wet air round their bodies, and brought to the students the somewhat cooler and drier air in the rest of the chamber, and so relieved the heat stagna- tion from which they suffered. The relief became far greater when cold water was circiilated through a radiator placed in the chamber, and so cooled the air of the chamber about 10^ F. 316 A TEXTBOOK OF PHY8IOLOCJY The experiments showed that l)reathi]ig increased percentages of COg, and diminished oxygen percentages of 2 to 3 per cent., had little- effect in modifying the frequency of the pulse, while the increased temperature and humidity of the air had a profound effect. If the percentage of COo in the chamber were suddenly raised up to 2 per cent., the subjects inside were quite imaware of this. If the air in the chamber were breathed through a tube by a man standing outside, none of the discomfort, experienced by those shut up inside, was felt. Similarly, if one of those in the chamber breathed through a tube the pure air outside, he was not relieved. The cause of the discomfort was thus proved to be heat stagnation due to the excessive heat and humidity, and absence of movement of the air. The wet and drj' bulb thermometers do not indicate the degree of this heat stagnation; this may be measured by the katathermometer described later (see p. 500). The cooling power of the atmosphere exerted on the skin depends far more on its movement than on its temperature; the air in ordinal y rooms with the windows closed is so still that the cooling power approximates to that in the tropics out of doors. The good effects of open-air life depend very largely on the wind and its cooling power stimulating the metabolism of the bod}'. It has been shown that Ihe will to perform either mental or physical tasks is diminished by hot, moist atmospheres, the pulse m increased in frequency, the arteiiaL blood-pressure lowered and the appetite diminished by such. CHAPTER XXXVI lyrETHODS FOR THE DETERMINATION OF THE RESPIRATORY EXCHANGE The respiratory exchange can be measured by collecting the expired air in canvas-rubber bags. The bags are large so that the air expired by a resting man for periods of half an hour may ■quite conveniently be collected. When it is required to determine i-raSi^es Eic 179. — ^Apparatus used for Determining the Total Respiratory Change IN Man. (C. G. Douglas.) the exchange dviring exercise, such as walking, running, swim- ming, etc., smaller bags may be used, and the air of one or two minutes' breathing collected. The subject of the experiment wears a mouthpiece fitted with inspiratory and exjiiratory valves. The nose is closed by a clip. By means of the valves, the outside 317 318 A TEXTBOOK OF PHYSTOlJXiV air is iiispirod. ami the cxpiicil aii' directed into tlic collectiiifi- bag (Fig. 179). The respiratory exchange is calculated by squeezing tlie contents of the bag through a meter, and thus measuring the volume of the air expired in the given time, and by determining the composition of samples of the expired air. For example, if it be found that a man at rest has breathed out on an average 7 litres per minute, and that the expired air contains, say, 4 per cent, of CO.^ and ir)-S() per cent, of Og, then, taking the percentage of O., in the inspired air under the conditions of the ol)servation* as 20-80, the percentage absorbed is 5 (20-80 -15-80). the amount of O., absorbed ig- =350 c.c. per '' - 100 minute. Likewise, the amount of CO., given out is 4 X 7000 100 = 280 c.c. |)er minute. In the case of small animals, another method of procedure is adopted. The volimie of CO.2 expired is estimated from the weight of CO.2 given out by the ai\imal. m hile the oxygen used is arrived at by subtracting M K A B C \) Fig. 180. — Tin: Haldaxe-Pembrey Respiration Aitaratcs. the loss in weight of the animal in a given time from the combined weights of CO2 and water given off by it. The apparatus suitable for a mouse or rat is illustrated in Fig. 180. A beaker serves as animal chamber ; this is closcfl liy a cork and pierced by inlet and outlet tubes and a thermometer. The cork is soaked in melted paraffin before insertion to secure air-tighf closure. The beaker is generally placed in a water- bath regulated to the desired temperature. Air is drawn into the chamber through a meter by means of an aspirator or filter pumj^. The incoming air is freed from CO.^ and water by being drawn through a bottle {M) containing soda fime, and another (iV) containing pumice and sulphuric acid. The issuing air is led through a pair of tubes {A, B) containmg sulphuric acid and pumice to remove the water, and another pair, C containing soda lime, D containing sulphuric acid and pumice. Tube C removes the COg, and D catches the water liberated from the soda lime. In actual practice, tubes C and D are du])licated, as a control. The duplicates should not change in weight during an experiment. From the increase in weight of tubes A, B during a given time the weight of Avater given off is obtained; ¥ov accurate wxn-k these volumes must be reduced to 0° C. and TOO mm. DETERMINATION OF THE RESPIRATORY EXCHANGE 319 the increase of weight in C and D gives the weight of CO2. The loss of weight in the animal is obtained by weighing the animal in the beaker before and after experiment. Then since the molecnlar weight of a gas in grammer. measures 22-4 litres under normal condition 44 of temperature and pressure, the CO., in grammes x ^ = volume of CO2 given out ; simihirly, the loss of weight of CO., and water vapour deducted from the loss of weight of the animal gives the weight of 32 oxvgen taken in; this in grammes x :=r2i—r = volume of oxvgen taken in. . e o 22-4 Such a method is not convenient for larger animals and for man. The respirator}' exchange in such has been investigated by placing the animal in a closed chamber which contains a known quantity of air. This air is circulated, the CO2 given off being absorbed by caustic alkali, and oxygen graduall}' added to replace that used up and keep the pressure constant. The oxygen used is known from the amount which has entered the chamber; the amount of COo absorbed is esti- mated by titrating the alkali. In some laboratories, large rooms have been fitted up for the special study of the respiratory exchange in man under varying conditions. The res]:)iratoiy exchange is greatly increased by muscular A\ork, as the following table shows : Subject. CO per 2 Output Minute. vet Output Minute. -M. F. L. H. Resting on coucli after breakfast Quiet walk of 225 yards in 2? minutes (3 miles per hour approximately) Riding bicycle 1 mile in 4 minutes 42 seconds . . Resting on couch Climbing cliff Swimming 337 1,06.3 1,103 301 2,438 3,804 374 1,257 1,218 345 2.404 3,361 Exposure to a cold wind may double the respiratoiy exchange of the resting man; by stimulating him to muscular activity it n.ay do much more than this. The Respiratory Quotient. — The volume of CO2 given out divided by the \olume of O^ taken in gives the respirator}^ quotient: CO2 by volume R.Q. 0.. by volume Thus, in the experiment on man, 280 c.c. of COg was given out, 350 c.c. of Oo taken in. 280 TheR.Q..-.= =0-8. 350 The res]iiratory quotient varies according to the nature of the food being oxidized in the bodv. On a mixed diet it is found to be about 0-85. 320 A TEXTBOOK OF PHYSIOLOGY With carboh3(lrate the quotient is 1. The following formula summarizes its decomposition: CfiHioO, + 60., = 6C0, + 6HoO. 6C0.,_, 6o; In the case of carbohydrate there is sufficient oxygen in the mole- cule for the formation of water ; oxygen is only required for the forma- tion of carbon dioxide. In the case of protein and fat part of the ox\^gen taken in combines with hydrogen to form water; the R.Q. is therefore less than 1. With protein it is about 0-82. The following formula has bsen suggested as summarizing its decomposition : C->Hii,NiA2S + 770o- 63C02 + 38HP + 9CO(NH,), + S03. Urea 07 = 77-^^- For fats undergoing direct katabolism in the bo:ly it is found to be about 0-7. The following formula summarizes the katabolism of olein : C3H.(Ci8H330,)3 f 80O., = 57CO, + 52H,0. ^0^=^..0-7l/ O, SO Muscular work, although greatly increasing the respiratory ex- change, may not affect the respiratory quotient. The respiratory c^uotient of animals previous to and during hibernation and during starvation is referred to under Fat Metabolism (pp. 439, 440). Internal or Tissue Respiration denotes gaseous interchange batween the blood and tissue fluids on the one hand, and the body cells on the others. A frog placed in nitrogen continues to joroduce CO2 for some hours, so does a frog whose blood is replaced b}^ physiological saline. Excised '^ surviving '" organs, artificially circulated, continue to use Oo and i>roduce COo. The glow organ of a glow-worm glows only in the presence of oxygen. These are proofs of tissue respiration. That the living tissues have a marked affinity for oxygen can be shown by injecting a solution of methylene blue intravenously. On killing the animal, it is found that, although the blood be blue, the tissues, such as the muscles, are uncoloured. Upon exposing the muscles to oxygen, they become blue, showing that the muscles have reduced the methylene blue, and thus decolorized it. Since methylene blue is a fairly stable compound, the great affinity of the tissues is well shown by the experiment. They store up but little combined oxygen, and the oxidative changes which occur in them are supposed to be due to enzymes known as " oxidases " and " peroxidases " (see p. 73). When a tissue is active, much more oxygen is taken from the circulating blood and mo.'e COg is given up to the blood. This gaseous interchange can be calculated by estimating the amount of CO2 and O2 in the blood going to and leaving the organ, and by DETERMINATION OF THE RESPIRATORY EXCHANGE 321 measuring the blood-flow through the organ in a given time. Such experiments have been made upon the heart, muscles, kidneys, salivary glands, and other tissues. In the following table some of the results obtained are given. The gaseous interchange may be expressed either in c.c. per minute or in c.c. per gramme of tissue substance per minute. Table showing Effect of Activity upon the Internal Respiratory Exchange. Or-jan. Beiting. Gas in c.c. per Min. ( to COo Artic^. Gas in c.c. -per Min. ()o COo Salivary gland Salivary gland Panci'eas Kidney . . 0-32 0-32 0-i9 0-57 0-20 0-20 1-20 0-93 1-71 2-95 1-58 0-60 /Stimulation of - chorda tympaai Injection of secretion Active diuresis jSalivary gland Hea.rt Intestine Liver !n< per Gnu. per Min. U-028 — 0-010 — 0-00 87 — 0-00.5 — (Fasting animal.) Gas per Grin, per Min. 0-052 — 0-045 — 0-0194: — 0-0.50 — (Fed animal.) Injection adrenalin Injection adrenalin Absorption of phy- siological saline The oxygen use of the heart is reduced during vagal stimulation and increases after its cessation. The use of ox\^gen by the heart is also greatly reduced Id}^ the injection of chloroform water into the blood. When the nerve of a muscle is divided, its metaboHsm is markedly decreased; the respiratory quotient is practically unaltered by the complete rest so induced. The oxygen use per minute per kilo- gramme of substance has been estimated as folloAvs: Muscle, 4 c.c- salivary gland, 25 c.c; pancreas, 40 c.c; intestine, 23 c.c; kidney, 26 c.c; liver, 30 c.c Energy displayed by a contracting muscle or a secreting gland is not in itself a manifestation of oxidation in the sense that the Avork of an internal combustion engine is a direct manifestation of the oxidative explosion in the cylinder; they are more to be compared to the running-down of an alarm clock. The clock is wound, and at a wiven moment the j^otential energj' of the spring is released. It must then be rewound. It is during the jieriod of " rewinding " that oxidation is increased and cm ample supph^ of blood is required. There is some evidence that the pressure of oxygen in the tissue-juices of glands approximates to that 'in the venous blood, while in muscle it is almost nil. The latter, therefore, on any diminution of blood-flow suffers from oxygen-want. The blood which leaves an organ is waruier, more acid, and altered in saline content. Each of these factors may aifl the dis- 21 322 A TEXTBOOK OF PHYSIOLOGY Fig. 181. — Sylvester's Method: Means of producing Inspiration. Fig. 181a. — Sylvester's Method: Means of producing Expiration. Fig. 182. — Schafer's Method of Artificial Respiration. (From Rowland's "Hygiene for Teachers.") DETERMINATION OF THE RESPIRATORY EXCHANGE 323 sociation of oxyhaemoglobiii. In jDarticular, by locally increasing the acid in the blood within the capillaries, the hard-working tissues dissociate oxygen from the oxyhsemoglobin and make the red corpuscle discharge its cargo of oxj^gen with rapidit3^ At the same time, by increasing the general acidity of the blood, the tissues provoke the respiratory centre to increased activity. The increased acidity of the blood not only modifies the dissociation curve of oxyhsemoglobin, but is accompanied by a lower percentage of COo in the alveolar air, a lower respiratory quotient, and diminished power of the hsemoglobin to combine with oxygen in the lungs. Artificial Respiration. — In this country two methods are in vogue. In the older method — Sylvester's — the subject is placed on his back, with a pillow or folded garment beneath the shoulders. The tongue is pulled well forward, the mouth kept open. Inspiration is induced by grasping the arms below the elbow, and gradually raising them above the head (Fig. 181 ). Expiration is produced by bending the arms. Fig. 1S)3. — Cat: Record of Respiration. A, Chloroform on between the arrows; B, COgon between the arrows; C, CO.^ on again. Time in seconds. and pressing them forcibly against the chest wall (Fig. 181a). These operations should be performed about twentj^ times a minute. The method has the disadvantage of being fatiguing to the operator. The more recent method — Schiifer's — has largely overcome this defect. In it the subject is placed face downwards, with the upper part of the chest raised by a pillow or some similar support. The operator stands at the side of the su^bject facing his head: then, placing his hands on the lowest ribs on either side, he slowh' brings the weight of his body to bear upon his own arms, and thus presses upon the thorax of the subject, and forces air out of the lungs. Then he gradually relaxes the pressure by bringing his own bodj^ up again to a more erect position without moving the hands (Fig. 182). The rhythmic ]iressure on the thorax helps to squeeze blood through the heart and lungs, and it is as important to effect this as it is to intro- duce air. The excitatory effect of CO^ upon the respiration might be made use of in cases of poisoning due to oxygen-want (carbonic 324 A TEXTBOOK OF PHYSIOLOGY oxide and nitrite, etc.) and in cases of drowning, suffocation and chloroform syncope (Fig. 182). To carry out the method most effec- tively there would be required an anaesthetic mouth-piece and rubber bag filled with oxygen in and out of which the operator has respired several times. This is then given the patient to breathe while arti- ficial respiration is done. To respirate children artificially it is best to put mouth to mouth (interposing a handkerchief) and rhythmically blow 11]) the lungs. A hand placed on the belly ])revents the stomach Jt it^S^rK* I'^iG. 184. -IHE ViVATOR Apparatus for Artificial Kespiration. (Siebe, Gorman and Co.) The api^aratus consists of a special pump, which, on the downstroke, delivers oxygen from a bag (connected to an oxygen cylinder) into the inspiratory tube of a mask, which is fastened or held tightly over the patient's nose and mouth. Having completed the downstroke and so forced oxygen into the patient's lungs, the pump on its return or upstroke not only sucks in a fresh supply of oxygen to be deUvered on the next downstroke, but also opens a valve, which is connected with the expiratory tube of the mask, thus allowing the expiratory recoil of the expanded chest and lungs of the patient free play. The valve i-emains open during the upstroke and automatically closes when the stroke is completed. The piston of the pumji then descends and delivers another supply of oxygen, and so on. being blo^^al up, or the gullet can be closed by pressing the larj^nx backwards. A pump has been contrived for this pm'joose, fitted with a face mask (Fig. 184). The stroke of the piston is arranged to open a valve at the end of the inflation so as to allow deflation of the lungs by the elastic recoil of the thorax. Such a pump cannot be used to suck air out of the lungs, for suction causes the walls of the small bronchial tubes to come together, and does not empty the alveoli. BOOK V CHAPTER XXXVII GENERAL METABOLISM AND DIETETICS Metabolism and reproduction are the chief characteristics of living matter. Wc laiow that complex bodies such as proteins, fats, and carboh3xlrates, are constant!}' taken into the body, and that each undergoes its own special metabolism. As the result of these reactions chemical energy is tran.sformed into heat and m.echanical work; waste products, such as carbon dioxide and urea are formed, and excreted from the body. The study of general metabolism concerns the intake and output of energy b}', and the processes of building up and breaking down which occur in, the body as a whole ; while the study of the special metabolisms deals with the exact chemical changes undergone by the various foodstuffs, and with the localization of such changes in the body. General Metabolism: Methods. — The general metabohsm of a man or animal may be investigated by two means: (1) Directh% by ascertaining the heat value of the foodstuffs taken in, and then measuring the heat given off, either as such or as work, the work performed being subsequently calculated as heat. (2) Indirectly, by drawing up a balance-sheet between the intake (the amount of food and amount of oxygen taken in) and the output (the amount of the various bodies excreted in the breath, urine, fseces, and sweat), and from these calculating the energy exchange. Of these, the second method demands a less difficult technique and is more generally employed. For very exact work a combination of the methods is used . The body is to be looked upon as a machine capable of performing work and liberating heat. In the living as in the inanimate world, there is no such thing as a loss of energy. All such apparent losses are merely transformations of energy, the chief transformation in the body being that of the chemical energy of the foodstuffs into work and heat. It is not possible, however, to account for the operations that go on in the human machine on the supposition that man is a thermo- dynamic engine. 326 A TEXTBOOK OF PHYSIOLO(JY The unit by which work is measured is the kilogramme-metre (kgm.). This is the force necessary to raise a kilogramme vertically through 1 metre from the earth's surface.* Fm. 185.— Bomb Calorimeter. (Berthelot.) - . Water jacket; B, water calorimeter; C, bomb; D, stirrer worked by motor G; E, thermometer; F, cable carrying wires to a and d. The imit by which heat is measured is the Calorie. This is the heat required to raise 1 kilogramme of water through 1° C. (preferably from 20° C. to 21° C). For smaller measurements the small calorie * As this force varies, owing to the shape of the earth being greater at the poles than at the equator, the unit known as the "erg" is now employed in exact work. This is the force which will impart to a resting grarame-mass a velocity of 1 centi - metre per second. One kilogramme-metre equals 980,000 ergs. GENERAL METABOLISM AND DIETETICS 327 ■^ToVio C^alorie), or gramme-calorie, is employed; while for the finest work the micro calorie, or milligramjiie-calorie, is used. In order to measure the amount of heat retained or given out by a man, it is necessary to know the specific heat of his tissues. This has been determined as 0-8. A hibernating dormouse weighing 10 grammes, and with a body temperature of, say, 4° C, when placed in 100 c.c. of water at 0° C. until cooled to 3° C., does not yield 10, but only 8, calories to the water. Consequenth^ if a 70 kgm. man has his temperature raised 1° C, he stores up 70x0-8=56 calories -of heat. The Intake of Energy. — The combustion of each of the foodstuffs liberates a definite amount of heat, be it l^urnt inside or outside the animal body. Exact m.easixrements of the heat of combustion of the different constituents of the body are obtained by means of an instru- ment known as the boiib calorimeter. The substance to be burnt is dried, weighed end placed in a strong steel bomb, the inside wall of which is protected either by thick enamel or platinum. The bomb is then filled with oxygen under pressure (20 to 25 atmospheres), and placed in a vessel (Fig. 185) containing a weighed quantity of water. This water vessel contains a delicate thermometer and a stirrer, D, which can be driven by a motor. It is also carefully protected by a jacket (A) — a vacuum jacket is best — from alterations in tem- perature of the surrounding atmoq^here. The temperature of the Avater is carefully noted, and then the substance is burnt in the oxygen by causing a A\ire with which it is in contact to glow. This is effected by passing an electric current through wires led into the bomb. Combustion is ra.pidly completed ; the temperature of the Avater is raised thereby, and the rise noted. From this by means of appropriate calculations allowing for the caloric capacity of the apparatus, etc., the heat liberated by the combusted substance is ascertained. In the calorimeter all the carbon combined in the molecule of foodstuff is converted to carbon dioxide, the hj'drogen to water, and the nitrogen is freed as nitrogen gas. In the body the carbon mostly is excreted as CO.,, and the hydrogen as water; biit the whole of the nitrogen and a small part of the carbon and hydrogen are excreted combined in urea. u.ric acid, creatinin, etc. These bodies have a considerable specific heat of combustion; therefore, in estimating the heat value of the protein in the diet, it is necessary to subtract the heat value of the nitrogenous excreta from the total value, obtained on burning the protein in the bomb calorimeter. The table on p. 328 gives the combustion value of some of the chief substances met with in the body, expressed in several terms. The Indirect Method. — The food given is carefully weighed, and its content in protein, fat, and carbohydrate, calculated from tables giving the analytical composition of the various foodstuffs. In more accurate work the amount of protein in the diet may be -estimated by determining, when the diet contains no other nitro- 828 A TEXTBOOK OF PHYSIOLOGY genous bodies, the total nitrogen excreted in the urine, and multiplying this by 6-25 — the average ratio of nitrogen (16 per cent.) to the total weight of protein (Vk"^ 6-25). starch Dextrose Cane-sugar Lactose (water Fat (human) Butter . . Caseinogen ]\Iuscle protein Legumin Urea . . Uric acid Hippuric acid Alcohol Butyric acid fiee Per Gramme of Substance (rj. cal.). 41U() H743 3955 39o2 !t.l4(t !t23u 5850 (435(1)* 5()50 (4150)* 5703 (4-203)* •2542 2750 5G6S 7080 51)40 Per Cramme Molecid'.r Per Gramme Per Gramme Weight of 0> used CO2 formed Substance ig'.cal.). {g. cal.). {kg. cal.). C.78-8 3530 2572 (i73-7 3509 2552 1353-t; ^ 3522 2562 1351-0 3520 25GO — -. 3353 4702 152-5 402-0 1014-0 325-7 5-22-7 32!) I 2047 3223 2902 32:-) I 2909 3177 3400 3208 2100 3252 1281 3392 3701 3207 2970 * The first is bomb vahie: the 8L>eond is value for body after subtracting value for urea formed, etc. Note that column 2 is kilogramme-calorics, the other columns gramme-calories. Let us suppose, for example, that the diet is calculated to contain (dry weight) 125 grammes of jn-otein. 500 grammes of carbohydrate, and 50 grammes of fat. From the chemical composition of each of these foodstuffs the amount of carbon and nitrogen is calculated — Protein Carbohydrate Fat .." Total Carbon Xilrogen Grammes). {Grammes) 02 20 200 . — 38 — 300 20 The energy value of such a diet in terms of heat is- Protein Carbohydrate Fat . ■. Calorics. 125x4-1= 51-2-5 500x4- 1 = 2050-0 50x9-3= '105-0 3027-5 The Output. — Since protein is the only body in the above diet which contains nitrogen and sulphur, the amount of protein katab- olism of the body can be arrived at by estimating carefully the amount of nitrogen or sulphur combined in the excreta. The nitrogen is most * For the food digested and utilized the values can be taken as protein 4, fat 9,. c.".rboh5'drate 4. GENERAL METABOLISM AND DIETETICS 329 usually chosen. This occurs mainh' in the urine, to a small extent in the fseces and sweat. The total nitrogen of the urine is usually' deter- mined by KjeldahUs process (see p. 455), and to this 1 gramme of nitrogen is added — that is, the average amovint excreted in the fseces. The nitrogen of the fseces is derived in part from unabsorbed food, and in part from the various secretions of the alimentary tract. The above average has been ascertained by experiments upon animals placed on a nitrogen -free diet. It has to be borne in mind that several days are required for the elimmation of all the nitrogen taken in in the case of some protems. The nitrogen is eliminated at varj'ing rates when different t\'pes of proteins are ingested. The ])roportion of sulphvir in m-ine to nitrogen is 1 : 5-2 — about the same as in protein. The determination of the sulphur excretion is therefore a guide as to the breakmg down of protein and a control of the nitrogen determinations. The determination of the protein metabolized from the sulphur excretion has the advantage that in general the sulphur of the protein is more quickly excreted than the nitrogen, but has the disadvantage that, being small in amoiuit, the experimental error is likely to be greater. Protein yields a certain amount of carbon combined A\'ith the nitrogen of the urinary excreta. It has been determined that for ever}' gramme of nitrogen excreted 0-67 gramme of carbon is excreted. This ratio is constant, so that it is not necessary- to estimate the proportion of carbon in the nitrogenous bodies of the urine. Protein on its oxidation also yields CO2 and water. The COg output is more easy to estimate than the water output of the body. • Of the carbon dioxide excreted a small part comes from protein, the remainder from fat and carbohydrate. The amount of carbon coming from protein is found by multiplying the amount of nitrogen excreted b}' 3-3, since the proj)ortion of carbon to nitrogen in protein is 3-3 : 1. Since the tissues contain far more fat than carljohydrate, any carbon retained in the bod}' is usually reckoned as fat. Each gramme of carbon represents 1-3 grammes of fat, the proportion of carbon to the total weight of fat. A small amount of carbon is lost as fat in the fseces. Let us suppose that with the above intake the output was — Carbon. Nitrogen. In urine 11 (16-5x 0-GT) l(>-o In faeces . . . . . . 5 l-O In breath .. .. .. 2o4 — 270 17-5 There is a retention in the body of 30 grammes of carbon and 2-5 grammes of nitrogen. This nitrogen = 2-5 x 6-25 = 15-62o grammes of protein. In this protein there is 2-5 x 3-3 = 8-25 grammes of carbon; so that 30— 8-25 = 21-75 grammes of carbon is represented as fat.. To estimate this as fat we must multiply the carbon b}' 1-3 (fat contains 76 per cent, of carbon), 21-75 x 1-3 = 28-275. Therefore on 330 A TEXTBOOK OF PHYSIOLOGY the above diet lo-625 grammes of protein and 28-275 grammes of fat were retained per day in the organism. The energy exchange can be obtained by deducting from th(^ energy value of the food eaten the amount of lieat represented by these. Protein Fat Calories. 15'625x4-l= 64 (ajipioximately) 28-275 X 9-3 = 263 327 Since 3,027-5 were suppHed, the amount of energy liberated is, therefore, 3,027-5 - 327 = 2,700-5 calories. Fia. 186. — Horizontal Section of Self-Registering Calorimeter for Experi- ments WITH Small Animals. (A. V. Hill r.nd A. M. Hill.) F, F, F, F, Vacuum between walls of a cylindrical Dewar's flask; A, incoming water from tank; D, D, D, D, section of lead tubing around outride of fiask; K, junction between outer lead tubing and T-piece E^ : E^ and £'.j. inlet and exit T-pieces containing the thermopile T ; H, H, coil of lead tubing inside flask; B, exit pipe for water; G, self -registering galvanometer. Another indirect guide to the energy liberated by the tissues under varying conditions is the amount of oxygen absorbed by them. This is a good guide in successive comparative experiments, since, provided the quality and relative proportion of the foodstuffs burnt are GENERAL METABOLISM AND DIETETICS 331 approximately the same, it is fair to assume that any change in the oxygen intake, and also in the CO2 outiaut, are due to the conditions of experiment, such as exposure to cold, warmth, wind, etc. The respiratory exchange is therefore often used to estimate the amount of energy liberated in the tissues. It is necessar}^ for very accurate work to remember that different foodstuffs liberate different amounts of energy for the same amount of oxygen absorbed. Thus, 100 grammes of oxygen will burn — 35 grammes of fat, giving energy equal to 325 calories. 84-4 grammes of carbohydrate, giving energy equal 346 calories. 74-4 grammes of protein, giving energy equal to 362 calories. to Given the respiratory quotient and total energy output of the body, calculations can be made of the relative use of glycogen and fat for each litre of oxygen consumed (see Respiratory Quotient, p. 319). Fig. 187. — Figure of Respik.atiox Chamber for JIan. The pir is drawn from the chamber l)y the rotary blower and pivS.sed over vessels A — E back to the chamber. Oxygen ma}' be added as required from F. The Direct Mcthod.—Tius is done by placing the man or animal in a respiration calorimeter. In the case of an animal it is difficult to estimate the exact amount of energy lost as muscular work; the animal is therefore in these direct observations kept as quiet as possible. The forms of water calorimeter which were first used have been given up, on account of large experimental error, and replaced by some :332 A TEXTBOOK OF PHYSIOLOGY form of air calorimeter. In Fig. 186 is shown a self-registering appar- atus, suitable for the study of small animals. It consists of a Dewar's flask, with the thermo-electric junctions npon the inlet and exit water tubes. These junctions are connected with a galvanometer, the deflection of which can be registered. The direct method is especially applicable to man, since the amount of Avork done can be measvired, and the amount of heat lost and the respiratory exchange calculated, at the same time. Special double- walled calorimeters adequately furnished with bed, chairs, etc., and de\'ices for performing mechanical work, have been built in some laboratories. Within the calorimeter is a coil of water-pipes, fitted with special metal discs, which quickly takes up any' heat liberated in the chamber. Cool water is made to flow through this coil and the volume ■ and temperature of the water entering and leaving it is accurately measured, and thus the heat output is calculated. Almost the whole of the heat given off by the body is taken up by the circulating water, for any loss of heat to the outside air is checked by maintaining equality of temperature between the inner and outer walls. This is insured by means of (1) thermo-electric couples con- nected with a galvanometer which detects any inequality ; (2) electric furnaces; (3) water coils placed between the outer and inner walls, hj means of which any difference in temperature is compensated. Adequate ventilation is maintained by some form of pump, and the carbon dioxide output and oxygen intake obtained after the fashion already described for determining the respiratory exchange; pre- cautions havv^ to be taken to secure the measurement of heat given off in the ventilation air (Fig. 187). For the performance of mechanical work a bicycle is used; the hind-wheel is replaced by a metal disc which revolves against a strap, the tension of which is measured by a spring balance. By means of friction the work done is thus converted into heat. The revolutions of the bicycle and the force required to turn the bicycle can be measured, and the work calculated from these data. How accurately such appliances can work is shown by the following: In several series of experiments extending over forty -five daj^s, the measurement of the amount of heat produced by the animal in the calorimeter equalled 99-53 per cent, of the heat calculated to have arisen from the combustion of food and body tissues. The following is an example of a five-day experiment on a fasting dog of 4-5 kilos weight: Calculated indirectlv from the nitrogen and carbon ex- creted = 259-3. Calculated directlv bv the calorimeter method = 261-0. CHAPTER XXXVIII METABOLISM DURING STARVATION Starvation may be brought about by withholding all food- stuffs from the body, or by withholding separately either proteins, water, or mineral salts. When all foodstuffs are withheld from an animal, and only water given, the body begins to live at its own expense, loss of weight ensues, and finally the animal dies. The time of death depends largely upon the state of nutrition at the start. The process of starvation is only painful in the last stages. Profes- sional fasters aj)pear in public from time to time, going without food for as long as forty days, with apparently but little inconvenience to themselves. From observations upon such, it appears that the ratio of metabolism to actual bodj- weight alters but little during starva- tion; in other words, the loss of w^eight and the lessening of the meta- bolic processes of the body proceed together. At the beginning of the starvation period, the nitrogen elimination in the urine quickly drops to a fairly constant level. The drop is quicker the greater the amount of nitrogen in the food eaten beforehand. For example, a dog receiving 2,500 grammes of meat daily excreted on the first daj' of starvation 60-1 grammes of urea; on the fifth day, 12-3 grammes. With a moderate nitrogenous diet — 1,500 grammes of meat — the excretion on these days was 26-5 and 14-8 grammes; with a diet poor in nitrogen, 13-8 and 12-1 gTammes. Day of JIvch X Moderate N Little y Starvation. in Food. in Food. in Food. 1 C9-1 26-5 13-S 2 24-9 lS-(i U-.-) n 12-3 14-S 12-1 8 10-1 12-1 10-7 From this day onward the nitrogen excretion remains more or less constant until just before death, when there occurs a sudden rise. The explanation is that the animal is hving on a minimum amount of its own protein, and getting nearly all its energy for the first day or so from its store of carbohydrate, and subsequenth^ from its body fat. This conclusion is reached by measuring the heat loss and by ascertaining the respiratory quotient, and calculating from this how much carbohydrate and how much fat are being metabolized. It is possible, since starving animals and man give a low respiratory quotient, that some of this fat may first be changed to carbohydrate and metabolized in this fashion. It is difficult, however, to say exactly 334 A TEXTBOOK OF PHYSIOLOGY what is causing the low respiratory quotient of the starving animal. It may be partly accounted for by the elimination of acetone bodies in the urine (see p. 4G8). When the store of fat is exhausted, the protein consumption and the urea output goes up and the end is then near. During starvation, the urine becomes considerably lessened in amount. Salts continue to be excreted, the amount of sodium chloride being markedly decreased, but that of potassium, calcium, magnesium, and phosphates increased. This is due to tissue destruc- tion, especiall}' of the bony tissues. Life persists at the expense of what may be termed the less important tissues and organs, as can be seen from the following table: Male Cat. Adipose tissue . . Spleen . . Liver T(!sticles Muscles Kidneys Skin Intestine Lungs . . Pancreas Bones Heart Brain 97 per cent, loss of weight. ()7 .")4 ■id 31 ■2("> •21 18 IS IT 11- An outstanding feature in starvation is the manner in which the blood, although some\\'hat decreased in amount, is kept more or less constant in composition. A similar principle applies to those animals which undergo periods of voluntary abstention from food. Previous to such periods they make special provision by storing up large supplies. One particularly interesting example is the salmon. While living in the sea, the food- supplies are taken in and stored as j)rotein and fat chiefly in the tail muscles and the fat depots of the body. During the migration up-river to the " spawning-ground," which lasts several months, no food is taken in, and the whole of the energy, spent in swimming and in the development of the sex organs, takes place at the expense of these food-supplies. Animals which hibernate also lay up a store of food previous to and Uve at the expense of this during the period of hibernation (see pp. 439, 440). Lack of Water. — The living processes of protoplasm are dependent on its water content. Water has been found to form 66 per cent, of the entire body of a well-fed ox, 57-9 per cent, of a well-fed pig, and 63-2 per cent, of a well-fed sheep. Since it is contmuously leaving the body in the urine, breath, sweat, and other secretions, it must be replaced. The amount of water lost under average conditions of temperature and humidity is about 1-25 per cent, of body weight diu-ing rest and hunger, 1-32 per cent, during rest and average diet, and 2-91 per cent, during hard work and average METABOLISM DURING STARVATION 335 diet. Depriving an animal of water Avill kill it more quickty than depriving it of the dr}^ proximate j)rinciples of the food. Water is taken in as such and in combination with the food. Fresh fruit and vegetables have a large water content. This water iaa,y be contained in the s^'stem of water-tubes of a plant, when it is more or less pure water, or it ma}- be in the form of " sap," when it is more concentrated and contains mineral salts and organic bodies in addition. Lean meat contains about 80 per cent, of water, so a carnivore almost gets enough water in its food. The proportion of Avater in various vegetables can be seen in the table on p. 349. Lack of Mineral Salts. — The v.ithholding of mineral salts from the diet also brings about death more quickh* than the withholding of the proximate principles. The salts of the body are partly in solution and partly combined with the organic substances. Those in solution are of the greatest importance in providing the proper medium for the living tissues. When salts are withheld, those combined with the organic substances of the bod}' become free to replace the salts in solvition, which are lost in the urine. The ions of sodium, potassium, and calcium, must be continually taken in with the food, to keep the proper relationship between these bases in the blood, so that the action of the ion of no one base pre- dominates. We knoAv that certain enzj-mic processes, such as the clotting of blood and milk, depend on the presence of calcium ions, and that muscular contraction is affected b}' the concentration of calcium, sodium, and potassium ions present in the blood. When calcium is withheld from the diet, the bones are gradualh' decomposed to replace the loss. Different results follow the withholding of one or other groups of salts. Thus, deprivation of chlorides is followed by marked symp- toms of inanition. This is due partly to gastric distiu-bance, and partly to the ascendanc}' obtained by the potassium ion, which worku deleteriously upon the bodily functions. When there is a lack of sodium salts as compared with potassium salts, or an abundance of l^otassium salts relative to sodium salts, such as occurs with a vegetable diet, the potassium of the salts ingested is in part replaced by sodium from the body, and some of the sodium salt so formed is excreted in the urine. This causes a loss of NaCl from the body, and a supply of NaCl becomes imperative. For this reason many vegetarian animals wander miles to visit " salt-licks " — lumps of crude rock salt. On an animal diet sufficient salts are introduced with the food itself. The desu'e for salt b}' the various human races varies with the pre- ponderance of vegetable food in their diet. The peasants in France eat four times as much salt as the town dwellers ; the carnivorous tribes of men do not know or do not value salt. Rice-eaters are an exception. Rice contains six times less potassium than wheat, ten to twenty times less than peas, twenty to thirty times less than potatoes. Rice- eaters, like flesh-eaters, do not require much common salt. In the Soudan the negroes burn a plant which yields an ash rich in sodium. 336 A lEXTlJOUK OF PHY.SlULUdY and use this for salt. During salt starvation the amount of chlorine in the urine constantly decreases, so that eventually the excretion of chlorine may stop. Lack of Alkali Carbonates. — If the alkaline bases be withheld, there ensues an acid intoxication of the body, and life thus endangered. Lack of Phosphates. — Lack of phosphates may seriously impair the bodily functions. The bony tissues are particularly affected. It is a question as to how far lack of phosphates affects the formation Avithin the body of phosphorized compounds such as phosphoprotein, and of phosphorized fats such as lecithin. The available evidence seems to show that these bodies can be S3"nthesized from organic bodies poor in phosphorus and inorganic phosphates. Lack of Iron. — Iron is of great importance to the organism, since it is contained in the blood-pigment, haemoglobin, and also in the nuclei of cells. It is necessary, too, for the oxidative processes initiated by oxidases. Lack of iron leads to ansemia, insufficient nutrition, and eventually to death. Although debated, it seems probable that iron may be utihzed when ingested in either organic or inorganic form. Iron is introduced into the body by various foodstuffs. This can be seen from the fol- lowing table, which shows the amount of iron in milligrammes in 100 grammes of dried substance: White of eocr . . trace Carrots S-6 Rice . . . . 1-2 Apples 13 Wheat flour . . 1-6 Cabbage 17 Milk 2-3 Beef 17 Peas . . 6-2 Yolk of egg . . 10-24 Potatoes 6-4 Spinach . . 33-39 Lack of Carbohydrates and Fats. — The result of withdrawing fats and carbohydrates from the diet depends on the class of animal. Carnivora can live for a long time on a diet consisting, as nearly as possible, of protein only, viz., lean meat freed from as much fat as possible. Omnivora or herbivora do not appear to be able to live on such a diet. The replacement of fat by excess of carbohydrate leads to the retention of water in the body. Fat starvation causes a form of •dropsy. The food eaten per diem should contain at least 60 grms. of fat. Lack of Lipoids. — There is some evidence that these may be synthesized in the body out of protein and carbohydrate. They are essential, and it is advisable that they should be in the diet. Lack of Vitamines. — The fresh foods contain certain active prin- ciples necessary for nutrition and growth, which may be removed by the modern processes of milling or canning food. If these are in- sufificient nutrition is gravely affected. The first knowledge of the effect of a deficit of these bodies wa« afforded by the study of the disease known as beri-beri. It is now conclusively shown that this disease is due to feeding (as the almost sole article of diet) on " polished " rice — that is to say, rice from which METABOLISM DURING STARVATION 33-; the outer husks have been removed. Under these conditions pains and weakness of the muscles in the Hmbs develop, with a lowering or comi^lete loss of sensibility; often cedema also supervene 3. and in some cases death rajDidly ensues. If instead of polished rice the whole rice be eaten, such symptoms do not develop. The addition of the '■ polishings " to polished rice also prevents the onset of symp- toms. The proportion of cases of beri-beri in the Java prisons was reduced from 1 in 39 to 1 in 10,000 when unshelled rice was substituted Fig. 188. — To show Effect of Vitamixe ox Xuteitiox. (Schaumann.) A, Pigeon fed on food containing no vitamine. unable to stand up; B, after adding vitamine to food the first day; C, the second day. for shelled rice. In some districts of the East the disease has com- pletely disappeared since this substitution has been made. The necessary substance is contained in the subpericarpal tissue of the rice; its nature has not yet been determined. The phosjihorized organic bodies which are abundant in the husk may be of consider- able importance to the organism. S3'mptoms similar to beri-beri may be induced in animals by feeding them on polished rice ; these symptoms are almost immediately relieved when an acid extract of the " polishings " is added, after neutraliza- tion, to the rice. 338 A TEXTBOOK OF PHYSIOLOGY Animals — e.g., pigeons — fed upon polished rice gradually lose weight, develop nervous symptoms al amino-acid content of a diet is important in regard to growth (see Fig. 189, A). The Effect of Fat. — Fat, when added to the diet, exerts a sparing effect upon the katabolism of protein. Thus, Avhen a dog was fed with 1,500 grammes of protein, its nitrogen excretion was equivalent to the katabolism of 1,512 grammes. On the addition of 150 grammes of fat, the nitrogen excretion equalled 1,474 grammes of protein. Carbohydrates exert a like or even greater sparing effect on proteins. The addition of fats or carbohydrates to a diet of protein, insufficient by itself, will enable an animal to attain nitrogenous equilibrium and even to store protein in the body. But the protein -supply cannot be taken below a certain minimum, a minimum which seems to vary with different foodstuffs. Thufj 30 grms. of protein suffice on a diet of potatoes, and 80 grms. on a diet of bread. On a diet largely consist- ing of potatoes the body can be run on a very low plane both of energy and protein value. For times of scarcity, then, the potato is invaluable. The most virile races of the world occupy cool climates and eat food- stuffs yielding high energy, protein, and fat values — e.g., meat and cereals. Few people recjuiring a diet of 3,500 colories can digest with comfort more than 500 grms. of carbohydrates, while the use of more than 120 grms. of protein is wasteful. About 1 ,000 calories have then to be made up from fat. and this means eating a little over 100 grms. Fat is easily digested, and does not cause the rise in heat production AA'hich protein, and to a lesser degree sugar, does. CHAPTER XXXIX METABOLISM UNDER VARYING CONDITIONS The body requires a certain amount of energy lor tlie })erformance of its functions during rest. This is known as the basal requirement, and is best ascertained by determining the respiratory exchange of a person in a state of complete rest twelve hours after the last meal, which should not have been rich in carbohydrate. Such a state is best obtained in bed, before rising, in the early mornmg, when the surrounding medium is uniform in temperature, the muscles are well rested, and other systems of the body, such as the alimentary system, are more or less inactive. -'^ + - __-;.\i ^ ^ -frJ-T- -U4-^- -X— 1-- — 2a- -i — I — 1— I I I I I I -r-o— t- -h^s-l— I r -t- : I I ! —-i I ! -W4-4- I I 1-V ---Xi FlU. lyU. — ]^IAGRAM TO ILLUSTRATE THE RELATION BETWEEN VoLUME OR WeIGHT AND Surface. (Waller.) The volumes are 1, 8, 27 c.cm.; the weights are 1, 8, 27 grammes; the surfaces are 6, 24, 54 square cm.; the ratio of increase is 1, 4, 9. Of this basal requirement it is calculated that 10 to 20 per cent, of the total energy is required for the maintenance of the work of circulation and respiration. The Weight of the Body and the Suriace Area. — The larger the mass of an animal, the greater its absolute energy requirements, and the greater its absolute consumption of material. While this is true for the absolute, it is not true for the relative amounts. The smaller the animal, the relatively greater is its energy out])ut. This is l)ecause, calculated per kilo body weight, small warm-blooded animals have a proportionately greater surface area. They have therefore need of a greater heat production, involving an increased metabolism. 841 342 A TEXTBOOK OF PHY.SiOLOGY This is seen in the following table from ex])eriments on animals during a period of twenty -four hoius' hunger: Animal. Horse Pig Man Dog Goose Weight in Energy released during 24 Hours' Starvation. Kilos. Per 1 Kilo Per 1 Cm. Body Weight. Surface. 441 11-3 948- 128 1!»-I 1078 64 32-1 1042 15 51*5 1039 3-5 GO- 7 967 This rule holds for larger and smaller animals of the same species, as may be seen from the following figure. The accompanying table shows the oxygen use per minuta in man in the first few years of life, and again at the age of puberty. Age, Years. C 9 14 17 Adults (22-43) Weight in Kilos. 11-5 18-4 21-8 36-1 44-3 ()6-7 O2 consumed O.y Use per per Min., Kilo of C.G. Body Weight. Relative Consumption of Oxygen to A dull (Standard= 100). 112-2 139-9 148-0 188-1 212-7 227-9 0-70 7-61 6-79 5-21 4-80 3-41 Per Kilo of Per Sq. M. Body Wei ght. of Surface. 285 160 223 145 199 137 152 125 140 123 100 100 The basal metabolism of man, measured under conditions of fast- ing and rest in bed, is 40 calories per horn- per sq. metre of skin sur- face, 37 for woman, 50 for boys of 12-13 years. The formula used for measm'ing the surface is A ^ W ^'^^^ x H O"^^ x 71*84. A = sq. metres ; W = weight in kilogrammes; H = height in centimetres. In young animals the increased metabolism may be due in part to the actual processes of metabolism being more active in the growing than in the adult animal. During the early months of their life infants appear to be an exception to the rule; their metabolism is much loAver than it should be as calculated from the body surface. The infant is kept warm, and sleeps quietly most of its time in cradle or pram. This very likely is not the case with the infant of the native Austra- liin or Terra del Fuegian. Infants are generally over-coddled, and are made more virile by some exposure to cold and exercise. In old age the metabolism is reduced. It is doubtful whether sex influences the metabolism in any degree. METABOLISM UNDER VARYING CONDITIONS 343 Work. — During work the metabolism is increased. This is due to the increased activity of the muscles. Investigation shows that this is mainly at the expense of the fats and carbohydi-ate, and but little at the expense of the proteins, unless there be a deficit of the two first. The respirator}^ exchange is greatly increased by muscular work (see p. 319). A subject pedalled a b'cycle sixteen hours out of twenty-four. The whole energy expended = 9,981 calories. The energy of the food taken = 5,138 calories. The energy taken out of the body substance = 4,843 calories. The energy derived from tissue protein only = 478 calories. As the man was an athlete in training, his muscles were not overdone, and thus the protein metabolism was scarcely increased. The experiment shows how body fat may be taken off by hard exercise. When no muscular work is done, as during the first hours of sound sleep, the metabolism of the body markedly decreases; during the waking hours it again increases. But if th^ individual keeps at rest and protected from cold, there is no increased metabolism during these hours. External Temperature. — A lowering of the external temperature •excites to more muscular movement, voluntary and involuntary, and thereby increases metabolism. Shivering helps to keep up the teinperatiu-e. Exi)o:;ure to cold wind may double the respkatory •exchange, even if the individual sits quiet in a chair and does not shiver. There is a relation between the cooling power of the atmosphere, the skin temperature, and the rate of metaboHsm. Thus the appetite is increased at a bracing place. The raising of the body temperature increases the metabolism. Feeding. — The taking in of food raises the metabolism, partly owing to the mechanical work involved in digestive processes, partly owing to the chemical processes. With some foods this may be very great — as much as 50 per cent, of the energy value of the food taken in. For instance, with a horse chewing hay, 48 per cent, of the energy value is used up in the work of mastication and digestion, whereas but 19-7 per cent, is so used in the case of oats. It has been calculated, for the caloric value of the food taken there is expended in heat pro- duction duiing digestion and assimilation — Fats . . . . . . . . . . about 2| per cent. Starches . . . . . . . . . . ,, 9 ,, Proteins . . . . . . . . . . ,,1" >> Proteins, having so high " a specific dynamic energy," are heating, thus more protein is consumed by man in cold, and less in tropical •climates. In the adaptation of an Englishman to a tropical climate diet is of great importance. On a diet of rice and bananas monkej^s .successfully withstand exposvn-e for hours to the tropical sun. CHAPTER XL DIETETICS Briefly stated, we take in food — ■ 1. To rebuild the living tissues. 2. To obtain energy for the biological processes. 3. To preserve the proper medium in which these i)ro- cesses can be carried out. The Selection o£ Foodstuffs. — Hitherto we have spoken of proteins. tats, and car):ohy(hates. .-oinewhat as if the}' were usually foi nd separately, as such, in the food materials in common use. This is not the case in regard to the majority of the commoner natural food materials. These are mixtures of all three classes of nutrients, as can be seen from the following tables. Nevertheless, the food materials can be grouped, according to their constitution, into those which are mostly protein, mostlj- fat, mostly carbohydrate, or mostly water. Some prepared foodstuffs, such as sugars and starches, or butter and oils, are almost exclusively one class. Pro- Fat Carbo- Total tein Weight hydrate Weight Caloric Weight in Weight in Value. in ( rms. in Grms. Gnus. Grms. Man (moderate work). . lis 50 500 674 £054 Man (hard work) 14.-. 100 450 695 3370 Man (moderate work) . . 101) 100 240 440 2324 Man (moderate work) . . 130 40 550 720 3160 Man (subsistence diet) o~ 14 341 412 1760 Man (active labour) . . 1.10 71 568 795 3G30 Man (moderate work) . . 12.-. 125 400 G50 3325 Man (aged ) 100 OS 350 518 2475 Woman (mc derate worl^) . ^ •s « S> •si 4 0? 1 a. ^ e '■^ |4 t — — . — — — — Fresh Beef: Brisket, edible . . — :)4-(i 1.V8 28-5 — 0-9 1,495 — as bought •23-3 41-t) 12-0 22-3 — 0-6 1,165 6d. 2,330 Flank, edible . . 59-3 19-() 21-1 0-9 1,255 — — as bought 5*5 56-1 18-6 19-9 — 0-8 1,185 5id. 2,400 Ribs, edible 57-0 17-8 24-6 — 0-9 1,370 — — as bought 20-1 45-3 14-4 20-0 — 0-7 1,110 1/- 1,110 Veal (average) . . — 70-0 20-2 9-0 — 1-2 755 — — Mutton: Neck, edible — ::,(rii l()-7 26-3 — 1-0 1,420 — — as bought 26-4 41-5 12-2 19-6 — 0-7 1,055 6d. 2,110 Leg, edible 63-2 18-7 17-5 1-0 1,085 — — ■ as bought 17-7 r)i-9 15-4 14-5 — 0-8 900 lid. 982 Pork: Flank, edible . . 59-0 18-5 22-2 — 1-0 1,280 — — as bought 18-0 48-0 1,5-1 18-6 — 0-7 1,065 9d. 1,420 Loin, edible 48-2 1.5-7 36-3 0-7 1,825 — — Middle, as bought ll>-7 38-() 12-7 28-9 — 0-7 1,455 v- 1,455 Fowls : edible . . (;3-7 19-3 16-3 1-0 1,04.5 — — as purchased 2-v;t 47-1 13-7 12-3 — 0-7 775 3/6 each. — Fish: Cod (whole )odible — 82- (i Ki-r) 0-4 — 1-2 S25 — — as purchased 52-5 38-7 8-4 0-2 — 0-6 165 4d. 495 Salmon (whole), edible — 04-() 22-0 12-8 — 1-4 950 — — as purchased . . 34- 'J 40-9 15-3 8-9 — 0-9 660 2/- 330 Turbot edible . . 71-4 14-8 14-4 - — 1-3 885 — — as purchased 47-7 57-3 (i-S 7-5 — 0-7 460 1/3 — Herring, fresh, edible 72-.") 19-. 5 7-1 — 1-5 C60 — — as purchased 42-(i 41-7 11-2 3-9 — 0-9 375 Id.ea. — Herring, smoked. edible — 34-(i 3()-9 1.5-8 — 13-2 1,355 • — — as purchased . . 44-4 19-2 20-. 5 8-8 — 7-4 750 Id.ea. — Shellfish: Oysters, edil>le — S()-9 (i-2 1-2 3-7 2- 1 235 — in shell, as pur- chased 81-4 1()-1 1-2 0-2 0-7 0-4 45 — — Lobster, edible . . 79-2 16-4 1-8 0-4 2-2 390 — — as purchased . . Cl-7 30-7 5-9 0-7 0-2 0-8 140 — — Eggs: edible (cooked). . — 73-2 14-0 12-0 — 0-8 765 — — in shell,as bought' 11-2 1 (55-0 12-4 10-7 " 0-7 680 1/- 850 DIETETICS 349 Table Showing Cumpo.sition, Food Valtte, a>-d Cost of Proteix FooDS (Continued). i !^ i « 0 •«* 38-3 3-5 . 2,165 Id. 3,711 Cheddar, as pur- 1 chased 27-4 27-7 3()-S 4-1 4-0 2,145 .7id. 3,432 Dutch, as pur- - chased — 35-2 37-1 17-7 — lO-O 1,435 7id. 2,296 Roquefort, as - -- - purchased Milt- — 3y-3 22-0 29-5 1-8 G-8 1,700 1/3 1,360 Whole, as pur- chased — S7-0 3-3 4-0 5-() It- 7 32.-J 2d. p. pt. 2,440 Skimmed — !)l)-.-) 3-4 0-3 5-1 0-7 170 Id. p. pt. — Condensed, sweetened — 2()-l) S-S 8-3 54-1 I-:) 1,520 4id. p. tin. — Beans: dried (4-4) 12-6 22-5 1-8 59-0 3- .J 1,605 2il. 9,630 Peas : dried (4-.-,) 9-5 24-G 1-0 62-() 2-9 1,655 2il. 9,930 Table showing Composition, Food Value, and C^st of Fat Foods. Salt Pork : Edible .. — 17-7 8-4 72-2 — 3-4 3,200 6d. 6,400 Belh', as pur- chased 8-2 16-2 ( • ( fi()-2 — 3-2 2,935 — — Butter 11-0 !•(» 85-0 — 3-0 3,605 1/4 2.704 Margarine . . 9-5 1-2 8.3-(t — 6-3 3,525 6d. 7,050 Cream, as pur- chased — 74-0 2-5 18-5 4-5 0-5 910 16 — Lard, refined — — 100 (t — — 4,220 8d. 6,330 Nuts: Almond, edible (2-0) 4-S 21-(» .-)4-9 17-3 2-0 3,030 3d. — as purchased 45-0 2' 7 11-5 30-2 9-5 M 1,660 6d. 3,320 Brazil, edible . . — 5-3 17-0 66-8 7-0 3-9 3,265 — — as purchased 49-6 2-ti 8-6 .33-7 3-5 2-0 1,655 8d. — Cocoanut, pre- pared 3-5 6-3 57-4 31-5 1-3 3,125 — — Walnut, edible (1-7) 2-5 27-6 .-)t)-3 11-7 1-9 .3,105 — — as purchased . . 74-1 0-6 7-2 i4-(; 3-0 0-5 .05 6d. 1.710 Ham: Smoked, medium edible 40-3 16-3 38-8 — 4-8 1,940 — — as purchased . . 13-6 34-8 14-2 33-4 — 4-2 1,675 1/- 1,675 Sausage, pork — 46-2 17-4 32-5 — 3-4 1,695 lOd. — Beef liver, edible . . — 71-2 20-7 4-5 1-5 1-6 605 — — as purchased 7-3 65-6 20-2 3-1 2-5 1-3 555 6d. 1,110 Sweetbreads, as as purchased . . — 70-9 16-8 12-1 — 1-6 , 825 — — Tripe — St;- 5 11-7 1-2 (1-2 0-3 270 (id. 550 350 A TEXTBOOK OF PHYSIOLOGY Tablk sjiowiNo Composition, Food Value, and Cost of Carbohydrate Foods. Wheat flour : Patent roller,' family grade Self-raising Wheat bread, white Wheat rolls, white i Wheat bread,brown' Rye bread Biscuits: Creamt crackers . . ! Oatmeal . . Oats (rolled) Rice Starch (tapioca) . . Starch (sago) . .! Sugar brown . . [ Sugar (granulated) j Honey Apples (dried) Currants (dried) . . Raisins, as pur- chased . . Figs (dried) Prunes, as pur- chased Chestnuts (dried): ' edible as purchased . . 1 1 , ! 1 1^ Oh 1 1 •4 t to Fuel Value Pound. Average P ' per Pound, (0-6) 12-8 10-8 M 74-8 0-5 1,640 Ifd. 11,646 (0-4) 10-8 10-2 1-2 73-0 4-8 1,600 2d. 9,600 (0-5) 35-6 9-3 1-2 52-7 , 1-2 1,205 — — (0-6) 29-2 8-9 4-1 56-7 1-1 1,395 — — 43-6 5-4 1-8 47-1 2-1 1,050 — — (0-5) 35-7 9-0 0-6 53-2 1-5 1,180 ~ — (0-6) 6-8 9-7 12-1 69-7 1-7 1,990 7d. 3,411 (0-9) 7-3 16-1 7-2 67-5 1-9 1,860 2^d. — (1-3) 7-7 16-7 7-3 66-2 2-1 1,850 2^d. — (0-2) 12-3 8-0 0-3 79-0 0-4 1,630 2^d. — (0-1) 11-4 0-4 0-1 88-0 0-1 1,650 4d. 4,950 (0-3) 12-2 9-0 0-4 78-1 0-3 1,635 3d. 6,540 — . — • — 950 — 1,765 2id. -^1 — — — — 100-0 — 1,860 2id. 11,320 — 18-2 0-4 — 81-2 0-2 1,520 — - — 28-1 1-6 2-2 66-1 2-0 1,350 — — 17-2 2-4 1-7 74-2 4-5 1,495 5d. 3,588 10-0 13-1 2-3 3-0 68-5 3-1 1,445 7d. 2,477 — 18-8 4-3 0-3 74-2 2-4 ■ 1,475 6d. 2,950 15-0 19-0 1-8 — 62-2 2-0 1,190 5d. 5-1 2,856 (2-7) 5-9 10-7 7-0 74-2 1 2-2 1,875 3d. 1 24-0 4-5 8-1 5-3 56-4 1-7 i 1,425 '■ 1 — Table ;jHo\vtng Composition, Food Value, and Cost of Watery Foods. as as Vegetables : Artichokes, purchased Asparagus, purchased Beans, edible . . Fresh string, as purchased Beetroot, edible as purchased Cabbage, edible as purchased Carrots, edible as purchased Cauliflower Celery, edible . . | as purchased Cucumber, edible as purchased { Lettuce, edible . . as purchased < Muslirooras (0-8) 79-5 (0-8) (1-9) (1-8) (M) 20-0 (M) 15-0 (M) 20-0 (1-0) 20-0 (0-7) 15-0 (0-7) 15-0 (0-8) 94-0 89-2 83-0 87-5 70-0 91-5 77-7 88-2 70-6 92-3 94-5 75-6 95-4 8M 94-7 80-5 88-1 2-6 I 0-2 16-7 1-8 2-3 2-1 1-6 1-3 1-6 1-4 M 0-9 1-8 M 0-9 0-8 0-7 1-2 1-0 3-5 0-2 0-3 3-3 7-4 1-0 0-7 0-8 0-3 6-9 0-7 0-1 9-7 M 0-1 7-7 0-9 0-3 5-6 1-0 0-2 4-8 0-9 0-4 9-3 1-0 0-2 7-4 0-9 • 0-5 4-7 0-7 0-1 3-3 1-0 0-1 2-6 0-8 0-2 3-1 0-5 0-2 2-6 0-4 0-3 : 2-9 0-9 0-2 : 2-5 0-8 0-4 6-4 1-2 365 105 195 180 215 170 145 125 210 160 140 85 70 80 70 90 75 210 Id. lOd. Id. id. |d. Id. Id. 2d. Id. 8d. : 4,380 126 4,160 2,260 3,000 1,960 1,680 840 420 900 315 DIETETICS ?51 Table showing Composition, Food Value, and Cost of Watery Foods {Continued) =0 0^ &: Protein. 6s t 1 Fuel Value per Pound. Average Price per Pound, etc.. Approx. Caloric Value for 1/. Vegetables (cont.) : Onions, edible . . (0-8) 87-6 1-6 0-3 9-9 0-6 225 — — as purchased 10-0 78-9 1-4 0-3 8-9 0-5 205 Id. 2,460 Peas,green{f resh ) edible (1-7) 74-6 7-0 0-5 16-9 1-0 465 — — as purchased . . 4o-0 40-8 3-6 0-2 9-8 0-6 255 Hd. 2,040 Potatoes (raw) edible (0-1) 78-3 2-2 0-1 18-4 1-0 385 — — as purchased . . 20-0 62-6 1-8 0-1 14-7 0-8 310 |d. 4,960 Rhubarb, edible (1-1) 94-4 0-6 0-7 3-6 0-7 105 — as purchased . . 40-0 56-6 0-4 0-4 2-2 0-4 65 id. 2,520 Spinach (fresh). as purchased . . — 92-3 2-1 0-3 3-2 2-1 110 Ud. 880 Tomatoes (0-6) 94-3 0-9 0-4 3-9 0-5 105 4'd. 315 Turnips, edible . . (1-3) 89-0 1-3 0-2 8-1 0-8 185 — — as purchased . . 3()-() 62-7 0-9 0-1 5-7 0-6 125 id. 3,000 Fruits : Apples, edible . . (1-2) 84-6 0-4 0-5 14-2 0-3 290 — — as purchased . . 25-0 63-3 0-3 0-3 10-8 0-3 220 2d. 1,320 Bananas, Jam- aica: edible (1-0) 75-3 1-3 0-6 22-0 0-8 460 — — as purchased 35-0 48-9 0-8 0-4' 14-3 0-6 300 6d. 600 Cherries, edible (0-2) 80-9 1-0 0-8 16-7 0-6 365 — — as purchased 15-0 76-8 0-9 0-8 15-9 0-6 345 4d. 735 Grapes, edible . . (4-3) 77-4 1-3 1-6 19-2 0-5 450 — — as purchased 25-0 58-0 1-0 1-2 14-4 0-4 335 6d. 670 Oranges, edible 86-9 0-8 0-2 11-6 0-5 240 — as purchased 27-0 63-4 0-6 0-1 8-5 0-4 170 iw. 1,360 Pears, edible (2-7) 84-4 0-6 0-5 14-1 0-4 295 — — as purchased 10-0 76-0 0-5 0-4 12-7 0-4 260 3d. 1,040 Plums, edible . . — 78-4 1-0 — 20-1 0-5 395 — — as purchased 3-0 74-5 0-9 — 19-1 0-5 370 2d. 2,220 Raspberries (2-9) 85-8 1-0 — 12-6 0-6 255 5d. 612 Strawberries : edible (1-4) 90-4 1-0 0-6 7-4 0-6 180 — — as purchased . . 5-0 85-9 0-7 0-6 7-0 0-6 j 175 4d. .325 Water-melon: edible — 92-4 0-4 0-2 6-7 0-3 140 — — as purchased . . 59-4 37-5 0-2 0-1 2-7 0-1 (>0 u\. 1.440 Animal : Milk . . — 87-0 i 3-3 4-0 5-0 0-7 325 ■ — — Oysters 1 — 86-9 1 1 6-2 1-2 3-7 2-0 235 1 1 — — 3r)2 A TEXTBOOK OF PHYSIOLOGY .''ooD Values in Hoiseiiomj .Mkasdies Fond'i KS Eattn. Dairy : ^^iH^' • • • ■ . • Skimmed and buttci- milk. . Cream, thin, 20% ) Cream, thick, m^o J Condensed milk: sweetened y unsweetened j Butter Cheese, Cream \ Chee c. Skim-milk - Cheer, American J Egi;s, whole . . Eggs, yolk . . Eggs, scrambled Meat'and Fish (cooked): Beef tea, clear soujjs Fish, lean \ cod, flounder . . ) Fish, fat /shad, salmon j Meat, lean \ Meat, medium fat V M- a% fat J Lamb chop (edible portion) Oysters, medium size (raw) Cereals & Vegetables (cooked): Bread, white or brown Vienna roll . . Crackers (Uneeda) .. Cereals, cooked, moist Cereals, eaten dry . . Shredded Wheat Gruels, cereal Thickened or cream soups. . Macaroni Potato, boiled or baked . . Potato, mashed Rice, boiled . . Corn, canned Peas, fresh . ■ Lima beans . . Squash . . Fruits: Apple, pear .. Apple sauce . . Banana Orange (jrape fruit . . Strawberries . . Dried tigs, dates, raisins Fruit jelly, sweetened Desserts: Custard Ice cream Sponge cake . . Pudding (rice, tapioca, bread) Alcohol . . Whisky, brandy, etc. (50% ) Wines (8-25«.o ) Miscellaneous : Sugar . . Hone}', marmalade . . Olive oil Olives Almonds, shelled . . Cocoa powders Actwd Amount. 8 oz. 8 .. Htmnehold Approximate. A "lass ,,. / A tablespoon l()gras. ' 20 10 15 50 15 40 Leaping teasp'n -[ A pat or ball i in. cube One Heaping ta);lesp n 5 oz. A teacup 50 gms. Leaping tablesjj'n ( Medium slice 50 „ -,' 5x3x1 in. 45 1(1 40 ., 7 „ 40 „ 5 ,, ■ 30 ., 8 oz. 8 „ 25 gms. 95 ., 35 „ 30 „ 35 „ 35 „ 25 „ 35 „ 120 „ 45 „ 100 ., 130 „ 80 ., 100 „ 100 „ 50 „ 40 „ 40 „ 20 „ 45 „ 12 „ 1 oz. 1 „ 8 gms. 10 ' „ 4 „ 7 -, 25 „ 10 ., A medium One 1 slice, 4 X 4 X i in. One F±eaping tablesp'n One " A soup plate Heaping tablesp'n One medium Heaping tablesp'n 1, medium size Heaping tablesp'n 1, medium size 1, One-half small Medium saueeri'ul Heaping tablesp'n Slice 2 x4x-Hn. Heaping tablesp'n A tablespoon Small wineglass Heaping tablesp'n A teaspoon 1 medium size Heaping tablesp'n Heaping teaspoon Calo- Pro- ries. tein. 160 80 30 00 70 35 SO 65 '' 5 70 75 55 45 5-20 35 105 '0 1.% 200 165 8 70 I 115 ! 30 : 35 20 110 , 75 160 , 25 90 I 40 35 : 35 40 20 20 75 70 100 : 70 1 35 40 350 160 55 135 75 80 85 85 15-50 33 33 37 15 1()5 50 \Fni. \Carbo- hydrnte. Gms- Gms. 7-5 9-5 7-5 1-0 0-5 3-0 0-5 3-0 2-0 2-0 2-0 2-0 — 8-5 4-0 5-0 4-5 2-5 4-0 5-5 6-5 5-0 2-5 5-0 4-0 3-0 1 •0-4-5 8-5 — 11-0 6-5 11-5 2-5 11-5 9-0 8-5 18-0 9-5 13-5 1-0 0-2 2-3 0-5 3-5 I-O 0-5 0-5 1-0 — 0-3 — 3-0 0-5 2-5 1-0 5-5 4-5 1-0 0-5 2-0 — 1-0 1-0 1-0 — 1-0 0-5 2-5 1-0 1-0 — 0-5 — 0-5 0-5 0-5 i-5 0-5 1-0 — 0-5 — 1-0 0-5 2-5 3-0 0-5 _.. 2-5 0-5 1-5 9-0 1-5 2-0 2-0 2-0 , 4-0 _. 1-5 5-0 13-5 2-0 3-0 CHAPTER XLI THE CHIEF FOODSTUFFS It is necessary to consider a iew of the commoner foodstutJs in more detail. Milk. — Cow's milk is a staple article of diet for persons of all ages. It is to be noted that milk is relatively a waterj^ and therefore not a cheap, food. Fresh cow's milk is amphoteric in reaction, with a specific gravity of 1028 to 1034. When skimmed, the specific gravity rises to 1033 to 1037. A little water added will again reduce the specific gi'avity, and a little colouring matter will help to cover up the fraud. Milk contains all the necessary foodstuffs — proteins, fat, lipoids, carbohydrate, water, and salts. The chief protein is case'n- ogen, a phospho-j^rotein, notable for its high content in the ringed amino acids— t^Tosin and tryptophane. A certain amount of coagu- lable protein — lactalbumin — is also present. Caseinogen is clotted by rennet. When this takes place outside the body, " junket " is formed. Caseinogen is easily precipitated from solution by acid. When milk goes sour on standing, lactic acid is formed as the result of the action of a bacillus — B. lactis — upon the sugar contained in milk. The lactic acid so formed precipitates the caseinogen as the " curds," leaving a clear fluid — the '' whey." The term " whey " is often given to what is left after caseinogen has been removed by any means. When milk is clotted, a clear fluid exudes after a time — '" rennet whey." If caseinogen be precipitated by acid, neutral salts or alcohol, ■■ acid," " salt," or '' alcoholic "" whey is obtained. Some whej^s — e.g., rennet, acid — contain lactalbumin: others do not, the albumin being removed with the caseinogen — e.g., alcoholic whev. The fats of milk are carried down with the caseinogen. Olein forms the chief fat (43 per cent.); palmitin (33 per cent.) and stearin (17 per cent.) are also present, together with 7 per cent, of fats of the volatile fatty acids — butyrin, caproin, and caprj'lin. It is this con- tent of volatile fatty acids which aids to distinguish butter from margarine. The fats occur in the form of fine droplets, each drop of the emulsion b?ing surrounded with a fine film of caseinogen. In the whey are contained the sugar lactose and the salts. The chief salt is calcium phosphate; the phosphate of magnesium and the chlorides of sodium and potassium are also present. Milk con- tains but little iron. The milk of different animals varies in the content of the chief constituents. The differences between cow's and human milk are discussed elsewhere (see p. 537). The composition 353 23 354 A TEXTBOOK OF PHYSIOLOCV of the milk of various animals can be seen in the following table (Konig) stated in parts per 1,000 of milk: Water. S71-7 Solids. Proteins. 35-5 Fat. ■ Sugar. Salts. Cow 128-3 36-9 48-8 7-1 Horse 9iK)-(; 99-4 18-9 10-9 66-5 3-1 Ass . . UDO-d 100-0 21-0 13-0 63-0 3-0 Goivt 869-1 130-9 36-9 4U-9 44-5 8-6 Sheep 835-0 165-0 57-4 61-4 39-() 6-6 Pig .. 8-23-7 167-3 60-9' 64-4 40-4 10-6 Dog . . 754-4 245-6 99-1 95-7 31-9 7-3 Cat . . 816-3 183-7 90-8 33-3 49-1 5.8 Elephant . . 678-5 i 321-5 30-9 195-7 ■ 88-5 6-5 The walius's milk contains as much as 43 per cent, of fat. By the action of a special fungus — the kephir finigus — the lactose of milk, which does not normally undergo alcoholic fermentation, ferments to alcohol (1 to 3 per cent.), giving with cow's milk the drink known as kephir, with mare's milk koumiss. It is a general drink in Bulgaria and the Steppes of Russia. Meat consists of the muscle of animals and fat, with a certain amount of connective tissue. Besides the visible fat in prime meat, there is a considerable amount of masked fat also in the fibres. The muscle also contains various extractives and other bodies. Eggs are an exceedingl}- valuable article of diet by virtue of their great digestibilit}-. The white of the egg consists chiefly of egg albumin, Avith a small amount of egg globulin, and a mucus-like body — ovo-mucoid. A small amount of sugar {0-5 per cent.), and traces of fats, lipoids, and salts (0-6 per cent.), are present. In the yolk there is present also the phospho-protein vitellin, fat, and the colouring matter lipochrome. The Cereals — wheat, barley, oats, rye, rice — are the most wideh" used articles of diet. They contain much starch, and have the great advantage of being cheap. In their husks are contained valuable salts and vitamines. Their proteins, besides not being so well absorbed as animal proteins, do not contain such an appropriate assortment of " bricks" for building animal tissues as do the animal foodstuffs. Some of the '■ bricks " — e.g., glutamic acid — are present in large quantity, and if used for body-building, must be broken down previous to resynthesis. It has been shown that proteins, such as zein (from maize) and hordein (from barley), do not by themselves suffice to give the appropriate nitrogen to the body. Oatmeal with 7 p' r cent, of fat, against 1 per cent, in wheat, is a verj' valuable article ot diet, and should figure largely' in the diet of all peoples inhabiting temperate zones. Flour is made from the endosperm of wheat. Generally the outer husk (bran), inner husk (sharps), and the germ, are removed during THE CHIEF FOODSTUFFS 355 the milling process, and white flour is obtained. Further, it Ls fre- quenth* bleached with acids, and white calcium salts added to give extra whiteness. There is economic loss in such bleaching processes, which are, if anything, injurious to the consumer. When milled Avhole, whole-meal is obtained; when only the bran is removed, " standard " flour results. The chief protein, gluten, globuhn-like in nature, when mixed with water, becomes viscid, forming a dough. Gluten consists of two portions — gliadin, soluble in alcohol; and glutinin. soluble in alkali. The viscidity is due to the gliadin. Grains poor in ghadin — e.g.. rice, oats — do not form a dough when mixed with Avater. Bread. — The dough formed from flour is not a suitable food, owing to its iniperviousness to the digestive juices. When made pervious by aeration, and baked, it becomes bread. This aeration is performed by carbonic acid gas generated by the action of the 3'east which is mixed with the dough, and of a diastase already present in the flour. The Pulses. — This group of dry foodstuffs contain in the dry state a large amount of protein and carbohydrate, and, being cheap, are valuable as articles of diet. They have the disadvantage, however, that their physiological availability — the amount absorbed during diges- tion— is considerably lower than with the animal foodstuffs. They cannot be eaten dr^-, and when mixed with water and cooked they become very bulky foods. The proteins of pulses and cereals do not seem to be composed of such suitable "bricks" for building animal tissues as are the proteins of animal foodstuffs. The Fruits are of value bj' reason of the anti-soorbutic principles, the organic acids, salts and water the}" contain. Certain fruits also contain appreciably large quantities of sugar. The banana, often classed as a fruit, contains a relatively large amount of nutriment. Green Vegetables are of value as introducing a small percentage of food, with salts, vitamines, and a certain amount of cellulose, which stimulates the peristaltic action of the intestines. The salts of the vegetable acids are converted into alkaline carbonates, and are of importance in regulating the acidity of the blood. The green foodstuffs, particularh' spinach, also introduce iron into the body. Chlorophyll is possibly a precursor of haemoglobin. Potatoes contain carbohydrate and a small amount of protein, but this is in a most available form. They also contain vitamines, and thus are of great importance to town populations. (H AFTER XLII DIET UNDER VARIOUS CONDITIONS If man had to take his nutriment as one article of diet, to get the necessar}- protein — 15 grammes of nitrogen — he would require: 1-J pounds of beef, or 8 pints of milk, or 3 pounds of bread, or 13 pounds of potatoes,* or 60 pounds of apples. A diet consisting of 125 grammes of protein, 50 grammes of fat, and 500 grammes of carbo- hydrate, is contained in approximately | pound prime lean meat, li pounds bread, 2 ounces butter, h pint milk, 1 pound potatoes, and 1 pound oatmeal. The fat is raised to 100 grammes in the army service ration — i.e., for hard work in the open air of this climate. Sex and Age. — Since man is generally bigger than woman and does more muscular work, he requires the bigger intake of energy. Men and women of equal surface area, and performing equal work, require the same energy intake. A family of father, mother, and four children (13, 11, 9, and 7 years) is estimated to require the food of 4-5 men. Boys over 13 require a full "man value" — viz., 3,400 calories — food as purchased, the loss in cooling and absorption is estimated to be 10 per cent. A woman or girl over 13 requires -8 man value. In old age there is a marked decrease in vitality and bodily activity. Old j^eople therefore need not, and do not, take in the supply of energy required in the prime of life. Old bedridden people live on a diet which probably does not yield more than 1,000 calories. Work. — It has already been mentioned how the oxygen consump- tion and CO2 output are increased by muscular work. Not only do the muscles perform more mechanical work, but the bod}' generally is called upon to do more " physiological '" work to meet their needs. Either protein, fat, or carbohj^drate, can yield the energy required for muscular work, but since such work can be done most economically at the expense of the last, a diet for hard muscular work should contain an ample supply of caibohydrate with enough fat to sustain the work between meals. Carbohydrate is used first, while fat, more slowly digested and absorbed, is used later. Temperament. — Some people are by temperament vivacious and active, others are more phlegmatic and quiet. The latter Avill expend less energy as muscular work than the former, and therefore require * Three to four grammes of nitrogen seem to suffice on a potato diet. 356 DIET UNDER \'ARIOUS COXDITIOXS 357 a correspondiugh' less intake of energy as food. If they take as much, they grow fat. Climate. — Cold increases the activity — i.e., the amount of muscular work i^erformed — heat diminishes it. In cold climates there should therefore be an increase in the energy intake, particularly in the form of fat, which, owing to its high caloric value, is vevy heat-giving. In the tropics, on the other hand, food must be cut down, particulfaly protein owing to its high specific dynamic energy. The diet of natives in Singapore averages CO grms. protein, 35 fat, and 2£0 carbohydiate. with e.n energy value of about 1,600 calories. The Nutrition of the Foetus. — During pregnancy, the embr\-o is nourislied at the expense of the mother through the placenta. It is during the last three months of pregnancy that the great increase in weight of the foetus occurs; at the same time, the mother's oxygen use increases about 25 per cent, above the normal. Calculation shows, however, that not more than 10 grammes of dry matter per day are required for adequate growth of the foetus. Anah'sis of the full-time foetus shows that an average child of 7 pounds contains nearly 400 grammes of protein, 300 grammes of fat, and 83 grammes of mineral ash, chiefly calcium and phosphoric acid. In regard to the c£uestion of the diet of the mother, therefore, it is obvious that no excessive demands are made upon her in the matter of food intake. Special diets are not required by the pregnant woman. All that is required is a slightly increased intake of simple protein and lime-giving foods, such as meat, milk, eggs, cereals, fruits, and vegetables. The more nearly a mother lives a normal healthy life, the better it is for the foetus. The Nutrition of the New-born Infant. — The new-born infant should be fed, if possible, by its mother. Every mother should do, and should be encouraged to do, all in her power to suckle her own infant. The mother's milk is best adapted to the needs of the growing child. It is sterile : it contains the right kinds and proportions of protein, lecithin, and salts. It has been shown that there is a proportion between the composition of the mother's milk and the rate at which the young grow. This is especially marked in quickly growing animals. Thus, a puppy doubles its weight in eight days; its mother's milk contains 7-1 per cent, of protein and 1-3 per cent, of ash. A child takes six months to double its Aveight ; human milk contains but 1-5 per cent, of protein and 0-2 per cent, of ash. The lecithin-content of the mother's milk varies somewhat with the relative weight of the brain to the body weight. Relatively, the larger the brain the bigger the lecithin-content of the mother's milk. In the calf the brain weight to body weight is 1 : 370; in the puppy, 1 : 30; in the new-born child, 1 : 7. In proportion, the milk of the different mothers contains lecithin in percentage of the total protein 1-4, 2-11, and 3-05 respec- tiveh'. It is well adapted to the child's digestive powers, and, what is also important, it contains bodies capable of increasing the child's immunity to any ailments which may befall it in early life. This last point was proved by the following ingenious "' changeling '' experi- 358 A TEXTBOOK OF PHYSIOLOGY ment: A male and a female mouse were rendered immune to a ]ioisou (abriii). Each was then mated to a non-immune companion. It was found that the offspring of the immune male and non-immune female possessed no immunity against the poison. On the other hand, the offspring of the non-immune male and of the immune female possessed such an immunity, which gradually increased after birth, and Avas therefore not derived solely from the placenta. The offspring were then changed. The immune female suckled the non-immune young, the non-immune female suckled the imnume young. It was found that the former soon acquired an immunity, the latter quickly lost their immunity to the poison. Of the infant mortality mider one year, and particularly under eight months, the great proportion of deaths — in some cities as large as 170 per 1,000, over 300 in Russia — is among artificially fed babies. It must be borne in mind that such deaths are largely among the very poor, and the artificial food in such cases is often inadequate, and certainly not kept sterile and clean. The case against artificial feeding is largely a case against careless or ignorant artificial feeding. With a properlj' prepared clean food, such as the child can digest, and eontainmg the "building stones" suitable for its adequate growth, there is every reason to believe that the child develops, in most cases, into just as health}^ a babe as does the breast-fed infant. The introduction of dried milk has proved of the greatest import- ance in lessening infant mortality. The mother shoidd be urged to suckle the child during the first months as much for her own sake as for the child's. The act of suckling exerts a tonic effect upon the uterus. It assists in stopping hsenior- rhage from the placental site, and helps to secure the proper involution of the uterus. The Secretion oS Milk — The Mechanism of Secretion. — During pregnancy, preparation is made for the feeding of the young. The mammary glands begin to increase in size — the engorged veins testify to the activity taking place ; there is great proliferation of the alveolar cells and duct epithelium. This takes place under the influence of a hormone produced by the corpus luteum of the mother, and possibl}^ by the foetus itself. Nervous connections of the gland are not essen- tial. The gland may be transplanted in the pregnant animal, and will continue to proliferate. After birth, the proliferated resting glands enter into a state of great secretory activity, possibly owing to the removal of an inhibitory influence from the foetus. The first secreted fluid is known as " colostrum." This is secreted for the first few days, and is then followed by the supply of the milk proper. The secretion is under both nervous and chemical agencies. The sucking efforts of the offspring are a great factor in producing a good supply of milk. For this reason, the new-born child should be frequently put to the breast, even though the supply of food be scanty. It has been shown in animals that various chemical bodies, such as pituitary extract (see p. 523), and extract of the involuting uterus, when injected, cause an increased flow of milk. It is stated, also, that in woman the injection DIET UNDER VARIOUS CONDITIONS 35^ •of some of the mother's oami milk or of a sterile solution of caseiuogeu into the buttock Mill cause an increased supply of milk. In medical practice, various lactagogues are employed to increase the flow of milk, such as extract of cotton-seed. It is doubtful if the supply of milk thus stimulated is adequate to the needs of the child. It is .probabh' better to supplement a deficient supply by careful artificial feeding. Milk is a true secretion. It contains proteins and carbohydrate not found in the blood-plasma. It contains, also, a proportion of saUs quite different to those found in the blood-plasma, the proportion of some salts, such as that of calcium, being so great that they could not be derived from the blood by such processes as filtration, diffusion, or osmosis. The phospho-protein caseinogen probably originates from the cell protoi^lasm of the mammary gland itself, possibly by a hydrolysis of the nucleo-protein of the gland, and subsequent synthesis to caseinogen. The milk fat comes partly from the fat of the food. An ingested fat, such as sesame-oil, may be traced into the milk, but only in ver}' small quantities. Most of the fat is probably formed in the gland by synthesis from the components of the mammary gland, probably the proteins. It is possible, also, that some is formed from the carbohydrate brought in the blood to the gland. The origin of the mi.k-sugar is not well known: possibly it is formed by a rearrangement of the dextrose brought in the blood to the gland. Certain drugs are secreted in the milk — a fact of import- ance to nursing mothers. Compounds of morphine, iodine, arsenic, mercury, and iron, are among such. The Composition of Human Milk.— Colostrum, the first secreted milk, has a high specific gravity— 1040 to 1060. It is richer than ordinary human milk in coagulable protein (albumin), and is yellower in colour. It is rich in special cellular elements, known as "' colostrum corpuscles." Human 21 ilk is whitish-blue in colour, with a specific gravity of 1026 to 1036. It is amphoteric in reaction, but has a lower absolute alkalinity and acidity than cow's milk. The caseinogen of human milk has a shghtly different chemical constitution to that of cow's millv. It is said by some authorities to have a carbohydrate moiety attached to it. With rennet, it yields a far less dense and uniform elot. The precipitate with weak acid is more easily soluble in excess. This accounts for the greater digestibility of human milk. The pro- portion of caseinogen to lactalbumin is smaller in human than in cow's milk, being in human milk 2 : 1, in cow's milk nearly 6:1. The fat of human milk is stated to be poorer in the volatile fatty acids than cow's milk. The composition of human milk varies greatly. Its average composition is probably respresented bj' the following figures, those of cow's milk being given for comparison : Water. Protein. Fat. Carbohydralc. Sails, Human . . Cow's 90-2 S7-4 1-5 .3-4 3-1 3-7 5-0 4-8 0-2 C-7 3(Hi A TEXTBOOK OF PHYSIOLOGY It will he seen that, in addition to the c|iialitative differences mentioned aljove, the qnantitative composition of hmnan milk is markedly different from that of cow's milk. Woman's milk is poorer ill proteins, richer in sugar, poorer in salts. Human milk is also richer in lecithin. In regard to the salts, it is to be noted also that they are present in quite different proportions to those of cow's milk. The following figure:^ rein-esent the content in 1.0(10 parts of mik: K./K XiiJ). VaO. MgO. FeSh- PPh- 67. Human U-S84 0-3.J7 0-378 ()-0.>3 (>0(»2 0-310 0-591 Cow's 1-Tl> ()•.-,! 1-9S ()■•_'() (»•()( 13.") 1-8-2 0-ns It will be seen that human milk is much poorer (six times) in cal- cium salts and in inorganic phosphorus, as well as being generally poorer in all salts. It is obvious, therefore, that, besides being im- possible to make cow's milk qualitativel}' like human milk, il 's quite out of the question to make it quantitatively the same. In the past, much has been written about humanizing cow's milk. To effect such is out of the question. If the old rule be followed, by which it was fought to bring about a correct human proportion of proteins, fats, and carbohydrates, in cow's milk — namely, to dilute with water and then add cream and sugar — it is obvious that the proportion of salts is disregarded. '' Humanizing " is therefore a very rough process at the best, and it is never worth while putting a. patient to ex]iense to buy so-called humanized milk. Artificial Feeding. — Artificial feeding is sometimes necessar}^ and the question then arises as to what food an infant should be given. The principles to be borne in mind in artificial feeding are that the food and receptacles shall be clean, and not teeming with micro- organisms; and that the food shall be easily digestible by the child, and contain the essential "" bricks "" necessary for its growth. Cow's milk is obviously the most handy substitute; as shown above, it is not possible to humanize it ; but it must be acknowledged that some of these attempts at humanizing have succeeded in rendering the cow's milk more easily digestible b}^ the child. Some authorities recommend the addition of barley-water, others of sodium citrate. In the table (p. 359) is set forth a method of feeding proved success- ful . It should be noticed that there is no need to use expensive lactose, and if the parent be too poor to purchase cream, a vegetable oil may be used. The large quantity of fat serves a double purpose: it nourishes the child, and at the same time ensures that the iniant is not constipated. The addition of the lime-water insurer; that the clot of casein is light and easily digestible. Generally sjjeaking, the patent infant foods b}' no means approxi- mate to the correct proportions of the constitu3nts of human milk; many contain starch, wh'ch a very young child cannot digest. The proteins are not readily soluble in Avater, and there is also a deficiency in fats. If milk is boiled, the anti-scurvy vitamines require to be replaced by the giving of orange or swede juice. DIET UNDER VARIOUS CONDITIONS 361 p ^ o +3 ^<^ srj .*=* 'k g "5 S o s '■^ ;?> -. S ' ' ic ^ cS "?: ~ -* o o o 4^ •~ ce 3 s P P, 1^ 1 » ^ o ■4^ I— ■^ CO 0! ro b a) ■~. >--o 5i CM g; ;h b ^> OJ OJ P > > ^^ W W K — . ac <- ^11 p C 00 oo o « CO CO CO CO t :<« s t- S. S^ s" o ' • ' ' ' ' ' ^ ' o — i e -* t- r^ C-l oc '* c ^ ^! "S Ol oi CO -# •^ LO CO "t; ^ C 6 Tf ^ t-^ CO o-i 00 Tt( ^1 Ol 3^1 (M (M CO -<* ^ 1^ ^ il t; ^. ^ ■* '-^ ~^ c^ '^ CO ^ -T^ l^ X "~ !M •M 00 CO Tt< CO i^ 00 C5 ___^ 03 ""'" o 1 sj C s m £h 1 ^ ^ o sc (K a; 2 1 H o cc o o 5 o 'o 1 "^ ^ p o eg 5-1 5 i^ o o o s o X (0 5 'o X 1 S S H _o a u o ^ s « CD o ,— — ' , \ a; ?■ S a S ^ „ ^ ^ ^ ^ ^ ^ ^ >^ «^ ^ t S "^ ci •§ a- ►-Jb M ^ CO CO CO CO CO CO CO CO CO CO ^ .* CQ s t ■2 ^^ u - ' ' •~ " " " " 2 o ^^ Ch 1 "— ( — ffl ^ rt CO CO CO CO CO CO o o o oc ■ — ~< ' a. -p o -^ "-*' 3 " •^ ' •■ *- *■ "^ •" (i; 1-2 ?1 d -t o oi C^""' GC oi Tt- CO ^ ^ ^ o ■~s 00 00 '"' _-. ' ^ ^ o . - -. +2 c o :: " I r :: ' - Si N 4^ ^ -3 _- -3 — ^ ^ ^ ■-^ -S -C CQ a k4 4^ £ +3 +3 4J 4J -4J 01 M -* (M CO •rr »s CO t^ OO o; 362 A TEXTBOOK OF PHYSIOLOGY Weaning.— The inilk of a mother begins to decrease in quantity at the end of the sixth or seventh month. It is therefore desirable that the child should be partially weaned at this time. A further reason is that the mother's milk is deficient in iron, and this deficiency begins to be felt about this time. It has been shown that the young embryo has stored within it sufficient iron to last it until it can begin to take other food. Thus, in the case of the rabbit, the embryo has enough iron stored until the young animal begins to run about and take green food. Fig. 191.— Peotein keqtjired fok Weight and Stjeface at Difeeeent Ages. (WaUer.) W, TF=Body weight in Idlos (1 mm. = l kilo); S, »S=bod3' surface in square metres (1 cm.= l square metre); s, s=body surface per 1 kilo body weight in square cms. (1 cm. = l gramme); N, iV^= protein per kilo body weight in grammes (1 cm. = l gramme). During the period of lactation, the mother's dietary must be liberal in the more nutritious foodstuffs. It must be remembered that she is called upon to supply amounts varying from 20 grammes on the first day up to about 1,000 gi-ammes at the end of the sixth or seventh month. As far as possible, also, she must be spared from grief or anxiety, which seriously affect the nvlk, causing digestive DIET UNDER VARIOUS CONDITIONS 363 disturbances and loss of weight. Since certain drugs are secreted in the milk, only such medicines as are prescribed by a medical man should be taken by her. The progress of an infant is best judged by a gain in Aveight, which should be steady — from 4 to 16 ounces per week, excepting during the first week of life Childhood. — It is obviously important that the gi'owing child should haAc an abundant supply of food material, especially protein and such material as is necessary for the growth of the developing organism. Further, it is to be borne in mind that the child is not only growing, but also that it is a small animal, and therefore has a relatively 1400C IZOOC lOOOC 800C 600C 400 ( 200C Fiu. 191a. — Table of Food Values sitowixg Calories Pukchasable peh Penny. (Nuel Pa ton.) greater surface area and a corresponding greater respiratory exchange (Fig. 190). Further, the child, when healthy, is always active while awake. From Fig. 191, it is obvioits that in the first few years of life, and again at the age of puberty, the food-supply should be parti- cularly liberal. In the diet of a growing child, the cereals and potatoes should figure largely. At first ground oats, later oatmeal or rolled oats, are of particular value, by virtue of the large amount of proximate principles, as well as the large salt content. Milk in various forms, eggs, meat, fresh fruit, should also 1)e incorporated in the dietar3^ CHAPTER XLIII SPECIAL DIETETIC METHODS, ALCOHOL, COOKING, ETC. Special Dietetic Methods. — Of these the best known is vegetarianism, either '" true "' or " false. " In " true " vegetarianism, no animal food whatsoever is eaten; in " false " vegetarianism, such animal ^oods as milk, cheese, and eggs, are freely consumed . There is little to be said against false vegetarianism, provided that sufficient of these animal foodstuffs are eaten, insuring a good supply of protein and not too much vegetable fibre. The proteins, too, are such in kind and amount that putrefaction in the large intestine is not great. To this "false" vegetarianism owes its popularity. In regard to " true '" vegetarianism, there is very little evidence in support of the main contentions of its devotees. It is said that, on anatomical grounds, man is not a carnivorous animal; that meat js therefore an imnatiu'al food, dangerous to health. Man's alimentary canal is very different from that of a rabbit, with its enormous caecum; and the monkey, his near relation, eats animal food, eggs, insects, etc., as well as nuts and fruits. Granted that excessive ingestion of animal protein induces unwholesome putrefaction in the large intestine, so that toxins are formed deleterious to health, this was no case against a moderate intake of meat. The most virile tribes of the world, past or present, were or are great meat-eaters. Trouble arises from over-indulgence; some meat-eaters, owing to lack of exercise, do not keep themselves fit, and therefore do not compare favourably- with vegetarians, who keep themselves fit. The evidence shows that a "fit ■■ meat -eater is of better physique and mental capacity than a "fit " vegetarian. True vegetarianism has the di-sadvantage of intro- ducing too much ballast, just as pure meat-eating introduces too little. Further, the physiological availability of such foodstuffs is considerably less, and the proteins are of less value for tissue -forming. Various other special dietetic methods — "raw food,"' '" purin- free,' "low protein" — have their adherents. In these days of adulteration and separation of natural foods it is quite possible that errors may arise in man's diet, but it is safe to conclude that if the general public devoted as much attention to keeping itself fit by proper muscular exercise in the open air, as it does to the question of diet, the latter would cease to be of such importance. Alcohol.- — When taken in small quantities, alcohol is burnt in the human body, serving as a source of energy. Thus, it has been shown 364 SPECIAL DIETETIC METHODS, ALCOHOL, COOKING 3(35 in an experiment on man in the respiration calorimeter that the addition of 72 grammes of alcohol (500 calories) to a fixed diet exerted a gi'eater sparing effect on the protein of the diet than did 130 grammes of sugar (515 calories). It is probable that alcohol in such small non-toxic amounts acts as a carbohydrate-sparer. It is possible, also, that a small amount of alcohol facilitates digestion. While there is no basis of fact for the assertion that dire effects are produced by the taking of a small amount of alcohol into the human system, there is great economic waste of food in their preparation. Energy is dissi- pated by the process of fermentation. There is in a gallon of beer only one-tenth of the energy of the barley used in its preparation, and, even allowing for the food value of the waste products used for feeding cattle, there is still a considerable loss of valuable energ}^ By \artue of its quick absorjation from the stomach, and the ease by which it is combusted, alcohol is of great service in medicinal doses in treatment of cardiac failure. The feeling of warmth promoted by alcohol is due to an increased blood-flow in the cutaneous vessels, so that alcohol, instead of keeping out the cold, may tend to make the body lose more heat. " Wine is a mocker,"' and he who is exalted by it is a lenient critic; hence its reputation ior promoting sociability. It removes the consciousness of fatigue and the feeling of care, and makes facile the play of thought and speech by weakening the higher function of brain-inhibition. The subjective impression of mental capacity, exalted under the influence of alcohol, is unconfirmed by test. Small doses have no effect, larger ones diminish the fineness of control and skill in handi-w'ork. A man under the influence of alcohol will make more mistakes in type-WTiting and in casting columns of figures. Habitual indulgence in alcohol, by banishing the pressing sense of dut}^, makes a man indifferent to the obligations of family and national life. It is the monotonous, confined existence in modern cities which impels him to such indulgence. He who lives a hygienic life, oxygenates his tissues by outdoor exercise, and thus keeps a cheerful, active mind, will need not the '" wine which maketh glad the heart of man,"' but the " bread ^^'hich strengtheneth man"s heart." Table showixCx Percentage of Alcohol ix the Commoner Spirits, WrxE.s, AND Beers (J'ke-War Ti-me'^). Spirits. Rum . . Alcohol per Cent. \ . . 43-45 i Wines. Port .. Alcohol per Cent. . . -25 Beers. English ale Alcohol per Cent. 5-7 Brandy Wlii-skV Gin . . 43-45 i . . 40 . . 35-37 Sherry Champagne Hock i Claret . . -21 . . 10-15 . . 10 . . 9 Stout . . English lager German lager .. 4-7 .. 4-5 .. 3-4 Tea and coffee owe their popularit}' partly to the alkaloid caffeine — a methyl-purin — partly to the aromatic ]irinciples contained in them. In small do-^es caffeine is stimulating: in large doses it is 366 A TEXTBOOK OF PHYSIOLOGY poisonous. When prepared properly — that is, when infused for only a few minutes and then poured off — tea is free from injinious effects, but the habit of taking strong tea every two or three hours of the day is to be condemned no less strongly than the taking of alcohol. Cocoa is more of a foodstuff, particularly if made with milk. It contains fat and a certain amount of theobromine — an alkaloid closelj^ related to caffeine. Cooking of Food. — This is accomplished bj' means of heat, either moist or dry. Cooking has certain advantages and certain disad- vantages, the former outweighing the latter. The chief disadvantage in cooking is that coagulable proteins are j^ossibly rendered more insoluble in the digestive juices, so that their digestion takes longer, although eventually it is just as complete. On the other hand, cooking kills bacteria and other parasites such as trichinse and tape-worms, which may be present in the food. The connective tissue of meats is rendered more soluble, the fibres disintegrated and made easier for mastication, especially by moist heat. In the cereals, the starch granules swell up and rupture the cellulose envelope, rendering the cell-content more accessible to the digestive juices. In vegetables, the woody fibre is also more or less disintegrated, the tissue rendered more tender, and the cell-contents more or less liberated. Dry heat also converts a certain amount of starch into dextrin- — e.g., as in the crust of bread. The chief forms of cooking are boiling, broiling, and roasting. The main loss in cooking is water — the loss increases with the length of time of cooking — in roasting a considerable quantity of fat (the dripping) is lost from the joint. When boiling is employed, the liquor should be used to prepare soup, otherwise a considerable proportion of proteins, extractives, vitamine, and salts, is lost. This is true both for meat and vegetables. The peeling of vegetables greatly increases such loss. The most economical forms of cooking are broiling and \>y casserole. In the prejiaration of food, various flavours and condiments are often added. When used in moderate cpxantities, these, by rendering the food " toothsome," have the effect of causing a " psychic '" flow of gastric juice, and therebj^ promoting digestion. On the other hand, the excessive use of condiments tends to upset the digestive apparatus. The appetizing effects of cooking enhance the pleasures of the table, but often lead to overeating, and so to nutritive disorders of sedentary workers. A certain amount of uncooked natural food should be eaten, such as fruits and salads. Meals should be restricted to three a day, and no food should be taken between meals. For the preservation of the teeth, it is necessar}' that the mouth be kept free from food for most hours of the day. BOOK VI THE PROCESSES OF DIGESTION CHAPTER XLIV THE MECHANISM OF THE SECRETION AND ACTIVATION OF THE DIGESTIVE FLUIDS For the proper digestion of the food, digestive juices are necessary. These are provided either by large compound glands which He wholly outside the alimentary canal, and are connected to it by ducts, such as the salivary glands, liver, and pancreas; or by glands which occur in the lining membrane of the alimentary tract itself. These are comparatively simple gland tubes, and line the whole of the stomach, small and large intestine. The lining cells of the alimentary canal also contribute to the secretion of mucus, which acts as a lubricant, protects the mucous membrane from too high a concentration of ingested material, and furthers the passage of contents down the gut. To understand rightly the processes concerned in the digestion of food, it is necessary that we stud}' — (1) the mechanisms b}' which the digestive fluids are provided ; (2) the means by which the enzymes they contain are activated or otherwise rendered efiicient digestive agents. The proper preparation of foodstuffs for digestion, and their adequate digestion, are matters of first importance to the general \\ell-being of the body. Discomfort and local pain occur when these functions are temporarily deranged ; malnutrition, anaemia, depression of spirits, and general ill-health, follow chronic indigestion. Digestion of the food is necessary, in the first place, in order to convert the complex, colloidal, non-diffusible, and insoluble protein, starch, and the fat, into simpler soluble, diffusible, and non-colloidal compounds, which are absorbed by the cells lining the alimentary tract. Secondly, it is necessary because some of the component parts of the food material introduced into the body are of little or no value to the bodj^ ; others are of intermediate value ; others, again, are so precious that without them the body camiot live. In order, there- fore, that these components maj' be sorted according to their true value, it is necessary that they be separated from each other by the hydro^ lyzing action of the digestive enz3anes. 367 368 A TEXTBOOK (^F PHYSIOLOCY Generally, throughout both the vegetable and animal world, we find foodstuffs are taken into the living cells in a state of simple solu- tion, either alread}^ dissolved in water, or brought into solution by enzymes and water secreted by the cells. From the protozoon which engulfs its food up to the mammal is this true. True also is it of the insectivorous plants, such as the sundew and pitcher-plant (the former entraj)s insects with nets, or the latter with lethal wells of w^ater); of the yeast or bacterium; and of plants generally. The Mechanism of Secretion. — Two methods of calling forth secre- tion are employed: (1) The nervous reflex; (2) the chemical reflex, or " hormone " mechanism. One or both of these mechanisms may be used to provide a juice. More exact details are given when each juice is considered separately. Nervous tissue has been elaborated for the especial purpose of quick transference of messages from one part of the body to another. The nervous mechanism is called into pla3' when rajiid secretion is wanted. The nervous mechanism is therefore used for the supply of the saliva and for the first flow of the gastric juice. While enough fluid for the immediate demands of the body is provided by the nervous mechanism, the chemical mechanism is present to insure the presence of an adequate amount of digestive juices for the thorough preparation of food and its complete digestion. For the liberation of the "hormone reflex,'' either (1) the prod- ucts of the digestion brought about by " nervous " flow, or (2) some constituent of the juices so secreted, is concerned in calling forth this " chemical " flow of juice. For example, in the stomach we find that the presence of dextrin and peptones — that is, the products of a salivary and gastric digestion respectively — liberate from the pyloric mucous membrane a body — " gastrin " — which is absorbed into the blood, and, reaching the gastric glands, excites a further flow of gastric juice. It may be also that there is something in the saliva able to bring this mechanism into action, for it has been noticed that swallowed saliva ap^Dcars to have the powder of evoking a flow of gastric juice. The flow of pancreatic juice is also brought about by a "' chemicaJ " reflex — namely, by the liberation from the duodenal mucous mem- brane of a body termed " secretin," which passes in the blood to the pancreas, and stimulates that organ to activity. There is evidence that the pancreas may also be excited to secrete by impulses reaching it through its nerves. This, however, does not appear to be the normal mechanism. In the case of secretion excited bj^ nervous mechanisms, it is probable that the nervous excitation of the gland evokes a "" hor- mone " in the gland itself, which excites the secretion. For example, an extract of resting salivary gland has no effect when injected into the blood, but an extract of the same gland, after stimulation of the chorda tympani nerve, is said to provoke secretion of saliva when injected. The exact natm-e of the substance provoking the flow of succus entericus is not well known. Undoubtedly, the acidity of the chyme entering the duodenum plays a most important part as regards the SECRETIOX AND ACTTVATIOX OF DIGESTIVE FLUIDS 369 provision of this juice in the duodenum. It is suggested that, for the other parts of the small intestine, the absorption of the products oi the digestion in the parts above evokes a messenger which, absorbed into the blood, calls forth a flow of appropriate juice in the regions . lower down the tract. The bile takes an important share in the preparation of the food for intestinal digestion — for example, in the emulsification of fats and the precipitation of protein from acid solution. A quick flow of bile is therefore required. In animals where a gall-bladder exists, the first flow of bile is probabh* provided by the contraction of the gall-bladder, which is excited by a nervous reflex. The reflex arises from the stimulus of food passing the pjdorus. A further supply of bile is provided from the liver by the action of "' secretin." This insures its presence in the intestine in amounts adequate to the food which is arriving there to be digested. Possibty, too, the products of digestion reaching the liver cause a further flow of bile. The reab- sorption of bile salts from the intestine stimulates the liver to secretion, but this is usualh' after the period of active digestion, and the bile secreted by this mechanism is generalh* stored in the gall-bladder, there being a correspondingly active secretion to replenish the depleted store. The following chart shows how different juices are pro\'ided: Juice. Mechanism. Saliva . . . . . . Nervous reflex. Gastric juice .. .. (1) Nervous reflex. (2) Liberation of gastrin (chemical reflex). Bile .. .. .. (1) Probably nervous reflex contraction of gafl. bladder. (2) By secretin (chemical reflex). (3) By products of digestion reaching liver. (4) By absorption of bile salts. Pancreatic juice .. .. (1) By secretin. (2) Probably also by nervous reflex. Succus entericus . . . . (1) By acid chjane. (2) By absorption of products of digestion. We have, therefore, to bear these mechanisms in mind \\hen thinking of the digestive disorders which may possibly arise. It may well be that in some conditions the flow of one or other of these juices is not evoked adequately, owing to a failure of the pro]ier stimulus for its secretion. . The Activation of the Juices. — In most of the juices the digesting agent, or enzyme, is in the form of a precursor, or zymogen. This zj'mogen must be converted into the enzyme, or "' activated," as it is termed, before it becomes potent. The enzyme of the saliva — " ptyalin "" — is probably activated by the bacteria of the mouth, or some other body present in the mouth, since in the horse it has been found that if the saliva be collected aseptically it manifests no digestive action. It is only when bacteria are allowed to enter the saliva that the enzyme attains its digestive power. Bacteria probably play a similar and important part in other parts of the alimentaiy tract, even when specific activators of the zymogens are secreted there. 24 ;no A TEXTBOOK OF PHYSIOLOGY The normal acti\ator of the gastric zymogens — joepsinogen and prorennin — is the hych'ochloric acid (HCl) of the gastric juice. It has been found, howexer. that these two zymogens may become converted into the active enzymes in conditions where little or no HCl is being secreted. In such cases, the exact activator is not known; it is quite probable that bacteria play a part. Similarly, the normal activator of the trypsinogen of the pancreatic juice is a substance known as " enterokinas^e," which is secreted in the succus entericus. But it is probable that an enzyme — "deuterase" — and calcium salts also possess the power of converting this zymogen. The other enzymes found in pancreatic juice are possibly secret ■^d as zymogens, but the exact nature of their activating agent is not known. The same must be said in regard to the enzymes of the succus entericus. The steapsin of the pancreas reqitires the presence of bile salts to act as co-enzyme. The enzyme loses its digestive power if these be dialyzed awaj". It is quite possible that in some conditions of digestive disturbance there is an inadequate liberation of the enzymes from the zymogens, in others an inadequate secretion of the zymogens. At j^resent, om- knowledge on these points is fragmentary. Juice. Proenzyme, Activator. Saliva Ptyalin Bacteria Gastric Pepsinogen Prorennin Hydrochloric aci Pancreati Trypsinogen Entcrokinase. Calcium salts. Deuterase. Bacteria (?). In regard to other enzymes, the present state of knowledge is in- sufficient for them to be tabulated. CHAPTER XLV DIGESTION IN THE MOUTH The Saliva. — The saliva is secreted from three pairs of glands in the region of the mouth. These are the parotid, tlie submaxillary, and the sublingual. It is also secreted by other minute glands con- tained in the buccal mucous membrane. The character of the saliva varies in the different glands. The parotid of man and most animals yields a thin serous (albumin- ous) saliva, while from the submaxillary gland " mixed "' saliva, partly serous or watery, partly mucous or viscid, is usually obtained ; in the rabbit, however, the secretion of the submaxillary glands is wholly serous. Saliva is a mixture of the secretions of all these glands. The parotid saliva of man is a thin, faintly alkahne fluid, containing but little protein and no mucus. Its specific gravity varies from 1003 to 1012. It contains a starch-splitting enzyme — ptyalin — and in most cases a small amount of potassium sulphocyanide, with a variable small amount of salts (0-5 to 1-6 per cent.) and gases in solu- tion (oxygen, nitrogen, and carbon dioxide). The oxygen in the saliva is greater in amount than that which is dissolved in water when exposed to the atmosphere. The excess must be secreted m the saliva. ^ . Submaxillary saliva varies according to the exciting conditions. In man, the submaxillary sahva is ordinaril}" a clear, viscid, alkaline secretion, with a specific gravity of 1002 to 1005, and about 0-3 to 0-5 per cent, of solids. It contains much mucin, traces of protein and the ferment ptyalin, potassium sulphocyanide, and inorganic salts, the chief of which are the chlorides of sodium and potassium, the phosphates of calcium and magnesium, and the bicarbonate of calcium and sodium. Traces of sulphates are also present. In the dog two kinds of submaxillary saliva are recognized: that pro- duced b\' stimulation of the chorda ty! ii r -1 B, body; P, pylorus; tudmal are contmuous with those ot the oeso- /j, incisura ano-u- phagus, and radiate over the stomach, to end at the laris ; PO, pyloric pylorus. The circular fibres completely invest canal, the whole stomach, being particularly well marked in the pyloric portion, especialh" at the pyloric sphincter. They also form a well-marked thickening at the incisura angularis. termed the " transverse band." The oblique fibres, starting as two strong bands from the left of the cardiac orifice, pass along the anterior part of the dorsal and ventral surfaces toA\ards the pylorus, gradually disappearing as they go. The structure of the glands varies in the different portions of the 379 380 A TEXTBOOK OF PHYSIOLOGY stoiiuich. The glands of the fundus are simple tubules lined with one layer of cells, somewhat similar to the crypts of Lieberkiihn of the smaller intestine. The glands of the cardia or body have short ducts with long, straight tubules. In these tubules arc two sets of cells. The central or chief cells are cubical in shape, and contain coarse granules, which are usually in greater profusion nearer the lumen. Lying in between the central cells, and to their outer side, are a number of large spheroidal cells, known as the " parietal " or " oxyntic " (acid-forming) cells. Each of these cells appears to be connected to the lumen of the gland by a number of small channels which pass between the central cells. In the pylorus the glands have long ducts, and the secreting tubules are long; and much branched, being often continued into the submucous Fig. 195. — Diagram showing the Position of the Stomaih. (Hurst.) -f'=Fundus; P.6'. = pyloric canal; ?7= umbilicus. tissue. Here, again, there is only one form of cell lining the gland, corresponding to the central cells, but distinctly less granular in nature. Corresponding to these different sets of glands we have, also, three distinct kinds of secretion or juices. The secretion of the cardia is neutral or faintly alkaline in reaction, poor in salts, rich in mucin, and containing in some animals (the pig) an amylolytic and probably a maltose-splitting enzyme (maltase). The juice of the fundus is characteristic in being acid in reaction. It contains peptic, rennet, and lipolytic enzymes. The secretion of the pylorus is alkaline in reaction, and contains a small quantity of proteolytic enzyme, no lipase, and much mucin. Gastric Juice. — The term " gastric juice " is now usually applied to the funda! secretion, which, in fact, must be regarded as the DIGESTION IN THE STOMACH 381 characteristic secretion of the stomach. It is a matter of some difficulty to obtain it pure; indeed, there is onl}^ one method — namely, that of making a gastric fistula. The older methods include — (1) the giving of ^aerf orated hollow balls of lead which contain food to birds of prey (the balls are sub- sequently vomited up); (2) the swallowing of a sponge to which a string is fastened, whereby it is subsequently withdrawn and squeezed ; (3) killing of an animal after giving some indigestible material to eat, and collecting the juice; (4) the withdrawal of the stomach-contents by the passage of an oesophageal tube three-quarters of an hour after a test-meal has been eaten. These methods give only gastric contents, the mixed secretions plus the ingested food and fluid, and we gain thereby no idea of what constitutes the true gastric juice. The first gastric fistula studied Avas one accidentally made hy a gunshot wound upon a Canadian, Alexis St. Martin. Beaumont took c A Fig, 196. — Pawlow"s Method of e.stablishing a Gastric Fistula. A, B, Incision; S, segment of stomach separated off; Ji, abdominal wall; e, mucous membrane; P, pylorus; 0, oesophagus; Rv, right vagus nerve; L>:, left vagus nerve. the man into his service, and published a small book, the result of patient years of observation. A fistula has been established in dogs, and observations made by several workers. A technique which leaves intact the blood and nerve supply has been recenth' perfected (see Fig. 196). In order that no food or saliva shall reach the stomach, an oesoph- ageal fistula is made by bringing the oesophagus out to the side of the neck, dividing it, and stitching both the upper and the lower end into the wound, so as to leave the orifice of each patent. Any food or saliva passing down the oesophagus falls out from the upper end, and does not reach the stomach (sham feeding). Through the lower opening substances can be introduced directly into the stomach. Tiie gastric juice obtained in this manner is a clean watery licjuid; its percentage composition varies in different animals. 382 A TEXTiiUOK OF i'HV8i(JLUGY Man. ]*<"J- Sheep. Water 99-44 U7-:}0 98-6 Organic matter, chw^y \iei)iii\\ .. .. .. 0*S2 l-Tl 0-4 Inorganic matter — (rt) Free hydrochloric acid 0-2-0-3 0-3(( 0-1 (h) Chlorides and phosphates of alkalies and alkaline earths (>l-(»-J (Hiij i 0-9 The specitic gravity is ()-()0l to 0-OKJ. The special characteristic of this juice is its acidity. This has four main functions: 1. To kill ingested bacteria in the stomach, and thus (a) inhibit the entry of pathogenic organisms into the body, and (h) prevent the early 2:>utref action of the ingested food. 2. To facilitate protein digestion. 3. To liberate the hormone secretin from its precursor in the duo- denal mucous membrane, and thus excite the flow of juices from the pancreas and liver. 4. To induce a flow of intestinal juice in the duodenum. In regard to the first function, it has been shown that the acidity of the juice in guinea-pigs is sufficient to kill the cholera vibrio or bacillus. If, however, the gastric juice were first neutralized, the introduction of the bacilli killed the animals. Apart from pathogenic bacteria, it is important that bacteria which split proteins and carbohj'drates be kept in check ; otherwise a large jjart of the ingested food would be wasted. Meat mixed with gastric juice, or a dead frog in a snake's stomach, will keep sweet and free from putrefaction for days. A considerable amount of controversy has taken place in regard to the nature of this acidity. It was at first believed to be due to lactic acid. That it is due to hydrochloric acid is shown conclusively by the fact that in an analysis of the juice there are more chlorme atoms found than can combine with all the bases. How far the acid is com- bined or free in the secreted juice is a matter of doiibt. Most of it is probably not free in the chemical sense, but so loosely combined that it is able to effect its physiological function. The difference is shown thus: (1) A solution of pure hydrochloric acid of the same degree of acidity, when heated quickly, gives off acid fumes; gastric juice does not until a sj'rupy consistency of concentration is reached; (2) hydrochloric acid of the same acidity will transform starch into dextrins, gastric juice will not; (3) the inverting j^ower of gastric juice upon disaccharides is not so powerful as an equivalent strength of hydrochloric acid. Nevertheless the acid in the pure juice certainh" reacts acid to such indicators as congo-red, dimethylaminoazobenzol, and therefore may be termed " jDhysiologically " active. HCl is freely dissociated into H and CI ions in such dilutions as are found in the stomach. Weak organic acids, such as lactic and butj^ic, are DIGESTION IX THE STOMACH 383 l>ut slightly dissociated. Hydrochloric acid readily combines with proteins, and this is known as " combined acid," for it dissociates very sHghtly. Under these circumstances, it will not give the reac- tions of free acid. Considerable importance is attached clinically to the proportion of the free acid to the combined. A small amount of acidity may also be due to the presence of acid salts. The Mechanism of Secretion. — ^ After a period of secretion, the granules of the chief cells have greatly decreased in number, and the colls have become shrmiken. These granules have given rise to the peptic ferment of the juice, for less ferment can be obtained from cells poor in granules than from those rich in granules. The granules are the precursor or zj'mogen. This can be shown as follows: Sodium carbonate destroys the active enzyme pepsin. Nevertheless, a sodium carbonate extract of the fundus, when rendered faintty acid with hydrochloric acid, manifests all the digestive actions of pepsin. The precursor is not destroyed b}^ sodium carbonate, and the extract of zymogen, when rendered acid by HCl, is converted into the enzyme. If the fundus is first treated with hydrochloric acid, and then with sodium carbonate, no active enzyme is obtained, for the zymogen is converted by the acid and the enzyme destroj-ed by the sodium carbonate. The parietal or oxj'ntic cells secrete the h^'drochloric acid, smce the acidity only appears in the jiiice of that portion of the stomach where they occur. This is not the only example of free mineral acid being excreted b}' glands. In a giant mollusc, Dolium, the salivary glands secrete H2S0^ (about 2 per cent, solution). This juice effer- vesces when it falls on a marble floor. It is strange that living cells should secrete so potent an acid, which is destructive to Ufe. The h3'di'ochloric acid is probably secreted in a combined state, which becomes active after secretion. The gastric juice is liberated by a double mechanism — ^nervous and chemical. The Nervous Mechanism. — The gastric glands have a double nerve- supply from the autonomic sj'stem: (1) the vagus, (2) the S3"mpathetic. It is not easy to excite directly the secretory fibres to the stomach and produce secretion, as can be done in the case of the salivary gland. On the other hand, the secretion can be excited reflexly, the afferent paths being the same as those which excite the secretion of saliva. The effect of psychic and other stimuli has been fully studied by means of sham feeding on the dog, in which oesophageal and gastric Hstulse have been established. Secretion results from — (1) the psychic element, (2) contact with buccal mucous membrane and the act of mastication, (3) the taste of food (see Fig. 192). The sight of food causes a secretion; in a hungry dog this contmues for as long as one and a half hours. If the animal is then given a sham meal, it is found that the amount of secretion obtained by the psychical stimu- lation is rather greater than that obtained by the introduction of the food into the mouth. 384 A TEXTBOOK OF rHV.SlOLUGY The psychical secretion, or " appetite juice," may be provoked by seeing, hearing, by smeUing food, and in human beings by memory alone. The thought of food makes the mouth of a hungry person " water," and the gastric juice flow. " Digestion waits on appetite " is a sound proverb. It is a disputed point as to whether food, by its presence in the stomach, nervously excites a flow of juice. It is now generally held that such is not the case, for introduction of food through an oesophageal fistula into a dog's stomach while it is sleeping excites no flow of juice. The same is true in the case of man. The secretion, excited either by the psychical reflex or by the reflex from the mouth, is abolished by cutting the vagi; this points to these nerves as containing the efferent secretory nerves to the stomach. Division of both vagi may give rise to absence of gastric movement and disorder of digestion; it has been performed below the diaphragm with little ill effect. The existence of the second mechanism of ijroviding juice complicates matters. It is difflcult to produce a secretion of gastric juice by stimulating the peripheral end of the vagus nerve, owing to the disturbing action of the nerve upon the heart. About four days after section of the nerve, when the cardio-inhibitory fibres have degenerated, stimulation of the peri- pheral end of the divided vagus excites, after a latent period of three to five minutes, a marked flow of gastric juice. It is difficult, however, to explain the long latent period. The Chemical Mechanism. — Secretion is called forth by the libera- tion of a hormone — '■gastrin" — and its absorption into the blood-stream. The '' gastrin " is stored in the pyloric mucous mem- brane, and is liberated by such bodies as dextrins, maltose, dextrose, peptones ; in fact, the products of digestion of a part of the alimentary tract at higher level than the pylorus. The products, when injected into the blood by themselves, excite little or no secretion. The gastrin is not destroyed by boiling. Variation of Composition. — It is held by some authorities that the juice obtained by nervous excitation does not vary in quality, whereas that secreted by the chemical mechanism (local changes in the stomach) shows marked variation in the quantity and nature of the juice. Thus, the secretion is said to be greatest in amount with meat, the digestive power greatest with bread. 100 grammes cut meat . . . . . . . . = 300 c.c. 250 „ milk = 200 c.c. Fats are said to increase the amount of pepsin, starch to lessen it. Others doubt this adaptation of the juice to the food eaten. The amount of juice may also vary with the amount and character of the salts in the food, its alkalinity or acidity. Thirst, muscular exercise, and a condition of plethora, markedly infiuence the quantity of juice secreted. The introduction of food into the ileum and into the rectum excites a flow of juice; at present, it is difficult to say whether by the nervous or chemical mechanism. The effect of food on the juice is given in the following order: DIGESTION IX THE STOMACH 3S5 Degree of Acidity. Degree of Digestive Activity. Duration of Secretion of J u ice. Meat Milk Bread Bread Meat Milk Bread, Meat 3Iilk The Digestive Processes in the Stomach — Peptic Digestion. — The peptic enzyme is proteolytic in nature, and acts only in acid medium (HCl 0-1 to 0-5 per cent.); in fact, it is probable that the true digestive l^rinciple is a combination — pepsin-hydrochloric acid. The proteui is first swollen and partially disintegrated by the hydrochloric acid, and then acted upon b}' the pepsin-hydrochloric acid. This can be shown by the following experiments: (1) Coagulated egg-albumin soaked in 0-3 HCl, and then washed and added to neutral pepsin, is not digested; (2) if the swelling of protein be stopped by the jiresence of bile, diges- tion is stoi^ped or greatly hindered. The peptic ezyme digests all proteins except keratin. Elastin is but little attacked. The other proteins, including gelatin, are easil}' digested, passing through the prelimmary stages of conversion into proteoses, primary- and secondary, to peptones and pejDtides (abiuretic bodies not giving the biuret test). The change is by no means so com^Dlete as in the case of the pancreatic enzyme, tr3'psm. It may be represented as follows : Protein > Acid metaprotein Primary proteoses (proto and hetero) Secondary proteoses (A, B^ C) Peptones (A, B) Peptides (giving no biuret test). The methods by which the presence of these bodies can be shown in the digest can be gathere I from the table on p. 386, which embodies the chief facts ascertained by recent research. It will be seen that the chief differences between them are brought out by their I'elative solubility on addition of a saturated solution o. ammonium sulphate, salicylsulphonic acid, or alcohol. It has been found that only a smill percentage of protein is converted into acid metaprotein (fornierh' called " syntoain "). Some of the primary proteoses are split off earlisr than the others; the same remark applies to the secondary proteoses and peptones. Therefore, quite early in the digestive pro?ess. peptones and peptides make their appearance. Tnis is to be explaine:! bv the fact that these bodies are not of the same chemical composition. For example, hetero- proteose 3delds, on decomposition, chiefly leucin and gl3'cin, -whilst proto proteose 3'ields much tv'rosin and indol. Similarly, with the second a^^y proteose <, one was found to contain much sulphur, another 886 A TEXTBOOK OF PHYSIOJ.OCJY but little; one mueh carbohydrate, another but httle. Their chemical nature in part determines the rate at which these bodies are spUt off from the protein ingested. Therefore, early in digestion there is a beginning of the sorting out of the special constituents of the different proteins — a sorting out to enable the body to choose the portions of the ingested protein requisite for the building of its own special proteins. In digests made in the test-tube, the maximmn of hetero- and proto -proteose occurs in half an hour, and then rapidly diminishes. One form of secondary proteose (B) showed similar variations, A gave its maximum in five to eight hours, C after two or three days, peptone in one to two months. Of the contents of a dog's stomach, after half to six hours' digestion of cooked meat, 90 per cent, consisted of proteoses, acid metaprotein accounting for the other 10 per cent. The peptones and peptides are absorbed as soon as they are formed in the stomach. Normally, this absorption is from 20 to 30 per cent, of the protein eaten. The toxin of protein-like bodies — for example, of tetanus and of snake venom — is rendered innocuous bj' gastric digestion. Salici/lsul- phonic Acid and Protun. Precipitation with Solubility in Alcohol. Biuret Test. Millon's Reaction. H\0.^ Tests. Precpitate Violet Native Globulins(haU' Insoluble + saturation ) coagulated Albumins (full on boiling s;.tin-dcion) Acid niL-ta- Half — Do. Do. Do. protein saturation Primary Half Hetero in- Precipitate Rose pink Hetero,feebIe ; proteose saturation soluble in soluble on proto, strong (hetero and 32% ; proto- boiling, proto) soluble in 80% reappearing on cooling tSecondary Two-thirds Partly in- Do. Do. + proteo.se A saturation soluble in 70% Secondary Full satura- Partly insol- Do. Do. One variety proteose B tion uble in 35% ; — ; (several partly solu- Others' + varieties) ble in 80O(, Secondary Full satura- Soluble in Do. Do. ])roteose C tion plus acid (HSOj 68-80% I^eptoncs Not pre- A insoluble Not pre- Do. — cipitated in QQ% : cipitated B soluble in Not pre- Do. -1- 96% cipitated Peptic digestion in the same period does not break down the protein so far as tryptic digestion. The fact that with prolonged gastric digestion in vitro all the end products of tryptic digestion are formed, except the hexone bases, would seem to afford support to the DIGESTION IN THE STOMACH 387 view that these bodies form the central nucleus round which the rest of the protein molecule is built. The Action of Rennet. — The rennet enzj-me runs parallel in secre- tion to })epsin. There is a prorennin in the mucous membrane, like pepsinogen, which is not destroyed by a weak sodium hydrate solu- tion, and is converted by hydrochloric acid ; but remiin, unlike pepsin, can act also in neutral and faintly alkaline media. The action of rennin is upon the caseinogen of millv. The molecule of this soluble protein is rearranged by the action of the rennin, so that a body called ■■ soluble casein " is formed. Here the action of the rennin ceases. This soluble casein, in the presence of calcium salts, forms insoluble casein, or the clot of milk. (1) Caseinogen + Rennin =Soluble casein. (2) Soluble casein + Ca salts ==Insoluble casein, or clot. Thus, if in a test-tube experiment rennin be added to some milk, from which the calcium salts have been removed by the addition of a soluble oxalate, its action proceeds to stage (1), and no clot forms. If after, say, fifteen minutes the milk be heated to 100° C, the rennet enzyme is destroyed. The addition of calcium salts now causes the clot to form, thus showing that the rennet enzyme is merely concerned in the rearrangement of the molecule, and not in the formation of the insoluble clot. Why a rennet enzyme should be provided to clot milk is somewhat a mj'stery, since unclottcd milk is digested by pepsin and trypsin. It is noteworthy that in plants, as well as animals, a rennet enzyme is found running parallel in secretion with proteolytic enzymes. The clotting may be merel}^ a result of the action of the proteolytic enzyme on the protein caseinogen. The Lipase of the Gastric Juice. — The presence of a gastric lipase has been established : at one time it was held to be due to a reflux of pancreatic juice through the pylorus. It exerts its maximum action in neutral or faintly acid medium. Therefore, normally its action in the stomach is not at all potent. Nevertheless, it is probably important, inasmuch as by its action neutral fats will be rendered slightly rancid, and these fats, on entering the small intestine, owing to this rancidity, will be far more easily and more finely emulsified than would otherwise be the case, and their digestion thereby greatly facilitated (see later, p. 395). The Action of Gastric Juice upon Starches and Sugars. — In some animals — e.g.. the pig — the starches will be digested by the amy- lopsin of the cardiac juice. By the stomach of man and the dog there is probably no amylopsin secreted. Nevertheless, the fact must not be overlooked that in the cardiac reservoir salivar}- digestion normalty proceeds for thirty to forty minutes. The hydrochloric acid of the gastric juice exerts but little or no hydrolyzing effect upon starches, dextrins, and the disaccharides. 388 A TEXTIiOOK OK F^HVSIOLOCY In man, but not in the dog, there is probably an invertase present Avhich converts canc-sngar into dextrose and levulose. Why does the Stomach not Digest itself ? — It may be asked: " Why does the stomach not digest itself i" There are ])robably several con- A TEXTBOOK OF PHYSIOLOGY bigger. In the rabbit, the orifice of the ])aiTcreatic duet is consider- ably below that of the bile (35 centimetres). The structure of the living gland can be particularly well studied in this animal, since the gland is spread in the mesentery in a thin, transparent layer which can be examined under the microscope. The cells are seen to resemble closely those of the parotid gland. Before secretion, they have been observed to be swollen and distended with granules; after secretion, the cells become shrunken, most of the granules have dis- a])peared. and are only seen near the lumen. In this gland, also, are certain little aggregations of tissue known as the " islets of Langerhans.'' The exact significance of these has been much debated. Some hold that they a-re the secreting alveoli in an exhausted condition. It is now, however, generally conceded that they represent the inclusion of another gland within the pancreas — a gland which is formed separate in certain fishes. The function of these islets is discussed in the chapter on internal secretions (p. 511). The Pancreatic Juice can be obtained by the insertion of a cannula into the duct, and making a temporary or permanent fistula. It is a clear, slightly viscid, strongly alkaline fluid. The composition of the juice varies, that secreted upon the establishment of a fistula being as a rule considerably richer in solids than that secreted some days later. Directly after Pancreatic Operation. Fistula. 00-08 97-68 9-02 2-3-2 lt-04 1-04 0-88 0-68 Water . . Total solids Organic Inorganic In cases where a pancreatic fistula has resulted from an operation in man, the amount of the secretion has been found tc vary from 600 to 800 c.c. per diem, and to have a specific gravity of 1007. The organic constituents are due to the enzymes contained in it, together with some heat-coagulable protein. There are also traces of leucin, tyrosin. xanthin, and soaps. The inorganic salts are mostly the chloride, carbonate, and phos]:)hate of sodium.^ The alkalinity of the juice is due to the two latter. In addition, there is pre.sent potas- sium chloride and the phosphates of calcium and magnesium. This juice is the most powerful digestive fiuid of the ahmentary canal. It contains several enzymes, the best known being the protein- sphtting (trypsin), fat-splitting (steapsin or lipase), starch-.splitting (amylopsin). and the rennet enzyme. It is probable that rennin and trypsin are to be regarded as side-chains of the same bod}-. The other enzymes can apparently be separated from each other, and are stated to vary in. amount in the juice according to the nature of the food. Thus, when the secretion on a milk diet is compared with that on a bread diet, it is found to contain half the tryptie, one- c|uarter the amylolytic, and six times the fat-splitting potency. Further evidence of the independence of the enzymes is — DIGESTION IN THE SMALL INTESTINE 397 1. The diastase does not appear in the juice until a month after birth, trypsin being present from the start. 2. Tryjasin can be precipitated and separated from the other enzymes b^'^ addition of collodion. It was at one time stated that the enzymic content of the juice was not only modified to meet the nature of the food, but, if necessar}^ new enzymes were manufactured to digest fresh articles of food in the diet. For example, on a mixed diet, the pancreatic juice contains no lactose-splitting enzyme (lactase). It was said that, with the introduction of a milk diet, a lactase became secreted in the pancreatic juice. The experimental evidence is now against this view, and by some workers the adaptation to the diet of the enzymic content of the juice is seriously called in question. The juice is said by some to contain several other enzymes, in particular a nuclease (nucleic-acid-splitting enzyme). Traces of erepsin, maltase, and lactase have been found. Fig. 197. — To show Effect of Injection of Secretin. (Bayliss and Starling.) A, Blood-pressure; B, drops of panereatic juice; C, drops of l)ile. The Mechanism of Secretion. — Reference has been made to the '■ hormone," or chemical mechanism of secretion. " Secretin " is stored as pro -secretin, especially in the duodenal mucous mem- brane, and in less amount in the jejunum. In the ileum there is none. To prepare it the mucous membrane is scraped from a piece of small intestine, thoroughly minced, and ground up with sand in a moT-tar. Tiie whole is then treated with 0-3 per cent, hydrochloric acid, and boiled. This coagulates the proteins and extracts the secretin, which is not destroyed by boiling. The clear fluid is filte.'ed off, carefully neutralized, and used for intravenous injection to pro- voke pancreatic secretion (Figs. 197, 198). Secretin is soluble in alcohol and ether. Not only acid, but water and oil call forth, by their i)resence in the intestine, a flow of pancreatic juice. So do such bodies as pepper, mustard, and alcohol. Soaps have a particularly potent 398 A TEXTBOOK OF PHYSIOLOGY effect, find it is quite possible that the profhicts of (ligestion may in some wa\ modify the enz\)nic content, soti])s calling forth steapsin, dextrins amylopsin, peptones trypsin, and so on. It is a question whether the secretion of the pancreatic juice may be reflexly excited by a nervous mechanism. Stimulation of the vagus causes a flow of juice after a long latent ]ieriod, ])robably by increasing the movements of the stomach and the flow of acid chyme into the duodenum. However, a secretion has been obtained when the outflow of chyme from the stomach Avas prevented, and the chemical mechanism thus excluded. In favour of the nervous mechanism is the fact that, in the dog, pancreatic juice begins to flow one to one and a half minutes after the ingestion of food, and before the entrance of the gastric contents into the duodenun^ Fig. 198. — To .shractically all the foodstuffs have been absorbed that are going to be absorbed. Little or no absorption of foodstuffs takes place in the large intestine. A certain amount of fermentation of carbohydrate, as the result of bacterial activity, may occur under normal conditions in the small intestine, but as a rule there is no putrefaction of proteins. CHAPTER XLVIII THE LARGE INTESTINE The Function of the Large Intestine. — Recently there has been Kome discussion as to whether the large intestine performs a useful function. By some surgeons it is regarded merely as a sewer-pipe, in which, as the result of bacterial action, the fer- mentation of carbohydrate and the putrefaction of protein proceed apace, so that he is to be considered a happy man who has rid himself of such an encumbrance (!). Such an opinion flies in the face of Nature and the laAvs of evolution. The trouble would appear to be that people, while clamouring loudty for modern sanitation, do not trouble to keep this " sewer-pipe " in a wholesome condition. In the large intestine, the greater part of the ingested water is absorbed into tiie body. This is curious, considering the disgust such feculent water \\ould give iis. It is very doubtful whether any products of digestion are absorbed in the large intestine. It was formerly believed that protein digestion was continued in the large intestine, and that an appreciable absorption of the products was absorbed into the system. Recent researches cast doubt upon this point. It may be that a small absorption of the products of protein digestion takes place. In rectal feeding", the nutriment so given is passed back by reversed peristaltic movements into the small intestine, and there digested and absorbed. Within a few minutes of giving an egg enema, the yellow fluid has been seen pouring from a duodenal fistula. . The absorption of water is of considerable importance to the body It is also of great convenience, since it conduces to the proper forma- tion of fseces and greatly reduces their bulk. As the result of extirpa- tion of the whole large intestine in a dog, it was found that the faeces passed each dsij were greatly increased in weight, and contained five times the normal amount of water. The absorption of protein was slightly diminished, but not that of carbohydrates and fats. In some waj' not at present adequately understood, the calcium and phosphatic metabolism is influenced by the large intestine. On a herbivorous diet, the amount of calcium excreted by the large intestine and passed in the faeces is considerably greater than on an omnivorous diet. On this latter diet, the proportion of calcium passed in the faeces compared to the urine is 75 : 25 ; on a herbivorous diet, the proportion may be 95 to 5. The large intestine is the playground of bacteria. The contents afford an ideal culture medium. Its glands secrete an alkaline 402 THE LARGE INTESTINE 403 mucus, and little or no oxygen is present. The conditions thus favour the growth of anaerobic organisms, and their action consists of oxidations and reductions, rather than of hydrolytic changes, such as are occasioned b}- enzymes. Proteins and carbohydrates are chiefly acted upon, fats but little. The action upon carbohydrates is often referred to as fermentation, that upon proteins as putre- faction. The same bacteria do not act upon both kinds of food- stuffs; indeed, they are antagonistic to each other to a certain extent. The protein-decomposing bacteria are of manj^ kinds, the chief of \^hich is Bacillus putrificus. They are anaerobes, working in the absence of oxygen. The bacteria which act upon carbohydrates, on the other hand, are aerobes, the chief being B. coli and B. lactis aerogenes. Protein decomposition leads to the formation of such bodies as sulphuretted hydrogen, methyl-mercaptan, marsh gas, ammonia, carbon dioxide, lower fatty acids, phenyi-acetic and phenyl -propionic acids, phenol, cresol. indol, skatol. The first-named bodies are generally passed ^je/- rectum ; the last four bodies are absorbed into the system, and are harmful. If only absorbed in small amounts, they are arrested in the liver, combined with sulphuric acid, and converted into the ethereal sulphates which are excreted in the urine. If absorbed in larger amounts, they escape this action of the liver, and there then follows a general feeling of unfitness and dei^ression, headache, and various other nervous symptoms, due to alimentary toxaemia. Normally, there is no formation in the large gut of putrescin and cadaverin, bodies which result from protein decomposition outside the body. These are only found in special conditions, such as dysentery and cystinuria. The difference between enzymic and bacterial action upon protein can be appreciated by placing in an incu- bator at 37^ C. two fiasks containing minced meat in alkaline fluid. The meat in one flask is acted upon by trypsin, bacterial action being stopped by some toluol; the meat in the other is acted upon by any bacteria which happen to be present. After two or three days, the flask containing the enzymic digest has a peculiarly faint, but not repulsive, smell: the flask containing the products of bacterial action stinks. Carbohydrate fermentation leads to the formation of carbon dioxide, hydrogen, butyric, lactic, and acetic acids. The two processes proceed simultaneously in different parts of the intestine. Generally speaking, carbohydrate fermentation leads to the formation of a greater bulk of gas of a less impleasant nature than the smaller amount of gas derived from j^rotein decomposition. Under normal healthy conditions, protein decomposition does not proceed to the same extent as outside the body. There is consider- able discussion as to the reason of this. It has already been mentioned .that there is an antagonism between the different kinds of bacteria, and the presence of carbohydrate ma 3" be partly responsible for this limited action. Milk in the diet, and especially milk-sugar — lactose — are said to be particularly efficient in limiting the putrefaction of 404 A TEXTB(J()K OF rHVSJOJ.OC^Y ])rotein, and this is believetl to be due to the fact that they give play to the growth of antagonistic lactic acid bacilli. Quite recently it became fashionable to take lactic acid bacilli by the mouth. This cannot be said to have been very effective as a cure, partly, perhaps, because man\' of the preparations sold were sterile. At the best it substituted the lesser evil — fermentation of carbohydrate for the putrefaction of j)rotein. The bacteria are killed off by the action of the healthy intestinal wall; while the contents swarm with bacteria, the mucous membrane and blood circulating within it are sterile. Foreign Imcteria, such as vibrios, appear to be killed if introduced into the large intestine. As the result of bacterial action, the pigment of the faeces — sterco- bilin — and one of the pigments of the urine — urobilin — together with its precursor urobilinogen, are formed from the bile pigments. Bile salts are also decomposed into cholalic acid, and either taurin or glycin. ' Cholesterin becomes converted into an allied body — copro- .sterin. The fact that extensive bacterial action takes place in the intestine does not mean that it is necessarily harmful ; indeed, when kept within limits, it is, if anything, helpful to the body. A certain amount of gas promotes the movements of the large bowel, and assists the removal of the waste material. Experiments have been made to test the value of the intestinal flora to the animal. Guinea-pigs delivered by Caesarian section, breathing sterile air, and fed on sterile food, pro- gressed as well as the controls kept non-sterile. Sterile chicks, on the other hand, did badl}' on sterile food. Some died in eighteen daj's, while, in about the same tnne as a starving control, others recovered when the bacteria of chicken faeces were added to their food. The guts of Arctic animals, such as the polar bear, are said to be almost sterile. Herbivorous animals obtain a great deal of the nitrogenous foodstuffs from non-protein compounds, especially asparagin. It is suggested that the intestinal bacteria of herbivora build up proteins which are utilized out of these amides. Asi:taragin camiot be utilized l)y carnivora. By the bacteria in the capacious caecum of herbi\'ora celhdose is split into glucose, lactic, butyric acids, etc. These are absorbed and utilized, and thus cellulose, which forms so large a bulk of the food, becomes a chief source of energy. Hydrogen and methane are also produced by the bacterial fermen- tation of cellulose, and constitute a small part of the flatus passed from the bowel. A certain amount of oxygen is set free and utilized. In balancing up the metabolism of cattle, these gaseous excretions, which leave the body both by wa^' of bowel and lung, have to be taken into account. Protein putrefaction is ahvays going on in the large bowel, even when no food is being taken. The jDroteins of the secreted juices are then decomposed. It is only when bacterial action is allowed to get. beyond proper limits that it becomes harmful. Excess of food and a sluggish large intestine favoiu- the condition. It is obvious that no more food, especially proteins, should be taken in than can be digested THE LARGE IXTESTIXE 405 and absorbed by the small intestine. Xo large excess of digestible foodstuffs should be passed, with the juices capable of digesting them, into the large intestine, for the products of digestion cannot be, or are not readily, absorbed there. ^lore important still, the movements of the large intestine must be aided hy the massage obtained by exercise of the abdominal muscles, by hard ])liysical work, and deep breathing. The great prevalence of trouble in the large intestine is due to loading it with excess food, and to the development of a sluggish colon by lack of exercise. Plain living and exercise, not the quack's pill or the surgeon's knife, are the cure for the troubles which arise in this region of the gut. The fortunes of pill- vendors are an index of the gluttony and sloth of man. Faeces. — The faeces consist of — ■ 1. Indigestible material, such as keratin and cellulose. 2. Material digested with difficulty — elastm, cartilage. 3. Superfluous and non-absorbed products of digestion — fatty acids, insoluble soaps, amino-acids. purin bodies from nucleo-protein, haematin from haenioglobin, toxic bodies with an aromatic nucleus. 4. Products of bacterial activity — indol, skatol. These are ab- sorbed and excreted in the urine as non-toxic compounds of sulphuric and glycuronic acids. 5. Components of digestive juices secreted by the alimentary tract — tryjDsin, diastase, cholalic acid, bile salts, lecithm, stercobilin from bile pigments, coprosterin from cholesterin. 6. Excretion of the intestinal wall — calcium and iron salts, epithelial cells, leucocytes. 7. Bacteria, forming a large part of the faeces, even half the weight. The faeces are as a rule alkaline or neutral in reaction. The bulk varies with the kind of food and kind of animal. In man, on a mixed diet, the daily amount evacuated is about 120 to 150 grains, containing 30 to 37 grains of solids; on a vegetable diet, 333 grains, and 75 grains of solids. The offensive smell is mostly due to skatol. The colour varies according to the food. Meat gives a dark, almost black, stool; large amounts of fat make the faeces clay-coloured: much bread im- parts a light colour. The breast-fed infant passes motions of the colour and consistency of mustard, acid in reaction, and inoffeiLsive in smell. Meconium, the dark-greenish faeces passed by the newly-born child, are similarly acid in reaction, and inoffensive. It consists of cells, and remains of bile and digestive fluids. There is no sign of am^ bacterial action. The chemical analysis of the faeces is not often undertaken in clinical laboratories. It affords valuable information in certain conditions . CHAPTER WAX THE MECHANICAL FACTORS OF DIGESTION The mechanical factor plays an important part in the processes oi digestion, and is intimately related with the chemical factors. The mechanical factor insures the proper subdivision and mixing of the food with the digestive secretions, exposes the products of digestion to the absorptive surfaces, propels them from one region of the gut to another, and finally discharges the waste material from the body. It is obvious that these processes must be conducted in an orderly fashion, otherwise the food might either be inadequately digested or Fig. 199. -Outlines of an Almost Instantaneous Radiograph of the Stomach OF a Cat during Digestion. (Cannon.) 0,'Cardia; P, pylorus; at 1, 2, 3, 4, 5, are indentations due to peristaltic waves passing towards the pylorus. inadequately absorbed. The kind and rate of movement in the different parts of the alimentary tract varies, therefore, according to the special digestive actions which are being effected in those parts. The muscles at the beginning and at the end of the alimentary tract are under voluntary control; the rest of the musculature of the tract, however, is of the smooth variety, automatic in action. The automaticity is dependent, for the most part, iipon the primitive nerve plexus (Auerbach's) in the w^all of the gut; it is influenced by 406 THE MECHANICAL FACTORS OF DIGESTION 407 impulses from the central nervous system. Some of the movements may be purely muscular in origin. To study the movements, animals or men are given food mixed Avith bismuth subnitrate, or, better, with bismuth oxychloride. The position and movements of the food is observed, by means of the ,X rays and the fluorescent screen, or b}^ almost instantaneous radiographs (Fig. 199) at various intervals after the taking in of the food. Tracings may be taken upon tissue paper laid upon a piece of lead glass* placed over the screen (Fig. 200). The great advantage of this method is that the normal passage of food through the alimen- tary tract can be observed over a long period of time, and the charac- teristic movements of each part, their normal rate and frequency, be Fis. 200. — Tkacixgs of the Shabow cast by the Stomach (Cat), showing Changes IN the Shape of the Organ at Intervals of an Hour during the Digestion OF A Meal. (Cannon.) accurately studied. The disadvantage of viewing the guts directly after operative procedures is that the normal movements are greatly interfered with thereby, or even abolished. Nevertheless, they can to a certain extent be studied by immersing the anaesthetized animal in a bath of warm Ringer's solution, before opening the abdominal wall. Movements of Mastication. — By an up-and-down movement of the lower jaw. the food is seized by the front teeth; by a side-to-side movement, it is chewed by the back teeth. The tongue and cheeks assist in this latter process by forcing the food between the grinding * The lead glass is used to protect the observer from the ill effects of prolonged exposure to X rays. 408 A TEXTBOOK OF PHYSIOLOGY surfaces until it is thoroughly chewed. In man. the duration of the process of chewing varies with the nature of the food and the tempera- ment of the individual. Some ]^)eople, generalh' 3'oung, chew their food much less than others. Great value is attached to thorough mastication by some, but many continue to bolt their food, as does a dog, often apj^arently without harm. The degree of chewing varies with the nature of the food, a hard, dry food requiring considerably more chewing than a soft, pappj^ food. Generally speaking, the food is chewed for twenty to thirty seconds, and in this time about 1 to 1^ grammes of saliva may be added to a mass which generally varies from 3 to 6 grammes. The pressure exerted during chewing may be as great as 270 pounds as measured by a sjiring d^iiamometer. Such great pressures are. how- ever, not usually employed, since a side-to-side grind is more effective than the direct thrust. Thus, the crushing-point of cooked meat to Naso- pharynx - Soft palate _ Oesophagus A B Fig. 201.— To show the Mechaxism of the First Stage of Swallowing. A, at rest; B. swallowing. a direct thrust varies from 15 to 80 pounds, with a grinding move- ment but I to 2 pounds pressure is required for cooked tongue, and but 40 jDounds pressm-e for tough beef. The softening effect of saliva upon the pressure required in chewing is also very marked. Soft crumb bread, for example, requires more than 60 pounds direct pressure, but when softened with a little saliva it can be masticated with a pressure of 3 pounds. The chewing of agreeable foodstuffs is of value in reflexly promoting a flo^^• of gastric juice, and perhaps causing a tonic contraction of the circular muscles of the stomach, thus regulating the stomach movements.- The Mechanism of Swallowing. — After a proper degree of ma.stica- tion, the food is gathered as a bolus at the back of the tongue. Then follows the complex secj[uence of events which constitute the act of swallowing. Forward movement of the bolus is prevented by the l^ressure of the tip and sides of the tongue against the hard palate and the teeth. It is impossible to swallow with the tongue relaxed. THE MECHANICAL FACTORS OF DIGESTIOX 400 Then, breathing being inhibited, there follows a short, sharp con- traction of the mylohyoid and hyoglossus mnscles. The action of the mylohyoid is to press the tongue upAvards against the hard palate, that of the hyoglossus to pull it backwards. The result of the com- bined action is a piston-like thrust, which propels the bolus into the phar\Tix. Its entrance into the naso -pharynx is prevented by the contraction at the same time of the palato-pharyngeus and levator palati muscles. The levator palati pulls the soft palate down against the posterior pillars of the fauces, which are approximated by the contraction of the palato-pharnygeus muscles. The bolus first strikes the soft palate, then the back Avail of the pharynx; it next passes between the pharyngeal wall and the epiglottis, the oesophagus ni the meantime being kej)t closed by the pressure of the larynx; the hj^oid bone and the larynx are now raised, the glottis approximated to the epiglottis, the respiratory tract thus shut off, and the gullet opened ; so that the bolus, propelled by the mylohyoid, glides into the open oesophagus (Fig. 201). This is the end of the first stage of deglutition — the stage voluntarily initiated. Then follows the second stage — the involuntary stage — namely, the passage of food down the oesophagus proper to the cardiac orifice of the stomach. In time past, conflicting opinions were held as to the relative importance of the initial impulse imparted in the first voluntary stage and of the peristaltic action of the oesophagus itself. From recent experiment by means of X rays, it would appear that this depends largely upon the nature of the food, solids and pappy foods being passed down by the peristaltic action of the oesophagus itself — liquids, on the other hand, passing quickly down by the impetus given by the j^iston action of the mylohyoid. The rate of the transmission in the different parts of the oesophagus is variable. It depends upon the nature of the muscle. Thus, in the goose, where the muscle is smooth, a uniform slow peristalsis takes place. It takes twelve seconds for a solid bolus to traverse 15 centimetres of gullet. In the cat, the peristalsis is rapid as far as the heart level (4 seconds), and slow (6 or 7 seconds) for the remainder — less than a third of the whole distance. It is at the heart level that the muscle changes from striated to smooth. In the dog, the peristalsis is quick through- out, the time taken for a solid bolus being 4 or 5 seconds from larynx to cardia. In the dog, the whole oesophagus is composed of striated muscle. In both the cat and dog, liquids travel much more quickly than the solid or semi-solid bolus. In man, the lower end of the oesophagus is composed of smooth, muscle, and a slower rate of peristalsis is observed in this region. X-ray observations upon man show that solids and semi-solids are moved down the oesophagus by peristaltic action, irrespective of the position of the body, and OAve practicalh* nothing to the prelimmary impetus, the time required for a AAcll-lubricated bolus being from 8 to 18 seconds, for a dry bolus seA^eral minutes. Liquids, on the other hand — e.g., milk containing bismuth — are shot rapidly through, the greater part of the oesoj)hagus. In the head-down position, they 410 A TEXTBOOK OF PHYSIOLOGY ascend the gullet in one-third of the time occvipied by solids in the normal position of the body. The Nervous Mechanism of Swallowing. — Swallowing is a reflex act, the nervous centre controlling it being situated in the floor of the fourth ventricle in the spinal bulb. The afferent impulses which provoke the reflex arise in the neighbourhood of the pharynx ; in the dog and cat, chiefly from the posterior wall of the pharynx, opposite the opening from the mouth — an area supplied by the glosso- phar3'ngeal nerve. Impulses also arise from the upper part of the soft palate, supplied by the ninth and the second part of the fifth nerves, and from the base of the epiglottis, supplied by the superior larjTigeal division of the tenth nerve. Fig. 202. — Diagrams of Positio:n of Shadow in (Esophagus at Intervals OF A Second after Swallowing. (Hurst.) In monkeys, the swallowing reflex is most easily evoked in the region of the tonsils ; in man, from the back wall of the pharynx and round about the base of the tongue. The abilitj' to swallow depends upon the presence of these special sensitive spots, as is shown by the fact that if a sponge moistened with cocaine be swallowed, and then pulled back by means of an attached thread, the power to sw^allow is lost for a time. "NMienever a bolus of food or saliva is made to stimulate one of these sensitive spots, sw^allowing involuntarity occurs. The chief efferent or effector paths are fibres running in the hypo- glossus to the hyoglossus, in the third branch of the fifth to the mylo- hyoid, in the glosso -pharyngeal and the pharyngeal branches of the vagus to the muscles of the palate and phar3^lx, and in the vagus to the oesophagus itseff. Stimulation of these fibres causes strong contraction of the oesophagus; section of both vagus nerves pro:luces THE MECHANICAL FACTORS OF DIGESTION 411 paralysis. The paralysis, however, passes off after a time in the non- striated part of the oesophagus, which is endowed with the property of performing peristaltic movements b}' virtue of its intrinsic nervous mechanism: a secondary- "" lower " reflex mechanism, dependent upon the nerve plexuses in the wall of the oesophagus. By this mechanism, the presence of the bolus in the oesophagus itself causes contractions, which push it onward towards the stomach. Nor- mally this mechanism probably plays little or no part, the peri- staltic movenients being controlled reflexly through the vagus nerve. After the oesophagus has been divided in an animal under moderate or light anaesthesia, a swallowing movement initiated in the upper seg- ment is followed by a movement in the lower segment. The peri- staltic wave of the latter must in this case be excited and co-ordmated reflexly through the central nervous system. In deep anaesthesia, how- ever, this reflex proi^agation of the peristaltic wave may be abolished, and a wave of peristalsis initiated in the upper segment of a divided ^^ V ¥»i Pig. 203. — Tracings of the Shadows of the Contexts of the Stoimach and Intestines (Cat's) made Two Hours after Feeding {A) with Boiled Leak Beef, (B) with Boiled Rice. (Cannon.) or Jigated oesophagus is not passed beyond the point of interruption. We conclude, then, that normally the contraction of the oesophagus is a part of the series of reflex nervous discharges initiated in the " swallowing centre " b}^ the stimulation of the afferent fibres. The Movements of the Stomach. — The movements of the stomach are adapted to the functions of its different parts. By the X-ray method it is seen that the fundus, or reservoir, is practicaUy devoid of movement. It exerts a tonic grasp on its contents, which tend to press them onwards whenever oj)portunity arises. Peristaltic waves arise from the middle of the stomach (1 to 6, Fig. 190), and pass in succession towards the pylorus. As food becomes discharged into the intestine, the circular muscle becomes tonically contracted so as to give a tubular form to the middle region, along which the peristaltic waves continue to pass. The contents of the fundus are thus gradually passed into the pylorus, and eventually the shadow of the fundus disappears (5, 6, 7, Fig. 200). The regular, wave-like contractions which pass over the pyloric end deepen as they go, and 412 A TEXTBOOK OF PHYSIOLOGY churn up the food when (he i\vIorie orifice is clo.scd, and pass it on to the duodenum when the orifice is open. These ehurtiing movements are the first movements noticed when an animal is examined under X rays after receiving a good 40 /, f 7.' , 1 2 3 4 ^ A Hours B Ficj. 204. — To SHOW Effect of Coksistency of Food upon the Rate of Leaving THE Stomach. (Cannon.) A, Light continuous line = potato of standard consistency; heavy continuous line = potato of thick doughy consistency; dash hue = thin gruelly consistency. B, heavy line = lean beet of standaz'd consistency; light line = lean beef of thin gruelly consistency. meal. After a short time, an annular constriction appears at the vestibule, and passes slowly over the rest of the pylorus, being followed by regular waves arising in the same regic«i. Then a little later (two i I 1 f 1?- / / / ' 1 / „/ Fig. 205. The continuous line shows the rate of disappearance from the stomach of a carbohydrate meal (biscuits, rice, pota- toes) moistened with water; the dotted line of a similar meal moistened with 1 per cent. NaHCO;. There is marked retardation of the latter. (Cannon.) 33 • 20 • • 1 10 1 / / / / y / Hours ^1 2 Fig. 20(3. The continuous line shows the rate of disappearance of a meal of protein (fibrin, fowl, lean beef); the dotted line that of same meal fed as acid protein. (Cannon.) to three minutes) the contractions which arise from the middle of the body make their appearance, the amount of contraction becoming much more marked when the vestibule is passed. These peristaltic THE MECHANICAL FACTORS OF DIGESTION 413 |i|=z waves do not pass into the duodenum, the muscular continuity between the parts being interrupted by a ring of fibrous tissue. The time of recurrence of the waves varies in different animals, and also with the nature of the food. In cats, there are generally four to six per minute; in dogs, about four; in man, three. Fat diminishes the number per minute, carbohydrate increases them. 40 ,30 1 20 10 0 U 1 2 3 4 Hours Fig. 207. — To show RetardiNc^ Effects of Fats upon Food leaving Stomach. (Cannon.) Light line = curve of mashed potato; heavy line = curve of mutton fat; dash line = curve of potato and mutton fat mixed. The opening of the pyloric orifice is co-ordinated with the acidity and the consistency and nature (Fig. 204) of the gastric contents. Generally speaking, carbohydrates leave first, proteins next, and fats last (Fig. 205). Carbohydrates as a rule leave the stomach quickly, but if fed with alkali their exit is retarded (Fig. 205). Feeding proteins with acid, on the other hand, hastens their normally slow exit (Fig. 200). Fats retard the exit of other foods (Fig. 207). When the acid contents of the stomach reach the duodenum, the pyloric irrw'W'ii'*riWhP'''WPl^^ -J I I L- Ficj. 208. — Record showing Cessation of Rhythmic Regurgitations of Fluid FROM Stomach into (Esophagus after acidifying Gastric Contents at A . (Cannon.) Upstroke = outHo\v, small oscillations due to respiration. Time in half-minutes. aperture closes. Thus, acid on the p3doric side oj^ens, on the duodenal side shuts the pyloric orifice, the regulation probably depending on a local reflex mechanism. The cardiac orifice is normall}^ kept shut. In the resting condition of the stomach the sphincter resists a tension of about 25 cm. of H2O. We are, therefore, not conscious of the rancid contents of the stomach. 414 A TEXTBOOK OF PHYSIOLOGY During digestion, the acidity of the contents causes the closure of the sphincter to become firmer. When the stomach is very full, and there is no acidity of the reservoir contents, rhythmic relaxation and contrac- tion of the cardiac orifice may occur, with the result that the stomach contents are regurgitated into the oesiophagus. This has been ex- perimentally' demonstrated on cats both l)y the X-ray method and Fig. 209. — Diagkam repeesenting the Pkocess of Rhythmic .Segmektation. (Cannon.) Lines 1, 2, 3, 4, indicate the sequence of appearance in a single loop. The dotted lines represent the regions of division. The arrows show the relation of the particles to the segments they subsequently form. by direct registration b}' means of a tambour placed in the oesophagus. The addition of acid immediately caused a cessation of such move- ments (Fig. 20K). That such a regurgitation occurs in man has been proved by the fact that lycopodium s]:ores swallowed overnight in a gelatin capsule Fig. 210. — Photograph of the Small Intestine segmentikg its Contents. (Cannon.) have been fomid in the mouths of persons next morning, although there was no trace of them in the mouth one to two hours after swal- lowing. It is suggested that the disagreeable taste in the mouth and the coated tongue of the dyspeptic may be due in part to particles of food regurgitated from the stomach, especially when there is a de- ficiency of hydrochloric acid in that organ. THE MECHANICAL FACTORS OF DIGESTION 415 The movements of the stomach and its si^hincters may be modified by the action of the vagus nerve. Stimulation of the peripheral end of the vagus nerve causes contraction of the cardiac sphincter, but after the intravenous administration of atropine the action of the same nerve on this sphincter becomes inhibitory. On vagal stimula- tion, the tone of the stomach increases, and the peristaltic waves augment. In some cases there may be a preliminary transitory inhibitory effect. The effect on the pyloric sphincter is imcertairi. It is probably dependent upon the condition, at the moment of stimu- lation, of the local nervous mechanism which controls that orifice. Sometimes it opens, and sometimes it closes. The sympathetic nerve is generally believed to be inhibitory to the stomach, but this action is ojDen to question. Fig. 211.— Segmentation of the Small Intestine in Man. (Hui>t ) Vomiting is controlled by a nervous reflex, and can be induced either centrally or peripherally. Tickling the throat between the pharynx and top of the oesophagus will often induce it. The effector fibres run in the vagus nerve. The cardiac orifice is relaxed, the body of the stomach rendered flaccid and dilated, and the tone of the pvlorus increased. A strong contraction occurs at the incisura annularis dividing the stomach into two separate portions. The stomach contents are then voided by a simultaneous contraction of the dia- phragm and the muscles of the belly wall. As vomiting proceeds, the stomach wall contracts down on the remaining contents; otherwise the stomach is essential^ passive during the act of vomiting. The Movements of the Small Intestine. — On observin. — Diagram to show the Hours which elapse after a Bismuth Meal BEFORE the DIFFERENT PaRTS OF THE COLON ARE REACHED, (Hurst.) minute), and the period of antiperistalsis lasts on an average about four to five minutes, and recurs after varying lengths of time, generally from ten to fifteen minutes. Antiperistalsis is the predominating movement of the first part of the colon. As a result, the contents are retained there for a considerable time, generally about two hours, and the absorption of water is greatly facilitated. It is probable that the arrival of new material ui the large intestine pushes on the contents beyond the antiperistaltic area, but it is possible that from time to time a wave of true peristalsis helps to push on the contents into the transverse colon. Thus far, true waves of antiperistalsis have not been observed in man, but there is reason to think that such take place in him no less than m animals. It is known that nutrient enemata are quickly passed back into the ascending colon, and, when large, may j)ass thence into the small intestine. THE MECHANICAL FACTORS OF DIGESTION 419 As the contents pass along the large intestine, they become sepa- rated into semi-solid globular masses. In the transverse and descending colon, antiperistalsis is very slight, and the predominating movement is a slow true peristalsis. The pelvic colon down to the acute flexure {P.R.F., Fig. 216) just above the rectum is the storehouse of fseces. Occasional long- continued waves of contraction force the contents well down into the pelvic colon, and eventually, by rendering the angle of flexure less acute, force some of the contents into the rectum. This leads to a desire to defjecate. These long-drawn movements are subject to the control of a centre in the lumbar spinal cord. They are probably evoked by distension of the gut stimulating the afferent nerve- endings in the pelvic nerve. The times taken for the passage of food through the large intestine in man are marked in hom-s in Fig. 215. Fig. 216. — Diagram of Rectum (Ilur.^t), showing Pelvi-Rectal Flexure (P.R.F.); F.ECES IN GoLO-s {F.); Houston's Valve (V.H.); Rectal Ampulla {R.A.); Levator Ani {L.A.); Internal Sphincter {I.S.A.); External Sphincter (E.S.A.). Defsecation. — To stimulate the desire to defaecate, the distension of the empty rectum by a small amount of fseces is sufficient (Fig. 216). Such an amount is normall}' passed into the rectum from the pelvic colon as the result of peristaltic action refiexly induced by the taking of food on an empty stomach. Hence the desire to defsecate after breakfast. The result maj^ also be brought about by physical exercises and a cold bath, or even by the muscular exercise involved in dressing. That it is the distension of the rectum, and not the actual contact of the faeces with the rectal mucous membrane, which leads to the desire to defsecate has been shown by inflating the rectum wuth a balloon. If the desire be not obeyed, the w^all of the rectum relaxes, the intrarectal pressure falls, and the desire passes away, only to recur when the intrarectal pressure is again raised by the advent of fseces. Defaecation may sometimes be started by voluntary effort. 420 A TEXTBOOK OF PHYSIOLOGY The glottis is closed after an inspiration, and the action of the dia- phragm and the abdominal muscles forces fseces past the pelvi-rectal flexure. When the desire to defsecate is obeyed, the rectum is further dis- tended by fseces bj^ raising the intra-abdominal pressure in the above- mentioned fashion. The contraction of the diaphragm after inspira- tion is the most effective agent in raising the abdominal pressure. This is aided by the crouching posture assumed. The contraction of the abdominal muscles, the flexion of the spine, the pressure of the thighs against the belly wall, and the contraction of the muscles of the pelvic floor, serve to sustain the increased abdominal pressiu'e. When the rectum is sufficiently distended, there ensue strong jjeristaltic contractions of the whole colon, which, in conjunction with continued contraction of the abdommal muscles and the relaxa- tion of the anal sphincters, force the fseces out, the final expulsion being aided by the contraction of the levator ani muscles, which draw the anal canal upwards, and also constrict the lowest part of the rectum. Although normally a voluntary process, defsecation may take place in involuntary^ fashion when the rectum becomes sufficiently distended with fseces. The fseces may become hard and dry when the voluntary aids to defsecation are lacking, and it may be difficult to expel the hardened masses. Defsecation is stated to be under the control of a centre in the lumbo-sacral region. The effector nerves run to the rectum in the sympathetic system by way of the inferior mesenteric ganglion and the hypogastric nerves, and in the pelvic nerves (nervi erigentes) from the third sacral nerve to the inferior hsemorrhoidal plexus. Stimula- tion of both sets of nerves leads to contraction of the rectum. It is probable, however, that the jDclvic nerves are the more effective, and that the hsemorrhoidal plexus may be regarded as a subordinate centre for defsecation, since a somewhat incomplete reflex act of defsecation can occur in the dog even when the lumbo-sacral cord is destroyed. The levator ani and the external sphincter muscles are supplied by the fourth sacral nerve. The action of these muscles, controlled from the spinal centre, is essential for the complete reflex. The lumbosacral centre is under control of excitatory or inhibitory impulses from the cerebrum, and when this control is withdrawn, as after division of the spinal cord, incontinence of fseces results. BOOK \ 11 CHAPTER L SPECIAL METABOLISMS Absorption. — The absorption of the foodstuffs takes place cliiefly ill the small intestine, and particularly in the middle and lower portions. Considerable discussion has taken place as to the mechanism of this absorption, and at first, when physiological science was young, such comparatively simple processes as filtration, diffusion, and osmosis, were evoked to explam it. It is now generally conceded that it is controlled by unknown forces of the hving cells lining this part of the alimentary canal. The chief evidence iipon which this conclu- sion is based may be summarized as follows : 1. If the mucous membrane be removed from a piece of intestine, the absorptive power is abolished. 2. Poisoning the cells by washing the mucous membrane with a dilute solution of sodium fluoride, or scalding them, destroys the absorptive process. 3. The absorption of water from the intestine takes place much more quickly than does diffusion through a dead membrane. 4. The rate of absorption of the products of digestion is too rapid to be explained by simpler physical processes. Peptone is absorbed from the intestine more readily than dextrose; on the other hand, dextrose diffuses through parchment quicker than peptone. Sodium sulphate is not readily absorbed from the intestine, yet it readily diffuses through parchment. 5. The absorption of water, saline and other salts (magnesium sulphate) is attended b}- a greatlj^ increased consumption of ox3'gen b\' the intestinal cells, showing that absorption, even of water, is an active process (see p. 321). 6. The animal's own serum, identical in composition and isotonic with the blood, is complet-elj' absorbed if introduced within a loop of intestine. 7. Certain products of digestion, such as those of fat, and probably of protein, are altered during their passage through the cells of the mucous membrane. The Metabolism of Protein. — In the intestine the protein is broken down into proteoses, peptones, polypeptides, and amino-acids. There 421 422 A Tf]XTB()()K OF PHYSIOLOGY is considerable difference of ojjinion as to how far it is necessary for piotein to be broken down before it can be absorbed. It depends to a certain extent upon the nature of the protein. Thus, casein, edestin, acid metaprotein, intro(htced directly into the small intestine, are not absorbed at all; egg-albumin, serum-albumin, are absorbed slightly (about 20 per cent.); and alkali metaprotein considerably (70 per cent.). Undoubtedly, these proteins are considerably modified, but to what degree is uncertain, before reaching the blood. Proteoses and pei^tones appear to be readil}^ absorbed from the small intestine, but it is doubtful whether they reach the blood as such. When they do, it is only in such minute cpiantities, difficult of detection, and out of all proportion with the amount actually absorbed. It is probable that the absorbed proteoses and peptones are converted into amino- acids by the cells of the wall of the intestine. It is known that the cells of the mucous membrane are very rich in erepsin. It has been shown that proteoses and peptones disappear from the lumen of an isolated loop of intestine which is perfused with defibrinated blood, and that no peptones can be detected in the blood. The amino-acids formed as the result of digestive processes within the lumen are also absorbed. In this process it is suggested the leucocj^tes present in the mucous membrane in some Avay play an important part. The question now arises, What becomes of these amino-acids, which either pass into or are formed within the intestinal wall ? It is a very complex one, and at present by no means fully eluci- dated. Before attempting to consider the t^^o main hypotheses, it is well to grasp the general idea luiderlying the processes of protein meta- bolism. The proteins of the food are necessary to the life of the animal. Without a certain amount of protein in the diet, the animal slowly but surely dies. This jDrotein is necessary for the repair and growth of tissue proteins. Two points are to be observed in this connection: first, that the animal's own proteins, which recpiire building afresh, differ in constitution — the protein of the muscles, for instance, differs from the protein of the kidney substance; secondly, the ingested proteins, from which these different proteins are to be replaced, differ even more widely in constitution. This is especially the case when the ingested protein is of vegetable origin. It is easily understood that only a portion of such ingested proteins may be of service to the animal in rebuilding its particular proteins. Such portion may be considerable or inconsiderable, according to the nature of the protein taken in. The process of protein digestion may be compared to house-breaking, the process of protein anabolism to the reconstruction of a number of new houses from the bricks of the demolished houses. Certain of the building-stones are of great value in rebuilding the new houses, others are of partial vahie, others are of little or no value at all. In protein anabolism, the amino-acids are such building-stones. Some are of great value — precious — others appear to be of lesser value. It has been shown by experiment that an animal can live when SPECIAL METABOLISMS 423 fed on the amino-acid products of a meat digest. If, however, it bo fed on selected amino-acids, it is found that on some it can stiU Hve, on others it gradually starves. For example, the monamino -acids by themselves do not support life, neither do the diamino-acids. On the other hand, the addition of ringed amino-acids, such as phenyl- alanin, tyrosin, and tryptophan, has been found to support life. So, too, proteins which do not contain these last amino-acids, such as gelatin and zein, fail to keep an animal alive. The addition of ringed amino-acids to such proteins renders them more life-supporting. From this point of vicAV, it is interesting to note that Nature provides the young growing animal with a protein — caseinogen — esjiecially rich in both tjTosin and tryptophan. The two hypotheses held in regard to the metabolism of protein differ (1) as to the place of selection of the building-stones — the amino-acids; (2) as to the form in which the material for reconstruc- tion is presented to the tissues. According to one view, the amino-acids pass as such into the portal blood. It is claimed that their j^resence there can be demonstrated by special indicators, such as /^-naphtha-sulphonic acid. The gut of the octopus is natural!}^ suspended in a bath of blood, and amino- acids are said to appear in this blood when protein is digested in the gut. The absorbed amino-acids are then taken in the portal blood to the liver, which controls their passage into the general circulation according to the needs of the body. Each amino-acid has its own special metabolism. It has been shown that, if such bodies as glycin, alanin, arginin, be perfused through the isolated liver, the urea content of the blood leaving the liver is increased. These amino-acids are only of partial value to the body. The nitrogenous moiety contained in them may perhaps be regarded as valueless, for it is rapidly excreted. These amino-acids are first deaminized, the ammonia split off being converted into urea, while the non-nitrogenous moiety remains. There is reason to suppose that this is first converted into a lower fatty acid, which then becomes converted into dextrose, a conversion of great importance in carbohydrate metabolism. In the case of alanin, for example, the process may be represented as follows: CH3CH.NH.COOH + H.0 - CH3CHOH.COOH + NH, Alanin Lactic acid 2CH3CHOH.COOH ^CeHiaOe (CsHgOs) Dextrose The fate of the monamino-dicarboxjdic acids, such as aspartic and glutamic acids, is probably the same. The diamino-acids, such as arginin and lysin, together with the closely allied histidin, are probably also broken down into nitrogenous and non-nitrogenous moieties, the nitrogenous being mainly excreted from the body in the form of iirea, the non-nitrogenous part being possibly converted into dextrose. It is not yet knoAvn sufficiently well what exactly happens to 424 A TEXTBOOK OF PHV.SIOLOGY tyrosin and tryptophan. These are of great vahie to the body, and in the liver they are probably modified into a form available for the tissues. It is certain that they are not rapidly destroyed, and their nitrogenous moiety excreted from the l:ody in the form of urea. If a non-nitrogenous moiety be split off, it may give rise to dextrose. Cystin (diamino-di-thio-lactic acid) is broken down in the liver, the sulphur moiety giving rise in part to taurin and in part to inorganic sidphates. It is possible that the carbon-containing lactic acid portion may give rise to dextrose. The fate of the other bodies is not sufficiently elucidated to be mentioned here, but, according to this hypothesis, they also each undergo their own special metabolism in the liver. The fact that there occur certain inherited but very rare errors of metabolism, such as alkaptonuria and cystinuria, is held to lend support to the hypothesis, which may be represented diagrammatically as follows; Portal, Blood ' Aninioiiiuns carbonate- (and carbamate) Products of Protein Digest ion. Mouamiao nionocar- boxylic acids, glycin, alanin, leucin Liver > Urea / Urea Monamino dicar- boxylic, glutamic, aspartic \ Diamiiio- acids, arginin, lysin Dextrose Urea ; Dex- trose Phenyl alanin, tyrosin, tryptophan Prepared for tissues Cystin Taurin Inorganic and sulph- ? dextrose ates An objection to this hypothesis is that it is not quite clear from what source the body derives all the bricks necessary for the rebuilding of its proteins. In these proteins, amino-acids, such as alanin and gtycin, are incorporated, and it is by no means clear from what source such amino-acids come. According to the second hypothesis, the amino-acids do not pass from the intestine into the blood. It is said — (1) that their presence there has never been conclusively demonstrated; (2) that if the circu- lation be confined to the intestinal wall and pancreas, heart, lungs, and muscles of respiration, the blood contains no proteoses, peptones, or amino-acids. It is therefore held that the amino-acids, during their passage, are — (1) either synthesized into protein, so-called " plasma protein " ; or (2) deaminized. with the formation of ammonia. The '' plasma protein "" is held to be a protein f-o built that all the cells of the body can abstract from it just the bricks they desire to rebuild their own particular protein. In building up this plasma protein, all the amino-acids of digestion are not used. Many are in excess — such, for example, as glutamic and aspartic acids, when plant proteins have been ingested. These are deaminized in the intestinal wall, and the ammonia thus formed passes to the liver as ammonium carbonate or carbamate, there becoming converted SPECIAL METABOLISMS 425- into urea. It may be assumed in this case that the non-nitrogenous, moiety formed as the result of deaminization is taken to the liver, being there converted into dextrose and, finally, in part to glycogen (see next page). In support of this view, it has been sho«n that a dog may be fed on digested protein (amino -acids), and kept in nitrogen equilibrium, even when its portal blood is short-circuited from the liver by an Eck's fistula (see p. 448). The blood coming from the intestine during periods of digestion is stated to be demonstrably richer in protein of a globulin nature. This view may be regarded as a modification of older ones concern- ing protem metabolism. According to these, serum albumin and serum globulin were formed in the intestinal wall, and passed into the portal blood. The views differed as to the subsequent fate of these proteins. According to one view, all protein was subsequent^ built up into living protoplasm before it was destroyed: according to the other, some of the protein, called " tissue protein,'' was built up into protoplasm ; the remainder was not so built up, but served as a source of energ}^ — the so-called '' circulating protein."' The speed with which an increased intake of nitrogen appears in the urine as urea is against the. view that such nitrogen has been built up into protoplasm. On the other hand, when we consider the rapidity Avith which protoplasm grows — e.g., yeast multiplying — we cannot put such a possibility out of court. As to whether any of the protein formed in the intestinal mucous membrane acts solely as circulating protein, there is at present no evidence. Much more work is required upon this intricate and difficult subject. Up till now, there can be said to be no established theory of protein metabolism, onh' two tentative hypotheses, of which the second, given above, appears the more probable — namely, that a special plasma protein is s^^lthesized in the intestinal mucous mem- brane, containing all the necessarj^ bricks for the rebuilding of the tissue- proteins. Excess of digested protein is deaminized in the intestinal mucous membrane, and the ammonia thus formed is short-circuited from the body as urea. Protein, or the amino-acids split from it, increases the rate of metabolism and heat-production stimulating the cells of the body to activity, having a specific dynamic action greatev than carbohydrate^ and much greater than fat. This stimulating action is traced to oxy- or keto-acids, the non-nitrogenous moiety of protein metabolism. CHAPTER LI THE METABOLISM OF CARBOHYDRATE The digestive processes reduce the carbohydrates to the mono- saccharides— dextrose, levulose, and galactose — the chief of which is dextrose, since cane-sugar and lactose normally form but an in- significant part of the diet. Dextrose is absorbed unchanged into the portal blood by the activity of the intestinal cells. The portal blood therefore becomes charged with sugar above the content nor- mally present in blood. The excess of sugar acts as a stimulus to the liver, which abstracts the excess, so that the blood leaves that organ supplied with about 0-01 per cent, of sugar — the normal content. The diffusible sugar retamed by the liver is elaborated into the non-diffusible colloid glycogen, and stored as such. There has been much controversy as to the ultimate fate of the glycogen. The generally accepted view is that there is a reversible ferment action in the liver. The ferment converts sugar into glycogen when the portal blood comes laden with sugar, and glycogen into sugar when the blood comes to the liver impoverished in sugar. (1) Dextrose (2) Dextrose t 1 I Glycogen (ilycogen /\ Fat Carbohydrate portion of i^rotein Another view is that glycogen is never again converted to dextrose in life, but is elaborated into fat, or it may possibly be combined to the proteins as a carbohydrate moiety. The balance of evidence is in favour of the first view. The glycogen quickly disappears from the liver after death, and dextrose is formed. It is also probable that this j^rocess takes place in life, and not only post-mortem. There seems to be good evidence, too, that when blood, with a low dextrose content, is perfused through the liver, it acquires dextrose. It is true that glycogen may give rise to fat under certain conditions, but the available evidence indicates that such fat, when metabolized within the body, is again broken down to glycogen and dextrose (see p. 440). Leaving the liver, the dextrose passes in the blood to the heart, and thence to the system generally, to be katabolized. The Katabolism of Dextrose. — Three views are held as to the manner in Avhich dextrose is normally broken down within the body. Accord- 426 THE METABOLISM OF CARBOHYDRATE 427 ing to one view — the least accepted— sugar is broken down by the body in the same way as it is by the yeast cell — that is, through inter- mediary stages to alcohol, and then to carbon dioxide and water. There is some proof of this taking place in plants, but the evidence for such a katabolism in the animal tissues is scanty. According to a second view, dextrose breaks down to glycuronic acid, and then to carbon dioxide and water. Until recently, this view has received wide acceptance. Gl^^curonic acid is closely related to dextrose, and is found in the blood and in the urine. All the recent evidence, however, tends to show that dextrose is normally broken down to lactic acid, and then to carbon dioxide and water. Tiie muscles are the chief seat of dextrose katabolism. In the absence of oxygen, lactic acid is not broken down, and may be detected in the urine and in the sweat — e.g., after hard muscular exercise, or when an excised muscle is tetanized in the absence of oxygen. (1) Dextrose (2) Dextrose (3) Dextrose I I I Alcohol Glycuronic acid Lactic acid /\ /\ /\ CO. H.O COj H2O CO2 H.2O We must now inquire with a little more detail into — (1) the glyco- genic function of the liver ; (2) the conditions necessary for the breaking down of sugar in the body. The Glycogenic Function. — By this function, the supply of dextrose in the blood is regulated, and kept at a constant amount (0-01 per cent.) adequate to the needs of the body. When the supply of sugar in the blood is large, as at the height of digestion, the dextrose is abstracted and stored as glycogen; when the supply of sugar in the blood is poor, then glycogen is converted into dextrose, and passes into the blood. Normally, the liver restrains any surplus supply of dextrose from reaching the systemic blood, and causing what is termed a hypergljjccemia. When hypergtycaemia results, the kidneys immediately eliminate the excess sugar, and dextrose appears in the urine, forming the condition known as glycosuria. The efficiency with which the liver performs this function is judged by the sugar content of the blood and urine. As a general rule, the urine o\\\\ is tested, but in special conditions the sugar content of the blood is also tested, for a small excess of sugar may exist in the blood Avithout causing glycosuria. Moreover, all glycosurias are not due to inefficiency of the liver and hyperglyesemia. To estimate the amount of dextrose, the blood is laked and diluted, shaken with colloidal ferric hydroxide (dialyzed iron), and then a small amount of sodium sulphate added. By this means the blood- proteins are precipitated. The sugar in the filtrate may then be estimated Iw Bertrand's process (see p. 468). The Sources of Glycogen — Carbohydrate. — That glycogen is largely formed from dextrose may be experimental^ proved by starving a rabbit, and subsequently feeding it with carrots — a diet rich in 428 A TEXTBOOK OF PHYSIOLOGY carbohydrates. During starvation, the glycogen content of the Hver falls very low; during feeding with abundant carbohydrate, the liver content becomes very high — e.g., 18 per cent, of the weight may be glycogen. As already stated, at the height of digestion the blood leaving the liver is poorer in dextrose than the blood reaching it. Perfusion experiments also show that dextrose is abstracted by the liver from defibrinated blood containing an excess of this sugar. Levulose also gives rise to glycogen; galactose gives but little. Pentoses do not ajjjDcar to be direct glycogen-formers. Protein. — Opinions differ widely as to whether glycogen arises from proteins. As the result of direct feeding experiments, many observers claim that feeding with proteins increases the amount of glycogen in the liver, even when proteins are fed which yield no carbo- hydrate group, such as caseinogen and gelatin. Other observers contend that i^roteins are glycogen-sparers rather than glycogen- formers; that, under such feeding conditions, the glycogen content of the liver is increased, because dextrose is spared in the bod}^ when there is an abundance of protein fed. The fact that glycogen does not disappear entirely from the body even during long-continued starvation would appear to indicate that proteins may serve as a source of glycogen. The conversion of protein into glycogen probably takes place by the deaminization of amino-acids, the non-nitrogenous moiety of such acids becoming converted into dextrose, and thence to glycogen. Perfusion experiments have shown that glycin, alanin, asparagin, act as precursors of glycogen. It seems probable that more sugar and glycogen arise from protein than is generally recognized. Fat. — In regard to the products of the digestion of fat, there is no evidence to show that glycogen arises from the fatty acids. On the other hand, there is evidence to show that glycerine gives rise to dextrose, and may possibly give rise to a small amount of glycogen. CH,OH CH.,OH I " I " CHOH ^ (CHOH), I I CH^OH CHO Glycerine Dextrose It is possible, also, that under certain conditions fat stored in the liver becomes broken down to form glycogen. Such fat, however, has been previously built up in the organism from dextrose and glycogen (see p. 440). The glycogenic function of the liver is very easily disturbed, and its continual disorder results in the disease dialDctes. The Influences affecting the Glycogenic Function — (1) The Nervous Influence. — First and foremost come nervous influences. Puncture of the floor of the fourth ventricle in the middle line in the region between the originof the eighth and tenth nerves causes hyperglycaemia, the disappearance of glj-cogen from the liver, and the appearance for THE METABOLISM OF CARBOHYDRATE 42!) the time being of much dextrose in the urine. If the animal has been starved previous to the puncture, no such riesult folloAvs. There is therefore, supposed to be a "' centre "' in this region of the medulla through which the glycogenic function of the liver is controlled. The result has been attributed b}" some authorities to the disturbance of the circulatory conditions of the liver, owing to interference with the vaso-motor centre. Such circulatory disturbance possibly does plf\y cu £ 2 D CL, to 3 CO " 3-25 0-17 30 016 2-75 015 2-5 OH 2-25 013 20 012 1-75 0-it 1-5 010 1 25 009 10 008 0-75 007 05 006 fin's 0-25 0 o n J 1 400 380 360 340 320 300 ! 'f ^v y x^^ \ n i"N ill^ 1 Id > \ \ < *1 Vi 260 1 1 %\ \ 220 200 180 160 140 / > \\ // K- / / / s s / / / / // t I 1 30 60 90 120 150 180 2l0 240 27C 300 Minutes. Fxa. 217. — Curves showlng the Relationship betweex the Goncextratios of Sugar in Arterial Blood, the Concextratiox of the Urixe, and the Rate OF Urine Formation, following Stimulation of the Splanchnic Nerve. (MacLeod.) a part, but it is more generally held that there exists a true glycogenic centre apart from the vasomotor centre. To this centre run afferent, and from it efferent paths. The afferent paths are not fully eluci- dated. Interference with other parts of the brain and nervous sj'stem may induce glycosuria. Fright causes glycosuria in a cat. If the vagus nerve be cut in the neck, stimulation of the central end produces gh^cosuria. This experiment has been interpreted as showing that the vagus contains afferent fibres to the glycogenic centre. It seems more probable ^hat the glycosuria results from the asphyxial 430 A TEXTBOOK OF PHYSIOLOGY condition wliicli results from the spasm of respiration induced by the vagus stimulation. The chief efferent fibres ultimately reach the splanchnic nerve. When the splanchnics are cut, puncture of the medulla induces no glycosuria. Stimulation of the uncut splanchnic nerves brings about glycosuria (Fig. 217). To sum up, in the medulla is situated a centre which regulates the glycogen metabolism of the liver. The vagus nerve possibly contains afferent fibre:; to this centre; the splanchnic nerve conveys efferent fibres from it to the liver. It is possible that this centre is directly affected by the sugar content of the blood supplied to it, and that some drugs which induce glycosuria act directly upon the centre, exciting in much the same manner as a puncture does. (2) The Chemical Influence. — Adrenalin plays a part in the regula- tion of the glycogenic function. It has been known for a considerable \ime that injection of adrenalin into the blood-stream causes glyco- suria. This is now attributed to the action of adrenalin upon the endings of the splanchnic nerves in the liver. Adrenalin has the property of stimulating in the body all the functions which the sympa- thetic nerves excite. It acts upon the so-called '' receptive sub- stance," which occurs between the sympathetic nerve fibre and the effector tissue. We may provisionally conclude that the liver performs its glycogenic function — (1) under the influence of nervous impulses brought from the glycogenic centre by the sj)lanchnic nerves; (2) under the influence of adrenalin brought by the blood. By some authorities it is held that the internal secretion of the pancreas also plays a part in regulating the glycogenic function of the liver. The evidence on this point is contradictory in nature. The Influences under which Sugar is Broken Down. — Various agencies have been or are held to intiiKuce the splitting of dextrose in the body. At one time, considerable weight was attached to the supposed presence of a glycolytic ferment in the blood. Recent evidence indicates that the presence of such an enzyme in the blood is more than doubtful. At the present time, great importance is given by many authorities to the action of an internal secretion from the pancreas. This internal secretion is believed to be derived from the "islets of Langerhans " in the pancreas. Circulating in the blood, it enables the tissues, particularly the muscles, to break down dextrose. The tissue fluid obtained from a mixture of pancreas and muscle can break down dextrose; extract of pancreas by itself has no such action; that of muscle but slight action on dextrose. The active substance obtained from the pancreas is not an enzyme. It is soluble in water and alcohol, not destroj^ed by heat, and is believed to activate the zymogen of a glycolytic enzyme present in muscle, or possibly in the leucocytes. The above statement has not been accepted by all workers. Pancreatic glycosuria is discussed more fully elsewhere. From the evidence, we tentatively conclude that in the normal body an internal secretion derived from the pancreas plays a part in the THE METABOLISM OF CARBOHYDRATE 431 breaking down of dextrose by the muscles. The parts possibly plaj^ed by the secretions of the suprarenal and pancreas are sho^\ai diagram- matically in Fig. 218. Glycosuria. — Dextrose may appear in the urine under any of the following conditions: 1. The liver, supplied with too much dextrose, is unable to deal with it all, so that an excess of sugar passes into the blood and is excreted by the kidnej's. 2. The liver, over-stimulated, suddenly turns a large amount of glycogen into dextrose, floods the blood with sugar, and thus induces glycosuria. 3. The glj'cogenic function of the liver remains normal, but the power of the body to break down dextrose is diminished, so that the sugar accumulates in the blood, and this leads to glycosuria. (Sugar Content) Blood Adrenal Secretion Liver. (Glycogen Store) Fig. 218. — Diagra.m indicating Influence of Panckeas and Sttprarenals on Carbohydrate Metabolism. (After Underhill and Fine.) 4. There is no excess of dextrose in the blood, but sugar forms within the kidney substance itself, and is excreted in the urine. 5. The amomit of dextrose in the blood remains normal, but the kidneys become more '' permeable " to sugar. Thus sugar, which is normally retahied in the body, passes into the urine. When glycosuria occurs, it may be due to one or other or a combination of these conditions. Glycosuria may be exi:)erimentally induced in various waj's, the chief of which are the following: 1. Alimentary Glycosuria. — This follows the ingestion of too much sugar — for example, 150 to 200 grammes of dextrose, and considerably less lactose, levulose, and galactose. Children sometimes eat ^ pound or even \ pound of sweets. Alimentary glycosuria is due to the " flooding '" of the liver with too much sugar. It is sometimes termed "■ glycosuria e saccharo." It may also be produced, but more rarety, 432 A TEXTBOOK OF PHYSIOLOGY by the ingestion of too much starch ("" glycosuria e aniylo "). Many healthy members of a German garrison were foinid to have sugar in the urine because too much starch Avas inchided in their dietary. Alimentary glycosuria occurs more readily in some individuals than others. Clinicians differ as to whether people in whom this glycosviria occurs easily are to be regarded as physiological or pathological. 2. Puncture {Neurogenous) Olyccsuria has been already men- tioned. It results from the disturbance of the glycogenic centre in the medulla oblongata which controls the conversion of hepatic glycogen into sugar. Clinical experience shows that a similar condition arises from meningitis (inflammation of the coverings of the brain), injuries to the brain and upper part of spinal cord,, tumours of the brain, especially of the fourth ventricle, cerebellar haemorrhage, and possibly from psychic shock, mental worry, and overwork. The increased mobilization of sugar in the blood may be secondary to the passage of adrenalin into the blood, and possibly the internal secretion of the pituitary gland. It has been shown that fright increases the output of adrenalin. It is possible that some of the drugs, such as caffein and strychnine, which cause glycosuria, act on the glycogenic centre. Injection of piperine and the giving of anaesthetics cause glycosuria, apparently due to the dyspnoea thereby produced, for it is abolished if oxygen be given simultaneously. The same holds true of the glycosuria induced by the stimulation of the central end of the vagus nerve. The results may be due to the effect partly upon the centre, and partly upon the perijsheral nervous mechanism. 3. Pancreatic Glycosuria. — The remarkable discovery was made at the end of last century that total extirpation of the pancreas results in a fatal glycosuria, while if a small piece of gland (one-fifth) be left in situ, or transplanted, no glycosuria results. The glycosuria has no relation, therefore, to the digestive secretory function of the pan- creas. Considerable discussion has taken place as to the cause of this glycosuria. Some have contended that it results from operative damage done to the splanchnic nerves and symi^athetic ganglia in the neighbourhood of the pancreas. This view now finds little acceptance. It has been suggested by others that after the extirpation of the pancreas the liver more actively j)roduces sugar. In an ordinary fasting animal, the liver loses more weight than the rest of the body, whereas in a depancreatized animal starving from glycosuria (the gland was removed in part at first, followed by subsequent destruc- tion of the remainder) the liver does not lose weight, although the total weight of the animal diminishes rapidly. The view most generally accepted. However, in regard to pan- creatic glycosuria is that there results a diminished utilization of sugar by the tissues. Possibly the hepatic control of sugar is also affected. As the simultaneous injection of a j)ancreatic extract prevents that glycosuria which follows injection of adrenalin, it has been suggested that the internal secretions of the suprarenals and THE METABOLISM OF CARBOHYDRATE 433 pancreas together control the sugar content of the blood. There is also evidence of a mutual retardation of action effected between the th\Toids and the pancreas. Thus, when the pancreas is removed, there oscur.s an increased metabolism of protein and fat, which is attributed to the unrestrained activity of the thyroid and supra- renal glands. These conclusions, if substantiated, afford a striking example of the mutual interdependence of the various internal secre- tions of the bod}^ (see later, p. 503). The fasting depancreatized animal contmues to excrete sugar. As regards the source of this sugar, it has been shown experimentally that injection of such amino-acids increased its formation. The sugar may therefore be derived from protein decomposition. The question of the formation of sugar from tissue protein has also been investigated by comparing the amount of dextrose (D) secreted in the lu'ine with the amount of nitrogen (X) secreted as urea, giving the so-called ^- ratio. When a depancreatized animal is fed on protein freed from all traces of carbohydrate, both dextrose and nitrogen are increased in the urine, but the ratio is not altered from what it was during fasting, which shows that the dextrose and the nitrogen of the urine have a common source. If all the non-nitrogenous moiety of protein were used to form sugar, the ^ ratio would be about 7. This can be seen from the following calculation: Protein contains on an average 52 per cent, of carbon and 17 per cent, of 2iitrogen; urea, CONoH^, contains 20 per cent, of carbon and 51 per cent, nitrogen. If 17 grammes of nitrogen derived from 100 grammes of protein are excreted as lu'ea, the latter accounts for 6^ grammes of carbon. This leaves 52-6§ = 45| grammes of carbon to be accounted for. In the gramme-molecular weight of sugar. C^H^gOg — 180 — there are 72 grammes of carbon. Therefore, if 72 grammes of carbon go to form 180 grammes of sugar, 4tJ grammes of carbon .„ , 180x45^- wiii form ^^ '*" ^180x136 3x72 ^113-3 grammes of sugar . D 113-3 _ • • ^.= -,_ = / nearly. jN 1 / In an animal suffering from pancreatic glycosuria, however, all the carbon is not converted; a D : X of about 3 to 4 being maintained. Dextrose may also be formed from the glycerine moiety of fats. It has been shown that in the condition of pancreatic glycosuria glycerine ^nelds an increase of sugar in the urine. It is to be concluded, then, that after extirpation or in certain diseased states of the pancreas dextrose may appear in the urine, and this sugar ma}- be derived from carbohydrates, proteins, and fats. 4. Phloridzin Glycosuria. — Phloridzin is a glucoside obtained from the root bark of cherry and apple trees. If it be injected intc an animal glycosuria results. If it be injected into one renal artery, sugar 28 434 A TEXTBOOK OF PHYSIOLOGY api3ear.s in the urine secreted by tliat kidney before it appears in the urine secreted by the other kidnej-. If it be mixed with defibrinated blood and perfused through an excised kidney, sugar is excreted. No hyperglyeaemia is induced, and no store of glycogen in the liver is requisite. The sugar is formed in the kidney inider the influence of the drug. The sugar does not come from the drug itself, since phlore- tin, the jjortion of the alkaloid which is free from dextrose, also causes glycosuria. Two sources of the sugar huxe been suggested : (1) Glucos- amine, the carbohj'drate-holding group attached to the blood-proteins ; (2) amino-acids formed within the kidney itself. The amount of sugar is often too large to be accounted for wholly by the first view. The administration, together with the drug, of alaniu and other allied amino-acids causes an increased sugar excretion. The nitrogen excretion of the urine is also increased by phloridzin, the jj ratio being 3-6 after all the hepatic glycogen has been got rid of by fasting. 5. Adrenalin Glycosuria. — The fact that injection of adrenalin causes gtycosuria has already been mentioned. It is believed that adrenalin normally aids the liver in the performance of its glycogenic function (see p. 428). Injection of adrenalin apparent^ increases the conversion of glycogen into dextrose, and thus floods the blood with sugar — a condition allied to puncture diabetes. Adrenalin causes glycosuria in starved animals, and also in animals which have been submitted to the administration of phloridzin. It is stated that the administration of adrenalin in increasing doses causes a deposition of glycogen in the liver, but not in the muscles, in rabbits from whom all traces of glycogen had been removed both by starvation and doses of str3^chnine. The convulsions produced by strj^chnine expend the last of the glycogen. This internal secretion therefore plays an important part in the production of glycogen from sugar, of sugar from gh'cogen, and of sugar from proteins. 6. Thyroid and Parathyroid Glycosuria. — After removal of both the th\Toid and parathyroid glands, the organism is said to show a diminished tolerance to dextrose. When the th^yroids alone are re- moved (see p. 515 for a discussion of the relationship of these glands to each other), there is no evidence of such diminished tolerance. It is necessary that the parathyroids be ali-o removed. The para- thyroids apparently influence carbohydrate metabolism in such r. way as to prevent the accumulation of excessive sugar within the organism. The thyroids probably have a function which is supple- mentary' to the action of adrenalin. Taking away the thyroids has been shown to lessen the glycosuria induced by a given dose of ad- renalin. Excess of thyroid, on the other hand, possibly causes glycosuria bv bringing about a more marked action of adrenalin (see p. 505). 7. Pituitary Glycosuria. — It is claimed that intravenous or sub- cutaneous injection of extracts of the posterior lobe of the pituitary gland causes a glycosuria in animals fed on an ordinary diet, and that this is due to an internal secretion which lowers the utilization of THE METABOLISM OF CARBOHYDRATE 435 dextrose in the organism. Conversely, removal of the posterior lobe is said to endow animals with an increased tolerance to excessive amomits of dextrose (see later, p. 522). The interrelation and exact mode of action of all these glands requires far more work before any clear and dogmatic statements can be made in regard to their control of carbohydrate metabolism. 8. " Salt " Glycosuria. — Glycosuria follows the injection of 1 per cent, solution of sodium chloride into the blood of an animal. It has been suggested that the salt renders the kidnej' cells more permeable to sugar. On the other hand, it is cj^uite possible that the ghcogenic centre in the medulla is affected. Injection of a soluble calcium salt (ionized calcium) abolishes the glycosuria induced b}' the sodium ion. Diabetes Mellitus. — In this disease, or rather in the collection of ])athological conditions grouped under this name, the patient generally passes much sugar in the urine. Cases maj^ be described as mild and severe. In the mild cases, the gtycosuria disappears when carbo- hyckate is removed from the diet, the trouble being due only to defective storage or oxidation of sugar. In the severe cases, the sugar cannot be thus removed from the urine. It is probable that the less .severe of such cases derive sugar from protein onl}', whereas the more severe and rapidly fatal cases derive it from fats also. The acetone bodies which often occur in the urine of diabetics are dis- cussed elsewhere (Urine, p. 468). Under the name diabetes are classed glycosurias of various origin — neurogenous, hepatogenous, pancreatic, etc.^ — a great number of such, but by no means all, being due to some defect in the pancreatic control of carbohydrate metabolism. For a full discussion, textbooks of pathology and medicine should be con- sulted. The tests for sugar in urine are dealt with under Urine (p. 467), CHAPTER Lll THE METABOLISM OF FAT The Absorption of Fat. — Fat i.s digested into fatty acids and glycerine, and brought into solution. The preliminary emulsification of the fat facilitates its digestion, not its absorption . The view once put forward, and now abandoned, Avas that emulsified neutral fat is absorbed in the particulate form M'ithout being split into fatty acid and glycerine. The absorption of fats from the intestine depends upon the solubility of free fatty acids and soaps in the bile. The bile salts increase the solubility of soaps in water ; they also prevent its gelatinization, and thereby greatly aid absorption. The lecithin of the bile also plaj-s an important part in the solution of fatty acids and soaps. Fats of high melting-points are not absorbed so well as fats with low melting-points; free fats are better absorbed than those enclosed in cell membranes. During absorption the dissolved fatty acids and soaps pass into the intestinal mucous membrane. Here, by the activity of the cells, they are again synthesized with glycerine into particles of neutral fat, and these pass into the lacteals, which fill Avith a milky white lymph known as chyle. The lacteals derive their name from this milky fluid, and were discovered through it. Leucocytes aid the passage of the synthesized neutral fat into the lacteals. They are to be seen in sections of the villi stained Avith osmic acid, crowded with particles of fat. Hoav the particles are handed on from the columnar cells to the leucocytes is unknoAA^n. Not all the fat eaten finds its -way into the lacteals. The fate of the remainder is unknoAvn. It probably passes into the blood, forming some linkage with the protoplasm of the plasma and corpuscles. The lacteals, then, act as an overflow, and protect the liver from being flooded Avith fat. Our methods of anatysis do not allow us to detect any increase of fat in the portal blood, but neither do they permit us to be sure of an increase therein of sugar or amino-acids during digestion. The circulation is so rapid that an immeasurably small increase of any of these substances must suffice to carry them aAvay. About 60 per cent, of the ingested fat is found in the chyle as neutral fat, and a small quantity (4 to 5 per cent.) as soaps. Anabolism of Fat. — From the lacteals the chyle passes to the recep- taculum chyii, and thence by the thoracic duct into the A^enous blood. During this passage the neutral fat is again broken down into soluble soaps, passing as such into the blood, so that there is no danger of the 436 THE METABOLISM OF FAT 437 fat plugging the small bloodvessels, as would be the case if it were in a state of fine emulsion. It is also better available for storage in the various fat depots of the body. The fat dejjots of the body are situated in the subcutaneous tissue, in the subperitoneal tissue, between the muscles, and around various organs of the body, such as the kidney and the eyeball. The depots of fat act primarity as the storehouses of a food possessed of great energy value. They also protect the bodj" from heat loss, and act as cushions, giving form and beauty to the body, preventing jarring, and giving support to the various organs. The haggard face, the chilly tempera- ment, and the falling down of the viscera, alike result from want of fat. Fat is also stored intracellularly in other cells — e.g., muscle fibres and the liver cells — beside those of the true adipose tissue, much of it in a masked form, probably combined with protein or other bodies, so that it does not react with fat .stains. The fat in the various depots is not always of the same character. It is more fluid in some parts than others. Chemically, also, the same difiference is found. This is shown in the following table: „ ^ „. ' Sp.Gr.at Melting. \ l°^''T Free Acid.. Fat of P^. foo°C. Point \ ^"""^^Z^ (See p. 55.) {See p. 55. ) ^ ^ - Back 0-8607 33-8 60-6 0-152 Kidney 0-8590 4S-2 52-6 0-163 Omentum 0-858S U-o 53-1 0-360 The fats of the subcutaneous tissue are chiefly compounds of oleic, stearic, and palmitic acids. From the fats of the liver, kidney, heart muscle, however, acids are found more unsaturated than oleic, belonging to the linoleic and linolenic series. The fat of milk is also characterized by the presence, in addition to the ordinary fats, of butjTic and other volatile fatty acids. The lower melting-jjoint of the fat of the pig's back may allow mobility of the tissues there, exposed as they are to the cool atmosphere. The melting-point may be adapted to keep the fat of any part soft, but not fluid. The melting-point of the subcutaneous fat is altered by covering the pig's back with a sheep's pelt. The fat stored within the body maj' arise from three sources: (1) Ingested fat, (2) carbohydrate,. (3) proteins. Fat from Fat. — That fat arises from ingested fat is easih' capable of demonstration. Nature makes experiment for us. It can be^ shown that the fat of the sea-dolphin has a high iodine value when the fish it feeds on have fats of a high iodine value. When the fish eaten have fats of a low iodine value, the iodine value of the fat of the dolphin falls. The fat of the fish-eating ducks has a high iodine value (84-8). that of farm duck a lower value (58-5). Horses fed on oats have an oily fat of a high iodine number similar to that of the 43S A TEXTBOOK OF PHYSIOLOGY oil contained in oats. The wild-boar, when feeding on acorns and beech-nuts, acquires a fat Avith properties akin to those of the beech and acorn oils. Many exact experiments have also been made to prove this point. An animal is starved to reduce its fat as much as possible, and it is then fed Avith a fat the properties of which, such as melting;point, iodine number, etc., are known. In addition, the iatty acid contained in the fat often has its own characteristic properties. Such fats are rapeseed oil, linseed oil, sesame oil, coco- butter, etc. After feeding a starved dog or goose with sesame oil, it was found that the fat was more oily, and the presence of the sesame oil could be demonstrated in the fat by shaking it Avith an equal Aolume of strong hydrochloric acid and a trace of a 2 per cent, alcoholic solu- tion of furfurol. A purple-red colour dcA^eloped Avhen sesame oil was present. The foUoAving figures show the effect of feeding mutton fat and of feeding coco -butter on dogs: -, ,^. Melting- j .. Fatty Melting. p^^^^l^ Iodine j^J Pom of Fat ^nimJa I'^'^^Tr,, ^'^^ribe.r. >^- Fat. ^^'' P- ^^-y (See p. 55.) Mutton 46-51 Coco-butter 23-28 Carbohydrate . . . . . . — The fed fat also goes in part into the milk, so that the iodine number and other properties of the cream are altered. The characteristic test for sesame oil is given by the cream yielded by a cow fed wdth sesame oil. It is probably of considerable importance that the right fat should be stored in order that the body may be kept hard and in good condition. The soft toAvnsman may OAve his softness to the quality of his fat as Avell as to lack of muscular dcA'^elopment. Fat from Carbohydrate. — Fat may also arise from the carbohydrate taken in as food. This is obv^ious to those engaged in fattening pigs or geese for market. Carbohydrate is the chief food given. It has been proved scientifically by giA^ing animals, after preliminary starA^a- tion, a diet containing a minimum of protein and much carbohydrate. By comparing these with controls — e.g., animals taken from the same litter — it can be shown that the experimental animals put on so much fat that even if it be supposed that all the non-nitrogenous moiety of the protein eaten AAcre converted into fat, yet there is more fat to be accounted for; this must haA^e come from the cai'bo- hA^drate fed. EA'idence in faA'our of the formation of fat from carbohj'drate is also obtained from the respirator}^ quotient (1) of hibernating animals Avhich are storing fat ^preparatory to their winter sleep, (2) of animals which are being fattened bA" forced feeding with large amounts of carbohydrate — ^for example, of geese stuffed to make fat livers for the preparation of jJdte de foie gras. Under these circumstances. THE METABOLISM OF FAT 439 the respiratory quotient, which for carbohydrate is 1, and under 1 for proteins and fats, rise? well above 1 — e.g., to 1-3 or 1-4. At first the diserej)ancy was attributed to experimental error, but the ex- planation now generally accepted is that carbohydrate is being turned into fat, and that in the process carbon dioxide is liberated, so that the respiratory quotient is raised above 1. The following formula siim- • niarizes the series of chemical changes which bring about this result : 13C«H,,0, = C,,H,„,0, + 23CO, + 26H,0 Pat from Protein. — -The question as to the formation of fat from protein is a vexed one. It cannot be denied that such a forma- tion is possible within the organism. From the amino -acids arising from autolyzed body protein or from digested protein the formation of carbohydrate may take place, and from this carbohydrate fat may well be formed. From the available evidence it would appear that, although such a formation is possible, the animal body under normal conditions doss not make use of this power. Under certain conditions, however, such as the development of larvae, the formation after death of a waxy body known as adipocere, and possibly in some cases of so-called fatty degeneration during life, such a transformation of amino-acids into fat does take place. It has been shown, for example, that some of the higher non-volatile fatty acids are formed when the larvae of the blowfly. Calliphora, are rubbed with Witte's peptone into a homogeneous mass. So, too, it has been shown that fl3'-maggots, estimated from controls to contain a known quantity of fat, when allowed to feed on blood of a known fat content, develop after a time much more fat than existed in them- selves and the blood together at the start of the experiment. Such exj)eriments have not been accepted, owing to the fact that fat may result in the blood from bacterial decomposition. Recent researches, however, tend to confirm rather than discount these results. In regard to the formation of adipocere, this is a wax-like m'xture of insoluble soaps, fatty acids, and ammonia, which is found in corpses exposed to water. It is quite possible that lower organisms may also play a part here, and its development from the body proteins is by no means proved. Positive results have been claimed from fesding experiments, but it has been pointed out that the calculations giving these were based upon a wrong assumption of the proportion ^vhich nitrogen bears to carbon in the meat fed. When the calculations are corrected, the formation of fat from protein is found to be unproven. The evidence of the most recent feeding experiments is contradictory, some observers claiming that a formation of fat from protein can be shown, others denying this. From what has been said above, we may conclude that there exists in omnivora no fat rigidly characteristic of each t^'pe of animal, for foreign fats may be stored as such. Recent work, however, is tending to show that an animal's own characteristic fat is formed from carbo- hydrate just the same as a plant's characteristic fat or oil is formed from these bodies. Different species of animals form a different fat 440 A TEXTBOOK OF PHVSTOLOOY when fed with the same carbohydrate. The figures given in the table (p.4c8) show that the fat deposited from the carbohydrate in the diet differs considerably from that of the same animal when fed on other fats, and ])robably represents the animal's own characteristic fat. It is this fat which makes for a hard body and physical fitness. The Katabolism of Fat. — Tn regard to the katabolism of fat, evidence is scanty. It is (piite probable that there exists two different forms of katabolism — (1) of the ingested fat taken: (2) of the fat formed within the animal's own body from other bodies. The fat of the food may be regarded as a wanderer. It is formed, in the first place, within some plant or animal from lower bodies, and, unless used up again within the i:>arent organism, it passes from plant to animal, and from animal to animal, until bmnt up and used in the processes of metabolism. Such foreign fat is eventuall,y burnt to carbon dioxide and water. The fatty acids, if saturated, are probably first broken down to the higher unsaturated fatty acids, and then to the lower unsaturated fatty acids, such as ;5-oxybutyric acid and aceto-acetic acid, and finally to COo and water. Fat Glycerine Saturated fatty acid ! Unsaturated fatty acids /\ CO^ HoO If, however, the^fat formed within the organism — for example, from carbohydrate in the time preparatory to hibernation — be kata- bolized — e.g., during hibernation — there is good evidence to show that such fat is broken down h\ \\a.\ of carbohydrate again. Fat I Carbohj'drate CO., H^O The best evidence in favour of this view has been obtained from the observation of the respiratory quotient of hibernating animals. Normally, fat gives a respiratory quotient of 0-7 (see p. 319)- This is the lowest of the figures given by the three classes of foodstuffs. In hibernating animals, however, much lower figures have been ob- tained—e.g'., 0-23 for the dormouse, 0-5 for the hedgehog. The explanation given for these low figures is that the stored fat is being converted into carbohydrate; and since carbohydrate contains more oxygen in its molecule, oxygen is used up in the process, and the respiratory quotient of the animal correspondingly reduced. The process may be summarized by the folloAving formula : 2C2H5(Ci8H330,)3 + 640^ = leCfiH.aO, + 1800^ + 8H,0 Olein Dextrose . C0.,_18_ •• Oo -64-"^^^ THE METABOLISM OF FAT 441 In man, during starvation, respiratory quotients below 0-7 have also been observed, and it is quite possible that, under these circum- stances, some fat is being converted into carboh3'drates, and meta- bolized in that manner. The Metabolism of Lecithin. — Lecithins are found in all the tissues of the body, partly free, partly combined with protein. Entering largely into the composition of the cell membrane, they are supposed to control the passage of bodies into the cell, in addition to pla3ing an important part in the chemical processes of the cell. The amomit of lecithin is diminished in the body by starvation, and also by wasting diseases and phosphorus-poisoning. Anabolism. — The various lecithins are probably continuously being formed in the organism. From experiments made hy feeding with foreign fats, it is found that such — e.g., linseed oil — are not built up into the lecithins of the body. That lecithin is formed in the organism is shown hx the fact that mice fed on a lecithin-free diet grew well, and brought forth young. It is possible that each animal has its own characteristic lecithm, and that the fatty acid molecules of these are developed from the carbohj'drate of the diet, and not from the fat. Lecithin is formed in green leaves ex^iosed to light. Katabolism. — When lecithin breaks down, it forms first of all glycerophosphoric acid and cholin, and subsequently glycerine, phosphoric acid, and fatty acid. The phosphoric acid is probabh' excreted in the urine as phosphates, and the other bodies burnt up in the organism. Under certain circumstances, the lecithin and its derivatives may be deposited in the cell as oily droplets, giving a condition similar to that known as "' fatty degeneration." Fatty Degeneration. — In certain diseases, and after the application of experimental methods, such as phosphorus-poisoning, the cells of certain organs show on microscopic examination the presence of fatty droplets within the cell. The nucleus of the cell may or may not be fragmented. Such a condition has been termed " fatty de- generation." Much experimental work has been done to prove the origm of this fat, and also the circumstances which bring about the condition. In regard to the latter point, one of the chief causes is a diminished alkalinity of the cell fluid. Fatty degeneration takes place in dying cell;;. In regard to the source of the fatty droplets, the chief views held are these: 1. That the fat is essentially an infiltration into the cells from the fat depots of the body. 2. That the fat is the " masked " fat of the cell which has become "■ revealed "" in droplet form — e.g.. that the fat is fat which was linked to protein, and has become dissociated and visible. 3. That the fat has been formed from carbohydrates of the cell, or from amino-acids produced as the result of the autolysis of the cell proteins. 442 A TEXTBOOK OF PHYSIOLOGY 4. That the fatty substance is derived from the lecithin of the cell. 5. That the fatty substance is a compound of cholesterin- cholesterjd oleate, possibly derived from lecithin. It is quite possible that there are various chemical bodies which give rise to the microscopical apiDcarance known as fatty degenera- tion. It seems very likely, also, that " fatty degeneration " varies in nature according to the tissue in which it is taking place. Obesity is usually the outcome of excessive feeding and lack of muscular exercise, particularly the latter. But this is not the only cause, for some people never become fat, however much they eat or however little exercise they take; others, while eating little and taking much exercise, show a tendency to fatness. The obesity of some may be associated with a greater absorption of foodstuffs from the ali- mentary tract rather than a greater intake of food; that of others is associated with an inadequate oxidation of the foodstuffs, a peculi- arity of their metabolism due, perhaps, to a deficiency of oxidases. An hereditary tendency to fatness is often seen in families. It is well knoAvn that different breeds of cattle vary in the readiness with which they can be fattened. The amount of the internal secretions of the sexual glands, and possibly also of the thyroid, may play some part in this tendency to fatness. Castrated animals and eunuchs become fat. This may only be due to laziness developed as a result of the loss of their sexual instincts, but is probably also due to the removal of some direct effect upon metabolism. At the menopause, many women tend to put on flesh. We know that the secretion of the thyroid promotes the metabolism of protein and fat, so that a deficiency of thjToid secretion may be a cause of obesity. Thyroid extract is frequently given with success in obesity, but its effects have to be carefully watched. For most cases, a restricted diet, mainly of protein, which of all the foodstuffs most promotes metabolism, and much exercise, is the best treatment. Fresh fruit and green vegetables are bulky, and satisfy the desire for a full stomach. They contain some 90 per cent, of water. The obese should eat these and avoid concentrated foods, such as sugar, fat, meat cooked with fat. The truly obese man is an unfortunate. Owing to the large amount of fat, he has much weight to carry, he cannot easily lose heat, his breathing movements are impaired, so that he readily becomes fatigued, quickly gets out of breath, and sweats profusely. The dura- tion of life in the obese is shortened. By giving a few minutes daily to physical exercise of all parts of the body, with bathing, massage, and skin friction, by active exercise on holiday, and a wdsety restricted diet at all times, the body can be kept fit and the protuberant belly of the middle-aged citizen avoided. CHAPTER LIII THE METABOLISM OF NUCLEIN Xtjclein linked on to protein forms the compound body nucleo- protein, the chief protein constituent of the cell nucleus. Little or nothing is kno^^^l as to the building up of nuclein or of nucleo -protein within the body. Such a synthesis is undoubtedly always taking place, but the exact nature of the precursors emploj'ed in the process is not known. In the adult body there is no evidence to show that the purin bodies of the food are used in the process. In the young, in the early months of growth, there takes place an abundant forma- tion of nuclein, and upon a food (milk) which contains practically no nuclein. During the incubation of the hen's egg, nucleo -protein is formed within the cells of the embryo at the expense of the food yolk, which contains almost no nuclein or its derivatives, Xuclem breaks down as follows : Nuclease of pancreas Nuclein Protein Nucleic acid Enzymes of tissues Turin bodies Phosphoric acid Carbohydrate Pyrimidin V adenin (hexose or bases = guanin pentose) (chiefly cytosin) Adenin and guanin are amino-purins, being respectively amino- pm-in and amino-oxypiu'in (c/. p. 50). In some cases, guanin alone is formed. Probably the ingested nuclein is broken down by the nuclease of the pancreatic juice to nucleic acid and protein. The nucleic acid thus formed is absorbed into the blood, perhaps by the action of the pale corpuscles, and taken to tissues, where it is further acted upon, particularly in tissues such as the spleen, liver, and thymus, which contain enzj^mes capable of breaking it down into the purin bodies adenin and guanin, phosphoric acid, carbohydrate and pjrimidin bases. The adenin and guanin thus formed are, by the 443 444 A TEXTBOOK OF PHYSIOLOGY action of the enzymes adenase and guanase present in these tissues, convei'ted by deamiiiization into hypoxanthin and xauthin respec- tively (r/. p." 50) : C5H3N4.NH2 + H2O =-■ C5H4N4O + NH3 Adenin Hypoxanthin C5H3N4O.NH, + H,0 - CjH.N.O. + NH3 Guanin Xanthiii By the action of oxidases also present in the tissues the hj^po- xanthin and xanthin are converted into uric acid (tri-oxy-purin). The whole process may be grajDhically represented as follows: Adenin -^ Hypoxanthin (by action of adenase) (+ 0 by oxidase) CgHaNj.NH, C5H4N4O (amino purin) (mon-oxy-purin) I i Guanin -^ Xanthin (by action of guanase) (+0 by oxidase) C5H3X4O.NH2 C5H4X4O2 (amino oxv-purin) (di-oxy-purin) I Uric Acid C5H4N4G3 (tri-oxy-purin) Some of the uric acid thus formed may further be converted into urea hy the presence of a uricohi;ic enz3'me. This enzyme occurs in the liver, muscles, and kidney's, and probably destroys a considerable amount of the uric acid formed in the bodj*. Indeed, uric acid, even when given in the food, owing to the presence of this enzyme, causes no increase in the uric acid output of the body. Uric acid is, however, regarded as the chief end product of nuclein and purin metabolism. The uric acid thus formed is taken to the kidneys for excretion, but in what form is not exactly known. Uric acid is about iovty times more soluble in blood than in distilled water. This is not attributable to the alkalinity of the blood (which is in reality neutral), since uric acid is also much more soluble in acidified blood-serum than in distilled water. Probably uric acid is carried in the blood in combination with some other organic body, and not, as was once generally sujoposed, with sodium salts (sodium urate and soditim acid urate). The nature of the organic complex is not known. It is by some supposed to be thyminic acid, but no such compound has yet been isolated from the blood. Experiment shows that the uric acid which occurs in the urine has two sources — an exogenous, from the purins of the food; an endo- genous, from the purins liberated by the breaking down of the cell nuclei, and possibly also from other bodies. The presence in the urine of uric acid of endogenous origin is shown by the fact that upon a purin-free diet uric acid is excreted in the urine. The amount then excreted is fairly constant for each individual. This excretion reaches THE METABOLISM OF NUCLEIN 445 its maximum during the early hours of the morning, and subsides to a minimum towards evening. It is apparently unaffected by the periods of digestive and metabolic activity following each meal, but more uric acid is excreted after a rich than after a poor, nitrogenous, purin-free meal. The amount of uric acid is therefore in some way associated with the degree of nitrogenous metabolism of the body. The excess of uric acid may be ascribed — in part, at least — to the increased functional activity of the body cells. Thus, severe muscular exercise is followed after several horn's by a rise in the amovmt of endogenous uric acid excreted. Also, in diseases where a large amount of cell dismtegration is taking place {e.g., leukaemias, fevers), the output of endogenous uric acid is increased. It is not affected by the giving of diuretics. While endogenous uric acid undoubtedly arises from the destruction of the cell nucleins, the question remains as to whether any can come from other sources. It is known that there is a large hx-poxanthin content in muscle, and it maj' possibly be that some uric acid, especially the increase after muscular exercise, comes from this source. The amount of endogenous uric acid is more than can come from nuclear destruction in the body. It has been demonstrated on birds that perfusion of the liver with ammonia and lactic acid leads to a formation of uric acid. There is no evidence that an}^ such sjTithesis of uric acid takes place in the mammal. In birds, such a synthesis is homologous to the formation of urea in the liver of a mammal, and therefore it is not to be expected in the latter. It must be concluded that the exact source of all the endogenous purin is not known. The exogenous origin of uric acid is proved by the fact that it is greatly increased in the urine by the giving of foods containing nuclein or purin, especially foods rich in nucleo-protein, such as sweetbreads, and those containing much hj^jDo- xanthin, such as meat extracts. All the purins administered in the food are not, however, excreted in the urine as uric acid; some are excreted as purins. The amount of uric acid formed in the organism varies with the kind of purin fed and the species of the animal which eats it. For example, in man, only one-half of the hypoxanthin administered as such appears as uric acid in the urine, and but one- fourth of the purin in nuclein w^hen that is fed. In the dog, compared with man, about ten times as much purin disappears in its passage through the organism; in the rabbit, about three times. There is doubt as to whether the methyl purins (caffeine, theo- bromine) lead to a formation of uric acid in the organism, or whether they are secreted as purins in the urine. One of the symptoms of gout is a permanent increase in the amount of uric acid in the blood — a " uricsemia." Various reasons have been ascribed as the cause of this. At one time it was believed to be due to defective excretion of uric acid by the kidney. Research does not lend much support to this view, although it is quite possible that the kidney changes Avhich occur late in the disease may to some extent affect the elimination of uric acid by the organ. 446 A TEXTBOOK OF PHYSIOLOGY It is suggested by some that the chief factor in gout is a defect in the transport of uric acid; by others it is beheved to be due to a deficient enzymic activity, particularly of the uricolytic enzyme ot the body. Others believe that gout is due to a toxni of uitestinal origin; yet again others deem it to be secondary to abnormal carbo- hydrate or fat metabolism. The whole question is sub judice. CHAPTER LTV THE FUNCTIONS OF THE LIVER AND SPLEEN The liver is developed as a tubular outgrowth from the duodenum. The ultimate endings of this tube break up into numerous fine ducts lined by ej^ithelial cells of large size — the liver cells. The whole makes a lobulated gland, the lobule belonging to each branchmg duct being separated from its neighbour by connective tissue (Glisson's capside). In this interlobular connective tissue run — (1) bile ducts, (2) branches of the portal vein (interlobular), (3) branches of the hepatic artery, (4) lymphatic vessels. In (1) bile, in (4) lymph flows from the lobules, in (2) and (3) blood flows to the lobules. The liver lobule has a large blood-supply. The hepatic artery brings oxygenated blood, and the portal vein blood containing foodstuffs which have been absorbed from the alimentary canal. The capillaries arising from the artery and portal vein anastomose as they radiate through the lobule, forming a network of fine branching vessels (interlobular branches). These unite in the centre of the lobule to form an intralobular vessel, which joins with others to make a sublobular vein, the fusion of sublobular veins finally forming the hepatic vein. The large branches of this gape open when the liver is cut. The bile canaliculi, the first comemncement of the bile ducts, are channels between the liver cells, and can be demonstrated by giving Guch a dye as sulph'ndigotate of soda. This is secreted with the bile, and distends and-stains the canaliculi. They can also be stained by Golgi's method. The liver is an organ of manifold functions, some of which have already been mentioned or dealt with. We propose in this section to group together the various functions of the organ in order that the scope of its activities may be appreciated. 1. The Formation and Excretion of Bile. — Within the liver the bile salts are synthesized, and the bile pigments are derived from the haemoglobin of effete blood-corpuscles. These, together with the other constituents of the bile, are secreted into the bile canaliculi, and pass thence into the intestine, there to fulfil the various functions already indicated (see p. 391). 2. The Glycogenic Function. — The liver acts as the storehouse of the colloid glycogen. This it forms from the dextrose brought by the portal vein, and under approjDriate circumstances reconverts it into dextrose for use in other parts of the body, particularly in the 447 448 A TEXTBOOK OF PHYSIOL(JGY muscles (see p. 427). The liver probably also forms glycogen from other bodies, including the non-nitrogenous moiety left over when certain amino-acids are deaminized, either in the intestinal mucous membrane or in the liver itself (c/. p. 424), 3. Storage of Fat. — Although the liver contains a certain per- centage of '■ masked '"' fat — that is, fat which is not visible to staining processes — under certain circumstances, such as during pregnancy and lactation, the liver contains large amounts of visible fat, the exact significance of which is not known. Thus visible fat in the liver, which occurs in " fatty degeneration," is not always a patho- logical phenomenon. 4. The Formation of Uric Acid. — The liver jiossesses deaminizing enzymes which are capable of converting purin bodies, such as adenin and guanin, into the oxypurins hypoxanthin and xanthin, and also oxidizing enzymes capable of converting these bodies to uric acid. It also in the mammal contains a uricotytic enzyme which turns uric acid into lu'ea. 5. The Formation of Urea.— The liver plays an important part in (he metabolism of protein, jjarticularly in the end processes of this metabolism which result in the formation of urea. The fact that urea is formed in the liver can be demonstrated in various ways : (1) Extirpation of the liver in the frog leads to a diminution in the amount of urea excreted, and an increase of ammonia bodies in the excreta. (2) In birds, such as the goose, there is a connecting vein between the portal vein and the inferior vena cava. Ligature of the portal vein on the liver side of this connection diverts the contents of the portal system into the inferior cava. Under these circumstances, there occurs in birds a marked diminution in the excreta of the amount of uric acid, the homologue of urea in the mammal, and a corresponding increase in the amount of ammonium compounds. (3) In mammals, a similar condition of affairs may be brought about by the operation devised by Eck, and known as Eck's fistula. The operation consists in making a communication between the portal vein and the inferior vena cava. As before, the portal vein is ligated as it enters the liver, and the portal circulation is thereby deviated from the liver. Under these circumstances, the amount of urea is greatly decreased in the virine, the ammonia content being greatly increased. It is generally stated that animals upon which this experi- ment has been performed show marked symptoms of metabolic dis- turbance, accompanied by signs of ferocity and bad temper. This apparently depends upon the nature of the diet given after the oj)era- tion. Dogs which have had such an experiment performed upon them, with the hepatic artery and vein ligated in addition, remain for many days after the operation quite happy and docile so long as they were fed on bread and milk. During this time they were becom- ing progressively thinner. Any form of meat in the diet, however, THE FUNCTIONS OF THE LIVER AND SPLEEN 44!) immediately brought on signs of surliness, and eventualh' induced convulsions. (4) In certain forms of liver disease the amount of vu'ea passed in the urine is markedly diminished, the amovint of ammonia bodies being correspondingly increased. (5) Perfusion of blood-containing ammonium carbonate through . the liver of a mammal leads to a marked increase in the urea content of the blood. This experiment was done originally upon the liver of a dog, but it holds true for all mammals. According to some autho- rities, amino-acids, such as glycin, alanin, arginin, also lead to the formation of urea when perfused through the isolated liver. This, however, is not accepted by all — at any rate, as a normal process. L^rea, therefore, is undoubtedly formed in the liver, the main precursor being compounds of ammonia. These compounds are particularly the carbonate, which may be graphically represented as ^^ .ONH, and the carbamate, Avhich may be figured as ^^/ONH^ The change to urea nuiy probably, therefore, be I'epresented as follows : ^^\ONHj ^ ^^ NH. > '-^ .NH, Ammonium carbonate Ammonium carbamate Urei Some of the urea formed in the liver may be derived from the conversion of uric acid to urea. It has been shown in the laboratory that creatin may give rise to urea. There is, however, no good evidence to show that such is the case inside the body. Most of the urea formed in the liver is derived from the nitrogenous part of the food taken in — that is to say, it is exogenous in origin. Alterations in the amoimt of nitrogenous food cause similar fluctua- tions in the amount of mea in the urine (see p. 455). The view held as to the form in which the j^reci^rsor of urea reaches the liver depends naturall.y upon which hyiDothesis of protein metabolism is put forward. According to the first view (p. 424), urea would be derived mainly from the amino-acids brought to the liver by the portal blood, particularly from such amino-acids as gh^cin, alanin. leucin. and arginin. According to the other view, no such acids exist in the portal blood. The precur.sor of most of the urea formed in the liver would in this case be the ammonia which has been broken off from the excess amino-acids during the process of their deaminization in the intestmal mucous membrane. This is transported to the liver in the form of the carbonate and carbamate, and converted into urea. Some urea might also be formed from excess amino-acids left over in the bloodstream after a tissue has 29 450 A TEXTBOOK OF PHYSIOLOCiV taken from the plasma protein the particular amino-acids of which it has need. Another part of the urea might also be endogenous in origin, being formed in the liver from the amino-acids resulting from the katabolism of protein in various parts of the body. The question as to whether urea is formed solely in the liver should probably, despite views to the contrary, be answered in the negative. There is apparentlj- a small formation of urea from endogenous i)re- curfcors in other parts of the body, particularly- the muscles. Per- fusion of the hind-limbs of an animal with defibrinated blood leads to an increase of' the urea content in the venous over the arterial blood. It is correct, however, to say that the main mass of urea execreted from the bodj' is formed in the liver from the nitrogenous moiet}'' of the j)rotein food taken in. 0. Protective Function. — Another important function of the 1 ver is its i)rotective function. This is manifested in various ways: (1) The nocuous products of protein putrefaction in the large in- testine, such as indol, skatol, phenol, tresol, are combined in the liver with sulphuric acid to form the innocuous potassium salt of the acid. NH :C8H6 + 0 = NH .CsHsOH Indol Indoxyl NH :C«H,OH + SO./ OK = ^^ ••CsH,.O.SO,K + H,0 Potassium Potassium indoxyl aoid sulphate Sulphuric acid (indican) CeH.OH + S0,< OK = CsH^.O.SOaK + H,0 Phenol Potassium phenol Sulphuric acid In cases of excessive formation these bodies are combined v.ith glycuronic acid also. (2) Drugs, such as chloral, camphor, etc., are combined with glycuronic acid in the liver, and rendered harmless or less harmful. (3) When acid formation is going on within the body — for example, the formation of aceto-acetic acid and f/-oxy-but\Tic acid during starvation, or in pathological conditions such as diabetes melliliis— the liver to a certain extent negatives the ill effects of such acids by combining them with ammonia, thereby markedly increasing the ammonia content of the urine. (4) The liver possesses the property of retaining within its cells poisonous minerals, such as phosphorus, arsenic, mercurj-. antimony. But little is known as to the exact manner in which this is accomplished. 7. Fibrinogen Formation, — The liver is possibly the organ in which the fibrinogen of the blood arises, also antithrombin when peptone is injected into the blood; this, according to the generally accepted view of blood-coagulation, renders the blood and lymph incoagulable —the result of such an injection. THE FUNCTIONS OF THE LIVER AND SPLEEN 451 8. Heat Formation. — The liver, by virtue of its manifold chemical activities, produces heat. 9. Venous Reservoir. — Lastly, the liver acts as a venous reservoir interposed in the portal circulation, and bj' \Trtue of this property prevents overdistension of the right side of the heart. The blood within it is expressed into the heart by the action of the diaphragm, and the vigour of the hepatic circulation therefore depends very much on the vigour of respiration that is on muscular exercise. In cases of failure of the right side of the heart the liver becomes greatly engorged with blood, and is felt pulsating below the margin of the ribs. The Spleen. — The exact nature of the main function of the spleen is a matter of surmise. The gland can be extirpated from man and animals without ill effects. It is stated to have been removed from athletes in classical times, to prevent " stitch." It appears probable that, after the operation, there is a compensator}' overgrowth or hAq^ertrophy of lymphatic tissue. It has been shown recently that after extirpation of the spleen more iron is lost than formerlj' in the urine; the spleen ma}' therefore be the regulator of the iron meta- bolism of the body. There is some evidence that in the spleen the effete red blood-corpuscles of the bod}^ are destroyed. It is question- able whether in adult life the spleen plays any part in the formation of red corpuscles, although it certainh' does so in the foetus. By virtue of its lymphatic tissue, the spleen gives origin to some of the lymphocytes of the blood, and pla3^s a considerable part in the purin metabolism of the body. During the first hours following digestion the spleen is swollen in size, acting like the liver as a blood-reservoir in the portal circulation. The spleen rh3ii;hmically contracts. The enlargement of the spleen in certain fevers — e.g., malaria, tyjjhoid — shows that it, like the lymph gland, is engaged in protecting the body against bacterial invasion. BOOK VIII THE FUNCTIONS OF THE KIDNEY CHAPTER LV THE URINE The urine, continuous^ secreted by the kidneys, averages about 1,500 CO. (50 ounces) in twenty-four hours. The larger part of this amount is passed during the day, but in certain diseased conditions more uiaj^ be passed during the night. For this reason, some clinicians have the urine passed during the twenty-four hours collected in two portions. The day urine is taken, say, from 8.30 a.m. to 8.30 p.m., the bladder being emptied at both these times. The remainder is the '■ night urine." Children pass considerabty less urine than an adult. At five years the daily amount is about 390 c.c, at twelve 3'"ears about 830 c.c, about fifteen the amount begins to approximate to that of the adult. As the urine passed at difi^erent times during the day varies con- siderably in composition, it is usual to take the total urine of twenty- four hours for purposes of chnical analysis. Various factors modify the amount passed. An increased secretion follows a large consump- tion of food or drink, and exposure to cold. On the other hand, in- gestion of little food or drink, exposure to heat, great muscular work, the conditions which produce sweating, lead to a diminished secretion. Normal urine is a transparent, limjjid, watery fluid, yellow in colour. When shaken in a test-tube, there is a little froth, which does not last long. When certain pathological bodies are present, particularly bile and protein, the urine is less mobile, and the froth much more marked. Thus, the presence of albumin may be indicated by the froth on shaking. The odour of healthy urine is described as aromatic. After stand- ing for some time, this changes to an " ammoniacal " smell, owing to the action of organisms {Micrococcus urece) which fall into it, and by their growth break down the urea present, with the liberation of ammonia. The specific gravity of urine, as tested by the instrument known as the urinometer. is on an average 1015 to 1025. These figures apply to the twenty-four-hour sample ; for samples casualh^ taken 4r)H 454 A TEXTBOOK OF PHYSIOLOGY it may var}' greatly. A urine may have a specific gravity below 1010 after much drinking, or as high as 1035 after much sweating. An abundant urine of low specific gravity is suggestive of some patho- logical condition, such as diabetes insipidus or chronic renal disease, while the passage of large quantities of pale urine of high specific gravity suggests the presence of sugar in the urine. If, on the other hand, the colour be high, some condition causing loss of water from the l)od\-, such as diarrha?a or fever, ma\' be present. The quantity of the solids in the urine per litre may be roughly estimated by taking the specific gravity of the urine at 15° C, and multiplying it by 2-33. The osmotic pressure, measured by depression of freezing-point, varies from - 0-8° to -2-7° C. The reaction of the urine, as tested by chemical indicators, is generally acid. To the ph3'sical test the urine, like the blood, is neutral (see p. 76). The acidity to Ltmus is due mainly to the acid phosphate of sodium (XaH2P04). When, however, urine is passed during the digestion of a meal, it is often amphoteric or alkaline in reaction. This is because the acid phos])hate in the blood is con- verted into disodium phosjohate (XaoHPO^). owing to the formation x)f the HCl of the gastric juice. The reaction of urine may also be alka- line after eating fruits and V3getables containing organic acids (citric, malic, etc.). These are converted in the bodj^ into alkaline carbonates, which are excreted in the urine. It is believed by some authorities that the acidity of the urine is in part due to the presence of volatile organic acids in the urine. It is stated that, if urine be distilled, the 2:)art which distils off is acid, owing to the presence of such volatile acids. For clinical purposes, the total acidity, and indirectly the am- monia, of the urine may be determined by a method in which the acidity is first estimated by titrating Avith ^^^^ XaHO. Xeutralized formalin is then added. The ammonia of the urine combines with this to form the neutral compoiuid lu'otropine, setting free the acids to which the ammonia is combined. A second estimation with f'jj NaHO gives this acidity, and from it the amount of nitrogen present as ammonia may be calculated by multiplying by 00014. The Transparency and Colour of the Urine. — Freshly voided normal urine is transparent, and possesses a ^^ellowish colour, the exact tint ■of Avhich fluctuates widely even in health according to the degree of dilution and the reaction of the urine. This colour is due chiefly to the pigment urochrome. Other pigments — urobilin, uroerythrin, iirorosein — also occur in normal urine under various conditions. Urochrome. — The origin of this pigment is not known. It is probablj- derived from protein, as it contains nitrogen and sulphur in its molecule. It yields no absorption bands when examined spectro- scopic ally. Urobilin is not present in freshly voided urine, but its chromogen is — urobilinogen. The darkening of urine on standing is due to the conversion of urobilinogen into urobilin. Urobilin, when present, THE URINE 455 gives one broad absorption band in the green between b and F. The urine containing it is generally dichroic, appearing red by transmitted, and green by reflected, light. If urobilinogen be in excess, it is found that an acid solution of dimethjdparaminobenzaldehyde (2 grammes in 100 c.c. 5 per cent. HCl), when added to the urine, turns red in the cold. With normal urine, such a red coloxu- is only developed on Leating. Ui'oerythrin confers a dark pink colour on concentrated urine. ■Spectroscopically, it yields two bands, one at E, the other at F. They are not well defined. Urorosein is an indol derivative. Composition. — Normal urine contains about 96 per cent, of water •and 4 per cent, of solids. The chief organic boclies are — Urea, uric acid, purin bodie3, creatinin, ethereal sulphates, neutral sulphur com- jjounds, oxalic acid, hippuric acid, enzjanes, pigments. The inorganic solids are — Chloride solids of sodium and potassium, sulphates, phosphates, carbonates. The Nitrogenous Constituents. — The chief of these are urea, am- monia, uric acid, creatinin, hippuric acid. There are various other substances in small quantities, including the purin bases. These vary in percentage according to the intake of nitrogenous food in the diet. With the exception of ci'eatinin, the amount of these bodies •excreted falls as the amount of the nitrogen in the diet is decreased. According to the diet the percentage of urea varies in relation to the percentage of other bodies, particularly to the percentage of ammonia. This is shown by the following analyses of such urines: Nitrogen-Rich Diet. Nitrogen-Poor Diet. Total nitrogen excreted Urea N Ammonia N Uric acid I\ . . •Creatinin N . . Undetermined N Almost the whole of the nitrogen taken in the food is excreted in the urine. Protein contains about 15 per cent, of nitrogen, and if 100 grammes are consumed, about 1 gramme nitrogen will be passed in the faeces, a trace in the sweat, and the rest in the urine. B}^ estimating the total nitrogen of the twenty-four hours' urine the intake of protein ■can be calculated. The Total Nitrogen of the Urine is estimated by means of Kjeldahl's method, or one of its modifications. The process is carried out in three stages: (1) The oxidation of the nitrogen present in the urine to ammonia; (2) the distillation and collection of this ammonia in a standard acid solution: (3) the ascertaining by titration of the amount of this ammonia. Griii3. Grm.s- 16-8 3-60 14-7 (S7-.5 per cent.) 2-20 ((il-7 i)er cent.) 0-49 (3-0 jj ) 0-12 (11-3 ,, ) 0-18 (1-1 »> ) 0-09 ( 2-5 ,, ) U-58 (3-6 >' ) 0-60 (17-2 ,, ) 0-85 (4-0 ) 0-27 ( 7-3 ) 456 A TEXTBOOK OF PHYSIOLOGY 111 the first part of the process, a known quantity of the mine is. heated in a long-necked, hard glass flask with strong sulphuric acid, and a little of the sulphates of j)otassium and copper are added to facilitate oxidation by raising the boiling-point of the acid. The ammonia formed is combined Avith the sulphuric acid to form am- monium sulphate. The heating is continued until the Hind becomes almost colourless. In the second jjart of the process, the excess of acid is neutralized by strong alkali (40 per cent. NaHO), an excess of alkali being added. Then the ammonia is distilled over into a standard acid solution (-j^ H.2SO4) containing an indicator such as methyl orange. The indi- cator is required to show that there is sufficient acid present to trap all the ammonia driven over. In the third part of the process, the excess of acid in the receiving flask is ascertained by titrating with standard alkali (j^^ NaHO). By subtracting this excess from the amount of standard acid originally taken, the amount of acid combined with ammonia is found. Multi- plying this amount by 0-0014, we arrive at the amount of nitrogen in the sample of urine. Urea is the chief nitrogenous waste sub.stance of the mammal. Its formula is /\H and it maj be regarded as carbonic acid (HoCOg), or ^^ \0H in which the two hj'droxyl groups (OH) have been replaced by two amine (XH^) groups. It has the same empirical formula as ammonium cvanate. from which bodv it was first prepared bj^ Wohler in 1828— CONKH, ^ ^'^ Nh! — the first synthesis of an organic substance out of inorganic material. Carbamic acid XHo ^^\0H may be jiresent in the urine as a salt, for example after experi- mentally excluding the liver from the circulation. It is apparently a precursor in the svnthesis of urea (see p. 449). Pure urea consists of colourless elongated crystals. It is extremely soluble in water, alcohol, and acetone, but insoluble in ether and chloroform. It possesses the j)roperty of dissolving connective tissue,, and may be used in making teased preparations — e.g., to isolate muscle fibres. It is also a good solvent for uric acid. It combiner with acids to form salts, such as urea nitrate and urea oxalate (Figs. 219, 220). THE URIXE 45- \A^hen solid urea is heated in a drj" test-tube, it first melts and then goes solid again. During the process ammonia gas is given off, and the body known as biuret is formed, which, with a little copper sulphate and some caustic potash, gives a pink colour. 2co<^;g2 =. XH3 + co<^;h, A Ho Biuret If still further heated, a body known as cyanuric acid (C3N3H3O3) is formed, which does not give the biuret test. Urea is precipitated from solution as a dense white precipitate by the addition of mercuric chloride. The presence of urea in urine may be shown by concentrating the urine by evaporation over a water-bath, and adding concentrated nitric or oxalic acid, when crj^stals of xn-ea nitrate or oxalate will be !■"[ ;. 219. — Urea Xitratk. Fig. 220.^Urea Oxalate. deposited. Crystals of urea may be obtained by rubbing the urea nitrate into a paste with barium carbonate — as a result, barium nitrate and urea are formed, with the evolution of carbon dioxide, and then extracting with alcohol, and allowing the alcohol to evaporate. Crystals of urea may also be obtained directly from concentrated urine by extracting with acetone, and allowing the acetone to evaporate. On heating with acids under pressure, urea is decomposed into ammonia and carbon dioxide. It is also split thus by the ferment urease present in certain bacteria and in the soya bean. When fuming nitric acid is added to urine, an evolution of carbon dioxide and nitrogen takes place, owing to a decomposition of the urea, as expressed liy the equation C0<^15- + 2HN0o = CO., + 2X, + 3K,0 458 A TEXTBOOK OF PHYSIOLOGY A similar reaction takes place when sodium hypobromite is added to urine, but nitrogen alone is evolved, the CO2 remaining combined to the alkali present in the solution. CO<5§2 + SNaBrO + 2NaH0 = 3NaBr + X, + 3HoO + Na.COg. Advantage is taken of this reaction for estimating the daily output of urea. The method is not very exact, since nitrogen is also evolved from uric acid and other bodies present in the mine. A known amount of urine is mixed with an excess of the hypobromite solution, and the evolved nitrogen collected. The apparatus employed, such as Dupre's, is generally graduated in percentages of urea. With Southall's ureo- meter (Fig. 221) one c.c. of urine from a special pipette is carefully injected below the bend of the tube which is filled with h3'i3obromite. If no such apparatus be available, the gas may be collected over water in a burette, and the amount of urea calculated from the fact that 01 gramme of urea yields 35-4 c.c. of nitrogen. A more exact method of estimating urea in urine is to heat some of the urine Avith magnesium chloride and hydrochloric acid. The urea under these cir- cumstances is broken down to ammonia, which combines Avith the acid jDresent to form ammonium chloride. The other nitrogenous constituents of the urine are not affected in the process. The amount of ammonia in the ammonium chloride thus formed is then determined by Kjeldahl's process. There is little information of clinical value to be gained from an estimation of the urea output alone. What is required is a knowledge of the amount of nitrogen taken in the diet, and the relative values of the urea, creatinine, ammonia, etc., excreted in pathological conditions. Clinical information of this character has yet to be collected. The precursors of urea and the site of its formation in the body have already been discussed. About 25 to 40 grammes of urea are excreted dai.y, the amount varying according to the diet. Uric Acid is the chief nitrogenous waste product of birds and reptiles. It occurs also in mammalian urine combined with alkalies. The empirical formula of uric acid is C.H^N^Og; it is tri-oxy-purin, and the formula may be graphically represented thus: HN— CO Fig. 221. Ueeometer. OC C— NH HN— C— N CO (see p. 50). About 0-4 to 0-7 gramme of uric acid is excreted in the human urine daily. It is a dibasic acid, and therefore forms two THE URIXE 459 classes of salts — the normal urates (Xa^f ) and the acid urates (XaHC). The chief urates present in the urine are acid sodium urate (C-H.^XaX^O) and normal sodium urate (C-H,Xa.,Xj0.j). Sometimes ammonium urate also occurs. Urates are frequently deposited from concentrated urme as a pinkish deposit coloured ])v uroerythrin. Such a deposit is sokible on heating or addition of alkaU. Urates are sometimes amor- phous, sometimes erystaUine, as "" thorn apples," fan-shaped clusters of prismatic needles (Fig. 222). To obtain uric acid quickly, a consider- able quantity of urine (about 100 c.c.) is taken, ammonia added till the reaction is alkaline, and then the urine saturated with ammonium chloride. Ammonium urate is ]Dreci]3itated. and from this precipitate uric acid may be obtained bv the addition of acid. If hydrochloric' Fig. 222. — Sjdil'ji Urate, x 3.50. acid be added to urine, and the urine be left to stand for twenty-four hours, crystals of uric acid fall out, usually highly pigmented Avith urorosein, and known as the brick-dust or cayenne-pepper deposit. Under the microscope, the crystals apjiear shaped like whetstones, barrels, wedges, rosettes, and coloured reddish-yelloA\' (Fig. 223). Uric acid is sometimes passed in acid urines, and known as gravel. Stones formmg in the bladder and kidney are often found to be com- posed of uric acid or urates. Uric acid is almost insoluble in \\ater. It is lield in solution in the urine partly bj' the alkaline phos]jhates. and partly by the in-ea preiont. It is readily soluble in alkalies. \Mien evaporated with nitric acid, it leaves a yellowish residue, Avhich turns purple on adding ammonia, and blue with caustic potash (the murexide test). Urates also give this murexide test, which depends upon the fact that a sub- stance— alloxantin — is formed from uric acid, and combines with ammonia to form ammonium purjiuratc. 460 A TEXTBOOK OF PHYSIOLOGY A strong solution of uric acid in alkali reduces Fehling's solution on heating, but not Nylander's solution (see p. (il). It will also reduce silver nitrate in the cold. If a drop of an alkaline uric acid solution be placed on a filter-paper, and a drop of silver nitrate solution be added, a blackened area of reduced silver results (Schiff's test). Uric acid is estimated quantitatively by precipitating it as am- monium urate, as described above, washing the precipitate carefully to remove all traces of chlorides, setting free the uric acid by the addition of sulphuric acid, and titrating with a standard solution of potassium permanganate imtil the rose colour, which at first dis- appears, just persists. Uric acid is both exogenous and endogenous in origin (see p. 444). It is increased by ingestion of bodies rich in nuclei (sweetbreads, etc.). In disease, it is increased when tissue destruction is going on, as in Fig. 223. — Uric Acid Crystals. (8avill. leukaemia and acute fevers. Much has been made of uric acid as a cause of gout. There is no evidence to show that its formation is increased in gout. It has no toxic properties, and there is nothing to justify its ill reputation, or the advertisements of the quack medicine vendors. The precursors of uric acid and the site of formation have already been discussed (p. 444). Purin Bodies. — Hypoxanthin, adenin, and xanthin, are present in normal urine in small amounts. These are supposed to be derived from the decomposition of nucleic acid. Methylxanthin results from the taking of coffee and tea which contain caffeine (tri-methyl- xanthin). and of cocoa which contains theobromine (di-methyl- xanthin). Guanin is present in the urine of several of the inverte- brata. Allantoin is the chief end-product of the metabolism of nuclein in some animals, and occurs in human urine in traces and in allantoic THE URINE 401 fluid. It is obtained on oxidation of uric acid by a ferment — uricase — or'by oxidising agents (ozone, permanganate of potash). HN-CO OC C— NH .,.- .. , „ n or^ HN— CO I CO + O + HoO = C0< I . ,, . HN— C— NH NH . CH.NH.CO.NH2 It can be synthesized out of glyoxylic acid (COOH.CHO) and urea, and is a diureid of glyoxylic acid. Creatinin (C4H.N3O) is excreted in the urine in such a very constant amount — about 1 gramme in twenty-four hours — that some have regarded it as a measure of the nitrogenous metaboHsm of the tissues (endogenous metabolism). Creatin, or methylguanidin-acetic acid is found in the muscles, and therefore in meat extracts. On heating with dihite HoSO^, it passes into its anhydride, creatinin. Creatin is excreted when the ])rotein substance of the body is being broken down, and occurs in the urine during starvation and fevers, also during lactation. The creatin which is eaten in meat is probably decomposed by the intestinal bacteria. The relationship of the creatin to the creatinin of the body is a matter of considerable complexity. Contrary to what was once believed, it is probable that creatinin is the mother -substance of creatin, and not creatin of creatinin. It is possible that creatinin is formed in the liver from some product of protein digestion, and that the creatin of the muscles is built up from the creatinin thus formed. The presence of creatinin in the urine is shown by adding a few drops of a saturated solution of picric acid and a little 20 per cent, solution of caustic potash. A transparent red colour is produced (Jaffe's test). Sugar in the ra-ine gives the same colour, but deeper and opaque. Thus, there is no difficulty in distinguishing between the two. Another test for creatinin is to add a few drops of a freshly pre- pared solution of sodium nitroprusside and 20 per cent, solution of caustic potash to the urine. A red colour is /y^ produced, which disappears on heating or on ^3 the addition of acetic acid. Oxalates occur in the urine combined with ^. ^ ^ calcium, and the salt is normally kept in solu- '^> tion by the acid sodium phosphate present. ^^ When precijiitated, it occurs as envelope or ^ ^^ dumb-bell shaped crystals insoluble in acetic ^^^ and easil}^ soluble in hydrochloric acid (Fig 224). IlaVe Crvstals. About 0-017 gramme of oxalic is excreted daily. iSavill.) This is mainly derived from the food, and is increased by the ingestion of fruits and vegetables, such as rhubarb, strawberries, tomatoes, spinach, cabbage. There are cases of " oxa- 402 A TEXTBOOK OF PHYSIOLOGY luriti " wlure the oxalates are precipitated, but as a rule are not increased, in the urine. Such patients generally suffer from an acid dyspepsia, and have less acid sodium phosphate than usual in the urine; hence the oxalates fall out of solution. Hippuric Acid (0,jHgN403) occurs in human urine in small quantities as sodium Jiip|)urate (J to i gramme daih'). It is much more plentiful in the urine of herbivorous animals, such as the horse. It is increased in man by the ingestion of fruits, such as mulberries and cranberries, Avhich contain aromatic acids which are oxidized to benzoic acid in the body, and also by taking benzoic acid as a drug. Hippuric acid is of interest, >since its synthesis from benzoic acid and glycin takes place by enzymic action in the kidney itself. If the kidney be perfused with defibrinated blood containing these two bodies, hippuric acid is formed. C,H5C00H + CH0NH2COOH = CHoNH.COCeHs.COOH + HgO. Hippuric acid separates as crystals from the urine of the cow or horse on standing after the addition of 125 grammes of ammonium sulphate and 7-5 c.c. of concentrated sulphviric acid to 500 c.c. of urine. The crj'Stals, on evaporation with strong nitric acid, form nitro- benzene, with the odour of oil of bitter almonds. Ammonia generally appears in small quantities in normal urine, its amount varying according to the diet. When acids are introduced into the body, or acid formation takes place in the organism, the amount of ammonia in the urine is increased. The ammonia pro- vided by the liver neutralizes the acids. This is sometimes the case in diabetes mellitus and in eclampsia of pregnancy. Again, ammonia may be increased in the urine when the liver, the chief seat of urea formation, is diseased. Normally, about 0-7 gramme of ammonia escapes conversion into urea. Chlorides. — The chief chloride is that of sodium (1 gramme per 100 c.c. urine). It is derived chiefly from the " salt " of the food. The presence of chlorides in urine maj^ be shown by addition of silver nitrate and nitric acid to the urine, when a white precipitate is obtained which is soluble in ammonia. Without the addition of nitric acid, the phosphates of the urine are also precipitated. To estimate the chlorides in the urine, they are precipitated by excess of standard silver nitrate in presence of nitric acid. The excess of silver nitrate is then found by titrating with a standard solution of potassium or ammotiium thiocyanate. using iron alum as the indicator (Volhard's method). Chlorides are diminished in amount in the urine in many febrile affections, particularly pneumonia. Sulphates and Neutral Sulphur. — Sulphur occurs in the urine in three forms: (1) The inotgaiiic sulphates; (2) the organic or ethereal sul- phates; (3) neutral sulphur. Inorganic l^ulyliates occur as the compounds of sodiiun and potas- sium. Thej' are readily detected by adding a solution of barium THE URINE 46a chloride and a little hydrochloric acid to the urine. A white precipitate of barium sulphate results. The acid prevents the precipitation of phosphates. Organic or Ethereal Sulphates are compounds of sulphuric acid with such bodies as indol, skatol, phenol, cresol. Their presence may be sho\vn b}- precipitating the inorganic sulphates and phosphates Avith alkahne barium chloride, filtering, and heating the filtrate almost to boiling with strong HCl. By this means the organic sulphates are decomposed, and form a faint white cloud of barium sulphate. If they are in excess, a white precipate forms. " Neutral Sulphur " is the sulphur present in urine, not in the form of sulphate, but as an integral part of the molecule of the organic substance— e.^., cystin. About 2^ grammes of sulphuric acid (SO3) are excreted daily. The inorganic sulphates are derived mainly from the protein katabolism of the food. Inorganic sulphates — e.g., Epsom salts — are not ingested as such, owing to their unpleasant bitter taste. The ethereal sulphates are conjugates of sulphuric acid with toxic bodies formed by putrefaction of protein in the intestine, especiallj^ of the tyrosin and tr;>'ptophan portions of the molecule. The phenol, cresol, indol, and skatol, there formed are absorbed into the portal circulation, and combined in the liver with sulphuric acid, and so rendered harmless. Normally, the inorganic sulphates are about ten to tAventy times more abundant than the organic. The relative proportion, however, is not, as has been supposed, a direct measure of the putrefactive pro- cesses in the intestine. It has been found that this proportion, and that of the neutral sulphur, varies with the amount of nitrogen in the diet, as shown in the following table : Nitrogen-Rich Diet. Nitrogen -Poor Diet. Volume of urine .. .. .. 1,170 c.c. 385 c.c. Total nitrogen . . . . . . i 16-8 grammes. 3-60 grammes. Total SO;j 3-64 „ 0-76 Inorganic 3-27 ., (90 %) 0-46 ,. (60-5 %) Organic 0-19 „ (5-2°:) 0-10 ., (13-2 %> Neutral 0-lS „ (4:-8 %) 0-20 „ (26-3%) The best guide to the extent of the intestinal putrefactive processes is now believed to be given by the amount of indican present in the urine. Indican is the indoxyl-sulphate of potassium formed from the indoxyl brought to the liver in the portal blood (see p. 450). NH.CgHjOH +SOo<^g = S0.<^^''H6^' + H,0. Indoxyl Acid Ind'can potassium sulphate 464 A TEXTBOOK OF I'H VSlOLOOY Indoxyl is formed from iiidol (C^H-N) and jnobably in the intestinal wall duiing absorption. Indol is formed as the result of bacterial action upon tryi)tophane. The best test for indican is to add to the mine some concentrated HCl containing a trace of ferric chloride. Upon shaking with a little chloroform, indigo blue, or occasionally indigo red, is formed. Normal mine gives but a trace of colour, if any; with excess of indican the colour is deep. Phosphates. — These are grouped as — (1) alkaline phosphates of potassium, sodium, and ammonium; (2) earthy phosphates of calcium and magnesium. The two grouj)S occur in about the ratio of 3 : 1. Phosphoric acid forms three series of salts: Normal ])hosphate, Na3P04,Ca3(P04)o; mono-hydrogen phosphate, Na,HPO,,Ca2H(P04); di-hj^drogen phosphate, NaH.,P04,CaH.,(PO4).^. The normal and Fig. 225. — Calcium Carbonate (fkom Human Urine), x 400. mono-hydrogen phosphates are alkaline to litmus, the di-hydrogen to acid. The three sodium phosphates and the di-hydrogen calcium phosphate are soluble in water, the other two calcium salts are in- soluble. The deposit of phosphates which sometimes occurs is due to the earthy phosphates being precipitated when the urine loses its acid reaction. When CO., is driven from urine by heating, such a deposit of phosphates sometimes occurs. It is distinguished from a coagulum of protein by the fact that it is readily soluble in acetic acid. The earthy phosphates yield a white crystalline precipitate on the addition of ammonia. The presence of phosphates generally may be shown by adding nitric acid and ammonium molybdate to urine. Upon heating this, a yellow precipitate is obtained. To estimate phosphates in the urine, some acid sodium acetate is first added to the urine to prevent the formation of free nitric acid THE URINE 4G5 from the uranium uitrate employed in the titration. The urine is heated to SO'' C, and the phosphates are then precipitated by a standard sohition of uranium nitrate. A little powdered solid potassium ferrocyanide may be added as indicator. This turns brown when the end-point is reached. One c.c. of the standard solution equals 0-005 gramme of phosphoric acid. Xormally, about 2 to 3 grammes of the phosphoric ion (Po^^i) are excreted daily. This is chiefly derived from the phosphorus compounds of the food, inorganic phosphates, and organic phosphorus compounds, such as phospho-protein, nucleo-protein, and lecithin. A considerable proportion of the phosphates is excreted by the large bowel, particularly the earthy jihosphates. The deposit of phosphates which sometimes occurs in the urine of children is probably due to an excessive amount of calcium in the m'ine arising from defective excretion by the large intestine. Carbonates. — These occur as the carbonate and bicarbonate, particularh" of sodium, after the ingestion of organic acids in vegetables and fruits. A crystalline deposit of calcium carbonate maj^ be found (Fig. 225). On addition of acid, the urine effervesces from the evolution of carbon dioxide. The urine of the horse or cow is normally alkaline, and cloudy with phosphates and carbonates. Abnormal Constituents of the Urine. — The chief abnormal constituents met with in urine are protein, sugar, blood, and bile. V, — s < — ♦ Proteins. — Various proteins may be passed in the urine. In the condition known clinically as albuminuria the serum albumin and serum globulin of the blood pass through the kidneys into the urine. The former is usually in larger amount. Such a urine always gives an abundant froth on shaking. "" Albumin "' in the lu'ine is detected by the following tests, Avhich mu.st be applied to clear urine — i.e.. filtered or centrifuged — if necessary: (1) The urine boiled after bemg faintly acidified with acetic acid. Albummous urine gives a coagulum. (2) On the careful addition of nitric acid a Avhite ring (precipitate) appears at the junction of the fluids. This ring does not disappear on heating. Other tests mentioned in the section on the proteins {p. 46) may also be u.sed. It must be remembered, however, that normal urine contams a trace of protein, and the tests employed should be such as will reveal onh' an increase beyond the normal amount. For quantitative clinical jjurposes, a special form of test-tube is used (Fig. 226). This tube is filled with clear urine up to the mark U, and a mixture of picric and cit ic acids up to the mark R. If albumin be present, a whitish-j'ellow precipitate forms. On leaving 30 Fig, 226, — E s bach's Albumixo- METEK. 4GG A TEXTBOOK OF PHYSIOLOGY this to stand for twenty-four hours, the amount may be read off on the graduations of the tube. The figures correspond to the number of grammes of albumin present per litre. Normal urine yields a " mucus " on standing, which appears to be a mixture of nucleo-protein and gluco-proteiu. This is derived from the urinar}- trnft. .Tii catarrhal conditions of this, the amount of mucus may be so much increased that a condition known as "' mucin- uria '"" is met with. A white precipitate, insoluble in excess, and increased on boiling, is indicative of " mucin." The test often succeeds better when the urine is previously diluted to half its strength with \\'ater. Another abnormal condition of the urine hometimes met with is due to the presence of proteoses in the urine. These appear in the urine when disintegration of tissue is going on during an infective disease — e.g., in pneumonia, when an abscess known as empj'ema is forming. A special form of proteosuria, known as myelopathic or Bence- Jones proteosuria, occurs with a condition of diffuse malignant tumour (sarcoma) of the bone-marrow. Proteoses may be distinguished from albumin by the fact that the precipitate with nitric or salicylsulphonic acid disappears on heating, and reappears on cooling. The Bence-Jones proteose is further characterized by the fact that urine containing it becomes opaque at a comparatively low temperature (60° C), with the formation of a sticky coagulum. If the reaction be acid, this coagidum disappears on further heating, and reappears on cooling. With strong hydro- chloric acid this proteose gives a sharp ring, which also disappears on heating and reappears on cooling. Blood. — The red corpuscles or the blood-pigment may pass into the urine. The former condition is known as '' haematuria,'" the latter as " hsemoglobinuria."" When the urine contains but little blood, it presents a peciiliar '' smoky " appearance; with larger quantities, the urine appears red or reddish-brown, according to the variety of blood-pigment present. The presence of blood is detected clinically by making some of the urine strongly alkaline with caustic soda, and boiling. Should blood be present, a reddish-brown deposit is formed, "u ith greenish fluid above. Various drugs taken by the i:)atient, such as senna, rhubarb, may yield a similar result. The " guaiac test " (see p. 112) also serves to identify blood. There are certain fallacies in this test. Iodides in the urine may give it; also the presence of saliva, through spitting into the pot, and pus. In hsematuria, blood-corpuscles may be detected in the sediment after centrifuging or allowing the urine to stand. The spectra of oxyhaemoglobin or methsemoglobin may be obtained ; more often the latter. Occasionally, alkaline hamatoporphjTin is met with in considerable quantities in the urine, giving it a dark, port-wine colour. This is generalh' due to poisoning by drugs, such as sulphonal. Such a urine will not give the guaiac test, owing to the absence of iron in hsematoporphyrin. To identif}^ it, the pigment should be converted into the acid variety by the addition of hydrochloric acid, and, if THE URINE 467 iiecessar}^ extracted with amyl alcohol. The spectrum of acid hsema- toporphjTin can then be identified. Sugars in the Urine. — The sugar which, under certain conditions, appears in the mine is dextrose or glucose. Rarel}^ levulose, lactose, or pentose, may be excreted. Glycosuria is a symptom of the disease known as diabetes mellitus. It does not follow, however, that every person who is found to have dextrose in the urine has diabetes, although it is probable. Traces of dextrose occur in normal urine, but not in sufficient amount to give the tests for sugar as generally applied. Various other substances in the urine, such as glj^curonic acid, vu-ic acid, creatinin, phosphates, may give a positive reaction with Fehling's solution, which is the test most frequently emploj'ed for the detection of dextrose. This is a matter of considerable importance, for the presence of one or other of these substances may lead to a false diagnosis of sugar in the urine, a serious error, and one which falls particularly hard on candidates for life insurance. Therefore, the tests for sugar in urine should alwa3's be carefully applied. Trommer's test is not to be recommended, owing to the haphazard proportions of the testing solutions — copper sulphate and potash. Fehling's test is best applied by boiling the Fehling's solution and the urine in separate tubes, and then mixing the two. If reduction occurs ivithont further heating, it is almost certainly due to the presence of dextrose in the urine. Gtycuronic acid and compound glycuronates, uric acid, creatinin, phosphates, do not cause reduction under these conditions. A positive reaction obtained with Nylander's test is strongly con- firmatory, for. besides sugar, only glycuronic acid and its compounds will reduce the bismuth salt. The phenyl-hydrazine test helps to differentiate sugar, but the most certain test of all is fermentation with j'east. This should always be applied. An approximate estimate of the amount of sugar present in the urine may be made by taking the specific gravity of the urine before and after it has been fermented with yeast for twenty -foiu^ hours. Each degree of specific gravity lost equals 1 grain of sugar per ounce of urine. The quantity of sugar in the urine maj' be estimated in various other wa_\'s. The methods given here are not ver}' exact, but sviffice for clinical work. The standard solution of Fehling is generally used. A measured quantity of the solution is taken, and kept boiling in an open dish, while the urine, suitably diluted, is run in from a burette until the blue cupric solution is entirely reduced and decolorized. Ten c.c. of Fehling's solution are reduced b}^ 0-05 gramme of dextrose. The unmodified Fehling's method is not to be recommended, owing to the difficulty of recognizing the end-point. The use of an indicator, such as ferrous thiocyanate, is helpful. The end-point is reached when a drop of the solution no longer turns a drop of the indicator red. This shows that there is 408 A TEXTBOOK UF PHYSIOLOGY no cnpric salt left, for a cupric salt, when brought into contact with the ferrous thiocyanate, oxidizes it to ferric thiocyanate, which is red in colour. A modified Fehling's solution (Pavy's solution) has strong ammonia added to it. As this keeps the red precipitate of cuprous oxide in solution, the disappearance of the blue colour is evident. The end-point is reached when the solution becomes colour- less. Pavy's solution is ten times less strong than Fehling, 1 c.c. being reduced by 0-005 gramme of dextrose. The urine should therefore be diluted more before carrying out the test. In another modification of the test (GJerrard's), the red deposit of the Fehling's solution is held in solution by the double cyanide of potassium and copper. Gerrard's solution is mixed and boiled with Fehling's solution. In Bertrand's modification, the cuproiis oxide precipitate produced by the presence of the sugar is dissolved in a solution of ferric sulphate in sulphuric acid. During the process of solution, an amount of lerrous salt becomes produced, which is equiva- lent to the amoimt of cuprous oxide. The ferrous salt is then measured by titrating with a standardized solution of potassium permanganate. It is the most reliable method for estimating sugar in simple solutions. The polarimeter may also be employed to estimate the amount of sugar in urine, but it is necessary that the urine be absolutely clear, and not high-coloured. Protein, if present, and any other levo- rotatory substances, must be removed before the measurement is made. In diabetic urine, various volatile acids, such as /5-oxybutyric acid and aceto-acetic acid, are wont to occur in conjunction with acetone. The acetone bodies are also excreted in starvation or on a diet of fat with a limited amount of protein, in certain fevers, severe anaemias, and phosphorus-poisoning — conditions in which the tissues are unable to use glucose. These bodies are closely related, as their formulae show, the bodies Avith the smaller molecule being derived from those with the larger: /i-oxybutyric acid, CH3.CH0H.CIl.,.C()0H. Aceto-acetic acid, CHg.CO.CHg.CO^H. Acetone, CH3.CO.CH3. They are most probably derived from an incomplete breaking down of amino-acids, particular^ in the liver, and are therefore indirectly derived from protein (see p. 423). In starvation and in the last stages of diabetes, in diabetic coma, they are probably also derived from the higher fatty acids of the body fat. /3-Oxybutyric Acid, a volatile acid, is levo-rotatory, and does not ferment with yeast. No satisfactory simple test has been devised for its detection in urine. It generally occurs combined with am- monia, and an idea of the amount of the volatile acids of the urine can be obtained by the method already given (p. 454). Aceto-acetic Acid may be tested for by adding ferric chloride to the urine. If present, a red colour is obtained ; if small in amount, it may be first extracted with ether, to which a little sulphuric acid is added. THE URINE 469 Acetone gives a peculiar fruity odour to the urine. It is best detected b}- Rothera's test. Ten c.c. of urine are saturated with ammonium sulphate by adding the solid salt, and a few drops of a solution of sodium nitro-prusside and 2 to 3 c.c. of strong ammonia- added. On allowing to stand, a colour appears like that of perman- ganate of potash. Urine containing acetone will also jaeld the charac- teristic odour of iodoform when an alcoholic solution of iodine and a, little strong ammonia are added to it. Levulose. — Levulosuria by itself is a rare condition, but levulose occurs in the urine with dextrose in cases of " mixed mellitu "ia." The polarimeter and the resorcin test are used for its detection. Lactose. — "' Lactosuria "" occurs sometimes in mothers Avho are suckling their children. The sugar may occur in quite appreciable amount in the urine. The chief points Mhich aid in its detection are these : it reduces Fehling's solution; it does not ferment with yeast; it yields characteristic small rosettes with the phenjd-hydrazine test (see p. 65). Pentose. — "' Pentosuria " is a rare condition. It may occur tem- porarily as the result of large ingestion of fruit, such as cherries, grapes, and plums. Occasionally, a pentose occurs in conjunction with dextrose in cases of glycosuria. There is a rare anomaly of metabolism in which pentose occurs regularly in the urine. 8uch a pentosuria is accompanied by no morbid symptoms, is probably harmless, and needs no treatment. The pentose in question is usually arabinose. The low melting-point of the osazone (160° C). the non- fermentation with 3'east, and Bials orcin test, serve to indicate the presence of a pentose in the urine. Bile in the Urine. — In the condition known as '" jaundice,'' bile appears in the urine. As the result of obstruction of the bile-passages^ bile enters the lilood. and so reaches the urine. The bile pigments generally confer a greenish or brownish colour on the urine. They may be detected by the play of colours formed when fuming nitric acid is added (Gmelin"s test). The presence of bile salts in the urine may be best shown by Hay"s sulphur test. If " flowers "" of sulphur are sprinkled on the surface of urine containing bile, the sulphur sinks readily. Alkaptonuria is due to an inborn anomah' affecting i^rotein meta- bolism. It is of interest as throwing light on the halfway stages of protein decomposition, for it seems probable that the breaking down of the tyrosin group is not carried so far as usual, rather than that an abnormal body is formed. In the urine, homogentisic acid (di- hydroxji^henylacetic acid) is secreted. OH ICH,.C00H OH 470 A TEXTBOOK OF I'HYSIOLOGY The urine is natural in appearance when passed, but on exposure to iiir gradually darkens from the surface downwards, until it ultimately becomes a deep brown-black colour. Such a urine reduces Fehling's solution, but does not give Nylander's test. With Millon's reagent it gives a yellow precipitate; the addition of ferric chloride drop by drop causes a passing blue colour. It does not ferment with yeast, nor rotate the plane of polarized light. After poisoning with carbolic acid, the urine may contain a similar body. Alka])tonuric in-ine may be distinguished from one containing the pigment melanin by the fact that the latter does not reduce Fehling's solution. Cystinuria. — Cystin, di-amino-di-thiolactic acid is the suljohur- holding product of protein decomposition. It is a condensation derivative of molecules of cystein — thio-amino-propionic acid. Taurin (of the bile acid — taurocholic acid) yields cystein on oxidation. It does not normalh^ occur in the urine. It is a rare anomaly, the Fig. 227. — Cvstin Crystals, x 350. result of an inborn error of metabolism. It affects particularly the male issue of the marriage of near relations, such as first cousins. Cystin only occurs in acid urine. Six-sided cr3'stals of cystin (Fig. 227) may form from the urine on the addition of acetic acid, but usually the urine yields a dejiosit of these crystals. They are soluble in alkali. If some of the deposit be placed under a cover- glass, and strong hydrochloric acid added, delicate prisms are formed as the acid reaches the crystals. These disappear if water be added. Dissolved in caustic potash, cystin gives a violet colour when fresh sodium nitroprusside is added and the solution warmed. An alkaline solution of cystin gives a black precipitate of lead sulphide when boiled with lead acetate solution. Stones composed of cystin have rarely been found in the bladder. Urinary Deposits. — The deposits of normal urine vary in character, according as they are deposited from acid or alkaline urine. The following occur in acid urine: THE URINE 471 1. Uric Acid. — These appear as a "' cayenne -pepper " deposit at the bottom of the specimen, the crystals being pigmented with uro- erythrin. In shape, the crystals resemble Avhetstones, dumb-bells, orange pips, etc., and are often grouped together in rosettes (Fig. 223) 2. AmorpJious Urates occur as a brickdust or pinkish deposit. The}- consist of masses of amorphous granules tinted with urinary pigment. They easily pass into solution when the urine is warmed or rendered alkaline. 3. Sodium Urate. — This occurs but seldom in adults; frequently, however, in the urine of the newly-born. In appearance, the crystals resemble the thorn-a])ple, little spheres with numerous spines radiating from them (Fig. 222). 4. Calcium O.ralate occurs as characteristic colovirless, shining, '" envelope " crj-stals (Fig. 224). In reality, they are small octahedra. In some cases, calcium oxalate occurs also in dumb-bells forms. They are insoluble in acetic acid and ammonia, but soluble in hydro chloric acid. Fig. 228. — Triple Phosphate Crystals. 5:-^ "'^A:^ 'Jilt Fig. 229. — Stellar Phosphate Crystals. (Savill.) Rarely, deposits may occur in acid urine of — (a) acid calcium phosphate (C'aHPO^) — rosettes of prisms or dumb-bells; (6) hippuric acid, especially after the administration of benzoic acid — colour- less four-sided prisms, insoluble in Iwdrochloric acid, soluble in am- monia; [c) cyst in — colourless hexagonal crystals, often thrown out of solution b}- the addition of acetic acid, soluble in ammonia; (d) cones of leucin and white sheaves of tATosin. In alkaline urine, the chief salts to be deposited are the phosphates. They are all soluble in acetic acid, and the amount of deposit is in- creased by bailing. There occur — 1. (a) Most commonly the Phosphate of Calcium, "Earthy" Phosphate, Ca3(P0^).,, generally as white amorphous granules, more rarely as colourless prismatic crystals radiating in clusters. (b) Ammonium Magnesium Phosphate, MgXHjPOj, or Triple Phosphate, especially in urine which has undergone ammoniacal fer- mentation. In appearance, they resemble coffin-lids or feathery stars — ■■ feathery phosphates "' (Fig. 22">). 2. Ammonium Ura'e, especialh- in cases of inflammation of the bladder — " C3^stitis."' Small s]:)hei'ical cr^-stals resembling sodium 472 A TEXTBOOK OF PHYSIOLOGY urate, usually associated Avith lri|)le ]ihosphate crystals and bacteria 3. Calcium Carbonate. — Occasionalh' in hinnan urine, hut com- monly in the urine of herhivora. In hinnan urine, generally as amorphous gramiles; more rarely, as in horse's urine, as dumb-bells or spheres (Fig. 225). They are easily soluble, with eflPervescence, in acetic acid. In the urine there may also occur epithelium from the kidney, bladder, and urinary passages, and in women from the vagina. In pathological urine there may occur — 1. Red blood corpuscles, either normal, swollen, or crenated. 2. White corpuscles, or "" pus " corpuscles. 3. Fatt}" globules in '" liiDuria." 4. Various forms of "' casts " of the kidne}' tubules. r'HAPTER LVT THE SECRETION OF URINE In unicellular organisms of low activit}- there is no special structure for the excretion of the waste products of metabolism; the general surface of the cell serves as a medium for their discharge. In onc- -COLUECTTl/B?; !?■' COWVOL COLLECT: TV/BE. UBCTERIC BUD NEPHRrc Bud GROWING Et.D (uretet-ic) nephric Tubule Glomerulus s^C0LLECT:ru3S;. (Urcte)-ic) COLLECTING TUBES (B) Fro. 230. — Illustratixg the Development of the Rexal Tvbule. (Keith, after G. C. Huber.) A, Growing end of collecting tubule with nephric bud attached to it. B, First stage of development of nephric bud into nephi-ic tubule. C\ Fully developed renal tubule. The part formed from the ureteric bud is represented in outline ; the part from nephric tubule is shaded. celled organisms of greater activity there exist special contractile vacuoles, which from time to time expel from the cell waste fluid, which may contain solid particles. In such a fluid the presence of uric acid has been demonstrated. 47;J 474 A TEXTBOOK OF PHYSIOLOGY In the metazoa, the taking \ip of waste products is done by special- ized organs — the nephridia — which are bathed by the body fluid. In the verte])rates there are three stages of renal development. First, the pronephros which represents a collection of ])riinitive nephridia and excretes the waste jH-oducts into the crelom. The pronephros is represented bj^ the kidney of fishes. Secondly, the mesonephros appears ; thirdly, the metanephros. The mesonephros is re])iesentc(l by the kidney of the amphibia, the metanephros by the kidney of birds and mannnals. In the development of the human embryo, all three stages are rej)resented, a transitory pronephros at the third Aveek, then the mesonephros, from which the genital organs are developed, and lastly, the metanephros or permanent kidney. The last is formed by the combination of two'elements : a nephric or secretory part, a duct or excretory part (Fig. 230). The kidney is a collection of these elements, the whole being held together by con- nective tissue, and compactly bound up in a covering capsule. The Minute Structure of the Kidney Tubule. — Each tubule starts in the cortex of the kidney as an expansion — the capsule of BoAvman — into which dips a tuft of capillaries — the glomerulus. The wall of the capsule is formed of flattened endothelium, and is involuted by the tuft of the capillaries. The cells covering the glomerulus form a sjaicj^tium. The glomerulus itself is a lobulated structure. The endothelium of the ca]3sule and other parts of the renal tubule rests upon a homogeneous basement membrane. The cajisule narrows to a neck, also lined by flattened e]:)ithelium, and this passes into the first convoluted tubule. Here the epithelium consists of cubical granu- lar cells, called, on account of the rod-like disposition of the granules, *' rodded epithelium." Leaving this convoluted portion, the tubule narrows and passes down into the medulla as a long, straight limb, lined with flattened epithehum — the descending loop oS Henle. Turn- ing suddenly ujiAvards, it again passes into the cortex as the ascending loop o£ Henle. Here the epithelium is cubical and granular. In the cortex the tubule again expands as the distal convoluted tubule, Avhere the epithelium once more becomes "rodded."" Finalh', the tubule opens into a collecting tubule lined with a more flattened epithelium. This conveys the urine to the pelvis of the kidney (Fig. 231a). The Arrangement of the Blood-Supply. — In the mammalian kidney the renal artery, after entering the substance of the kidney at the hilum, breaks ujd in the boundary zone between cortex and medulla into a number of small vessels, which anastomose with each other, and give off branches both to the cortex and to the medulla. Of these, the arterise rectse pass downwards into the medulla, and form capillaries around the descending and ascending loops of Henle. The main blood-supply, however, j)asses by straight (interlobular) branches into the cortical zone. These give off on all sides small branches, which pass to the glomeruli. From the glomeruli pass efferent veins, which are of smaller calibre than the afferent arteries. These veins ]>artake of the nature of a " portal circulation," since from the glomeruli THE SECRETION OF URINE 475 they pass among the tubules of the cortex, and there again form a second capillary system which anastomoses with the capillary system Fig. "iSlA. — Diagram of Course of Two UiUNiFKKors Tri'.ULEs. (Klein.) ./, cortex ; B, boiuidaiy zone ; C, papillary zone of medulla : aa', supeiKcial and deep layers of cortex free from glome- ruli. •23lR. — Diagram of Distribution OF Bloodvessels in Human Kidney. ( Ludwig. ) ai. Interlobular arteries ; ri. interlobular veins ; g, glomerulus ; cti, stellate vein : ar, vr, arteria; and ven;^ rectte forming bundles ; ab, vb ; vp, venous plexus in the papillffi. of the medulla. Both systems then join to form the efferent veins, which anastomose in the boundary zone, Avliers^e larger veins run 476 A TEXTBOOK OF l»HVSlOJ.O(;^' to the hiluiii of tlie kidney, and together form the renal win (Fig. 23lB). Such an anatomical arrangement of tid)ules and blood-.siipply suggested to Bowman, who first described it. in 1840. that the urine had a double source of origin — glomerular and tubular. He suggested that the water and salts of the urine were filtered from the blood in the glomeruli, while the organic constituents of the urine were secreted by the tubules, especially by the convoluted portions. Ludwig laid stress on the vas efferens leaving the glomerulus being narrower than the vas afferens, and put forward the view about the same time (1844) that water and crystalloids of the blood filtered through the glomeruli, and the urine was concentrated from this by resorption in the tubules. A controversy arose aroimd these tAvo views, which resolved itself into a question of principle. The LudAvig view was the more mechani- cal one. It sought to minimize the unknown forces of the living cells, and to make the excretion of urine a question of filtration through the glomeruli and concentration by physical means in the tubules. The adherents of the Bowman view attributed special selective activity to the glomerular and tubular cells. The secretion of urine, to them, was a vital function, and not to be explained by known physical processes, such as filtration and osmosis. The glomerular epithelium secreted water and salts (NaCl, etc.), the tubules the sjiecific urinary substances (urea, etc.) and some water. The activity of the kidney was regulated by the amovmt of water and urinary substances in the blood, and the velocity of flow of the blood through the kidney. This is the view which has steadilj' gained supjDort. In the course of the controversy two salient facts have emerged: (1) That a concentration by resorption of dilute urine in the tubules cannot be brought about by such physical forces as osmosis; (2) that in the secretion of urine the kidney cells are performing work. In regard to the first point, it soon became clear that those physical forces which had been evoked by the Ludwig school, such as diffusion and osmosis, could not concentrate the weak urine supposedly filtered through the glomerulus. When blood and urine are placed on either side of a parchment membrane, water passes b}^ dialysis from the blood to urine. The electrolytes in normal urine are more concen- trated than in the blood. In the case of the urine passed after drinking a quart or two of water the opposite condition pertains. The kidney Works either way against osmotic force. It may secrete a urine Avith far more salt than in the blood, or a urine with almost no salt in it at all. In regard to the second point, it has been demonstrated that during the process of active secretion the amount of oxygen taken up by the kidney from, and the amount of CO.^ given up to, the blood i"s greatly increased. This is seen from the following figures: 0„ per minute . . . . . . 4-35 c.c. 5-58 CO.j per minute 1-88 c.c. 3-93 c.c Urine per minute . . . . O-Oo c.c. l-o3 c.c Work per minute .. .. 327*0 g.cms. irGl-Og.cn c.c. c.c. g.cm.s. THE SECRETION OF URIXE The work may be performed in an excretory direction or in an absorptive direction. For instance, to concentrate through a semi- permeable membrane the urine from the chloride content of the blood (0-38 per cent.) to that of normal urine (0-8 per cent.) requires the expenditure of a large amount of work on the part of the kidney cells. It would also require a large expenditure of work to separate, as after large libations, a urine consisting of little more than water. The questions in dispute, then, at the present time are these: (1) Is the Avork of the kidney performed in activeh^ secreting sub- stances in the glomerulus and in the tubules i or (2) is it secreting in the tubules only ? or (3) is the work performed in concentrating urine in the tubules ? or (4) is it concerned in all these processes ? Oi - 005- L,s(}, Ha^O^. Rlnqer- Solution. Fig. 2.32. Line^oxygeii consumption; black aroa = urine excreted. (Bareroft and Straub.) Valuable evidence has been adduced by the study of the action, upon the internal respiration of the kidney, of various substances, such as sodium chloride, Ringer's solution, urea, caffeine, and sodium sulphate — substances which stimulate the flow of urine, and act as diuretics. The last three substances, when injected into the blood, cause a diuresis which is attended by a markedty increased absorption of oxygen: 5 per cent, sodium chloride and Ringer's solution, on the other hand, cause a diuresis Avhich is unattended by any such increased oxygen absorption (Fig. 232). When the kidney cells have been poisoned b}^ mere iric chloride, the oxAgen consumption of the kidney almost stops. Sodium sulphate is then practically Avithout action in 478 A TEXTBOOK OK F^HYSIOLOGY causing diuresis; .sodium chloride still eoatinues to do so. Also it is found, under these circumstances, that if the blood be much diluted with Ringer's solution, the chlorine content of the mine closely approximates to that of the blood. From these experiments it would seem that the excretion of such bodies as urea and sodium sulphate call forth the cell activity of the kidne}', while chlorides do not. Such experiments, however, do not negative the view that work may also be spent in actively concen- trating the urine in the tubules. The theoiies of Bowman and Ludwig have been variously modified as the result of the ever-extending researches into the nature of the renal functions. The following are the chief modifications: 1. A modification of the original view of Lildwig. A dilute urine containing all the urinary constituents is filtered through the glomeru- lus, and becomes concentrated by cell activity during its passage through the urinary tubules. 2. Modifications of the original view of Bowman, (a) Water and salts are filtered through the glomerulus, and the organic constituents are actively added by the tubules. (6) The water and salts are actively secreted by the glomerular cells, and the organic substances by the cells of the tubules. 3. A combination of the above views — namely, that water and salts are either filtered or secreted from the blood in the glomeruli, and that the tubules have a double function — (a) to add the organic constituents of the urine by cell activity in one part of their course; and (6) to concentrate the urine by a similar agency in another part. It will be .seen at once that research resoh^es itself into an inquiry into — 1. The function of the glomerulus and its mode of action. 2. The functions of the tubules. The Function of the Glomerulus, — Three points have to be .settled: (1) Is a dilute urine filtered through the glomerulus ? or (2) are only the Avater and salts of the urine isolated in the glomerulus ? and (3) if so, is it by a simple physical process, such as filtration, or by an active process of cell secretion ? Those who uphold the filtration hypothesis base it, in the first place, uj)on the arrangement of the bloodvessels of the glomerulus. As measured in histological preparations of injected kidney, the afferent artery appears to be of greater bore than the efferent vein. It is suggested that this develops a high filtration jiressure in the capillaries of the glomerulus. It is claimed that evidence of this is afforded by the results of various expsriments which are directed towards the increase of the arterial pressure within the kidney, either by producing a general rise of arterial pressure or a local rise by causing vaso-dilatation within the organ. Whenever the pressure is thus raised — as, for example, by stimulation of the sj^inal cord after section of the renal nerves, or during the injection of large amounts of fluid, Avhich temporarily leads to a condition of plethora — there is an in- creased floAv of urine. When, however, the arterial pressure is lowered, THE SECRETION OF URINE 479 either locally, as b}' ligature of the renal artery, or generally by division of the spinal cord in the neck, then the secretion ceases. When the arterial pressure in the renal artery is diminished, as by stimulation of the spinal cord without previous section of the renal nerves, or of the splanchnic nerve, or by haemorrhage, then the flow of urine is diminished. Such experiments undoubtedly shoM" that, the flow of urine is increased, when the renal arterial pressure is high, and diminished when it is low. The results may, however, be correlated with the flow of blood through the kidney. \^'Tien the flow of blood is increased or diminished, so also is the secretion of urine. Against the filtration h}T3othesis is the fact that ligature of the renal vein, which certainly raises the pressure in the renal capillaries to the full arterial pressure, not oul}' causes no increased flow of urine, but stops it altogether. Again, when the renal artery is iigated for a few minutes, and the liga ture then removed, the floAv of urine does not immediately begin again for an hour or so, and, when it does, the character of the urine is pathological — it contains albumin. On the filtration hypothesis, it is assumed that F (the filtration pressure) = P (the kidney arterial pressure) ~p (the glomerular pressure ) . ¥ = F — jJ- This being the case, then, in the condition of F — {j^ + p^) — where/*/ indicates a slight obstruction to the flow in the ureter, and therefore a rise of glomerular pressure, and a consec£uent diminution of the filtration jiressure — there should be a diminished flow of urine. This, however, has been shown experimentally not to be the case. Indeed, under these conditions, there is an increased flow of urine, and if phloridzin is administered to the animal^ there is an increased ex- cretion of sugar as the result of this obstruction. The obstruction stimulates the kidney to secrete. Further, it may be pointed out that, according to the views ex- pressed in the section on capillary pressure, it does not seem possible for a high filtration pressure to exist within the glomeruli. The pulsatile force is transmitted to, and expands, all j)arts of the kidney. The histological examination of the kidne}- shows no evidence of membranes so arranged as to allow filtration from the capillaries into the capsules. There is nothing to keep the membrane separatmg blood and urine open and rigid as a filtration membrane. The capsule and tubules are surrounded by a membrane, but this is so arranged as to limit their expansion and allow the passage from capillary to lumen of tubule bj' osmotic or other forces set up within the tubule by the active secretion of the renal cells. The structural arrange- ments point to a pull of fluid from capillary to tubule, not to a mechani- cal push produced by blood-pressure. The process of secretion at the glomerulus must be just as much an act of cell activity as is the formation of the corresponding waste fluid in unicellular organisms, or in worms which have their nephridia bathed in blood-sinuses — conditions which clearly negative the filtration hypothesis. 480 A TEXTBOOK OF PHYSIOLOGY Whatever the nature of the mechanism may be, tlie passage of Avater seems to be carried out with a minimmn amount of work on the part of the kidney, as is shown by the fact that an intravenous injection of 5 per cent, sodium chloride solution causes a diuresis imattended by any increased oxygen absorption. The total osmotic pressure of the blood is equal to seven atmospheres, and if water were separated from the blood through a semi -permeable membrane, work woiild have to be done to overcome this pressure. If the water and salts of the blood, and not the urea, sugar, etc., were separated, the osmotic pressure overcome would be considerably higher than the blood- pressure. After dilution of the blood with 0-9 per cent. NaCl solution to pro\'t)ke diuresis, it Avas found that the kidney secreted urine M'hen the blood -pressure Avas loAvered even to 18 mm. Hg. Water flows from the ureter A\hen circulated through the blood- vessels of the dead kidney. In contiguity lie the renal A'essels, glomeruli, and the tubules, and it is probable that the membranes which separate these allow leakage in the poisoned or dead kidney. It becomes then an indifferent matter Avhether the Avater takes the channel of the tubules or A^enules. The kidney substance imbibes the water, becoming converted, so to speak, into a bog or morass. When a 0-75 per cent, solution of NaCl is perfused through the excised kidney of the ox, the filtrate varies very slightly from the jierfused fluid, and stoppage of the renal A^ein increases its amount. In the living kidney, the stoppage of the renal A^ein arrests the secretion of urine. It has been suggested that one function of the glomerulus is to act as a pulsating mechanism ^^laced at the commencement of the tubule. Undoubtedly, Avith each heart -beat the ui'ine is driven forAvard out of the tubules into the pelvis of the kidne3^ The whole kidney expands with systole and shrinks on diastole, and not only blood is expressed from the renal A^eins, but urine from the collecting tubules by each systolic expansion. The pulsatile expansion of the kidney is necessary for the normal secretion of urine. The Nature of the Glomerular Secretion. — At the present time it is impossible to say what is the exact nature of the secretion of the glomerulus. Probably the mechanism is such that water and salts, especially' chlorides, pass through with great ease. In cases Avhere by injury or operation the tubules in the medulla haA^e been largely destroyed, and the glomeruli in the cortex left intact, a much more Avatery urine is secreted. The proteins and the sugar of the blood are held back, by the glomerular membranes, since normal urine contains only traces of these bodies. When the glomeruli are damaged, these bodies may pass through into the urine, especially the blood-proteins. Direct leakage then takes place. It is a matter of doubt whether any of the nitrogenous constituents pass into the urine at the glomerulus. It may be concluded that its main function is the separation of water and salts. In the frog, the renal portal A^ein is the main blood-supply of the THE SECRETION OF URIXE 481 urinary tubules, and ligation of this vein affects but little the amount of urine secreted. On the other hand, ligation of the renal arteries which supply the glomeruli causes a cessation of the urinary flow. As a small amount of secretion may then be excited by the injection of a diuretic, it is concluded that the tubules can secrete some water. The Secretory Function of the Tubule. — If the kidne\- tubules are damaged by a poison, autl a solution of sodium chloride added to the blood, the excess of chloride quickly passes into the urine. On the other hand, if urea is added to the blood, it is not excreted. This experiment indicates that the chief secretory function of the tubules is to add the waste nitrogenous products to the fluid separated from the glomerulus. Confirmatory evidence has been obtained by mjecting into the blood of an animal an organic d3'e, such as indigo-carmine, which is sesreted in the urine. The site of secretion can only be ascertained after stopj)nig the glomerular secretion of water. This is effected b}' the fall of blood-pressure Avhich follows a section of the spinal cord. Under these circumstances, the convoluted portions of the tubules of the kidney are found filled with pigment granules. In the bird, after ligation of the ureter, there follows a ■deposition of urates (which correspond to the urea of the mammal) within the cells of the tubules. Uric acid and its salts can be stained with silver nitrate, and demonstrated AA'ithin the cells of the tubules, the stain being developed by a solution of hydro quinone. Vacuoles akin to excretory vacuoles have been described in the cells of the convoluted tubules. These gradually grow in size, and eventually' void their watery and granular contents into the lumen of the tubule. In thirst}' animals fed on dry food the cells fill up most of the lumen, and are full of granules. After diuresis, the cell are shrunken and the lumen is wide. Resorption by the Renal Tubules. — The evidence so far adduced in favour of resorption is far from conclusive. It is claimed that, after removal of the medulla of the kidney, there tends to be secreted a urine which is much more Avatery. It is also claimed that such a function is indicated b}' notable differences in the rate of secretion of two salts when injected into the blood in equal amounts of their equivalent solutions — e.g., of NaCl and NagSO^. The difference is equall}' well explained by a selective secretory activity. The kidney has the special function of turning out from the blood foreign salts, and of keeping constant the concentration of normal salts in the blood. " Pigment casts "" have been found in the collecting tubules after the injection of carmine into the circulation, and this may point to a coneentration of the urine, possibly in the second convoluted tubules. Onl}' a little carmine is to be found in the first convoluted tubules, for the glomerular secretion of water washes it on as it is secreted there. This is the best evidence so far adduced in favour of resorption within the urinary tubule. The concentration of urea in the blood is O-o to 0-6 per mille, 31 482 A TP:XTB00K OF PHYSIOLOGY and 30 grammew of urea may be secreted per diem. To effect this by resorption, 60 litres would have to be concentrated to 2 litres. Such an active resorption is possible for the amount of blood flowing through the kidnej^s is very large. It has been estimated at 300 to 600 litres, and even at 1,800 litres, per diem — an amount ample enough to allow resorption to play an active part. Intravenous injection of concentrated salt or sugar solution pro- duces diuresis both by exciting the renal cells and by making the blood more watery. The water is drawn into the blood from the tissues, and the concentration of the blood thus rapidly brought back ta normal. The diuresis is not large because the body holds to its water. The intravenous injection of isotonic and h3q:;otonic solutions both excites the renal cells and accelerates the blood-flow through the kidney; the water thus introduced produces much diuresis. Urea acts as a powerful diuretic, and causes vaso-dilatation of the kidnej'. Caffeine likewise, but this acts when the renal vaso-motor nerves are destroyed. Caffeine causes little diuresis in thirsty animals. To sum up, the balance of evidence at present available seems to indicate that the water and salt content (particularly chloride) of the urine are secreted by the action of the glomerular cells, and that the organic constituents of the urine are added by the cell activity of the tubules. The evidence in favour of a concentrating mechanism in the tubules is slight, but it is most probable that the urine is the l)roduct of the give and take of the renal cells, bathed as thej' are by the contents of the tubule on one side, and by the lymph which percolates from the capillaries on the other. There are diuretic substances in the blood which stimulate the kidney to secrete, e.g., urea; and the secretory activity depends on the amount of these substances — that is, on their concentration and on the volume of the blood passing through the kidneys per diem. The above view is strengthened by the fact that development ally the kidney has a double organ — a secretory and an excretory part. The Passage of Urine along the Ureters. — The urine collects in the pelvis of the kidnej-, and passes thence down the ureters to the bladder. The ureters are smooth-muscle tubes lined by transitional epithelium. The muscle is arranged in a circular outer and a longi- tudinal imier layer. It is probable that ganglion cells are j^resent between the muscular layers throughout the entire length, but they are particularly abundant in the upper and lower thirds. Under the influence of the secretorj- pressure, and in the erect man under the influence of gravity, the urine j)asses into the begin- nings of the ureter, which then by peristaltic movements passes the urine down into the bladder. These peristaltic movements occur regularly about everj^ ten to twenty seconds, being more frequent the greater the amount of urine, but the presence of urine in the ureter does not seem to be necessary to evoke them. They proceed over the ureter at a rate of about 20 to 30 millimetres per second. There is some doubt as to the exact nature of these movements. It ^^•as held that they were mj'ogenic in origin, because the middle THE SECRETIOX OF URINE 48S third of the ureter was believed to be devoid of a local gaiiglionated nervous mechanism. Such, however, is now known to exist, and it is highh' i^robable that the smooth muscle of the ureter executes^ these rhythmic peristaltic movements by virtue of a local nervous^ mechanism. Although the ureters are supplied by extrmsic nerves, the exact action of these is somewhat doubtful. It is stated that stimulation of the splanchnic fibres, which reach the ureter through the renal l^lexus, produce acceleration of the upper end of the ureter, wliile stimulation of the h^-pogastric nerves has a similar accelerator}' effect upon the lower end of the ureter. The ureters enter the bladder obliquel}' at the upper corners of the trigone of the bladder. This oblique course prevents a regurgita- tion of urine. The orifice of the urethra is closed by the thickened circular fibres at the base of the bladder — the internal sj)hincter — and bj' the voluntary muscle — the compressor urethrae — outside the bladder. The urine, therefore, gradually' accumulates in the bladder, and this gradually relaxes to accommodate its load. The incoming urine raises the pressure within the bladder up to about 15 to 20 c.m. of HgO. At this point the desire to micturate usually manifests itself, and the urine is voided. If, however, this be not done, the bladder further relaxes, and the desire passes aAvay for the time being. The Act of Micturition. — During the time that urine is accumu- lating within the bladder the organ performs rhythmic movements. As the organ fills, these gradually increase in force, until some urine is forced j^ast the internal sphincter, and then micturition may reflexly take place. This is the case in the decerebrate or spinal animal, or in the invoknitary micturition of children with weak control. Normalh', however, the reflex is curbed, and when there is desire to micturate, the passage of urine into the first part of the urethra is aided by the voluntary efforts of the individual. The intra-abdominal pressure is rai.sed b\' closing the glottis, so holding the diaphragm in the inspiratorj' position, and by contracting the muscles of the abdominal wall. The passage of a few drops of urine through the internal sphincter stimulates the sensory nerve-endings of the pelvic nerve. As a result of this, the sphincter of the bladder is reflexly inhibited, while the body of the bladder contracts dowai and voids its contents. IVIicturition is therefore a reflex act, the centre for which is situated in the lumbar spinal cord. This centre is, in the adult, imder the control of the will, but in the new-born this is not the case. A baby, for the first iew months of its life, passes urine in response to the demands of the lower, and not of the higher, reflex arc. It has to be taught control. In some, the nervous mechanism concerned in this reflex is overexcitable, so that even in adult life, when the cerebral control is cut off, either bj^ sleep or excitement, urine is reflexly voided. The efferent nerves concerned in the reflex are chiefly the pelvic nerves. In some animals the hypogastric nerves are also con- 484 A TEXTBOOK OF J^HV.SIOJ.OGY cerned. As indicated, the action of these nerves varies in different animals. It is possible that both are usually concerned in the act of micturition, particularly in raising the tension for the initial prt)- cess. The pelvic nerves, when stimulated peripherall}^ usually cause a marked contraction of the body of the bladder, and an inhibition of the sphincter of the trigone, while the hypogastrics cause an inhibition of the wall of the bladder. The latter are therefore mainly in action during the accumulation of urine within the bladder; the pelvic, on the other hand, during the voiding of the viscus. The hypogastric supply of the bladder affords an example of what is known as an " axon-reflex." If all the nerves connected with the inferior mesenteric ganglion be divided with the exception of the right hypogastric nerve to the bladder, then stimulation of the central end of the left hypogastric nerve will cause a contraction of the right half of the bladder. The explanation is that the preganglionic fibre branches in the ganglion, one branch forming a cell station with the right nerve, another branch continuing in the left nerve to the bladder. vStimulation of the left nerve therefore can influence the bladder through the cell station in the ganglion. The last drops of urine are expelled from the urethra bj^ the con- tractions of the bulbo-cavernosus (accelerator urinse) muscles. The act of micturition can be stopped by the contraction of the com- pressor urethrse, but it is difficult to do this when the reflex is in full action. BOOK IX THE FUNCTIONS OF THE SKIN AND HODY TEMPERATURE CHAPTER LVII THE FUNCTIONS OF THE SKIN One function of the skin is to confine and support the soft parts with a strong, pliable, elastic cover, and protect them from harm. Its structure is adapted to these functions. The skin, by virtue of its blood-supph' and sweat glands, also plays a great part in regu- lating the temperature of the organism, and by virtue of special nervous structures affords information of the nature of the surround- ings in which the organism finds itself. The skin, in addition, acts as an organ of excretion, and to a certain extent as an organ of absorption. In some animals, the skin serves a respiratory function. The skin consists of two parts — the epidermis, or outer skin, and the cutis vera (true skin), or corium. The epidermis consists of stratified squamous epithelium, and has no bloodvessels. The most external laj^er is known as the stratum corneum, or " horny layer." Its cells are largely composed of keratin, and are of a scaly nature. This layer is particularly thick in the jDalms of the hand and soles of the feet. The next layer inwards is known as the stratum lucidum. Its cells appear clear and free from granules. Within this layer is another, known as the stratum granulosum. Its cells are charac- terized by the presence of granules of eleidin, a substance which stains deeply with hsematoxylin. Beneath this comes the deepest layer of the epidermis — the rete mueosum, or stratum Malpighii (the IMalpighian layer), the cells of which are not horny, but protoplasmic in nature. It is in this layer that there is dej)osited the pigment melanin, which gives a characteristic black colour to the skin of the dark races. The cells are in more than one layer, those in the deepest are columnar, those above polyhedral in shape. They multiply in the deepest layer, and are gradually pushed out, and undergo the change into horny matter as the older layers are Avorn off. Tissue lymph soaks between the cells, and keeps up the transpiration of 485 486 A TEXTBOOK OF PHYSIOLOCY water from the surface. The lymph .'ffords niHtciial wliereby the chemical change into keratin is effected. The true skin — dermis, or corium — consists chiefly of connective tissue. The outermost layer is a dense fibrous tissue, which is thrown into multitudes of papillae or ridges. Corresponding to those are the patterns, seen on the surface of the epidermis, which cover the ridges. The patterns on the finger tips are peculiar to each individual, and afford finger prints for identification. This layer is well supplied with plexuses of capillary vessels, and also contains some of the organs of sensation, such as Meissner's corpuscles, etc. The deepest layer of true skin consists of fatty or adipose tissue. Besides serving as a fat dejjot, it is of importance in keeping the heat within the J''iG. 233. — MicKuscoPE, Low Poweii. Section through the Skin. A, Horny layer of cells; B, layers of soft growing cells; C, thick connective-tissue coat ; D, fat layer ; E, sweat-gland and duct ; F, hair ; O, sebaceous gland ; H, papilla of hair; J, small artery; K, muscle of hair; L, capillaries. "body. Arctic mammals are protected by thick layers of blubber. It also acts as a cushion, and gives softness of contour and beauty ■of form to the body. In some positions — e.g., neck, scrotum — plain muscles fibres are found in the corium. Connecting the two layers of the corium is a loose fibrous-tissue layer. Hair follicles are found in all parts of the skin of man, except in that of the palms of the hand and of the soles of the feet. They are developed from the Malpighian layer, which grows downwards into the corium. They consist of various layers corresponding to the epidermis and dermis, the hairs growing up from a layer of cells known as the hair bulb. Smooth muscle fibres, forming the pilo-motor nerves, are attached to each hair follicle, and cause it to stand erect THE FUNCTIONS OF THE SKIN 487 when in action. Nerves end in plexuses within the outer layers of the follicle. The mouths of sebaceous glands also open into the upper part of the hair follicles. These glands are situated in the Malpighian layer, and are of a comi^oiuid saccular form, and lined by cubical ■cells. The thick epidermis protects the underlying structures from the ceaseless frictional contact with the external world, and wards off wounds and invasion by pathogenic organisms. The nails were originally weapons of offence, as well as of defence. The hairs shoot off the rain, and keep the body dr\'. They also, when touched, stimulate organs of sensation. Tne fur of animals prevents loss of heat by convection. Man developed as a tropical animal, with scanty hair, and endures the cold of the temperate and Arctic ■climates b}" fashioning clothes of the hair of animals or fibres of plants. The fat of the deep layers protects against heat loss, aiid also serves as fat depots for the body against times of stress (starva- tion). The ceruminous glands of the ear, by the odour and bitter taste of their secretion, are said to prevent insects entering the external ear. The sebaceous glands, by their secretion — the sebum — -keep the skin supple, and protect it from the drying effects of the atmosphere, and from the ill-effects of immersion in water. Moreover, pathogenic organisms cannot grow through this secretion. The sebum is of a fatty or waxy nature, containing fatt}' acids, which render it acid, and iso-cholesterin. It is continuously secreted by the sebaceous glands, Avhich occur mainly in the regions supplied Avith hair, the mouths of the glands opening into the hair follicles. Tne secretion is squeezed out of the gland by the contractile action of the smooth muscle supplying the base of the hair follicle. Sweat Glands. — From the stratum Malpighii are developed sweat glands. These lie in the deeper layer of the corium, and are particu- larly abundant in the palms, soles, forehead, and axillae. There are estimated to be per square inch of skin: Neck, back^ Back 417 Buttocks J Chest and abdomen . . • • ^>]}l^_ Thigh, inner surface . . • . 570 Thigh, outer suviace . . . . 554 The gland proper is situated in the dermis. It consists of a coiled tube, lined with a single layer of secreting cells, arranged upon a basement membrane, on the inner side of which lie some smooth jnuscle fibres. The dusts are lined with cells in the corium, and form Forehead . . . . 1,258 ■Cheeks 548 Hand, palm . . 2,736 Hand, back .. 1,490 Foot, scle . . 2,(538 Foot, back 924 Xeck, front and sides . . 1,303 488 A TEXTBOOK OF PHYSIOLOGY a spiral passage through the epidermis, and so reach the surface of the skin. The perspiration, or sweat, is a watery fluid (99 per cent, is water), generally neutral or faintly alkaline in reaction. The 1 per cent, of solid.s is chiefly sodium chloride and fatty bodies, as is seen from, the following table: Water . . . . 98-88 Solid.s .. 1-12 Salts . . 0-57 Sodium chloride 0-22-0-33 Alkaline sulphate.s, ]ihosi)hates, lactates, and potassium chloride 0-lS Fats, fatty acids and cholesterol 0-1] Epithelium . . 0-17 Urea . . . . 0-08 Usually the excretion of urea by the skin is negligible, but during a day's march on a ver\' hot da}^ as much as 12 per cent, of the total nitrogen outj)ut ma}- be excreted in the sweat. Sometimes a pink sweat is secreted in the axillae, coloured, it is said, by products of putrefaction absorbed from the large intestine. The amount of sweat varies largety with the temperature of the surroundings and the heating of the body by muscular work — e.g., 600 grammes on an ordinar}-, and 3,000 grammes on a warm day in which considerable exercise is taken. The function of the sweat is to moisten the skin and to cool the bodj- by evaporation. As the evaporation of 1 gramme of water requires 540 calories, we see the cooling efficiency of the sweating mechanism. A man without sweat glands was only able to work in the hot sun by wetting his shirt frequent!}-, and so artificially making good the absence of sweat. In a hot chamber his bod}- temperature quickly became febrile. The importance of the sweat as an excretion of material is little or nil. Sweating is under the control of the central nervous sj^steni; the centre is stated to be situated in the floor of the fourth ventricle, and is provoked by a rise of temperature of the blood which circulates through it. >Such a rise is generally produced by muscular Avork. Experimentally it can be shown that the warming of the carotid blood induces sweating. It may also be stimulated b}' increased con- centration of COo in the blood, as in asphyxia, and by certain drugs known as diaphoretics — e.g., mori^hine. The centre is also affected by afferent nervous impulses. Stimula- tion of the central end of the sciatic nerve causes sweating reflexh'. Such sweating is associated with a vaso-constriction in the limb, showing that the vaso-dilatation of the skin, which generally accompanies sweating, is not a necessar}-, although a favourable, condition. The efferent channels for the sweat nerves run in the .sympathetic system, arising from the thoracic region of the .spinal cord (see pTcO)- Communication is established with the .sympathetic ganglia by the white rami communicantes of the various nerves. Leaving the ganglia, THE FUNCTIONS OF THE SKIN 481> the grey rami commumcantes establish connection with the nerves supplying the skin of the various parts of the body (sea p. 750)- After the spinal cord has been divided, sweating does not take place in the parts below the lesion. Sweating is provoked in the pads of a cat's foot on stimulating the peripheral end of the sciatic nerve. A few beads of sweat will appear if the nerve be stimulated just after amputation of the foot, but its amount is very scanty in tha absence of blood-flow. The secretory pressure of the sweat, when this is obstructed, rises higher than the blood-pressure. Sweating, therefore, is the result of an active secretion, and not a mere mechanical transudation of fluid from the blood. It is accompanied by an electrical variation in the skin current, as maj' be demonstrated in the pad of the excised cat's foot, if this be led off to the galvanometer, and the sciatic nerve excited. The nerve-endings in the sweat glands may be paralj^zed by atropine, and stimulated bj^ pilocarpine and physostigmine applied localh\ Transpiration of water from the bloodvessels through the skin is continually taking place. The skin is thus kept supple and moist. The loss of water by transpiration is insensible perspiration, and it increases with the temperature of the skin. Sensible perspiration is produced by the action of the sweat glands. Absorption by the Skin. — For a body to be absorbed by the un- broken skm, it is necessary' for it either to be of a fatty nature or to be administered in fat. Thus, it is stated that cod-liver oil rubbed into a weakly child serves as a source of nutriment. Mercury has been administered in the form of an ointment. Watery fluids are not absorbed. For such a fluid to pass into the tissue lymph, it is necessary to abrade the skin, as in vaccination. A foreign protein injected subcutaneoush^ sensitizes the body, so that a subsequent injection of a trace of the same protein made a few weeks later may produce shock, or death, the phenomena of anaphy- laxis (see p. 111). The mere washing of the uninjured skin by the solution of foreign protein has no such effect, showing that none is absorbed. The Respiratory Function of the Skin. — The amount of CO^ given off by the skin of man is very small. It increases markedly during sweating, and mav become two to four times as great as before. This is seen in the following figures obtained from a naked man: Water per Hour. CO2 per Hour. Temp. 0 jAir 29-8= 35-4° 38-4° C. C. c. c. 22-2 grammes 0-37 gramme 50-3 „ 0-35 IOC'S „ 1-04 grammes 158-S ,, 1-23 490 A TEXTBOOK OF PHYSIOLOGY When clothing is Avorn, the increased COg and water output occurs at a lower temperature : Temp, oj Air. Water per Hour. CO2 p(ir Hour. 28-9° C. 31-8° C. 32-7° C. 33-4° C. 50-S grammes 110-1 119-1 122-3 0-33 gramme 0-30 0-37 0-80 These observations were carried out in still air in a respiratory chamber. In frogs and kindred animals, the exchange is great enough to enable the animal to live without lungs. There is a special pulmo- cutaneous circidation for this purpose. The Function of Pigment. — The value of pigment in the Malj)ighian layers of the skin of man is to protect against the lethal cflect of intense sunlight. Rays are absorbed by the pigment of the skin, and converted into heat-rays, which in their turn increase the transpiration of water from the cutaneous capillaries, and stimulate the cutaneous nerve -endings, and jjrovoke sweating. Thus, the energy of the sun is sweated off the body of the black man. On the other hand, rays penetrate to the blood of the white man, and are absorbed by the haemoglobin, and there converted into heat-rays. Moreover, the rays j^roduce sunburn in the skin of the white man, resulting in joig mentation. The white man, therefore, to keep whik . has to wear clothes and to shelter himself from the sun, while the black man is happy naked. The white man wears white clothes in the tropics to reflect and scatter the sun's rays; also these, by entangling air, lessen the loss of heat by convection and evapora- tion. Thus, the clothed white man cannot do field labour and be comfortable in the tropics, and fans are of the utmost necessity for securing his comfort and efficiencj^ indoors. The naked black man is physiologically efficient for life in the tropics. The absorption of rays by the skin of the negro is jDrobably the reason why the photograph of the naked negro is less distinct than that of the white man, from whose skin more rays are reflected. The j)igment is not derived from blood-pigment, but belongs to a group of bodies known as melanins. The pigment of the hair and skin of the negro has been found to contain about 15-5 per cent, of nitrogen, 3-6 per cent, of sulphur, and a trace of iron, the pigment of the hair containing less nitrogen than that of the skin. The pigment is probably derived from t3Tosin by the action of an oxidase. In addition to the function of protection against the uun's rays, })igment is used among animals for various other purposes. Animals, such as the Arctic fox and hare, may undergo seasonal change of colour for jarotective purposes, changing a brown, soil-colour summer coat to a Avhite, snow-colour winter coat. The change seems to be THE FUNCTIOXS OF THE SKIN 491 more than one of colour, for a white rabbit, or an Arctic hare in its winter coat of Avhite, is immune to an intravenous injection of nucleo-protein, which produces in the pigmented animal coagulation of the blood. Pigment is used for purposes of offence as well as of defeni-e. It is particularly marked in reptiles, amj)hibia, and fishes. Pigmen- tation also plays a marked part in the sexual relationships of some animals, particularh' of birds. The male bird is decked in vivid colours, especially in the springtime of active com'tship. True albinos are devoid of pigment, and their irises are pink owing to the reflexion of light from the blood circulating therein. CHAPTER LVin THE TEMPERATURE OF THE BODY Man, in common with other mammals, belongs to the group of warm-blooded or homothermic animals. In this group the internal temperature of the body, under normal circumstances of life, is kept aj^proximately constant. During the katabolic processes of the body heat is constantly evolved, chiefly in the muscles and the glands. It is estimated that, of the 1,700 calories of heat produced per diem by a man of 11 stone when fasting and resting quietly in bed, about 1,200 calories are pro- produced in the muscles, and 500 in the glands. On the other hand, loss of heat is constantly occurring from the surface of the body by radiation and convection, and b}' the evaporation of sweat. A certain amount of heat is also lost through the lungs. It has been calculated that an adult man in a ;itill atmosphere of medium temperature loses 43-7 per cent, of his heat by radiation, 31 per cent, by convection, 20-6 per cent, by evaporation of sweat, 1-2 per cent, in warming in- spired air, 1-5 per cent, in warming the food and drink, 1-8 per cent, in performance of external work. These proportions vary with the temperature, as is shown by the following table : Extern II ' Total Heat Tempenitiire. produced. Deg. C. Cal. per Kg. 7-6 83-5 15-0 63-0 20-0 53-5 25-U 54-2 30-n. 56-2 Loss hy Con- vection and Loss hy Radiation. Evaporation. Cal. Cal. 71-7 11-8 49-0 14-0 37-3 16-2 37-3 16-9 30-0 2()-2 As the temperature rises the loss by convection and radiation decreases, and that by evaporation rises. The Normal Temperature. — The normal temperature of man is usually stated to be 98-4° F. This is the temperature as ascertained by taking it in the mouth or axilla. This method is liable to con- siderable error. A more correct idea of the true internal temperature may be obtained by taking the temperature in the rectum, or b}' passing water and holding the bulb of the thermometer in the stream of urine. 492 THE TEMPERATURE OF THE BODY 493 The rectal temperature is normally about 99-6° F., the '' urhie " tem- perature about 99° F. Owing to the loss of heat from the surface, the temperature of the skin is not so constant as the internal temj)erature of the body; in fact, it shows considerable variation according to the surrounding conditions. For example: Indoors. Ten Minutes after a Swim in Sea. Chest . . 30° C. 24° C. Cheek . . 32i° C. 25i° C. Neck . . 33° C. 31° C. Back of hand . . 31° C. 24i° C. Arm . . .. 3]i°C. 29|° C. Abdomen . . 33° C. 26|-° C. Leg . . 32° C. 30J ° C. In a cold wind the cheek temperature may be as low as 15^ C. In hot, moist atmospheres the skin temperature rises up to the internal temperature of the bod}'. Too much uniformity of skin temperature is undesirable. p. 7 8 9 10 11 12 1 2 3 i 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 0. 99*6 37 37 37 37 37 37 36 36 36 36 36 36 36 56 W W4 ^ ^ S ^. W? / \ .^ ^ N \ •^cf pit-n / \ 00 9S-8 / \ 11 AST) / \ 00 98-4 / \ 8Q 98-2 / \ VR <»s-n / \ 67 07-8 / \ S6 *)7-6 y^ \ 44 fl7-4 1 / ^^^^ fl7-? \ / 99 Fig. 234. — Daily Vaki.atiun of Temperature of Man. (M. S. Pembrey.) While the rectal temperature represents the body temperature, that of the mouth rises and falls with the cooling power of the atmo- sphere. It is therefore illusory to fix the mouth temperature at any given figure. In the Arctic region, when the outside temperature ranged from 12° to 30° C. below zero, and that of the engine-room of the ship was 37° C, the mouth temperature varied from 34-58° C. to 37-45° C— i.e., 5-17° F. The mouth is cooled through the floor of the mouth rather than through the inspired air. After drinking hot fluid, the mouth will give too high a reading. The temperature of man shows a daily variation dependent for the most part upon muscular activity. It rises during the day to a maximum about 6 p.m., and falls during the night to a minimum about 2.30 to 3 a.m. Night work, depending largely upon its severity. 404 A TEXTBOOK OF PHYSIOLOGY reverses or tends to reverse this curve. In nocturnal birds the tem- perature rises during the night, and falls during the daj'. On travelling from Australia the curve adjusts itself as night becomes day. The clergyman, the navty, and the sailor, show temperature curves which vary 'with the occupations and mode of life of each. A man resting in bed shows the same variation, but not to so marked an extent. The diurnal variation is accounted for b}^ the " restlessness " during the day as compared with the deep rest of sleep during the earh' night hours. It is more difficult to get absolute rest in the light and noise of daytime. Infants, in the first few weeks of life, show no marked variation. The taking of food, especially if it be warm or involve much work on the part of the glands and muscle? cf mastication, may raise the general temperature of the bodj- slightly. It plays no part, however, in the production of the daih^ variation, which is approximately the same whether a man be taking food or starving. Muscular activity raises the body temperature. After a three- mile race the rectal temperature in a man not in good training was as high as 105° F., and did not reach normal again until the sixth hour after the race. After a strenuous game of football, rectal tem- peratures of 102° to 103° F. are the rule. This is owing to the large amount of heat liberated by the muscles during musciilar work (see p. 552). If the subject be unsuitably clothed, and do hard muscular work in a warm, windless atmosj)here, there may result " heat-stroke." Such a danger arises in the marches of soldiers in close formation on warm, windless days. This is because the loss of heat from the body cannot, under these conditions, keep j^ace with the heat production. The subject, owing to his clothing and the high external temperature, cannot lose heat rapidly enough bj' convection and sweating. The clothes entangle air, and keep it stationary. This air is warmed and moistened by the skin, and thus the body is enclosed in a layer of stagnant humid air. In a crowd, too, the air is confined between the bodies of the people. Wind sweeps the stagnant air out of the clothes, and by throwing off the coat and opening the shirt we gain relief. The clothing should be adapted to the requirements of climate and occupation, not to fashion. The highest temperature recorded with recovery is in a case of malaria (45° C.) or 113° F. ; the lowest tem^Derature with recovery, 22-5° C. It has been shown that rabbits lowered to 31° to 34° C. breathed more slowly, and could not raise their temperature by shivering. At 26° to 29° C. their nervous co-ordination was damaged, and they were easily hjqDnotized. At 26° to 22° C. the arterial pressure began to fall ; stimulation of the skin provoked twitches. At 19° C. the vital centres became paralyzed, and death ensued. The tempera- ture in local peripheral parts may be lowered far more, and these parts recover from the temporary " numbness." Prolonged and excessive cold leads to local death and gangrene (frost-bite). Generalty speaking, the internal temperature of birds is warmer THE TEMPERATURE OF THE BODY 495 than mammals, and the temperature of small warm-blooded animals is in most cases higher than that of large ones. This can be seen from the following table : Hedgehog . . 34-8"-35-5° C. Man, rectum . . 37-2" (98-96^ F.) Dog . . 37-5^-39-5° C. 1 „ axilla . . 3(v9= (98-45=' F.) Rabbit . . . . 38-3°-39-9° C. ! „ mouth .. 30-87° (98-36° F.) Guinea- pig . . 37-3°-39-5° C. Infants . , 37-6^ Pigeon . . 41-0°-42-5° C. The lower vertebrata, such as reptiles, fish, amphibia, are cold- blooded— that is to say, they maintain their bod}- temperature scarcely above that of the surrounding air or water. Fish may be frozen, and recover if carefully thawed. A frog in winter becomes cooled down, and hibernates; in summer it is warmed up, and becomes active. The mammal, by maintaining a uniform body temperature, is active in all the seasons. A hibernating mammal changes from warm- to cold-blooded when food becomes scarce in the winter. A hibernatmg animal will not allow itself to be frozen. It wakes up, and in a short while becomes warm-blooded. In between these two classes — warm- and cold-blooded — come the rarer egg-laying marsupial;; of Australia, such as Echidna and Ornitho- rhynchus. The power of these animals to regulate their body tempera- ture at a constant level is less well developed than in mammals, but their temperature in a cold atmosphere is always manj- degrees above the surrounding medium. For example, the normal tempera- ture of Echidna is — At 4° C 25-5° C. At 20° C 28-6° C. At30°C. 30-9° C. At 3.5° C 34-8° C. The Regulation of the Body Temperature depends upon nervous control. In young birds just before hatching, and in prematurely born mammals, this mechanism is not working, they have to be kept warm. A child born at the seventh month has to be carefully wrapped in cotton-wool, or even placed in an incubator. At birth at full time, on the other hand, the heat-regulatmg mechanism is working in man, and for this reason so much care need not be taken to prevent heat loss. Some mammals, such as the rabbit, which is born naked, do not acquire the power of regulation until a considerable time after birth. The newly-born guinea-pig, on the other hand, is born covered with hair, and can regulate its temperature. The newly hatched chick can regulate its temperature; the naked young of mam' birds, on the other hand, are not able to do so. The evidence as to the existence of a centre regulating the temperature of the body is conflicting. It is known that lesions of the central nervous system in certain regions — e.g., the optic thalamus and corpus striatum, pons, and medulla — produce an upset of the power of heat regulation, but it would not be exact to describe any one of these sites as the " heat -regulating centre " of the body. 496 A TEXTBOOK OF PHYSIOLOGY The nervous sj^stem regulates the body temperature iii two ways : (1) By the control of the sites of production — the muscles and the large glands; (2) bj^ the control of the structures concerned in heat loss- — the cutaneous bloodvessels, the sweat glands, etc. That heat is developed in the muscles has been demonstrated (see p. 552). It has not been shown in other organs, but the respiratory exchange in the glands proves that heat is developed therein. The circulation through a gland is so rapid that the heat formed therein is at once distributed through the body; thus even the most delicate thermo- meters fail to shoAV that the gland is hotter than the blood. The Regulation of Heat Production is controlled reflexly through the sensitivity of the skin to changes of temperature. The sensation of cold increases the tone and activity of the muscles; shivering in- creases muscular activity without displacing the layer of air which is in contact with, and warmed by, the body. It may increase the heat production of a man at rest from 50 to 90 per cent. The cooling of one leg in a bath of cold water may provoke local shivering in that leg. Exposure to cold leads us voluntarily to increase our muscular movements. We move about, stamp our feet, and beat our arms, in order to keej) warm. A certain degree of exjoosure to cold is therefore valuable. It stimulates the tone, metabolism, and activity, of the body, and in this lies the healthiness of open-air life. The activity of the body provoked bj' cold leads to an ampler ventilation of the lungs and a more vigorous circulation of the blood. By raising the metabolism, it increases the appetite and better digestion of food, thus lessening the bacterial decomposition of food in the large bowel, and preventing the absorption of toxic j^roducts therefrom. The cooling effect of the wind is far more powerful than that of the surrounding temperature, and is the most important quality of open fresh air. It not only €ools, but by its varying stimulation of the skin prevents monotony of sensation and invigorates. Ideal outdoor conditions are the radiant heat of the sun warming the ground and thereby the feet and those parts of the body turned towards it, together with a cooling wind blowing on the face. On the other hand, the sensation of heat produces relaxation of the muscles, a lessened tone and activity, and diminished metabolism. Too warm an atmosphere — in particular, one that is windless and monotonous- — is therefore disadvantageous, on account of its relaxing effect. The Regulation of Heat Loss is accomplished by the nervous control of the loss of heat from the skin by radiation, convection, and evapora- tion. This regulation is brought about through the vaso-motor oentre and the centre controlling sweating. The afferent channels concerned in the regulation of the cutane nis bood-supply are chiefly those from the skin. The sensation of cold causes a constriction of the cutaneous bloodvessels, and thus diminishes the loss of heat. On the other hand, a sensation of warmth induces a flushing of the THE TEMPERATURE OF THE BODY 497 <3utaneous vessels, which greatly facilitates heat loss by convection ■and radiation. Sweating is controlled by a centre in the medulla which is stimulated reflexly, or directly by the temperature of the blood passing through it. When this temperature is raised by warming the ■carotid arteries, visible beads or drops of sweat are secreted by the «weat glands, and these, by the cooling produced by their evaporation, greatly aid in the cooling of the surface of the body. The effect of raising the external temperature upon the water output, the heat production, and the carbon dioxide output of the body is seen in the iiccompanying charts (Figs. 235, 236). i i Wa'cr Output CO2 Outpi-ct SaUiraJtiort detitit ..^- Fig. 235. — The Effect hf kaisin.;; the Exters.ax Temperatfue ox the Water Output and Heat Productiox. Saturatiox Defk it ixdicates Relative Saturatiox' of Air with Moisture. (Rubner.) ■^ VfaOr Output of fastinq (lop. i 1 i i / *> <, Saturatinn, deticit y. / d \ -^. .--- -— 1 _ --^' . — Tctn percL ure 75 10 ^ ^ ^5 ^ ^ Fig. 23(). — The Effect of raising External Temperature ox Water and Carbon Dioxide Output. (Rubx-ier.) The amount of heat lost in the expired air may also be regulated. Warming the carotid artery leads to increased breathing, and this increases the evaporation of water and heat loss. The loss of heat by evaporation demands further consideration. The rate of evaporation from a Avet surface at body temperature in still air depends directly upon the vapour pressure of the surround ing atmosphere, and is independent of either the temperature or barometric pressure of the atmosphere. The skin may be regarded as a porous wall backed by capillary vessels, by means of which moisture is supplied. The capillaries are profoundly affected by physical conditions without — e.g., constricted by cold — and by phj'siological •conditions within — e.g., flushed with wine. Simple diffusion of aqueous vapour away from the body would be 498 A TEXTBOOK OF PHYSIOLOGY I'elatively a very slow process; but as aqueous \apour lias a density of onh 0-62. air being taken as unity, and as the cooler air of the atmosj)here is warmed and expanded by the body heat, the body itself sets uja convectional currents which greatly accelerate the loss of vapour. At 32° F. saturated air holds l,'^Jth of its weight of water vapour, at 59° F. J^th, and at 86°, F., ^Qth.. The body warms up the air in contact with it, and saturates it at skin temperature. The air entangled in the clothes thus warmed and saturated cannot escape easih^ if the atmosphere is still. Wind carries away the air as fast as, or much faster than, the skin M-arms and saturates it. Thus, wind enormously increases the cooling of the body surface both by convection and evaporation. The skin resjaonds to a cold dry wind by vaso-constriction and diminished transpiration of water. The skin becomes pale and dry. and the heat loss is thus cut down. We seek shelter, and put on more clothes. On warm, close days the skin becomes flushed and moist, we throw off clothes, and make use of fans. Water vapour is a far better conductor than dry air, and tin s damp cold air feels raw and chill, while dr}^ cold air is pleasant. Water has 240 times the thermal conductivity and 3,000 times the heat capacity of air. The particles of cold or even freezing water in a winter fog strike the cold nerve-endings, and by cooling these give us an unpleasant chilly sensation. The fog, by penetrating into our clothes, robs these of their protecting value. The intensity of the temperature sense depends on the difference between the blood-temj)erature within the cutaneous capillaries and the surface temperature of the skin without. The fog gives us a shower of cold particles of water, while a cold dry wind constricts the bloodvessels of the skin, and, while having a far greater cooling effect, dees not give us the same sensation of chill. Water vapour, like glass, is almost opac{ue for the least refrangible rays — the infra-red — and transparent for the middle luminous anel calorific radiations. Thus, on a cloudy day the water vapour both scatters and absorbs the dark heat rays, and less heat reaches the earth. On tl e other hanel. clouds after a sunny day. just as a glass-house, ]3revent the escape of the dark heat rays from the earth, and cause a w^arm night. On a clear night these rays raeliate into space, anel the earth cools. The transparency and eliathermancy of the air are properties of the greatest importance, since living energj' is derived from the sun's light and heat. Water vapour and dust in the atmo- sphere serve both to soften the scorching power of the sun and to prevent the rapiel scattering into sj^ace of the heat gained by the earth. The motive-powers of the atmosphere are convection and evapora- t ion produced by the sun's heat . The Avinds arise from the elisi^lacement of the warm moist and therefore lighter air by cold heavier air, and the rain falls as the moist air becomes condensed in higher altitudes or against colel lanel surfaces. The beauty of earth anel sk}^, the glories of sunrise and sunset, depenel upon the particles of dust and vapour in the atmosphere. The particles reflect anel scatter the shorter rays and transmit the longer. At sunrise anel sunset the oblique rays pass THE TEMPERATURE OF THE BODY 409 through a much greater depth of atmosphere; hence the greater splendour of the colours. As the temperature of the air and surrounding objects is made to approach that of the body, loss by radiation and convection becomes small, then nil. Finally, as the air temperature comes to exceed that of the body, heat passes from the air to the body. The body, however, does not become heated so long as the air is dry. The sweat glands come into action, and the body heat continues to be lost by conversion of water into aqueous vapour. The difficulty of main- taining the thermostatic equilibrium of the body increases when the conditions become such that the whole elimination of heat is by evaporation. A man can stay in a dry atmosphere at a temperature sufficient to cook his dinner. He can keep cool by sweating. He cannot stand a water or steam bath above bod}^ temperature without becom- ing overheated. Immersion for a few minutes in a bath at 110° F. raises the rectal temperature to 103° F., greatly accelerates the breath- ing and pulse, loA^ers the arterial pressure, and flushes the skin. On standing up suddenly, a sense of faintness ensues. A cold shower- bath taken now at once constricts the skin, slows the j)ulse, raises the blood-pressure, and removes all sense of faintness, w^hile the rectal temperature still remains at 103° F. Baths cold and hot are a most potent means of altering the meta- bolism both of the skin and of the whole body. The amount of heat lost by evaporation is ver}^ great under con- ditions of hot dry atmosphere. Thus, it was estimated that 10 litres of water were lost from the body during a ride at a temperature of 45° C. in South California. In a dry hot atmosphere, such as the stokehole of a steamer in the tropics, the men are kept cool by sweating, the forced draught of air to the furnace insuring this. The amoiuit of drink required ma}' be enormous — e.g., 15 pints of water a day. In certain factories, mines, etc., where the air is warm and moist, it is of great economic importance to keep the air in movement, or the vapour pressure down to a level commensurate with the performance of efficient work, and main- tenance of comfort and health. A regulation made for weaving- sheds and spinning-mills is that the wet-bulb thermometer should not be allowed to rise above 75° F. The amount of water lost from the bodj- during a march m.iy be calculated by weighing the body before and after the march, supposing no food or drink is taken, and no faeces or urine passed during the march. The weight of oxygen taken in balances approximately the weight of carbonic acid given out. The water retained in the clothes may be estimated by weighing the clothes before and after the march. Such estimations, coupled with those of pulse-rate and body tempera- ture, have shown the value to soldiers of opening or taking off their tunics in hot weather. If the evajooration of sweat and convection is made easy, fatigue and danger of heat-stroke are prevented. It has been calculated that a resting soldier weighing 70 kilogrammes, 500 A TEXTBOOK OF J'H VSlOJ.O(;Y while marcliing with a load of 31 kilogrammes, produces 7-73 calories per mimito. or enough heat to raise his l)ody by 1^ C. in 8-7 minutes. This shows the importance, then, of jn-operly clothing the soldier for marching in hot weather. The thermometer gives the average temperatuie of the surround- ings; it tells nothing as to the rate of cooling — the matter of greatest importance to the body. The katathermometer has been introduced to measiire this. This is a large-bulbed spirit thermometer which is warmed a))o\'e body temperature. The rate of cooling is determined as the meniscus falls from 100° to 95° F. with a stoj)- f\ watch (Fig. 237). A factor is determined for each instrument, by means of which is reckoned the rate ,| of cooling per sq. cm. of surface per second at body ^ temperature. The dry-bulb katathermometer indi- cates the rate of heat loss bj' radiation and convec- tion, the wet-bidb by radiation, convection, and evap- oration. The difference betweeii the two gives the rate of cooling by evaporation. The instrument shows the g]-eat cooling effect of wind, and is of value in investigating the conditions of the open air and of ventilation in buildings (see p. 31(5). Clothes. — The cutaneous fat is the natural garment of the body. The warming value of fat may be gathered from the fact that with a temperature difference of 18-2° C. a layer of skin, 2 millimetres thick, lets through 0-00248 calory per minute, whereas 2 millimetres, of skin ])lus 2 millimetres of fat lets through only 0-00123 calory. Anointing the skin with grease Avards off " frost-bite "' in those exposed to cold and wet. The grease prevents the macera- [ ^^f;! tion of the skin hy water. If water soaks into the %M,i^ skin its non-conducting power is greatly reduced. c/fy ,v/:7 Exposure to sea water can be borne much better than fresh water because salt Avater, owing to its Pig. 237. — The isotonic properties, does not macerate the skin. K.\TA Thkkmo- Channel swimmers thickly cover their bodies Mith ducedirom Phi/, grease, and are noted for the thickness of their Trans. Boi/. cutaneous fat. The vernix caseosa of the new-born, ***'"'■•) washed off by the midwife, is designed to protect it from wet and cold after birth. Clothes increase evaporation and lessen loss of heat b}' convection and radiation, in still air io an extent of 47 per cent. At 18° C. a clothed man of 74 kilos lost 79 calories per hour clothed, and 124 calories per hour naked. The clothes entangle and render -stationary the air within their cellular structure and between their layers. The more garments A\e put on over one -another, the more laj^ers of entangled air. To keep us warin, the clothes must prevent the wind sweeping away the entangled air; to keej) cool, the wind must have free i>\a.Y. When dry, cellular, wool, or cotton THE TEMPERATURE OF THE BODY 501 clothes are equally good- — e.g., flannel or flannelette of the same thickness; but flannel prevents heat loss much better than cottoa when wet. The wet cotton touches the skin while the wet elastic hair fibres stand f)fE and keep air entangled. Silk or cotton is the coolest garb for summer, and flannel the best for damp, cold weather. Overclothing throws out of use and weakens the natural defensive mechanisms of the body against cold. Man has immense imiate powers of withstanding cold, evolved in his long struggle with Xature. Excessive exposure to cold produces local death, or death of the whole body; but if a man survive exposure — e.g.. after a shipwreck — ho recovers, and does not suffer from such ills as are commonly attributed to -chill. Darwin describes the inhabitants, including mother and baby, of Tierra del Fuego standing in the cold sleet naked, but greased with fish oil, and the}' haA'e to keep down the population to the food supply by infanticide. Babies, especially among the poorer classes, are generally overclothed and kept in too warm and stagnant atmospheres to the detriment of theii' vitality. This is a cause of the high mortality of infants in industrial towns. The amount of clothes worn by individuals depends much on habit. We can accustom ourselves to few or many clothes. The young and vigorous want few clothes, while the old, in whom the fires of life are weakening, want manv. BOOK X THE FLNCTIONS OF THE DUCTLESS (tLANDS CHAPTER LIX INTERNAL SECRETIONS The metabolism is greatly affected by what are known as the " internal secretions." In certain glands there is elaborated material which, instead of being discharged from the glands by a system of ducts as an " external " secretion, passes from the gland cells into the blood or lymph as an " internal secretion."" Such may come from glands which have no system of ducts — e.g., the th;vToid, supra- renal— or they may come from glands which are also provided with a system of ducts — e.g., pancreas, testes — and have therefore both an " external "' and an " internal " secretion. Of late, researches have been extremely p/olifie in this branch of jjhysiology. So much is controversial that it is only possible to indicate what appear to be the characteristic functions of each gland ; even these cannot be stated in a dogmatic manner. With the evolution of the multicellular organism there takes place a differentiation of organs corresponding to a division of labour, and an interworking of these organs is established. It is hard to say, then, what are all the functions of any one organ, since an organ, in jjei-forming these, not only fulfils its own life, but aids the functions, growth, and nutrition of the other organs of the body. Thus, the blood carries the heat developed in one part from that part to another, and thereby affects the working of the body; it carries the hormone^ "' gastrin " and " secretin," which provoke secretion of digestive juices; it carries urea from the liver, where it is formed, to the kidney, v\'here it excites that organ to secretion. The muscles yield carbonic acid and other acids, which, going to the respiratory centre, control the respiration. The action of the secretions we are considering form part of this interworking system, and the keynote of their action is their interdependence on one another. The whole body is bathed internally ^\ith tissue fluid or lymph, and it is necessary that this fluid colloidal complex contain ov have linked to it various salts in proper proportions, also a number of internal secretions. The diminution or excess of any 504 A TK XT HOOK OF PH VSJO!.0( ;^' one of these seeic'ticii-; will alter the motaboUc conditions of the- body. sf)jn''t iine-< in an aiiaVolie. somotiTnos in a katabolic direction. _ A possible example of thia ■f interdependence has al- -| ready been referred to _ E under carbohydrate meta- rp ^ bolisni. It is suggested I 2 that normally internal se- ^ E eretions from the pancreas. c T. suprarenal, thyroid, and f r- possibly other glands, help ' .£ to regidate carbohydrate ^ metabolism." When all 1 these are present in cor- t rect amounts, the meta- J holism proceeds in orderly f fashion. If, however, the J _ balance be upset — for ex- j-f ample, by too little of the ~ I r pancreatic secretion being i ^1 present — then the kata- I Z f^ holism of sugar is de- ^-1 ranged. Too much sugar i^ ^tS therefore accumulates in '. E_- the blood, and the eondi- ^ ^c tion of glycosuria results. '% ^- In the development of ZTc sexual characteristics a ■= I balance between variou.s X %■ internal secretions is con- ~.= cerned — for examj)le, the Z ~ testes or ovary, and the .J suprarenal, thymus, and \ in the female possibly the 7 thyroid gland. The action ■^ of these internal secretions ? has been investigated by -§ various methods, chief of ■-1 which are the extirpation, = transplantation of the ■^ gland, and the in'jection = -^ of gland extracts. Clinical I 'Z cxjierience has yielded " -^ valuable information. ^ Although the exact ~ extent of the dej^endence of the action of the various internal secretions one on another is to a large extent conjectural, the fa-^t that such an interworking does take ])lace has been experi- INTERNAL SECRETIONS 505 mentally demonstrated. The active principle of the suprarenal gland — adrenalin — produces certain Avell-known effects ; for instance, it pro- duces a rise of blood-pressm-e. From Fig. 238 it Avill be seen that, after the nerves to the thyroid gland have been stimulated, the injection of the same amount of adrenalin in the same time gives a greater rise of blood-pressure than it did before the stimulation of these nerves. This is the more re- markable, since a second injection of adrenalin, without stimulation of the thvroid nerves, normally gives a smaller rise of blood-pressure than before. This increased action of adrenalin is abolished if the thyroid be excised before its nerves are stimulated, but is obtained when extracts of the th\Toid gland are injected into the animal just previously to the dose of adrenalin. These exjieriments, then, give definite evidence of the interworking of the secretions named, and it is probable that the other secretions also interact, some in an anabolic and some in a katabolic direction. The Organs of Generation — Testes. — The testis is generally regarded as a "double "" gland, consisting (1) of germinal cells, which form the external secretion or eloment.i concerned in reproduction; (2) of interstitial cells, which form an internal secretion intimately coimected with the general metabolism of the body and the acquisition of second- ary male characteristics. The view that the interstitial cells act as a separate gland is not accepted by all authorities, but the foUowing^ facts go to support the view. It is stated that, when the vasa deferent a are tied, the germinal cells atroj^hy. but the interstitial cells persist. Exposure to X rays is known to render animals impotent, but does not change their secondary- sexual characteristics. Histological examination in such cases shows that the generative cells are de- stroyed, but the interstitial cells are not damaged. The effects of castration have long been known. As a direct local rcr^ult the animal is rendered impotent, and the accessory sexual apparatus atrophies. Generally, the sexual development of the animal is arrested; the so-called secondary sexual characteristics are not acquired (Figs. 239, 240); the general metabolism is so affected that the animals tend to laziness and fatness. An excessive growth of bone is also frequently brought about. These results are due to th& cutting off from the bod}- of the internal secretions of the glands. It makes no difference whether the seminal vesicles be left or removed. The results of transplantation experiments show that thesecondar}' male characteristics may be developed by this means — e.g., the spurs and comb of the cock, or the large thumb of the male frog. If the testicle be transplanted in infancy, no sj^ermatozoa develop, but the gland becomes composed of large quantities of interstitial cells, and the secondary male characteristics are acquired. It is stated that a testicle so transplanted into a female tends to give her body male characteristics. The internal secretion of the testes has been held to exert marked influence upon the general health and mental and muscular activity of the individual. It is claimed that a substance — spermin (C-H^jN2)' i500 A TEXTBOOK OF PHYSIOLOGY — isolated from testicular extracts, may be used to increase neuro- muscular activity and lessen fatigue, and Ibui; be of service in old age, when the testes are failing to act. Some advertised patent medicines on the market claim on untrustworthy evidence to give wonderful rejuvenating effects. They contain a certain amount of extract of boar's testicles. Whether the general effect of excision or transplantation upon metabolism be so great as is supposed by some, it is obvious that upon the grooving animal the effects are far-reaching. For instance, in man, not only are the secondary male characteristics called forth — e.g., the beard, the large larynx, etc. — but the growth of the skeleton is affected, so that it is possible to differentiate between the male and female skeleton. It is probable that s'uch secretions may be held partly responsible foi the different outlook of man and of Fig. 230. — Herdwick Ram (Normal). The effect of castration on horn-growth is well seen ric. 2-10. Herdwicx Wether WITHOUT HORXS VISIBLE. (Marshall.) -woman upon life, the cerebral processes differing according as the nervous system is bathed with testicular internal secretion or with ovarian internal secretion. The Prostate Gland. — It is believed hy some that an internal secretion of the prostate gland has an important action on the forma- tion and ejaculation of spermatozoa. There is, however, little evidence for this view. It is generally believed that the prostatic secretion aids the movements of the spermatozoa. The Ovary. — The interstitial cells of the ovary play much the same part in the female as the interstitial testicular cells in the male. Extirpation of both ovaries in young girls prevents the onset of men- struation, and brings about notable alterations in their appearance. When the ovaries are removed after jjuberty, menstruation ceases and pregnancy is prevented. There follow some atrophy of the breasts, uterus, and vagina, and a tendency to obesity. That these effects are not nervous in origin, as was once believed, is shown by the fact that transplantation of the ovary induces once INTERNAL SECKETIONS 507 more heat, or " oestrus,"' in spayed animals. Further, the injection of extracts of ovaries in an oestrus state, or the grafting of such into these animals, produces the signs of heat in them. It is also stated that as the result of tiansplantation of an ovar}" into the growing male the teats and breasts become enlarged, and may even form milk. ■ \^ ■ ^j'y - ■ £^ ^^/^^^ Fig. 241. — Section through StrpRARENAL Body of Dog showing Zones of Cortex AND Medulla. (Swale Vincent, drawn by Mrs. Thompson.) c, Capsule; m., medulla; z.f., zona faseiculata; z.g., zona glomerulosa; z.r., zona reticularis. The corpus luteum, into which a Graafian follicle develops after discharge of the ovum, is believed to exert considerable influence by jaelding an internal secretion. This controls the fixation of the ovum ■■)(IS A TEXTBOOK OF PHYSIOLOGY within the uterus, probably by maititainiug an increased metabolism of the uterus during the earh' stages of pregnane}-. The eorpus hiteum also furnishes, in the initial stages of pregnancy, an internal secretion which stinndates development of the mammary gland. The Suprarenal Bodies. — Each suprarenal gland consist of a cortex and a mcdidla. The cortex, the cells of which are arranged in charac- teristic colunmar fashion, is derived from the mesoblast associated with the urogenital system, the Wolftian ridge. The medulla is of nervous origin, and its cells are arranged in strands which enn:esh lacunar veins. Manj^ of these cells are characterized by their affinity for chromium salts, and are therefore known as chromophil cells. Such chromophil cells are also found in the ganglia of the sympathetic f ./,^\ Fig. 242. — .Skctiox thkougii a Group of Chromophil Cell.s in^kferior Cervical Ganglion of a Dog. (Swale Vincent.) nervous system, and in accessor}- suprarenal masses which are often found connected with the abdominal ganglia of this system (c/. Fig. 242). Little is known concerning the function of the cortex of the supra- renal glands, but it has l;een suggested that it interacts with the sexual glands influencing the acquirement of sex characters. In manj- cases of sexual precocity an abnormal development of the cortex of the suprarenal has been found. Far more evidence has been obtained as to the function of the medulla of the sujirarenal. whicli appears to be of great importance to the organism. Addison long ago pointed out that the fatal disease known by his name was ahvays attended by. and therefore probably due to, disease of the suprarenal glan(3s. The disease is characterized by these symptoms: a gradual increasing muscular weakness, bronzing of the skin, and vomiting. INTERNAL SECRETIONS 501) It has'been shown that extirpation of the suprarenal glands almost invariably causes death. The fatal result was at one time attributed to an accumulation of toxic bodie-; within the organism. Such toxic Fig. 2-43.— .Showing Rise of BLOOD-niEssrKE due to Release of Rkessure ox ScrpRARENAL Veik. (Ffom " Internal .Secretions," Swale Vincent.) (Gardner and Gunn.) The vein has been compressed for some time and was released at point signalled. bodies were believed to be destroyed by the glands. It is now known that the chief function of the suprarenal medulla is to furnish as an internal secretion an active principle — adrenalin. Adrenalin, as its structural formula shows — OH CHOH.CH0NHCH3 _ — is An aromatic bod}- nearly allied to t^Tosin, and is probably derived from t^Tosin. The best-known function of adrenalin is its power to induce con- striction of the smooth muscle of the arterioles, 'and thereby cause a rise of arterial pressure (Fig. 238, a, b). The supply of adrenalin to the blood is under the control of the splanchnic nerves. If these be stimulated the arterial pressure is raised, but not after extirpation of the suprarenals (Fig. 245). This is only one of the functions of adren iliu, for an intravenous injection of adrenalin acts upon all smooth muscle supplied by the no A TEXTBOOK OF PHYSIOLOGY sympathetic system, and in every case produces the same eflfects as does excitation of the sympathetic nerves (see Figs. 240, 247). It is probable that (his action is manifested throucrh the " receptive substance " Fig. 2-iA. — Thxc'Im: .sikaving Kffixt on Carotid Pressure of Ax.esthetized Dog bv Intravenous Injection at Signal of an Extract from the Chromo- riiiL Bodies of Three Dogs. 165. '%y. 84- l-'iG. 245.— Pithed Animal. (T. K. Elliott.) A Effect of stimulation of both splanchnic nerves; 118 mm. Hg rise of pressure. B, Ditto, after removal of intestines; 48 mm. rise of pressure. C, Ditto, after removal of suprarenals; no rite of pressure. uhich eifects the union between the sympathetic nerve fibre and the smooth muscle. This receptive substance depends for its action upon the integrity of the muscle rather than upon the integrity of the nerve INTERNAL SECRETIONS ill fibre, as is shown by the fact that, after the s^-mpathetic nervea have been cut and allowed to degenerate, the receptive substance is still capable of responding to adrenalin. There is evidence that adrenalin acts in conjunction with the internal secretion of the thjToid ; also with that of the pancreas, and possibly other internal secretions. Fig. 246. — Recokd of Movement of Isolated Rabbit's Heart during Perfusion wiTH Ringer's Solution, showing Effect of introducing Adrenalin (1 in 100,000) into Circulating Fluid for a Period of Thirty Seconds. (Dixon.). The heart is greatly accelerated and the force of beat increased, corresponding to a stimulation of the sympathetic nerves to the heart. The Pancreas. — The pancreas is an example of a gland which affords both an external and an internal secretion. The internal secretion of the pancreas is believed to play a part in the regu- lation of carbohydrate metabolism, to be necessar^^ for the primary stage in the oxidation of sugar within the bod\^ (p. 430). Possibly it also plays a part in regulating the glycogenic function of the liver. It is believed b}' many that this internal secretion is afforded by the islets of Langerhans (Fig. 248), which may be looked upon as a separate gland included within the pancreas. The islets vary in size in different animals. In certain teleostean fishes the islet material is largeh' separate from the gland which forms the external digestive secretion. Some have regarded the islets as the exhausted acini of the pancreas. It has. however, been recently shown that the 512 A TEXTBOOK OF PHYSI0LO(;^' exhausted acini stuiu quite differently from islet tissue. By other authorities the islets are looked upon as rudimentary pancreatic cells, but the evidence for this cainu)t be considered satisfactory. The Function of the Thyroid and Parathyroids.- The thyroid gland lies in front of the trachea, and consists of two lobes, each about 2 inches long and 1 inch wide, joined by an isthmus. The jiara- > f tj . ■■ 0 - \ - r^lA A \ A 1 '^ \ * \ o t^W' A. 1— H . ,ij nnffllffllmniml fllll!l iiHlmlliml ^mhmmmmmmMi Fro. 247. — Record of Artekial Pressure and Intestinal Movements in Cat. (Dixon.) At A, 1 c.c. of 1 in 20,G(>0 adrenalin was injected into a vein. The arterial pressure rigew, the intestinal movements are inhibited, both cifocts corresponding to stimulation of the sympathetic nerves. thyroids in mammals are small oval bodies 6 to 7 millimetres in length, 3 to 4 millimetres in breadth, 1-5 to 2 millimetres in thickness. They are usualty stated to be four in number, and varying in position in different species of animals. The thyroid develops as a median endodermal downgrowth from the tongue; to this the lateral lobes from the fourth cleft are added. A consideiable portion of the adult lateral lobes are derived, however. INTERNAL SECRETIONS 513 zym. cap. -Mi-,. _-Jt^ C> fi I. bid. c. '42^?;. i^^:-av .■%tjS;|^^A^t::0!^ rV.. — ''^ — ; . ••■ia ti-f.ns. '■. -c.a.c. - zym . .Fig. 24S.— Islet of Lixjerhans from Splenic End of Pancreas of Dog, (Vincent and Thompson, drawn by Mrs. F. D. Thompson.) V.d. c. Red blood-corpuseles; c.a.c, central acinar cells of pancreas proper; cap., blood capillaries; i., islet of Langerhans; I., lumen; trans, c, transitional cells; zym., zyraogenous tissue. for. caeo. raphe of tongue hyoid {2nd & 3rd arches) susp. ligament thyr cart. (4th & 5th arches, sup. parathyr. from 4th cleft inf. para thyr. thymic strand thymus (3rd cleft) Fig. 249.— Diagram showing Dkvelopment of the Thyroid and Thymtts. (Keith.) The thi-ee parts of the thyroid body are indicated by a stippled liie; the position nf flip i-iarathvroids on the posterior aspect of the lateral parts is indicated. of the parathyroids on the po? 33 514 A TEXTBOOK OF PHYSIOLOGY from the median portion (Fig. 24f»). The cells fir.st form notworks^ of solid cords. These separate into solid masses, within which lumina may appear. The mature gland consists of rounded closed spaces or vesicles filled with a colloid material, and hy a single layer of low ', e. ves. \ '■ •'•,''..'*•.' *'<" ^'•'•''t*.: ■"T e. iiiterves. :'•. if \"\ c. ves. Fig. 250.— Thyroid of Normal Dog. x 120. (Swale Vincent.) c. Colloid; e. ves., epithelium lining vesicles; e. interves., ejtithelial intervesicular tissue; c. ves., colloid vesicle. Fig. 251. — Pakathykoid of Normal Dog. x 120. (Swale Vincent.) S.C.C., solid columns of cells; bl.v., bloodvessel. columnar cells (Fig. 250). The vesicles are separated by connective tissue, which carries the bloodvessels and nerves, Avith which the gland is most plenteously supplied. The parathyroids are built up of closely packed polygonal cells divided up by connective-tissue septa into areas of various shapes (Fig. 251). INTERNAL SECRETIONS 515 There is a coti^iderable divergence of opinion as to whether the thp-oids and parathyroids are one and the same tissue, or whether the\- are quite distinct glands with markedly different functions. According to the tirst view, the two tissues are essentially the same, and all grades from normal th;^Toid to normal parath^Toid tissue may be found when the glands of a series of different animals are studied. The difference in appearance is to be attributed to the presence of colloid. After excision of the thyroid colloid a,ppearrj in the par?.- thyroid (Fig. 252). Developmentally. the parathyroids arise from the third and fourth gill clefts, the thyroid from a median remnant in the ventral wall of the embryonic pharynx. These glands arise at different times, and come therefore only secondarily into relation with each other. - --vrN::-": •'•'>>"''•*'■'''•' Vi"^-''< ••• .• -...•.■j.'...Tr— ^- "^*- *••(. .-•. :.~} 'C«'-*.- /' ••••.■,"•. ,r.-'t •• -'.•. ■ .•■ ■^-.^ jv-^"; '!"i"''\,V' "••••'• 'v'.'. "..'■.'■ »..; :.;»S'»-V- •.".•■ .«.>.■..■•.■■■-.■■.■■•- ■:..^' •■: : FiQ»r 2^.— Parathyroid of \ Dog Eighty-Three Days aftek Thyroidectomy. v-^3HO"y\^^,-G Vesicles, Some of ^VHICH contain Colloid. (Swale Vincent ) r. ve<.. Colloid vesicle; e. ves., epithelium of colloid vesicles; e. interve-s., intervesicular epithelial cells. Attention was tirst drawn to the function of the th3Toid (including the paratluToid) by clmical observations. In certain districts the gland enlarges in adults, forming what is known as a '' goitre." This appears to be due to an infection through the drinking-water of the district of the alimentary tract b}' a living organism. Goitre has been experimentally produced by drinking the residue filtered from such Avater, and cined by the taking of thymol. Goitre is very localized, hence the name " DerbAshire neck.'" The thjToid enlargement Ls pathological in nature, and often entails a deficiency of thyroid function. The children of mothers suffering from such a deficiency of thjToid function suffer from a condition known as " cretinism." Such endemic cretinism is common in Switzerland, and in the central and Gilgit valleys of India. It varies with the prevalence of the " endemic goitre.'' The "' cretinism " is due to toxic agencies acting upon the th\Toid and j)arath3T:oids of the unborn. 516 A TEXTBOOK OF PhnSIOLOGY There are in general two types of cretins, the )nyxaMlematoiis and the nervous. Tne nervous type, met Avith chiefly in India, are generally deaf and dumb. The ui)i)er Iiml)s often assume a position of right-angled flexion, with the thumb drawn into the palm and the lingers closed over it. The lower litnbs exhibit a " knock-kneed " spasticity. These cretins suffer from convulsive movements of the head, nystagmus, internal squint, and idiocy. The myxoedematous type shows marked interference with the growth of the skeleton, leading to a stunted, pot-bellied appearance. There is usually a marked lack of mental efficiency, a child of twelve Fig. 253. — Non-Goitroxjs Cketixs. (Pliotograj)hs kiucily Jent by -Or. Robert Hutchison.) to sixteen having the intelligence of a child of two or three. The appearance remains childish throughout life. Often fattv tumours make their appearance in the region of the collar-bone. When thvToid deficiency first manifests itself in the adult, the effects upon growth are naturally absent. A gradual swelling of the skin sets in, frequently accompanied by nervous disorders, such as headache, languor, convulsions, mental disturbances, dulness, drowsi- ness, or ev^en hallucinations. The skin becomes wTinkled, dry and rough, swollen generally, but with a '* solid oedema," hence the name *■ myxoedema " (mucous oedema). The swelling is at first most notice- able on the face (see Fig. 254). The hair becomes scanty, the scalp dry and scaly. The teeth often become carious. INTERNAL SECRETIONS 517 C'retins and cases of myxoedema show marked iiuprovement when fed upon thyroid gland. It was noticed that a condition — " cachexia tM-reopriva " — similar to myxoedema was induced when the goitrous thyroid was removed b}' operation; hence it became customary always to leave a piece of thyroid tissue. In contrast to the condition due to lack of thp'oid activity is that known as "exophthalmic goitre," or "Graves' disease" (Fig. 255). In this disease the th3'roid is generally enlarged and overactive. This "overaction '' manifests itself in "nervous " symptoms — exoph- thalmos and tachycardia. On account of the nervous symjjtoms, Fig. 254. — Typical Case of Myxcedema. (Photograph-^ kindly lent by Dr. Robert Hutchison.) A, Before treatment; B, after treatment. the disease has been regarded by some as primarily a lesion of the sympathetic nervous system, and not of the thp'oid gland. A possible explanation of this may be that man3' of the symptoms are due to the increased action of adrenahn upon sympathetic nerve endings, this increase being due to the excessive thvroid secretion (cf. p. 519). The result> of extii^pation experiments, on the whole, support clinical observation. There is, ho^^'ever, much contradiction in the evidence, owing to the fact that extirpation of the thyroid and of the parath3Toids produces different effects in different species of animal. It is difficult to produce all the symptoms of myxoedema as a result of thyroid deficiency; possibly, therefore, some other factors come into 518 A TEXTBOOK OF PHVSI()L()(^Y this disease. By those Avho beheve that thyroid and parathyroid aie glands with different functions it is claimed that extirpation of the thyroid produces symptoms akin to myxoedema. with sometimes a slow death; while extirpation of the para- Ihyroids produces the licrvOus symptoms of tetany convulsions and a quick death. The evidence in favour of and against those views is very conflicting. Undoubt- edly, in some cases the removal of the thyroid produces the '" myxoedematous," and of the ])arathyroid8 the " nervous " syndrome; but in some cases thyroid i-emoval produces iii addition the nervous symptoms, or these alone; while extirjia- tion of the parathyroid, instead of pro- ducing the nervous symptoms of tetany, calls forth '' cachexia. " or deficient meta- bolism of myxoedema. A substance rich in iodine has been isolated from the thyroid, called iodo- thyrin or thyreo -iodine. The active part of the colloidp.l protein secretion of the thyroid is often stated to be this sub- stance. Recent evidence, however, tends to show that this is not the case. The true secretion passes into f,y,P: T^io^^ iTrV^ri" f Vie' nerves (the superior laryngeal) to the gland are Pig. 25o.^A Typical Case of Exophthalmic Goitre in a YoTTNG Woman. (From "Index of Differential Diagnosis," T. Wright and Sons, Ltd.) Stimulation of depressor Stimulation of nerves, depressor. Stimulation of thyroid nerves. Fig. 256. — To show the Effects of Stimulation of the Depressor" Nerve without and with Stimulation of the Nerves (Superior Larvng'eal) to the Thyroid. (Asher and Flack.) stimulated, as is demonstrated by the fact that certain actions are augmented by this, just as they are by an intravenous injection of INTERNAL SECRETIONS 519 thjToid extract. For example, if the depressor nerve be stimulated before and after excitation of the th\Toid nerves (or injection of thyroid extract), the fall of blood-pressure is greater in the second case (Fig. 256). Likewise, if adrenalin be injected, the rise of blood- pressure is greater in the second case (Fig. 238). The injection of any of the commercial preparations of thp-oid extract produces these effects, but not the separated product, " iodo- th^Tin." As to the exact chemical nature of the active body, nothing definite is known. Its iodine content, no doubt, is of great importance, but is not the sole factor. -■""■''"!'"'■' '.■■■■ '.■■'.-■■■;-:.'.■:■••. \'?^ ■*t^-. -l/.c. Hx. n^ii Fig. 257. — Poetion of Thyjius Glaxd of a Mo>rKEY. Low Power. (From Swale Vincent, drawn l)y Mrs. ThomiJson.) c, Cortex; H.c., Hassal's concentric corpuscles; m., medulla. The Carotid Body is a mmute structure situated at the bifurcation of the common carotid arter3^ It is richh' supj)lied Avith nervous ■elements, and probably belongs to the group of chromophil tissues, with a function akin to that of the medulla of the suprarenal gland. The Thymus Gland. — In its development, the thymus gland arises from the gill-clefts, and may be apparently entodermal or ectodermal in origin, or both (Fig. 257). In man and the rabbit it is ento- dermal, in the mole it is ectodermal, in the guinea-pig and pig it has a dual origin. At birth it Aveighs about i ounce, and is relatively a large organ. It increases in size and weight for some years after birth, probably until puberty, and then atrophies slowly. It is subdivided by connective tissue into lobes, and each of these is made up of several Ir)bules, which are divided into a darker cortex" 520 A TEXTBOOK OF PHYSIOLOGY and a pale medulla. All the lobules in eaeh half of the thymus are attached to a cord of medullary substance, as may be seen if the organ is pulled apart. The thymus resembles in structure a tymphatie gland, but germinal centres are absent, and there is nothing to cor- res])ond with a lymph sinus. The cortex is crowded with lymphocytes, and is very vascular. The medulla is more open in texture, and is characterized by the presence of the concentric corpuscles of Hassall. c h k- d e / fj Fig. 258. — Mesial Sagittal Section through the Pituitary Body of an Adult Monkey. (Herring, from Quarterly Journal of Experimental Physiology.) (I. Optic chmsma ; h. tongue-like jiroeess of pars intermedia : c, third ventricle ; d, anterior lobe : e, epithelial cleft of posterior lobe : k, epithelium of pars inter- naedia extending over and into adjacent brain substance. The dark shading indicates anterior lolie proper ; the lighter shading shows the position of the epithelium of pars intermedia : ij, nervous substance of posterior lobe ; /, epithelial investment. These are generallj- regarded as degenerated products of entodermal epithelium. Some authorities maintain that the thymic cells are not true lymphocytes, but are of entodermal origin. The Function of the Thymus. — By virtue of its lymphatic tissue, the thymus gives origin to the h'mphocj'tes of the blood, and possibly INTERNAL SECRETIONS 521 also plaj's some part in the purin metaboHsm of the body. In some hibernating animals it also acts as a storehouse of fat. It has long been known to butchers and others that the thymus persists in castrated animals, and atrophies with the onset of puberty in the intact animal. It has been shown, also, that the atrophy is accelerated should the bull be used for breeding purposes or the imsj)ayed heifer become pregnant. It is also suggested that the extirpation of the thymus- interferes with the growth of the skeleton. Rickets has been attri- '!S^-, i9 55 -y.n. Fig. 259. — Sectiox through Portions of Pitttitary Body of Dog, showing Glandular and Nervous Portions and the Pars Intermedia. (Swale Vincent, drawn by Mrs. Thompson.) c. Cleft in glandular portion between glandular portion proper and pars intermedia; f.g., glandular portion showing three kinds of cells; p.i., pars intermedia; p.n.., nervous portion. buted to disease of this organ. The evidence in favour of such views is not conclusive. It has recently been stated that tadpoles fed on thyi-oid became diminutive frogs, while those fed on thymus became giants. The Pituitary Body.— The pituitary body consists of three portions: (1) The anterior, (2) the intermediary, (3) the posterior lobes. The anterior and intermediary lobes have a common origin from a portion of the glandular epithelium of the stomodseum, known as Rathke's pouch. Quite early a differentiation between the U\o portions takes 522 A TEXTBOOK OF PHYSIOLOGY place. The intermediate part is closely adherent to the wall of the posterior lobe; its cells are clear, and tend to form colloid; the anterior l)ortion is formed of columns of granular cells separated by blood- channels (Fig, 258). Tne posterior lobe, or infundibulum, is nervous in origin. It is an invagination of the portion of the develojiing braiii known as the thalamencephalon. In some animals, such as the cat, it retains its central cavity; in others this becomes entirely obliterated. Early in development it becomes closely associated with cells of the pars intermedia, so that eventually the posterior lobe becomes a com- posite structure of intermediary and nervous epithelia — a mass of gland cells, neuroolial cells, and nerve iibres (Fig. 2511). .,... ^^^.^j^iiv«''i^wwwiwV'^/«'''^^''^"''-^'''*v,v...- (( 3 c - BV r ■^j-fT •. - J MILK h 1 niiiK/lfiliiiM 1 1 1 1 1 IN 1 II 1 1 :Li : i'iiHiii>H|i'Hi'HlnH'e Nipple OF A Lactatixg Cat. (Dixon.) At A pituitary extract was injected. The Functions oJ the Pituitary Body. — The chief evidence of the physiological action of the pituitary gland is obtained from clinical experience and pathological findings, and from observations upon the effects which follow injection or feeding extracts of the gland. Owing to its anatomical position, it is difficult to obtain satisfactory evidence by means of extirpation. It has been claimed that the removal of the gland invariably causes death, often in thirty-six hours. Many such deaths are tmdoubtedly due to post -operative shock. Recently, skilled experimenters have succeeded in keeping animals alive several months after removal of the pituitary. The effects claimed to result from its removal are thus contradictory. The injection of extract of the anterior lobe is Avithout phj'siological action. Injection of extract of the intermediary and posterior lobe INTERNAL SECRETIONS . 523 •causes a rise of blood-pressure, accompanied by marked diuresis. A second injection . generally does not affect the arterial pressure, but the diuretic action is still marked — in fact, the active substance may be regarded as the most potent diuretic known. The smooth muscle of the pupil and uterus is also affected by pituitary extract, and it is used by clinicians to promote contractions of the uterus. The contractions of the bladder are also increased in the dog and rabbit by the injection of pituitary extract. The excitability of the pelvic nerve supplying this viscus is increased, while that of the Fig. 261. — A Case of Acromegaly. (Photograph kindly lent by Dr. T. Heuell Atkinson.) The head measurements are — Circumference, 2o| inches; from forehead to chin, 11 inches; from nape of neck to chin, over nose, 2.5 inches. The lower jaw pro- trudes 1^ inches in front of the upper. The two hands measure 6 inches across the root of the thumb and 5 inches across the root of the fingers. When closed the hand measures 15^ inches round. hypogastric nerves is unaltered. Pituitary extract has no action upon other organs supplied by the autonomic system, such as the heart and the salivary glands ; an action upon the intestine is doubtful The extract of the infundibidum is also a powerful galactagogue, and the active substance can be obtained from both the intermediary and posterior lobes (Fig. 200). The active substance is probal)Iy derived from both lobes, but chiefly from the intermediary lobes. Its •exact nature is unknown, liut its action is closely allied to bodies of the digitalis series, and it apparently acts directly upon muscle rather "than upon the nerve or nervous connections. r,24 A TEXTBOOK OP PHYSIOLOGY The function of the anterior lobe is suggested by clinical records of the results which accompany its disease; thus the affection known as " acromegaly " is associated with a hypertrophy of the anterior lobe. This affection begins about puberty, and is characterized by progressive increase in the size of the face and limbs (Kig. 261). The disease nins a s1oa\' course to a fatal issue. Some attribute the development of giants to hypertrophy of this organ. Excessive growth is also found associated with h\q)ertrophy of the cortex of the Buprarenal gland, and there may be some internal secretion common to the two glands which stimulates growth. It has been suggested that the pituitary gland plays a part in regulating the calcium metabolism of the body. The evidence of this is inconclusive. It is also claimed that the posterior lobe helps to regulate carbohydrate metabolism, and that after its removal an increased tolerance to carbohydrate is induced. There is some evidence that the pituitary interacts with the thyroid and sexual glands, esi^ecially the ovary. Thus, after extirpa- tion of the thyroid the pituitary is said to show an increase of colloid material, while during pregnancy, it is stated that the pituitary increases in size — an effect also produced by removal of the ovaries in women and in animals. The Pineal Body is a small pinkish body situated on the dorsal aspect of the brain, underneath the posterior region of the corpus eallosum. It consists chiefly of neuroglial and secretory cells, made up into a number of follicles often resembling adenoid tissue. There is little phj-siological evidence of any internal secretion of this body. Clinically, it is suggested that disease of the gland is associated in some cases with obesity, in others with abnormal sexual development and gigantism. BOOK XI THE TISSUE OF MOTION CHAPTER LX THE MECHANISM OF MOVEMENT A UNICELLULAR orgaiiism, such as the amoeba, moves by the flowmg of its protoplasm in one or other direction, the rest of the cell flowing after the protrusion or pseudopodium. In other unicellular forms, the development of one or more cilia or flagella enables the organism to move, often with a relatively high rate of speed. In the multi- cellular organizations this function of motion has been assigned to special cells. Such cells are termed the muscle cells. The full}^ specialized muscle cell contracts with a force, rapidity, and frequenc}', far bej'ond the poAver of less specialized protoplasm. Its greater power and efficiency have been acquired by the development withm the protoplasm of long, and exceedingly slender, contractile structures — the muscle fibrils — lying parallel to the long axis of the cell and in the direction of motion. Fibrils vary in the degree of differentiation. Some exhibit a marked cross-striation, and are termed striated; others are unstriated. The fibril affords the essential mechanism of rapid motion. In the higher animals the principle of locomotion is that the moving part first becomes angular in shape, and then straightens itself out against some resisting substance; the principle being the same whether the organ of locomotion be fin, wing, or leg. Force exerted against resisting water, air, or earth, and reacting in proportion to the resist- ance, imparts movement to the body of the animal. The principle of the lever is applied in the various movements of the body. There are three kinds or orders of levers (see Fig. 262). (1) The first order, in which the fulcrum (F) lies between the force applied (P) and the resistance overcome (W), as exemplified in a pair of scissors; (2) the second order, in which resistance {W) lies between the fulcrum {F) and the force applied (P) — e.g., in nutcrackers; (3) the third order, in Avhich the force (P) lies between the fulcrum {F) and the resistance ( W). as, for example, in a pair of sugar-tongs. By means of levers the power applied max be augmented or the rauge and rapidity of movement increased. In the body the power is usually 525 526 A TEXTBO(JK OF PHYSIOLOGY applied to the bonew in such a way that the latter is the case. In order that the inuscies may be packed within the skin and the body made as compact a« possible, the power is ap]jlied at the insertion of the muscles close ti> the joints or fulcra. All three orders of levers are exemjilified in the bodj-. Belonging to the first order is the move- ment by which the head, jointed to the top of the spine, is nodded backwards and forwards by the neck muscles (Fig. 262, 1.). Another example is the straightening movement of the forearm bj' the action of the tricejis muscle. The power is applied at the insertion of the muscle into the ulna just above the elbow-joint, which is the fulcrum, and the resistance (the weight of the forearm) lies bejond. Range and rajiiditj* of movement of the hand are here gained at the expense of power. The second ordei of lever is seen in the movement by which the calf muscles raise the body on tiptoe (Fig. 262, II.). The power is applied at the back of the heel, the fulcrum is at the toes, and the weight of the body falls on the foot at the ankle-joint. Here power is gained at the expeu.ie of range of movement. I. II. III. [ W r Fig. 2G2.- W P F P W DfAGRAM OF Three Kinds of Lever Action. /', Fulcrum ;P, power; W, weight. I. The head is -litcd back by neck muscles. II. The toes rest on. the ground, and the body is raised l)y the calf muscles. III. The forearm i- bent up by the biceps muscle. Examples of the third order of lever are numerous. In the bending of the forearm on the upper arm (Fig. 262, III.), the power is applied by the biceps muscle to the radius just below the elbow-joint, the fulcrum is at the elbow, and the resistance is the weight of the fore- arm and hand. The bending and the straightening of the leg at the knee-joint are other examples. In all these movements rapidity and range of movement are obtained at the expense of power. We usually empL-y that combination of levers which require the least muscular effort. It is easier to carry a weight with the arm hanging fully extended, when it is slung to the shoulder by the bones and tendons, and the muscles have only to maintain the grip of the fingers, than it is to carry it with the arm bent, and much greater muscular effort. Man is constantly devising methods to save the expenditure of muscular effort. Thus a drayman pulls a beer -barrel up an inclined plane, which bears a large part of the weight. THE MECHANISM OF M0VE:\[EXT 527 The muscular work done by a man is calculated by multiplying the Aveight lifted by the height of the lift. Thus 2 kilogrammes lifted through 2 metres gives 4 kilogramme-metres of work. \Mien a man runs upstairs very fast he may. in lifting his bod}', do seventy times more work in a minute than a navvy does in the same time who is steadily shovelling up earth. The man, however, is spent at the end of such an effort; the navvy can continue to shovel leisurely for hours. Excess either of rate of work or of load a\ ill lessen efHcienc^^ and diminish output. vScientific management determines the suitable rate and load for each kind of labour. The Erect Posture. — With the assumi^tion of the erect posture one of the chief functions of the system of levers of the human body became that of maintaining the centre of gravity of the body within the bod}'. Since the centre of gravity of a body always tends to take up the lowest possible position, it must lie over the base of support, otherwise the body will topple over. A dead man cannot, without support, be made to stand in the erect posture. If a man standing erect faints, the head tends to fall forward on the chest, the trunk forwards at the hip-joints, and the whole body forwards over the ankle-joints. Although the body is balanced by muscular action, the weight of the body is borne by the bones and ligaments, and thus fatigue is avoided. In the stork the bones of the leg can be so locked together to balance the body that the bird can sleep restfully standing on one leg. In man the main- tenance of the erect posture is more of an effort, so that for this, as well as other reasons, he seeks rest in the recumbent posture. The bod}' is maintained erect by the following means : The head is balanced by the muscles so as to rest on the top of the vertebral column. As the centre of gravity lies in front of the joint, the head tends to fall forwards in a sleejjy man ; the neck muscles must act to keep it from doing so. The vertebral column forms an elastic rod supporting the head and trunk ; below it is fixed immovablj' to the broad pelvic basin, into which presses the weight of the abdo- minal organs. The centre of gravity of the body is situated near the front of the last lumbar vertebra. If a plummet-line could be dropped from the centre of gravity, the line would j)ass a little behind the line which joins the two hip-joints. The trunk thus tends to fall backwards at the hip-joints; this is prevented by the strong ligament which passes from the pelvis to the femur across the front of each joint. Thus the joint is locked and the muscles passing from the trunk to the thighs have simply to balance the body upon the heads of the thigh-bones. To do this but little effort is required. At the knee the plummet-line dropped from the centre of gravit}^ would pass through a line joining the posterior jiarts of both joints. The weight of the upper part of the body th;is presses upon the flat articular surfaces of the tibiae. The great extensor muscles in front of the thigh prevent the knees from bending, and the body from falling backwards whenever balance is disturbed. Owing to the check liga- 528 A TEXTBOOK OF PHYSIOLOGY ments which lock together the femur and the tibia, the knee can neither be overextended nor bent to one side. In a man standing at attention the pkimmet-line drawn from the centre of gravity passes in front of the Jine joining the two ankle-joints; the body is prevented from falling forwards by the action of the calf muscles. The weight of the body thus transmitted is borne by the spring of the arch of the foot; the balls of the toes and the heel rest upon the ground. The centre of gravity of the body is always kept over the base of support by varjdng the attitude of the bodj^ Thus a man stoops when carrying a child on his back, but Avalks erect if it be on his shoulders. If the child be on his arm he leans back, and to the other side. In most of the Herculean feats of strength exhibited on the stage, the strong man supports enormous weights, not by muscular effort, but by so placing his body that the bones form pillars of support on which the weight rests. In young children the centre of gravit}^ is high, for the head is large and the small feet form but a narroAv base. A slight push from behind brings the centre of gravity outside the base, and the child must move its feet quickly forward or fall. Thus the tiny child has many tumbles, for the brain has to learn by exj)erience how to carry out rapidly the appropriate movements. The younger a child the more he tends to stand with his feet wide apart. The tottering old man also widens his base of support by using a staff. The body is equilibrated by means of the proprioceptive mecha- nism of the body (see p. 6.54) and the co-ordinating influence of the cerebellum and the cerebrum. Walking. — On standing on one foot the body is inclined to that side, so that the other leg is left free to move. In w^alking, one leg, say the right, is slightly bent at the knee and planted down in front of the other. The weight of the body is throAvn on this leg, Avhile the left leg, raised on the toes by the action of the calf muscles, forms a straight stiff rod. The left leg, by giving a push to the ground, next throAvs the body forAvards. Thereupon the right leg straightens up, Avhile the left, slightly bent at the knee, swings forAvard as a pendulum and comes doAvn in front of the right. It is noAV the turn of the right leg to push off, and of the left leg to bear the Aveight of the bodj\ The length and rapidity of the step in Avalking naturally depend on the length of leg. A duck Avaddles, a hen nnis. The longer a pen- dulum the slower it swings. Thus it is difficult for a long and a short man to keep pace, and a regiment cannot maintain a regular march Avhen the men are fatigued, for each soldier then falls into his OAAai natural SAving. Running. — In rinming, both legs momentarily lea\'e the ground. The muscles act far more poAA^erfully than in Avalking. The body is raised and thrust forAAard, not only by the contraction of the calf muscles of the hind-leg, but by the ixjAverful action of the extensors of the thigh, Avhich straighten the bent knee of the forward leg. The body thus propelled forAA'ards leaves the ground, Avhile the hind-leg THE MECHANISM OF MOVEMEXT o29 ••swings forward as a pendulum for the next thrust. The exact changes which take place during rapid movement have been analyzed by- taking a succession of instantaneoiis photographs on a tilm. 8uch a film passed at a correct speed through the cinematograph lantern faithfully reproduces the movement; the different photographs succeed each other so rapidly that they fuse together and give the sensation of a moving object. In real life we only get a fused impres- sion of the position of a moving animal. If an artist drew a horse in some of the attitudes revealed b}- instantaneous photography it would be deemed unnatural. The position of the feet in walking and nmning can be well seen in the footprints made in the firm, wet sand left by the receding tide. o4 CHAPTER LXT THE STRUCTURE AND PHYSICAL PROPERTIES OF MUSCLE The Structure of Muscle. — In the vertebrate animals, the muscles develop from cells which line the primitive coelom or body cavity. These cells become invaginated as buds from the c(jelomic .surface, to form a roM- of myomeres along each side of the animal. These flatten, so as to form two plates, the inner of which gives rif.e to con- nective tissue, the outer to the striated muscle of the body. The cells which are about to become muscle (the sarcoblasts) undergo a great lengthening, and show signs of nuclear activity. The division of the nucleus is amitotic — there is no division of the cell body — and many nuclei are formed in one cell. At this stage fibrils, or, as they are sometimes termed, sarcostyles, gradually appear in the sarcoplasra of the sarcoblast, faint at first, l)ut gradually becoming more distinct. The}' first appear on the inner side of the cell, gradually pushing the nuclei to the outer side. The formation of fibrils goes on until each cell appears a mass of fibrils, with but little interfibrillar sarcoplasm. Each fibril is composed of two kinds of substance, differentiated by staining and refractive liower. One substance — the isotropic — does not stain readily and is singly refractile; the other — the anisotropic substance — stains readily and is doubly refractile. Each substance is dei)osited alter- nately with the other at regular intervals in the fibril. Thus, after suitable treatment the fibril may be broken uj) into sarcomeres, or sarcous elements. The lines of cleavage take place in the isotropic substance; each sarcomere consists of a portion of anisotropic sub- stance, with half a portion of isotropic substance on either side of it. As all the sarcous elements of the neighbouring fibrils are in jierfect alignment — isotropic with isotropic, anisotropic with aniso- tropic— the general effect is to give the fibres that cross-striped appearance from which cross-striated muscle gets its name. The difference in the degree of differentiation of muscle is well seen in the human body. The musculature of the trunk and limbs (the skeletal muscles) djflfers from that of such internal organs as the bladder, intestines, uterus (smooth or non-striated muscle), and also from that of the heart (cardiac muscle). Voluntary or striated muscle is composed of a number of separate fibres joined together to form the muscle. Tiie character and number of these fibres varies considerably with different muscles. In some thev are ]iale and delicate — so-called pale or white muscle: in others 530 .STRUCTURE AND PHYSICAL PROPERTIES OF MUSCLE 531 the\' are coarser and coloured red by the presence of a pigment — red muscle. In general, it is found that this difference corresponds to a difference in function. The white muscles are those which are called upon to perform quick movements over short periods, whereas red muscles are those which perform less quick movements, but for longer periods of time, and often without any marked intervrls of rest. Thus, the leg muscles of the chicken are red, the breast muscles white; oa the other hand, the breast (flying) muscles of the Avild-goose are red. The length of the fibres also varies greath' with different muscles ; from some muscles fibres 12 centimetres long have been obtained. 7nus.n.~ — Fig. 2G3. — Longitudinal .Section of a Piece of Muscle from the Sucker Cata- STONius. X 1000. The Relations of the Dark and Light Elements during Contraction of the Fibril are shown in A, B, C. (After Daklgren and Kepner.) cap.. Capillaries; sar., sarcoplasm; mus. n., muscle nuclei; «., connective tissue nuclei; Q, anisotropic material; j., non-staining isotropic material. Each muscle fibre shows under the microscope longitudinal and transverse striations. The fibres are composed of groups of fibrils (sarcostyles), between which is a varying amount of clear, finely granulated protoplasm — the sarcoplasm. Some are rich in sarcostjdes and poor in sarcoplasm; others are rich in sarcoplasm, and contain relatively few sarcostj^les. In this lies the difference between j)ale and red muscles. For example, the red soleus muscle of the rabbit contains much sarcoplasm ; the pale gastrocnemius is composed mainly of sarcostyles. The sarcoplasm evidently affords material for sustained action to the sarcostyles, which are the contracting elements. In ri^or In tetanus 532 A TEXTBOOK OF J'H^SIOLQGY Smooth Muscle. — A smooth muscle fibre develops from a single tell with a single nucleus. Such cells specialize in the embryo out of the mesenchyme. Fibrils are deposited Avithin the cell, sometimes around the nucleus, sometimes to one side of it. In the latter case, the nucleus may appear on the side of the cell. The fibrils are homo- geneous, and vary in number. There is a considerable amount of sarcoplasm in the smooth muscle fibres, which generally take the form of elongated spindles with thin tapering ends. Occasionally, as in the aorta of 3^oung mammals, the ends may l)o branched. Cardiac Muscle. — The structure of cardiac muscle has been dealt with ill the section on the circulatory s\-steni (p. 122). The Physical Properties of Muscle. — In speaking of muscle, we gener- ally mean striated muscle, since this is the kind of muscle which forms the flesh and has been most investi- gated. The living muscle fibre is semi-fluid and translucent. Its fluid nature has been shown by the fact that a nematode worm has been observed to traverse it, and after the jiassage of the invader, the muscle substance to return to its previous ordered structure. Muscle is very extensile and elastic. The former property is shown by the fact that but a small stretching force is required to change its shape, the latter by the fact that when this stretching force is taken off the muscle resumes its previous form. Living muscle has a Avide range of this elastic property; it requires a very considerable force to overstep its limits. If a stretching Fig. 264.-EXTEXSIBILITY of Muscle ^0^'^© ^e applied suddenly and in- iK Various States. (Waller.) creased by equal increments, a living Tested by 50 grammes applied muscle extends most at first and for short periods. then by less amounts till the limit of its extension without rupture is reached. Conversely, on removing the extending force, the muscle returns at first quickly and then more slowly to its original form. Rubber and most inorganic bodies, such as metal rods, on the other hand, extend almost equally for each increment of the extending force, and return almost equally as the stretching force is removed. Dead muscle is less extensible and less elastic than living muscle (Fig. 264). A contracted muscle is more extensible than a resting one. This gives us the paradox that, if a muscle A\ere loaded bj' a weight Fatigued .STRUCTURE AND PHYSICAL PR0PERTIK8 OF MUSCLE 533 greater than it could lift, it would actually lengthen during its .stimulation. The above properties are of great importance in the body. If a nui.scle were not readily extensible, the sudden contraction of one set of muscles would tend to rupture those muscles (the antagonizers) which perform the opposite action. Moreover, the contraction of a muscle acting through an elastic medium is more efficient than through a rigid medium. It is far less jerky in its effects. The smooth working of the various body movements and of the circulation depends greatly upon this elastic property. The muscles are kept in a slight state of tension, so that no time is lost in " hauling in the slack." The elastic property of the muscle insures its return to the normal state after any contraction has been performed. Again, if the contracting muscle were not more extensible, there would always be the risk, when trying to lift a heavy weight, that the muscle would rupture either itself, or its tendon, or the bones to which it is attached. Of these three structures, the muscle is least often ruptured. Muscle is also excitable or irritable — that is to say, it responds with a contraction to different forms of stimulation. A nmscle may be stimulated directly or indirectly through its nerve. An excised muscle maj' be directly stimulated by any sudden change in its physical state — b}' mechanical, chemical, thermal, or electrical stimuli. Striking a muscle or pricking it causes its contraction; sudden heating or cooling of a muscle may cause it to contract. Among chemical excitants, we find that the application of such substances as ammonia, dilute acids, strong saline solutions, induce muscular contraction. Excitation follows any sudden alteration in the concentration of electrol}i;e8 in the fluid bathing the muscle fibre:. In experimental work, the electrical method is most generally emplo3'ed for purposes of stimulation, since it is convenient, easily graduated and less injurious to the tissues.* The source of the electro- motive force may be a Daniell or a Leclanche cell. To make and break the current, a mercury or a spring key is used, preferably the latter. To protect the preparation from the current, a short- circuiting key is used (the Du Bois-Re3'mond key). When shut, the current is short-circuited through the metal blocks, which are attached to a wooden or vulcanite base; when open, the current flows to the preparation to be excited. Sometimes it is desired to reverse the direction of the current, or to shunt it into another preparation. For this purpose, special forms of keys are used. For making the actual stimulation of the preparation, electrodes are used. These may be made of needles insulated by a small piece of cork, and soldeced to pieces of fine insu- lated conductmg wire. Such ordinary metal electrodes tend to polarize, owing to the electrolysis which takes place in the tissue fluids at the pouit of application. For accurate work, therefore, noii- l)olarizable electrodes are required. A form connnonly employed * Ihc student is advi.ied to consult a practical n'.anr.al fur details of apparatus. 534 A TEXTBOOK OF PHYSIOL* )(iY consists of a smooth amalgamated zinc rod dipyjiug into a saturated solution of zinc sulphate contained in a U-tuhe. Into the other limb of the tube is inserted a glass flange carrying a plug of kaolin paste made up with physiological saline solution. The kaolin plug is pulled out to a point which serves as the electrode, or pieces of lamp-wick soaked in the paste may be employed to make the contact. p]lectrical stimulation may be made either with a constant current or with an induced current. With the former, the current from the cell or battery is led by a make-and-break key direct to the muscle preparation (Fig. 265). Stimulation is effected at the moment when the current is caused to flow (at make) (Fig. 2BQ), or stopped from Fig. 265. — Plan of the Use of a Constant Cukkent to Stimulate. Fig. 266. -ClKCUIT ARRANGED WITH ShORT-CiRCUITING Ke:- : KeY ShUT. OPENING Key = Make Shock. Fig. 267. — Circuit arranged with Short-Circuiting Ktv: Key Open. Closing. Key = Break Shock. flowing through the preparation (at break) (Fig. 267). There is no sign of stimulation while the current is actually passing through the muscle, provided the current be not too strong. If the current be strong or the muscle injured, a long-continued contraction may take place both in frog and human muscle. When muscles are degenerating, it is found that the j)assage of even a relatively weak current maj^ cause this jorolonged contraction, sometimes termed '' galvano-tonus." The contraction which occurs at the make is stronger than the contraction at the break of the constant current. The make con- traction starts from the kathode, the point where the electric current leaves the muscle; the break contiaction starts from the anode, the STRUCTURE AND PHYSICAL PROPERTIES OF :\IU8(:LE 535 point Avhere the current enters the muscle. Tne alteration of concen- tration of electrolytes under the kathode heightens, while that under the anode dejjresses, excitability durmg the passage of the current. When the current is broken, the effects are reversed (see p. 5S3). To alter the strength of a constant current, a piece of apparatus known as the rheocord is used. In its simplest form this consists of a Avire wound to and fro across a board, with a terminal at either Fi:;. 2GS. — To illustrate the Prixciple of the Rheocord. end and a movable contact or slider between them (Fig. 2t3S). In use, the cell is comiected to the two terminals A, B, and the prepara- tion comiected to the end A, at Avhicli the current enters, and to the slider S. The current from the cell can now pass either through the preparation or back along the wire of the rheocord. Tiie amount which will pass in either direction is determmed by the position of S. The fall of potential in the rheocord is from .4 to B; therefore, when Fiti. 209. — Diagram of an Induction Coil and its Connections. >S is near to A, the fall of potential from .4 to S is small, and but little of the current will pass to the preparation. Tiie amount of current, therefore, going to the preparation is directly proportional to the fall of potential between .4 and S. It is also inversely proportiona' to the resistance of the circuit through the nerve. Tnis resistance, however, need not be considered, since the resistance in the nerve is so many times greater than that caused by any change in the position oiS. r)8C A TKXTBOOK OF PFfVSrOLOCY The ccn.stant current i.s not often employed, since it is of low electrciuctive foite (E.M.F.), and, owing to its comparatively long duration, it tends to cau.^-e i)olarization of the tissues, due to the dissociation of electrolytes from the colloid of the muscle substance.. The induced current is therefore more convenient, since it has, as compared with the constant current, a comparatively high E.M.F. , and, being of very sh(;rt duration, does not induce so much polariza- tion of the tissues for ortlinary exjieriments it is practically nil. The induction coil comjjrises two coils — the primary and the^ secondary. The primary coil is made up of a few turns of thick copper wire wound around an iron core. The secondary coil consists of a large numler of turns of insulated fine copper wire. Each turn of wire in the primary coil induces an effect in every turn of the Avire of the secondary coil. By this means, therefore, the low E.M.F. of the current in the primary circuit is transformed into a current of high E.M.F. n the secondary circuit, the intensity of the current fceing jDroportional to the number of turns of wire in each coil. It has been found that the E.M.F. of this current var:"ef — 1. D'rectly with the intensity of the change of current in the primary circiit. The greater the change, the greater the induction. 2. Eirectly as the rate of change. The more rapid the change, the greater the induction. 3. With the argle between the coils. When the secondary coiH is at right angles, there is no induction. It is greatest when the wirea are parallel to each other— ?.e., in the ordinary position. 4. Inversely as the distance between the coils, being greatest when the secondary is completely over the primar}' coil. The induced current is in the op^DOsite direction to that of the jrimar}' circuit at make, in the same direction at break. When the induced current is employed for purposes of stimula- tion by means of single shocks, the current from the battery is led into the primary coil of the " induction coil '" by means of the two top binding screws. There is no direct connection of the muscle with the battery, this beirg placed in connection with the secondary- coil of the ajoparatus, and protected from stimulation, except when wanted, by a short-circuiting key. A make-and-break key is placed in the jrimary circiit, and the current in the primary coil made to induce an exciting current in the f-econdary coil of the apparatus, either by closing tl e kej' (the make induced current) or by opening it (the break induced current). An induction shock is produced cnly at make or break not while the current is flowing. The strength of the induced current may be adjusted by varying the distance between the primary and secondary coils. General^ speaking, an experiment is begun with the coils far apart, and the .'eccndarj' coil then advanced until the stimulus becomes effective (Fig. 269). The contraction obtained from a muscle at the break of an induced current is stronger than that caused by the make of the current. This is because there is at make a momentary self-induced current in the primary coil which is opposite in direction to that of the battery STRUCTURE AND PHYSICAL PROPERTIES OF MUSCLE 537 current. At the break of the current, an extra cuiTent is also pro- duced hi the ])riiuar\^ coil in the .same direction as the battery current ; but the primary circuit being broken, it cainiot delay the rapidity of the fall of the battery cm-rent. When rapidly induced shocks (50 to 100 per second) are required (the so-called faradic or tetanizing curi'ent), the primary circuit is rapidly made and broken by means of Wagner's hammer. The wires from the battery are connected to the two l)ottom screws of the primary coil (Fig. 270). It will be seen that the current passes, via the pillar A and spring H. through the primary coil to the electro-magnet E. This becomes an electro-magnet, and pulls down the piece of steef on the spring H, and thus breaks the circuit. E then, being no longer a magnet, releases the spring hammer, which flies back, and again completes the circuit; and so the process is repeated. Every time the hammer is attracted to the magnet the current is broken, and a break r.c Fig, 270. — Diagram to show the Action of Wagner's Hammer. shock induced; every time it tlies back a make shock is induced Here again the make is less in intensity than the break shock. The make-and-break shocks can be equalized by placing a wire from the binding screw (7) to the top binding screw (1) of the primary coil, and screwing up the top screw S^ out of the way, and at the same time screwing up screw S^. The current now passes into the primar}^ coil b^' this wire. E, as before, becomes a magnet, and pulls down the armature. This short-circuits the current back to the battery. There is still left, however, a circuit for the extra break current (7, W, 1,PC, E, H, A, 7), and this reduces the strength of the break current in the secondary coil, thereby equalizing the make and break currents (Fig- 271). Proof is required to show that a muscle is really stimulated directly, and not indirectly, through the nerve-fibres and nerve-endings in the muscle '. The direct excitability of muscle is shown by the following experiments: (1) Parts of muscles which contain no nerve- fibres — for example, the end of the frog"s sartorius — respond to direct 538 A TEXTBOOK OF PHVSTO].OGY stimulation. (2) Muscle Avill contj-act in response to certain chemical stimuli — e.g., ammonia — which do not excite nerve. (3) The Sonth American arrow-poison curare abolishes the action of nerve by paralyzing the nerve-endings in the muscles; yet, under these condi- tions, the muscle is directly excitable. The experiment is generally made as follows: Both the sciatic nerves are dissected out in the thighs of a frog in which the cerebral hemispheres have been destroyed. Fig. 271. — Diagram to show the Action of the Helmholtz Side-AVire. Round one thigh, but not including the nerve, a ligature is tied. Curare is injected into the dorsal lymph sac, and circulates everywhere but in the ligated thigh. The upper ends of both sciatic nerves are certainly exposed to the action of the 'drug. It is found that stimula- tion of the nerve -supply to the ligated side j^roduces a contraction of that leg, whereas stimulation of the nerve to the other leg does not. Direct excitation of the muscles, however, causes a response in both legs. The block is therefore in the nerve-endings. CHAPTER LXII THE CONTRACTION OF MUSCLE The great property of muscle is its power of craitractility. When a muscle contracts — 1. It undergoes a change in shape, becoming; -horter, tenser, and thicker. 2. It becomes, as we have seen, more elastic and my the contraction, a 539 r>40 A TEXTBOOK OK 1»H VSlOl.O(;Y time tracing is simiiltaneously recorded on tlie drum. Tills may be. done either with a tuning-fork or. better, with an electro- magnet chronograph. When working with single induction shoclis, the exact point at which the stimuhis l.s thrown into the muscle is obtained by placing Fit.. 21A. — The Si.mple Lever with Aftek-Loadixg Screw. F, Clamp; L, lever; M, muscle. the kjniiograph in the primary circuit. The drum carries a metal striker, which, as the drum revolves, strikes against a piece of metal mounted on the stand of the drum but insulated from it. One wire is attached to the metal stand of the drum, the other to the insulated metal. The current in the primary circuit is therefore Fig. 274. — Diaor.v.vi of the Apparatcs for Recordixg a Sixgle Mu.scular Contraction. rapidly made aad broken when the striker hits and passes the insulated metal (Fig. 274). In recording a muscle curve, the muscle may have a weight directly pulling on it. Th<- muscle is then said to be '^ loaded." If, however. THE CONTRACTION OF MUSCLE 541 the weight be so arranged that the muscle only raises it during its contraction, it is then said to be '" after-loaded." When the resistance is slight, so that the muscle can change its shape during contraction, Fig. 275. — A Single Muscular Contractiox {Frog'.s Gastrocnemius). From I to 2 is the latent period; from 2 to 3, the period of shortening; from 15 to -i, the period of relaxation. Time in ,,^7^ seconds. the curve yielded is said to be " isotonic." Its length alters, but the tension remains eqnal throughout the contraction. This is the case when the contraction is I'egistered by such forms of apparatus as Fig. 27<>. Upper curv nemius left -CoMPAKisux OF Contractions of Reu and White Muscle of Rabbit, stimulated indirectly. (M. S. Pembrey.) ;t' is response of the red soleus, and lower c\irve that of the white gastroc- L Time marker, 50 per second. The tracing to be read from right to are shown in Figs. 272. 273. When the mu.scle contracts against a lar^re resistance, I0 that it can shorten but little, the recording lever gives an " isometric " curve. The muscle in these conditions remams of approximately the same length, but alters in tension. 542 A 7 KXTBOOK OF PHYSIOLOGY The length of tjuie taken by a single contraction or twitch varies greatly with the kind of muscle employed. In general, the response of the gastrocnemius of the frog occupies about one-tenth of a second (Fig. 27'>). The following table gives examples of the time of various muscles Seconds. Tortoise: Peetorali- major .. *. .. .. 1*8 Semi-nsfmbranosus Frog : gastruf-neniius . . Hyoglo-*sus (tongue) Rectu« abdominis Wing muscle of w asp . . Wiug mu.Mole ot honey-bee Win2 mu.'«'le of bumble-bee 0-r, 0-12 0-2.'i 0-17 0-009 0-005 n-n04 The muscle curve may be divided into three periods — the latent period, the period of contraction, and the period of relaxation. In the ordinary grajjhic curve of the frog's gastrocnemius these periods occupy approximately , i,^, ^^^y, and j,^;„ of a second respectively. In such a curve, the length of the latent period does not represent the true latent period of the muscle. It is, in reality, much too long, and is due largeh' to the inertia of the apparatus. This may be shown by contrasting the graphic curve, in which the muscle pulls upon the writing lever, which is made to record upon a smoked surface, with the curve obtained when a muscle is excited, and its change of shape recorded photographically. Under these latter conditions, the latent period is but (»-001 to O-OO") of a second. This latent period is probably due x>> the time taken by the impulse to reach sufficient muscle fibres to bring about a change in the shape of the muscle. Although in the graphic curve the length of the latent period is mainly due to the inertia of the apjiaratus, it is partly due to another factor — namely, that the contracting muscle is more extensile. With delicate recording apparatus it can be shown that the latent period, representev a straight line in the ordinary- muscle curve, should be rvj -shaped, owing to the fact that, as the muscle starts to contract, it becomes more extensile, and is stretched somewhat by the- recording lever; thus the true beginning of the AAAAAAAy^.i^i^A^v*~"v77~ period of contraction is as a rule not '■ recorded. Fig. 277.— Cukves. it Arrested When the muscle is " indirecth- " CosTRACTioNs OF UxLOADED stimulated— that is, when the impulse MvscLE. (Kaiser., . ,, x j.- • i x ^i, causmg the contraction is sent to the muscle through the nerve supplying it — the time taken for the impulse to jiass down the nerve through the nerve-endings to stimulate sufficient fibres to induce contraction adds considerably to the latent period of contraction. For this reason, the latent period of direct stimulation of a muscle is shorter than that for indirect stimulation of the same muscle. In general, it may THE COXTRACTION OF MUSCLE 543 be stated that the shorter the whole period of the muscle twitch, the shorter the latent period, and vice versa. The Period of Contraction is the period daring which the mnscle shortens until the maximum shortening is reached. It is the period Fig. 278. — Vekatrix Curve. (Waller.) of rising energy. In graphic curves, this is represented as too long, sirice the recordmg lever owing to inertia tends to rise too high. This can be demonstrated by arresting the lever at different heights during the process of contraction. At a certain point before the Fig. 279. — The Effect of Temper.\tube upon the Contraction of the Gastrocnemius Muscle. (Pembrey and Phillips.) The time is marked in ^Jo second. The tracing should be read from right (u kft. Figmres on curve are the temperatures of the salt solution. summit of the curve is reached it will be found that the lever as soon as it touches the arresting body, immediately starts to fall. That point marks the true height of the contraction (Fig. 277). Tne difference in the contraction time of different muscles is mainly due to difference m anatomical structure. The quickly con- 544 A TKXTBOOK OF PHVSIOIJKJY Iracting nm.scles are those rich in sarcostvlcs, the slowly contracting muscles those containing abundant sarcoplasm ; many muscles are mixed. It has been suggested that, when the number of sarcostyles I'lG. 280. The npper curves show the latent period and movements of two levers on muscle at 15° C, the lower curves at r>° C. It will be seen that the latent period is shorter at 15° C. than at 5° C, also that the rate of conduction given by the dif- ference in the latent periods is quicker at 15° C. than at 5° C. (V. J. Woolley.) are not greatly in excess of the amount of sarcoplasm, the muscle curve may show two summits — the first due to contraction of the sarcostyles, the second due to contraction of the sarcoplasm. This is Fig. 281. — The Effect of Load upon the Contraction of the Gastrocnemius Muscle. (A. P. Beddard.) the explanation sometimes afforded of the curve given by the vera- ti'inized muscle (Fig. 278). It is also suggested that the slow response of a fatigued muscle may be a response of the sarcoplasm after the quickly responding sarcostyles have ceased to respond. For example, THE COXTR ACTION OF MUSCLE 545 in a fresh state, the triceps femoris of the rabbit gives a quick response; when fatigued, it yields a long-drawn-out curve. The Period of Relaxation is from the maximum shortening of the muscle to the position of rest. The relaxation has been thought to be due to an active process, but there is little evidence of this beyond • the fact that there ar^ special changes going on diu'ing it (see p. 554). The Conditions which affect Muscular Contraction. — Beside the ■constitution of the muscle and the effect of drugs, such as veratrine, the muscle response is affected by other conditions, such as the strength of stimulus, the temperature, the amoinit of load, and previous activity. The Strength of Stimulus. — Striated muscle gives a graduated response according to the strength of stimulus. With a weak (minimal) stimulus, it just contracts. The contraction then increases in amount with the strength of stimulus until a maximal contraction is obtained, after which no increased contraction is obtained, however much the current be strengthened. The minimal contraction is due to the FlJ. 282i^-^OXTI>"UATION OF THE EXPERIMENT IN Fli. 231. SiNGLE COXTEACTIOXS 'of THE G.\.STROCNEMIFS WITH DIFFERENT LoADS. (A. P. Bcddaid.) The figures on the curves represent the veights in grammes hung at the axis of the lever; actual load on muscle \va,s in each case one-fifth. Magnification, o. Tcmg,erature, 12" C. weak stimulus only spreading to a few fibres. Probably any stimulus which is^ft'ectupl makes the fibres affected contract maximally. Temperature. — Cold (0" to 3^ C'.) lengthens the whole curve, especi- ally the latent period and the period of contraction. The rate of con- fluction is also lessened by cold (Fig. 280). Frequently the relaxation is incomplete. shoAving a " contraction i-eniainder." At first the height of the contraction is increased, then dimmished. Gentle warmth (25^ to 35° C.) increases the rate of all stages of the curve, and greatly increases its height ])artly due to an ineitia effect of the lever (Fig. 270). Heat (42° C. in the frog) coagulates the muscle proteins, and brings about a condition of " heat rigor." Load. — An increase in load is found generally to decrease the amount of contraction, and lengthen the latent period (Figs. 281. 282). When, however, a muscle is fresh and in good condition, the first few increments of load may give an increased height to the contraction. When the work done bj- the muscle is calculated — Work done ^ load lifted x height o4G A TEXTBOOK OF PHYSIOLOGY — it will te found that the amount of work done at first increases with the load, and then diminishes, giving a " curve of load." The actual height through which the weight is lifted is obtained ])v dividing Fig. 283. — Fatigue: Fkog's Gastrocne.mits. (\\'alkn.) Direct excitation; 125 successive maximal contractions at intervals of li seconds,, showing at the outset increase of height and of duration, later (kcrca^:ng height. The exhaustion has not been pushed to the end. the height of the curve by the magnification due to the recording lever. For purposes of " load " experiment, it is better to use the form of apparatus shown in Fig. ^73, since the load can then be applied directly below the muscle. Fig. i;S4. — Fatiguk Cukves uf B, Saktokius Muscle in Kikgek's .S(iectio>^; G, Sartorius after FiFTESN-MiNurE Immersion ik Guanidik 0*1 per Cent. SoLUTUix. (Camis.) Tin.e in seconds. The staircase effect is seen and also tlie depressant effect of guanidin in high concentrations. Previous Activity. — When curves are taken from a j^erfectly fresh muscle preijaration, the first few may show an improvement in the degree of contraction. This is known as the '' staircase effect," and THE CONTRACTION OF MUSCLE 54' it is suggested that it is due to the beneficial action of the meta- bolites formed in the previous contractions. When the contractions are made to follow each other without any pause they finallj' become less and less, and the relaxations become more and more draAm out, a well-marked "' contraction remainder '' usuall}' aijpearing, until eventually the muscle gives no contraction at all; the muscle is " fatigued " (Figs. 283. 284). ■■ Fatigue " is due mainly to the accumulation of the products of acti\aty within the muscle — in part, however, to the usmg up of food material. The fatigue products are acid in nature — chiefly lactic acid. Fatigued mu.^cles j^laced in oxygen recover more quickly (Fig. 285). If the muscles be made to conti-act in an atmo.sphere of oxygen, lactic acid does not appear, and the onset of fatigue is much dela3"ed or postponed altogether. Recent evidence tends to show that B^ CO/VT-/fAC k A ■ -^ /PCL finA'^ ^rre/f £Arc/s/o/v I? 15 »8 21 ?+ Fi(;. 28.5. — Changes ix Length of a Pair of Excised Gastkocnemii aftei; Fatigue. (W. M. Fletcher.) .1. Exposed to oxygen; B. exposed to air. Load 3 grammes, temperature Iir ('. The ordinates are measured directly from the record; levers magnified six and a half times. 27 lactic acid is not normaily a waste product, but a stage in the metabolic changes of the muscle. A muscle through which the blood is cir- ctdating is fatigued only when either the load, or the frequency of contraction is made too great. Thus the muscles of the skilled Avork- man perform thousands of contractions without fatigue. So with the respiratory muscles and the heart. To secm"e the maximum output of athletes or workers, load and frequency must be carefully adjusted to prevent overstrain. Summation. — If a muscle be given two stimuli m quick succession, the effects of the two are added together — " summated "' — and a bigger curve is obtained than either of the single curves would have been if recorded .separately (Fig. 286). If, however, the interval between the stimuli be very short, so that the second stimulus falls within the latent period of the first stimulus, then, if this be maximal, no summation is obtained, the curve is unaffected by the second 54S A TEXTBOOK OF PHYSIOLOGY stimulus. Jf, however, the first stiniuhis is not producing a maximal contraction, then the second stimulus will add itself to the first, and again a greater effe3t is obtained than would have obtained by either -separately. Flu. 286. — SuPEKPOsiTiON OF Two Single Coxtkactioxs. ISach contraction is recorded alone by a break shock caused by opening a fixed key: both keys are then set, and the recording plate striking them open successivelj-. causes two stimuli and a summation of the two contiaction.". F.m. 287. — CoMFOsiTioj. of Tetanus. (Waller.) Stimuli caused by a spring interrupting a primary circuit by vibrating in and out of a mercury cuj); the vibration frequency is increased by shortening the spring. THE CONTRACTION OF ilUSCLE rAif Fig. 288. To be read from right to left. Photographic curve of sartorius muscle by isometric method. At first two submaximal stimuh, followed by two pairs of maximal stimuli, then by a tetanus, followed by another pair of single responses. The tension set up in the mufcle during tettni:s is greater thfn the maximal tension, of a single twitch. [0. R. Mines.) ikX. [-^S:xU ^.^Lauu^ Fig. 289. — Spontaneous Movements in Toad's Sartokivs in 7 pee Cent. Sodiusi Chloride. (G. R. Mines.) Temperature 8° C. Time in seconds. A • 1 ■ \ • i Fig. 290.— Biceps Cruris of Frog in Sodiu.m Chloride 0*65 peu Cent., Potassium Chloride 0*05 per Cent. (G. R. Mines.) A period of one second is marked below. 550 A TPLXTBOOK OK PHYSIOLOUV Owiiig to this ))roperty of summation, a iiinnber of successive stimuli may cause a number of contractions l>et\\x-en Avhich the muscle does not properly relax. The greater the fre({uency of the stimuli, the less the relaxation between each contraction, until at last a long, fused, compound curve is obtained, known as the " complete tetanic curve." Tetanus is produced by„ about 30 to 50 stimuli per second in the case of frog's striated muscle. The number varies Avith the tem})erature and the state of the muscle. When Avarmed. more stimuli are required; when cooled, less are needed. If the muscle be fatigued, fewer stimuli are required to induce the complete tetanic contraction. LLiliiUiiJlU X X V X X ^ X nMIMIglilBIHiUlSHli J, -, -, r Kci OS-/, Fig. 291. — Sakturius of Frog, sumulated ALTEKNATiLY \mth »jalvaxic Current AND IndtjctiOjST Shock at Thirty-Second Intervals. (G. R. Mines.) Each response to an induction shock is marked with a cross. At the beginning of tracing the muscle was in NaCl 0*7 per cent. ; at arrow fluid was changed to NaCl 0-65 per cent., KCl O'OS per cent. The genesis of tetanus is studied by employing the vibrating reed. By varying the length of the reed, the number of stimuli per second is easil}' regulated, and all forms of incomplete to complete tetanus may be obtained (Fig. 237). Incomplete tetanus is sometimes termed " clonus." Ankle clonus may be elicited in certain nervous conditions Avhen the foot is suddenly bent up. PoAverful alternating currents, A'ibrating frequently to and fro in opposite directions — e.g., 1,000,000 per second — may be passed through muscle Avithout producing excitation, and with suitable apparatus, such a current may be sent through several peojole and electric lamps. The foriUer feel nothing, Avhile the lamps gloAv. THE CONTRACTION OF MUSCLE 551 Muscular "" Tone."' — During life, the muscles, never fully relaxed, are kept in a state of incipient conti-action. or '" tonus '" — a condition dependent upon their connection with the central nervous system. The muscles are ceaselessly influenced by their nervous centres, whit-la ill turn are excited b}' messages reachuig them from all parts of the body, particularly the skin, joints, and the muscles themselves. This tonus makes for a general " wakefulness " — a readiness to contract — on the part of the muscle. It also plays a considerable part in the production of heat within the body, being reflexly in- creased by sensations of cold, and relaxed bj' sensations of warmth. It is also affected by mental states, such as excitement, anger, fear. X X X X X X X X X '7Z \[C'(Uo^y, t /^-ar/ t K- ^X -'^y- t Na CI '77. Fig;. 292. — Saktokius of Frog, stimulated at Intervals of Thirty .:>econu!s Alternately with Galvanic Current and Induction Shocks at x . (G. R. Mines.) Spontaneous Movements. — Amphibian muscles in saline solutions exhibit sjjontaneous movements (Fig. 2S9). These movements will continue in concentrated curare solution, indicating that the source of the movements lies in the contractile substance of the muscle fibres. This is also proved by experiments on muscle containing no nerve endings, e.g., the non -neural regions of the sartorius muscle. Potassium chloride at first increases the movements, often causing a very rapid rhythm (Fig. 280), and then stops them entirely. Its effect on the excitability of the muscle tOAvards galvanic currents of long duration, m hich is increased m this condition of the muscle, is a further exaltation and then depression (Fig. 291). The addition of calcium chloride leads to an immediate diminiition or cessation of the move- ments and a fall in the excitabilitv towards galvanic currents (Fig 292). CHAi'TKR Lxnr THE PRODUCTION OF THERMAL AND CHEMICAL CHANGES IN MUSCLE That muscular exercise i)roduce.s warmth is a familiar observation. For this reason, hard muscular exercise is uncongenial on a ver\' hot day, but is resorted to when the temperature is low, since, under these conditions, even the habitual loafer is often constrained to beat his arms across his chest or stamp violently to keep his feet warm. It is somewhat difficult to show by means of the mercurial thermometer the development of heat during the contraction of the excised muscle, even when a very sensitive thermometer is inserted between the mviscles of the thigh, and the sciatic plexus stimulated. It has been calculated that during a tetanus of two to three minutes^^ duration the temperature of a frog's muscle rises on an average- about 0 ir/^ C. If Couples. Fig. 2!);?.— SixOLE-PAiR Thermopile connected to Galvanometep.. The production of heat can not only be shown but measured hy means of a thermopile. If a thermopile (Fig. 293) be placed between the calf muscles of a resting limb of a frog, and another between the- calf muscles of a limb which is made to contract, and the two thermo- piles be then connected with a galvanometei . it will be found that contraction liberates sufficient heat to cause a deflection of the gal- vanometer needle. When both sets of muscles are at rest, no de- flection takes place. For accurate work, special forms of apparatus are used (Fig. 294). The muscle fibre has been regarded as a heat engine. It has been suggested that the contraction is produced by the production of heat in the locality of the fibril, which contracts under the influence of heat. Such a conception is erroneous. The muscle is rather to be regarded as a chemical machine Avorking at constant temperature. It has been calculated that to behave as a heat machine it would be necessary to keep up a temperature difference of 10(V C. at two points not more- THERMAL AND CHEMICAL CHANGES IN I^IUSCLE 553 than a few t^i apart. This would mean an almost infinite loss of heat by conduction between the two points. It is inconceivable that such differences of temperature exist. It has been shown, moreover, that the heat is not formed solely during the period of contraction of the muscle. It is formed both during the contraction and during the relaxation (Fig. 295). There is, moreover, no constant ratio between the amount of work done and the amount of heat evolved. High, initial tension and strong excitation favour the production of heat. Fia. 294. — Double TutRMoriLE, Each of a Pair of Sartorii being in Contact WITH One Set of Junctions. (A. V. Hill.) ,-l, .1. Junctions of iron and constantan in contact with front sartorius, M; B, B, junctions in contact with rear sartorius, M' ; K is bone of pelvis held by clamp, I) ; G, copper leads to galvanometer: E. electrodes — only two out of four shown. Arrow shows direction of current. Only six instead of twenty-four to thirty junctions shown. An isolated frog's muscle at 15-5° C. continues for about five houra to carry on the normal oxidative processes of life, but at a declining rate. This is due to the gradual exhaustion of the oxygen supply, and to the gradual accumulation of waste products other than CO.j. Possibly, also, the supply of oxidizable material becomes exhausted. The initial process of contraction consists largeh*, if not entirely, of the liberation of potential energy, which is manifested as " tension energ}^ " in the excited muscle. This potential energy' is capable of l^eing used indifferently for the accomplishment of -^Aork or the pro- duction of heat. The efficiency of the whole of the processes, in- cluding those of recovery, is sometimes as high as 50 per cent. — that 554 A TEXTBOOK OK I-HNSIOLOOV is to say, 50 per cent, of the energy of the foodstuffs katabolized may appear as Avork, an efficiency much greater than that of a steam engine (10 per cent.), and greater even than the best petrol engine (30 per cent.).* In the muscle machine, the " free energy " which is ti> become mechanical or thermal energy is stored in certain unstable chemical compounds, one of which is possibly the lactic acid precursor. During the preliminary stage of the contractile process, certain molecules are liberated in the muscle under the iuHiience of oxygen /00 7 fo Fig. 295. — Galvanometer Deflection showing Fall of Temperatuf.e of Muscle .^TTEE Excitation in Nitrogen, in Oxygen, and Warmed when Dead as Control. (A. V. Hill.) The curve for living muscle in nitrogen nearly coincides with control curve, but the curve for living muscle in oxygen after nitrogen is very considerably displaced to the right, showing continued heat ])roduction during relaxation of the muscle. and with the production of heat — for example, lactic acid from its unstable precursor. Tnese produce " tension energy," occasion the contraction, and are then, under the further action of oxygen during the relaxation, removed or re^ilaced in the muscle substance complex with the evolution of heat. It is conceived, therefore, that heat is developed in three stages: (1) During process jDreliminary to contraction; (2) during contraction; (3) during relaxation. The Mechanism of Muscular Activity is by no means clear. As we have seen, the application of the laws of the thermodynamics to * The efficiency of a labourer seems to be 20-25 per cent. THER:MAL and chemical changes IX MUSCLE 555 muscular contraction has afforded valuable information. The pheno- menon of contraction has also been studied fro]n the point of vieAv of the osmotic properties of the muscle. It has been suggested, after due consideration of the time relations of the contraction and the distance in the fibril through which osmotic force has to act. that muscular contraction may be brought about by this force. Provisionally, we may suppose that lactic acid is set free, and that combmes Avith protein to form a salt, with a conse- quent rise of osmotic pressure in the dim bands of the muscle fibrils, which therefore swell at the expense of the water in the light bands. Granting that this may be so, Ave do not knoAV hoAv the osmotic equi- librium is upset by the stimulus or restored during ielrixation. The Changes in the Chemistry of Muscle — 1. The Chemical Con- stitution of Muscle. — If muscle be taken from an animal and minced, and then squeezed, a plasma can be expressed horn it. This, like blood, possesses the propertA' of coagulating at body temperatuTe under suitable conditions. Upon analysis, it contains from 75 to 78 per cent, of Avater, 20 to 24 per cent, of organic and about 1 to 2 per cent, of inorganic bodies. The chief organic bodies are the proteins, of Avhich there are from 18 to 20 per cent. Various classifications and names have been given to these proteins. Avhich apparently A^ary in their properties according to their method of jweparation, the species of animal used (mammals, birds, reptilia, etc.), the condition of the muscle at the time of death, and the degree of post-mortem changes. To illustrate the chaos which perrades the nomenclature of these proteins, it may be men- tioned that the name '' myosin " has been given by different in- A'estigators to at least three different bodies. Tne most generally accepted classification of these proteins is into — (I) Myosin, or paramyosinogen, Avhich forms about one-fifth; and (2) myogen, or myosinogen, Avhich forms the other four-fifths Traces of albumin and globulin are also present, but these probably come from the blood and lymph, and not from the muscle proper. In the plasma of "" red " muscles the colouring matter is also present. This consists of haemoglobin or a closely allied conipound protein — myohgematin. Myosin, ov paramyosinogen, is a globulin soluble in dilute salt solutions Avhich coagulates on heating al about 45° to 50"" C. It is pi'ecipitated by AAcak acids, dialysis, half-saturation Avith ammonium sulphate, etc.. and gives the other reactions characteristic of globulins (see p. 51 ). It is characterized by its power of passing at body tempera- ture— probably under the influence of an enzyme derived from the muscle — directly into an insoluble modification known as myosin fibrin. Myosin (by eiizymic action) t MVOSI.N I-ICKIN. ^^).">f5 A TEXTBOOK OF PHY8IOLO(;V Myogen, or myosinogen, on tlio other hand, is an albuniin. It gives the characteristic reactions for such, and is therefore not [,re- ci])itated by dialysis, and only by com])lete saturation with ammonium sulphate. Its heat coagulation tem]:!erature is from 55° to 60° C. Unlike myosin, it is ap]iarently not coagulated at body temperature by an enzyme, but passes without such assistance somewhat slowly into a variety known as sohible myogen fibrin, which is coagulated by heating to l)ody temperature (37 to 40° C.) into insolu])le mj'ogen fibrin. Myogex •Soluble .Myogex J'ibrix (I)v heat at 37 '-40° C.) Insoicble Mvooex J-'ibrix. In the residue left after the exjiression of muscle jjlasma there is a protein which has been termerl myostromin. This is of the nature of a nuclein. This, together with some sclero-protein, the collagen of the fibrous tissue, probably forms the framework of the fibres. The sclero-protein collagen yields gelatin on boiling. Xucleo-protein is also present in the nuclei. A certain amount of fat is present, either in the fibre itself or in the interstices of the framework. Other bodies separable from the plasma comprise — Fats in small amounts. Glycogen in variable amounts, varjdng with the " freshness " of the muscle, its state of " activity "' or " rest." Generally, it is from 0-5 to 1 per cent. It is present also in larger amounts in embryonic than in adult muscles. Dextrose in traces only if the muscle be absolutely fresh. Inosit, CgHg(OH)^ + H.,0, a benzene compound having approxi- mately the same formula as dextrose, and sometimes termed musclfr sugar. It does not give the ordinar}- tests for sugar, is not fermented b}' yeast, and is without action upon polarized light. Sarcolactic Acid, CgHgOg, an isomer of the lactic acid formed by the fermentation of the lactose of milk. It is present only in fatigued or dying muscle. Nitrogenovs Extractives, the chief of which are creatin (sec p. 461); hypoxanthin, and xanthm (see p. 444). It is claimed that there is also present a complicated nitrogenous body known as Phosphocarnic Acid. It yields as cleavage products succinic acid, lactic acid, phosphoric acid, C0.>, a carbohydrate body, and a body known as carnic acid. Inorganic Salts. — The chief of these is the jiotassium phosjihates. Traces only of chlorides and sulphates are found. In addition, salts of sodium, magnesium, calcium, and iron, are found, their relative amounts corresponding to the order given. THERMAL AND CHEjMICAL CHANGES IX :\njSCLE 557 2. The Chemical Changes induced by Activity. — The methods used for investigating tissue respiration shoAV that an increased amount of oxygen is used up, and more CO., formed, when muscle is contracting than when at rest. If the hind-limb of a frog be tetanized, it will be found the plasma expressed from the muscles gives the colour reactions for lactic acid. The muscles of the resting limb give no such reactions. If the limb be made to contract in an atmosphere of oxygen, no lactic acid is formed, for it is only when the muscle is made to con- tract with an msuflficient supply of oxygen that this acid is formed. Such is the case in man during excessive muscular exercise. The lactic acid then formed can be shown in the urme and in the sweat. In the blood it plays an important part in the production of the carbon dioxide: (4) passes from a semifluid to a firm, solid state, or rigor. After death, this rigor supervenes in a more or less definite order — first the jaws, then neck, trunk, upper and lower limbs. The rate of onset varies. Generally, several hours elapse; but if just previous to death the muscles have been greatly fatigued, paiticularly in the absence of oxygen, the changes may set in at once. Soldiers are said to have been found standing dead in the trenches, with the rifle held to the shoulder, probably due to .shell-bm'st and oxygen deprivation t)y carbon monoxide. After a time — generally two to six days — this 558 A TEXTBOOK OF PHYSIOLOCV rigidity passes off. [u wasting diseases, rigor may not appear at all. or appear early and pass off quickly. Rigor is maitily due to the formation of lactic acid in the absence of oxygen. The lactic acid thus formed alters the normal reaction of the nmscle, and brings about coagulation of the muscle proteins. If the accumulation of lactic acid be prevented, either l)y the presence of oxygen or l)y perfusion of the muscle with saline, rigor does not supervene. Rigor may also be induced in muscles by ])lunging into boiling water. In this case, "' heat rigor "" takes place. The proteins of the muscles are coagulated without any attendant chemical changes, such as acid formation. Similarly, soaking in distilled water brings about a "water rigor." A water pressure of 400 atmospheres produces rigor of the muscles of terrestrial and shallow-water animal;;. Smooth Muscle. — Although smooth muscle is generally found in organs which [lerform slow movements, in some animals noted for quickness and grace, such as the squid, there exists nothing but smooth muscle. In the higher animals it gives motility to organs over which there is no voluntary control; hence the name " involuntary " muscle. In addition to a slow rate of contraction, with a long latent period, smooth nmscle is characterized bj^ the fact that it cannot be thrown into complete tetanus. Its contraction is of the nature of a single twitch. Smooth muscle, like striated muscle, responds to a gradation of stimuli, and shows thermal, chemical, and electrical changes. In chemical composition it is probably much the same as striated muscle. It undergoes bo*:h chemical and heat rigor. Smooth muscle possesses the property of tonus — a condition of sustained muscular contraction, which is influenced in the direc- tion of further contraction or relaxation by the nerve-supply. Aug- mentor or accelerator nerves increase tonus, inhibitory nerves relax. This double nerve-supph' is a characteristic of smooth muscle. Smooth muscle is also characterized by the propertv of rhyth- micity — periods of contraction alternate with periods of rest. This seems to be a function of the nnascle itself. Such is observed in the stomach, intestine, bladder, spleen, and other organs. Associated with smooth muscle are local nervous networks or plexuses, such as Auerbach's and Meissner's plexuses in the intestine. These endow the muscle with the property of peristalsis — co-ordinate and recurring waves of contraction, j^receded by waves of relaxation which together force the contents along the muscular tube CHAPTER LXIV • ANIMAL ELECTRICITY " Various tissues of the boch- displa\- electrical currents when in action or when injured. Such currents are sometunes referred to as " animal electricity." If a nerve-muscle j reparation be placed upon a glass plate, and by means of a glass rod the free end of the nerve be allowed to touch the muscle, a contraction occurs (Fig. 2C6). This is an experiment contrived bv Galvani to prove the existence of animal electricity. In his first experiment, Galvani used metals. He found that if the hind-limbs with the skin removed be sus- pended from an iron stand by a copper hook passed through the lower part of the vertebral column, contraction of a leg occurs every time it is made to touch the iron stand. He supposed that this contraction was due to animal elec- tricity. Volta insisted that it was due to the completion of tho circuit between the two metals by the wet tissue of the frog. From the contro- vers}' between Galvani and N'olta came about the invention of the galvanic battery, and the development of electrical science. The discovery of the electric fishes gave the crowning proof of animal electricity. The Malapterurus was known to the ancient Eg^qstians. and figured in their monuments. The electric eel of South America gives a most powerful shock. The natives used to exhaust wild-horses by driving them into a marsh infested with these eels, and so capture them. Animal currents now play an important part in the study of abnormal conditions of the heart. It was at first believed that natural currents pre-exist in normal resting tissues, but it is now kno^ni that these currents only occur when the chemico-physiological condition of the tissue is altered by activity or injury. The Electromotive Properties of Muscle and Nerve. — ^If a normal muscle or nerve be connected by a pair of non-polarizable electrodes to a galvanometer, no deflection of this instrument takes place, show- ing that normal muscle or nerve is isoelectric. Perfectly' '' normal " mu.scle is difficult to obtain, since it is necessarily injured m the pre- 559 Fig. 290. — Diagram OF Galvaxi"s Ex- terimext. cox- tkaction without Metals. r)()() A TEXTBOOK OF PHVSIOLO(;^ paration. A muscle which has been soaked iii normal saline several hours after its preparation is isoelectric. If a muscle which is at rest in such an isoelectric condition be damaged — e.g., by heating — it is found that there is now an electric current flowing through the galvanometer. In such an injured muscle Fig.I Eoxit YartccLLon/. Fig.EL ElactrotonuH Fig. 297.— Diagrams to Illustrate Current of Lnjury, Negative V'akiatio.v, Current of Action, Electrotonus. the injured part corresponds to the positive element of a galvanic battery. The cuiTent therefore flows in the muscle from the*injured part to the normal part; outside the muscle it Hows through the gal- vanometer from the normal t ) the injured part. Tne ' current of injury ' is usually described in terms of the direction of the current through the galvanometer; therefore, the site of injury is said to be negative (or zincative, like the zinc of the batterv) "to the normal " ANIMAL ELECTRICITY 561 tissue (Fig. 297). The current of injury can be simply demonstrated by Galvani s experiment already quoted. It may also be shown in nerve by placing the cut surface of the nerve on one plug of kaolin and the uninjured part on another. Then, if the attached muscles be sufhciently excitable, on bringing the kaolin plugs into contact with strong saline, which is a good conductor of electricity, the muscles contract (Fig. 298). Fig. 298.— Diagram of the Experimext to show the STiMrLAXiON of a Xerve BY ITS OWX '-CURREKT OF INJURY." Fig. 29!». — Diagram of the Experiment ox Secondary Twitch. Fig. ;?(iO. — Diagram of the Experiment to show the Stimulation of a Muscle BY THE " Current of Action '' of Another Muscle. A similar condition pertains when anv part of a muscle or nerve is more active than the rest. The active j^art in reference to the current tlu'ough the galvanometer is negative to the resting part. Such a current is termed the " current of action." It may be simply ishoM-n by laj'ing tAvo nerve-muscle preparations, A and B-, ujDon a glass plate, and placing the nerve of one muscle (A) along the other muscle (B). Upon exciting the nerve of B, the mu.scle contracts, folloAAed immediately by a contraction of A. Similarly, if B be 36 562 A TEXTBOOK OF PHYSIOLOGY tetanized through its nerve muscle, A also passes into the tetamc state The muscle A is stimulated to contraction by the current of action in A, and not by an3^ spread of the exciting electric current. This is shown by using the beating heart and a nerve muscle pre- f^bt o cd o 0 O; O (H +s- paration. If the nerve be placed upon the beating heart, the muscle contracts with each beat of the heart. Occasionally, if the nerve be ver}' excitable, the muscle contracts at the end as well as at the beginning of the heart's contraction. If two muscles be pressed together, excitation of either causes. ANIMAL ELECTRICITY 563 contraction of both. In this case, the current of action in one muscfe excites the other directly (Fig. 300). Normally, the presence of such currents is shown by the use of the galvanometer and sj^eciai apparatus (Fig. 301). If an injured muscle be led off to the galvanometer and stimulated, it is found that on each single contraction, or, better still, on tetanus, the current of injin-y is diminished or may be overbalanced, since 7b Lever K iOcm. Fig. 302. — Keith Lui as Moist Chamber and Electbodes. A, Glass rod; B, B, tubes containing platinum electrodes; the leading off electrodt^ are glas.s tubes tilled witb Ringer's solution plugged by filter candles containing zinc sulphate and below by cotton-wool wads D, D, connected to muscle ; E, ebonite trough with glass sides enclosed in felt F ; G, Ringer's solution immersing lower part of muscle; t1 , inlet. -/, outlet for fluid; A', accessory outlet for totallj' immersing muscle when •/ i~ closed. the change from rest to action is greater in the uninjured part than in the injured part. This diminution of the injury current is termed ''negative variation" (Pig. 297). When uninjured tissue passes into action, there is what is termed a '• diphasic variation." This is because first the part proximal to the stimulus is active, theti the distal i^art: the action is not simul- taneou.'i throughout the whole of the muscle. When A is active 564 A TEXTBOOK OF PHYSIOLOGY and B at rest, there is a current of action through the gah'anometer from B to A; when both A and B are active, there is no deflection. When B is active and A at rest, there is a current through the gal- Aanometer from A to B. If the transmission of the active state from A to B is quick, the isoelectric interval is naturally short; if it be long, the interval is .correspondingly increased. Thus, the rate of transmission of the wave of activity may be measured. In the nerve trunk of a frog it is about 30 metres per second; in striated muscle about 1 metre per second; in the frog's ventricle about ^\ metre per second. Eio. 303. TvriCAL Excuesion of Sartoeius Muscle to Single Inductios Twitch. (Keith Lucas.) Read right to left. In the heart, the current of action induces a triphasic variation. This can probably be explained as follows : Sujipose one non-polarizable electrode (B) is placed on the base of the ventricle, another (A) on the apex. The excitator}" wave enters the base of the ventricle by the A.-V. bundle. B is now negative to A. It passes then to the apex. A is now negative to B. The ventricles contract in such a mamiei •that the apex finishes contracting before the base. The blood is A^Tung out from the ventricle, and the muscle round the arterial orifices is the last to contract ; B finally, therefore, becomes negative to A. The response of the heart in terms of negativity is therefore B, A. B (base, apex, base). Cutaneous Currents. — Normally, the skin of all vertebrate animals is traversed by an electric current from without inwards (Fig. 305). This current appears to be caused mainly by the action of the cutaneous glands, or of active secreting single cells in the skin. When the pad "ANIMAL ELECTRICITY 565 of a cat's foot is made to sweat by stimulation of the sciatic nerv-e, the pouring out of the sweat is accompanied by an increase (a positive variation) of the ingoing current. If, however, the effect of the nerve be abolished by atropme, such a result is no longer obtained. The normal current of the skin is found to be increased by direct excita- tion, this increase or positive variation being reduced or abolished by the local application of atropine, chloroform, or carbon dioxide. ___ + 04- / \ ■ + 03- \ - + 02 V ■ + 01- / \ - 0 STIM. i ■J- \ \ -01- / i -02- / ■ ' \ -03- \ - —04.- , / • o > "/ - V-- Vu;. 304. — Analyzed Uii'hasic Eesponsk uf Saktoeius at 18° C. (Keith Lucas.) Salivary Glands. — In the submaxillarv gland, which has been especially studied, the resting current flows through the gland from the surface to the hilus, and therefore from the hilus through the galvanometer to the surface (Fig. 306). When the gland is made to secrete by stimulation of the chorda tympani nerve, the hilus becomes still more galvanometrically positive — an effect abolished by atropine. vStimulation of the cervical sympathetic nerve has the opposite effect. Retinal Currents. — If the ej^eball and the retina be connected to a galvanometer, a " current of rest " is observed, the direction of M'hich depends on whether the outer or inner surface of the retina mii A TEXTBOOK OF PHYSIOLOGY be used, (Fig. 307). When light falls upon llie retina, a complex variation ensues, depending upon the strength and. duration of the stimulus, upon the condition of the eye, whether adapted to light or dark, fresh or fatigued, and upon the nature of the light, whether Avhite or coloured. In the isolated retina there is first a positive and then a negative variation when light falls on it. When the light is cut oflf, a positive variation is produced. As the result of a momentary flash there is a short latent period — 0-01 second — followed by a short negative A^ariation, followed by a large positive variation, quickly Inner surface Fig. 305. — ^Skin Current. Fig. 300.— i^LAMD Current. followed by another diminution of the positive variation, and then by a long-drawn-out increase of the positive variation. Electric Tissues. — In some fishes there is developed a tissue capable of ])roducing electricity. These fishes are either elasmobranchs, such as the rays (Raia ocellata, R. Isevis, etc.) and the torpedo fish (Tetro- narce), or teleosts, such as the electric eel (Gymnotus), the somewhat similar elongated fish (Mormyrus), the star-gazer (Astroscopus), and the electric catfish (Malapterurus). The electric tissue consists of Current of injury from optic nerve. Retinal current di- rected in the retina from rod surface to fibre Surface. Fig. 3U7. St Series of plate-like units know^i as electroplaxes (Fig. 308). Tiie ^lectroplax lies in a compartment of connective tissue embedded in a j'elly-like mass, through which the nerve and blood-supply pass to it. In some cases it is to be considered as a single cell with many nuclei, in others a fusion of cells — a syncytium. The discharge is composed of about 200 shocks per second, and the E.M.F. may be siiflficient to kill other fish in the neighbourhood. In the discharge of the organ the current flows through the organ from the ventral t^iithe dorsal surface, and through the gah^anometer from the dorsal ANIMAL ELECTRICITY 567 to the ventral surface. In Gymnotus the shocks are from tail to head, in Malapterurus from head to tail, the direction dependmg upon the point of entrance of the nerves to the organ. A giant ganglion cell and its nerve tibre, branching multitudinously, su]:>plies the whole of each electric organ in this fish. Blaze Currents.— After any living tissue has been strongly tetanized for a short space of time, a •■ blaze "' current follows in the same direction as the tetanizing current. This is a sign of life: dead tissue does not give it. Seeds have been tested by this means, and their germinating power thus demonstrated. Electrotherapy. — Electricity is largely employed in the treatment of disease. It may act by producing either chemical or thermal effects. In the first case, the galvanic electric current is used, smce it causes a stead}^ migration of positive ions to the negative pole, and of negative ions to the positive pole. It may be emplo3'^ed thera- peutically for three purposes: (1) To produce an alteration in the ionic Fig. 308. — Xeevous Structures Stippled, Striated Structures indicated by Lines. (Redrawn from Dalilgren and Kepner.) a. Diagram of muscle fibre; h, of clectroplax of Baja hat is ; r, diagi'am of electroplax of Raja Ice vis. content of a region, as is probabh^ the case when used for promoting the absorption of fluid effusions. (2) To cause a formation and accumulation of new chemical bodies at the poles. Such bodies may have a caustic action, and be used for the destruction of hair follicles (superliuous hairs), nsevi, etc. (3) By means of the current to introduce curative ions through the skin — the " ionic method of medication."' The faradic cuiTent cannot be used for the above purposes, since the current is frequentty made and broken. The ions then migrate in sudden movements or jerks, and act as a stimulus to excitable tissue, such as muscle. The faradic current is of great value in the treat- ment of parah'sis. If an interrupted cuirent be made to oscillate with extreme rapidity across the bod\', the ions do not have sufficient time to act as a stimulus, and remain more or less stationar3^ fnder these conditions, ix po\\eiful current (3 ampsres), six times stronger than a current -)r>K A TEXTBOOK OF PHYSIOLOGY nc-cessaiy to kill if j)as.sed in ono direction only, may be oscillated without any contraction being jiroduced, provided it be oscillated fre(iuently enougli. Tl.e result of such a current is an agreeable sensation of heat. 1 his forms the basis of " high-frequency " treat- ment, or " diathermy/' When those high-frequency currents are passed through the body, jiart of the electrical energy is transformed into heat, which is prcduced in all jiarts, both superficial and deep, in which the ciUTent flows. The effects of diathermy, so far as can be seen, are produced through their thermal action, and the same results can bo obtained by the simple use of hot baths. BOOK XII THE NERVOUS SYSTEM CHAPTER LXV THE NEURON The nervous mechanism was evolved to correlate the multicellular organism with its surroundings and facilitate the pcoi^er inter- action of the various organs. We have seen in previous chapters how the heart, the vaso-motor mechanism, the respiratory and diges- tive mechanisms, are all correlated to the body needs by the aid of the nervous system. We have now to consider how, by the aid of the nervous system, the animal adjusts itself to its environment. The unit structure of the nervous system is the neuron. It con- sists of a nerve cell, with its processes. The neuron may have a variety of forms, according to the function it subserv^es (Fig. 309). Those engaged in the perception of the outside stimulus are small, with short processes — as, for example, the receptor cells, concerned in olfactory and \'isual sensations. On the other hand, neurons which conduct impulses to distant parts are supplied Avith one or more long and a number of short processes. The cells of the anterior horn of the spinal cord are an example of this type of neuron. They have several processes, and are termed multipolar. In the living cell body there ma\" be seen a large, well-defined nucleus, and numerous gi'anules floating in a homogeneous fluid. On treatment with alcohol, the cell contents are precipitated as Nissl's granules — discrete masses which stain with methylene blue. These are not found m exhausted cells, and disappear from those cells whose axons are divided and functional activity arrested. Of the processes, all but one are short, and branch like the roots of a tree, till they end in small, bud-like expansions, known as gemmules. These processes are known as dendrons. The long process, known as the axis cylinder, or axon, conies Away from a 2>art of the cell in which there are no Nissl's granules — a part known as the axon hillock. The axon is character- ized by its length and by the fact that it does not divide until near its final terminations. The axon, or axis, cylinder is the essential conducting part of the nerve-fibre. Mam- such fibres go to make up the anatomical "' nerve." Such fibres may be either medullated or non-medullated. 56JI 570 A ri:XTB()Ulv OF THYSlOLOCiY Medullated nerves are so called because in them the axon is sur- rounded hv a cylinder of fatty material, forming the medullary sheath. This sheath is interrupted at regular intervals. Such points are known as the nodes of Ranvier. The neurilemma is a nucleated sheath of fibrous tissue, and is continuous over the nodes of Ranvier. A non-medullated nerve, sometimes called a grey fibre, in con- tradistinction to the white medullated nerve, consists merely of an axon surrounded by the nucleated neurilemmal sheath. Fig. 309. — Diagrams of Different Kinds of Nerve Cells. External Arrows AT Perceptory (Receptor) Surface; Internal Arrows at Discharging (Effector) Surface of Cell. (RedraA\-n from Dahlgren and Kepner.) a. Nerve cell with no process; h, nerve cell with one process at effector end organ attached to muscle tibre; c, nerve cell with end organs on two processes; d, nerve ' cell with impulse path independent of cell; e, nerve cell with multiple perceptory end organs; /, nerve cell with multiple perceptory and discharging end organs. Medullated fibres are those of the brain and spmal cord, and the cerebro-spmal nerves; the non-medullated are the post-ganglionic fibres of the sympathetic nervous system. Speculations, based on the concentration of ions in the various parts of the nerve fibre, have been jiut forward concerning the transmission of the nervous impulse. Histological means (staining with solutions of silver nitrate containing a little nitric acid) seem to show that chlorides occur in abundance along the course of the axon. Salts of potassium appear mainly at the nodes of Ranvier, and just outside the axon in the medullarj' sheath. They are demonstrated by treat- THE NEURON 571 ing the nerve with cobalt sodium hexanitrite, and after washing differentiating as a black precipitate by adding ammonium sulphide. Such methods destroy the integrity of the nerre, and set free the salts from their combination with the colloidal living substance. It is claimed that there is laid down in the cytoplasm of the cell for the purposes of conduction a .system of neuro-fibrils, which run J^ -^ \ Zj^n ! I v;«' i'lG, 310. 1, Large Betz cell from human cerebral cortex, .showing Xissl's granules and cone of origin of axon at the base. 2, Medium-sized pyramidal association cell. 3, Anterior.cornual cell. 4, Posterior root ganglion cell. (Mott.) from end to end of the cell processes. According to some authorities, the neurofibrils are not confined to one nerv^e unit, but freely leave one neuron and pass into another, thus forming a network throughout the whole nervous system. The study of the living nerve cell does not reveal the>e fibrils; they are artefacts produced by the method of preparation. Fit;. '311. — PuKTinx ciF A Medullated Xekve-I-'ibhe fK'M >. Mammal. Another type of neuron is the bipolar nerve cell (Fig. 309). In mammals, these occur only in the ganglia m connection with the eighth nerve; in fishes, they are found in the spinal ganglia also. The cell bod\' is elliptical in shape, with two processes given off from the two ends of the ellipse. Such a cell is the parent cell of the unipolar 572 A TlvVTliOOK OF PHV,SI()LOGY spherical cell found in the spmal ganglia of mammals. The two pro- cesses of the bii)olar cell gradually a])])roach each other during develop- ment until they combine to form a T-sha]ied junction. In the cortex of the great brain are other characteristic neurons; the cells are pyramidal in shape; branching dendrons arise from each angle of the p^Tamid, and an axon from the middle of the base (Fig. 310). In the cerebellum are found neurons with large, pear-shaped cells, with a single axon at the base, and a wonderfully branched den- dritic process at the stalk end. Throughout the grey matter of the brain and spinal cord there are small association cells, knowai as the Golgi cells, characterized by the fact that their axons, after a short course, divide into many terminal branches. r^-'. Fig. 312. — Two View.s, taken at Twknty-five Minutes" Inteeval, of the f-AAJK Nerve-Fibee growing from A Group of Embryonic Spinal Coed Cells into THE LvMPH (Ross Harrisoii.) Microscopical preparations of the central nervous system are iden- tified largely by the type and arrangement of nerve cells. The neurons are held together by a suj)porting tissue, known as neuroglia. Thej' are brought into relationship with one another through their end terminations — the dendrons and the axon. These processes do not fuse together; the}' are in contiguit}', not in con- tinuity. The intertwining branches form a synapse; one neuron, conducting an impulse, induces an impulse in another through the synapse. The synapses onh* allow conduction in a forward, not in a backward, direction. For example, a stimulus can pass up a motor nerve-fibre as far as the anterior horn cell but not bevond it into THE NEURON 573 the spinal cord. It has been suggested that the genimules at the end of the dendrons are amoeboid in nature, so that this contiguity may be rendered more complete at some times than at others — for example, that they may be separated during sleep. There is no evidence in favour of this view. The above statement embodies what is known as the neuron theory. Of recent years, the' theory has come in for a considerable amount of criticism. Some lir.ve affirmed that neuro-fibrillce pass from one neuron into another. Doubt has also been expressed as to Avhether the neurons are genetically single cells, and whether regenerated nerve-fibres are to be regarded as parts of a single cell. It is obvious that, should either of the above contentions be true, the neuron theory', as origmally enunciated, is no longer valid. On the whole, recent evidence tends rather to conform the theory than otherwise. The development of the nerve cell has been watched in living preparations made from the embryo, and the outgi" )wih of the axon obser\'ed (Fig. 312). -><- Fig. 313. -^Portion of Rexal Epithelium of Fkog, showing Effector (Motor) Nerve Pnding.s ix Cells. ( Redrawn after Smirnow, from Dalilgren and Kepner.) Those nerve-fibres which conduct inwards towards the nervous system are termed ingoing, or afferent ; those which conduct outwards, the outgoing, or effereiit. The nature of a nerve may be ascer- tained— (1) bj' observing the results of its se3tion; (2) by studying the effects produced when the cut ends of the nerve are stimulated. If an afferent nerve be divided, there results a loss of sensation in the area supplied bj' the nerve. Stimulation of its peripheral end yields no result; stimulation of its central end, on the other hani, calls forth some. If it be sensation, the nerve is termed sensory; if some form of movement, excito-motor ; if inhiV)iti<)n. excito-inhibitory ; if a secretion, excito-secretory. Section of an efferent nerve parah'zes some function, the movement of muscle, striped or smooth, secretion of a gland, etc. Stimulation of the central end of such a nerve is without result ; and stimulation of the peripheral end produces the action which it normally excites. This action may either be in a direction of increased activity — augmentor — or of decreased activity — inhibitory. If it excites a muscle, it is termed motor; if the bloodvessels, vaso-constrictor ; if it 574 A TEXTBOOK OF PHYSIOLOGY cause the .secretion of a gland, secretory. Similarly, it may be nuisculo-inhibitory, vaso-inihihiloiy, secreto-inhibitory, etc. Most nerves of the body are mixed nerves, containing both afferent and efferent fibrt^s. The Reflex Arc. — The sensory neuron, when stimulated through its ner\e-ending. transmits its impulse inwards, passes it on to the efferent neuron, which transmits it outwards, and effects some action or other. This chain — sensory surface (receptor), afferent conductor (the joining synapse), the efferent conductor, the reacting organ, or effector — forms what is known as the reflex arc. In any reflex arc at least two neurons are essential. Genera ll_\', a third neuron connects the afferent and efferent neurons, and in many reflex arcs several connecting Jieurons are interposed in the reflex path. The receptors are classified according as LA they respond to stimuli from — (1) without _^ =r.—z^^j£^ .j^"'l the body (extero-ceptive) ; (2) from the animal's own tissues — e.g., the muscles, tendons, joints, or the labjTinth of the ear (proprio-ceptive) ; (3) from the viscera (entero-ceptive). The Conductors consist of the axons of afferent and efferent neurons, and the synapse between these. The code of interaction between the afferent and efferent conductors of the spinal cord has been studied in what is known as the " spinal animal " — that is, an animal in which a division of the cord has been nuide in the lower cervical region. Such an animal can Ik; kept in health with careful attention, and studied months after the initial effects of the lesion have subsided Fig. 314. — Effector Nerve (see p. 674). The conduction of the nervous Endings in Muscles of impulse in a reflex arc differs materially from KUh^e.') ^^'^^'^^^ ^""" conduction in the nerve-fibre only. This is mainty owing to the interposition of the synapses. Conduction across a synapse is much slower than along a nerve - fibre, and is easily fatigued. Want of oxygen particularly causes failure of conduction at this point, and drugs such as nicotine painted on ganglia paralyze the synapses in them. The s_>niapse interposes a valve-like action in the chain of conductors, permitting conduction of the impulse in one direction only — namely, from the receiving afferent to the effecting efferent neurons. The Effector Organs form the connection between the efferent nerve and the cells of the tissue affected. In some cases they have a definite structure — for example, the motor end-plate in muscle. In other cases there is merely a '" receptive substance," dependent for its nutrition rather on the cells of the tissue than on the nerve- fibre with which it is in connection. It therefore does not degenerate THE NEURON i:n') when the nerve is severed. Such receptive substance may be acted upon by chemical substances, and a " chemical reflex " thereby evoked. For example, adrenalin acts upon the effector organs in connection Avith the sympathetic system, and evokes actions identical with those obtained b} stimulation of the various sympathetic nerves. The effectors are concerned — (1) in effecting the movements of voluntar}' muscle; (2) in regulating the action of smooth and cardiac nauscle; (3) in evoking the secretion of glands. The functions of these effectors have already been dealt with in their various sections, and are also considered in connection with the central nervous system (c/. cranial nerves) and the autonomic system (p. 748). A knowledge of the functions of the nervous S3'stem is best acquired by a study of two units: (1) The neuron; (2) the reflex arc. Fig. 315. — Diagram or Simple Reflex Arc. The Function of the Neuron. — The cell body governs the nutrition of the whole neuron. Its power of nutrition probabh' depends upon the nucleus and the protoplasm which, when j^recipitated by reagents, forms Nissl's granules. The exact chemical nature of these granules is not knoAvn. The\- may be of the nature of nucleo-protein, for they have a great aftinity for basic aniline dyes, such as methA'lene and toluidin blue. When a nerve cell has had a long spell of continuous activity, these granules become dimmished — '" chromatolysis,"' as it is termed, occurs (Fig. 316). Such, for example, is the case in the nerve cells of the swalloM' after a day's flight. It was found that if one ej-e of a dog be bandaged, and the other eye kept active by leadmg the animal about for twenty-four hours, that in the part of the brain concerned with the vision of the active eye chromatolysis had occurred, but not in the part of the brain connected with the resting eye. Chromatolysis takes place during asphyxia and m certain fevers. It also occurs in the nerve cell when the axon is cut. In this case, further changes occur, the cell bod}" becomes swollen, the nucleus goes to one side of the cell. By observing in which cells thi.i -econdarv v^ 576 A TEXTBOOK oF PHYSIOLOGY retrograde degeneration occur.s, the nerve cells c(jnnected Avith ]y.\r- ticiilar nerve-fibres can be traced. It has been shown, moreover, that such a degeneration ma}^ occur in other cells closely connected ■with the severed neuron; for example, cutting the j^osterior roots of a nerve causes chromatolysis in the closely connected cells of the anterior horn of the sjiinal cord. The nutritive function of the nerve cell is most clearly seen in the axon after its section. When an axon is cut, the part of the axon cut off from the nerre cell undergoes Wallerian or primary degen- eration. The Effects of Section of the Axon. — In the first place, the conduc- tion of impulses is interrupted. A current of injiay is set up in the nerve which soon subsides, and is followed by a gradual loss of excitability and conductivity; the loss begins in the most central part of the cut peripheral end, and graduall}' j)asses towards the periphery. h J B C Fig. -MC'. A «ho\\s pericellular chromatolysis of anterior horn cell: B shows perinuclear chro- matolysis; C shows degeneration with vaciiolation of the cytoi>lasni. (M.ott.) FolloA\ing u})on this, Wallerian degeneration occurs. The complex lipoid material of the medullated coat splits up, and the lecithin it contains breaks down, yielding cholin and fatty acid. The staining properties of the myelin change, oAving to the setting free of oleic acid, and thus the degenerate fibres, two or three weeks after their section, stain black with Marchi's fluid. Normal fibres do not stain so. By this staining reaction it is possible to trace the course of degenerating fibres in, and so unravel the structure of, the central nervous system. Tne myelin breaks up into droplets, and finally is absorbed. The nuclei multiply in the fibre, and finally the axon goes and the nucleated sheath is alone left. Old degenerated fibres' are marked bj-^ their failure to stain with the Weigert-Pal method. Regeneration of Nerve. — Even during the degeneration of the axon the first regenerative change begins to take place. Tnis consists of THE XEUROX .)/7 the proliferation of the neurileminal cells of the isolated j^art, to form a large number of spindle cells. At the same time, the products of Fi.i. 317. — Wallekian Dkuexekatiox ix a Cat. Marchi Method of Staining. X 600. (Mott, from AUbutt's " System of ilcdicinc") degeneration are removed by invading leucocj^tei, possibly also through the agency of these spindle cells themselves, so that, when Fig. 318.^ — A, .Section rNDEK High Power sHo^vI^-G Regeneratiox aftek .*^e<:ti<;in OF Sciatic Xerve of Kitten, One Month after Operation. Active Re- generation HAS occurred, as SHOWN BY OUTGROWTH OF XeUKOFIBRII-S ACROSS THE Seat of Lesion, x 300. B, the same x 80. (Mott.) all signs of degeneration are removed, the isolated part of the ner^e- fibre consists of these proliferated spindle cells. 37 578 A TEXTBOOK OF PHY8I0L0GY Under suitable conditions, the nerve-fibre may become regenerated, wdtli the formation of a now axon, medullary sheath, and neurilemma- (Fig. 318). There is considerable difference of opinion as to what exactly are the suitable conditions, and also as to what is the exact part played b}' the spindle cells in this regeneration. It is held by some authorities that " peripheral regeneration " or " autogenetic regeneration "' may take place — that is to say, that full regeneration of the peripheral ]iart may occur without an\^ connection being made with its original nerve cell or some other nerve cell. Such a view cannot be accejited, for it has been shown that in all exi^eriments favouring this view the possibility of the central influence of a nerve cell has by no means been excluded. When precautions are taken — as, for example, enclosing the nerve in a sterilized rubber cap, or transplanting to regions, such as the peritoneal surface of the stomach, where no invasion of nerve-fibres occurs — then no regeneration takes place. The central influence of a nerve cell is necessary' for the true regenera- tion of nerve. If no central . connection is made, the regenerative changes will not pass bej'ond the stage of the formation of spindle cells. The question then arises as to Avhat is the function of these sjaindle cells. According to the view of central regeneration, they serve merel}' as a scaffolding down which the new axon grows from the central end of the nerve. According to another view, the spindle cells, under the influence of the central nerve cell, develop into the new peripheial nerve-fibre, some spindle cells developing into axon, some into medullary sheath, and some into the new neurilemma. The former view is generally accepted. CHAPTER LXVI THE PHYSIOLOGY OF THE NERVE-FIBRE Nerve may be stimulated by natural or artificial stimuli. Natural stimuli are applied to the '" receptor " mechanisms of the body, such as the nervous elements concerned in sight, smell, taste, hearmg, touch, temperature. These are dealt with later. A nerve may be artificially stimulated in various ways : mechanic- ally, by pinching ; thermally, by a hot wire ; chemically, bj- placing on the nerve a few grammes of sodium chloride, or some glycerme; electrically, the induced cuiTent is commonly employed in experi- mental work upon nerve. As judged by the effects of its stimulation on a muscle, nerve responds to minimal, submaximal, and maximal stimulation. The response, if any, is probably always maximal, but as bj* a weak stimulus only a few nerve-fibres are stimulated, the number of muscles-fibres which contract are corresponding^ few; hence the minimal con- traction evidenced by the lift of the muscle lever. In a mixed nerve, all the fibres are not equally excitable. For example, on gradually increasing the stimulation of the sciatic nerve of a frog, first the flexor muscles, and then the extensor muscles, are excited to contraction. Similarly, in a mixed nerve, the vaso-constrictor fibres respond to a stimulation weaker than that which affects the vaso-dilator fibres. The nerve of a nerve-muscle preparation is not equally excitable in all parts of its course. Immediately after making the preparation, the nerve is most excitable at its upper end. After a time this passes off, and the most excitable part progressively descends towards the muscle. A nerve- fibre is also more excitable in the neighbourhood of the mam branches severed durmg its preparation. The increased excitability is probably due to changes in the nerve provoked by injur}-. The excitabilitv of nerve is modified by various factors. It is increased by slight cooling below room temperature, and decreased by greater cold. It is increased by gentle warmth. Loss of water at first increases and then abolishes excitabilitN-. Chemical sub- stances affect nerve in various ways. Carbon dioxide, chloroform, and ether depress the excitabilitv. If a constant (polarizing) electric current be passed through a nerve, it increases the excitability around the negativ'e pole — the kathode — and depresses it around the positive pole — the anode. The rate of conduction of the nerve-impulse is computed to be 579 580 A TEXTBOOK OF PHYSIOLOGY from 83 to 100 metres per second. It may be estimated as follows, using the sciatic -gastrocnemius preparation of the frog : The re- cording drum is arranged at a fast rate, with a " striker " for com- pleting the circuit of the primary current of the induction coil. To the secondary coil are attached two Du Bois keys in the manner showai in the diagram (Fig. 31!)). From these pass two pairs of electrodes, one of Avhich will be applied to the upper portion of the nerve, the other to the lower portion. The latent period of the muscular con- traction is determined, iirst for stimulation by the upper pair of electrodes, the lower ])air being short-circuited by closure of its Du Bois key; then for stimulation by the lower pair of electrodes, the upper pair being short-circuited. The difference in time of the latent periods is determined by recording underneath the curves the vibra- tions of a tuning-fork oscillating 100 times per second. This difference represents the time taken for the nervous impulse to pass along the length of nerve between the two pairs of recording electrodes (Fig. 320). The length is measured in millimetres, and the velocity of the Pig. 319. Diagram of the Experiment un the Kate of Transmission of a Nervous Impulse. transmission of the nervous impulse thus calculated. The rate of con- duction may be measured more accm-ately by means of an electro- meter and determining how long it takes for the " current of action " to pass between two points of a nerve. The velocity may be ascer- tained in man by estimating the time taken for the impulse to pass along the length of nerve from the clavicle to elbow, by stimulating first at one point, then at the other, and recording the contraction of the thumb muscles by means of tambours. The impulse is conducted along a nerve in both directions. This ean be shown by the following experiments: The iliac end of a dis- sected sartoiius muscle is divided into two portions (Fig. 321). Stimu- lation with a weak induction shock at a or a', whsre there are no nerve-fibres, produces a contraction of the one half of the muscle; excitation at b or b', where there are nerves, evokes contraction of both halves. Again, the graciHs muscle of the frog is completely .separated into two portions by a tendinous intersection (Fig. 322), Both halves of the muscle are supplied by a single nerve, the individual fibres of which divide and supply both halves of the muscle. Stimula- tion at a or n, where there are no nerve-fibres, causes only the THE PHYSIOLOGY OF THE NERVE-FIBRE 581- corresponding half of the muscle to contract; but excitation at b or b\ where the nerves lie, will cause both halves to contract. The " action current '" spreads along a nerve in both directions. The rate of conduction in nerve is modified by various factors. Cooling decreases, gentle warmth raises, the rate. Exact measure- ments of the relation of temperature to conductivity do not affo;rd proof that the transmission of nervous energy is a chemical rather tlian Fig. 320.— Velocity of Motor Ijipulse ix Human Neemi:. (Waller.) a physical process. Its nature is unknown. Chloroform and manj- other poisons chminish and then abohsh the conductivity. Unlike muscle, the excised nerve, as the result of activity, shows no measurable mechanical, thermal, or chemical changes. Like muscle, it shows electrical phenomena^the current of injury, the current of aetiF I'HY.SIOLOGY flowing in the nerve from the muscle, it is said to be ascending; if towards the muscle, descending (Fig. 323). In other words, it depencls upon the position of the point of entry of the current (the anode), and the point of exit (the kathode). When a cuiTent begins to flow at make, excitability and conductivity is diminished in the region of the anode and increased in tlie neiL'h born-hood of the kathode; when the current Fig. 323. — A, As " Asce:st)isg " Ctterext. B, A " DE5CE>-Drs"G " CtrRREifT. ceases to flow, the condition of de^^ressed excitability and conductivity at the anode gives Avay, swings back, it may be said, to a condition of raised excitability and conductivity, thus affording a stimulus. Simi- larly, at the kathode the condition of raised excitability and con- ductivity swings back to a condition of lowered excitabilitj' and conductivity. At make, therefore, the kathode is the exciting electrode; at break, the anode. With weak currents, only the more efficient stimuli excite. The sudden increase when the current is made is more effective than the sudden '' swing-back" at the anode when the current is broken: therefore, with weak cuiTents in either direction, contractions occur only at make : Ascending. Descending. Make. Break. Make. Break. C. O. C. 0. With medium currents in both directions, there occur contractions at make from the kathode p.nd at break from the swing- back at the anode : Ascending. Descending. Make. Break. Make. Break. C. C. C. C. With " strong"' currents, the effect is mcditied according to the direction of the current. AVhen the current is ascending, the anode lies between the exciting kathode and the muscle. Around the anode the excitability and conductivity are so depressed that no impulse gets through to the muscle, whicli is therefore only stimulated from the anode at break. This stimulation sometimes induces a tetanus, known as " Ritter's tetanus."' With a strong descending current, the kathode being next the muscle, the impulse generated at the kathode at make is not blocked in any way, and causes a contraction. At break, however, the depressed excitability and conductivity which supervenes in the kathodic region is sufficient to block ths impulse arising from the anode at break. We have, therefore : THE PHYSIOLOGY OF THE NERVE-FIBRE 5.S3 Ascending. Make. Break. 0. C. Descending. Make. Break C. 0. This regular order of contractions for currents of different intensities is known as " Pfliiger's law of contractions." The altei'ed conditions at the anode and at the kathode can bo proved by stimulation in these regions bj' single induction shocks, using ordinary electrodes. Fig. 324 shows the result of such an experiment. Pig. 324. — Showing Effect of Stimulation in Regions of Kathode and Anode. The above alterations of excitability are sometimes referred to as ■' electrotonus "'; they are better described as " electrotonic alterations of excitability." The term " electrot3nus " is best emplo3'ed for the electrical currents which occur in the nerve itself in the parts outside that through which the constant current passes. The current which ^ I ' Anelectrotonic ^ I ' Current Fig. 32.J. — Showing Direction of An electrotonic and Katelectrotonic Currents. is found in the neighbourhood of the anode is termed the anelectrotonic ■current, that in neighbourhood of the kathode the katelectrotonic. Galvanometric observations show that the anelectrotonic current Hows towards, and the katelectrotonic current away from, the polarized region (Fig. 32.1). o84 A TEXTBOOK OK PHY810L0(;\ \Vlu>n the |)olarizing current is broken, there occur ''' after-elcc tro - tonic currents." In the intrapolar region it is in the opposite direction (unless the current has Ijeen strong and of short duration, when it is in tlie same direction); outside the kathode it is, as before, away from the polarized area; outside the anode it is at first towards, and after- wards awa}^ from, the polarized area. Anelectrotonic Previously Katelectrotonic area polarized area area first > < > then < If the nerve be excited by a tetanic current, the electrotonic currents are weakened and the polarizing current strengthened bj'- the " current of action." The " paradoxical contraction " of muscle takes place when the branch of a divided nerve is stimulated with a constant current, and is due to the electrotonic current spreading along the branch towards the point where the nerve-branches ccme together, and thus exciting the fibres of the nerve which supplies the muscle. CHAPTER LXVir THE RECEPTOR MECHANISMS -CUTANEOUS SENSATIONS The Receptors are classified as Extero-ceptive : Xoii- Distance: Touch, heat, cold, j)ain, taste; and Distance: Smell, sight, hearing. Proprio-ceptive : labryinthine (semicirculai- canals), and kinaesthetic (muscles, tendons, and joints). Entero-ceptive : those of common sensibility (thirst, hunger, and pain). In regard to the extero-ceptive mechanism, certain general formulae or laws have been formulated to describe the relations between ex- ternal stimuli and conscious reactions. The most important of these is known as the "law of specific sense energy,"' or '' Miiller's law." It states that — (1) different stimuli acting upon the same sense mechan- ism produce the same kind of sensation; (2) the same stimulus acting ujion different sense mechanisms calls forth different sensations. For example, stimulation of the optic nerve, whether b}' the normal means of stimulation (the so-called " adeciuate " stimulus), the vibrations of the ether, or by abnormal mechanical means, such as a blow^ on the eye (a so-called "inadequate" stimulus), evokes the sensation of light. Another important law, known as Weber's law, states that " the just noticeable increase of a stinnilus bears a constant ratio to the original stimulus," or " two stimuli, in order to be discriminated, must be in a constant ratio, the latter being independent of the abso- lute magnitudes of the stimuli." The actual value of ihis ratio, although constant for any one sense mechanism, varies from organ to organ. For example, if one candle added to ten just perceptibly increased the illumination, ten candles would have to be added to a hundred to do so, and one hundred to a thousand. The validity of this law has been hotly contested, since the experimental methods employed to establish it have yielded very inconstant results. Un- doubtedh', some relation of the kind enunciated by Weber's law does exist, since all judgments involve comparison. Touch, Heat, Cold, Pain. — ^\'ith the exception of taste, the non- distance receptor mechanisms mainl^^ come luider the class of '■ cutaneous sensations,"" and are located in the skin. The Structure of the Receptors of Cutaneous Sensation. — There is a dearth of knoAvledge as to the structure of the receptor mechanism concerned in the sensations of touch, heat, cold, and pain. In the skin various nerve-endings have been descri])ed : 585 58(3 A TEXTBOOK OF PHYSIOLOGY 1. Several forms of end-organs or terjninal cori^uscles, such as Meissner's corjjuscles, Kraiise's end-bulbs, Ruffini's organs, and the corpuscles of Pacini or Vater. Such terminal corpuscles consist of a coarse nerve-fibre or knot of branches surrounded by a semifluid intercellular substance enclosed in a capsule. Meissner's Corpuscles are oval bodies about -^.^l . to jl. inch in length. Each corpuscle consists of flattened cells surrounded by a capsule, around which one or two medullated nerve-tibres wind, to enter at the upper pole. The medullated coat is lost at the point of entrance. These corjiuscles occur particularly in the papillae of the true skin, esiDcciall v in the jjalms of the hands and in the soles of the feet. Krause's End-bulbs have the form of aiv encapsulated bulb, the axon of the medidlated nerve entering its lower extremity to ramify among the ovoid cells contained within the capsule. They occur particularly in the conjunctiva, the mucous membrane of the mouth, the glans penis and clitoris, and the ligaments of joints. They also occur on the under-surface of the toes of guinea-pigs and in the wing of the bat. RuffinVs Organs are found in the subcutaneous tissue near the sweat glands, and in the coriura of the fingers and toes; they lack distinct capsules. The Pacinian Corpuscle (Fig. 328) occurs in the subcutaneous tissues of the palm, fingers, sole; in the sexual organs; in the deep layers of connective tissue near joints; and in the mesentery. Each corpuscle is of oval shape, and consists of forty to fifty lamellae End concentrically arranged. The lamellae are formed Bulb of the ^f connective tissue, and covered with endothelium. juNCTivA. A lymph space exists between each lamella and its (Krause.) neighbour. A medullated nerve-fibre enters at one pole. Its axon passes through all the lamellae to the central core of the corpuscle, ramifies therein, and ends in small terminal buds near the distal pole of the corpuscle. 2. Nerve-endings in comiection with tactile hairs. Fine medullated nerve-fibres form a network in the outer coat of the hair follicle, and, losing their medullary sheath, run parallel to the hair, and finally penetrate and end in the inner layer of the hair sheath (Fig. 329). 3. Single nerve-fibres pass to the under-surface of the epidermis, lose their medullary sheath, and divide into fine filaments, which end among the cells of the epidermis (Fig. 330) . Various other special forms of nerve-endings liave been described in different animals — for example, in the bill of the duck, the skin of the whale, etc. Methods of Investigation. — The sensation of touch or pressure is investigated by a series of hairs of different thicknesses attached at right angles to Avooden rods. The hair is applied perpendicularly to the skin, and the amount of j^ressure required to bend visibly any Fig. 326 RECEPTOR MECHANISMS— CUTANEOUS SENSATIONS oST Fm. 327.^Nerve Endins in a Special Connective Tissue Organ in the Deeper Part of the Cutis, x 320. (Ruffini, from " Quain's Anatomy.") «, Sheath of entering nerve: h, sheath of terminal organ; c, blood capillaries; d, d, ter- minations of axons; e, spindle-shaped connective tissue core in which these terminations ramify. Fig. 32S. — Pacinian Corpuscle. i'lG. 329. — Shoaving Sensory Nekve Endings at the Base of a Haie. (Redrawn after van Gehuchten, from Dahlgren and Kejiner.) 588 A TEXTBOOK OF PHYSIOLOGY hair being iinown, the threshold vahie of the sensation of pressiue can be accurately determined. For ordinary' clinical purposes, the presence or absence of sensation to the touch of cotton-wool is usually employed. To test relative sensitiveness or the power to discriminate the part touched in various parts of the skin, the distance between the points of a jjair of comjjasses is measured when the points are just sensed as touching two jilaces. Temperature sensations may be tested with a hollow pencil-shaped rod in which water of various temperatures is circulated. A more common method is to use the bottom of test-tubes containing water at various temperatures. Pain may be tested with the prick of a needle-point. The Sensations of Touch or Pressure. — Pressure-pointg are closely related to the distribution of hairs, each hair having a pressure-point Fig. 330. — iSensoky Nekve End-Organ in Exteenal Epithelium of Pig's Snovt. (Redrawn after Retzius, from Dahlgren and Kepner.) on the surface corresponding to the situation of the hair follicle. Some pressure-points have no such relation to the hair follicle. In hairless parts it is suggested that pressure is associated with the corpuscles of Meissner and of Pacini. These jjressure organs are not directly stimulated, since the}' do not reach the exposed surface of the skin. The excitation is produced by the variation in pressure in the neighbourhood of the end-organ, as can be shown by the fact that they are stimulated either by pushing against or jjulling on a hair. The extent of the surface to which the stimulus is applied is an important factor. For example, a greater pressure per unit is required for an area of 0-25 square millimetre than one of 0-5 square millimetre. The optimum surface is about 0-5 square millimetre. Above or below this area the amount of pressure required is increased. It has been found that the hair}^ parts are more excitable and more easily fatigued than the smooth areas of the skin. In estimating weights, it is easier to compare them applied succes- sively than simultaneously. Further, the rapidity with which the RECEPTOR MECHANISMS— CUTANEOUS SENSATIONS o8!J stimuli are successively applied influences the judgment. Generally speaking, the slower the rate of change, the higher must be the stimulus value. It is also easier to judge of a difference in weight than to say whether such a weight is heavier or lighter than another. It is easier to detect an increase in weight than a decrease. The experi- mental results are so variable that it cannot be said that Weber's law has been proved to hold good for tactile impressions. The most sensitive parts are those which ws use habitually as organs of touch. Thus, the under-surfaces of the tips of the fingers and the palms of the hand are far more sensitive than the skin of the gluteal region. Sensitiveness is also marked in the parts of the body habitually moved, and increases from the joints towards the extremities. It is also greater along the transverse axis of a limb than in the same distance along the long axis. The following table shows in millimetres the distance in various laarts of the body at which the ]ioints of a compass are appreciated as separate: Tip of tongue . . Under surface of tip of finger Red part of lip Under surface of second phalanx of finger Upper surface of tip of finger Tij) of nose Ball of thumb Centre of palm Under surface of tip of great toe Upper sufrace of second ])halanx of finger Eyelid According to these degrees of sensitiveness, it is possible to locate with precision the exact spot touched. Most people are imable to localize a touch on the second, third or fourth toe to the exact toe touched. By education the local sign is developed. The sensitiveness of the skin is increased after massage or salt baths, blunted by cold, anaemia, venous congestion, or after the appli cation of solutions of certain drugs, such as atropine, chloral, etc. In regard to absolute sensitiveness, the most sensitive parts of the body are the forehead, temples, back of hand, and forearm. These .are said to be able to detect a pressure of 0-002 gramme. Many ex- periments have been made to determine the frequency with which pressure stimuli must follow each other to ]:>roduce a fused sensation, but the results are discordant. The length of time a sensation per- sists after removal of the stimulus varies greatly in different parts. In the finger it vanishes almost at once, on the forehead it persists for some little time, after a moderately strong stimulus. The Information derived from Tactile Sensations. — From the tactile sensations, associated with the kinsesthetic sensations, which occur when the object presses heavily or is moved, we derive in- formation as to form, size, and nature, of the body touched. It may be small or big, smooth or rough, etc. When a large area of the 1-1 Under surface of lower third of 2-3 forearm . . 15-0 -r-5 Cheek Temples 15-8 22-6 4-.-> Forehead . . 22-G (>-8 Back of head 27-1 l)-8 Back of hand 31-6 (>•;-)- 7 Knee 3(3-1 S-9 Buttock . . 44-6 I1-3 Forearm and 1 Neck "g 4.5-1 54-1 11-3 Upper arm, thigh, •entrc of bac k" f)7-l 11-3 r>90 A TEXTBOOK OF PHYSIOLOGY skin is uniformly pressed upon, the sensation of pressure soon disappears; when a finger is immersed in a bath of mercury, the sensation of pressure is Hmited to the area dividing the regions of different pressure. Judgments are formed from the sensations received on the supposi- tion that there is no displacement of the body from the normal position. Such a displacement ma^^ lead to an erroneous juflgment . as exemplified by the experiment of Aristotle. A pea or marble placed between the first and second fingers, held in the normal position, feels one body. If the fingers be crossed, and the pea be so placed as to touch the outer side of both fingers, two peas are felt. So, too, the tip of the nose, touched by the fingers in this position, gives the sensation of two noses, particularly if the eyes be closed at the time. The local sign attached to the sensations, when received in the brain, is definite and precise. It is for this reason that a patient's nose shared in a headache after a surgeon had transplanted a piece of skin from his forehead to his nose I The Sensations of Temperature. — ^Sensations of temperature can be evoked from the Avhole of the skin; the fiont part of the nares; from the mucous lining of the beginning (mouth, pharynx, oesophagus) and end of the alimentary tract (the region of the anus); from the cornea, conjunctiva, and penis. The spots stimulated by heat and cold are different. Cold spots are more numerous than hot spots, especially over the extremities. They are generally arranged in curved lines. The curves of the hot and cold spots do not, however, coincide. It has been suggested, but the evidence is very slight, that Krause's end-bulbs and Ruifinis organs are respectively the special structures associated with the appreciation of cold and warmth. Two views are held as to what constitutes the adequate stimulus of these sensations. According to one view, the chief factor is the alteration of the end-organ temperature, whatever that may be, a I'ise of temperature in the end-organ cieating a sensation of warmth, a fall in temperature producing the sensation of cold. Upon this view, it is somewhat difficult to account for the sensation of cold which persists after removal of a cold body. During this time the temperature in the end-organ is rising. For example, after a cold penny (2° C.) has been applied to the forehead for thirty seconds, the sensation of cold mav persist for twentj- seconds after its removal. According to the second view, a skin area gives no temperature sensation when it is at the so-called physiological zero of temperature. This point shifts with the conditions to which the part is exposed. Any alteration of temperature will give rise to a sensation the intensity and character of which depend upon the difference from this i^oint of reference. Thus, if one hand is put into hot and another into cold water, and then both into tepid water, the "hot" hand feels it cold and the "cold" hand warm. Probably it is the difference between the surface and deej) skin te^mperatm'e (surface and deep sense organs) which gives the intensity RECEPTOR MECHANISMS— CUTANEOUS SENSATIONS 591 of sensation : the surface and deep sense organs may be compared to a pair of thermo-electric junctions. The adequate stimulus depends not only on the intensity of the stimulus, but upon the actual size of the region stimulated. It is probably for this reason that water at 37° C. feels warmer to the whole hand immersed in it than does water at 40° C. to one finger only. The degree of sensation evoked also depends upon the thermal capacity and conductivity of the body applied to the skin. The parts of the body in which the thermal sense is most acute are the tip of the tongue, the eyelids, cheeks, lips, and belly. The laundress tests the warmth of her iron with her cheek, and not with her hand, and the bared elbow is used by a good nurse to test the temperature of a hot bath. The temperature sensations regulate to a large extent the tone of the skeletal muscles, the vaso-motor tone, the activity and metabolism of the body. The play of wind, sunlight and shadow stimulate the nervous system and prevent monotony. The Sensation of Pain. — It seems probable that special " pain spots " exist for the appreciation of pain. They have a long latent period when subjected to weak stimulation, and do not react easily to rapidly alternating or oscillating stimuli. They do not coincide Avith pressure-points, and are about four times as numerous as these. It has been suggested that the free nerve-endings in the skin are the special organs excited. In support of this view, it has been showai — 1. That diminution of the surface area stimulated does not diminish the effectiveness of the stimulus. 2. That the electrical stimulus is more effective than any other form. 3. That the first sensation produced by the application of a corrosive is one of pain. It is stated also that from the cornea only sensations of pain arise, and that here the only receptive elements are the intra-epithelial nerve-endings. It is probable, however, that pain may arise from excessive stimu- lation of the organs connected with the other sensations of the skin. Excessive heat or cold produces the same kind of sensation of pain. Protopathic and Epicritic Sensibility.— A careful study of the sensory changes associated with the experimental division and regeneration of cutaneous nerves in trained observers, has led to a new classification of the sensibilities of the skin. In the area supplied by the severed nerves the sensations of heat, pain, and cold, were lost, also sensa- tion of touch to cotton-wool, and to the pulling of the skin outwards. Pressure inwards was appreciated and well localized — that is. deep pressure — due to sensation in the underhung muscles. After seven weeks, sensibility to pin-prick returned, but it required a higher minimal stimulus than the normal parts, and produced a peculiar unpleasant sensation which radiated and tended to be localized in remote parts. Water of 38° to 50° C. was recognized as hot, and r)92 A TEXTBOOK OK PHYSIOLOGY of C^ to 24" C. as cold; but no sensations of warmth or coolness were experienced from water at intermediate temperatures. The areas where these sensations were experienced corresponded to hot and cold spots previously jnarked out. This kind of sensibility to pain and tempei'ature is termed proto- pathic. Its chief characteristics are its high threshold stimulation value and the fact that it depends upon the existence of specific end- organs. It probal^Iy represents a more primitive t\'pe of nervous organization. After a variable time the skin again became sensitive to light touch, compass-points were discriminated, and varying degrees of temperature appreciated. This more delicate organization is termed the epicritic system. Epicritic sensibility is characterized by low threshold stimulation value. Its re-establishment may depend on the completion of a single regenerative process, rather than on the regeneration of a special system of epicritic nerves. The central connections of the conductors associated with these various sensations are dealt with later. CHAPTER LXVIII TASTE AND SMELL Taste — The Receptor Mechanism. — The taste buds probably form the receptor mechanism for tlie sensation of taste, for the sense of taste is absent from those parts of the tongue where these organs do not exist, and is most acute in the regions where they are most abun- dant. Further, section of the glosso-pharyngeal nerve, the nerve of taste, leads to a degeneration of the sensory cells in these buds. The taste buds are found in many of the fungiform and in all the circumvallate papilloe of the tongue: to a certain extent also on the A l-'iG. 331. — MicKoscopic View of Section throttgh Circumvallate Papu^l.!-: A, epithelial layor: B, taste buds; P, gland; E, subepithelial Ivyei-; G, luuscJe. soft palate and the surface of the epiglottis. They a.re best seen in the circumvallate papillae. These are eight to fifteen in number, and form at the base of the tongue a V, with the apex backwards: it is calculated that there are more than 30,000 taste buds in this region in the ox. They are far more numerous in the embrj'o at the sixth to the seventh month than in the adult. Many of them subsequently become infiltrated with leucocytes and destroyed. The fungiform (fungus-like) and filiform (rod-like) papillae of the tongue are concerned in the sensations of touch, temperature, and pain. The taste buds are minute oval bodies embedded in the epithelial layer, and communicating with the surface by a funnel-shaped opening 5£3 38 094 A TEXTBOOK OF PHYSIOLOGY — the laste pore. Into this pore the hair-like processes of the true gustatory cells project. These cells are delicate rod-Hkc cells, with a central nucleus surrounded by granidar protoj^lasni. Around the tapered base of the cell are the fine ramifications of the nerve of taste. The taste cells are supported externally on either side by columnar cells — rhe sustentaciilar cells. These form no connection with the gustatory nerve (Fig. 332). Fig. :'>i2. — Taste Brn in Tongue of Man. (Kcdraxui after Hein-ani), from Dalilgren and Kepner.) g. '.. Gustatory or taste cells; sup. c, supporting cells; nv. f„ nerve fibrils. There are four sensation qualities of taste, sweet, salt, acid, and bitter. They may be investigated by applying to the tongue test soititions of various strengths at bod}' temperature with a fine camel's- hair brush, or by placing a measured volume of the solution on the tongue For exact localizing Avork, a form of instrument such as shown ill Fig. 333 may be used. It is usual to employ ether and chloroform vapour with this instrument, since it ha,S; been found that ether vapour blown on the tongue j^roduces the sensation of bitterness, and chloroform vapour a sensation of sweetness. Fig. 333. — Apparatus for testing Taste Sensations. A. Z. two-way tap; E, insufflating bulb; C, D, odoiir chambers; 1, 2, clips. The nature of the stimulus for taste is chemical. It is necessary for a body to be in solution for the sensation to be evoked. A dry TASTE AXD 8MELL 595 substance — e.g., solid quinine — applied to the dry tongue evokes no sensation of taste Again, a ciystal of quartz gives the sensation of touch and cold, but not of taste. A cr3^stal of common salt of the same size gives not only these sensations, but that of saline taste. There is no evidence to show that the sensations of taste can be elicited by mechanical stimulation of the tongue. It is probable that the sensations evoked by electrical stimulation are due to the electrol\-tic decomposition of the saliva. The various taste sensations are grouped in different areas of the tongue. The responsiveness to bitter substances is confined mainly to the back and edges of the tongue. Acid is tasted all over the dorsum^ except a small anterior part just behind the tip. Salt and sweet are likewise apj)ieciated all over the dorsum, except for an antero-median area of the dorsum, a little posterior to the insensitive area for acid. " Sweet "is, however, in most people liest appreciated at the tip of the tongue. It has been argued that this distribution points to special receptors for each form of taste, and in support of this it is stated that saccharine is sweet tp the tip and bitter to the back of the tongue. In like manner, stilphate of magnesia is bitter at the base and sweet or acid in the region of the tip. Further, the drug Gymnenia sylvestre affects the sensation of sweetness. After chewing the leaves of this plant, sugar no longer tastes sweet nor quinine bitter. The sensations of acid and salt are unaffected. There is apparent!}' no relation between the chemical structure and taste of substances. For example, sugar, lead acetate, and chloroform, ail taste sweet; magnesium sulphate and various alka- loids, like quinine and strychnine, evoke bitter sensations. The application of sugar and salt at the same time to opposite sides of the tongue increases the effectiveness of both stimuli (c^. simul- taneous contrast in vision, p. 634), Again, after tasting Aveak sulphuric acid, distilled water has a sweetish taste {cf. successive contrast, p. 634), It is to be noted that flavours are either smells or combinations of taste and smell. Thus, a man with cold in the head cannot aj)preciate the fine flavour of wine. If the nose be held, an onion, when bitten, is indistinguishable from an apple. The smell of a strong cheese will destroy the api^reciation of the taste of fruit. The nerve distribution for taste is associated in the posterior thiixl with the glosso-pharyiigeal nerve, and in the anterior two-thirds with the lingual branch of the fifth. The course of the taste fibres is complicated and still in doubt. The fibres from the anterior two- thirds lea\-e the lingual nerve and pass backward along the chorda tympani nerve to join the seventh nerve in the Fallopian aqueduct. They pass in the seventh nerve as far as the geniculate ganglion, A\here some join the nerve of Wrisberg and pass to the nucleus of the ninth nerve ; others are said to pass along the great superficial petrosal nerve to Meckel's ganglion and to rejoin the fifth nerve. The fibres from the posterior third of the tongue pass to the brain by wav of the glosso-pharyngeal nerve. 590 A TEXTBOOK OF PHYSIOLOGY Smell.^ — The Receptor Mechanism is formed by the olfactory cells situated iu the mucous membrane of the upper meatus of the nose, and covering the vipper part of the superior turbinate bone and nasal septum. The middle and inferior meatus constitute part of the respiratory tract. The nasal mucous membrane, or Schneiderian membrane, is thick and of a yelloAvish hue, in marked contrast to the reddish tint of the respiratory portion of the nose. In section it is seen to consist of an epithelial layer — the olfactory epithelium — which 'rests upon a basement membrane, and separates it from the deeper mucous layer or corium (Fig. 334). Fig. 334. — Skction of Olfactory Epitheliitm of the Fowl, showing sup. c. Sup- porting Cells; sen. c, Sensory Cells; and ba. c. Basal Cells. (Eedrawn fi'om Dahlgren and Kepner.) The receptor olfactory cells lie in the ej^ithelial layer. They possess a central nucleus surrounded by a small quantity of protoplasm, from which there passes towards the surface a narrow round filament with a cilium attached. A smaller similar process, arising from the base of the cells, arborizes with the terminal ramifications of the olfactory nerve. Supporting these cells are other " sustentacular cells." These have a knife-handle-like shape, the upper half being cylindrical in shape, and often provided with stiff cilia attached to the free border. The lower half is narrow, and ends in a long process which joins with the neighbouring cells. At the boundary of the TA.STE AND SMELL 597 epithelial layer with the loose underlying connecti\'e tissue there are found supporting " basal cells."' These are irregularl}- cubical, being broadest at the base and tapering towards the surface. The Mode of Excitation. — Smells are not destroyed by passing the air containing them through a long tube packed with cotton-wool. It is estimated that such a tube removes particles r^o^-^jx^ cubic milli- metre in size. It is known that a gramme of musk will give off its odour for years, and not weigh appreciably less at the end of the time ; 0-01 milligramme of meicaptan diffused in 230 centimetres of air is perceptible to the sense of smell — i.e., 0-00000004 milligramme per litre, or a dilution of 1 in 50,000.000. A hound will follow every zigzag that a fox takes across country. It is obvious, therefore, that the mode of excitation is as subtle as that of the retina by light. Substances of low molecular weight either have no odour or tend to irritate the nose rather than evoke the true sense of smell. Increase in molecular weight often increases the property of smell — for example, of the paraffins. In the series of alcohols also there is an increase in the intensity of odour as the molecular weight increases. The Investigation of the Sense of Smell. — ^Keenness of smell may be investigated roughly by preparing a series of solutions of camphor from 1 in 1,000 to 1 in 1,000,000, and placing them in flasks holding 10 to 15 c.c, and having an opening of 17 millimetres diameter. For A Fig. 335. — The Olfactometer. more accurate work, the instrument kno\vn as the olfactometer is used (Fig. 335). This consists of two concentric cylinders, the inner one of which ends in a nose-j)iece. The outer cylinder (-^4) is lined with an odorous substance. It will be seen that, when the inner cylinder (B) is pushed in level with the oiiter one, air mhaled through the instru- ment does not pass over this substance: but the more the cylinder is drawn out, the greater the area of the odorous substance exposeti to the indra\^ai air. The extent to which it is necessary to draw out the inner cjdmder to recognize the odour is the measure of the responsiveness of the nose to that particular stimulus. A classification of different smells is verj' difficult, almost impracti- cable. Such classifications have been made, but they cannot be re- garded as satisfactorj'. There is an antagonism between certain odours — e.g., iodoform is masked by balsam of Peru, musk by bitter almonds, ammonia bj' acetic acid. The sense of smell may be fatigued. After smellmg tinctiu-e of iodme, alcohol and copaiba balsam are odourless. Some people do 51)8 A TEXTBOOK OK I ' in'« J ( ) I .i )( ; Y not appreciate certain smells — e.g., Jiiignonette. .Such " anosmia '" is probably congenital, but temporary anosmia may occur in disease of the nose and in nerv^ous conditions. It may be induced by the, application of drugs, such as cocaine. Parosmia (perverted sense of smell) and hyjierosiuia (increased sensibility to smells) may also occur in neivous conditions (hysteria, etc.). Taste and smell, as we have seen, are intimately related. Jt is possible for them to be antagonistic. This fact is made use of by the physician. Thus, " tinct. aurantii," by its odour, counterac.ts the bitter taste of quinine, and effervescing saline drinks (taste) mask the flavour (odour) of castor oil. The central connections for smell are made l)y means of the olfac- tory lobes of the brain (see p. 71.")). CHAPTER LXIX THE SENSE OF VISION Section I The Receptor Mechanism. — The perception of the rapid undula- tions of the ether is usually confined to specialized nerve cells, the visual, cells. Some low forms of life have a rudimentary eye or eye- spot (Fig. 336, e). The visual cells may be scattered over the body Fig. 33'J. — Individual Flagellate Chla!mvdomo>-as Reticulata. (Redrawn from Dahlgreu and Kepner.) e, Eyespot with, pigment and lens: nu., nucleus; c. v., contractile vacuole. X 1,000. surface, but usually are aggregated together with accessory tissues to form a specialized organ of vision, the eye. Various complicated forms of eyes are described among the invertebrates. In the higher animals the recejitor mechanism for vision is contained in. the retina,, the delicate nervous layer lining the posterior portion 599 «00 A TEXTBOOK OF PHYSIOLOGY^ of tlic eyeball. The rest of the eyeball is an accessory mechatiisnt for focussing the vibrations of the ether upon the retina, in order that light may not only be ap])reciated, but vision rendered distinct. . It is convenient, therefore, first to study the structure of this apparatus,, and also the ])hysical laws which apjoly in connection with vision. The Anatomy of the Eye. — The eye may be compared to a camera, with its framework, its system of lenses, its diay)hragni, and its sensitive plate. The framework of the eyeball consists of an outer tough, opatjue, fil)rous coat — the sclera, or sclerotic. In front, this becomes- transparent, and forms one of the systiem of lenses — the cornea. At the back, the sclerotic is pierced by the optic nerve, which then spreads out over the posterior two-thirds of the e^-eball to for^n the sensitive^ plate — the retina. Between the sclerotic and retina lies the black pigmented and vascular coat, the choroid. Within the eye is sus- pended the lens and its supports, dividing the eyeball into two chambers: (I) That between the cornea and the front of the lens — the " aqueous chamber " — containing a watery fluid (the " aqueous ") ;' (2) that between the posterior surface of the lens and the retina — the vitreous chamber — containing a glassy, jelly-like mass (the " vitreous humour '"). The aqueous chamber is incompletely divided into two by the diaphragm, oi iris. To understand the mechanism by which rays of light are rendered distinct upon the sensitive retina, it is necessary for us to study in detail these accessory parts. Accessory Parts and their Functions. The Conjunctiva covers the anterior part of the sclera, and is reflected over the inner aspects of the upper and lower eyelids. It consists of several layers of stratified epithelium. The anterior surface of the cornea is covered by a similar epithelium continuous with that of the conjunctiva. The conjunctiva is kept moistened by the secretion of the lachrymal glands — the tears. The Lachrymal Glands. — The lachrymal glands closely resemble in structure a serous gland. They are situated in the upper outer angle of the orbit, and jjour out their secretion by sev^eral ducts situated on the inner surface of the ujiper lid. Normally, the amount of secretion is just sufficient to keep the conjunctiva moist, and enable the e3relids to work smoothly. It is drained away by a small orifice — placed at the inner angle of the eye, and thence into the lachrymal sac and to the nasal duct which opens into the inferior meatus of the nose. Excessive secretion is induced by foreign bodies acting on the conjunctiva, irritating vapours in the nose, and by painful emotion, leading to the formation of tears. The eyelids, besides moistening the conjunctiva during the process of winking, protect the eyeball,, and, by means of the eyelashes, shade the eyes. They consist of folds of skin and areolar tissue, kept in shape by a plate of fibrous tissue — the tarsus. In the skin are contained sweat glands, sebaceous (Meibomian) glands, and the eyelashes. Beneath the skin are fibres of the muscle which closes the lids — the orbicularis palpebrarum.. THE SENSE OF VISIOX COl Inserted into the middle portion of the tarsus of the upper lid are fibres of the muscle which open the eye — the levator palpebrse suiserioris. The Cornea is the transparent layer in the front of the eyeball. In the adult human being it is about 1 millimetre thick. It is the first of the sjstem of lenses of the ej'e-camera. It is continuous at its edges with the sclerotic, forming the corneo -sclerotic or sclero -corneal junction. The angle at which the cornea joins the iris within the eyeball is known as the corneo-iridic or filtration angle. O.N. FiC4. 337. — Horizontal Sectiok or Eyeball. (Parsons and Wright.) C, Cornea; Aq., aqueous humour; /., iris; S.L.L., suspensory ligament of lens; C.P., canal of Petit; E.B., external rectus: Scl., sclerotic; Cher., choroid; Bet.y retina; H.M., hyaloid membrane; 31. L., macula lutea; O.N., o"j5tic nerve; R.A^, retinal artery; O.D., optic disc; I.B., internal rectus; Vii., vitreous humour; C.B., cihary body; C.Sck., canal of Schlemm; L., lens. Microscopically, the cornea consists of a layer of stratified epithelium, in which ramify numerous delicate nerves, resting upon a homogeneous layer (the anterior homogeneous layer of Bowman), Beneath this layer the transj)arent fibres of the cornea proper are arranged in laj'ers, each successive layer being at right angles to the next. Lying in minute tissue-fluid spaces between the fibres are connective-tissue cells, known as the corneal corpuscles. In the proper substance of the cornea there run delicate plexuses of nerve- fibres derived from the ciliary nerves. Posterior to the cornea proper comes a transparent elastic membrane (Descemet's), on the inner surface of which is the single layer of flattened epithelial ceils lining 602 A TKXTBUOK OF PHYSIOLOGY the aqueous chamber. These, at the coiiieo-iridic angk^ become reflected on to the iris, the menibraue stop])ing short at tb(; angle. The inner flbres of the cornea in the neigh V)oiirhoo(l of the corneo iridic angle continue on as longitudinal li])res- cribriform ligameni. This ligament is also composed of circular iibres, which are continued.'' with those^sunouudiiig the venous canal of iSchlenim (Fig. 33S). Ciliary Stroma \ YlG. 338. — T«> SHOW DtTAILS OF THE CRIBRIFORM LiGAMEXT, ClLIARV ^irSCLE, AM) CoRNEO-iRiDic Junction. (Thouiison Henderson.) The outer fibres of cribriform ligament start at « and end at a'. The inner fibres start at h and spread out to act as fibrils of origin to the longitudinal fibres of the ciliary muscle. P, pigment epithelium of iris; P.L.M.. posterior limiting mem- brane of iris continuous with hyahne layers (H.L.) of ciliary body; l>.J^.,Des- cemet's membrane. By its inner longitudinal fibres it serves as a j)oint of attachment for the ciliary muscle and the dilator pupillee; by its outer longitudinal fibresjt is connected to the sclera, the fibres passing backwards internal to the canal of Schlemm. The circular fibres heljo to keep the ciliary mu.scle in position. The Sclerotic Coat (Sclera) is extremely tough, being made up of white fibrous tissue with a small amount of yellow elastic tissue. It is pierced at the back bj* the optic nerve, and at various parts by the veins bringing blood from the eyeball (the venae vorticosse). The muscles' moving the eyeball are inserted into the sclera just behind THE SENSE OF VISION 003 the cornea. On its inner surface there is a layer oi brown-l)lack pigment cells (the lamina fusca). The sclera is connected by loose connective tissue to the structures internal to it — the ciliary borty and the choroid — the space thus formed being knowi: as the supra- choroidal space (Fig. 345). The Choroid is the vascular coat for the posterior part of the eye. It is connected with the ciliary body and the iris, and, together with them, constitutes the vascular tract, or uvea, of the eye. Lying between the sclera and the retina, the function of the choroid is to nourish these structures, ]}articularly the retina. Its pigment also absorbs the light which passes through the retina. The choroid consists mainly of networks of bloodvessels held together by a stroma containing branched pigment cells. There is an outer la3'er of larger blood- vessels, and an inner close network of wide capillaries Next to the retina is a homogeneous elastic membrane, which may be 2 jjc thick. A similar elastic membrane lies at the back of the cornea, and covers the iris and ciliary processes. The fluid within the eyeball is contained b}' this membrane, and it is probably of great importance in the maintenance of the intra-ocular pressure. The Ciliary Body lies just behind the corneo-scleral junction, being continuous with the choroid behind and with the iris in front, and consists of two portions — -an outer muscular portion, the ciliary muscle, and an inner non-muscular portion. The latter is dividerl into two parts — the pars plana and the pars plicata. The Ciliary Muscle is composed of smooth muscle, anci also consists of an outer portion and an inner portion. The fibres of the outer portion (Brdcke's muscle) run in a meridional and radial direction. They arise from the portion of the cribriform ligament derived from the cornea, and pass backwards to be-inserted in part into the choroid, in part into the suspensory ligament of the lens. The inner portion consists of circular fibres (Mijlier'.s muscle). It arises indirectly by interstitial tissue from the internal fibres of the cribriform ligament, and forms a sjihincter roimd the margin of the lenti. The Pars Plana is the posterior smooth portion of the ciliary body. The Pars Plicata is the anterior inner portion of the ciliary body, so called because it is thrown into many folds^the ciliary processes, about seventy in number. Lying in the connective tissue of these processes are networks of wide capillary tufts. Each process arises from a base of connective tissue continuous with the stroma of the iris, and each is covered by columnar epithelium, within which is a set of pigment cells. Between the processes lie the interciliary grooves, lined by pigmented cubical cells, and continuous with the radial furrows on the back of the iris. The sensory nerve supply of the ciliary body comes from the ophthalmic division of the fifth nerve. The ciliary muscle is supplied b}' the infeiior division of the third nerve. The long posterior ciliary arteries supply' the ciliary body with blood. 604 A TEXTBOOK OF PHYSIOLOGY Functions of the Ciliary Body. — The ciliary inusclc effects the ac- commodation of the eye (see hiter, p. (U4); the ciliary processes secrete the aqueous humour, the pigment in the ciliary bodies assists the ins in preventing h'ghl passing through the periphery of the lens. The Iris is the pigmented curtain or diaphragm which lies in the aqueous chamber, dividing it into an anterior chamber in front and a posterior chamber behind. The ajserture in the centre forms the pupil of the eye. At its base, where it is thinnest, the iris is con- tinuous with the anterior part of the ciliary body, both as regards stroma and the pigmented and epithelial cells, which lie on its posterior surface. The epithelial cells on tlie front of the iris are reflected at the corneo-iridic angle on to the back of the cornea. Both sets of epithelial cells, anterior and posterior, lie on basement membranes, in between which there is a delicate network of connective tissue containing the pigment cells which give the iris its characteristic colour. This connective tissue contains a network of capillaries which run into a large vein at the base — the circulus iridis major. It also forms lymph spaces, which connect by minute crypts at the base of the iris w^ith the aqueous fluid in the anterior chamber. By these crypts, therefore, aqueous fluid can pass into the lymph spaces of the iris, and thence into the iris veins. In this connective tissue, also, lie the muscle fibres of the iris. These are of the smooth variety, and consist of two sets: (1) Circular fibres, developed mostly near the free pupillary margin, and sphincter in action— -the sphincter pupillae; (2) meridional fibres arranged about the radial furrows of the iris. These fibres arise from the innermost strands of the cribriform ligament, and terminate in the connective tissue of the sphincter pupillae. The sensory nerve of the iris fe the nasal branch of the ophthalmic division of the fifth nerve. The motor nerve to the sphincter muscle is the inferior division of the third nerve. This has its cell-station in the ciliary ganglion, and passes to the iris as the short ciliary nerves. The nerve to the dilator pupillae is the cervical sympathetic. Its cell-station is in the superior cervical ganglion, and the fibres reach the eye through the ophthalmic division of the fifth and the long ciliary nerves. The Function of the Iris. — The function of the iris is to regulate the amount of light admitted to the eye, and to diminish spherical and chromatic aberration (see later, p. 609). Its action is reflex. It contracts when strong light falls on the retina (the light reflex). When light falls on one eye, the pupil of the other eye also contracts (the consensual light reflex). The iris also contracts during accommodation of the eye for a near object, during sleep, and under the action of certain drugs known as myotics — e.g., morphia, which acts centrally, and pilocarpine, eserine, etc., which act locall}' . Besides stimulation of the third nerve, section or paralysis of the cervical sympathetic nerve will cause contraction of the pupil. Dilatation of THE 8EN8E OF VISION 605 the bloodvessels of the iris will help to bring about its expansion, and constriction its contraction. The iris dilates normally in weak light or in the dark, and when the eyes are at rest. It also dilates under the influence of strong emotion and of pain, particularly if the pain is in the region of the neck. r!ertain drugs, knoAvn as mydriatics, produce dilatation of the pupil. Such are atroi)ine, homatropine, Avhich act locally, paralyzing the terminations of the third nerve; cocaine, which acts locally, stimulating the endings of the sympathetic nerve; curare, which acts centrally. Fia. 339. — Diagram showing Nekvb Supply of the Iris. (Dixon.) ///., Third nerve;/, preganglionic fibre to ciliary ganglion; mierated as follows: THE SENSE OF VISION 607 1 Adjacent to the choroid is a single layer of polygonal pigment cells, from which elongated processes containing fine pigment (fuscin) granules pass into the next layer, and end between the rods. 2 The receptor mechanism of the eye, the layer of rods and cones A rod consists of an outer elongated part, about 30 f-i long and 2 ^i broad It is transparent, transverse!}- striated, and in it are to be .found f)he minute pigment granules which form the " visual puq)le." The uiner jjart of the rod spreads out somewhat in the shape of a carrot, the upper part being longitudinally and the lower part trans- versely striated. From the tip arises a rod-fibre, which pierces the external limiting membrane, and swells out as the rod granule or nucleus, finalh' passing on to form a varicose synapse ' (see Fig. 340 A cone also consists of an inner and outer portion. The outer portion IS ta]7ering and pointing, about one-third the length of the corresponding portion of the rod. It is transversely striated, and contains no pigment. The inner part of the cone is broad, and ends in a cone-fibre. This is somewhat thicker than that of the rod, but, like it, pierces the external limiting membrane, contains a nucleus or granule, and ends as an arborizing sjiiapse. 3. The external limiting membrane is a well-defined membrane formed by the outer processes of the sustentacular fibres. The susten- tacular fibres of Mil Her reach from this layer to the internal limit- ing membrane. This membrane serves to support the rods and cones 4 The external nuclear layer is made up of the rod and cone granules (the auclei of the rod and cone fibres), and also of fine fibres belonguig to the supporting cells of the internal limiting membrane (Fig. 340;. 5 The outer molecular layer is really a synapse layer, consisting of the ramifying interdigitations of the rod and cone fibres and the synapses of the cells in the next layer — the bipolar cells (Fig. 340). It also 'iiutains a few supporting cells, probably of a neuroglial nature (> Tht inner nuclear layer consists chiefiy of the bipolar cells which form the first neuron (Fig. 340). One process, as we have seen, arborizes in the preceding layer; the other passes into the inner molecular layer of synapses, to end around the terminations of the dendrites of the ganglion cells of the optic nerve. In this layer are also oval cells, termed spongioblasts, which send a single process into the inner molecular layer, and other small cells, termed amacrine cells, Avhich send a short process into the outer molecular layer. There are also a few bipolar cells. The large oval nuclei of the supporting fibres of Miiller are found in this laj^er. 7 The inner molecular layer is a synaptic layer containing the synapses of the bipolar cells, and of the ganglion cells. It also contains neuroglial cells. 8. The layer of ganglion cells consists of the large flask-shaped ganglion cells which constitute the second set of neurons (Fig. 340). <;08 A TEXTBOOK OF PHYSIOLOGY Their deiulrites pass outwards to arborize in the inner molecular layer; their axons pass in towards the optic nerve, forming 9. The layer of non-meduUated nerve-fibres (Fig. ?Ai)). 10. The internal limiting membrane is formed by the expanded bases of the supporting fibres of Midler. Section II LAWS OF DIOPTRICS The generally accepted hypothesis of the phenomena of light is that first enunciated by Thomas Young — namely, that light is a mode of motion of the ether which pervades sjiace. By the molecular movements of luminous bodies the ether is caused to vibrate in a series of waves, forming a ray of light. The component particles of the ray move at right angles to the direction in which the ra3" is travelling, just as do the particles of water in the waves caused by disturbing the smooth surface of a pool. Waves of big amplitude give rise to a sensation of bright light, small waves to one of dim light. All the waves are of very rapid rate of vibration— 435,000,000 to 764,000,000 per second. Outside these limits the eye is not stimulated, although there are present both infra-red and ultra-violet rajs. Beyond the ultra-violet rays come the Rontgen rays, and below the infra-red the electrical waves in unbroken sequence. The light rays, with the low rate of vibration, give rise to the sensation of red, those with the high rate to that of violet. In between Ave have the colours orange, green, blue, indigo, gradually merging into one another. Ordinary sunlight, as Isaac Newton showed, is composed of this series of colours blended together. Light travels through the ether at about 190,000 miles per second. A ray, falling upon a polished surface, is reflected, the angle with the perpendicular of the reflected ray being equal to that Avhich the incident ray makes with the same perpendicular. When a ray passing through one transparent medium, such as air, meets perpendicularly another medium, such as water, part of it passes into the new medium, and part is reflected upon itself. If, however, the ray meets the new medium obliquety, the part which passes into the medium is bent out of its course, or refracted. This refracted ray is in the same plane as before, and in the case of a x&.y passing from a rarer to a denser medium the deflection is toAvard the perpendicular. The laAV for single refraction is that, AA^hatever the obliquity of the incident ray, the ratio of the sine of the incident angle to the sine of the angle of refraction is constant for the same two media, but \^aries Avith different media. This ratio of the angles is known as the index of refraction, and, knowing this index for any t\A'o media, the direction which Avill be taken by a ray of light can THE SENSE OF VISION G09 he calculated. Water refracts the ray more than air, and glass more than water. When a ray meets obliquely a piece of glass with j)arallel surfaces, part of the light is reflected and part is refracted — bent towards the perpendicular to the surface. On again emerging at the other surface, it is bent back again to its former direction, and therefore passes on not in the same line as that in which it struck the glass, but in one j^arallel to it. So, when light falls obliquely on the sides of a prism, it is doubh' bent, the amount of deflection depending upon the shape and material of the prism. A similar effect is caused bj^ lenses, both biconvex and biconcave. A biconvex lens will bring to a focus all ra^^s parallel to its principal axis — that is to say, parallel to the line which passes through the centres of curvature of its tAvo surfaces. Such a point is termed the principal focus of the lens. Couversety, rays starting from the principal focus will emerge from the lens in a parallel direction. Spherical Aberration. — It has been stated that parallel r-dys falling upon a biconvex lens meet at the focus. In practice, however, this is not the case, as may be seen by trying to focus the sun's rays on a piece of paper with a burning-glass. The image of the sun can not be reduced to an absolute j^oint, because tli^ rays which meet the circumference of the lens are more refracted than those which fail nearer the middle of the lens. This is known as the spherical aberration of the lens. If the outer rays be cut off by interposing a diaphragm, it is found that the image is made sharper. The iris acts as a diaphragm and sharpens the image in the e3'e. If the central part of the lens were made more refrangible than the outer jjarts, then the rays nearer the centre Avould be more refracted than the outer rays, and a similar result obtained. Such is the case with the lens of the eye. Chromatic Aberration. — It is found that, as is the ease with a prism, owing to the dift'erent degrees of refrangibility of the variou.s rays constituting white light, the latter is split uj) or dispersed into its component colour.5 in passing through a lens. The violet ra,ys are bent most, the red rays least. Therefore, if a screen be inter- posed before the focus, there will be an image with a violet centre and a red edge; after the focus there will be an image Avitli a red centre and a violet margin. This is known as chromatic aben'ation. Opticians remedy this by combining lenses of differejit powers of dispersion, forming therebj' the so-called compound achromatic lens. In a S3'stem of lenses there exist six cardinal points. If the position of these be known, then the direction of all rays through the S3'stem can easih' be traced. These six cardinal points are the first and second focal, the first anrl second principal, and the first and second nodal points. The first focal point is the point so placed that all raj'S from it, after passing through the system, emerge parallel to the axis of tho- 39 ()10 A TEXTBOOK OF PHYSlOLOaY system. The second focal point is the point to which parallel rays arc gathered after |)assing through the system. The principal point is situated on the principal axis at the point where the vertex of the spherical surface and the plane perpendicular to the axis meet. Rays which pass through the fust principal ])oint after refraction pass through the second principal point. The nodal point corresponds to the centre of curvature of the lens. It is the ])oint where a ray, falling perpendicularly on the surface^ and therefore passing through without refraction, cuts the axis. Rays which pass through the first nodal point after refraction seem to emerge froin the second nodal point in a direction parallel to that of the incident rav. Fig. 341. — Diagkams to illusteate Refraction. In the simplest form of optical system, where there are only two media separated from each other by a spherical surface {d, p, e, Fig. 341 ), n, the centre of curvature of the surface, is known as the nodal point. A line drawn from a through the vertex of the spherical surface (p) gives the optic axis (OA). Rays parallel to OA in the less refractive medium {S) will be brought to a point (F.,) on the optic axis in the more refractive medium {R) — the posterior principal focus. Rays parallel to OA, proceeding from E, will be brought to a point {F^) on the optic axis — the anterior principal focus. The principal point is at ^j. In the eye, there are several surfaces between the various media, ])ut smce the refractive indices of some are approximately the same — THE SENSE OF VISION 611 e.(/., those of the aqueous humour and the cornea — the refracthig surfaces may be regarded as three in number: anterior surface of the cornea, the anterior and posterior surfaces of the lens. There are three refractive media— the aqueous humour, the lens, and the vitreous humour. These surfaces and media are arranged in such a manner that rays of light travelling from a distance — i.e., parallel rays — are brought to a focus upon the retina at the point known as the yellow spot, the principal focus of the eyQ. The line drawn through the centres of curv^ature of the cornea and lens to this spot is known as the optical axis of the eyeball {dr, Fig. 341). Many careful measurements have been made to determine the cardinal points of the normal eye. The following measurements have been deduced: ;aiiterior) jjriiicipal lcit.us of eye :l (posterior) principal focus . . iirineiual uoiut . . First ( ..., Second (pu^sLenui; pi First principal point . , Second principal point First nodal point Second nodal point . . !2-832() mm. in front of cornea. 22-647 mn:. behind cornea. 1-7532 „ 2- 1101 „ 6-9685 „ 7-3254 „ The princij^al j^oints and nodal points are so close together that they may be combined, giving what is known as the schematic or reduced ej-'e. In such a schematic eye, the path of the rays leading to the formation of the image upon the retina can be mapped out. The rays of light travelling from A and B, the extreme point of the image, and falling parallel upon the surface, are not refracted, but pass straight through the nodal point [K) to the retina. The angle formed by these lines is known as the visual angle. The rays jjarallel to the axis from A and B are refracted through the j^rincipal focus, and cut. on the retina, the first rays passing through the nodal point at a' and 6' resi^ectivejy. Hence an inverted object [a' b') is produced upon the retina. The eye, however, is not a mathematically correct instrument. The various refractive surfaces are not usually so centred that the optic axis coincides Avith the line drawn from the point viewed to the fovea centralis of the retina — the visual axis. The angle of one axis to the other, where they meet at the nodal point, is usually about 5 degrees, but may })e as great as 12 degrees. Moreover, since the centre about which the eye rotates is in the optical and not in the visual axis, the line of regard (the line joining the j)oint-view to the centre of rotation of the eye) does not coincide with the line of vision. There is a certain amount of spherical aberration in the normal e\Q. This is not of much consequence, since it is corrected by the action of the iris. There is also some chromatic aberration, which is not, however, generally appreciated psychologically. It can be demonstrated by looking at the sky through the upper part of a window, and holding the edge of a card parallel to the upper side of the Avindow-frame, passing it from below upAvards and from above doAvnAvards. When the card covers half the pupil, the window-frame. ars continuous. The Perception of Light, and the Relation of the Sensation to the Stimulus. — We have seen that the sensation of light is due to the stimulation of the receptor mechanism of the eye by means of the vibrations of the ether. According to the amplitude of the.se vibra- tions, so the sensation of light varies in intensity. According to the length of time the waves fall upon the retina, so the sensation varies in duration. The sensation evoked lasts much longer than the stimulus. The sensation of a flash of lightning or of an electric spark, for example, is much longer than the time during which vibrations are actually falling on the retina. When the stimuli fall in sufficient^ quick succession, the sensations become fused, so that a lamp swung quickly in a circle gives the sensation of a ring of light. In moving pictures such a fusion of sensation takes place. For such a fusion to take place, it is necessary for the stimuli to be about ten a second for weak light, and forty a second for strong light. The length of interval varies with different colours, being longest with blue, shortest with yellow, and intermediate with red. From the consideration of an electric light and a candle it is obvious that the intensity of the sensation varies with the luminous intensity of the object. Following Weber's law, it is foimd that it is easier to distinguish a slight difference in brightness between two feeble lights than the same difference in brightness between two bright lights. The smallest difference which can be appreciated in the case of the eye moderately stimulated by light is about -^ ,\^, of the total luminosity. The total sensation is greater in amount when light falls on a large area of the retina than when it falls on a small area. The eSect of a stimulus also varies according as it falls upon an eye accustomed to the daylight (the light-adapted eye) or an eye which has been attuned to the dark (the dark-adapted eye). Upon croing from the light into the dark, it is impossible at first to see any- thing; but after a time the eye becomes adapted to the darkness, (322 A TKXTBOOK OF PHYSIOLOGY and suirouuding objects are localized and identified. The sensitive- ness of the retina has increased many times. Conversely, on emerging from ditrkness to light, one is '" dazzled," owing to this extreme sensitiveness. This soon passes off, and the eye becomes " light- adapted." Experiment seems to indicate that the different regions of the retina have different functions. The peripheral regions are found to be relatively more sensitive than the fovea to feeble stinnili — that is, to light of moderate or short wave-lengths. On the other hand, the central portion of the retina resj)onds particularly to bright light — light of long wave-lengths. When the eye becomes adapted to the dark — " dark-adapted " — the increased responsiveness of the retina under these circumstances is in the regions outside the fov^ea. It is much easier to perceive stars of small magnitude when looking sideways than when looking directly at them. It is for this reason, also, that a star ina.y be suddenly observed in the heavens during a movement of the head, and yet, when that part of the heavens is scanned directly, it cannot be seen. On the other hand, as already stated, it is known that it is in the fovea centralis that vision, especially form sensation, is most acute. We alwa3'S look directly at a thing when we want to appreciate its shape. At the same time, the pupil is contracted to shut out peripheral rays. In order to differentiate similar objects grouped closely together, it is necessary that these shoidd subtend an angle of a certain magni- tude at the nodal point with resjject to the eye. Further, in order that objects ma^^ be differenliated, it is necessary that their contiguous margins and the .space between should form an image on the retina, which should n>>t be less than a certain length. It has been found that a subtended angle of 63-75 seconds, equivalent to a retinal distance of 0-00463 millimetre, is necessary for discrimination. Double stars, which sul)tend an angle less than this, appear to the naked eye as single stars. The acuteness of vision at the fovea is ordinarily tested b}' noting the distance at which letters, which at a given distance subtend an angle of 5 minutes at the eye, can be read. This method may be applied either to ascertain what error of refraction may exist in the eye, or, if this be absent or corrected, what the acuteness of vision in the particular eye is. We shall see later that it is also in the region of the fovea that the different colours are best appreciated. The so-called duplicity theory supposes that there are two distinct visual mechanisms in the retina — one that of the rods and visual purple, upon which depends achromatic reactions, especially under conditions of darkness adaptation; secondly, that of the cones, which serves achromatic responsiveness in bright light, and also chromatic responsiveness. This view is not altogether accepted, but it is sup- ported b}^ the fact that a great abundance of rods and visual purple is found in animals which see badly in broad daylight, but which have good '" twilight vision."' Such animals are the bat, owl, and hedgehog. Cones, on the other hand, predominate in the retinae of THE SENSE OF VISION 623 animals which have acute daylight vision — e.g., birds, such as the pigeon and chicken — but which see imperfectly in feeble or artificial light. Further, in cases of total colour-blindness (achromatopsia), the spectrum is seen merely as a band of light of varying intensity, the greatest brightness being in the regions outside the fovea, while in man}'" eases a blind spot (scotoma) is found in a position corresponding to the fovea. In such cases there is good vision in twilight, but in da3'light a marked diminution in the acuity of vision, a fear of strong light (photophobia), bad fixation leading to nystagmus (quick side- to-side movements of the ej'es). In cases of nicotine-poisoning, with visual trouble (tobacco ambly- opia), there is a loss of acuity of vision and deranged colour sensation. It is the region of the fovea which is affected. In cases of " night-blindness " (hemeralopia or nyctalopia) there is, in comparison with the normal colour sense, a shortening of the violet end of the spectrum, and an impaired responsiveness to light or short wave-lengths. For this reason, a person suffering from this condition is vmable to see well in twilight or artificial light, and is said to be night-blind. This condition is inherited, transmitted by the females, but present only in the males of a family. The Perception of Colour. — When white light is passed through a prism, it is broken u}) into a number of colours, owing to the greater Fig. 354. — Wheel for mixing CoLorRs. refrangibility of some rays than others. To most people, the spectrum is made up of six distinct colours: Red, orange, yellow, green, blue, violet. Normal individuals may therefore be said to be " hexachromic." A few people, however, can, like Newton, see a seventh colour — indigo — between the blue and the violet. Thev are " heptachromic." White light is therefore made up of a fusion of these colours. This can be shown by passing the colours through a second prism, when they are recombined to form " white " light. It is not necessary, however, that all the colours be fused to give <524 A TEXTBOOK OF PHYSIOLOGY a sensation of white. It has been shown that various pairs of colours, when mixed, will give the sensation of " white." The mixing can he done by placmg the colours upon a wheel or top which is quickly rotated (Fig. 354). It is better, however, to superimpose on a white surface the different colours from two spectra. The chief pairs of colours which give white are red-green, blue-yellow. Such colours are termed " complementary." If in a good hght one of these colours in the form of a disc or letter be viewed steadily for a time on a white surface, and the gaze then turned to another white surface, the disc or letter will appear after a time in the comple- mentary' colour. This is Imown as the negative after-image. After beholding a red letter, a green letter will appear as the after-image, and so on. ' The different colours of the spectrum vary in luminosity. Nor- mally, the yellow is the brightest part of a spectrum. But the lumin- osity of a colour may vary. Thus, any of the colours of one spectrum may be made of equal luminosity with the yellow of another spectrum by increasing the intensity of the white light used to form the spectrum. With feeble light, the maximum luminosity shifts to the green, and the colours of the red end of the spectrum become less easily perceived than those of the blue end. This accounts for the order of the changing colours of a sunset or the change of colours in a flower garden as tAvilight passes into night. Saturation. — Besides luminosity, a colour possesses a degree of saturation. By this is meant the extent to which it is mixed with white lic^ht. A fully saturated colour is entireh" free from white light, svich as the sodium flame in a dark room. When colours are mixed which are not complementary, we get *' shades." As many as 160 shades have been observed in the spectrum; some shades, such as purple, are not present in the spectrum. When two colours are mixed which are nearer in the spectrum than the complementary colours, a colour is obtained of the part of the spectrum between the two. If the colours are farther apart in the spectrum than the complementary colours, then a colour mixed with white light is obtained — an unsaturated colour. By taking the three colours red, green, violet, or, according to other authorities, four colours — red, yellow, green, blue — all the colours of the spectrum may be obtained by mixing in . varying proportions. These are known as the fundamental colours. In the mixing of pigments, the nature of the pigment substance has to be taken into account. A blue and a yellow pigment, when mixed, give green, not white. This is because the blue pigment absorbs the red and yellow rays from white light, and reflects the blue and green rays. The yellow pigment reflects red, yellow, and green, and retains the blue. When the pigments are mixed, the green rays are the only ones not absorbed. By examination of the light reflected from any pigment with the jDocket spectroscope, it can be seen what ravs are reflected and what are absorbed. THE SENSE OF \'ISIOX 625 Colour Vision. — ^Numerous theories have been advanced to exphiin the phenomena of colour vision. The two classical views are those of Young-Helniholtz and of Hering. The Young-Helmholtz Theory. — This theory assumes that there -are three separate substances in the retuia stimulated by the wave-lengths of the three fundamental colours — red, green, and violet. Simultaneous excitation of all three gives the sensation of white, while absence of stimuli gives that of black. The colour sensations depend upon different degrees of stimulation of these three substances (see Fig. 355). From the diagram, it will be seen that orange is due to a large stimulation of the red, and lesser stimu- lation of the green and violet substances. In the sensation of yellow, the red and green elements are almost equally excited, and the violet but little, and so on according to the manner indicated in the diagram. Violet. Fig. 3.55. — Schema to illustrate the Young-Helmholtz Theory of Colour Visiox. (Helmholtz.) The curves represent the intensity of stimulation of the three colour substances: 1, The red-perceiving substance; 2, the green-perceiving; 3. the violet-perceiving. Vertical lines drawn at any point of the spectrum indicate the relative amount of stimulation of the three substances for that wave length of the sj^ectrum. The Hering Theory. — -According to this view, the fundamental <;olour sensations are red, yellow, green, and blue. These are grouped together in pairs — red-green, blue-yellow, and in addition black And white (black-white). In the retina are three corresponding substances — the green-red, blue-yellow, and black-white. These substances may be stimulated either in an anabolic (a buikling-ui)) Fm. ;J5b. — The Edeidge-Green Colour Perception Lantern. The lantern consists of four discs: three carrying seven coloured glasses — Clear, red A, red B, yellow, green, signal green, blue, i)urple — and one carrjTng seven modifying glasses— Clear, ground glass, ribbed glass, and five neutral glasses. Each disc has a clear aperture. The diaphragm is gi-aduated in respect to three apertures to represent a o|--inch railway signal bull's-eye at 60C, 800, and 1,000 yards respectivelj- when the test is made at 20 feet. The colours are brought successively into view by moving one or more of the handles to position, denoting the colour or modifier in use, on the scale at the top of the lantern. The classi- fication of colour perception is as follows: Heptachromic appreciatihg in the spectrum Hexachromic appreciating in the spectrum Pentachromic appieciariiig in the spectriim Tetrachromic appreciating in the spectrum Trichromic appreciatir^g in the spectrum Difhi'oraic appreciating in the spectrum Totally colour-blind appreciating I^ight and Shads only. Red Orange Yellow Green Blue Indigo Violet Re(i Orango Yellow Green BUk- -- Violet Red — Yellow Green Blue — Violet Red — YeUow Green "— — Violet Red — — Green - ~ Violet Red — Violet explained that all colours appeared modifications of blue and j'ellow. The brightest and purest yellow he called yellow; a slightly darker and not so pure a yellow was green to him. A darker yellow still €28 A TEXTBOOK OF PHYSIOLOGY p^ o o g .2 cfi j3 c2 O § -5 ^ .§ g li P a b II II C2 _o li s ^ ?: 02 _C ^^ S CO a; O oQ H!H II II II I! LO( JY hearing powers. In cetacea there are 1|, in man 2-|, and in the rodent Coclogcnys paca 5 whorls to the cochlea. The External Ear. — Tn mammals this varies greatly in form, from the rigid, almost immovable structure of man to the easily movable organ of most mammals, which in some ma^- be rigid, in others flapping. The external ear consists essentially of two ])arts — the auricle, which acts as a sound-catcher and reflector; and the external meatus, by which the sound-waves are conducted down to the drum-hccid, or tympanic membrane. The external ear is also protective in function. The bitter waxy secretion, or cerumen, and the outward pointing hairs, ■deter insects from entering, while the varying curvature makes it difficult for foreign bodies directly to im])inge upon the tympanic membrane. The tympanic membrane separates the external from the middle ear. It is firmly fixed in a l)ony groove, and lies obliquely to the lumen of the meatus, the lower margin being farther in than the upper. The membrane consists mainly of connective tissue, to- gether with a little elastic tissue. Some of the fibres radiate to the circumference from the umbo, a point just below the centre of the membrane, the others being arranged circularly about the same point. Into the membrane the first of the three bones of the middle ear is inserted in such a way as to render the membrane conical in shape, with the con- vexity towards the meatus. The membrane thus curves slightly outwards, and is not uniformly stretched in all dimensions. The value of this arrangement is that very slight changes of air-pressure produce relatively large move- ments of the membrane, and It also enables the membrane to vibrate to a great range of tones. The condition of the membrane is examined by the use of a specu- lum and the reflected light from a mirror with a central hole, attached to the forehead of the observer (Fig. 374). Across the middle ear stretches a chain of three small bones, or ossicles — the malleus, or hammer; the incus, or anvil; and the stapes, or stirrup. The stapes is inserted by ligamentous tissue into the fenestra ovalis. The function of the ossicles is to interpose a solid element which — Diagram uf J^ak, biiuwixci Ossicles. A, Malleus; B, incus; C, stapes; D, ex- ternal auditory meatus; E, tympanic membrane; F, foramen rotiinchnn; H, Eustachian tube ; K, utricle ; L, saccule ; M, semicircular canals; N, cochlea. The shaded part of internal ear, the bony labyrinth, is full of perilymph; the white part, the membranous laby- rinth, is full of endolymph. therefore relatively great effects, HEARING 645 conducts the vibrations of the tympanic membrane to the fluid of the internal ear, which in its turn excites the receptor mechanism. In the frog we find onl}^ a single cartilaginous rod — the columella. A chain of bones, however, has considerable me- chanical advantages. The handle of the hammer is inserted into the tympanic membrane, and leads upwards to the head, which is placed above the level of the tympanic membrane, and is fixed in position by ligaments which pass to a fissure in the bone, one from a delicate forward pointmg process — the processus gracilis — another from the head of the malleus to the roof. This is one of the fixed points about which the bones rotate. The anvil is in such a position that its conical process points downwards. This process ends by bending imvards to a flattened knob — the lenticular process. From the base of the anval, ligaments pass to the posterior wall of the cavity, while the head of the anvil articulates with the malleus. The stapes is fixed by the head of the stirrup to the lenticular process of the anvil, and passes horizontally to be inserted by the foot of the stirrup into the oval window. Fig. 374. — View of Tymvaxic Mem- bra>;k. Fig. 375. — Method of Examixatiox of the Ear Drum bv Reflected Light. The malleus and incus rotate as one bone round a horizontal axis. When the handle of the malleus is pushed inwards, the head of the bone moves outwards, carrying with it the body of the incus, excessive movement being prevented by the ligaments of the malleus. The descending process of the incus is thereby moved inwards, and pushes the stapes against the fenestra ovalis. The chain acts as a bent lever, .so that, when the malleus moves a certain distance, the stapes moves but two-thirds of that distance; the resulting impact, owing to the order of the lever, is increased b}'" half, and since the area of the tympanic membrane is about twenty times as great as that of the base of the stapes, the force falling upon the oval window at the base of the stapes is about thirty times as great as that falling on the tym- panic membrane at the umbo. For this reason, it is easy to understand that hearing is seriously interfered with when the action of the ossicles is deranged b3' middle-ear disease. 646 A TEXTBOOK OF I'H V.SlOL. — Diagram of Membraxotjs I;Abyrixth. (Keith.) Into the central portion of the osseous labyrinth — the vestibule — - the fenestra ovalis opens. Anteriorly from this there arises a con- voluted tube — the osseous cochlea— which is wrappel around a central Fi i. 377. PS.Q. -Diagram of Right Internal Ear, seen from Above. and Wright, "Practical Anatomy.") (From Parsons Cock., Cochlea; Prom., promontory; CO., carotid canal; E.T.. Eustachian tube; I. A.M., internal auditory meatus; Ve-ot., vestibule; F.H.E., fovea hemielliptica lodging utricle: CI'., crista vestibuli; St.. stapes fixed in f'-nestra walls; Aq.F., Fallopian aqueduct (for facial nerve); Aq.V .. at^ueductus vestibuli: S.S.C, P.S.C, E.S.C., superior, posterior, and external semicircular canals. pillar — the modiolus. The tube is divided into two by a septum parth' bony — the spiral lamina — and partty membranous— the basilar 048 A TEXTBOOK OF PHYSIOLOGY membrane. The up]jer spiral .section, or staircase, is called the scala vestibuli, the lower one the scala tympani. The scala vestibuli begins at the fenestra ovalis, and ascends to the top of the whorl. Here it connects bj' way of an opening in the lamina spiralis —the helicotrema— with the scala tj'^mpani, which descends to the fenestra rotunda. A membrane — that of Rei.ssner — cuts off a part of the scala vestibuli, the scala media, membranous cochlea, or cochlear canal. This is bounded by the basilar membrane below, and ends blindl}'" at the top of the cochlea. Like all the membranous structures, it is filled with endolymph ; the other two staircases, being bony, are filled with perilym]ih. In section, the scala media is triangular. Fig. 378.— Section (Low Powkk) thkough Takt oi' Cochlea, sH<.)\viNa Membranous Canal of the Cochlea. (After Retzius.) A, Basilar membrane; B, rods of Corti; C, hair cells; D, fibres of auditory nerve; E, tectorial meml)rane; F, membrane separating ofE membranous canal of cochlea : G, wall of cochlea. Within this membranous cochlea, or scala media, is contamed the organ of Corti, the receptor mechanism for hearing. The organ of Corti is set upon the upper aspect, or in respect to its position in the head, the anterior aspect of the basilar membrane. It runs almost tlie whole length of the cochlear canal, and consists of a set of elongated, cylindrical, rod-like cells, the outer and inner rods fixed by an exjjanded base to the basement membrane. These meet at their upper ends like the beams of a sloping roof, the outer cells fitting into a socket in the inner cells. The inner rod may be compared in shape to the ulna, and the outer to a swan's neck, head, and beak. From the head of each rod a flattened process projects, the process of the inner cell overlapping that of the outer, and giving, when seen from above, an appearance like the keyboard of a piano. The inner rods are about half as numerous again as the outer, two outer rods thus fitting into three inner ones. It is con- jectured that there are about 6,000 inner and 4,000 outer rods. Intern- HEARING 64f> ally to the inner rods is a layer of columnar cells of the same height as the rods, with about fifteen to twenty short, stiff hair-like processes arising in crescentic manner from the surface. These are known as the inner hair cells. Externally to the outer rods there are also hair cells — the outer hair cells. There are generally three or four rows of these, each cell being supported outside by a supporting cell, known as Deiters' cell. These c;ells are broad at their base of attachment to the basilar mem- brane, and pass as narrow processes to be attached to a fenestrated membrane, or membrana reticularis, which arises as a sort of lattice- work from the upper portions of the rods, and serves to support the free hairs of the hair cells. A similar membrane supports the inner hair cells. Outside the hair cells are several rows of columnar sup- porting cells devoid of hairs, which become continuous with a layer of cells lining the whole of the cochlear canal. Rising from a con- nective-tissue structure on the spiral lamina there arches over the whole organ a homogeneous membrane — the membrane tectoria. aujic n)fC Fig. 379. — Sectkjx of Organ of Corti of a Youxg Guinea-Pig. (Redrawn from Dahlgren and Kepner.) dx.. Cells .0? Claudius; li.c. Hensen's cells; d.c, Deiters' cells, or .supporting cells; aud.c, auditory cells, or hair cells (outer); p.c., oiiter and inner pillar cells; i.aud.c. inner auditory cells, or hair cells; n.fi., nerve-fibres; vi.t., membrana tectoria; ,S.S.C., cells lining sulcus spiralis. Situated in the spiral lamina is the spiral ganglion, from which the fibres of the nerve of hearing arise. Processes from these nerve cells pass along to and around the hair cells, the bases of which do not touch the basilar membrane. The central connections of these nerv^es go to the acoustic nuclei in the pons (see p. 699). The part of the membranous labyrinth corresponding to the vestibule consists of two membranous sacs — the saccule and the utricle — connected by a small canal. From the saccule arises the cochlear canal. In connection with the utricle are three membranous semi- circular oanals, which lie within three correspondmg bony semicircular canals. These latter open into the posterior and superior aspect of the vesrihule. This apparatus probably has no connection with hearing, and is dealt with later (see p. 054), €50 A TEXTBOOK OF PHYSIOLOGY Sound. — Sound is the sensation ])roduccd through the organ of hearing by the vibrations emanating from vibrating bodies. Such vibrations travel by the air at the rate of 1,100 feet per second. Physiologically, sounds may be divided into noises anii musical tones, although one may merge imperceptibly into the other — as, for example, the tuning-up of an orchestra. Many so-called noises are in reality more musical than otherwise. Vibrations of the air at regular intervals produce what is termed a musical somid; vibrations at irregidar intervals produce an unmusical sound or noise. Sounds may differ in pitch, intensity, and quality or timbre. The pitch of a note depends upon the frequency of the vibrations in a given time. The more frequent the vibrations, the higher the note; the less frequent, the lower the note. The range of tones employed in music varies between 30 and 4,000 per second, although it is possible for the ear to perceive notes and vibration-rates as high as 40,000 per second. The relation between frequency of vibration and the pitch of a note is best shown by means of the siren. When the wheel is rotating slowly, nothing is heard but the puffs of air; as the speed increases, the puffs begin to fuse, and then produce a low buzz, rising with increasing speed to such a height that the note finally becomes decidedly unpleasant. The sensibility to pitch varies in different people, as does the power of distinguishing notes of nearly the same vibration. This latter defect may generall}'' be improved by training, although there are certain people who are " tone-deaf." They can only discriminate a few tones, and find it impossible to recognize a time or to sing in tune. Such people only recognize the tune of the National Anthem by the fact that others are standing up with their hats off. The extreme range of the human voice is about half the range of the human ear for musical tones. The intensity or loudness of a note depends upon the amplitude of vibration of the sounding body. This is well seen in the tuning- fork. When the fork is vibrating visibly, the note is loud, and as the visible vibrations pass away, so the note diminishes in loudness or intensity, the pitch remaining the same. If the ear be held to a vibrat- ing tuning-fork, it will be found that the note is loudest when the limbs are vibrating in a plane at right angles to the external ear, since in this position the air is most disturbed, causing a greater difference in pressure upon the tympanum. The quality or timbre of a musical note enables us to tell the instrument bj^ which it is j)roduced. It is easy for most people to distinguish between the human voice, the note of the violin, and the note of the clarionet. This is due to the characteristic wave-forms which are being produced in each case. Just as no two great waves of the sea are exactly alike, but differ in the shape of the crests and wavelets, so the wave-forms of different musical instruments vary. The tones emitted are really compound tones, and contain numbers of wavelets or " overtones." The fundamental tone is due to that HEARING 651. of the large wave; the quality is determined by that of the large wave and the wavelets. The simplest musical tone is produced by a body like a tuning- fork vibrating in simple harmonic motion — that is to say. in such a manner that the waves are all of equal size. This can be seen by the tracing made by a vibrating tuning-fork (time-marker) iqion a revolving kjinograph. Such a sound is uniform, weak. a.ud dull, and quickly becomes monotonous. If two tuning-forks be .sounded, one of which vibrates twice as fast as the other, there can be heard the tones of the two forks and a combination of the torjes The Fig. 380. -To ILLUSTRATE THE FORMATION OF A COMPOUND WaVE rRi'M TwO Pendular Waves. (Helmholtz.) and B, Pendular vibrations, B being the octave of A. If superposed so that e coincides with d" and the ordinates are added algebraically, the non-pendular curve 0 is produced. If .superposed so that e coincides with d' the non-pcndular curve D is produced. form of vibration will vary according as the forks produce at the same time rarefaction or condensation, or one is producing rarefaction while the other is producing condensation of the air (curves C and D, Fig. 380). From an indefinite series of such \nbrations, of which the period of vibration of the fundamental is always a multiple of the least frequent of the series, an infinite variety of curves may be obtained, yielding musical tones having the same fundamental pitch, but differing in quality according to the character of the wavelets. The character of the musical notes of different instruments may be analyzed by means of resonators. A note resonates in a cylinder having the same wave-length of vibrations that constitutes the original note, or an exact divisor of the wave-length of that note. If different 652 A TEXTBOOK OF PHYSIOLOGY notes be .sounded together, a cylinder will resonate witli and reinforce the note of corresponding wave-length. So, too, will tense strings. This can be ascertained on the piano. If straws be attached to the wires, it will be seen that, when one note is struck with the loud pedal raised to remove the action of the damper, other strings than the one struck are vibrating at the same time. This is because their vibration numbers correspond to the overtones. It is the overtones which, when not excessive, give a i:)leasant fulness to the note. Uneven overtones give a rough, penetrating note. When two different notes are sountled at the same time, they interfere with each other, alternately strengthening and weakening each other, and giving a succession of f)hases known as beats. The number of beats per second depends upon, and is equal to, the differ- ence of the rate of vibration of the two partial tones. A difference of one vibration gives one beat per second, of two vibrations twa beats per second. When beats come very quickly, the alternate strengthening and weakening is lost, and a whirring, dissonant sound results. In harmony, or consonance, there is an absence of beats. The greatest consonance is obtained from the same note with the same overtones. After that come the octave notes, corresponding to the note sounded. Then follow various chords, producing varying degrees of consonance. Theories of Hearing. — In the present state of knowledge it is not possible to give any full and satisfactory explanation of the function of the cochlea. The problem to be solved is whether sound-waves produce movement of the hair cells of the organ of Corti, and, if so, the nature of the movement and the means by which it is produced. It is generally held that some form of mass motion, the exact nature of M'hich is not clear, is normally produced in the perilymph through the to-and-fro action of the footplate of the stapes upon the mem- brane of the fenestra ovalis. This mass movement of the perilymph causes synchronous movements of the membrane of the fenestra rotimda, and also affects the endolymph, producing therein waves of compression and rarefaction. As the result of these waves, it is believed that either the basilar membrane or the tectorial membrane is caused to vibrate, and thus the hair cells are affected. Various considerations arise as to the nature of the vibration of such mem- branes. Is the vibration throughout the whole length, or only in part, or in some particular part for a particular sound ? According to the view of Helmholtz, each portion of the basilar membrane is set into reciprocal vibration by tones of a different pitch, high tones being produced by vibration at the basal extremity, where the membrane is narrowest, low tones in the apex of the cochlea, where the membrane is widest and most lax. Except for the fact that Helmholtz supposed that only musical tones were perceived by the cochlea, and that noises were appreciated by the vestibular apparatus, his view still meets with wide acceptance. It HEARING 653 is now recognized that niuscial tones and noises are not f undamentall}'- different, and that both are perceived by the cochlea, the vestibular apparatus having nothing to do with hearing. I On embrj^ological grounds it does not seem probable that a membrane of mesoblastic origin would stimulate hair cells of epiblastic origin. It has also been pointed out that in some animals — for example, the pig — the basal portion of the organ of Corti rests ujDon a bony plate which takes the j^lace of the basilar membrane. To meet these objections the view that the tectorial membrane vibrates has been put forward by several observers. As originally put forward, it assumed that high-pitched tones ca;ised a vibration of the basal end of the membrane, and in descending the scale more and more of the membrane was set in vibration, until with the lowest tones the whole membrane vibrated. Such an explanation fails to account for the ability of the musician's ear to perceive separately the different sounds from an orchestra which reach it simultaneously, and, furthermore, does not account for partial defects — " tone-gaps " — in the range of hearing. The view has therefore been modified on the lines of the Helmholtz view, and it is now suggested that the tectorial membrane vibrates to different tones in different parts of the cochlea in the same manner as suggested for the basilar membrane. It is pointed out that the tectorial membrane gradually increases in breadth from base to apex after the manner of the basilar membrane, and that, by virtue of its elasticit}", transverse flexibility, and the fact that it is attached on one side only, it makes a better and more sensitive vibrator than does the basilar membrane. Auditory Judgments. — -In arriving at auditory judgments, we are aided bj' other senses and by knowledge previously acquired. Nor- mally, we refer sounds to the exterior of the body, and from the nature of the sound determine Avhat it is, its direction, distance, and so forth. According to its quality and loudness, we pronounce a sound to be a gunshot fired in a certain direction, close at hand, or far away. The direction of a soiuid is determined largely by the force with which it strikes the two ears. Judgment of direction is aided by turning the head from side to side, so that first one ear and then the other receives the sound fulh'. It is easier to judge the distance of noises than of musical sounds. The power to judge the distance of the source of sound depends on previous experience. Therein lies the effect of distance imparted by the operatic chorus, which, on leaving the stage, by singing more and more softly, gives the impres.sion of passing farther and farther into the distance. CHAPTER LXXI THE PROPRIO-CEPTIVE MECHANISM Inasmuch as the force of gravity is continuously acting upon the organism, it i.s necessary for it to develop some mechanism by which its position in regard to gravity may be appreciated, and also, when moving, its successive positions in space. In the lower organisms, such a mechanism is developed from the epithelium, and is of such a nature that the perceiving tissues are stimulated by the positions of small heavy bodies which press against them b}^ the force of gravity. WTien the organism moves or changes its position, such bodies will affect the sensitive surface by their inertia, or the latter may be stimulated by the flow of Hu.:d over it. In higher animals, the sensitive receptor e Fig. 38!.— Tekta'CI-ocyst (Statocyst) of a Medusa. (Redrawn after Hertwig from Dahlgren and Kepner.) Stl. is the statolitfi tuclosed in a pedicle which sways with the animal's motion and affects the hairs which project from the surface. mechanism has become removed from the surface of the bod}^ and has come to lie within the head in the vestibular apparatus, and within the body in connection with the muscles, tendons, and joints. The proprio-ceptive mechanism is the mechanism of sense of position and movement — the mechanism by which we are able to poise our bodies in space, by which, also, we are able to adjust our muscular movements to a great degree of accuracy, especially the movements of the limbs. It is this mechanism which enables a man to shave in the dark or with his eyes shut. By the proprio- ceptive mechanism of his head he is aware of its position; by the 654 THE PROPRIOCEPTIVE MECHANISM Cm5 proprio-ccptivc mechanism of the body he is awixrc of the position of the razor in his hand, and is able to adjust the blade so as to shavo without, at any rate, badly cutting himself. In this, of course, he i ; aided by cutaneous tactile sensation, but this, as wo shall see later. is not the factor controllintr tlic main movements. The Proprio-ceptive Mechanimi of the Head — The Labyrinthine Sensations play an important part in the equilibration of the body. The receptor mechanism for these is, as the name signifies, contained within the bon}'' labyrinth of the middle ear, the utricle, and the three membranous semicircular canals. The utricle connects with the saccule, and lies in the vestibule of the internal ear. From i.»*- •/• ^-^ ^jtL- L'ti' n' m;k \i'ii > .' i.i.ii Crista of the AirpuxLA of the (jfUiNEA-i'ic. (H. I'nngle, tioin " Quain's Anatomy.") In lowest part of section nerve-fibres are seen passing through the bone to the loose tissue below the crista. The epithelial cells of the crista are pear-shaped sur- mounted by hairlets projecting into a mucinous material. it also arise the three membranous semicircular canals which lie within the bony semicircular canals, and connect with the utricle by five openings. The bony semicircular canals arise from the posterior and superior aspect of the vestibule, each canal havmg at one end a swelling, or ampulla. They are arranged at right angles to one another, two in a vertical and one in the horizontal plane. The latter is known as the external canal. It lies horizontally, with its curves outwards and the ampulla in front. Of the vertical canals, one is termed the anterior, or superior, the other the posterior. The horizontal canals occupy approximately the same plane. The superior canal lies in a plane inclined at an €56 A TEXTBOOK OF PHYSIOLOGY angle of about 37 degrees to the coronal plane, and the posterior canal at an angle of about 37 degrees to the sagittal plane. The superior canal of one side forms, therefore, an angle of 15 degrees with the posterior canal of the opposite side. There is a considerable space between the bony and the membranous canals. The former are filled with jDerilymph, the latter with endolymph. The special receptor mechanisms lie within the utricle and the ampullar of the semicircular canals. The specialized structures of the ampuUse are known as the cristse. The}^ consist of specialized nerve-epithelial hair cells and supporting cells, which lie upon a base- ment membrane, supported uj)on a hillock of subendothelial tissue, through which pass the nerve-endings of the vestibular part of the eighth nerve, to arborize around the hair cells. In the utricle and saccule there are somewhat similar structures, known as the maculae (Fig. 383). These have, in addition, crystals of calcium carbonate (otoliths), which lie among the hair cells. Fig. 383. — Portion of the Macula of a Mou.se, treated by Golgi'8 Method to SHOW Nerve-Endings in the Sensory Cells (sen.c). (Redrawn after V. Lenhossek from Dahlgren and Kejjner.) h.m.. Basement membrane; sup.nu., nuclei of supporting cells; ?(»'./., nerve-fibre. The vestibidar ganglion, or ganglion of Scarpa, lies in the internal auditory meatus, an upper nerve-branch connecting with the utricle and the ampullae of the superior and external canals, a lower nerve- branch with the saccule and the ampullae of the posterior canals. Centrally the fibres enter the medulla oblongata in the region of the restiform body, and make connections as described later (see j). 699). The first proof that the semicircular canals are concerned with equilibration was adduced by Flourens in 1828. He showed that injury of one canal produced rotatory movements of the bodj^ the axis of rotation being at right angles to the severed canal. He noticed that the disturbances, like those produced by injury of the cerebellum, were of a co-ordinated nature, due to one set of muscles contracting while another set relaxed. For many years Flourens" work pas.sed unnoticed, but since then it has been many times confirmed. The extirpation of both labyrinths is attended with most marked upset of equilibration. THE PROPRIOCEPTIVE MECHANISM 657 The extirpation of one labyi'iath in an animal immeiiately affects the resting attitude of the animal, and also its movements in spa -e. In the frog, the head is incline 1 to the side of the lesion. In swimming, • the operated side is lower in the water, with an abluction and exten- sion of the limbs of the opposite side, particularly the fore-limb. In the pigeon, destruction of the msmbranous labyrinth produces marked disturbances of equilibration. The bird is unable to rest quietly, and is continuoush' performing inco-ordinate movemsnts. After a time these pass off, and it learns to a certain extent to co- ordinate its movements bv means of sii{ht and touch. Fig. 384. — Effect of Destkuctiox of Labyf.ixih ox Ox:: I, ';;)iral endings; iJ, dcndi'itic endings; sk, connective-tissue sheath of spindle. shifting rho head from one plane to another after rotation is familiar in the children's game, where, after turning round quickly with the forehead resting on the poker, the subject stands up and tries to walk straight out of the door or to touch a certain person. Comparative anatomy also supports these results. It has been shown that Japanese waltzing mice and tumbler pigeons have ab- normal semicircular canals. The mode of excitation of the receptor mechanism is generally believed to be due to the inertia of the fluid within the canals. Rota- tion of the head causes a lag of fluid and pressure in the opposite direction, which acts upon the hair cells of the ampulla. Owing to the small size of the canals, there is probably no actual movement of the fluid, but nierety positive and negative alterations of the fluid - pressure within the canals. THK PROPRIOCEPTIVE MECHANISM 659 It is possible that sense of movement is referable to the semi- circular canals, and sense of position to the end-organ of the utricle. Here the solid particles — the otoliths — play a part by acting upon the hair cells with varying pressures, according to the position of the head. The Proprio-ceptive Mechanism of the Body. — The sensations concerned in '" kinsesthetic sense," or the " muscular sense," as it is sometimes called, arise from the muscles themselves, the joints, and tlie tendons. As the receptor mechanism special sensor^' nerve ter- minations have been described in muscle, the neuro-muscular spindles. These are long, fusiform structures in connection with the muscle tibres. Into them passes a medullated nerve, which final]}'' breaks up into a non-medullated plexus surrounding the modified muscle fibre (Fig. 386). In connection with the tendons are found the organs of Golgi — • small fibrous capsules containing a plexus of non-medullated nerve- fibres derived from a branch of medullated nerve. Somewhat similar varicose nerve terminations are also found in the synovial membranes and ligaments of joints. Fig. 380. — XEUK(;-T-H:KDi>'wrs Nkkve I':]xd-()k(;a>- in R.^bbit. (Redrawn after Hiiber and De Witt from Dahlgien and Kepner.) The nerve-sui)ply t.> these structiu-es is large. It is computed that t wo-thirds of the fibres of the mixed sciatic nerve are connected with the proprio-ceptive system, and sensory in function. By means of these terminations, information is conveyed to the central nervous system as to the degree of contraction or relaxation of a muscle or sets of muscle, and also as to the degree of extension or flexion of a joint. The position of a limb may therefore be fairly well localized, even with the Gjes shut. Such information is of great importance in guiding and co-ordinating the movements of a limb. Such impitlses do not necessarily affect the consciousness, but they are of value in aiding the extero-ceptive mechanism in determining the size and shape of liodies — as, for example, the amount and nature of nuiscular movement necessary to feel completely over the surface. This sense is of particular value in determining the size of a body in the dark. The weight of a body is also gauged by determining the amount of muscular contraction necessary to prevent it falling or to raise it. The condi- tion of this mechanism may be investigated by testing the judgment of the indixndual in regard to moderate weights, and also in regard to " deep pressure." Deep pressure sensation — e.g., the presstire of a 6G0 A TEXTBOOK OF PHYSI0LO(;V pencil-point — is connected with this mechanism, and persists when the cutaneous nerves have been cut. The nerves connected with this sense pass into the cord by the posterior roots, and have their cell-stations in the posterior root ganglion. The distribution of the fibres is referred to later (see p. 673). The sense of "balance" is due to a co-ordination of impulses received from the eyes, the semicircular canals, and the organs of cuta- neous and kinaesthetic sensibility. The aiinian is particulajly depen- dent iipon his sense of vision. He also derives much information as to the position of his luachine by cutaneous sensations fi cm his seat and from the ])lay of the wmd on his cheeks. "J'he '" feel " of the joy- stick in which kinsesthetic sensations play a part is also important, as well as the impulses received from his vestibular apparatus. The Enter o-ceptive Mechanism. — The entero-ceptive mechanism is associated with the sensations arising from the alimentary tract from the beginning of the gullet down to the rectum. Various forms of receptor mechanisms have been described, varying in nature from free expansions of dendritic nerve-endmgs to the elaborate Pacinian corpuscle. The total number of afferent hbres to the viscera is small not more than those contained in a single ])osterior root. By means of this mechanism, the orderty sequence of the movements of the digestive tract is insured, usually without involving consciousness of the process. The different parts of the tract vary to different forms of stimula- tion in their power to provoke conscious sensitivity. From the beginning of the oesophagus to the junction of the rectum the alimentary tract is insensitive to tactile stimuli. Heat and cold do not excite the mucous membrane of the stomach ; the colon is almost insensitive; the gullet and anal canal, on the other hand, are sensitive, to thermal stimulation. Chemical stimuli also vary in effect. Alcohol produces a feeling of warmth in all parts, whereas glycerine has a localized stinndatory effect i;pon the anal canal. The mucous membrane of the ceso])hagiis and stomach is insensitive to stimulation with weak hj'droehloric acid. The sensation of thirst is due to changes in the mouth, throat, and stomach. It is generally brought about by a drying of the mucous membrane of the throat after the inhalation of dry or dusty air, or the ingestion of salt or dry food. Wlien water is long with- held, it is possible the terrible sensation of thirst also arises from an altered condition of the blood. The sensation of hunger is evoked bj- the contractions of the con- tracted empty stomach. It may be satisfied to a certain extent by swallowing the saliva to induce relaxation, hence the efficacj- of chewing tobacco. Normally, food induces such a relaxation. It maj'-, however, be induced by swallowing an}- solid material. Thus, the natives on the Orinoco appeased their hunger in the time of need by eating baked earth. The distension of the stomach thus induced satisfies hunger by stopping its movements. The sensation of fulness after a large meal is due to dilatation of the stomach. THE PRUPRIO-CEPTI\ E MECHANISM 661 The call to defaecatioii is due to distension of the rectum, and may be evoked artiticially. e.g., by the introduction of fluid, or of a balloon and its distension to a pressure of about 50 mm. Hg (see p. 419). Pain is due t(j the stretching of the ahmentary tract by obstruction or overdistension. Colic is due to a tonic contraction of the gut, which prevents peristalsis from forcing on the contents of the gut. Vague sensations, such as uneasiness, tingling, tickling, are due to some form of abnormal stimulation As a rule, pain in the alimentarj' tract is not well localized, but is more accurately localized in the fixed than in the movable viscera. The nerves subserving the pain sensation are the sympathetic, and the pain is referred to the superficial cutaneous areas supplied by those nerves which are in connection with the same segment of the cord as that from which the sympa- thetic supply of the viscus is derived. The stimulation of the sympathetic nerves produces an irritable focus in the cord, and this gives rise to hyi)er- sensitivity and so to pain felt in the peripheral tissues connected with that Fio. 387. — Diagram to explain segment of the cord. In the case of the stomach, the hypersensitivity affects the seventh, eighth, and ninth thoracic nerves; of the intestine, the tenth and eleventh thoracic; of the rectimi, the first, second, and third sacral. An irritant applied to the skin in the area where the pain is felt mav take possession of the sensory nerve and the attention of the patient so that those from the viscus have no efifect. Referred Pain and Counter- Irritation. (Dixon, after Mackenzie.) The diagram shows, also, how irritants to tho slcin may cause local dilatation of the vessels bv an axon reflex. CHAPTER LXXn THE SPINAL CORD The nerve-fibres act as conductors connecting ihe receptor and effector mechanisms. The conductors form the nerve trunks of the body— the cranial and the spinal nerves — and the tracts within the central nervous system. The conductors are the processes of the nerve cells, or neurons ; these interlace and form synapses, through which the nervous energy is transmitted from one neuron to another. We have to consider the ingoing neuron, which connects the gensory nerve-ending, or receptor, to the central system, and the efferent neuron — the final common path — which connects the central system to the effector organ. The axons, or conductors, of these two sets of neurons form the mixed nerve trunks of the body. The arrangement of each spinal nerve is as follows: On the postero-lateral aspect of the spinal cord there enters the posterior root, which has a ganglionic swelling upon it — the posterior root ganglion. From the antero-lateral aspect of the cord emerges the anterior root. The two roots combine to form the spinal nerve. In all the thoracic nerves, and some of the sacral, there are not only large fibres which pass to the body-wall structures, and are known as somatic fibres, but also small fibres which supply the viscera and the involuntary muscle of the body, and are known as splanchnic fibres. The course of these latter fibres is dealt with when the autonomic system is considered (see p. 748). The fibres of the posterior root form the great afferent system, the fibres of the anterior root the great efferent system. Section of a posterior root leads, therefore, to a cutting-off of the impulses which come both from the extero-ceptive and proprio-ceptive mechanisms^ that is, the sense organs which receive impulses from the outside world, and those which initiate the impulses which arise in the inner world of the body itseK. In the case of the spinal nerve, the former impulses include those of touch, temperature, pain, and the latter those of the kinsesthetic sense. Section of an anterior root causes a paralysis of the muscles and any other effector organ supplied bj' the nerve. Wallerian degeneration affects the axons, which are cut off from the cell bodies of the neurons. The cells which give origin to the fibres of the posterior root are situated in the posterior root ganglion; those of the anterior root fibres in the anterior horn cells of the spinal cord. As a consequence of section of an anterior root, the nerve-fibre deg.enerates toAvards 662 THE SPIKAL CORD {)0:j the periphery. The path of degeneration which follows section of the posterior root depends upon the site of section. If it be between the ganglion and the cord. then, since the nerve cells are in the ganglion, degeneration will take place in the parts of the fibres Avhich enter the spinal cord; if. on the other hand, it be peripheral to the ganglion, then the nerve-fibres will degenerate towards the periphery, where the}^ form connections with the various rereptor mechanisms. Tho Degeneration of efferent and of afferent Degeneration of efferent fibres below a fibres below a section of entire nerve. section of anterior root. Degeneration of afferent H'oves bcl3\\- a section of posterior root beyond the ganglion. Degeneration of afferent fibres above a section of posterior root above the gangb'on. Fig. 388. — Diagr.\m5 to illvstk.^te Walleeiax DEGEyEEATiox of Xerve-Roots (Waller.) ingoing afferent fibre from the posterior root ganglion makes a variety of connections. These are best considered after the structure of the spinal cord has been described. The Structure of the Spinal Cord. — The spinal cord is the long strand of nervous tissue which passes down the vertebral canal from the base of the brain to the level of the first lumbar vertebra — a length of about 18 inches. It develops in three zones from the neural tube (Figs. 389, 360). From it are given off the anterior and posterior roots of the spinal nerves. In the cervical and again in the lumbar region there is an enlargement from Avhich arise respectiA^ely the nerves- GC-t .\ TKXIBOOK OF I»HVSJ()|J)(;Y of the braiihial and lumbar i»luxiiscs. In these enlargenient.s the cord is more or less oval in section ; in other ]mrts it is nearly ronncl. Down the centre there runs a fine canal lined ))y ciliated ei)ithelinm, while post root gang. spongio-bl. germ, cells middle zone t- inner zone ant root Fig. 3S0, — Diagkamjiatic Section showixg the Three ZOiS^ES of the Smnal NErRAi, Tube AT the Sixth Week. (Keith.) post mes. (from post roots j post /at (from post roots) ^margin, (from post roots) crossed pyram. (from motor cortex) asc. cerebellar outer zone middle zone. inner zone asc. cerebellar \' cerebellar (fror.i cerebellum) ant', pyram (from motor cortex) Fig. 390. — DiAcnAiuiATic Section of Spinal Cord to show the Parts formed in THE Three Zones of the Embryonic Spinal Cord. (Keith.) two fissures in the middle line dip into the cord anteriorly and pos- teriorly. The anterior fissure is more or less open — a kind of furrow — the posterior fissure is practically' closed, being formed mainly (>f supporting neuroglial tissue. On section, the spinal cord is seen to l^e composed of white and grey matter. The latter is centrally placed in the shape of an H. The joining limb of the H passes on either side of the central canal THE SPINAL CORD 665 The grey matter consists luaiiily of nerve cells and tiieir non- inedullated processes ; the white matter of the axons, or medullatecl nerve processes. The nerve-fibres in the spinal cord are devoid of neurilemmal sheath. The neuroglia, the supporting tissue of the cord, is intimately woven into the structure of the cord, particularly of the grey matter. Round the central canal it forms the substantia gelatinosa centralis, and around the head of each posterior horn of grey matter is another collection of neuroglia, the substantia gelatinosa Rolandi. Fig. 391. — Diagrammatic Section THROUGH SpIXAL CoRD IX ThOKACIC Kegiox. (.Parsons and Wright.) Fig. 392. — Diagrammatic Section of SriXAL Cord through Cervical Exlakgement. (Parsons and Wright ). Fig. 393. — Diagrammatic Section of Spixal Cord through the Lumbar Exl.vrgement. (Parsons and Wright.) The grey matter in each half of the cord is divided into a posterior horn, a lateral horn, and an anterior horn. In it are various groups of cells, the chief of which may be classified as — ■ 1. Posterior horn cells. These are small multipolar cells, chiefly of commissural function. 2. Clarke's column of cells — cells, more or less bipolar in form, situated on the imier aspect of the posterior limb of grey matter, near its junction with the connecting limb. From it axons pass into the cerebellar tracts. 3. Intermedio-lateral gi'oup — a group of cells situated chiefly in the lateral liorn. From it axons pass out into the sympathetic svstem. 6B6 A TEXTBOOK OF PHYSIOLOGY 4. Anterior horn group — groups of large multipolar cells from Avhich the efferent fibres of the anterior root arise. The white matter of the spinal cord consists of tracts of fibres Avhich run mainly up and down. There are fibres— (1) from the posterior root ganglia of the spinal nerves, Avhich ascend or desoend in the spinal cord; (2) from the grey matter of the spinal cord, which ascend to the brain ; (3) from the grey matter of the brain, which . DiAGK.VM T(J SHOW THE VaKIOUS ENDUUENOt'S AND EXOGENOLS TKACi'S OF SriNAi, Cord. (Mott.) 1, Anterior horn; 2, commissural fibres: 3, posterior horn; 4, crossed pyramidal tracts; 5, direct cerebellar tract; 6, ant cro- lateral ascending tract: 7, endogenous (oval area of Flechsig): 8, endogenous tract (Gombault and Philippe's tract); 9, endo- genous cornu commissural tract; 10, rubro-spinal and spino-thalamic tract; II, direct pyramidal tract; 12, postero-median column (of Oo]l); 13. postero- external column (of Burdach); 14, pjstero-internal triangle (endogenous;; 1."), comma tract (endogenous); 10, Lissauer's tract: 17, teotn-spinal. spino-tcctal, vcstibulo-spinal, and cerebro-sjjinal fibres. OGS A TEXTBOOK OF PH Y8I0L0GY The Tracts arising from the Posterior Root Ganglia, and passing into the Cord (Posterior Columns) — The Paste to- Median Tract {of (•oil). — The cell-stations are in tlio posterior root ganglia, especially the sacral and linnbar. I'he fibres first enter the postcro-lateral cohmui, and then pass into the postero-median, lying dorsally close against the postero-median fissure (12, Fig. 395). Thej- pass np to the gracile nucleus situated at the junction of the cord with the spinal l)ulb. givino- off manv collaternls on the way. DefUtc nucleus '^i^\ Direct cerebellar Tactile (discrimination) Joint and muscle senses (sense of position) rjon-sensory recepto' (Clarke's column) Deep sensation Superficial sensation Part of Gower's tract entering cerebrum by superior cerebellar peduncle Tactile Gracilis- cuneatc nuclei Pain, heat, and cold ■Tactile receptor -Pain receptor -Heat receptor Cold receptor Fir 396. — Diagram to itLrsTRATE the Afferent Systems to Cei!ebrum Ai>ii> Cerebellttm. (Mott.) ThePostero-Lateral Tract {of Burdach). — The fil)res arise like thepre- cerling and pass in a more external position, to end around the cells- of the cuneate nucleus at the base of the spinal bulb (13, Fig. 395). The Marginal Tract {of Lissauer) lies just external to the posterior horn of grey matter. The fibres arise from cells in the posterior root ganglia. They are very fine asc;ending fibres, Avhich gradually form. THK SPINAL (OHi) r;(J!t synapses with the posterior lioru cells. Possibly they are connected also with the sympathetic system. The Comma Tract {Descending) intermingles with the tracts of the postero-median and postero-Iaterai columns. It consists of the descending processes of the afferent fibres of posterior root ganglion cells, Avhich branch when they reach the spinal cord. Possibl}' some fibres of this tract arise in the spinal cord itself. 'th0^^^ Direct ,.. cerebellar tract Pyramidal tract ■Pre-pyramidal (rubro-spinal) Deiters' spinal tract (vestibulo-spinalj Anterior horn cell Fig. 397. — Diagk.vm to illustrate the Various Paths of Traksmission from Brain to Spinal Motor Netjkoxs. (Mott.) Tracts which pass from the Cord to the Brain (Lateral Columns) — The Dorsal Sjjino-Cerebellar (the direct or ]:)osterior cerebellar tract of Flechsig). — The large fibres of this tract are derived from cells in Clarke's column of the same side, and pass in a postero-lateral marginal position (5, Fig. 395) into the spinal bulb, and thence by the rest if rm body to the anterior portion of the superior vermis of the cerebellum. The Ventral Sptno-Cerebellar Tract (or ascending antero -lateral or ventral cerebellar tract of Gowers) arises on the opposite side from (>70 A TEXTBOOK OF PHYSIOLOGY scattered pcsteiior horn cclLs, aud ])os.sibIy from cells of Clarke's- column. It passes up in the aiitcro-lateral marginal position of the spinal cord, and passes through the bulb and pons, to enter the superior vermis of the cerebellum by the superior peduncle. The Spino-Thalamic Trad consists of a scattered group of fibres lying just internally to the ventral spino-cerebellar tract. Its fibres pass upwards, to end mainly on the same side in the optic thalannis. Some, however, end <»n botli sides in the anterior corpora quadrigemina (10, Fig. 395). Tracts which pass from the Brain to the Spinal Cord — The Cortico- Spinal or Pyramidal Tract. — This tract, consisting of the axons of the large pyramidal cells which exist in the motor region of the cerebral cortex (see p. 723) passes down through the Ijrain stem in a ventral ]iosition to the base of the bidb. where most of the fibres cross to the other side, forming the motor decussation. These crossed fibres come to occupy within the spinal cord a postero-lateral position (Fig. 397). They gradual^ terminate during their passage doA^ai the cord around the cells at the base of the posterior horn (some say round the cells of the anterior horn). The fcAv uncrossed or direct fibres pass doAvn on the margin of the anterior fissure of the spinal cord ; some end around the cells of the same side, some pass across the anterior commissure, and end around the cells of the opposite side. The Bulr/O- Spinal Tract (or jjrep;^^-^ midal tract of Monakow). — The fibres of this tract arise from the cells of the opposite red nucleus of the mesencephalon, and, crossing in the mid-brain (Forel's decussa- tion), pass through the pons and bulb to the spinal cord, occupyhig therein a somewhat triangular space just anterior to the crossed pyramidal tract (Fig. 397). The fibres terminate around or approximate to the anterior horn cells. The Veslibulo-Spinul Tract (antero-lateral descending tract of Loewenthal). — -This consists of fibres Avhich arise from Deiters" nucleus, situated in the upper part of the medulla and lower parts of the pons varolii, and pass down into the spinal cord in an antero- lateral position, mingling to a certain extent with the fibres of the ventral spino-cerebellar tract. It constitutes a pathway for impulses which pass from the cerebellum to the spinal cord ; its fibres end by arborizmg in the proximitj^ of the anterior horn cells. The Olivo-Spinal and Thalamo- Spinal Tracts (tract of Helweg) occupy an antero-lateral position opposite the anterior horn. The fibres pass from the thalamus by waj^ of the inferior olive of the bulb into the cervical region of the spinal cord, where they gradually dis- appear. Their destination is not certainly knoAvn. Fibres which pass from one Part of the Spinal Cord to Another (Commissural Fibres). — ^These fibres, of which there are many, are not grouped into very definite bundles. Manj^ pass up in the lateral columns, others in the so-called anterior basis bundle, and form connections with the posterior longitudinal bundle. of the brain stem; others lie posteriorly near the postero-median fissure, and form what is known as the septo-marginal tract. THE SPINAL CORD 671 The position of the various groups of cells aud of the above tracts have been traced by various means: 1. Wallerian degeneration (c/. p. 663) : If a nervous lesion be made, .such as hemise<;tion of the cord, and the animal kept alive a sufficient time for the nerve-fibre to degenerate, the path of the degenerated hbres is then easily'' traced by certain methods of staining. Thus, tv/o or three weeks after such a lesion, degenerated fibres stain black with Marchi's fluid, owing to degradation of the myeline and setting free of oleic acid. At a much later stage the degenerated fibres do not take the Weigert-Pal stain, while normal fibres stain deeply. The pathological investigation of clinical cases by this method affords valuable evidence, especialh^ in the case of the sensory tracts, where the feelings, etc., of the patient have been carefully investigated. 2. Method of retrograde degeneration: The position is traced of the cells which show chromatolysis as the resvilt of a nervous lesion — e.g., section of an anterior root about three weeks before death. The degeneration of different groups of cells which follows amputa- tion of the leg at different levels points to a definite connection of certain groups of anterior horn cells with definite muscles. 3. Histological methods — such as the silver chromate method of Golgi,* or intra vitam staining with methylene blue. Certain neurons, wnth their processes, are picked out in their entiret}'. 4. The myeUnation method : The Weigert-Pal method differentiates the myelinated fibres from those which are not yet myelinated. The development in the foetus of the medullary sheath of medullated nerves takes place at different times in the various tracts. It occurs first in the fibres which enter the cord from the sj)inal nerves; next in the commissural fibres between different parts of the spinal cord; then in fibres which pass from the sijinal cord to the cerebellum; and last in the tracts which pass from the great brain to the spinal cord (the pyramids). The last become myelinated after birth. The Neural Arcs, — We are now in a position to consider the chief neural arcs through which sensory impidses are received, transmitted, co-ordinated, and made effective: the spinal, cerebellar, and cerebral arcs. The ingomg fibres, whose end processes make connection with the receptors at the periphery, pass in by the posterior root, in the ganglion of which their cells are situated, to form various connections in thespinai cord. The chief of these are illustrated in Fig. 397. and may be summarized as — 1. With the posterior horn cells of the same side. 2. With the anterior horn cells of the same side. 3. With the posterior liorn of the opposite side. 4. With Clarke's column of the same side. 5. With the lateral horn of the same side. 6. With segments of the cord higher up, and with the gracile ^ This method consists in hardening the uei-vous tissue in potassium chromate, and soaking it in silver nitrate, thereby causing a deposition of silver chromate in the nerve coll anfl its processes. 672 A TEXTBOOK OF [»HYSl()L()(;V and cnmeate nuclei of the nicdiilla throiiL'h llic postoro-inctliaii and postero-lateral columns. 7. With other segments of the cord lower doAvn ])y the coinina tract. The Spinal Arc. — This arc, in its sim])lest plan, may be regarded as being made up of the ingoing afferent fibre, Avhich ends around the anterior horn cell of the same side, and the efferent filjre from this cell. It is probable that the ingoing neuron ends around the T)osterior horn cells of the same side, and a connecting neuron joins up these cells to the anterior horn cells. The Cerebellar Arc — To the Gerebcllum. — Impulses troju the posteri(jr root neurons reach the cerebellum by several ways : ( 1 ) On the same side by processes which end in Clarke's column, and then bv the neurons of this eolmnn, the axons of which form the dorsal spino-cerebellar tract, which goes to the superior vermis by way of the inferior peduncle. (2) On the opposite side by means of neurons of posterior horn cells, axons of which form the ventral spino-cerebellar tract. This passes to the superior vermis by the superior peduncle. (3) By the postero-median and postero-lateral columns to the gracile and cuneate nuclei in the spinal bulb, and thence bv neurons the axons of which pass to the cerebelhim by the inferior peduncle (the arcuate fibres, see pp. 689, 6£0). From. tJie Cerebellum axons pass to Deiters' nucleus, which lies in the upper part of the bulb, and is connected with the vestibular branch of the auditor}' nerve (see p. 698); thence by the vestibulo- spinal tract to the spinal cord. Connection with the spinal cord is also made by way of the posterior longitudinal bundle. The Cerebral Arc — To the Cerebrum. — (1) The axons of the posterior root neurons pass up to the gracile and cuneate nuclei of the bulb bj^ the postero-median and jDostero-lateral columns; (2) the axons of the neiirons (the intermediate neuron) of these nuclei pass to the thalamus by a tract known as the mesial fillet; (3) the axons of the third relay of nem-ons (the upper neuron) pass from the thalamus to the cortex. From the Cerebrum by the cortico-spinal (pyramidal) fibres, crossed and direct, to the anterior horn cells. Since the cerebellum is also connected with the cerebrum, it is iDOssible for impulses from the spinal cord to reach the cortex via the cerebellum, and also to pass to the S]>inal cord from the cortex through this organ. The Functions oJ the Spinal Cord. — The chief functions of the spinal cord are to act — (1) as a reflex centre; (2) as a conductor of impulses to and from the brain. The Spinal Cord as a Conductor. — This function has been dealt with in the description already given of the position of the various tracts. It remains only to indicate that the impulses coming into the spinal cord from the exteroceptive and proprio-ceptive mechan- isms vxndergo a redistribution according to their function and destina- THE SPINAL CORD 673 tion. This has been worked out hirgely from careful clinical observa ■ tions made upon patients who are suffering from definite cord lesions, the nature of the lesion in each case being determined subsequently by post-mortem examination. The impulses connected with pain €ross at once to the opposite side, and ascend in the sj)ino-thalamic tract. Thermal impulses do not cross quite so soon, but take a very similar course. Tactile impulses pass up on the same side for four or five segments of the cord, and then cross, to ascend in the anterior region of the cord. Kinsesthetic impulses, concerned with Homolateral impulses underhing lu'isciilxi- sensibility (passive positiuQ aud of movement), also jf touch and pressme for a few segments Homo-lateiul •unconscious impulses iunderlying co-ordination .and reflex muscular tone Hutero-latcial unconscious afferent im- pulses under- lying muscular co-ordinatiuu and reflex cone All impulses of pain, of Iicat ■ and cold (hetero-Iat-ral) Impulses of touch aud pressure (hetero-lateral) Fig. 398. I, Fibres in po-^terior column; 2, fibres in Clarke's column; 3, fibres to cells of pos- terior horn; 4, fibres to cells of anterior horn; .5, fibres to cells of lateral column: 6, dorsal cerebellar tract; 7, ventral cerebellar tract; 8, spino-thalamic and tcctal tracts; 9, ascending fibres in anterior columns. (W. Page ^lay, bir jiermission of the editor of Brain.) the sense of passive position and movement. ]iass up in the postero- median and postero-lateral columns of the same side. Impulses con- cerned in co-ordination and reflex muscular tone which do not enter into consciousness, pass up on the same side in the dorsal spino- cerebellar, and on the opposite side in the ventral spino-cerebellar tract (Fig. 398). The Effect of Transverse Secfio7i. — The effect of transverse section depends according as it is partial or complete. Section of one half (hemi-section) leads to a loss of movement on the same side as the lesion in the parts supplied by nerves arisiag below the site of injury. It also leads to a partial loss of sensation in the same area. The kinges- 43 C74 A ^1 KXTBOOK OF PHV^SI()L()(;^' tlietic and tactile sensations are niarlvediy inipa.red, wliile tliose of pain and teniperatxu-e, which cross soon after entering the cord, are but little aifected (Fig. 386). Degeneration takes place on the side of the lesion in the motor tracts — e.g., the pyramichd, rubro-spinal. In oom])lete section — for example, in the thoracic area — there is paralysis below the site of the lesion of sensation and of all the vohmtar}' muscles, and of some of the inv^oluntary, on both sides of the body. This leads to a total loss of movement, a lowering of the blood-pressure, and loss of control of the various sphincters. If the section be made high up in tlie cervical region, the muscles of respiration, including the dia- phragm, are paralyzed, and death results. In the spinal cord there takes ])lacc an upward degeneration in the ascending tracts, and a down- ward degeneration in the descend- ing tracts. The Cord as a Reflex Centre. — In addition to conducting im- pulses to and from the higher parts of the central nervous system, the spinal cord acts as a reflex centre. Afferent messages entering the cord are received, and diverted into appropriate efferent channels. Such reflexes are regulated by a certain code,- Avhich is ai)plicable to all the reflex reactions carried out by means of the central nervous system. The system has been most conveniently worked out in the case of the ■' spinal animal " — that is to say, an animal in which the spinal cord is separated from the higher parts of the central nervous system, which may, or may not, be destroyed. Such an operation at first results in '• spinal shock." After the familiar operation of pithing a frog without destroying the spinal cord, the animal lies in a state of flaccidity, irresponsive to any form of stimulus. After a time it recovers movement of the hmbs, and assumes a nearly normal sitting position. In response to a jDinch, the hird-limb is drawn away; if a piece of paper moistened with acid be ])lcced on the side of the belly, the animal attempts to sweep away the irritant by movements of the hind-limb of the same side (Fig. 399), or, if the stimulation be sufficiently intense, by movements of the limbs of both sides. Placed in water, the animal will perform swimming movements, swimming, however, somewhat more deeply than usual, owing to the head being held in a lower position than normal. With higher animals— e.gr., the dog— the effects of such an operation Fig. :]99.— Showing Reflex Action vy COKD AFTER REMOVAL OF EnTIUE Braik. The beaker contains weak siilpluii-ie acid. THE SPINAL COIU) 675 a b Fig. 400. — .SaowiNu Reflex Action .^fter Removal of Brain. In a weak acid is applied : 5 shows reflex efforts at removal of the stimuluj Fig. 401. A, The recfptivo tieid for the scratch reflex as revealed after low cervical transactiou, //• marks position of last rib. B, Diagram of spinal arcs involved. L, receptive or afferent nervc-j^ath from left foot; B, receptive nerve-path from opposite foot; Ra, Fj3, receptive nerve-paths from dorsal skin of left side; FC, the Anal common path, in this case to a flexor muscle of th:* hip; Pa, Pd, proprio-s])inal neurons. (From Sherrington's "'In- tegrative Action of the Xervous System," by permission of Yale University Press and Messrs. Constable and Co., Ltd.) 076 A TEX 1 BOOK OF l'H^SlOLOGV lire ccmsidcnibly more la.sling and nioic tumplcx. Below the site f f the lesion there is total loss of sensation in the skin, the skeletal muscles are inert and flabby, the 8])hincters are toneless, there is increased loss of heat, and the arterial ])rcssure of the animal falls from 40 to 50 mm. Hg. After a few days many of these symptoms }iass away. The arterial pressure rises to normal; the sphincters again act, so that urine and faces are passed in a normal manner; the skeletal muscles recover their tone; and sensory stimuli applied to the skin evoke reflex muscular responses. It is upon such an animal that the code of reflex actions has been worked out. A second section of the cord at a lower level does not renew the shock. Tlio Tig. 402. .4. Scratch rcfusx interrupted by a brief Mexion-rcflex. The time of applitation of the stimulus evoking scratch reflex is shown by the lowest signal line; that for iiexion-reflex by line immediately above. Time in fifths. The scratc*h reflex returns with increased intensity after the interruption. B, Similar to A, but the scratch reflex is interrupted later and returns more slovJy and with marked irregularity in its beat. (From Sherrington's " Integrativi- Action of the Nervous System," by permission of Yale University Pr^ss and Messrs. Constable and Co., Ltd.) shock is caused, then, by cutting off the spinal from the higher centres, not by the lesion of the spinal cord itself. The chief reflexes studied have been — 1. The flexion reflex. A harmful stimulus applied to the hind-foot causes the withdrawal of the foot from the site of injury — an actiwi often accompanied by extension of the opposite hind-limb. 2. The extension reflex. The application of gentle pressure to the pad of the flexed limb induces the movements of extension of that limb, and of flexions of the opposite limb — i.e., the movements of walkins in the normal animal. THE SPINAL CORD 677 o. The scratch reflex. Light stimulation of the " saddle "area calls forth movements corresponding to the familiar scratching movements indulged in by dogs removing a tiea or other irritant from this area. The first point to be observed in regard to such reflexes is that a given .stimulus always evokes the same response. Thus, a pin-prick applied to the foot alway.s evokes the flexor and not the extensor response. The reflex is localized. Another important point is that only one reflex can have charge of the final effector path at once. Just as it would be very embarrassing if the telephone exchange permitted several callers to speak at once down the same final transmitting wire, so would it be if various afferent calls had possession of the final effector path at the same time. All kinds of inco-ordinate move- ments Avould be evoked. Any such inco- ordination is therefore prevented by the law that only one reflex at a time can have charge of the final common path. This is exemplified as follows: If the stimuli" in- ducing the flexor and extensor reflexes be applied to the foot at the same time, one or other reflex is evoked, and not a com- bination of the reflexes. The same final common path is used in both reflexes, and is taken jjossession of by the stronger stimulus. If the stimuli be of equal inten- sity, but entering different levels of the cord, then there is a further code of rules. For instance, if, while the animal is performing the scratch reflex as the result of a stimulus applied to the saddle area (/? of muscles is relaxed. Thus, when the flexors contract and draw up the leg, the extensors are relaxed (Fig. 407); and Avhen the ex- tensors extend the leg. the flexors are relaxed. Each movement is brought about by co-ordinate contraction of one group of muscles and relaxation of the antagonists. On this depends the perfect balance of the movements of a technician or musician. In the body, it is difficult to get a reflex which does not either a.ntagonize or reinforce other reflexes. This is Avell illustrated by Fig. 409. Here the final motor neuron is that to the vasto-crureus of the dog. It is excited by stimulation of the ear. fore-foot, tail, and ])ressure on the pad of the foot of the same side, and by stimulation of the shoulder and nocuous stimuli to the hind-foot of the opposite ""''"i Li: show that as the strength of acid is increased the reflex is more quickly performed. The beakers contain respectively, from left to right, O-l, 0-2, 0'3, 0*4, Ov"), and 1 per cent, sulphuric acid. side. It is inhibited b}" stimulation of the shoulder of the same side (the scratch reflex), and by nocuous stimuli of the hind-foot of the same side. Not only do sensory stimuli (the extero-ceptive mechanism) react upon the reflexes of the bod}-, but the impulses which arise from the muscles themselves and from the joints and tendons (the proprio- ceptive mechanism), and from the viscera (the entero-cej^tive mechan- ism), also play a part in determining the effector nature of reflexes. The chief points in connection with spinal reflex action may be summarized as follows : 1. Reflexes are lo^al.zed, definite, and purposive. 2. Owing to the interposition of synapses in the course of the reflex arcs, there is marked delay in the rate of conduction therein, A« compared with the rate of conduction in nerVe. The synapses also <;S0 A TEXTB()(JK OF PHYSIOLOGY exert a valve-like action, so that conduction manifests itself in one direc- tion only . The spiapscs also offer a varying degree of resistance to the im]uilse, so that, generally, a reflex is localized ; but inider the influence of certain [joisons, .such as strychnine, a slight stimulus will evoke tonic nuiseular spasms over the whole body. 3. In the reflex arc there is a summation of stimuli ; a succession of stimuli, each of an intensitj-' insufficient to evoke a response when ajiplied alone, will eventnally provoke a response. 4. Excessive stimulation leads to a fatigue in the synai)ses, whicli occurs princi^mlly in tlie connection between the nerve and the effector organ. Via. 406. — iStitATfH Reflex evoked bv a Relatively Feeble Stiaujlation and iJiSAPrKAfayG xinder that Stimulation. ( )i^ increasing the intensity of the stimulns the reflex reappear.';. It does not r. 'appear on reveiting to the original intensity of stimulation. Time in seconds. {From Sherrington's "Integrative Action of the Nervous System," by permission of Yale University Press and Messrs. Constable and Co., 'Ltd.) 5. When fatigue is not evoked by too frequent transmission of an impulse, it is found that subsequent impulses call forth a reaction more easih'. This " facilitation," as it is termed, is really the basis of habit. By facilitation, good habits, if sufficiently repeated, obtain preference over bad ones, if these are not often repeated. Training C(Misists largety in the proper adjustment of the necessary reflexes, and in this the law of facilitation takes a great jjart. The whole of education consists in the obtaining of facilitation for fit paths, and in the inhibition of unfit ones. 0. iSucli inhibition is a law of reflex action. Only one impulse can have possession of the final common path at the same time, unless. THE SPINAL CORD 08 1 it be of a, aimilar nature. Stimuli of a harmful or sexual nature aro the most potent in obtaining command of the final common path. The spinal cord has already been referred to as the reflex centre concerned in micturition and movements of the large intestine. In. Fiii. 4:07. — Uial;i:\m imjicatixo Conxkctions axu .Actiuxs of Two Afferent Spinal Root Cells (a axd c) ix Regaed to their Reflex Influence on the EXTENSOPv AXD FlEXOK MuSCLES OF THE TwO KXEE?. a, Aiferenc fibre from skin below knee; a', afferent from flexor muscle of knee — i.e., in ham.string nerve; e and e', efferent neurons to extensor muscles of the knee, loft and right; 5 and 5', efferent neurons to flexor muscles; E and E', extensor muscles; F and F', flexor muscles. The sign + indicates that at the synapse which it marks the afferent fibre a (and a') excites the motor neuron to dis- charging activity, the sign — indicates that at that synapse the afferent fibre a (and a') inhibits the discharging activity of the motor neurons. The effect of strychnine and tetanus toxin is to convert — into +. (From^ Sherrington's •' Integrative Action of the Nervous System,'" by permission of Yale University Press and Messrs. Constable and Co., Ltd.) di.seases of the si)iiial cord affecting these centres, these processes will be impaired. It also contains the centres controlling the erection of the penis and the ejaculation of the seminal fluid. The spmal cord is also normally concerned in the process of parturition. It is- (582 A TEXTBOOK OF imYSlOLOGY •possible, however, for this to take place when the influence of the cord is removed. The condition of the s])inal coi'd is investigated in man by sition again. In the Lower vertebrates, the brain is formed h\ the enlargement of the anterior end of the spinal cord, and bj- the widening and division of the central canal to form ventricles. Upon this primitive brain- stem are developed swellings in connection with the senses of most importance to these lower forms — namel}', the sense of smell and the sense of sight. Usually, one or other of these is predominantly -688 A TEXTBOOK OF PHYSIOLOGY developed. The brain of the frog is seen in Fig. 413. In reptilia, the brain is long and narrow, much increased in size. It begins to show marked differentiation with the apjoearance of the neopallium — the higher cortex, or brain proper. In birds, the brain is broad and highly developed, the greatest development being in the sizs of the striate bodies (corpora striata). The thalamus and optic lobes are also highty organized. Fig. 416. — Position assumed by Frog after Removal of the Entire Bkain: It LIES Limp and Flaccid. The fmiction of the brain may be studied on the frog. If the cerebral hemispheres be destroyed, preferabty by forceps by dissection, and the bleeding stopped by wax (Kg. 414), the frog, when the shock has passed off, will exhibit spontaneous movements such as swimming when placed in water, and turning over if placed on its back. If the corpora striata and optic thalami be destroyed, the shock is greater, but the animal on recovery can still jump, swim, climb an inclined board, and maintain its equilibrium. If the cere- bellum and medulla oblongata are destroyed, the power to maintain equilibrium vanishes, and the respiratory movements of the nares and of the floor of the mouth cease. The animal lies in a listless condition (Fig. 416), but still shows co-ordinated movements Avhen stimulated, since the spinal cord is still intact. Section I THE MEDULLA OBLONGATA AND PONS VAROLII The Medulla Oblongata. — ^The medulla oblongata may be regarded as the expanded upper end of the spinal cord; indeed, it is sometimes termed the spinal bulb. In this region, the central canal gradually becomes more superficial, and eventually opens out, to form part of the fourth ventricle. On either side of the middle line posteriorly there are seen, at the lower end of the medulla, prominences which represent the terminations of the posterior cohunns of the cord. Each postero-median column ends in a prominence on either side of the middle line, known as funiculus gracilis, each postero-lateral in a more laterally placed funiculus cuneatus. Prominent in the mid-line anteriorly are the pyramids, which are composed of the pyramidal fibres coming from the cortex, and have not yet crossed. The decus- sation of these fibres takes place at the lower end of the medulla. THE BRAIN 689 The lateral columns of the spinal cord pass outwards to the cere- bellum, forming its inferior jjeduncles, or, as they are also calbd, the restiform bodies. Between the lateral and anterior columns there is, on either side, an oval swelling, known as the olive. Sections of various levels of the medulla reveal important changes, as compared with the cord. It is seen that, as the result of two decussations, the central canal is set backwards and gradually opens out into the fourth ventricle, and that the grey matter of the cord becomes broken up and scattered. New groups of grey matter also make their appearance. The chief groups of grey matter are — (1) The nuclei of the posterior columns — the nucleus gracilis and cuneatus, on either side, at the lower level of the medulla (Fig. 418); MCrR St.A Fig. 417.- The Fouuth Ventkicle. (Parsons and Wright.) S.C.Q., Superior corpora quadrigomina ; I.C.Q., inferior corpora quadrigemina ; F, fillet; S.Cr.P., superior cerebellar peduncle; M.Cr.P., middle cerebellar peduncle; CI., Clava; F.C., funiculus cuneatus; F.G., funiculus gracilis; E.T., Eminenti i teres; S.F., superior fovea; St.A., striae acusticpo; T.A., trigonum acustici; I.F., inferior fovea; T.H., trigonum hypoglossi; T.V., trigonum vagi. (2) the inferior olivary nucleus.!, which makes its appearance in the mid-level (Fig. -119); (3) the nuclei of the cranial nerves, the twelfth to the ninth appearing from below upwards at various levels. The Nuclei of the Posterior Columns. — Around the cells of the gracile nucleus end the fibres which ascend in the postero-median column of the cord (Goll) ; around those of the cuneate nucleus those of the postero-lateral column (Biuxlach). From the cells of these miclei arise fibres which — (1) pass inwards and cross the middle line, to ascend as the mesial fillet (Fig. 419); (2) pass inwards and upward;! on the same side to the cerebellum by the restiform body — the internf i 44 Gitd A TEXTBOOK OF PHYSIOLOGY arcuate fibres (Fig. 418); (3) deeply inwards across the median raphe,, to become external on the ventral aspect of the medulla, pass thence superficially around the medulla, to enter the cerebellum by the inferior j)edinicle — the external arcuate^fibres (Fig. 418). The inferior olive is a characteristically shaix'd mass of grey matter. From its cells li})res pass to the cerebellum by the inferor pedmicle of the same side, but chiefl}' by that of the opposite side — the olivo- cerebellar fibres. Funiculus gracilis " ' "_ Postero-mediaii fissure '" l-'uniculus cuneatus Nucleus gracilis ~ Desjendiug root of fifth Bundle from funiculus, cuneatus .Ji..-- Substantia Rolandi' — , liundle of Flechsig _1 Pyramid tract bundles — V — I )ocussation of pyramids - '^P^-: ■.,^ Caput of anterior horn — — Antero-median tissun \ Fkj. -il8. — Section across the Loweu Paut or the Metiulla OBLoNCiATA in the Middle of the Decussation of the Pyramids. MACiNiFiED about G Dia- meters. (E. A. Scha-fer, from " Quain's Anatomy.") Cranial Nerves. — The cranial nerves do not conform to the spinal arrangement of an anterior and posterior root, the tAvo forming a '■ mixed " nerve. Some of the cranial nerves consist almost wholly of motor or effector fibres. In most of the nerves the fibres are somatic ; in certain nerves there are splanchnic fibres also. The cell-stations of afferent nerves are situated in ganglia, cor- res2)onding to j^osterior root ganglia, on the course of the nerve outside the central nervous system. The effector fibres arise from groups of cells or " nuclei '' corresponding, in the case of somatic fibres, to the anterior horn cells, and of splanchnic fibres to the lateral horn cells of the spinal cord. THE BRAIN 691 The Twelfth Nerve, or Hyjjoglossal. — This is a purely motor nerve siipplj'ing the muscles of the tongue. It arises from a nucleus of grey- matter situated dorsally close to the middle line (Fig. 419). The nerve passes ventrally outwards. ii The Eleventh Nerve. — Anatomically, this nerve consists of two parts — the spinal and the accessory portions. The accessory portion arises from the medulla,, and is, in reality, a part of the tenth nerve. It arises from the same nucleus as part of the tenth nerve (Fig. 419), and supjilies splanchnic fibres, which run eventually in the tenth \estibular nucleu Uenc. fibres of vestib Dorsal nucleus tenth Fascic. solitiU- ^ Restiform body 5. X-icleus of twelfth Subst. gelat. I lesc. voot of fifth Subst. gelat. - Xuel. ambig. - I--suing fibres of tenth ksuiii^ fibres of twelfth — ^ Uiiphe Thalamo-olivary tract Hilus oliva; ( )livary nucleus Kxt. arouate fibres Fibi-es of twelfth and - po.sterior longitudinal bundle Anterior -Jongitudinal liundle Pyramid Arcuate nucleu Til.. 4] 9. — Sectiox across the Medull.\ Oblongata at about the Middle of THE Olivaby Body. jMagxified 6 Diameters. -(E. A. Scba^cr, from " Quain's Anatomy.") nerve. These fibres are chieflj" cardio-inhibitory and visccro-motor. The spinal fibres supply two muscles — the trapezius and the sterno- mastoid. The Tenth Nerve {the Vagus, or Pnoumogastric). — This is composed of afferent and efferent fibres — somatic and splanchnic. The afferent fibres have their cell-stations in the ganglia of the trunk and root. The ingoing fibres from these bifurcate after the manner of posterior root fibres. The upgoing branches are short, and end around cells <)i)2 A lEXTBOOK OF PHYSIOLOGY known as the jirincipal nucleus (Fig- 419). The descending fibres (corresponding to the comma tract of the cord) are longer, and pass into a tract of fibres knoAvn as the funiculus solitarius (Fig. 419). In this tract also run corresponding fibres from the ninth nerve, and the intermediate nerve of Wrisberg. The efferent fibres arise chiefly from the so-called nucleus ambiguus ■(Fig. 419), and also from the upper part of the same nucleus as the eleventh nerve. The afferent sensations brought u]) bj^ the tenth nerve are concerned with the respiratory and circulatory systems. Impulses from the superior laryngeal nerve inhibit inspiration, and bring about expiration and coughing. Those from the lung alveoli Optic ., Chiasma Optic Tract Crus . . . Cerebri {Olfactory Bull?) (Optic Ner^'e) I'iG. 420. — Anteko-Inferior View of the Crura, Poks, and Bulb (Diagka.-mmatic), TO ILLUSTRATE THE SUPERFICIAL ORIGIN OF THE CRANIAL KeRVES. regulate the depth and frequency of inspiration, and possibly also of expiration (see p. 296). Those from the heart (depressor nerve), which generally run in the vagus, go to the vaso-motor centre, and reflexly bring about a fall of arterial pressure, owing to vaso-dilata- tion especially in the splanchnic area. Other fibres of the vagus have a pressor effect, and cause a rise of arterial pressure. Central stimulation of this nerve also brings about reflex inhibition of the heart. The effector functions of the vagus nerve may be summarized as motor to the levator palati, the constrictors of the pharynx, the muscles of the larynx, and to the smooth muscle of the bronchi and bronchioles, to the muscles of the walls of the oesophagus, stomach, THE BRAIN 093 and small intestine. It is inhibitory to the heart, and secretory' to the glands of the stomach, and possibly of the pancreas. The Ninth Nerve, or Glosso-Pharytigeal Nerve, is essentially au afferent nerve, the cell-stations of its fibres being the jugular and petrosal ganglia. The ingoing branches from the ganglia branch, on entering the medulla, passing slightly upwards to the cells constituting the ninth nucleus, and downwards in the fasciculus Fig. 421. — Diagram to illustrate the Position or the Bulbar Nuclei of the Cranial Nerves. Posterior aspect of the fourth ventricle exposed by removal of the pons and cerebellum. Motor nuclei indicated bj' horizontal lines, sensory nuclei ))j' dots. Median group of motor nuclei, ///, IV, 17, XII. Lateral group of motor nuclei, V in, VII, X, XI. Sen- sorv nuclei. Is, VIII, IX. Cora I'lu. 422. — Lateral View of the Kight Half of the Bulb and Pons exposed BY A Vertical Section, and imagined AS Transparent. (After Ert).) In tliis view the lateral group of motor nuclei. Vm, VII, X, XI, lie farth-r from tho surface of section, and ard indicated by lighter lines than the median group of motor nuclei. ///, IV, TV, XII. solitarius. The afferent fibres are concerned with the sensation of taste in the posterior third of the tongue, and with common sensation of this region and of the upper ]iart of the pharynx. In the nerve also run some effector fibres. These arise mainly from the upward continuation of the nucleus ambiguus, and supply the constrictor muscles of the pharynx, the stylo-pharyiigeus, and levator palati muscles. The nerve also contains effector secretory fibres to the parotid gland, the cell-stations of which are not exactly ktiown. These pursue a somewhat devious course to reach the gland (see p. 374). 694 A TEXTBOOK OF l'H^SIOL(K^Y The white matter of the spinal bulb consists oi conducting tracts, Loth ingoing and outgoing. The chief ingoing afferent paths are — 1. The mesial fillet. The fibres of this tract arise from the gracile and cuneate nuclei, immediately cross the middle line and pass up in close ])roximity to and on citlier side of it (Fig. 39H). This crossing forms the sensory decussation; the iibres of the tillet eventu- ally reach the optic thalami (Fig. 484). 2. The cerebellar tracts of the cord pass up through the medulla to reach the cerebellum (Fig. 431). They occupy part of the area known as the reticular formation (foiinatio reticularis). 3. The spino-thalamic tract passes through, and joins Avith, tlu' mesial fillet to reach the thalamus. Fit:. 423.- -Plan of the Oruun of thk Twelfth and Texth Nfuves. (A. E. Schafer.) py>\, Pyramid; ri.XIL, nucleus of hypoglossal; XII., hj^poglossal nerve; d.n.X.XI., dorsal nucleus of vagus and accessory; n.amh., nucleus ambiguus ;/.«., fasciculus solitarius (descending root of vagus and glosso-pharyngeal; /.6'.?2., its nucleus; -Y., issuing fibres of vagus; g, ganglion cell in vagus giving origin to a sensory fibre; d.V ., descending root of fifth; c.r., corpus restiforme. 4. The external and internal arcuate fibres, which arise from the gracile and cuneate nuclei, and pass to the cerebellum either by an external course from the opposite side or by an internal com'se from the same side. The outgoing fibres take part in the formation of the chief reflex arcs (Fig. 397) : 1. The vestibulo-spinal, which arises in the u])per part of the medulla in Deiters' nucleus. 2. The rubro-spinal, coming from the red nucleus of the mid- brain. 3. The pyramidal tracts from the cerebral cortex. These lie anteriorly throughout the great part of the medulla, but in its low or THE BRAIN (J9.5 Motor nucl-ev part most of the fibres cross the middle line, to become the crossed pyramidal tracts of the cord, thus forming" the motor decussation. Tracts which may perhaps be grouped as conducting in both directions are — 1. The olivocerebellar fibres, which connect the inferior olive to the cerebellum. 2. The posterior dorsal longi- tudinal bundle fibres, in which run fibres in both directions b?t\vcen the medulla and the anterior basis bundle of the cord, and the pons and mid -brain. This tract lies dorsalh^ to the mesial fillet, just below the central canal and fourth ventricle. The chief fibres of this tract come — -(1) fi'om the nuclei of the third and sixth nerves, being concerned in the regulation of eye move- ments, and by way of the seventh nerve in the movements of the accessory apparatus, such as the ■e3-elids and eyebrows ; (2) from Deiters' nucleus to the cord in con- nection Mith the equilibration of the body ; (3) from the twelfth nucleus l^y waj- of the seventh nerve to the orbicularis muscle of the mouth. In close association ventrally with the posterior longitudinal bundle (sometimes classed as part ■of it) is tbo anterior longitudinal bundle, or tecto-spinal tract. In it run libres from the roof of the mid-brain to the cord. \Ventra,l hm-n The Functions of the Medulla Oblongata. — The medulla, like the spinal cord, acts as a conductor and as a reflex centre. The centres are those associated with the functions of the nerves arising from it, of which the vagus nerve is the chief. Here, therefore, are situated the centres concerned in the regulation of the heart-beat (the cardio-motor centre), the regu Jation of the peripheral resistance (the vaso-motor centre) FlU. 424.— DiAGKA.M OF A FiBRE OF THE PosTEKiOR Longitudinal Bundle ARISING FROM A CELL OF DeITEES' ^iucLEUs. (E. A. Schafer, from " Quain's Anatomy.") the 696 A TEXl !',(»( J K OF PHYSIOLO(;V centre for respiration, and other centres already' refcried to, such as those for the provision of saliva and gastric juice for mastica- tion, swallowing. ])honation, and vomiting. The destruction of the medulla l)rings about dcalh, owing to re- spiratory failure. Tlie body of a ])ithed mammal may be kept alive for some hours by artiticial res])iration. The bl()Otl-y)ressure, however, is low, owing to the destruction of the chief vasomotor centre. Accessory motor root of fifth Motor nucleus of fifth ~.' Sensory nucleus of / fifth -^ Sensory root fibres of fifth Part of superior olive Grey matter lateral fillet White matter of cerebellar hemisphere Fifth nerve Piphe bundle- of fifth Posterior long, bundle Auterior long, bundle Central tract ■..,_, y >.,_, Central nucleu.s --^2>=^»-» ¥^^^' Fillet Fibres of yens Fibres of pons Nuclei pontis Fibres of pon."! liaphe Nuclei pontis Fibres of pon* Fig. 425. — Section across the Middle of the Pons. Magisified about 4 Diameters. (E. A. S'chafer, from " Quain's Anatomy.") The Pons Varolii is a continuation of the medulla oblongata^ surrounded by transverse fibres, which form the middle or transversa peduncles of the cerebellum ; a large part of the anterior portion of the pons is made ujd of these transverse fibres passing from one^sido of the cerebellum to the other (Fig. 425). It acts as a conductor to ingoing and outgoing fibres, and in it are situated the nuclei of the eighth to the fifth cranial nerves. Passing up through the pons ?.re the fibres of the ventral spino-eerebellar tract and of the mejial fillet. Passing downwards through the pons are the fibres of the pyramidal tract from the cortex, which in this region lie ventralU^ somewhat- scattered among the transverse fibres. The rubro-spinal fibres also pass downwards. In this region the^^ lie in the reticular formation. THE BRAIN 697 FIBRES TO NUCL.LEMNISCI &CORPORA QUAORIGEMINA PYRAMID NERVe-ENOINGo in organ of corti Fig. 426. — Plak of Course and Connkctions of the Fibkes forjung the Cochlear Root of Auditory Nerve. (E. A. Schafer.) r., Resliform body; v., descending root of fifth nerve; tub.ac, tuberculum acusticum; n.acc, accessory nucleus; s.o., superior olive; n.tr., nucleus of trapezium; n.vi., nucleus of sixth nerve; VI., issxiing root-fibre of sixth nerve. TO VERMIS FIBRES O VESTIBULAR ROOT NERVE ENDINGS IN MACULAE e, AMPULL/E pji Fig. 427. — Plan of the Course axd Connections of the Fibres FoiniiNG the Vestibular Root of the Eighth Nekve. (E. A. Schafer.) r., Restiform body; V, descending root of fifth nerve; y., principal nucleus of vesti- bular root; n.d., ceU of the descending vestibular nucleus; D, nucleus of Deiters; B, nucleus of Bechterew: n.t.. nucleus tecti (fastigii) of the cerebellum; p.l.h., posterior longitudinal bundle. (>9S A TEXTBUOK OF PHYSIOLOGY dorsally to tlie mesial fillet (Fig. 425). More dorsal still, in a position corresponding to that in the medidla oljJongata, lies the ])osterior longitudinal bundle, its fibres making eonnections both upAvards and doAViiwards. The chief masses of grey matter are — I . Deiters' nucleus. 2. The nucleus pontis. 3. The superior olive. 4. The nuclei of the eighth to the fifth cranial nerves. The Nucleus of Deiters is an important mass of gre}' matter lying at the lower end of the ])ons, and partly in the upper part of the spina] l)ulb. Around the large cells constituting^ the nucleus end fibres from the vestibular nerve and the dentate nucleus of the cerebellum. /^//i Fig. 4-28. — Fla:s (Tkaxsverse) of the Okigin of the .Sixth and of the Motor Pabt of the ISeventh Nerve. (E. A. Schaler, from " Quain's Anatomy.") VI., Sixth nerve; VII., seveiitli nerve; a.VIl., ascending part of root of seventh, shown cut across near the floor of the fourth ventricle; g, genu of seventh nerve- root; n.VI., chief nucleus of the sixth nerve; n.'VI., accessory nucleus of sixth; n.VIl., nucleus of seventh; d.V., descending root of fifth; pyr., pyramid bundles; VIII.v., vestibular root of eighth nerve. From the cells of the nucleus arise fibres \vhich pass doAvinvards through the medulla oblongata, into the antero-lateral position of the cord— the vestibulo -spinal tract. Other fibres pass inwards to the middle line, to ascend and descend in the posterior longitudinal bundle (Fig. 427). The ascendmg fibres go chiefly to the sixth and third nuclei, the descendmg to the anterior horn cells of the cord. In close proximity to this nucleus, formmg in reality its upper part towards the cere- bellum, is the nucleus of Bechterew. The Nucleus Pontis is the name given to the grey matter lying between the crossing fibres of the jjons, aroimd the cells of ^vhich end fibres from the frontal and occipital cortex- — the fronto-pontine THE BRAIN OS)i) and cortico-pontine fibres. From the cells arise the transverse fibres, which cross the middle line, and pass by the middle peduncle to the A^ermis of the cerebellum. The Superior Olive is a small mass of grey matter closely associated with the co-ordination of the movements of the eyes with the mechanism of equilibration. The Nuclei of the Cranial Nerves. — The eighth nerve is a wholly afferent nerve. It consists of two portions — the cochlear and the vestibular. The cochlear portion is concerned with hearing. Its ceU-station is in the spiral ganglion of the cochlea. Peripherally, the nerve processes arborize around the hair cells of the organ of Corti. Centrally, the axons pass into the uppermost part of the medvxlla oblongata. They branch on entering ; one set of branches ends in a nucleus — the accessory nucleus— just anterior to the restiform body (Fig. 426); the other around cells in what is laiown as the tuber- culum acusticum, or acoustic tubercle, a mass of grey matter resting upon the outer aspect of the restiform body. From the cells of these nuclei arise fibres which go to form the lateral fillet (Fig. 426). The fibres from the accessory nucleus pass transversely across in the tract known as the trapezium, making in their course connection with the superior olive and trapezoid nucleus of i\\Q same and opposite sides, and then turning upwards in the lateral fillet to reach the nucleus of the lateral fillet and the inferior corpus quadrigeminum. The fibres from the tubercidum acusticum cross the floor of the fourth ventricle superficially as the striae acusticae, and, dipping inwards at the middle, pass with those of the trapezium to the superior olive of the opposite side, and thence to the lateral fillet and inferior corpus quadrigeminum. The vestibular portion of the eighth nerve is concerned with the mechanism of equilibration. It arises from the cells of Scarpa's ganglion in the vestibular portion of the internal ear. The ingoing fibres divide into ascending and descendmg branches. The ascending branches connect with the principal vestibular nucleus (Fig. 427), a mass of grey matter situated just external to the nucleus of Deiters, with which it makes intimate connection by means of collaterals. The descending fibres end in the descending vestibular nucleus, which lies below the prmcipal nucleus. Many fibres of the vestibular nerve pass directs by Avaj' of the restiform body to the roof nuclei of the cerebellum. The seventh nerve is mainly motor in function. It arises from a group of cells — the ssventh nucleus — which lie's in the recticular forma- tion just below and somewhat external to the nucleus of the sixth nerve. The fibres pursue a somewhat devious course inside the pons. At first they pass inwards towards the middle line; then dorsally towards the floor, and iq:)wards to a slightly higher level of the pons; then, encircling the sixth nucleus, they turn outwards, and emerge from the lateral margin of the pons (Fig. 428). The fibres supply 700 A TEXTBOOK OF PHYSIOLOGY tho muscles of expression of t he face. Pai'alvsis of the nerve leads to a characteristic "" facies " — an expressionless, vacant look. In addition, the stapedius muscle of the ear and certain muscles of the scalp are also supplied. Certain afferent fibres belonging to the nerve of Wrisberg also run in the seventh nerve. Their cell-station is in the geniculate ganglion. The fibies ])assing inwards from the ganglion divide into ascending and descending branches, the latter connecting with the ninth nucleus. Periplicrally, the fibres pass into the large superficial petrosal nerve and the chorda tympani nerve, and thence to the fifth nerve, furnishing the sensation of taste to the anterior two-thirds of the tongue. From the nerve of Wrisberg also come secretory fibres which go to supply the submaxillary and sublingual glands through the chorda tympani nerve. The sixth nerve arises from a group of cells situated on either side of the middle line just below the floor of the upper part of the fourth ventricle (Fig. 428). The fibres form the motor nerve to the external rectus muscle of the eyeball. From the sixth nucleus other fibres ascend in the posterior longitudinal bimdle, to emerge with the third nerve and supply the internal rectus muscle. The oculo-motor nerves^ sixth, fourth, and third, contain muscle-sense fibres, the ganglion cells of which are to be foimd in the nerve trunks. The fifth or trigeminal nerve has three nuclei in the medulla: one connected with the central connections of the sensory cells of the Gasserian ganglion — the jirincipal sensory nucleus of the fifth ; and two connected with the motor functions of the nerve — the chief and the accessory motor nuclei (Fig. 429). The afferent fibres of the nerve enter the pons, and bifurcate into ascending and descending branches, The ascending pass to the principal sensory nucleus, which lies just laterally to the principal motor nucleus. The cells of this nucleus give rise to fibres most of which cross the middle line and pass in the mesial fillet, to end in the optic thalamus. Some fibres ascend in the mesial fillet of the same side. The descending fibres form a well- marked tract, which descend in the reticular formation (the descending branch of the fifth) into the cervical part of the spinal cord. In its course it forms connections with the motor nuclei of the pons and medulla. It lies in close association with the substantia gelatinosa Rolandi. The nervo acts as the nerve of common sensation to the face, eyeball, nose, and mouth. The fibres connected with the gustatory nerve-endings in the anterior two-thirds of the tongue run in this nerve. The motor fibres, which form but a small part of the nerve, arise chiefly from the principal motor nucleus, which is situated laterally below the floor of tho fourth ventricle (Fig. 429). Some arise from the accessory nucleus, which is situated higher in the pons, and in part in the mid-brain (see Fig. -129). The fibres are motor to the muscles of mastication, the tensor palati, the tensor tympani, and the anterior belly of the digastric muscles. THE BRAIN 701 Fia. i2i). — Fi.AN OF THE Okigin and PiKLATioxs OF THE FiiTH Nehve. (Cajal, from " Quain's Anatomy.") A, Gasserian ganglion; B, accessory motor nucleus; C, main nucleus; D, seventh nucleus; E, twelfth nucleus; F, sensory niieleus of fifth; G, cerebral trace of fifth; a, ascending branches; 6, descending branches of sensory root-fibres; c, d, e, ophthalmic, maxillary, and mandibular branches of fifth. 702 A TEXTBOOK OK PHVS[()L()(;V Section IT THE CEREBELLUM The' Structure of the Cerebellum. —Tlu; little brain, or cerebellum, consists of a middle lobe, or vermis, and two lateral hemispheres. Its surface is thrown into manj^ folds, which in section give it a tree- like appearance — the arbor vita>. The oigan consists of a grey cortex, and wliitc matter Avithin. In the latter, near the middle line, are a i -- • '* Vui. 430. — Section of Cerebellar Cortex. (Sankey, from " Quain's Anatomy.") a, Pia mater; h, molecular layer; c, cells of Pur^dnjc; d, granule layer; e, white centre. ganglia of grey matter — -the roof nuclei — and in the middle of each lateral lobe the dentate nuclei. It is from these nuclei that the axons which leave the cerebellum arise THE BRAIN 703 In a section of the cerebellar cortex three layers are to be dis- tinguished, the most characteristic of which is the one in the middle, in which occur the flask-shaped cells of Purkinje (see Fig. 430). The apical dendrites of these cells ramify in the external laj^'er, Avhile the efferent axon passes doAvn internally into the central layer of white matter. Afferent tendril fibres aborize round these cells. External to the Purkinje cell laj^er is the outer molecular layer, which consists of irregular star-shaped cells, neuroglial cells, and the dendrites of the Purldnje cells. The axon of the star-shaped cell runs parallel to the lajmr for a certain distance, and then turns down to arborize around the Purkinje cells. Internal to the Purkinje cell layer is the nuclear layer, or inner molecular layer, therein afferent fibres — the so-called moss fibres- arborize, forming curious mossj^-like figures. In this layer are small star-shaped cells, irregular cells of Golgi, and neuroglial cells. The underlying white matter is composed of the afferent axons of the tendril and moss fibres, and the efferent processes of the Purkinje cells. The cerebellum is connected to the brain-stem by three pairs of peduncles: The inferior, or restiform body, to the medulla; the middle to the pons; the superior to the mid-brain. It is by these three sets of channels that it receives messages from, and sends messages to, the other parts of the central nervous system. The connections of the cerebellum may be tabulated as folloAvs : Afferent Fibres to the Cerebellum. — From spinal cord — (1) By the dorsal spino-cerebellar tract (direct cerebellar tract of Flechsig) to the lower part of the vermis: (2) by the ventral spino-cerebellar tract (antero-lateral ascending of Gowers) to the upper part of the vermis by the superior peduncle. From the medulla by the inferior pe 4k .)/• ?w. ^ <. ,.«- • ^ 4 '« ■' , .1.' » ■ '* n (A >^ ■ < as » • ^/i:^^ r 4 « > * «', m IV ^v Pig. 441.— Cell Lamination of the Gyeus Post-Centralis. (Mott.) . ■'' ■"'•" .■"■•< i I ;^^i ^ ^u 1 '/"- f.* ♦♦ ♦. ^ ft .■ « # p. i 4 f yn&ni IV ■r ]-'ia 44:2 — FiBHE Arrangement and Cell Lamination in the Motor Area. (Mott.) 726 A TEXTBOOK OF PHYSIOLOGY The middle cell lamina is next developed, and is believed to be concerned in the reception of sensory stimuli. It is most marked in the sensory regions of the cortex. In man, it develops in the sixth month of foetal life. M i^ >°. V« ^1 ^tt ^, it » • • • * » - ": '• • >>% v^ ''•'■- "^ * «>. 4" 'm Vj '-^^^'Vii *-^'^ ■n IV ^v Fig. 443.— Fibre Aerangement and Cell Lamination of Visual Area. (Mott.) Last to be developed is the outer cell lamina. It is suggested that this is concerned in pyschic processes, and is particularly marked in regions concerned in these processes, especially in the frontal area of the brain. THE BRAIN 727 The differences in thickness and structure are Avell seen in Figs. 441-443. In the motor area the second lamina is thick, the third lamina is thin, and the fourth lamina contains the charac- teristic large pyramidal cells of Bstz. In the " visuo-sensory " area the third lamina is thick, and is divided into two by a strand of fibres — the line of Gennari. The " visuo-psychic " area, except for the absence of the large Betz cells, resembles more the motor than the sensory area. It is obvious that from a study of the histological structure of areas of which the function is knowxi valuable indications may be obtained as to the function of the parts of the cortex of which the function has not been clearh^ ascertained. The Evidence from Myelination. — It has been found that groups of fibres going to certain regions of the cortex in the embryo acquire their medullary sheaths earlier than other groups. These regions of the cortex have been shown to correspond closely with the " sensory areas " of the cortex. The Localization of the Receiving Sensory Mechanism. — The receiving station for cutaneous and kinoesthetic impulses has been localized in the ascending parietal convolution, which lies just behind the fissure of Rolando (Fig. 444). Cutaneous sensations have also a receiving station in the callosal gyrus on the mesial aspect of the brain (Fig. 444). It is probable that the various sensations are repre- sented in special parts of these regions. It is known that during their passage from the cord to the thalamus the various sensations become grouped, and it is probable that the final neurons from the thalamus to the cortex establish communications with definite areas. The motor and sensory areas around the Rolandic area are in close connection. It is for this reason that epilepsy is preceded by the sensory " aura," and stimulation of the sensory area leads to movements which, with Aveak stimluation, are localized in that area of the motor cortex which is in most intimate communication. The receptive area for vision is situated in the occipital regions on both the outer and inner aspect of the brain (Fig. 444). The area varies considerably in extent, being larger in the dog than in mail. In man, the main centre is around the calcarine fissure on the mesial aspe3t. The occipital part of the brain is connected with the thalamus, external geniculate body, and superior corpora quadrigemina, by means of the optic radiations. For instance, stimulation of the upper surface of the right occipital lobe causes eye movements downwards and to the left; of the posterior part, eye movements upwards and to the left; of the mesial surface, a turning of the eyes laterally to the left. Extirpation of both occipital lobes induces complete blindness; .ablation of one occipital lobe causes a crossed hemianopia. The vision of the fov^ea is not impaired, since it is represented on both sides of the brain. In min, the visuo-sensory region is confined to the mesial aspect •of the brain. A lesion of the whole of the left cuneate lobe causes 728 A TEXTBOOK OF PHYSIOLOUY right hemianopia — blindness in the right half of each visual field. A lesion of the region above the calcarine fissure causes hemianopia in the right lower part of the visual fields of both eyes; of the region below the calcarine fissure, in the right upper part of both visual fields. The external surface of the occi})ital lobe is probably concerned in ])sychi(! ))rocesses connected with the recognition of the things seen. sensibilityP^ojecfion- ,Av^ii5!:2^ Parietal and temporal centres of association .Olfactory and gustatory projection centre '«ntre of association Fia. l-4'l. — Diagrams of the "Centrks of Projection" and "Centres of Association." (Bolton, after Flechsig.) The small dots are placed in the cliief focus of each centre of projection; around these chief foci are regions (larger clots) to which a smaller number of projection-fibres pass. The receptive area for hearing is situated in the superior temporal lobes (Fig. 444). It is connected with the inferior corpora quadri- gemina by the auditory radiations, which pass through the most posterior part of the internal capsule. The effect of stimulation points to this region of the brain as being concerned in hearing. In THE BRAIN 729 the monkey, it induces a pricking of the opposite ear, with a rotation of the head to the opposite side. Ablation effects are not so con- chisive, as it is difficult to tell whether an animal, like a monkey, is deaf or not. Clinical evidence points to the central part of the lobe as the true receiving station — the audito-sensory area — and to the area just behind this as the part concerned in the psychic processes — the appreciation of the s'gnificance of the sound heard. The receiving stations for taste and smell are probably present in the anterior part of the temporal lobe, particularly in the deeper aspects. Electrical stimidation of the hippocampal region causes movement of the nostril and lip of the same side. The evidence of the effects of ablation and of clinical observation are by no means conclusive. It has been suggested that sensations of hunger and thirst are received in the cortex of the anterior part of the temporal lobe in its outer part. The Association Areas. — The cortex as a whole is to be regarded as one great association centre concerned in the storing of sensations as memories, and the association of present with past impressions, resulting in the power of discrimination, inhibition of emotion, and judgment. There is evidence that there is some localization of these functions. It has already been pointed out that the external aspect of the occipital lobe in man is concerned with the appreciation of the significance of things seen. Further, in the angular gyrus of the brain, on the left side in right-handed people, there is thought to be the ■" visual word area," by means of which the meaning of written words is appreciated. So, in regard to hearing, it has been pointed out that the posterior part of the temporal lobe is probably concerned in the appreciation of the meaning of the sound heard, and in this region is also situated the auditory word centre, which enables the appreciation of the word heard. These centres belong to one of the three great areas which have been designated as association areas. These areas are the posterior — -in the parieto-temporal region — chiefly concerned in sensorial function; the middle — in the island of Reil; and the anterior — in the prefrontal region. All these regions are intimately connected by association fibres. The exact function of the island of Reil is not known. In regard to the frontal region, it is suggested that this is the centre concerned in voluntary attention, memory, and thought. Dementia is associated with the disorder of this region, the degree of permanency varying according to the degree of dissolution of the area. If this region be not developed, then the subject is generally permanent^ imbecile (amentia), temporarilj' insane, or liable to the onset of insanitj'. In the frontal region the outer cell lamina is particularh- well marked. It is the last to develop, the first to regress. Speech. — The functions of the cerebral cortex are well illustrated in the power of speech. To give an answer to a question directed to him, a man must — 730 A TEXTBOOK OF PHYSIOLOGY 1. Hear the noise — The receiving mechanism. 2. Api^reciate the meaning of the noise (the words) 3. Associate it with former stored impressions 4. By judgment formulate the answer 5. Clothe the answer in words 6. Associate this answer with the motor centres concerned in the activation of the muscles taking part in the production of speech movements — lips, tongue, larjmx, etc. 7. Send impulses down the efferent tracts to the nerves to these parts, and cause the muscles to functionate — The discharging mechanism. The association mechanism. IiG, 445. — Diagram of Left Cerebral Hemisphere, showing Approximate Positions of the Centres concerned in Speech. (From Purves Stewart's "Diagnosis of Nervous Diseases.") Similarly, a great number of processes are concerned in the appre- ciation of written words and in the power to express the answer in writing. It was at one time believed that a certain part of the brain, known as Broca's area, was especially concerned, as the special co- ordinating centre, in sj)eech. This area is unilateral, and is situated in a right-handed person in the left inferior frontal convolution. It is undoubtedly in intimate connection with the neighbouring motor areas concerned in the movements of the tongue, lips, and larynx, but it has been shown that it may be diseased without any disorder of speech (aphasia) resulting. The cases of " motor " aphasia, which were said to be the result of a lesion of Broca's area, are now said to be due to a lesion of the lenticular nucleus, and to a varying extent of an area known as Wernicke's area. The former lesion involves the external capsule, and possibly the anterior part of the internal capsule, and causes an inability to articulate (anarthria). Wernicke's area is situated in the supramarginal and angular gyri, comprising the " visual word centre," and in the posterior part of the superior temporal sphenoidal lobe, comprising the " auditory word centre." A lesion of the area results in " sensory aphasia," THE BRAIN 731 varying according to the extent of the lesion. Sometimes the impair- ment of intelligence is very marked ; in other cases, as in the so-called cases of '' motor " aphasia, it is but little affected. If the auditory area be destroyed, there results a loss of spoken word appreciation (sensory aphasia), with great diminution of mental powers. If the occipital lobe be affected, there will result alexia, or word blindness — an inability to ajDpreciate the meaning of written words. It will be seen that it is improbable that tiiere is any localized speech centre, as suggested by Broca. Disorders of speech are due to local lesions, bringing about a loss of continuity between the cortical centres concerned in the power of speech. "' Motor " aphasia, there- fore, is probabh' not due to a lesion of Broca's area, but principally to a lesion of the lenticular nucleus, causing an inability to articulate, often combined with a lesion of the sensorv area of Wernicke. <:^^- Fiu. 446. — ^Diagram of Speech Centres. (After Bramwell, from Purves Stewart's "Diagnosis oE Nervous Diseases.") Similarly, in the power to read and to clothe thoughts in writing there is involved a number of centres connected by association fibres (see Fig. 446). Reaction Time. — -Various methods have been devised for measuring the " reflex time," or, as it is usually termed, the " reaction time," of conscious processes, such as sight, hearing, the response being by movement or speech, etc. The subject is usually told to perform some movement, recorded on a drv;m, such as to open an electric key or to depress a lever, directly he receives the stimulus, which is also recorded — e.g., the ringing of a bell, the appearance of a coloured disc. The " reaction time " is made up of the time taken in the conduction of the impulse to and from the brain, and of the processes in the brain. From the knowledge of nerve conduction and of the reflex times of simple arcs we can measure the reaction time of more complicated cerebral processes. The more complicated the process, the longer the time. Thus, if a man has to move his right hand when a red disc 732 A TEXTBOOK OF PHYSIOLOGY is shown, and his left liaiid when a green one is shown, the time is con- siderably longer than if he has to make a simple motor resj^onse with one hand to any kind of disc. Still more complex is the process when the subject has to speak different words in response to different forms of stimulation. Mind and Consciousness. — Extero-, proprio-, and entero-ceptive im- pulses stream into the central nervous system from the time of its embryonic development until death, ceaselessly modify the pattern of its structure, lay down the pathways of reflex actions, and establish habits. A very large proportion of these impulses, and particularl}'- the proprio- and entero-ceptive, never enter nito consciousness, and yet occasion actions which are perfectly adapted to the end in view. Fig. 447. — Diagram of the Apparatus for the Determination of Reaction Time. (W. G. Smith.) The clectro-magnotic tuning-fork T, with 100 vibrations per seccud, is connected with two Daniell cells and with the chronograph 0. By means of either of the two Du Bois keys, K^ and K2, the chronograph can be short-circuited. The key A'j is closed and K.^ is open; the tuning-fork is set vibrating, but does not affect the chronograph. The subject, whose reaction time is to be determined, is told to listen for the sound of the opening of the key K^, and to close the key A""., directly he hears the sound. When the key K^ is ofjened the chronograph vibrates in unison with the tuning-fork and the vibrations are recorded upon a revolving drum; the closure of the key iVg by the subject of the experiment brings the chronograph to rest. The number of vibrations recorded upon the drum gives the reaction time for sound in yw^^''^ ^^ ^ second. For example, the character cf the saliva secreted is adapted according as sand or bread is put into the mouth. In the one case a watery saliva is secreted, in the other a saliva containing the ferment ptyalin. It might be argued that the salivary centre felt, judged, and willed an appropriate action, and yet none of these processes enter into consciousness. We each have from moment to moment of our waking life a general consciousness of well-being or the reverse, maintained by proprio- and entero-ceptive impulses arising in the organs and tissues of the body, coujjled with a tone of feeling evoked by extero-ceptive sensations. These arouse in us from time to time emotions of in- difference, pleasure, pain, affection, hate, sex, etc. The more powerful extero-ceptive sensations not only enter into consciousness, but so alter the pattern of the brain structure as to store memories — in what THE BRAIN 733 manner we have no knowledge. The sensations of the present moment may arouse one or other of these memories to which it is attmied. Our actions are controlled from moment to moment by the sensations which stream in at the present time, and the memories of j)ast sensa- tions which are aroused b}^ these. Our knowledge, opinions, and beliefs are, then, the result of the supply of sensations furnished by impulses acting on the brain struc- ture. Without such sensations, no mind or consciousness would be manifest. The extero-ceptive mechanism plays an all-important part. This is well seen in the case of Helen Keller, who, deaf and dumb, and uneducated, when her ej^'es were closed, fell asleep. Memory forms the basis of our experience and knowledge, and our so-called voluntary actions, initiated by the cerebrum, result as in- evitably as a spinal reflex action from the synthesis of present and Fig. 448.— Reaction Times to Touch, Hearixo, Stciit. (Waller.) memorized sensations, some of which inhibit, and others facilitate, motor response. Education thus becomes of supreme power in moulding the actions of a man's life. As the pattern of the brain is ceaselessly altered by instreaming sensations and metabolic processes, the personality of a man alters from moment to moment. The babe develops into the man of genius, and he, if he lives long enough, becomes a dotard in his old age. By the time he is in his second childhood the personality of his prime manhood has left him, for this de]:)ends on characteristic responses to sensations, and these can no longer be aroused in a brain the structure of which has deteriorated with age, and from which the store of memories has largely vanished. We must remember that the work of a genius is the accumulated result of successive and innumerable moments of interaction of sensations, present and memorized. His output results from the inborn cpialities of the sense organs and brain structure on the one hand, and education on the other — the storage of his experience — and that of humanity handed on by oral or written 734 A TEXTBOOK OF PHYSIOLOGY tradition. At oiie moment the man of genius may be conscious of nothing but the desire to visit the privy, and at another moment he may be conscious of the word which makes perfect a line of poetry. Consciousness leaves us when the brain is suddenly rendered anaemic by closure of the carotid arteries. It leaves us in sleep, and when a chemical agent, such as nitrous oxide or other anaesthetic, interferes with the play of chemical and physical forces in the nervous tissue. The nervous tissue acts as a transformer of energy, and when it becomes inactive or is destroyed, that form of energy which we call consciousness ceases. CHAPTER LXXIV SLEEP Sleep is to be regarded as the period of rest of tiie great brain, and to a certain extent of the central nervous system and of the body generally. It is probable that absolute lack of sleep would kill a man even more speedily than absolute lack of water, and certainly more quickly and painfully than the withdrawal of food. Yoimg puppies three to four months old, deprived of sleep for four to five daj's, died either at once or, if then allowed to sleep, after a few days. The younger the animal, the more speedy its death. The body temperature began to fall on the second day, until just before death the temperature was about 5° C. below normal. The number of blood-corpuscles became greatly diminished, and after death mam"- capillar}' haemorrhages were found in the brain. It is probable that the greater the animal's need of sleep, the quicker its death from sleeplessness. Dogs sleep, probablj-, on an average twice as long as man, who normally sleeps about one-third of his life. Some men require considerably less sleep than others; wh}-, it is difficult to say. Children require, according to age, from twelve to ten hours' sleep, women and men from eight to five hours'. Birds apjjarenth- require less sleep than mammals. Some mammals require considerably more sleep than others. This is partly due to the character of the sleep, a short profound sleep being as efficacious as a longer less deep sleep. Man is a deep sleeper; the dog is a light sleeper. The companionship of the dog has helped man to attain to his supremacy. But for the companionship and guardianship of the light sleeper, the deep sleeper would have been destroyed by night-prowling, man- eating enemies. Many observations have been made upon man to determine the phj'siological conditions during sleep. Most marked is the loss of consciousness. It is stated that sleep is more profound in the half of the brain which has been active during the day, so that right- handed people when asleep flick away a fly with the left hand, while true left-handed people perform such an act with the right hand. The depth of the loss of consciousness may be gauged b}' stimuli, such as the ringing of a bell at half-hour intervals during the sleep, the dropping of a lead ball from a given height on to a lead plate, or the application of electrical stimuli of known intensit}-. By such means it has been determined that the greatest intensity of sleep occurs after about an hour to an hour and a half from the onset of 735 736 A TEXTBOOK OF PHYSIOLOGY sleep. From the third hour onwards the sleep in many cases is of a light type. In some cases there is a second rise in the intensity of the depth of sleep in the fourth to fifth hours after onset. This form has been said to occur particularly in persons of a nervous tempera- ment. Although the greatest refreshment from sleep occurs during the first hours, it has been shown that the subsequent hours are also effectual. It is easier to do complicated mental work after several hours' sleep than after only a iew hours' sleej), although simple mental acts can be performed equally well after but a few hours' sleep. It is in the waking hours that dreams occur, and they are generally of short duration.^ The dreams of healthy sleep are frequently of the past or of a fantastic nature. Only in broken sleep is the day's work continued or present-day affairs worried over. In healthy sleep the parts of the brain most active during the day should rest most pro- foundly during the night. The parts of the brain do not fall asleep or wake at the same instant. Response to sound sensations are the last to go and the first to return. In addition to the great brain, the other parts of "the central nervous system are also resting. The respiratory centre is affected. Respiration is slowed and deepened, and frequently becomes some- what periodic (Cheyne-Stokes) in type. The reflexes are depressed, the knee-jerk is scarcely present or absent altogether. The rate of heart-beat is slowed, the heart beats less forcibly, and the arterial pressvire falls, during sleep. Owing to the relaxation of the muscles and of the bloodvessels in the warm, quiet state of the body, the blood stagnates in the peripheral capillaries and veins, and the circulation is much less rapid. Less oxygen is required, and the blood moving slowly through the capil- laries fulfils the metabolic needs of the resting tissues. It furnishes a reserve supply of " munitions " for active service during the waking period. In the brain, also, the venous side of the circulation is more con- gested and the blood-flow sluggish. When the sleeper is aroused, the tone of the muscles, skeletal and vascular, at once increases; the blood is sent from the periphery to the viscera, and the velocity of the blood-flow is increased through the brain. The general meta- bolism is lessened during sleep. The carbon dioxide output and the oxygen intake show a marked decrease. The bodily temperature also falls to its lowest point during the night. In the early morning hours the bodily metabolism is at its lowest ebb. The bodily secretions are diminished during sleeji. The " night " urine in healthy persons is less in quantity and more concentrated than the day urine. The amount of saliva is also decreased, and possibly, also, the alimentary juices. The onset of sleep is flavoured by muscular and mental fatigue and by the withdrawal of all stimuli of the extero-ceptive nervous mechanism, especially light and sound. Fatigue produces a metabolic condition of the nervous tissue which tends to put in abeyance the power of response to stimulation ; SLEEP 737 with the weakening or withdrawtxl of the stimuli the ab83^ance becomes complete. Tlie over-fatigued soldier falls asleep in a dug-out in spite of the enemy's shells bursting around him. We ordinarily favour the onset of sleejD by seeking the warm, quiet, and dark atmosphere of our beds, where the excitements of the outside world are at a minimum. Sleep has been attributed to a lessened circulation of blood through the brain, caused hy the dilatation of the vessels of the skin and of the siDlanchnic area. Rest in an armchair in a warm room after a heavj^ meal conduces to sleep. Exposure to cold wind repels it. The periodicity of sleep has been attributed to a gradual loss of tone of the vaso-motor centres. When awake the vessels of the body are so regulated that the blood-supply of the brain is ample, but as fatigue of the vaso-motor mechanism ensues the blood-supply to the brain gradually lessens, and the increasing ansemia induces the onset of sleep. Fig. 4i9. — Cobka Hypnotized by Stroking, and made Stiff and Strai ;kt. Another view of sleep is that it is due to the accumulation of waste products or fatigue toxins within the body. It has also been suggested that the synapses of the neurons are interrupted in slee^) by an amoeboid retraction which blocks the conduction of impulses. There is no evidence of this. There is no single theory which satisfactorily explains the phe- nomena of sleep. Narcosis. — The unconsciousness induced by volatile anaesthetics is due to chemical change of the nerve cells. As the result of prolonged ansesthesia, degenerative changes are induced in the nerve cells and elsewhere. The volatile ansesthetics easily permeate the cell protoplasm. Theie is no need to evoke the lipoid nature of the cell membrane as an explanation. When administration of the anses thetic ceases, the volatile anaesthetic diffuses again from the cell into the blood, and the state of anaesthesia gradually passes off as the drug is breathed out. Hypnosis. — -The condition of hypnosis superficially resembles that of normal sleep. It may be induced in many animals merely by holding them in a strange posture, as in the well-known " experi- ment um mirabile," which consists in placing a fowl on its back Avith its beak to a line chalked upon the ground. In man it is produced 47 738 A TEXTBOOK OF PHYSIOLOGY b}' suggestion, generally, but not necessarily, verbal in nature. It is essential that the subject have the idea of sleep and be prepared to surrender himself to the treatment of the operator. Experiment shows that the condition differs in several respects from normal sleep. The bloodvessels of the skin are constricted, the volume of the limbs is diminished, the blood-volume of the face, and probably the circulation through the brain, is increased. The pulse and respirations are usually quickened. The individual becomes an automaton. The judgment powers of the higher centres are in abeyance, but the receptive centres are alert. Thus, the subject may imhesitatingly perform an order if not too extravagant or believe a fact suggested to him. If told to perform a certain act at a certain hour, the act may be done; if told that he is paralyzed, the subject may act as if such were indeed the case. Hypnosis has been practised in medicine, but is of doubtfvd value, except, perhaps, for certain nervous disorders. Operations can be performed in the hypnotic state, but such operations are better per- formed under ordinary narcosis. The whole subject is surrounded by quackery and li3S. Hibernation. — Certain animals retire at times to their shelters and pass into a torpid state known as " hibernation." Such animals include insects, amphibians, reptiles, and mammals such as the dor- mouse, squirrel, hedgehog, marmot, bat, beaver, and bear. As the name implies, hibernation generally occurs with the approach of cold weather, but this is not necessarily the case. Some animals begin to hibernate in summer, or will hibernate Avhen kept in a warm room away from cold. Cold is not the cause of hibernation; in fact, intense cold stops it. It is a device for seciu-ing the continu- ance of life during a period when food is lacking. Before hibernating the animal puts on fat. It has been suggested that the state is a narcosis induced by the accumulation of COg within the body. The body temperature falls, the excitability of the nervous system is depressed, the frequency of respiration is slowed, and the heart force and frequency are much reduced. The awakening from hibernation is characterized, in warm-blooded animals, by a sudden rapid rise of body temperature, accompanied by a greatly increased discharge of carbon dioxide from the body. CHAPTER LXXV SOUND PRODUCTION AND SPEECH The power of speech is indicative of the high cerebral development of man. Animals possess the power of sound production, but not of speech. Among the insects sound is produced chiefly by a rapid rhythmic movement of one hard part against another, such as the chirping of crickets and grasshoppers. The groan of the death's- head moth is possibly produced by the moth drawing air through its tracheae, but more probably by a rapid movement of the palps against the proboscis. Among the animals higher in the scale of evolution soimd is produced by a blast of air upon elastic mem- branes. The voice of amphibians is due to the driving of air jiast the tightly stretched membranes of the larynx ; the same is true of the song of the bird and of the voice of mammals and man. The speech organs are — (1) The wind chest (the lungs) with the wind tubes (the bronchi and trachea); (2) the sound-producer (the larynx); (3) the sound modifier (the cavities of the mouth, nose, and throat). The wind chest drives the air through the reed instrument (the larynx); the vibration of the reeds (the vocal cords) produces the I)itch of the sound, and the mouth and nose cavitj% resonating like the tube of a trumpet, amplifies certain overtones and gives the quality which determines speech. The proper management of the breath is most important. We have seen that the breathing is regulated by the partial pressure of CO., in the alveolar air, or, rather, by the concentration of acid (H+) ions in the blood. We can alter the breathing by means of the ^will only within narrow limits. A shortage of air and a rise of the partial pressure of CO.2 will inevitably cut short the most eloquent periods, and give the speaker a catch in his breath. We must learn to speak with a full lung, on the complemental and not on the tidal air-supply. The contraction of the belly muscles muyt balance the positive pressm'e in the thorax diu*ing the singing of a sustained note, so that the circulation may continue unimpaired. The stammerer fails to use his diaphragm properly; the bellows of his wind chest is at fault, or, more correctly, the nerve centre which plays upon the bellows. The vocal cords vibrate in much the same way as do the lips in blowing a trumpet. In a reed pipe the air is stopped intermittent^ for a moment, and then let pass by the vibrating tongue or reed, so that a set of pulses 739 740 A TEXTBOOK OF PHYSIOLOGY is given to the air, which is alternately rarefied and condensed; the number of these pulses is determined by the length of the " tongue " (pendulum). The audible sound is produced, not by the " tono^ue itself, but by the pulses of the air. By placing the middle and fore finger lightly on either side of the thyroid cartilage and singing a sustained note, one can feel the cords vibrate. A blast of air blown through a sheep's trachea and larynx will give forth a sound when the cords of the larynx are tightened (Fig. 450). The blast force.3 the cords towards the mouth, and they swing back owing to their elasticity. The larynx consists of a stiff-walled cartilaginous box divided by the membranous vocal cords into two chambers of unecpial size, one above the other. The cords, placed one on either side and opposite each other, can be tightened or slackened, thickened or thinned, shortened or lengthened, moved towards or away from each other, so as to leave either a wide or narrow slit — the rima glottidis — through ^vhich the air blast passes. Pig. 450. — Expkrimental Sounds prodtjced by Blowing through Sheep's Trachea. The vibration of the cords can be discerned in man by means of the laryngoscope. A small flat mirror (Fig. 451) is attached at an angle to a long handle, so that the mirror can be passed to the back of the throat and the reflection of the rima glottidis seen, when a light is cast upon it from another mirror. This second mirror, a concave one, is fastened to the forehead, and has a central hole in it for the eye, and is placed so as to reflect the light of a lamp on to the small mirror (Fig. 452). If an intermittent source of illumination is used, and the number of intermissions is the same as the number of vibrations of the vocal cords, these appear as if stationary; but if the intermissions are not quite at the same rate, then the cords ajopear to be slowly moving. SOUND PRODUCTION AND SPEECH 741 This optical method employed for determining the rate of vibration is that of the stroboscope. Lesions of the vocal cords or of the neuro- muscular mechanism which prevent their vibration cause loss of voice. The height of a tone in such a two-lipped reed pipe as the larynx depends on the length, thickness, and tension, of the cords, and to a certain degree on the strength of the air-blast. Pig. 4.51. — Examination of the I, formation of first polar body (pb^) : each tetrad divides into two dyads; E, first polar body formed, two dyads in it and in the egg; F, preparation for the second division; G, second jiolar body (pb^) forming and the first dividing : each dyad divides into two single chromosomes ; H,- final result: three polar bodies and the egg nucleus ( ? ), each containing two single chromosomes (half the somatic number); c, degenerates and is lost. the egg-centrosome, which now produced; (2) in higher animals, accessory sexual glands (the prostate, vesiculae seminales, and glands of Cowper), which aid in the formation GROWTH AND REPRODUCTION 765 of the seminal fluid; (3) the intromittent organ, or penis, by means of which the semen is introduced into the female during the act of sexual intercourse, or coitus. The Testes. — The testes consist essential^ of two sets of cells — (1) the interstitial cells, which plaj' a part in the acquisition of second- ary sexual characteristics; (2) the germinal cells, from which the spermatozoa are developed, and passed by a long system of ducts to the exterior. The testis is enclosed in a thick capsule, known as the tunica albugmea. From this capsule septa pass into the testis, dividing it into a number of compartments. In the compartments are long convoluted semmal tubules, lined by the germinal epithelium. In the different layers of epithelium the various stages of the " matura- tion of the spermatogonia," spermatogenesis, or may be seen. Most external^, lying upon the basement membrane, are the spermatogonia, supported by elongated " nurse cells," or the '' cells of Sertoli." Next comes two laj^ers of spermatocytes — large cells with marked karj^o- kinetic n iclei — and then the la3'er of spermatids — small cells with a well-marked round nucleus (Fig. 471). spermatozoon tail— p.iddle piece- head- Sertoli cell- A. spermatocyte II spermatocyte I spermatogone wall of tubule B. EiG. 471. .1, Diagram of a sperinatozoon; B, diagram showing th? origin of spermatozoa ivova. the living cells (spermatogonia) of the tubules of the testicle. (Kdth.) The spermatids also exhibit various stages of transformation to spermatozoa. In this process the nucleus becomes elongated to form the head of the cell, the main mass of cytoplasm goes to form the middle piece, While a filament of cj^toplasm grows out to form the whip-like tail (see Fig. 471). Wiien fully mature, the spermatozoa become detached, but connect themselves for a time with the free end of the Sertoli cells. The seminal tubules are supported by a number of fine connective- tissue fibres, in which run the bloodvessels and lymphatics, and in which are also situated the interstitial cells which play so important a part in the acquisition of the secondary male characteristics (see p. 505). The convoluted seminal tubules of each compartment pass to join with a few straight tubules (the tubuli recti), to form a network known as the rete testis. From this emerge the vasa efferentia (twelve to fifteen 766 A TEXTBOOK OF PHYiSIOLOGY or acrosome Nucleus End knob Middle piece Envelope tail Axial ment fila- in number). These form the epididymis, the tubules gradually uniting to form the vas deferens. The vas deferens is associated mth the nerves and bloodvessels of the testis in forming the spermatic cord. The Accessory Glands. — The exact func- Apical body, ^j^j^ q£ ^j^^ accessory glands is not quite clear. The accessory secretions, mixed with the testicular secretion, are believed to aid the movements of the spermatozoa, prob- abl}^ owing to their alkalinity. It is stated that extirpation of the prostate causes sterility, owing to the withdrawal of its secretion. The prostatic secretion is serous and milky in appearance, amphoteric in °^ reaction. That the accessory apparatus is of value is shown b}^ the fact that it develops at puberty, and this development is prevented by earty castration. Castration after puberty leads to an atrophy of the aparatus. The Seminal Fluid. — The seminal fluid consists of the external secretion of the testes combined with the secretion of the glands of the vas deferens, of the glands of CoA\^ier, and of the prostate and vesiculae seminales. It is a whitish viscous fluid, alkaline in reaction, contains about 90 per cent, of water, and is of a specific gra^^ty of about 1034. The inorganic substances (0-9 per cent.) consist chiefly of sodium chloride and the phosphates of calcium and magnesium. The organic bodies of the semen consist of nuclein attached to protamine, some albumin and proteose, fats, and the lipoids lecithin and cho- lesterin. I The spermatozoon is the active agent j of reproduction contained in the male • ejaculation. It varies in form A^dth dif- FiG. 472.— Diagra:*! of Si'ek- ferent tj^pes of animal, but in all higher MATozooN. (Redrawn from forms consists essentially of a head piece, Wilson's "The Cell," etc.) ^ ^-^^^^ ^-^^^^ ^^^ ^ flagellum-like tail piece. In man the head is pear-shaped (Fig. 472). Movements are made by the lashings of the flagellum- like tail. The movements are increased bj^ weak alkali, inhibited by acid or distilled water. The penis serves the purpose of introducing the seminal fluid in the sexual apparatus of the female. It consists largely of erectile End piece GROWTH AND REPRODUCTION 767 tissue, which, under the influence of dilator nerves, becomes engorged with blood, leading to the erection of the organ. The urethra passes through the corpus spongiosum of the penis. The period of sexual life begins m the male with the onset of puberty, and continues more or less throughout life. There is un- doubtedly a decline in fertility in the later 3'ears of life, but it is not uncommon for men of seventy or even eighty 3^ears of age to become the fathers of children. The Reproductive Processes in the Female. — The sexual apparatus of the female consists of the egg-bearing organ, or ovary, in which the eggs are matured, and the womb, or uterus, in which the foetus is developed from the fertilized ovum, or oosperm. Accessory to these are the oviducts, or Fallopian tubes, which conduct the egg "=1 TOXICA HLBUGlNe* ^,^^ STBOMA CAPSULE bOuATEO NEST -RIPENING OV OiiCUS PROliGERUS Fig. 473. — Diageammatic Section of Fig. 474. — Ripe Graafian Follicle Ovary of Fifth-Month Fcetus, at Puberty. (Keith.) showing Nests of Germinal Epi- thelium and Unripe Graafian Follicle. (Keith.) to the uterus, and the vulva and vagina, bj' means of which the male element is introduced into the female, and through which the^fuU- time foetus is passed into the world. The ovary consists of — (1) the germinal cells, which by maturation provide the female gametes, the ova; (2) the interstitial cells, which furnish an internal secretion concerned in the development of the secondary female characteristics (see p. 506). A fibrous stroma carries the bloodvessels, lymphatics, and nerves, which suj)pl3' the organ, and its cellular elements form the so-called interstitial cells which produce the internal secretion. The cells of the germinal epi- thelium lie just beneath the external capsule — the tunica albuginea. These divide to produce the oogonea, which, in developing into ooc3i:es, gradually sink inwards into the stroma and are surrounded bj' a laj^er of stroma cells. Thus is formed an immature Graafian follicle. Eventually the stroma cells divide to form a layer round the ooc3^te and a laj'er of cells which surround the follicle. These \.\\o laj^ers 7G8 A TEXTBOOK OF I'Fn'SlOLOGY multiply, and a fluid becomes secreted between them, so that a mature follicle is formed, the outer layer of cells forming what is known as the membrana granulosa, which is enclosed in a fibrous capsule derived from the stroma, and an inner ovum surrounded by a mass of cells, known as the discus proligerus, the remainder of the follicle being filled with fluid, the liquor foUiculi. When fully mature, the follicle is of such a size that it bulges the surface of the ovary, and after a time ruptures, shedding the ovum into the abdominal cavity in the neighbourhood of the Fallopian tube. This process is known as ovulation. The rupture is brought about by cellular activit}- within the follicle. The external wall of the follicle towards the surface of the ovary is thinned away during the growth, so that it ruptures CORONA RftDIATA GERMINAL VESICLE (nucleus) VOLK GRANULES ZONA RADlATA UMBILICAL CORD I ,,U>, T) ■ AMNION V*-'^ LEG BUD Fig. 47.5. — The Parts of a Mature Hitman Ovum. Diameter -jl-^ Inch. (Keith, after Van der Stricht.) + 3 TIMES Fig. 476. — Human Embryo and Its Membranes at End of First Month : Embryo about \ IxrH, THE Envelope of Embryonal Mem- branes ABOUT AN Inch. (Keith, after Kcnmann.) finally under the strain of the fluid secreted within the follicle. After the rupture, the cells of the membrana granulosa proliferate to form a yellowish tissue, known as the corpus liiteum. Connective-tissue septa carrying bloodvessels become developed in the corpus luteum. The corpus luteum is normally about | inch in diameter. At the end of three weeks it begins to diminish in size, so that it is a mere scar at the end of two months, and is absent at the end of six months. If, however, impregnation takes place, the corpus luteum grows in size, until at the end of the second month it is '^ inch in diameter. It remains this size until the sixth month of pregnancy, when it gradually decreases in size and becomes converted into scar tissue. The functions of the corpus luteum have already been mentioned (p. 507). GROWTH AND REPRODUCTION 769 The human uterus is a more or less pear-shaped muscular organ ■about 3 inches long. It consists of the main upper part, or body, and of the neck, or cervix. The internal cavity is about 2^ inches long. It is lined by a mucous membrane consisting of a single layer of epitkelium and numerous mucous glands resting upon a fibrous sub- mucous coat. Normalh', especially in those who have not had children, the cavity is almost absent, being more or less of the nature of a narrow chamiel. The oviducts enter into the upper part of the body; the cervix connects with the vagina below. The vaginal canal is noteworth}^ for its power of extensibility during parturition. It is lined by a mucous membrane. This is thrown into ruga3, or ridges. The channel is lined by a stratified epithelium. In the mucous membrane are glands which pour out a faintly acid secretion. The Sexual Life oi the Female. — In woman, the period of sexual activit}" begins about the twelfth to seventeenth year of age, varying with race and climate, being earlier in Southern and later in Northern races. In the temperate zone the e.ge is about thirteen to fifteen. Besides the acquisition of the secondary female characteristics, the beginning of sexual life is betokened by the onset of menstruation, a monthly loss of blood from the uterus — the menses. This lasts from two to six days, and usually from 100 to 200 c.c. of fluid, partly blood, partly mucous uterine secretion, are lost. The mixture is dark in colour, and clots very slowly or not at all. Just previous to each period of menstruation the whole genital tract becomes more richly supplied with blood, especially the uterus. The mucous membrane of this organ becomes swollen, partly by congestion of blood and lymph, and partly b}^ a certain amount of cell proliferation. This, known as the constructive stage, is followed by the destructive stage. The bloodvessels rupture and form hsematoma below the mucous membrane, the epithelivnn of which eventually ruptiires, and menstruation proper then ensues. At the cessation of menstruation there is a period of repair (about seven days), in which the uterus returns to its normal state. Then follows a period of rest, or quiescence, generally lasting about twelve or fourteen days. The exact relationship of menstruation to ovulation is not known. The shedding of the ovum is usually believed to precede menstruation. The two processes are intimately related, and depend upon the presence of the ovar^^ When these are removed, menstruation ceases. Men- struation also ceases during pregnancy and during the puerperium — the six weeks after child-birth. During lactation, also, it is usually absent. Women of the poorer classes often suckle their children more than a year, in the hope of deferring its return, and therefore the chance of fertilization. This is not necessarily the case. Pregnancy may take place soon after the birth of a child, even before the onset of menstruation. The first stage of menstruation is attended Avith a certain auiount of physical discomfort, amounting in some cases to pain, which 49 770 A TEXTBOOK OF PHYSIOLOGY passes off during menstruation. The emotional nature of women may change at this time. The period of active sexual life in the female ceases about forty- five to Mty 3'ears of age — the climacteric. The menopause is often attended with nervous symptoms, and is the period of life at which certain ailments are more prone to develop. The Process of Insemination. — ^The process of insemination varies in different species of animals. In fishes, the sperm is shed into the water in the neighbourhood of the eggs. With frogs, the male clasps the female, and pours the male secretion over^the eggs as they are shed. In birds, the semen is introduced into the cloaca by the male organ, and incorporated in the egg before it is laid. In mammals, the egg is not shed, and the male secretion is deposited in the female tract by introduction of the penis — the act of coitus. This act is accom- panied iDy erection of the organ. This is brought about by an engorge- ment with blood of the vessels of the penis, so that the organ becomes greatly increased in volume, its blood-pressure raised, and its temperature increased. The accepted explanation is that, under the influence of the nervi erigentes, the arterioles of the organ become much dilated, while the efferent veins become compressed by the action of such muscles as the ischio-cavernosus, the transversus perinrei profundus, the bulbo-eaverncsus. The erection is controlled by the presence of a centre in the sj)inal cord. If the centre be destroyed, erection is no longer possible. The afferent stimuli to this centre may come locally from the filling of the testes with semen; from the excitation of the sensory nerves of the penis; from the filling of the bladder (especially noticeable in 3'oung children); from the rectum, as when haemorrhoids (piles) are present. Stimuli may also come from the great brain — the sexual emotions. In animals, the sense of smell plays a considerable part in the process. Ejaculation of the semen is caused by strong peristaltic contrac- tions of the muscles of the vesiculee seminales forcing the semen into the urethra. The incoming semen distends the urethra, bringing about a rhythmic contraction of the bulbo-cavernosus muscle, which ejaculates the semen from the urethra. A contraction of the ischio- cavernosus and transversus perinsei muscles also occurs at this time, but these probabl}'^ play but little part in the actual ejaculation of the semen. Ejaculation is brought about reflexly through a centre in the cord. The impulses are brought to the centre by mechanical stimulation of the sensory nerves to the penis. It may, however, be caused in sleep as the result of pressure of semen in the vesicles, or by emotional impulses from the great brain (sexual dreams). It is computed that there are about 60,000 spermatozoa in each c.c. of the ejaculation, the volume of Avliich is about 5 c.c. In the female, a corresponding series of events takes place during sexual intercourse. Reflexly excited, the clitoris becomes engorged and erected, the Fallopian tubes and the uterus perform peristaltic GROWTH AND REPRODUCTION 771 contractions, by this means passing down the mucous content of the uterus to the os uteri. The uterus is also said to raise itself, and sink more deeply into the vagina, possibly to facilitate the entrance of the semen into it. Finally, a copious secretion takes place from the uterus and walls of the vagina about the same time as the ejacula- tions of the semen by the male. The sexual act is usually attended with considerable nervous excitement, and followed by a period of lassitude . Fertilization. — Fertilization consists in the union of the male and female gametes. In the higher animals, the spermatozoa of the male are deposited by the sexual act in the neighbourhood of the uterine cervix. Stimulated probably b}- the vaginal and uterine secretions under chemiotactic influence, they seek out the ovum. They ascend the uterus " against the stream." The activity of the cilia of the uterine mucous membrane is such as to impede their Fig. 477. — Mature Ovum of a Bat, showing the Separated Polar Bodies, the Female Proxucleus and the Formation of the Male Pronucleus from ^ the Head of the Spermatozoon. (Keith, after Van der Stricht.) In this case the tail-piece has not been loft behind. progress. Only one spermatozoon is necessarj^ for fertilization. The race is to the strong, and j)erhai3s to the fleet, since it is calculated that they move from 16 to 20 centimetres in an hour — about the distance from the os uteri to the Fallopian tube. It may be, however, that the winning spermatozoon is deposited within the uterus itself as the result of the relaxation of the cervix uteri which takes jilace during coitus. This, hoM'ever, is not necessarj-, since fertilization may take j)lace when the spermatozoa are deposited only in the entrance to the vagina. The time taken for fertilization is not known, but it is known that the spermatozoa may remain active in the vagina for a period of three weeks. The actual fertilization is said to take place most commonly in the Fallopian tube, and not within the uterine cavity. The head and middle piece of the fertilizing spermatozoon pass into 772 A TEXTBOOK OK PHYSIOLOGY the ovum, the tail, or flageUum, being (generally) left behind. From the head the male pronucleus is formed (Fig. 477) ; this combines with the female pronucleus to form the oosj)erm, thus completing the process of fertilization. A- B. C. Fig. 478. — Showing the Prodttction of the Morula from the Ovum. (Keith.) A, Ovum after first division; B, after second division; C, morula stage. The stimulus supplied by the spermatozoon may be imitated by altering the relation of the cell membrane of the ovum to its environment ; thus it has been shown that an unfertilized frog's eggs may be made to develop into tadpoles by the prick of a pin. einbnjogenic pole £::',bryogeiiic pole inner cell mass I ,enueloping layer uegetatiue pole Fig. 479.— The Blastula Stage uegetatiue pole enueloping layer Fig. 480. — The Blastocyst Stage. (Keith, after Van Beneden.) The tadpoles, however, do not develop into frogs. It has been ascertained that the chromosomes in the parthenogenetic larva of frogs are of the reduced type. This is a matter of interest, and probably explains the failure of the method to produce complete GROWTH AND REPRODUCTION 775 frogs. It also sheds light upon the incompleteness and the unlikeness of an embryonal rudiment to a human foetus. The organs existing in ovarian dermoids are rarely of the same completeness as those of parasitic foetuses. This indicates the value of the spermatozoon for the production of a complete individual. Similarly, the eggs of the sea-urchin may be made to develop by placing them in sea-water containing a small amount of magnesium chloride. Nevertheless, from the point of view of heredity, the male pronucleus plays an important part. Segmentation. — ^After fertilization, the oosperm becomes fixed in position in the uterus, and then undergoes a series of divisions, first into two cells, then into four, until a mulberry-shaped mass of cells, the morula, or, when large, blastula, is formed (Fig. 479). In this morula a cavity then appears, forming a hollow sphere — the blastocj^st — which is single-layered except in one part. The inner cells of this part then proliferate, and convert the sphere into a double-layered gastrula with a small pore (the blastopore) connecting the ca\ity with the exterior. The outer of the cell laj-ers is known as the epiblast, the inner as the hypoblast. Between these two layers a third laj^er develops, knoA\ai as the mesoblast (Fig. 481). The developing organism now differentiates the various systems concerned in the division of labour of the bodj'. Different systems become evolved from the three layers : From the Epiblast. The epidermis and its de- rivatives— e.gr., hair, nails, glands, and muscle of sweat glands, etc. The epithelium of the nose and mouth, and the glands opening into them ; the anterior lobe of the pituitary gland. The central and peripheral nervous systems. From the Mesoblast. The supporting tissues of the body: bone, connec- tive tissue. The muscles except those of the swe at glands and iris. The blood and lymph systems. The excretory system ex- cept the epithelia of bladder and urethra. The cortex of the supra- renal gland. The generative system. From the Hypoblast. The epithelia of the ali- mentary tract, including the glands entering it. The epithelia of the re- spiratory tract. The epithelia of the Eu- stachian tube and tym- panum. The epithelium of the thy- roid and of the thymus. - The epithelia of bladder, urethra, and accessory sexual apparatus. Implantation.^The ovum is usually fertilized in the oviduct, or Fallopian tube. It is then passed by ciliary action into the uterine cavity, where in the morula or blastula stage it embeds itself in the mucous membrane of the uterus by means of a phagocytic action of its outer layer, which is now known as the tropho blast. The corpus luteum is believed to exert considerable influence through its internal secretion upon the process of implantation. Immediately after fertilization of the ovum, the normal mucous membrane of the uterus, the endometrium, undergoes a great increase 774 A TEXTBOOK OF PHYSIOLOGY in thickness, forming itself into two laj-ers — a compact superficial and a deej) spongy layer. It is now known as the decidua, and is divided into three portions — the decidua basalis, or serotina, upon which the ovum rests ; the decidua reflexa, or capsularis, which encloses the embedded ovum; and the decidua vera, the remaining portion of the mucous membrane not in contact with the ovum (Figs. 482, 483). At first a space — the decidual space — between the two latter parts represents the remains of the true uterine cavity. These eventually come into contact, and fuse in the human subject in the fourth month of pregnancy. MUCOUS ' MEMBRANE ROPHOBLAST MUCOUS Membrane of f UTERUS Fig. 481. — Showing Origin of the Primitive Ccelom, the Mesoblast, and Cavity OF the Amnion during Development of the Human Ovum. (Keith, after I. H, Bryce.) From the developing embryo, two membranes are formed — ^the chorion and the amnion (Fig. 482). The chorion is the outer layer. It early divides into two — an outer fused mass of cells, or syncytium ; an inner layer of cells, or Langhans' layer. During the first six weeks the whole chorion becomes covered with vascular villi. These, how- ever, soon disappear except in the region of the decidua basalis, where the ovum is attached. Here is formed the chorion frondosum, its villi and the decidua basalis fuse together, and form the placenta. Within the chorion is the closed sac — the amnion — filled with fl\iid, in which the embryo is bathed. The placenta is formed as a separate organ about the third month of pregnancy, gradually increasing in size according to the foetal needs until full term. It is formed by a fusion of the decidua basalis and the chorion frondosum (Fig. 484). Blood-sinuses become developed in both the maternal and foetal portions, so that the maternal and foetal blood GROWTH AND REPRODUCTION 775 come into intimate juxtaposition, although, separated by cellular membranes, the}' do not actually mix. Through the action of these membranes oxygen and nutrient material are supplied by the mother to the fcetus, and the waste products of metabolism of the foetus transferred from the foetus to the mother. Parturition. — After an intra-uterine life of varying duration accord- ing to the species, the foetus is expelled by the process of parturition, or labour. In woman, this occurs at about the end of 2S0 daj's. "Labour" is divided into three stages: (1) The first stage, which results in the dilatation of the cervix of the uterus as the result of rhjiihmical contractions which become more and more frequent; cavity of uterus .decidual cells syncytium basal layer of chorion mesoblast of chorion decidua reflexa decidua serotina- cavity of amnion decidual cells, syncytium basal layer of chorion uterine vessel embryonic epiblast ■archenteron rimitiue coelom cavity of uterus esoblast of chorion Fig. 4S2. — Section through Ovum embedded ix the AYall of the Uterus (F. W, Jones, after Peters and Silcnka, from Keith's "Human Embryology."). (2) the second stage, in which the foetal membranes are ruptured and the foetus is expelled, usualh' head first, from the uterus b}' means of prolonged, sustained contractions of the uterus occurring at frecp ent intervals; (3) the third stage, in which the after-birth is expelled. The whole process may take thirt}' hours or more in a primipara — a woman who is having her first child. In subsequent births, the process is usually considerably shorter. What factor induces the onset of 776 A TEXTBOOK OF PHYSIOLOGY labour is not known. The j^rocess is normally reflexly controlled through a centre in the lumbar cord, although the presence of this centre has been shown not to be necessary. At term the uterus is D£ClOUA VERA '^N^DECIDUA RETLECTA ,0ECIDUA QASALIS lA. Blastodermic VESICLE. DE.C1OUA VER/^ OECIDOA VERA Fig. 483. — Section of Uterus showing in Diagrammatic Manner the embedded- Ovum AND the UifFERENTIATION OF THE DeCIDFA INTO THREE Parts. (Keith.) uterine vessel- suomuc layer^ of uterus decidua syncytium syncytium. basal layer. mesoblast of chorion blood space IiG. 484. — Diagrammatic Section of the Decidua Serotina (formed from THE Mucous Membrane of the Uterus) and Chorion to show the Manner IN which the Placental Blood Spaces are formed. (Keith.) of large size, reaching high u^ into the abdomen. After delivery by the process of " involution," it returns again within the pelvic cavity. The involution is said to be due to the autolytic action of intracellular GROWTH AND REPRODUCTION 777 enzymes within the uterine wall, within three months. It is a rapid process, and is complete Serum Test for Pregnancy. — Recently there has been devised a serum test for pregnancy. It is based upon the view that durmg pregnancy the maternal serum acquires the power of digesting the " specific " albumin which passes into the circulation from the placenta. In order to test if a subject be pregnant, the blood-serum of the sub- oein artery artery muscular coat blood spaces vein chorionic villus decidua serotina -chorion amnion. decidua vera decidua reflexa ceroiK- Fia. 485. — Showino Arrangement of the Amnion, Chorion, and Decidua in THE Third Month, and the Formation of the Placenta. (Keith.) ject is added to specially prepared placental tissue placed in a dialyzer. If the tissue is digested and amino-acids pass through the diah^zer, it is deemed a sign of pregnancy. Normal serum is stated not to have such digestive powers. It is true that the test is more often positive in the pregnant than in the non-pregnant, but the test is by no means certain, and it is said that by it even males are occasionally reported to be pregnant. 778 A TEXTBOOK OF PHYSIOLOGY Heredity. — It is a familiar proverb that " like produces like." " Men do not gather grapes of thorns, or figs of thistles." To account for this continuity of species, various hj-potheses have from time to time been propounded. It was at one time believed that a miniature animal existed preformed either in the spermatozoon or, more probably, in the ovum. Microscopy showed that such was not the case. The view of " epigenesis " states that in the egg, which is entirely different from the structure of the adult, there is a successive formation of new parts which do not exist as such within the egg. That like should produce like there must, however, be some directing force within the egg. Darwin belie ved that the parents contributed minute particles of all their own tissues to the reproductive cells, and thus secured physical continuity of species — the theory of pangenesis. The most commonly accepted view is that in the simple repro- ductive cells there exist, probably in the chromatin content of the nucleus, complexes which determine the course of development of the fertilized ovum. These germ cells themselves were produced from the pre-existing germ cells of the fertilized ovum from which each parent developed. The somatic cells of the develojDing embryo, and therefore of the adult, are in reality the custodians of the germ cells. They do not form new germ cells; they merely contribute to their growth and development. The germ plasm is continuous from one generation to another. Since nuclear material is contributed by both parents, and since in the formation of the germinal elements such material undergoes reduction in amount by a special method of cell division, it affords an adequate exjjlanation of why like should produce like, and yet at the same time why there should be such a marked difference between the offspring and the parents, and also between offsjjring themselves. A litter of puppies resembles its parents, but there may be marked variations in colour, temperament, and other characteristics of the puppies. The question arises as to how these variations are to be accounted for. Are they to be accounted for by heredity or by environment ? It is asserted that heredity plays a large part on tin plea that in the case of the new-born puppies the ante-natal environment has to all intents and purposes been the same. But this is not so; the condi- tions, even in the womb, will no more be the same for each puppy than they are for each egg in a mass of frog's spawn developing in a pond. The slight variations in chemico-physica) conditions may have the jjrofoundest effect on development. The further question arises as to whether environment after birth can in any way influence hereditary characters. It is not a question of gathering figs of thistles, but whether a bad fig-tree can by environment be made to yield a strain of good figs. This is a question of great importance to the sociologist. Lamarck asserted that " all is pre- served in reproduction and transmitted to the offspring, that Nature has made individuals to acquire or to lose by the influence of the GROWTH AND REPRODUCTION 779 circumstances to which their race has been for a long time exposed, inckxding the results of excessive use or disuse of an organ." Of recent years, the action of legislators, sociologists, and others, has been directed to the belief that, by giving a good supply of fresh air, exercise, proper sanitation, better education, the individuals will grow up stronger and healthier, and thus provide a better race. But will such methods convert bad stock into good stock ? The test lies in the offspring. According to one school of thought, such environmental conditions, although making improvement in the individual, will not better the race. The hereditary factor is all-important. Such is the view of Mendelism. The essence of the Mendelian principle is very easily expressed. It is, first, that in a great measure the characteristics of organisms are due to the presence of distinct, detachable character separately transmitted in heredity; and, secondly, that the parent cannot pass on to offspring a character which it does not itself possess. Each germ cell, ovum, or sj)erm may contain or be devoid of any of these characters; and since all ordinary animals and plants arise by the union of two germ cells in fertilization, each resulting individual maj- obviously receive in fertilization similar characters from both parents or from neither. In such cases the offspring is " pure " bred for the presence of the character in question, or for its absence. On the other hand it may be developed from the union of dissimilar germs, one con- taining a character, the other devoid of it; the individual is then cross-bred, or heterozygous. A population thus consists of three classes of individuals — those pure-bred for the presence, having received two doses, of a character; those pure-bred for the absence of the character, having received none of it; and the cross-breds, which have received one dose only. A plant, though cross-bred for talhiess, may be as tall as one pure-bred for tallness. A dwarf plant, whatever be its parentage, can only produce dwarf offspring. Not having talhiess, it cannot transmit that projaerty. A cross-bred tall plant can, by self-fertilization, produce both tall and dwarf offspring. Fowls with silky feathers cannot, if bred together, have offspring with normal feathers, but two birds, normal to all apj)earance, can, if the}^ be cross-bred in that respect, produce silky off- spring. These results are explained by assuming that a character may be either dominant or recessive. In breeding, the transmission of these characters is said to follow a definite law — Mendel's law. When a dominant and a recessive character are crossed, the first cross-bred generation possesses the dominant character, which may be represented as D(R) — e.g., the cross between a tall and dwarf pea possesses the dominant character of tallness. The issue of such cross-breds (impure dominants) in the second generation will be 25 per cent, pure dommant, 50 per cent, mixed (impure dominants), and 25 per cent, recessive. In such a generation interbreeding of the dominants will breed only dominants, of the recessives only recessives, but inter- 7S0 A TEXTBOOK OF PHYSIOLOGY breeding of the mixed impure dominant type again yields 25 per " cent. D, 50 per cent. D(R), and 25 per cent. R. 'I'his ma}- be tabulated as follows: D K \/ D(R) 1L> 2D(R) IR D 1D+2D(R)+1R R Many experiments to prove this law have been made both upon plants (peas, beans, maize, wheat, stocks, etc.) and animals (mice, rats, poultry, canaries, moths). In peas, for example, it is claimed that tall stems, yellow cotyledons, brown-skinned seeds, and round seeds are dominant characters; while dwarf stems, green cotyledons, white seeds, and wrinkled seeds are recessive characters. Among animals, dominant characters are short hair in rabbits, hornlessness in cattle, crest in poultry, brown eyes in man, etc.; recessive are long hair in rabbits, horns in cattle, absence of crest in poultry, grey and blue eyes in man. The explanation given of this law is that these characters, dominant and recessive, are segregated in two different sets of germ cells. Although the law derives support from many characters, such as those mentioned above, and from various hereditary diseases and mal- formations of the human race, such as brachydactyly, it does not explain all hereditary phenomena. The cross-breds of a white and black, when intermarrying, do not produce 25 per cent, pure white, 50 per cent, mixed. 25 per cent, black, but oflff?pring of varying degrees of duskiness. Following Mendelism, the modern school of eugenists, bent upon the "improvement" of the race, maintain that race improvement is solely a matter of breeding from good stock. This may undoubtedly lead to physical fitness, but it is very questionable as to whether it is the only way. It is also a difficult question to determine at what fitness we are to aim. It is well known that " genius " cannot be made to breed true. A genius in a family is a " spontaneous " varia- tion, as much as a child with six fingers. How do such " spontaneous " variations arise ? Darwin stated that new varieties of species arose by the cumulative effect of natural selection upon small fluctuating variations. It is of first-rate importance to ascertain how new varieties, healthy, intel- ligent, honest, diseased, feeble-minded, and criminal, arise. Can the parents' drunkenness, for exami:)le, affect the germ plasm ? At present, " eugenic " principles seem of little help. Darwin confessed: '■ Our ignorance of the laws of variation is profound." It still is. It has recently been suggested, as the result of observations in the vegetable kingdom, that species arise from one another by dis- GROWTH AND REPRODUCTION 781 contiiiuovis leaps and bounds — by ■"mutations."' "The new species appears all at once; it originates from the parent siaecies without any visible preparation, and without any obvious series of transitional forms." This is the mutation theory of De Vries. It would seem, then, that the distinctive characters of a species may arise in two ways: (1) By the accumulation of fluctuations; (2) suddenly by mutation. The extent to which the acquired conditions of environment are transmitted, if at all, still remains to be settled. That such environ- mental conditions are of great importance is indicated by experiments upon bacteria. It is knawn that virulent organisms may be attenuated by growths upon special media, and that such diminution of virulence is maintamed so long as the environmental conditions remain the same. This would point strongly to the conclusion that the effects of the environment of the race induced by improved conditions may be mamtained in the offspring so long as the better environmental condition ^ are maintained. Herein lies the great hope of the humanitarian. The Determination of Sex. — The determmation of sex has long been a matter of popular speculation, but only recently of scientific inquiry. In consequence, many theories, although of historic interest, are scarcely of scientific value. Such, for example, are the views that S3X is determmed by parental desire; by the element of the more healthy parent; by the relative age of the parents; b\" the relation of coitus to menstruation; or whether the ovum comes from the right ovary or the left. It is generally believed, and to a certain extent it is supported by statistical evidence, that more male babes are born in and after times of stress, such as war and famine. The disproportion between the sexes (women are more numerous) is to some extent accounted for by the more difficult passage of the male babe into the world, owing to his larger head, and to the more precarious occupation of males in the community. In recent lines of inquiry, efforts have been made to ascertain whether sex is predetermmed in the sexual elements, or whether sex is determined by environmental conditions of the o\iTm after fertilization. Evidence has been accumulated in favour of both views. In support of the environmental view, it is claimed that well-matured frog "s spawn develoJ)S into an excess of females, and that ill-matured eggs of certain caterpillars yield an excess of males. Differences of temperature, by affecting the nutrition of the mother, have been shown to exert an influence upon the sex of the offspring of the primitive worm Dinophilus. An experiment of great interest is one upon the annelid worm Ophryotrocha puerilis. When a female of this species, with no trace of hermaph- roditism, having ripe ova, was divided into two, the head portion of thirteen segments regenerated seven segments, and, on being killed, it was found that the ova and female apparatus had atrophied, and that the animal was now male, with a functional testicular portion 782 A TEXTBOOK OF PHYSIOLOGY developed. It is suggested that, owing to the amputation and dimin- ished nutritive conditions, the indifferent germ cells had developed into male cells. On the other hand, experiments in the breeding of mice have shown that nutritive changes and the age of the parents have made but little difference in the proportion of the sexes. That feex in certain cases is largely determined b}^ the conditions of general metabolism is illustrated by the effects which follow castra- tion, by infection with e, parasite, of several varieties of crabs. In all cases the castrated male takes on female characteristics, and even defends the parasite as if he were protecting his eggs. The castrated female shows no sign of altered structure or instinct. It has been suggested, in the case of the crab, that the parasite alters the composition of the male's blood, which tends to bring about a female condition, which may be followed by the onset of female characteristics, or even the production of female organs from indifferent germ cells. On the other hana it may be an internal secretion effect from the traces of female tissues present in male. In support of the view that sex is predetermined in the ovum is the fact that "' identical " twins — that is to say, twins arising from the same ovum and included in a single chorion — are always of the same sex. More conclusive is the fact that, in certain mosses, spores of identical appearances, asexually produced, are predetermined as male- or female-producing elements. In the primitive worm Dinophilus, the large fertilized ova develop into females, the small fertilized ova into males. The same is true for the vine pest Phylloxera, and for the rotifer Hydatina. In certain parthenogenetic invertebrates, such as the Hymenoptera, the unfertilized eggs give rise to males, the fertilized eggs to females. Whether fertile queens or infertile worker bees are developed from female larvae depends on the nature of the food given them. As to the influence of the male element, it has recently been shown that certain animals, especially insects and arachnids, produce two forms of spermatozoa. Half the spermatozoa have in their nucleus an odd chromosome, or x chromosome; half have not. In the ova the X chromosome is always present. Union of a spermatozoon con- taining the .r chromosome with the ovum produces a female; union of a spermatozoon without the x chromosome produces a male. By some, maleness and femaleness are regarded as Mendelian characters, like shortness or tallness: If sex be due to some factor, like the x chromosome, it is possible, on the Mendelian interpretation, that males and females may both be cross-breeds (heterozygous), or that the male alone may be heterozygous, the female recessive, or the female heterozygous and the male recessive. Experiments tending to support the last view have been made upon the currant moth. It is asserted that in vertebrates castration suppresses the maleness, but does not induce any expression of female character- istics. On the other hand, the castrated female, while losing her female characteristics, tends to develop markedly those of the male. Further proof is needed of such a view. GROWTH AND REPRODUCTIOX 783 It will be seen that we are still far from understanding the circum- stances which lead to the determination of sex. In some cases it is apparent!}^ due to an initial difference m metabolic rhji;hm, in others to a predetermined morphological difference m the sex units. Death. — Death is the total cessation of the cell activities of the individual. Cells are always dying and bemg replaced within the indi\adual. After a time, however, either by the process of decay following a natural adolescence and maturity, or more often as the result of disease or accident, one of the vital functions fails, the general metabolism of the body ceases to be efficient, and death ensues. The custodianship of the genetic by the somatic cells is finished. Yet, if the former have fulfilled their function, the individual does not wholly die; life continues in the offspring. On death, there is a transformation, but no destruction of energy. The disintegrating cells pass into materials of lesser complexity, some or all of which are again worked up into the complex forma- tions of life. Thus continues the ceaseless life and death cycle of the ages. INDEX Abdomen, movements of, iu respiration, 306 Aberration, cliromatic, 609 — of lens, spherical, 609 Absorption iu tlie stomacli, 388 — of fat, 436 — of food, 421 — power of, 30 Accessory glands, 766 Accommodation, mechanism of, 614 Aceto-acetic acid, 468 Acetone, 469 Achromatic lens, 609 Achroodextriu, 67 Acid, asimrtic, 41 — /3-oxybutyric, 468 — fatt}^, 53 — glutaniiuic, 41 — glycuronie, 63 — hiematiu of blood, 94 — hiematoporphyrin of blood, 94 — metaprotein, 50 — monocarboxylic, 36 Acromegaly, case of, 523 Adenin, 50 Adrenalin, 41 — action of, 505, 509 — effects of injection of, 504 — glycosiu'ia, 434 -- vaso-constriction caused by, 238 Afferent fibres, 753 — nerves, 245 Age, diet under various conditions, 356 Agglutinin, 109 Agglutinins, 110 Air, aveolar, 281 — bubbles of, in heart after decompres- sion, 309 — collection of, apparatus for, 281 — composition of, 281 — changes by breatliing, 293, 312 — complemental, 279 — residual, 280 ■ — supplemental, 280 — tidal, 278 — volume of, 278 Alanin. 40 Albumiuo-meter, Esbach's, 465 Albuminoids, 48 Albumins, 48 Albuminuria, 465 Alcohol, 364 — as source of energy, 364 — compounds, 34 — food value of, 352 ^85 Alcohol, percentage of, in spirits, wines, and beer, 365 Aldehydes, 35 Alkali carbonates, lack of, 336 — metaprotein; 50 Alkaline haamatin, reduced, of blood, 94 — luematine of blood, 94 Alkaptonuria, 469 Allantoin, 460 Allorhythmia, 135, 138 Altitude, high, efiect of on blood, 79 Alveolar air, 281 analysis of, 291 collection of, apparatus for, 281 composition of, 281 — ■ — gases in, pressure of, 269 Amblyopia, 623 Amboceptor, 109 Amino-acids, 44, 422, 423, 424, 425 Amitosis, 756 Ammonia, 462 Ammonium magnesium })hosphate, 471 — urate, 471 Amnion, arrangement of, 777 Amceba, changes exhibited by, 2 — pro tens, 1 Amorphous urates, 471 Amphibians, larval stage of, 276 Ampulla of guinea-pig, crista of, 655 Amylolytic enzymes, 71 Amylopsin, starch digested by, 399 -Anabolism, 441 — of fat, 436 Anacrotic wave, 215 Anaesthetized dog, respiration and blood- pressure of, 290, 291, 293, 294 Anaphylaxis, 111 Anelectrotonic current, 583 Animal, decerebrate, lung volume and blood-jjressure, 278 — electricity, 559 — fat, melting-point of, 438 — life, cycle of, 258 Animals, exjieriments on, dining period of liunger, 342 — hccmoglobin in, 90 Ankle clonus, 684 Anode, region of, stimulation in, 583 Antigen, 109 Antitoxins, 108 Aortic blood -pressure, 178, 197, 198, 199 excitation of depressor and, 177 Apncea, 299 — forced breathing followed by, 299 Appetite, 384 50 786 A TEXTBOOK OF PHY8I0L0GY Aqueous huiuour, 255 Arginin, 42 Army, British, peace diet of, 345 Arteria^ rectse, 474 Arterial cannula, 186 — pressure, 168, 186 circumstances aUccting, 1?2 curves, relations of, 149 measurement of, 186 of kidney, 247 record of, in cat, 512 — pulse curve, 215 — system, pulse wave in, 217 — wall, deformation of, effect of surround- ing tissues upon, 190 Arteries, contracted, elongation of, with rise of internal pressure, 184 — coronary, circulation in, 238 — elasticity of, 184 — relaxed, elongation of, with rise of internal pressure, 184 — structure of, 124 — velocity of flow in, 208 Arteriole muscle, pressor atierent impulses affecting, 231 Avytenoids, 742 AAscending " current, 582 spar tic acid, 41 Asphyxia, 306 — effect of, 168 — of rabbit, 304 Association areas, 729 Astigmatism, 612 Atmosj^here, effects of, 499 — temperature of, 499 — See also Air Atmospheric pressure, diminished, eflects of, 307 increased, 309 Auditory judgments, 653 — nerve, course and connection of fibres, 697 Auricle, right, 119 of calf, 121 Auriculo-ventricidar bundle, 121 — node, 120 Autolysis, 69 Avogadro's hypothesis, 17 Axis cylinder of nerve-fibre, 569 Axon, 569 — section of, effects, 576 Axon reflex, 484 Bacteria, life cycle of, 258 Bacterial action in intestinal digestion, 404 — haemolysis, 107 Barcroft's blood-gas apparatus, 262 Barfold's test, 61 Basilar membrane, 648 Bathmotropic fibres, 173 Baths, effect on metabolism, 499 Beckmann's apparatus, 27 Beef, composition and value of, 348 Beer, alcohol percentage of, 365 Biceps, cruris of frog, 549 Bile, 391 Bile, excretion of, 447 — How of, 369 — formation of, 447 — functions of, 394 — in urine, 469 — mechanism of secretion, 394 — organic salts of, 392 — pigments of, 393 — secretion of, mechanism, 394 Binocular vision, 630 Biological force, 15 Biotic energy, 15 Bismuth meal, 407, 418 Biuret, 46 Blastocyst, 772 Blaze currents, 567 Blind spot, 621 Blood, 75 — absorption coetticieuts for, 263 — acid hpematin of, 94 — acid hrematoporphyrin of, 94 — alkali of, diflusiblc, 77 non-diffusil)le, 77 — alkaline ha?matin of, 94 reduced, 94 — amount of, 78 — analysis of, 80 — carbon dioxide of, 290 — clotting of, 101 — coagulation time of, 103 — corpuscles of, 86 — — pale, 97 functions of, 98 origin of. 98 red, 86 ■ chemistry, 90 enumeration of, 87 • fats of, 90 function, 89 — ■ origin, 88 white, enumeration, 98 — -count, diflerential, 98 — effect of high altitude on, 79 — electrical conductivity of, 80 — fixing agent of, 97 — flow of velocity, 203 — gases of, 259, 263, 275 extraction of by pump, 259 pressure of, 269 — heemoglobin of, estimation, 96 — human, analj'sis of, 81 Haldane's apparatus for determining tension in, 273 oxygen cuives of, 266 — in urine, 466 — osmotic [iressure of, 80 — oxygen capacity of, 264 — partial, 269 — platelets of, 99 — pressure of, 186 aortic, 178 capillary, 221 carotid, of pithed cat, 230 fall of, 177 in nipple of cat, 522 in veins, 225 INDEX 787 Blood -pressure, inllueneeofpostiueon, 198 rise of, due to pressure on supra • renal vein, 509 — reaction of, 76 — specific gravity of, 76 — spectra, 93 — supply of kidney, arrangement of, 474, 475, 478 — tests for, 112 biological, 113 chemical, 112 guaiacum, 112 microscopical, 112 spectroscopical, 112 — thrombin of, 102 — velocity of, diagram showing general relations of, 206 in veins, 225 — vertebrate, colour of, 76 — viscosity of, 80 — See also Circulation Blood -gas, analysis of, by Topler pump, 261 — apparatus, Barcroft's, 262 — pump, Hill's, 260 Bloodvessels, structure of, 124 Body, chemical composition of, 33 — fluids, circulation of, 115 — proprio-eeptive mechanism, 659 — temperature of, 492 — weight of, and sui-face area, 341 Bomb calorimeter, 326 j8-oxybutyric acid, 468 Boyle's law. 17, 22 Brain, 685, 716 — afferent systems to, 668 — blood-pressure in, 222, 240 — centres of, 728 — circulation in, 239 — • cortex, 722 — fore part of, 686 — ■ functions of, 716 — hemispheres, 709, 716 — human embryo, 685 — localization of parts of, 721 — of dog, crucial sulcus of, 723 — of frog, 686 removal of, 688 — removal of, reflex action of cord after, 675 — results of stimulation, 722 — section through cerebral hemisphere, 709 — speech centres, 730 — tracts from cord to, 669 670 — transmission from, of spinal motor neurons, 669 — weight of, 716 — See also Cerebellum Bread, 355 Breathing, abdominal, influence of, on the pulse, 191 — anatomical considerations of, 284 — ert'ects on blood-pressure, 237 — mechanics of, 284 — regulation of, 289 — types of, 192 Bronchial tubes, 277 Burdach, postero-lateral tract of, 668 Cadaverin, 403 Caisson disease, 309 Calcium carbonate, 472 from human urine, 464 — oxalate, 471 crystals, 461 Calories of foodstuff's, 328 Calorimeter, bomb, 326 — for experiments with small animals, 330 Cane-sugar, 64 Cannula, arrangement of, for recording blood -pressure, 187 — arterial, 186 Capillaries, circulation of, 218 in, rate of flow, 221 — velocity of flow in, 208 Capillary blood-pressure, 221 Carboliydrate, 427 — fat from, 438 — foods, composition and value of, 350 — metabolism of, 428 — of plasma, 85 Carbohydrates, 59 — lack of, 336 Carbon, compounds of, 34 — dioxide, deficiency of, eftects, 302 — — ■ excess of, effects, 302 in blood, 263, 275 Carbonal group of organic compounds, 35 Carbonates, 465 Carbonic acid gas, 19 Carboxyhffiuioglobin, 91 Carboxyl group of organic compounds, 36 Carchesium, colony of individuals of, 3 Cardiac cycle, 143, 144_^ — impulse, 153 — muscle, 532 — nerves, 171 — — of dog, 172 ^ of frog, 171 ' - — valves, surface relations or, ] 53 Cardiometer, 166 Carotid artery, velocity of pressure curves, 207 — blood -pressure of, in pithed cat, 230 — body, 519 — pressure, cft'ect on, of anesthetized dog 510 Castration, 505 — effect of, on horn-growth, 506 Cat, blood-pressure, 230 — ovum of, before maturity, 9 — vagus divided in, 300 — vagus intact in, 300 Catalysts, 68 Cataphoresis, 31 Caudate nuclei, 715 Cell, S — anterior horn, 576 — division of, chromatin chanijes during 757 — lamination in motor area, 725 of gyrus post-central is. 7'M 788 A TEXTBOOK OF PHYSIOLOGY Cell, lamination of visual area, 726 — mciotic division of, 762, 763 — naked, 1 — reproduction, 756 Cells, camera lucida drawing of, H — daughter, distribution ol' clironiosonies to, 757, 763 — gas-secreting of Paradise fisli, 271 — survival of, 13 Celluloses, 65 Cephalin, 58 Cereals, 354 — composition and value of, 352 Cerebellar arc, 672 — cortex, section of, 702 Cerebellum, 702 — afferent fibres to, 703 — afferent systems to, 668 — efferent fibres to. 703 — functions of, 705 — structure of, 702 — tracts of, 704 Cerebral arc, 672 — circulation, 239 — cortex, development of, 722 of mole development of, 722 — • — structure of, 723 — function, 716 — hemisphere, 709, 716 — — positions of centres concerned in speech, 730 — pressure gauge, Hill's, 240 Cerebro-spinal fluid, 254 Cerebrum. Sec Brain Cervical ganglion of dog, section through chromophil cells in, 508 — sympathetic nerve, in rabbit, dissection of, 176 Chauveau's hwmodromometer, 204 Cheese, composition and value of, 349 — food value of, 352 Chemical composition of the body, 33 — influence affecting the glycogenic function, 430 Chemiotaxis, negative, 12 — positive, 12 Chemistry of red blood-corpuscles, 90 Chest, influence of, on the pulse, 191 — register of sound, 743 Cheyne-Stokes Breathing, 299, 300 Chicken, heart of, muscular connection between aiiricles and ventricles in, 140 Childhood, diet of, 363 Chlorides, 462 — distribution of, 33 Chloroform, effect of. on arterial pressure o( dog, 201 -on heart volume of dog, 201 Chlorophyll, 257 Cholesterol, 58 Cholin, 57 Choroid, 603 Chorion arrangement of, 777 Chromatic aberration of lens, 609 Cliromoproteins, 48 — of limbs. 243 Chromosomes, 757, 758, 761, 762, 763, 764 Chronotropic fibres, 173 Cilial-y body, 603 Circulation, artificial .schema of; 183 to show eflect of gravity on, 194, 196 — capillary, 218 — cerebral, 239 — complete, time necessary for, 209 — - coronary, 238 — effect of change of postiu'e on, 194 — examination of microscoi)ical, 219 — fretal, 248 — in generative organs, 248 — in head, 242 — of blood, course of, in mammals, 142 — of limbs, 243 ; — of nitrogen in Nature, 259 — of salivary glands, 243 — ■ — physical factors, 179 — oftheb.dy fluids, 115 functions of, 604 — muscle, 602, 603 — • portal, 246 — pulmonary, 236 — renal, 247 — special, 236 — times, 210 — Sec also Blood Circumvallate papillse, 593 Climate, diet under varying conditions of, 357 Clothes, 500 Clotting of blood, 101 Coagulation of blood, 101 Coagulative enzymes, 72 Cobra, hypnotized by stroking, 737 Cochlea, membranous, 648 — section of, 648 Cold, effect of, on sino-auricular node of dog, 139 — exposure to, 499 Cold-blooded animals, 495 Collagen, 48 Colloids, 29 — surface tension in, 31 Colostrum, 359 Colour-blindness, 623, 626 — degrees of, 626 Colour of vertebrate blood, 76 — perception of, 623 — perception lantern, Edridge-Green, 627 — • reactions of i)roteins, 46 — saturation, 624 — tests for proteivis, 52 — vision, 625 — • — ajiparatus, Leonard Hill, 628 — • • — Hering theory of, 625 — ■ — Young-Helmholtz theory of, 625 Colours, wheel for mixing, 623 Comma tract, 669 Complement, 109, 110 — ■ deviation of, 110 Complemental air, 279 Compounds, inorganic, 33 — orgiinic, 34 JNDEX 789 Conductors, neivoiis, 574 Conjunctiva, 600 — human, end bulb of, 586 Conjunctival reflex, 682 Connective tissue, 5 Consciousness, 732 Consonance, 652 Consonants, sounds of, 746 Cornea, 601 Corneo-iridic angle, movements of, 614 — junction, 602 Coronary circulation, 238 Corpora quadrigemina, 768 Corpus luteum, 507 Corte's organ, 648, 649 of guinea-pig, 649 Coughing, mechanism of, 295 Cranial autonomic fibres, summary of, 752 system, 751 — nerves. 690 nuclei of, 699 superficial origin of, 692, 693 — nuclei, 708 Crank lever for muscle registration, 539 Creatinin, 461 Cretinism, 515 Cretins, non-goitrous, 516 Cribriform ligament, 602 Crico-arytenoid muscles, lateral, 743 I^osterior, 742 Crico-thyroids, 743 Cricoid, 742 Crural nerve, excitation of, 244 Crystalloids, 29 — dialysis of, 29 Cud chewing, 390 Current, constant, effects of, 581 — of action, 561 — of injury, 560 Currents, blaze, 567 — cutaneous, 564 — retinal, 565 Cutaneous currents, 564 — sensation, 585 receptors of, 585 Cybulski's photohsematochometer, 205 Cylindrical tubes, flow of fluid in. 179 Cystin, 43 — crystals, 470 Cystinuria, 470 Cystoplasm, degeneration of, 576 Cytotoxins, 111 De-aminizing enzymes, 72 Death, 783 Decidua, formation of. 774 Defsecation, 419 Deglutition, mechanism of, 408 Deiters, nucleus of, 698 Dendrons, 569 Depressor fibres, 177 — nerves, excitation of, aortic pressure and, 177 effects of stimulation, 518 — ■ — in rabbit, dissection of, 176 " Descending" current, 582 Dextrius, 66 Dextrose, 62 — katabolisni of, 426 Diabetes mellitus, 435 Diaphragm, action of, 284 — • movements of, 284 — spasm of, expiration, 297 inspiration, 297 Diastole, 144 — duration of, table showing pulse- frequencies, 170 with different pulse frequencies, 168 Diastolic filling of heart, 160 Diathermy. 568 Dicarboxylic acid, 3ti Dicrotic ware, 215 Diet, chemical composition of, 328 — nitrogen-poor, sulphates in. 463 — nitrogen-rich, sulphates in, 463 — peace, of British army, 345 — under varying conditions, 356 Dietaries of the world, 346 Dietetic methods, special, 364 Dietetics, 325, 344 Diffusion of gas, 17 through a liquid film,' 20 Digestion in the mouth, 371 — in the small intestine, 391 — in the stomach. 379 — mechanical factors of, 406 — peptic, 385 * — processes of, 367, 385 Digestive action of pancreatic juice, 399 — fluids, secretion and activation of, 367 Dioptrics, laws of, 608 Dipeptide, 45 Diplopia, 631 Disaccharides, 63 Divers, 311 Dog, sinu-auricular node of. effect of clamping, 139 effect of cold on, 139 Dog's heart, outline of, 137 Dorsal spino-cerebellar tract, 669 Dromotropic fibres, 173 Ductless glands, function.s of, 503 Dudgeon sphygmograph, suspension method of, 211 Duodenum, mucous membrane of, acid extract of, 39S Dyspncea, 299 Ear, diagram of, showing ossicles, 644 — examination of, method, 645 — external, 644 — internal, 646 right, 647 — rabbit's, lesions produced by ultra- violet light on, 13 Edridge-Green colour perception lantern, 627 Effector organs, 574 Eggs, 354 — composition and value of, 348 Eighth nerve, course of, 697 vestibular portion of, 699 790 A TEXTBOOK OF PHYSIOLOGY Elasticity of arteries, 184 Electric tissues, 566 Electrical change of heart, 133 — conductivity of blood, 80 Electricity, animal, 559 — constant current of, 534 Electro-cardiogram, 134 — and musical aortic murmur in man, 156 — and rough aortic murmur in man, 155 — carotid pulse of dog, 155 — heart sounds of dog, 155 — • normal, 132 — of complete heart-block, 133 — showing regularly occurring ventri- cular extra systoles, 133 — ■ Avave of, 214 Electrodes, Keith Lucas moist chamber and, 563 Electrometer, capillary, 562 — records of eyeball responses to light, 618 Electro-motive force, 536 — properties of muscle and nerve, 559 Electrotherapy, 567 Electrotonus, 583 Embryo, human, 768 — rabbit's, cells from, 14 Endolymph, 647 Endotoxins, 109 Energy, direct method of estimating, 331 — intake of, 327 — output of, 328 English vowel sounds, 746 Entero-ceptive mechanism, 660 Enterokinase, 401 Enzymes, 68, 369 — amylolytic, 71 — coagulative, 72 — de-aminizing, 72 — lipolytic, 71 — pancreatic, activation of, 398 — properties of, 70 — proteolytic, 70 — sucrolytic, 71 Epicritic sensibility, 591, 592 Epithelium, 5 Equilibration, 656 Erythrodextrin, 67 Esbach's albumino-meter, 465 Esophoria, 631 Ether, effect of, on heart of dog, 201 Evaporation, 497 Exophoria, 631 Eye, accessory jmrts of, 600 — adjustment of, 612 — anatomy of, 600 — cardinal points of, 611 — examination of, methods, 641 — hypermetropic, rays in, 616 — images of truncated pyramid, 634 — investigation of, apparatus for, 637 — movements of, 630 — myopic, rays in, 617 — of frog, examination of, 640 — of rabbit, examination of, 641 — right, perimetric chart of, 639 — See also Vision Eyeball, formation of, 712 — horizontal section of, 601 — light responses to, electrometer records of, 618 — schema of, 223 Faeces, 405 Fat, 53, 428, 437 — alisorjition of, 436 ■ — acid value of, 55 — anabolism of, 436 — effect of, in metabolism, 340 — forms of, 55 • — from cajbohydrate, 438 — from protein, 439 — iodine value of, 55 — katabolism of, 440 — lack of, 336 — melting point of, 55 — metabolism of, 436 — neutral, 53 — of milk, 437 — of pig, 437 — of red blood-corpuscles, 90 — • specific gravity of, 55 — storage of, in liver, 448 — volatile fatty acids in, 55 Fatigue, 546 Fatty acids, characteristics of, 55 Fatty degeneration, 441 Feeding, artificial, 360 — metabolism raised by, 343 Fehliug's solution, 467 — test, 61 for sugar in urine, 467 Fenestra ovalis, 646 — rotunda, 646 Fermentation test, 62 Ferments, 68 Fertilization, 771 Fibrinogen, formation ot, 450 — of plasma, 84 Fish, composition and value of, 348 — cooked, com])osition and value of, 352 — swim-bladder of, 271 Fistula, gastric, Pawlow's method of establishing, 381 Flechsig tract, 669 Flour, 354 Fluid, How of, effect of introducing re- sistance, 181 — — in branching tubes, 180 -in cylindrical tubes, 179 — — in rigid and elastic tubes, 182 in tube of varying diameter, 180 ■ of velocity and resistance heads, 180 — jiericardial, 254 • — pleural, 254 Fojtus, circulation of, 248 — nutrition of, 357 — ovary of fifth-month, 767 Food, absorption of, 421 — calories table, 328 — composition of, 348 — cooking of, 366 — selection of, 344 INDEX (91 Food, value of, 345, 348 table of, showing calories, 363 Foods, carboliydrate, composition and value of, 3c 0 — fat, composition and value of, 349 — protein, cost of, 348 — watery, composition and value of, 350 Foodstufis, 352 Fourth ventricle, 689 Freezing-point, determination of lowering of, 27 Frog's heart, contraction of, 128 diastolic pressure of, 129 — — excitability of, 131 lever for recording, 127 Fruits, composition and value of, 351. 352, 355 Fundus of eye, 642 Galactose, 62 Galactosides, 57 Galvani's experiment, 559 Galvanometer, deflection of, temperature of muscle and, 554 — single-pair thermopile connected to, 552 Galvanotaxis, positive, 12 Galvano-tonus, 534 Ganglia, function of. 751 Gas, analysis of, Haldane's apparatus for, 282 — bubbles of, in arteries of intestines, 309 in veins of intestines, 309 — diffusion of, 17 through a liquid film, 20 Gas laws, 17 Gases, blood, 259 extraction of, by pump, 259 — pressure of, 269, 275 — solubility of, in salt solutions, 20 Gastric contents, acidity of, deficit, 389 excess, 389 examination of, 388 — juice, 380 action of, on starches, 387 -on sugar, 387 chemical mechanism of, 384 composition of, vai'iation, 384 lipase of, 387 mechanism of secretion, 383 nervous mechanism of, 383 secretion of, 374 variation of composition, 384 Gastrin, 384 Gastrocnemii, excised, length of after fatigue, 547 Gastrocnemius, contractions of, with different loads, 545 effect of temperature upon, 543 effect of load upon contraction of, 544 — of frog, contraction of, 541 fatigue of, 546 Gay-Lussac's law, 17, 23 Gelatin, 48 Generation, organs of, 505 circulation in, 248 Geniculate bodies, 708 Gland current, 563 Glands, accessory, 766 — • salivary, 565 Globulins, 48 Glomerular secretion, nature of, 480 Glomerulus, function of, 478 Glosso-pharyngeal nerve, 693 Glucoproteins, 48 Glucosamine, 63 Glutaminic acid, 41 Glycin, 40 Glycogen, 66 — • source of, 427 Glj'cogenic function, 427 — — influences aff"ecting, 428 of liver, 447 Glycosuria, 427, 431, 467 — adrenalin, 434 — alimentary. 431 — pancreatic, 432 — phloridzin, 433 — pituitary, 434 — puncture (neurogenous), 432 — salt, 435 — thyroid, 434 Glycuronic acid, 63 Goitre, exophtlialmic, case of, 518 GoU, posterior-median tract of, 668 Gonium pectorale, 4 Gout, symptoms of, 445 Gowers' tract, 669 Graafian follicle at puberty, 767 Gracilis, nervous impulse in, 581 Graham, gas effusion of, 18 Gravity, centre of, 528 Growtli, 755 — • effect of vitamine on, 338 Guaiacum test for blood, 112 Gymnema sylvestre, 595 Gyrus post-centralis, cell lamination of, 724 Hfemachromogen, 94 Hremacytometer, Thoma-Zeiss, 37 Hematuria, 466 Hiemautogram, 216 Hffimin crystals, 113 preparation of, 112 Hiumoblast, 89 Htemodromometer, Ghauveau's, 204 Hiemoglobin, animal, 90 I — of blood, estimation of, 96 ' — ■ solution, eff'ect of, on oxygen curve. 267 Haemoglobinuria, 466 Htemolysis, 105 — bacterial, 107 — by foreign sera, 106 , — by snake venoms, 107 — chemical, 106 — physical, 105 — produced by vegetable poisons, 107 Hsemophilia, 104 Haemorrhage, transfusion in, 228 Hair follicles, 486 — nerve endings at Ijase of, 587 792 A TEXTBOOK OF PHYSIOLOGY Haldane-Penil)iev resiiiiation apiiaratiis. 318 llaldane's apparatus for deterniiiiing tension in luimaii blood, 273 — gas analysis ap{)anitus, 282 Hammer of Wagner, action of, r>37 Haploscopic vision, 63r> Haptophors, 108 Harmony, 652 Head, circulation in, 242 — proprio-ceptive mechanism of, 655 — register of sound, 74-1 Hearing, 643 — reaction time to, 733 — receptive area for, 728 — receptor mechanism foi-, 643 — theories of, 652 Heart, anatomy of, microscopic, 122 — attachment of, arterial and venous, 151 — compensatory pause of, 131 — contractility of, 129 — diagram of, showing course of lilood, 1 42 — diastolic filling of, 160 — electrical change of, 133 — embryonic, divisions of, 117 — examination of, modes, 152 — excitability of, 128 — frog's, contraction of, 169 lever for recording, 127 ■ — hoi'se, tracings fiom, 145 — human, sinu-auriculai junction in, 120 — movements of, 144 in situ, 151 — muscle, 127 — musculature of, 152 — nerves of, 171 — nutrition of, 158 — perfused, of frog, 144 — physiology of, 127 — point of primary uegati\ity, 138 — preparation of, diagram of, apparatus for, 164 — pressure curves of, aortic and intra- ventricular, 146 — rabbits perfused with Locke's solution, 159 perfused witli Ringer's solution, 100 record of, movement of. 511 — right side of, diagram of, 150 — sounds of, 154 — Stanniused, tetanizing of, 131 — surface relations of, 153 — systolic output and work of. 163 — tissue of, conduction of excitatory wave, 134 — turtle's, sinu-auricular junction in. 120 — venous cistern of, 147 — vertebrate, nervous elements of, 123 type of, 118 ■ — volume of output, tracing showing, 167 Heartblock, complete, electro- card iagrara of, 133 ^ Heat coagulation, 46 — formation of, by liver, 451 — loss of. regulation of, 496 — production of, regulation, 496 Heat stroke, 494 Helicotrema, 048 Helmholtz side-wire, action ot, 538 Helweg tract, 670 Henle loop, 474 Henry's law, 19 Heredity, 778 Hering theory of colour vision, 625 Heteronomous vision, 632 Heterophoria, 631 Heterotyjie mitosis, 762 Hexoses, 59 Hibernation, 738 Hill's blood-gas jiump, 260 — cerebral pressure gauge, 240 — colour vision apparatus, 628 — pocket sphygmometer, 189 Hippurie acid, 462 Histidin, 42 Histones, 47 Homonomous vision, 632 Hormone reHex, 368 Hormones, 394, 397, 503 Horns, growth of, effect of castration on, 506 Horopter, 631 — vision, 633 Horse blood, analysis of, 81 crystals of, oxyhfemoglobin from, 91 Hunger, sensation of, 660 Hiirthle's spring manometer, 188 Hydrogen generated from a Kipp's appara- tus, 18 Hyperglycfemia, 427 Hypermetropia, 010 Hyperphoria, 631 Hyperpno-a, 299 Hypersusceptibility, 111 Hypertonic solution, 24 Hypnosis, 737 Hypoglossal nerve, 691 Hypotonic solution, 24, 26 Hypoxanthin, 50 Imbibition, phenomena of, 31 Immune body, 109 Immunity, 105, 107 Impulse, nerve, 7 Incus, 644 Indican, 463 Induction coil, connections of, 535 Infant feeding, 360 — newborn, nutrition of, 357 Inorganic compounds. 33 Inotropic fibres, 173 Insemination, process of, 770 Internal capsule, 709 — secretions, 503 Intestines, arteries of. gas bubbles in, 309 — bacteria of, 403 — large, 402 function of, 402 — — movements of, 418 — movements of, record of, in cat, 512 — pendulum movements of, 410 — peristaltic contraction of, 417 INDEX 793 Intestines, small, digestion in, 391 functions of, 401 movements of, 415 segmentation of, 415 segmenting its contents, 411 — veins of, gas bubbles in, 309 Iodides, secretion of, 377 Iodine value of fat, 55 Ions, 28 Iris, 604 — function of. 604 — nerve supply of, 605 Iron, lack of, 336 In-adiation, 634 laocholesterol, 58 Isotonic solution, '24 Jacquet's sphygmograpii, imlse tracini; by, 215 Jecorin, 58 Jugular bulb, position of, 213 — pulse, waves of, 214 Juices, activation of. 369 — digestive, 369 — pancreatic. 396 Katabolism, 441 — of dextrose, 426 — of fat, 440 — of plasma, 85 Kata thermometer, 500 Katelectrotonic current, 5S3 Kathode, region of, stimulation in, 583 Ketones, 35 J Kidney, arterial pressure of, 247 — blood-sup[>ly of, 474, 475, 47> — circulation in, 247 — functions of. 453, 478 — of cat, decompressed, 310 — schema of, 223 — secretory function of, 481 — tubule of, minute structure of, 474 resorption by. 481 secretory function of, 4^1 Kipp's apparatus, hvdrogen generated from, 18 Kjeldahl's method of analysis of urine, 455 — process, 329 Krause's end-bulbs, 586 Krogh's microtonometer, 270 Labyi'inth, membranous, 647 — of pigeon, effect of destruct'on of, 657 Labyrinthine sensations, 655 Lachrymal glands, 600 Lactose, 65, 469 Langerhans, isk-t of, from pancreas of dog, 513 Laryngoscope, 740 Larynx, 277, 740 — examination of. 741 — muscles of, 743 — nerve-supply of, 295 — stimulation of, 295 — view of, 742 — vowels produced by, 745 Lecithins, 56 — metabolism of, 441 Lens, 605 — achromatic, 609 — cardinal points of, 609 — convexity of, 614 Lenticular nuclei, 715 Leucin, 40 Leucocytes, 97 — migration of, 99 Leucocytosi^, 99 Lever action, kinds of, 526 — simple, with after-loading screw, 540 LcTOlose, 62, 469 Ligaments, suspensory, 605 Light, effects of, on retina, 618 — - phenomena of, 608 Limbs, circulation of, 243 Lipase of gastric juice, 387 Lipoids, 53, 56 — lack of, 336 — of plasma, 84 Lipolytic enzymes, 71 Liquids, diffusion in, 21 Lissauer, marginal tract of. 668 Liver, circulation in, 246 — fat of, storage, 448 ' — function of, 447 protective, 450 — glycogenic function of, 447 — heat formation by, 451 — protective function, 450 — venous reservoir of, 451 Load, effect of, in muscle, 545 Local sign of touch, 589 Locke's' solution, rabbit's heart perfused with, 159 Locomotion. 525 Loewenthal tract, 670 Lubrication, forms of, 6 Lucas, moist chamber and electrodes, 563 Lungs, blood-pressure of, 279 — circulation of, 236 — diffusion of gases within, 270 — lobe of, small, volume of, 279 — preparation of, diagram of apparatus for, 164 — right, resjiiratory movement of root, 287 — surface relations of, 153 — ventilation of, 292 — volume of, 279 Lymph, 250 — composition of, 251 — formation of. 252 — movement of, 254 Lymphocytes, 97 Lysin, 42 Mackenzie's polygraph, 212 Macula of mouse, 656 Magnesium, sulphate of, injection, Tiaube- Hering curves after, 301 Malleus, 644 Maltose, 65 Mammals, circulation in, course of, 142 794 A TEXTBOOK OF PHYSIOLOGY Man, co)iipros8ioii oU'ects on, 308 — decompression t'H'ccts on, 308 Manometer, Hiirthle's spring, 188 — niercmia], arrangement of, for record- ing blood-pressure, 187 Manubrium sterni, 28.') respiratory movemeuts of, 286 Marclii method of staining, 577 Marching, 499 Mastication, movements of, 407 Meat, 354 — cooked, composition and value of, 352 Meatus, external auditoiy, stimulation of, 295 Medulla oblongata, 688 formation of, 688 functions of, 695 section of, 690, 691 Medullated nerves, 570 Medusa, tentaculocyst of, 654 Meiotic division of cells, 762 • Meissner's corpuscles, 586 Membranes, semi-permeable, 21 action of, 25 Mesencephalon, 706 Mesonepliros, 475 Metabolism, 325 — during starvation, 333 — methods, 325 — of carbohydrate, 426 — of fat, 436 — of lecithin, 441 — of nuclein, 443 — of protein, 421 — protein excess -with, 339 — special, 421 — varying conditions of, 341 Metanephros, 474 Metaprotein, 43 Metaproteins, acid and alkali, 50 Methfemoglobin, 93 Microscope, projection, side elevation of, 562 Microtonometer, Krogli's, 270 Micturition, act of, 483 Mid-brain, 706 — red nuclei of, 707 — section of, 707 Milk, 353 — composition and value of, 349, 352 — fats of, 353 — how from nipple of cat, 522 — human, colour of, 359 composition of, 359 — secretion of, 358 Mind, 732 Mineral salts, lack of, 335 Mitosis, 757 — heterotype, 762 Molecular complexity, law of, 16 Molisch's test, 62 Monakow tract, 670 Monocarboxylic acid, 36 Monosaccharides, 59 Moore's test, 60 M otion, tissue of, 525 Motor area, efl'ects of ablation of, 721 ■ lamination of, 725 — decussation, 670 — impulse, velocity of, 581 Moutli, digestion in, 371 — shape of, in sounding vowels, 745 Movement, mechanism of, 525 Movements of body, level' principles, 525 — of heart, 144 in situ, 151 Miiller's law, 585 Muscarine, injection of, effect upon dog's heart, 175 Muscle, activity of, 546 — arteriole, pressor alferent impulses affecting, 231 — board, 539 — cardiac, 532 — change in form of, 539 — chemical changes in, 552 induced l)y activity, 557 — chemical constitution of, 555 — chemistry of, changes in, 555 — ciliary, 603 — contraction of, 539 apparatus for recording, 540 conditions affecting, 545 Frog's gastrocnemius, 541 period, 543 period and movements of levers on 544 superposition, 548 • — differentiation of, 530 — electromotive properties of, 559 — excitability of, 533 — extensiljility of, 532 — fatigue of, 546 — inhibition of, 678 — injuries of,, by electricity, 560 — irritability of, 533 — laryngeal, 743 — lateral cricoarytenoid, 743 — of rabbit, contractions of, 541 — physical properties of, 530, 532 — posterior crico-arytenoid, 742 — reciprocal excitation, 678 — i-elation of, 545 ' — rhythmicity, 558 — section of sucker catastonius, 531 — smooth, 532; 558 — spontaneous movements of, 551 — stimulation of, 561 — stimulus of, 545 — structure of, 530 — thermal changes in, 552 — time of contraction, 542» — tonus, 558 — unloaded, contractions of, 542 Muscular activity, mechanism of, 554 — ^ tissue, 5 — " tone," 551 Mritton, composition and value of, 348 — fat, melting-point of, 438 Myelination, evidence of, 727 Myogen, 555, 556 — fibrin, insoluble, 556 INDEX 795 Myopia, 616 Myosin, 555 ilyosinogei], 555, 556 JU'ostroniin, 556 ^lyxcedema, case of, 517 Narcosis, 737 Nature, nitrogen in, circulation of, 259 Nerve cells. 570 — crural, 244 — eighth, 697, 699 — electromotive properties of, 559 — endings, effector, in muscles of lizard, 574 — fibres in muscle spindle, 658 medullated, from a mammal, 571, 572 physiology of, 579 regeneration of, 578 — impulse, 7 — regeneration of, 576, 578 — roots, "Walleriau degeneration of 663 — stimulation of, 176, 561, 573, 579 — supply of iris, 605 Nerves, afferent, 245, 573 — cardiac, 171 of dog. 172 of frog, 171 — cranial, 690 nuclei of, 699 — depressor, effects of stimulation, 518 — efferent, 573 — iris, 605 • — lai-yngeal, 295 — medullated, 570 — non-meduUated, 570 — seventh, 698 — sixth, 700 — spinal accessory, 691 mixed, 749 — splauchnic, 429, 510 — tenth, origin of, 694 — trigeminal, 700 — twelfth, origin of, 694 — vagus, 173, 241, 298, 691 — vaso-motor. 229, 242, 246 Nervous centre, connections of, in secre- tion of gastric juice, 374 of saliva, 374 — conduction, 574 ■ — elements of vertebrate heart, 123 — impulse, rate of transmission, 580 — structures, stippled, 567 — system, 569 autonomic, 748, 750 stimulus, 7 sympathetic, aiTangement of, 748 Neural arcs, 671 Neurogenous glycosuria, 432 Neuroglia, 572 Neuron, 569 — function of, 575 Neuro-tendinous nerve end -organ in rabbit, 659 Nicotine, action of, 229 Night-blindness, 623 Nissl's granules, 569 Nitrogen in blood, 263 — of urine, 455 Nitroxyhiemoglobin, 92 Non-goitrous cretins, 516 Nose, function of, 277 Nuclein, metabolism of, 443 Nucleoproteins, 48 Nucleus of Deiters, 698 — pontis, 698 Nutrition, effect of vitaniine on, 337 — of heart, 158 Nuts, composition and value of, 349 Nylander's test, 61 for sugar in urine, 467 Obesity, 442 Odour-producing glands, 6 Olein, 54 Olfactometer, 597 Olfactory epithelium of fowl, 596 Olivo-spinal tract, 670 Ontogeny, 3 Ophthalmoscopes, 639, 640 Opsonins, 109, 110 Optic fibi'es, relations of, 713 — thalamus, 710 Organic compounds, 34 Osmosis, phenomena of, 22 Osmotic pressure, 21, 22 of blood, 80 Osseous labyrinth, 646 Ovary, 506, 767 — foital, 767 Ovum, human, 768 development of, 774 — embedded in uterus, 776 — embedded in wall of uterus, 775 — implantation of, 773 — maturation of, 764 — morula from, 772 — of bat, 771 — of cat before maturity, 9 — of toxopreustes, 759 — segmentation of, 773 Oxalates, 461 Oxblood, analysis of, 81 Oxidases, 73 — action of, 444 Oxygen, atmospheres of, lung exudation in, 303 — capacity of blood, 264 — consumption of, relationship of arterial pressure to, 169 relationship of pulse to, 169 — ■ curves of human blood, 266 — excess of, effects, 303 — in blood, 263, 275 — percentage of, in respiration, 293 — use of, in man, 342 — want of, effects, 304 Oxyhaemoglol^in, crystals of, from horse blood, 91 Oxyproline, 42 679 A TEXTBOOK OF PHYSIOLOGY Paciuiau corpuscle, 586, 587 Pain, 661 — referred, and counter-irritation, 661 — sensation of, 591 Falniitin, 54 Pancreas, 511 — nuclease of, 443 — secretion of, 395 Pancreatic enzj-nics, activation of, 398 — glycosuria, 432 — juice, 396 digestive action of, 399 flow of, 368 mechanism of secretion, 397 Paradise fish, gas-secreting cells of, 271 Paramyosinogen, 555 Parathyroid glycosuria, 434 — of dog, after thyroidectomy, 515 — of normal dog, 5T4 Parathyroids, function of, 512 Pars plana, 603 — plioata, 603 Parturition, 775 Pawlow's method of establishing a gastric fistula, 381 Pentosans, 63 Pentose, 469 Pentoses, 59, 63 Peptic digestion, 385 Peptones, 40, 43, 51 Pericardial fluid, 254 Perilymph, 646 Perimeter, 638 Perimetric chart of right eye, 639 Peristalsis, true, 417 " Peristaltic rush," 417 — wave of small intestine, 417 Perspiration, 488 Phakoscope, 613 — rays of light in, 613 Pharynx, 277 Phenyl alanin, 41 Phenylhydrazine test, 61 Phloridzin glycosuria, 433 Phosphate crystals, 471 — of calcium, 471 Phosphates. 464 — distribution of, 33 — lack of, 336 Phosphatides, 56 Phosphoproteins, 48 Photohaematochonieter, Cybulski's, 205 Phototaxis, 12 Phylogeny, 2 Physico-chemical physiology. 17 Phytocholesterol, 58 Pigments, bile, 393 Pineal body, 524 Pituitary body, 521 functions of, 522 of adult monkey, 520 — glycosuria, 434 Placenta, 774 — blood space, formation of, 776 — formation of, 777 Plant life, cycle of, 258 Plasma, 82 — carbohydrate of, 85 — fibrinogen of, 84 — katabolism of, 85 — lipoids of, 84 — proteins of, 83, 424 — salts of, 85 — serum albumin of, 84 — serum globulin of, 83 Plasmolysis, 24 — effect of, in Tradescantia discolor, d Plethysmograph and piston recorder 230 Plethysmographic; method, velocity flow by, 206 Pleura, fluids of, 254 Poisons, vegetable, hceniolysf produced by, 107 Polarimetric tost, 62 Polygraph, 213 — Mackenzie's, 212 Polypeptides, 40, 43, 45 Polysaccharides, 65 — reactions of, 66 Pons varolii, 688, 696 section of, 696 Pork, composition and value of, 348 Portal circulation, 246 Post-dicrotic wave, 215' Posterior longitudinal bundle, 695 Postganglionic fibres, 750 Postirre, effect of, on circulation, 194 — erect, 527 Precipitins, 111 Predicrotic wave, 215 Preganglionic fibres, 749 Pregnancy, serum test for, 777 Presbyopia, 616 Pressure, arterial, 186 — bottle, arrangement of, for recording blood-pressure, 187 — osmotic, 21, 22 — sensations of, 588 Pronephros, 474 Proprio-ceptivc mechanism, 654, 659 Prostate gland, 506 Protamines, 47 Protein decomposition, 403 — digestion of, 385 — - digestion, products of, 424 — foods, cost of, 348 — katabolism, 328 Proteins, 39, 43, 428 — chemical properties of, 45 — classification of, 47 — compound. 48 — constitution of, 39 — derived, 50 — excess of, in metabolism, 339 — fat from, 439 — in urine, 465 — metabolism of, 421 — of plasma, 83 — physical properties of, 45 — required for weight atdifterent ages,362 Proteolytic enzymes, 70 Proteoses, 40, 43, 51 INDEX 7i)7 Protopatliic sensibility, 591, 592 Protoplasm, 8 — luovenieiits of, 11 Ptyaliii, actiou of, 378 Pulmoiiarv circulation, 236 Pulse, 211 — curve, arterial, 215 — frequency of, duration of systole and diastole with, 168 — intluenceof abdominal breathing on, 191 chest on, 191 — investigation of, by spliygmographs, 212 — rates, average of, 216 — tracing of. by Jacquet's sphygmograph, 215 — venous, 213 — wave in the arterial system, 217 Pulses, 355 Purin bases, 49 — bodies, 49, 460 Purkinje, cells of, 703 Putresein, 403 Pvrimidin bases, 49 Pyrolin, 42 Rabbit, siuu- auricular node of, effect of excision, 140 Rabbit's heart, a. v. bundle cut, stimula- tion of right vagus nerve, 136 Reaction time, 731 — — apparatus *or determination of, 732 Receptors, lOS, 574 — mechanism of. 585 — of cutaneous .sensation, structure of, 585 Rectum, showing pelvi-rectal flexure, 419 Reflex arc, 574 simple, 575 — centre, spinal cord as, 674 Reflexes, 674, 676, 678, 680, 682, 684 — tendon, 684 Refraction, 610 Regeneration, peripheral, 578 Renal epithelium of frog, 573 — tubules, development of, 473 resorption by, 481 secretory functions of, 481 Rennet, action of, 387 Reproduction, 755, 760 Reproductive organs, female, 767 male, 764 Residual air, 280 Respiration, 192, 257 — air changes in, 293, 312 — apparatus. Haldane-Pembrey, 318' — artiHcial, 323 Schiifer's method, 322 Sylvester's method, 322 vivator aj)paratus for, 324 — chamber for man, 331 — Cheyne- Stokes, 299, 300 — effect of emotion on, 202 — interna], 320 — mechanism of, 276 — record of, in cat. 323 — regulation of, 289 — tissue, 320 Respiration, tracing of, 304 Respiratory centre, 294 — exchange, determination of, 317 increase of, by muscular work, 319 internal, eflect of activity upon, 321 — function of the skin, 489 — quotient, 319 Retina, 606 — eftects of light on, 618 — functions of, 619 — human, diagram of, 606 — images on, 615 — of frog, 620 — of rabbit. 620 — structures of, 606 Retinal currents, 565 Retinoscopy, 617 Retz cell from human cerebral cortex, 571 Rheocord, principle of, 535 Rhinencephalon, connection of, 714 Rhj-thmic automaticity of heart, 127 Ribs, first pair of, 285 — lower-, movement of, 287 — movement of, 285 — respiratory movements of, 286 — upper, movement of, 286 Rice, polished, 336 Rigor mortis, 557 Ringer-solution, 477 — rabbit's heart perfused with, 160 Rubro-spinal tract, 670 Ruffini's organs, 586 Running, 528 Saccharose, 64 Sacral autonomic system, 751 Saliva, 371 — composition of, 372 — paralytic secretion, 375 — quantity of, 373 — secretory pressures of, 376 .Salivary glands, 565 — — circulation of, 243 — — schema of, 223 Salkowski's test, 58 " Salt " glycosuria, 435 — solutions of, solubility of gases in, 20 Salts, inorganic, 394 — of plasma, 85 — organic, 392 — proportion of, in blood, 266, 267 Saponification of fat, 53 Sartorius muscle, curve of, 549 excursion to, 564 fatigue curves of, 546 nervous impulse in, 581 of frog, spontaneous movements in, 549 stimulation of, 550 Scala media, 648 Schiifer's method of artificial respiration. 322 Sciatic nerve of kitten, regeneration of, 577 Sclera, 602 Scleroproteins, 48 793 A TEXTBOOK OF PHY810L0GY Scratch reflex, 676, 677, 678, 680 receptive field for, 67 f' Sebaceous glands, 487 Secretion, 368 — meclianism of, 358 Segmentation of ovum, 773 — rli_ytliniic, 414 Semicircular canals, 655 Seminal fluid, 766 Sensations, cutaneous, 585 Sensory mechanism, localization of, 727 — path from peripheral nerve. 711 Sera, foreign, liwniolysis by, 106 Serin, 40 Serum allmmin of plasma, 84 — globulin of plasma, 83 — test for pregnancy, 777 Seventh nerve, function of, 699 origin of, 698 ' Sex, determination of, 781 — diet under various conditions, 356 Sexual characteristics, 504, 505 Sexual life, female, 769 Shellfish, composition and value of, 348 Sigliing, 296 Sinu-auricular node, 119 Sixth nerve, origin of, 698, 700 Skiascopy, 617 Skin, absorption by, 489 — current, 566 — effect of atmosphere ujwn, 499 — electric currents of, 564 — function of, 485 of pigment, 490 — parts of, 485 — respiratory function of, 489 — section of, 486 — sensations, 585 Sleep, 735 Smell, 593 — excitation of, 597 — receiving stations for, 729 — receptor mechanism of, 596 — sense of, investigation of, 597 ■ paths in connection with, 715 Snake venoms, hfemolysis by, 107 Snellen's test-types, 637 Soaps, 55 Sodium urate, 459, 471 Solubility of gases, 2 3 Solutions, hypertonic, 24 — phj'siological, 26 Sound, 650 — experimental production of, in sheep's trachea, 740 — intensity of, 650 — pitch of, 650 — production of, 739 — quality of, 650 — Mave, formation of, 651 Sounds of the heart, 154 Spectra, blood, 93 Speech, 729 — centre of, 731 — production of, 739 Spermatozoon, 765, 766 Spherical aberration of lens, 609 Sphingomyelin, 58 Sphygniograph, Dudgeon, suspension method of using the, 211 — investigation of, pulse by, 212 — Jacquet's, pulse tracing by, 21 5 Sphygmometer, armlet, 188 " — Leonard Hill pocket, 189 Sphygmoscope, 188 Spinal accessory nerve, 691 — arc, 672 — bulb, white matter of, 694 — cord, 662 • — ■ — -as reflex centre, 674 commissural, fibres of, 670 conductor, impulses of, 672 effect of, transverse section through, 673 embryonic, 664 exogenous tracts of, 667 functions of, 672 posterior columns of, necrotic areas in, 311 reflex action of, 674 sections of, 665, 666 structure of, 663 tracts. 666 tracts from brain to, 669, 670 tracts of from posterior root ganglia, 668 — nerve, mixed, arrangement of, 749 Spino-tlialamic tract, 670 Spirits, alcohol percentage of, 365 Spirometer, 280 Splanchnic area, 198 — nerves, effect of stimulation of, 429, 510 — organs, 246 Spleen, 247 — function of, 447, 451 Stapedius, 646 Stapes, 644 Starch, action of gastric juice on, 387 Starches, 65 Starvation, metabolism during, 333 Stearin, 54 Stereoscope, 635 Stimulus of muscle, strength of, 545 — of nervous system, 7 Stomach, absorption in, 388 — contents, examination of, 388 — digestion iii, 379 — digestive processes in, 385 — movements of, 411 — of cat, changes in shape during diges- tion, 407 digestion in, 406 shadows of contents after feeding, 411 — outline of, 379 — position of, 380 — why not itself digested, 388 Stress, lines of, 758, 759 Stromuhr, 203, 204 Strychnine convulsions in frog, 684 Stylonychia, enucleated, fragments of, 700 Sulilingual gland, 374 INDEX 799 Submaxillary glaud, o74 Succus entericus, 400 mechanism of secretion, 400 use of, 401 Sucker catastonius, muscle of, 531 Sucrolytic enzymes, 71 Sugar, action of gastric juice on, 387 — concentration of in arterial blood, 429 in urine, 429 — content, in glycosuria, 431 — in urine, 267 — splitting of, 430 Suggestion, effect of, 234 Sulphates, 462 — inorganic, 462 — organic, 463 Sulphur, neutral, 462, 463 Summation of muscle, 547 Superior olive, 699 Suprarenal body, 508 of dog, section of, 507 Surface tension in colloids, 31 Susjwnsory ligament, 605 Swallowing, mechanism of, 408 — nervous mechanism of, 410 — shadow in cesophagus after, 410 Sweat glands, 487 Sylvester's method of artificial respiration. 322 Synapse, 572 Systole, 144 . — duration of, table showing pulse- frequencies, 170 with ditferent pulse frequencies, 168 Systolic output and work of heart, 163 Tactile sensations, 589 Taste, 593 — bud in tongue of man, 594 — effect of, 233 — nerve distribution for, 595 • — receiving stations for, 729 — receptor mechanism of, 593 — sensations, apparatus for testing, 594 Temperament, diet under various condi- tions, 356 Temperature, body, 492 — effect of, on muscle, 545 upon gastrocnemius muscle, 543 — external, effect of raising, 497 metabolism increased by, 343 — normal, 492 — regulation of, 495 — sensations of, 590 — variations of, 493 Tendon reflexes, 684 Tensor tympani, 646 Testes, 505, 765 Toet-types, Snellen's, 637 Tetanus, 550 — composition of, 548 Thalamo-spinal tract, 670 Thalamus, function of, 710 Thermometer, Kata, 500 Thermopile, double, 553 Thermopile, single-pair, connected to galvanometer, 552 Thermotaxis, negative. 12 Thirst, sensation of, 660 Thoma-Zeiss hemacytometer, 87 Thorax, compression of, 163 — movements of, in respiration. 306 Thrombin of blood, 102 Thymus gland, 519 — development of, 513 — function of, 520 — gland of monkey, 519 Thyroid, 742 — ■ development of, 513 — function of, 512 — glycosuria, 434 — of normal dog, 514 Tidal air, 278 Tissues, combination of, 5 — formation of, 3 — gases in, pressure of, 269 Toad, auricle and ventricle of record of contraction, 128 Tone, muscular, 551 Tonometers, 264 Topler pump for blood-gas analysis, 261 Torpedo Ocellata, auricle-ventricle of, 130 Touch, reaction time to, 733 — sensation of, 586. 588 Toxins, 108 Toxophor, 108 Trachea, 277 Tracts, spinal cord, 666 Transfusion in hemorrhage, 228 Transport, mechanism of, 115 Traube-Hering curves, 301 Trigeminal nerve, 700, 701 Trioses, 59 Tripeptide, 45 Trommer's test, 61 — — for sugar in urine, 467 Trophoblast, 773 Trypsin. 399 Tryptophan, 42 Tympanic membrane, 644 view of, 645 Tyrosin, 41 Ultra-violet light, lesions produced oit rabbit's ear by, 13 yeast cells photographed by, 10 Umbilical vessels, 248 Urea, 456 — formation of, 448 — nitrate, 457 — oxalate, 457 Ureometer, 458 Ureters, passage of urine along, 482 Uric acid, 444, 458, 471 — — crystals, 460 formation of, 448 source of, endogenous, 444 ' — exogenous, 444 Urinary deposits, 470 Urine, 453 — abnormal constituents of, 465 800 A TEXTBOOK OF PHVSJOLOCY Urine, analyses of, 155 — bile in, 469 — Wood in, 46ti — - colour of, 454 — - composition of, -155 — formation of, rate, 429 — nitrogen total of, 455 — nitrogenous constituents of, 455 — passage of, through ureters, 482 — proteins in, 465 — secretion of, 473 — sugar in, 431, 467 — transparency of, 454 Uriniferous tubules, course of, 475 Urobilin, 454 Urochrome, 454 Uroerythrin, 455 Uterus, ovum embedded in, 776 Vagi, intluence of, 296 Vago-synipathetic, excitation of, 170 — stimulation of, contraction of frog's heart showing, 169 Vagus, in cat, 300 — influence of, upon respiratory move- ments, 296 Vagus nerve, 691 electrical changes in, 298 in rabbit, dissection of, 176 inter-auricular septum of, 124 periphereal end of, effect of stimu- lating, 241 excitation, 173 stimulation of, in cat's heart 175 Valin, 40 Vascular system, changes of i)ressure in, 227 Vaso-constrictor nerves, 233, 238, 242 Vaso-dilator nerves, 242 Vaso-motor centie, reflex action, 233 — mechanisms, 246 — nerves, 229 distribution of, 231 Vegetables, composition and value of, 350 — green, 355 Vegetarianism, 364 Veins, blood-flow in, rate of, 226 — blood-pressure in, 225 — blood-velocity in, 225 — structure of, 125 — velocity of flow in, 208 — venous pressure of, 226 Velocity ot blood, in veins, 225 — of biood-flow, 203 Venous pulse, 213 Venous reservoir of liver, 451 Venous system, pressure in, 226 Ventilation, principles of, 312 Ventral spino-cercbellar tract, 669 Ventricle, right, of calf, 121, 122 Veiatrin curve, 543 Vertebrate heart, type of, 118 Vestibule, 647 V'estibulo-spinal tract, 670 Viscosity of blood, 80 Vision, binocular, 630 — near point of, 615 ■ — paths concerned in, 712 — reaction time to, 733 — receptor mechanism of, 599 — sense of, 599 Visual angle, 611 — area, cell lamination of, 726 — judgments, 633 — tract, 712 Vital force, 15 Vitamines, effect of, on growth, 338 on nutrition, 337 " — lack of, 336 Vivator apparatus for artificial respira- tion, 324 Vocal cords, positions of, 744 Volatile fatty acids in fat, 55 Vol vox globator, colony of cells, 4 Vomiting, 415 Vowels, produced by larynx, 745 — shape of mouth in sounding, 745 Wagner's hammer, action of, 537 Walking, 528 Wallerian degeneration, 576 • in cat, Marchi juethod of staining. 577 Warm-blooded animals, 495 AVater, 33 — diffusion of gas through, 20 — lack of, 334 — vapour, 498 Weber's law, 585 Weaning, 362 Weight, at different ages, protein for, 362 Wernicke's area, 730 Wheel for mixing colours, 623 Wines, alcohol percentage of, 365 Work, diet under various conditions of, 356 — inetabolism increased during, 343 Woultfc's bottle, 18 Xanthin, 50 Yawning, 296 Yeast cells, jihotographed by nltravi(jlet light, 10 Young-Helmholtz theory of colour vision, 625 Zollner's lines, 636 Zymogen, 369 lilLLINO AiW SONS, LTD., PRINTERS, Gl'IIDFORD, ENOLAND QP34 F59 Copy 1 Flack 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