PHYSIOLOGY FOE DENTAL STUDENTS PHYSIOLOGY FOR DENTAL STUDENTS BY R^GV PEARCE, B.A., M.D., Associate in Physiology, Western Reserve University AND ^ J. J. R. MACLEOD, M. B., D. P. H., Professor of Physiology, Western Reserve University FIFTY-NINE ILLUSTRATIONS, INCLUDING TEN COLOR PLATES I ST. LOUIS "V") C. V. MOSBY COMPANY 1915 s COPYRIGHT, 1915, BY C. V. MOSBY COMPANY I'ress of C. V. Aloxlm C'ln St. Louis PREFACE. A knowledge of the fundamentals of human physiology is essential in the training of the dental student, because physiology constitutes, along with anatomy, the basic science upon which all medical and surgical knowledge is founded ; and dentistry is a highly specialized department of surgical practice. To oper- ate on the teeth without knowing something about the physi- ology of the body as a whole, would reduce the dentist to the level of a craftsman who, although perhaps very highly skilled in his technical work, was yet quite ignorant of the nature of the machine upon a part of which his work had to be done. But there are also practical reasons why the dentist should be familiar with physiology, for good health, and not good looks alone, depends very largely on sound teeth. The neglect of this fact may cause disturbances in bodily functions to which, at first sight, the teeth may apparently bear very little relation- ship ; thus, extreme emaciation, with its consequent lowering of the normal resistance of the body towards disease and infection, is well-known to be frequently due to no other cause than some abnormal or pathological condition affecting the teeth ; and, on the other hand, this very condition itself may become intract- able to the most skilled dental treatment and hygiene, if meas- ures are not taken at the same time to improve the general health. Although it is obviously beyond the province of the dentist to undertake the treatment of these general conditions, yet it is most important that he should be sufficiently familiar with the normal functioning of the human body to be able to recognize what is really at fault. A knowledge of the laws of nutrition and dietetics must therefore form a most important part of every course in dentistry, and these have received particular attention in this book. The physiology of the digestive system, of the circulation of the blood and of the nervous system is scarcely less important. The pain and shock produced by a dental operation may cause considerable disturbance in the action of the heart or in the dis- tribution of blood in the body, and this disturbance, especially VI PREFACE. in cases in which the heart and the blood vessels are diseased, may become so pronounced as to render a certain amount of medical skill necessary. Or if, to avoid such pain, it be deemed advisable to administer anesthesia, then must the dentist be constantly on his guard that no more than the proper amount of anesthetic is given, which he can- do intelligently only by observing the condition of the nervous and circulatory systems. Besides knowing something about the physiology of the body as a whole, the dentist must be particularly familiar with the local physiology of the mouth, such as the finely coordinated nervous mechanisms involved in the acts of mastication and swallowing and the secretion of saliva. He must understand the nature of the sensations of the teeth and buccal mucosa, and be on the lookout for any lesions of the cranial nerves that sup- ply the muscles and other tissues adjacent to the mouth cavity. The chemistry of the saliva has demanded special attention because of the very interesting scientific investigations which are being prosecuted 'regarding the nature of the undoubted relationship that exists between changes in the saliva and the in- cidence of dental caries. To adequately describe the present status of this work we have found it necessary to devote some space (in the. second chapter) to a review of the main physico- chemical principles which may regulate the reaction and neu- tralizing power of saliva. Whenever the occasion presented itself to do so, we have given a brief description of the general nature of the diseases in which dental involvement is possible. A few simple, but very instructive, laboratory demonstrations are described in an appendix at the close of the book. We have found that such demonstrations furnish an invaluable aid in the teaching of the subject. To facilitate a clear understanding of the subject, diagrams have been used whenever necessary, and many of these have been specially drawn for the work. To Prof. T. Wingate Todd and Mr. P. M. Spuruey, the authors are deeply indebted for the valuable assistance which they gave in the preparation of these. R. G. PEARCE. J. J. R. MACLEOD. CONTENTS. INTRODUCTORY: THE CHEMICAL BASIS OF THE CELL. CHAPTER I. Page The Scope of Physiology — The Physico-chemical Basis of Life — The Chemical Basis of Animal Tissues — Water — Proteins — Lipoids — Carbohydrates 17 CHAPTER II. THE INFLUENCE OF PHYSICO-CHEMICAL LAWS ON PHYSIOLOGICAL PROCESSES: ENZYMES. Properties of Crystalloids — Osmotic Phenomena in Cells — Reac- tion of Body Fluids — Colloids — General Nature of Enzymes or Ferments ' 26 CHAPTER III. DIGESTION: NECESSITY AND GENERAL NATURE. Digestion in the Mouth — The Salivary Glands — The Nerve Supply of the Salivary Glands — The Reflex Nerve Control of the Sali- vary Secretion — The Normal Stimulus for Salivary Secretion (Direct and Psychological) — General Functions of Saliva 37 CHAPTER IV. DIGESTION: THE CHEMISTRY OF SALIVA AND THE RELATIONSHIP OF SALIVA TO DENTAL CARIES. Organic and Inorganic Constituents — The Reaction of Saliva — The Method of Measurement of Neutralizing Power of Saliva — The Deposition of Tartar and Calculi 46 CHAPTER V. DIGESTION. Mastication — Deglutition or Swallowing — Vomiting 53 vii Vlll CONTENTS. Page CHAPTER VI. DIGESTION: IN THE STOMACH. Mechanism of Secretion of Gastric Juice — The Active Constituents of Gastric Juice — The Movements of the Stomach — The Open- ing of the Pyloric Sphincter — Rate of Discharge of Food from the Stomach '. 60 CHAPTER VII. DIGESTION: IN THE INTESTINE. Secretion of Bile and Pancreatic Juice — Functions and Composi- tion of Pancreatic Juice and Bile — Chemical Changes Produced by Intestinal Digestion — Bacterial Digestion in the Intestine — Products of Bacterial Digestion — Protection of Mucous Mem- brane of Intestine Against Autodigestion — Movements of the Intestines — The Absorption of Food — Resume of Actions of Digestive Enzymes 71 CHAPTER VIII. METABOLISM: ENERGY BALANCE. Introductory — General and Special Metabolism — Energy Balance — Caloric Value of Foods — Basal Heat Production — Influence of Food, Muscular Work, Atmosphere, and Size of Body 83 CHAPTER IX. METABOLISM: THE MATERIAL BALANCE OF THE BODY. Starvation-Nitrogen Balance — Protein Sparers — The Irreducible Protein Minimum — Varying Nutritive Values of Different Proteins 91 CHAPTER X. THE SCIENCE OF DIETETICS. The Proper Amount of Nitrogen — Chittenden's Experiments — The Most Suitable Diet for Efficiency — Chemical Composition, of the Common Foodstuffs 99 CONTENTS. ix Page CHAPTER XI. SPECIAL METABOLISM. Special Metabolism of Proteins — Urea — Ammonia — Creatinin — Purin Bodies — Relative Importance of Proteins, Fats and Carbohydrates in Metabolism 108 CHAPTER XII. SPECIAL METABOLISM. Metabolism of Fats — Metabolism of Carbohydrates — Metabolism of Inorganic Salts — Vitamines 115 CHAPTER XIII. THE DUCTLESS GLANDS. Introduction— Thyroid and Parathyroid Glands — Adrenal Glands — Pituitary Gland— Spleen— Thymus Gland 124 CHAPTER XIV. ANIMAL HEAT AND FEVER. Animal Heat — Normal Temperature — Factors Concerned in Main- taining the Body Temperature — Regulation of Body Tempera- ture— Fever 134 CHAPTER XV. THE BLOOD. Introduction — Physical Properties — The Corpuscles — Erythrocytes — Haemoglobin — Enumeration of Blood Cells — The Origin of the Erythrocytes — The White Cells — Leucocytes — Lympho- cytes—Functions of the White Cells— The Blood Platelets— The Blood Plasma 140 CHAPTER XVI. THE BLOOD. The Defensive Mechanism of the Blood — Coagulation of the Blood — Antibodies in the Blood— The Process of Inflammation — Toxins — Antitoxins — Ehrlich's Side Chain Theory — Anaphy- laxis — Phagocytosis — Opsonins 147 X CONTENTS. Page CHAPTER XVII. THE LYMPH. Lymph Formation — Lymphagogues — Lymph Reabsorption — The Movement of Lymph 155 CHAPTER XVIII. THE CIRCULATION. Introduction — The Heart — Anatomical Considerations — Physiologi- cal Properties of Heart Muscle — Character of Cardiac Con- traction— The Sequence of the Heart Beat — The Action of Inorganic Salts on the Heart — The Vascular Mechanism of the Heart — Definition of Terms — Events of the Cardiac Cycle — The Heart Sounds — Diseases of the Cardiac Valves 159 CHAPTER XIX. THE CIRCULATION. The Blood Flow Through the Vessels — The Part the Heart Plays— The Part the Vessels Play — Arterial Blood Pressure — Factors That Maintain the Blood Pressure — Velocity of Blood Flow— The Return of the Blood to the Heart — Circulation Time — The Effect of the Circulation of the Blood Itself — The Pulsa- tile Acceleration of the Blood Flow — The Pulse — The Circula- tion in the Lungs 171 CHAPTER XX. THE CIRCULATION. The Influence of the Nervous System on the Circulation of the Blood— The Nervous Control of the Heart— The Cardiac Nerves — Accelerator Nerves — Inhibitory Nerves — Interrelation of Inhibitory and Accelerator Nerves — The Cardiac Center — The Cardiac Depressor Nerves — The Nervous Control of the Blood Vessels — Vasomotor Nerves — Vasoconstrictor Nerves — Vasodilator Nerves — Vasomotor Reflexes — The Effect of Grav- ity on the Circulation— Haemorrhage — Chemical Control of Circulation— Asphyxia— Nitrous Oxide— Cocain 184 CONTENTS. XI Page CHAPTER XXI. THE RESPIRATION. Introduction — The Internal Respiration — Oxidation in the Tissues — Relation of Oxidative Process to Muscular Activity — Physi- cal Laws Governing Solution of Gases — Haemoglobin — Rela- tion of Oxygen to Haemoglobin — The Mechanism of the Res- piratory Exchange — The Effect of Carbon Dioxide on Oxy- hsemoglobin— The Exchange of Carbon Dioxide 197 CHAPTER XXII. THE RESPIRATION. The External Respiration — Structure of the Lungs — The Mechan- ism of the Respiratory Movements — The Part the Diaphragm Plays — The Part the Thorax Plays — The Movements of the Lungs — Respiratory Sounds — Effects of Respiration on the Circulation — Artificial Respiration — Volumes of Air Respired — Mechanism of Gaseous Exchange in Lungs 207 CHAPTER XXIII. THE RESPIRATION. The Nervous Control of the Respiration— Reflex Respiratory Move- ments— Chemical Control of the Respiration — The Effect of Changes in the Respired Air on the Respiration— Mountain Sickness — Ventilation — The Voice — Mechanism of the Voice — Speech 219 CHAPTER XXIV. THE FLUID EXCRETIONS. The Excretion of Urine — Composition of Urine — Organic Constitu- ents— Urea — Ammonia — Uric Acid— Creatinin — Inorganic Con- stituents— Abnormal Constituents — The Organs of Excretion — The Blood Supply of the Kidney — Nature of Urine Excretion — Micturition — The Secretions of the Skin — The Sweat Glands — The Sebaceous Glands — The Mammary Glands 229 XJi CONTENTS. Page CHAPTER XXV. THE NERVOUS SYSTEM. General Nature and Structure of the Nervous System in Different Groups of Animals — Fundamental Elements of the Reflex Arc — Integration of the Nervous System 239 CHAPTER XXVI. THE NERVOUS SYSTEM. Reflex Action — The Nerve Structures Involved in the Reflexes of the Higher Animals — The Receptors of Pain, Touch, Tempera- ture— Local Anesthesia and Analgesia — The Afferent Fiber — Choice of Paths on Entering Spinal Cord — The Nerve Center — The Efferent Neurone — Types of Reflexes — Spinal Shock — The Essential Characteristics of Reflex Action — Muscular Tone and Reciprocal Action of Muscles — Symptoms Due to Lesions Affecting the Reflexes 244 CHAPTER XXVII. THE NERVOUS SYSTEM. The Brain Stem — The General Course and Functions of the Cranial Nerves, Particularly of the Fifth and Seventh — Relationship of the Fifth Nerve to the Teeth and to Neuralgia — Referred Pain Through this Nerve — Sensitiveness of the Tooth — Tri- facial Neuralgia — Relationship of the Seventh Nerve to Bell's Paralysis 256 CHAPTER XXVIII. THE NERVOUS SYSTEM: THE BRAIN. Influence of the Brain on the Reflex Functions of the Spinal Cord — Functions of the Cerebrum — Cerebral Localization — Experi- mental and Clinical Observations — The Sensory Centers — The Mental Process — Aphasia — The Cerebellum — Relationship to Body Equilibrium — The Semicircular Canals — The Sympa- thetic Nervous System — General Characteristics — The Course of Some of the Most Important Pathways 267 CONTENTS. Xiii Page CHAPTER XXIX. THE SPECIAL SENSES: VISION. Optical Apparatus of the Eye — Formation of Retinal Image — Changes in the Eye During Accommodation from Near Vision —The Function of the Pupil — Imperfections in the Optical System of the Eye — Long and Short-Sightedness — Astigma- tism, etc. — The Sensory Apparatus of the Eye — The Functions of the Retina — Blind Spot — Fovea Centralis — The Movements of the Eyeballs — Diplopia — Judgments of Vision — Color Vision — Color Blindness 279 CHAPTER XXX. THE SPECIAL SENSES. Hearing — The Cochlea — How Sound Waves are Transmitted to this by Tympanic Membrane and Auditory Ossicles — Causes of Deafness — Taste — Nature of Receptors* for Taste — The Location of the Four Fundamental Taste Sensations — Rela- tionship Between Chemical Structure and Taste — Association Between Taste, Common Sensation of Touch, and Smell — Action of Certain Drugs on Taste — Smell— Nature of the Re- ceptors of Smell (the Olfactory Epithelium) — Nature of Stimulus 291 CHAPTER XXXI. THE MUSCULAR SYSTEM. The General Properties of Muscular Tissues — Contractability — Irritability — The Simple Muscular Contraction — Tetanic Con- traction — Effect of Load — Elasticity of Muscle — Chemical Changes Accompanying Contraction — Rigor Mortis 300 CHAPTER XXXII. REPRODUCTION. Fertilization — The Accessory Phenomena of Reproduction in Man — Female Organs — Male Organs — Impregnation — Ovulation — Pregnancy — Birth 303 APPENDIX. Fundamental Demonstration in Physiology 309 ILLUSTRATIONS. Fig. Page 1. Dialyser 27 2. Cells of parotid gland showing zymogen granules 40 3. The nerve supply of the submaxillary gland 41 4. The changes which take place in the position of the root of the tongue, the soft palate, the epiglottis and the larynx during the second stage of swallowing 55 5 Diagrams of outline and position of stomach as indicated by skiagrams taken on man in erect position at intervals after swallowing food : 61 6. Diagram of stomach showing miniature stomach separated from main stomach by a double layer of mucous membrane 62 7. Diagram of time it takes for a capsule containing bismuth to reach the various parts of the large intestine 80 8. Diagram of Atwater-Benedict Respiration Calorimeter 86 9. Dietetic chart (colored plate) 104 10. Cretin, 19 years old 126 11. Case of myxo3dema 127 12. Photographs showing before and after onset of acromegalis symptoms 132 13. Thomas-Zeiss Haemocytometer 142 14. Diagram of circulation (colored plate) 158 15. Position of the heart in the thorax 160 16. Generalized view of the vertebrate heart 161 17. Diagram of valves of heart 162 18. Dissection of heart to show auriculo-ventricular bundle 165 19. Diagram showing relative pressure in auricle, ventricle and aorta 168 20. Diagram of experiment to show how a pulse comes to disap- pear when fluid flows through an elastic tube when there is resistance to the outflow 173 21. Apparatus for taking tracing of the blood pressure 174 22. Apparatus for measuring the arterial blood pressure in man. . 176 23. Jacquet Sphygmocardiograph 181 24. Pulse tracing made by sphygmograph 182 25. Effect of stimulating vagus and sympathetic nerves on the frog's heart 185 26. Tracings of arterial blood pressure 186 27. Curve chart 203 28. Diagram of structure of lungs, showing larynx, bronchi, bronchioles and alveoli 207 xv Xvl ILLUSTRATIONS. Pig. Page 29. The position of the lungs in the thorax 209 30. Hering's apparatus for demonstrating the action of the respir- atory pump 210 31. Diagram to show movement of diaphragm during respiration 211 32. Position to be adopted for effecting artificial respiration 215 33. Diagram of laryngoscope 225 34. Position of the glottis preliminary to the utterance of sound. . 226 35. Position of open glottis , 226 36. The position of the tongue and lips during the utterance of the letters indicated 228 37. Diagram of the uriniferous tubules, the arteries and the veins of the kidney (colored plate) 232 38. Diagram of urinary system 236 39. Schema of simple reflex arc 240 40. Diagram of nervous system of segmented invertebrate 242 41. The simplest reflex arc in the spinal cord 244 42. Diagram of section of spinal cord, showing tracts '247 43. Reflex arc through the spinal cord, in which an intermediary neurone exists between the afferent and efferent neurones (colored plate) 247 44. Course of the pyramidal fibers from the cerebral cortex to the spinal cord (colored plate) 248 45. Under aspect of human brain 257 46. Vertical transverse section of human brain 258 47. Diagram of the dorsal aspect of the medulla and pons, show- ing the floor of the fourth ventricle with the nuclei of origin of the cranial nerves (colored plate) 260 48. Diagram to show areas of referred pain in distribution of fifth nerve due to affections of the various teeth (front view) (colored plate) 262 49. Diagram to show areas of referred pain in distribution of fifth nerve due to affections of the various teeth (side view) (colored plate) 264 50. Cortical centers in man 270 51. The semicircular canals of the ear, showing their arrange- ment in the three planes of space 276 52. Formation of image on retina 281 53. Section through the anterior portion of the eye 282 54. A, spherical aberration; B, chromatic aberration 285 55. Errors in refraction 286 56. Semidiagrammatic section through the right ear 292 57. Diagrammatic view of the organ of Corti (colored plate) 292 58. Tympanum of right side with the auditory ossicles in place. . 294 59. Schema to show the course of the taste fibers from tongue to brain . . 296 PHYSIOLOGY FOR DENTAL STUDENTS CHAPTER I. INTRODUCTORY: THE CHEMICAL BASIS OF THE CELL. The Scope of Physiology. — Physiology is the study of the phenomena of living things, just as anatomy or morphology is a study of their structure. The study of anatomy is most logically pursued by starting with the simplest organisms and gradually proceeding through the more complex forms until man is reached. Except for certain fundamental functions, such as nutrition, which are common to all cells, this method is not the most suitable one to pursue in physiology, because in the low- est organisms all of the functions are crowded together in a lim- ited number of cells — indeed, it may be in one single cell. It is easier to study a function when it is performed by a tissue or organ that has been set apart for this particular purpose than when it is performed by cells that do many other things. Another reason for paying more attention to the functions of higher rather than lower animals is that the knowledge which we acquire may be more directly applicable in explaining the functions of man, and therefore in enabling us more readily to detect and rectify any abnormalities. During the embryonic development of one of the higher ani- mals, a single cell, the ovum, produces numerous other cells, which become more and more collected into groups, in many of which the cells undergo very marked changes in shape and structure, or produce materials, such as the skeleton or teeth, which show no cell structure whatsoever. Thus we have formed the tissues and organs, each having some particular function of 17 18 PHYSIOLOGY FOR DENTAL STUDENTS. its own, although certain functions remain which are common to all. In other words, as the organism becomes more and more complex, there comes to be a division of labor on the part of the cells that comprise it. The conditions are exactly like those which obtain in the development of a community of men. In primeval communities' there is little division of labor, every indi- vidual makes his own clothes, hunts his own food, manufactures and uses his own implements of war, but as civilization begins to appear, certain individuals specialize as hunters and fighters, others as makers of clothing, others as artisans. Although, in its first stages, this division of labor may be far from absolute, for every member of the community must still fight and take part in the building of his hut, yet it soon tends to become more and more so, until, as in the civilized communities of this twentieth century of ours, specialization has become the order of the day. A good example of a one-celled animal is the amoeba, which is often found floating in stagnant water, and which consists of nothing more than a mass of tissue, or protoplasm, as it is called, and yet this apparently simple structure can move from place to place, it can pick up and incorporate with its one substance par- ticles of food with which it comes in contact, it can store up as granules certain of these foodstuffs, and get rid of others that it does not require ; it grows as a result of this incorporation, until at last it splits in two and each half repeats the cycle. In other words, this single cell shows all of the so-called attributes of life : movement, digestion and assimilation of food, growth and repro- duction. No one of these properties is necessarily confined to living structures alone, for some perfectly inanimate bodies may exhibit one or other of them, yet when all occur together, we consider the structure. to be living. In the higher animals, these functions are performed by the so-called systems, such as the digestive, the circulatory, the res- piratory, the excretory, the motor, the nervous and the reproduc- tive, each system being composed of certain organs and tissues which are designed for the special purpose of carrying out some particular function, or functions. One function, however, is com- mon to all of the organs and tissues, namely, that of nutrition, THE CHEMICAL BASIS OF THE CELL. 19 which includes the process by which the digested food is built up into the protoplasm of the cells, tor assimilation, and that by which the resulting substances are broken down again, or disas- similation. It is by these processes that the energy of life is set free; the energy by which the tissues perform their functions, and which appears as body heat. Every cell in the animal body is therefore a seat of energy production, and at the same time each is a machine for converting this energy into some definite form of work. In this regard the animal machine is quite unlike a steam engine, where energy liberation occurs in the furnace, but conversion of this to movement occurs in the pistons. The furnace and the machinery of the animal body are part and par- cel of the same structures, and the digestive, circulatory, respira- tory and excretory systems are more highly specialized for the. purpose of transporting fuel, the oxygen to burn it and the gases produced by its combustion to and from the Hying cell. These processes of assimilation and disassimilation constitute the study of metabolism, the practical side of which is included in the science of nutrition. The Physico-Chemical Basis of Life. With the object of ascertaining to what extent the known laws of physics and chemistry can explain the fundamental processes that are common to all cells, we must make ourselves familiar, first of all, with the chemical and physical nature of the constitu- ents of the cell, and secondly with the physico-chemical laws which govern the reactions that take place between these con- stituents. The same laws will control the reactions which take place in the juices secreted by cells; for example, in the blood and in the secretions, such as the saliva. The Chemical Basis of Animal .Tissues. — Certain substances are found in every living cell and in approximately equal quan- tities; hence these may be considered the primary constituents of protoplasm. In general they consist of the proteins, lipoids, in- organic salts, water, and probably the carbohydrates. Protoplasm is the substance composed of these primary constituents. By its 20 PHYSIOLOGY FOR DENTAL STUDENTS. activity the protoplasm produces the secondary constituents of the cell, which arc not the same in all cells, and which include the granules of pigment or other material, the masses of glycogen, the globules of fat or the vesicles of fluid which are found em- bedded in the protoplasm. By whatever process we attempt to isolate its constituents, we of course kill the cell, so that we can never learn by analysis what may have been the real manner of union of these substances in the living condition. All we can find out is the nature of the building material after the structure (the cell) into which it is built has been pulled to pieces. If the chemical process by which we disintegrate the cell is a very energetic one, for example, com- bustion, we always find the elements, carbon, hydrogen, nitrogen, oxygen, sulphur, phosphorus, sodium, potassium, calcium, chlo- rine, and usually traces of other elements, such as iodine, iron, etc. If the decomposition be less complete, definite chemical compounds are obtained, namely, water, proteins, lipoids, car- bohydrates, and the phosphates and chlorides of sodium, potas- sium and calcium. We shall proceed to consider briefly the main characteristics of each of these substances and their place in the animal economy. WATER. — This is the principal constituent of active living organisms, and is the vehicle in which the absorbed foodstuffs and the excretory products are dissolved. It may be said indeed that protoplasm is essentially an aqueous solution, in which other substances of vast complexity are suspended. Water, on account of its very unique physical and chemical properties, is of prime importance in all physiological reactions. These properties are : its chemical inactivity at body temperatures; its great solvent power (it is the best known universal solvent) ; its specific heat, or capacity of absorbing heat ; and, depending on this, the large amount of heat which it takes to change water into a vapor — latent heat of steam. These last mentioned properties are made use of in the higher animals for regulating the body temperature. Of great importance in the maintenance of the chemical bal- ance of the body are the electric phenomena which attend the solution of certain substances in water. This will be discussed THE CHEMICAL BASIS OP THE CELL. 21 later in connection with ionization. Water has also a very great surface tension. It is this which determines the height to which it will rise in plants and in the soil, and which no doubt plays a role in the processes of absorption going on in various parts of the animal body. PROTEINS. — The great importance of proteins in animal life is attested by the fact that they are absolutely indispensable in- gredients of food. An animal fed on food containing no protein will die nearly as soon as if food had been withheld altogether. Proteins are complex bodies composed of carbon, hydrogen, oxy- gen, nitrogen, and, in nearly all cases, sulphur. Some may con- tain in addition phosphorus, iron, iodine, or certain other elements. The proportions in which the above elements are found in different proteins do not vary so much as the differences in the chemical behavior of the proteins would lead us to expect. In general the percentage composition by weight is : Carbon 53 per cent Hydrogen 7 per cent Oxygen 22 per cent Nitrogen . , 16 per cent Sulphur Ito2 per cent The essential differences in the structure of the molecules of different proteins have been brought to light by studies of the products obtained by partially splitting up the molecule. We are able to do this by subjecting protein to the action of super- heated steam, or by boiling with acids or alkalies in various con- centrations, or by the action of the ferments of digestive juices or by bacteria. The cleavage produced by ferments or bacteria is much more discriminate than that brought about by strong chemical reagents ; that is to say, the chemical groupings are not so roughly torn asunder by the biological as by the chemical agencies. At first the proteins break up into compounds still possessing many of the features of the protein molecule. These are the proteases and peptones, and they consist of aggregates of smaller 22 PHYSIOLOGY FOR DENTAL STUDENTS. molecules, which can be further resolved into simple crystalline substances. These have been called the building stones of the protein molecule, and although they differ from one another in many respects, they have one feature in common, namely, that each consists of an organic acid having one or more of its hydro- gen atoms' substituted by the radicle, NH2. Such substances are called amino bodies. For example, the formula of acetic acid is CH3CDOH. If for one of the H atoms there is substituted the NH2 group, we have CH,NH2COOH, which is amino acetic acid, or glycine. The same sort of substitution may take place, not alone in the simple organic acids containing one acid group, but also in those containing two acid groups, as in amino-succinic acid, COOH. CH2(NH2)COOH, or in acids containing the aro- matic or benzene ring group, as in the case of tyrosine, C6H4OH. C2H3. NH2COOH, or again there may be two amino acid groups present, as in the diamino acid, ornithin or diamino- valeric acid, C4H7(NH2)2COOH. That the large and complex protein molecule is really built up out of these amino bodies has been very conclusively shown by Emil Fischer, who succeeded in causing two or more of them to become united to form a body called a polypeptid. When several amino bodies were thus synthesized, the polypeptid was found to possess many of the properties of peptones, which we have just stated are the earliest decomposition products of protein. Proteins differ from one another, not only in the nature of the amino bodies of which they are composed (although certain of these are common to all proteins), but also in the manner in which the amino bodies are linked together. We shall see the practical value of knowing what are the amino bodies in a given protein when we come to the subject of dietetics (see p. 99). The proteins of the cell are classified into two groups. The first includes the simple proteins, such as egg and serum albumin ; and the second, the compound proteins, from which non-protein groups can be split off. As primary cell constituents, the follow- ing simple and compound proteins are important: albumin, globulin, nucleoprotein, and the glycoproteins. They are all of the nature of colloidal substances (sec p. 32), and therefore are THE CHEMICAL BASIS OP THE CELL. 23 either precipitated or coagulated when solutions containing them are boiled or have inorganic salts dissolved in them. Albumins are characterized chiefly by their great solubility in water. Three forms are of importance: egg albumin, lactal- bumin of milk, and serum albumin. Globulins occur principally in the muscle proteins, and are insoluble in water, but soluble in dilute neutral salt solutions. Many consider that the albumins and globulins are only nutri- tive materials from which the protoplasm manufactures the compound proteins which are the essential cellular proteins. Nucleoproteins, both in quantity and in relation to their activ- ity, are probably the most important constituents of the cell. They have a very complex structure, and occur in many varieties. They consist of a combination between protein and a substance called nucleic acid, which, on being broken up by chemical means, yields phosphoric acid, a simple sugar called pentose, and nitrogenous substances known as purine bases, and pyrimidines. The purine bases are of great interest, because they are the ante- cedents in the body of uric acid, which, being relatively insoluble, may become deposited from the body fluids and cause gout or gravel. That it is possible to have an enormous variety of nucleo- proteins can be imagined when we consider that there exist differ- ent sorts of purine bases, of carbohydrates, and of amino bodies. The nucleus of the cell contains a nucleoprotein which is particu- larly rich in purin bases and is often called nuclein. Phosphoproteins are compounds of phosphoric acid and simple proteins, without any nucleic acid. An example is the casein of milk (see p. 105). Glycoproteins are compound of carbohydrates with proteins. The mucin of saliva is an example (see p. 46). Insoluble proteins resemble the coagulated proteins, and are left behind after the extraction of the other proteins from the cell. •LIPOIDS. — These include all the substances composing a coll which are soluble in fat solvents. Besides fats and fatty acids, the most important of these substances are lecithin and choles- terol. 24 PHYSIOLOGY FOR DENTAL STUDENTS. Lecithin is widely distributed in the animal body, and is V«T\- important in the metabolism and in the physical structure of the cell. It consists chemically of glycerine, fatty acid, phosphoric acid, and a nitrogenous base called cholin. Cholesterol is another widely distributed lipoid. It is not in reality a fatty body, but rather resembles the terpencs. Lecithin and cholesterol are abundant in brain tissue, in the envelopes of erythrocytes, and in bile. The fats exist mainly as secondary constituents of the cell, being deposited in very large amounts in certain of the connective tissue cells of the body, in bone marrow and in the omental tis- sues. Chemically, the tissue fats are of three kinds : olein, pal- mitin, and stearin, each having a distinctive melting point. They are compounds of the tri-valent alcohol, glycerine, and one of the higher fatty acids, oleic, palmitic, or stearic acid. Besides those that are present in the animal tissues, fats made up of glycerine combined with various lower members of the fatty acid series occur in such secretions- as milk. In order to understand the influence which fats have on general metabolism, it is important to remember that they differ from the carbohydrates in contain ing a very low percentage of oxygen and a relatively high per- centage of hydrogen and carbon. Thus, the empirical formula of palmitin is C51H9808 or C3Hg(C16H3102)3, that of dextrose C6H1206, and of protein C72Hll2N18OaaS. THE CARBOHYDRATES are also mainly secondary cell constitu- ents, although it is becoming more and more evident that they are also necessary as primary constituents. In general they may be defined chemically as consisting of the elements C, H, and 0, the latter two being present in the molecule in the same propor- tion as in water; thus, the formula for dextrose is C6H]20G. The basic carbohydrates are the simple sugars or monoxuc- cliarides, such as grape sugar or dextrose. When two molecules of monosaccharide become fused together with the elimination of a molecule of water (thus giving the formula C^H^Ou), a secondary sugar or disaccharide results. Cane sugar, lactose (or milk sugar) and maltose (or malt sugar) are examples. If sev- eral nonsaccharide molecules similarly fuse together, polysac- THE CHEMICAL BASIS OF THE CELL. 25 cliarides having the formula (C6H1005)n are formed. These in- clude the dextrines or gums, glycogen or animal starch, the ordi- nary starches, and cellulose. Since so many molecules are fused together, it is not to be wondered at that there should be so many varieties of each of these classes of polysaccharides, for, as in the case of proteins, not only may the actual "building stones" of the molecule be different, but they may be built together in very diverse ways. The polysaccharides may be hydrolyzed (i. e., caused to take up water and split up) into disaccharides, and these into monosaccharides by boiling with acids or by the action of diastatic and inversive ferments (see p. 36). CHAPTER II. THE INFLUENCE OF PHYSICO-CHEMICAL LAWS ON PHYSIOLOGICAL PROCESSES: ENZYMES. Having learned of what materials the cell is composed, we may proceed to enquire into the chemical and physical reactions by which it performs its functions. The cell, either of plants or of animals, may be considered as a chemical laboratory, in which definite reactions are constantly going on, being guided, as to their direction and scope, by the physical conditions under which they occur. A study of the material outcome of these reactions constitutes the study of metabolism, to which special chapters are devoted further on. At present, however, we must briefly examine the physico-chemical conditions existing in the cell which may give the directive influence to the reactions. Why should certain cells, like those which line the intestine, absorb digested food and pass it on to the blood, whilst others, like those of the kidney, pick up the effete products from the blood and excrete them into the urine? We must ascertain whether these are processes depending on purely physico-chemical causes, or whether they are a function of the living protoplasm itself, a vital action, as we may call it. In general it may be said that the aim of most investigations of the activities of cells is to find a physico-chemical explanation for them, and it is one of the achievements of modern physiology that some should have been thus explainable. A large number, however, do not permit of such an explanatic-n, and this has induced certain investigators to believe that there are some animal functions which are strictly vital and can never be explained on a physical basis. The ' ' phys- ical" and the "vital schools" of physiologists are therefore always with us. From the standpoint of physical chemistry, the cell may be considered as a collection of two classes of chemical substances, 26 CRYSTALLOIDS. 27 called crystalloids and colloids, dissolved in water, in the lipoids, or in each other, and surrounded by a membrane which is per- meable towards certain substances but not towards others (semi- permeable, as it is called). On a larger scale, the same general conditions exist in all of the animal fluids, such as the blood, the lymph, the secretions and the excretions, so that we may study the laws with a view to applying them to both cells and body fluids. Properties of Crystalloids. — As their name implies, these form crystals under suitable conditions. When present in solu- tion they diffuse quickly throughout the solution, and can readily Fig. 1. — Dialyser made of tube of parchment paper suspended in a vessel of distilled water. The fluid to be dialysed is placed in the tube, and the distilled water must be frequently changed. pass through membranes, such as a piece of parchment, placed between the solution containing them and another solution. This process is called dialysis, and the apparatus used for observing it, a dialyser (see Fig. 1). Dialysis differs from filtration, the latter process consisting in the passage of fluids, and the sub- stances dissolved in them, through more or less pervious mem- branes as a result of differences of pressure on the two sides of the membrane. If instead of using a simple membrane, such as parchment, we choose one which does not permit the crystalloid itself to diffuse, but permits the solvent to do so — a semipcrmeablc membrane, as it is called, — a very interesting property of dis- solved crystalloids comes to light, namely, their tendency to ex- 28 PHYSIOLOGY FOR DENTAL STUDENTS. pand in the solvent, that is, to take up more room by attracting the solvent through the membrane. Cell membranes are semi- permeable, but they are too small and delicate for experimental purposes, for which we use one composed of a precipitate of copper ferrocyanide supported in the pores of an unglazed clay vessel. If a solution of -a crystalloid — say, cane sugar — be placed in such a vessel and this then submerged in water, it will be found that the cane sugar solution quickly increases in volume, or, if this be prevented by closing up the vessel and connecting a pres- sure gauge with it, a remarkably high pressure will become devel- oped. This is called osmotic pressure, and it is a measure of the tendency of dissolved crystalloids to expand in the solvent. It has been found that the laws which govern osmotic pressure are identical with those governing the behavior of gases. Therefore, the osmotic pressure would be expected to be proportional to the number of molecules of dissolved crystalloid and such is the case for the sugars, but it is not so for the saline crystalloids, such as the alkaline chlorides, nitrates, etc. These cause a greater osmotic pressure than we should expect from their molecular weights. Why is this ? The answer to the question is revealed by observing the behavior of the two classes of crystalloids towards the electric current. Solutions of sugars or urea do not conduct the current any better than water, whereas solutions of saline crystalloids conduct very readily. The former are therefore called non-electrolytes and the latter electrolytes. The reason for these differences has been found to be that molecules of electro- lytes when they are dissolved break into parts called "ions," and each ion carries a charge of electricity of a certain sign, i. e., positive or negative. Whenever an electric current is passed through the solution, the ions, hitherto distributed throughout the solution in pairs carrying charges of opposite signs, now line themselves up so that the ions with one kind of electrical charge form a chain across the solution along which that kind of elec- tricity readily passes, and in so doing carries the ions with it. This splitting of electrolytes into ions is called dissociation or wnization. The ions which carry a charge of positive electricity and which therefore travel towards the kathode or negative pole CRYSTALLOIDS. 29 (since unlike electricities attract each other) are called kathions, and the negatively charged ions that travel to the anode, anions. Hydrogen and the metallic elements belong to the group of kathions ; oxygen, the halogens and all acid groups, to the anions. These facts may be more clearly understood from the following equations : In water, or in a solution of a non-electrolyte, molecules of H20 or non-electrolyte exist thus: H20 H20 H20 H,0 H20 H20 H20 H20 H20 In a solution of an electrolyte, the molecules split into ions thus: Na* 01- Na+ Cl- Na+ Cl- Na* Cl- Na+ Cl- Na+ Cl~ Na+ Cl- Na+ Cl- Na+ Cl~ When an electric current passes through a solution of an electrolyte, the ions arrange themselves thus : Kathode" Anode* Na+ Na+ Na+ Cl- Cl- Cl~ .Na+ Na+ Na+ Cl~ Cl- Cl~ Na+ Na+ Na+ Cl- Cl- Cl~ To return to osmotic pressure, the ions influence this as if they were molecules, so that when we dissolve, say, sodium chloride in water, the osmotic pressure is almost twice what it should be, because every molecule has split into two ions. Osmotic Phenomena in Cells. — Over and over again we shall have to refer to these physico-chemical processes in explaining physiological phenomena. For the present it may make matters clearer if we consider how osmosis explains the behavior of cells when suspended in different solutions. The cell wall acts as a semipermeable membrane. Thus, if we examine red blood cor- puscles suspended in different saline solutions under the micro- scope, we shall observe that they shrink or crenate when the solu- 30 • PHYSIOLOGY FOR DENTAL STUDENTS. tions are strong, and expand and become globular in shape when these are weak. The shrinkage is due to diffusion of water out of the corpuscle and the swelling, to its diffusion in ; that is to say, in the former case the osmotic pressure of the surrounding fluid is greater than that of the corpuscular contents and vice versa in the latter case. In this way we have a simple and con- venient method of comparing the relative osmotic pressure of dif- ferent solutions. When the solution has a higher pressure, it is called hypertonic, when less, hypotonic, when same, isotonic. It is evident that the body fluids must always be isotonic with the cell contents, and that we must be careful never to introduce fluids into the blood vessels that are not isotonic with the blood. A one per cent solution of common salt is almost isotonic with blood, and is accordingly used for intravenous or subcutaneous injections, or for washing out body cavities or surfaces lined with delicate membranes, such as the conjunctiva or nares. Reaction of Body Fluids. — Closely dependent upon these properties of ionization are the reactions which determine the acidity and alkalinity of the body fluids. When we speak of the degree of acidity or alkalinity of a solution in chemistry, we mean the amount of alkali or acid, respectively, which it is nec- essary to add in order that the solution may become neutral to- wards an indicator, such as litmus. This titrible reaction is how- ever a very different thing from the real strength of the acid or alkali; for example, we may have solutions of lactic and hydro- chloric acids that require the same amount of alkali to neutral- ize them, but the hydrochloric acid solution will have much more powerful acid properties (attack other substances, taste more acid, act much more powerfully as an antiseptic, etc. ) . The rea- son for the difference is the degree of ionization ; the strong acids ionize much more completely than the weak. As a result of this ionization, each molecule of the acid splits into H-ions and an ion composed of the remainder. To ascertain the real acidity we must therefore measure the concentration of H-ions. (These considerations also apply in the case of alkalies, only in this case OH-ions determine the degree of alkalinity. ) This can be done accurately by measuring the speed at which certain chemical REACTION OP BODY FLUIDS. 31 processes proceed, that depend on the concentration of H-ions. The conversion of cane sugar into invert sugar is a good process to employ for measuring the speed of reaction. But even this refinement in technique does not enable us to measure the H-ion concentration — for now we must use this ex- pression when speaking of acidity or alkalinity — of such impor- tant fluids as blood and saliva, in which there is an extremely low H-ion concentration. If either of these fluids be placed on litmus papers, the red litmus turns blue, but all that this signifies is that the litmus is a stronger acid than those present in blood or saliva, so that it decomposes the bases with which they were combined and changes the color. If we employ phenolphthalein, which is a much feebler acid, then blood serum reacts neutral and saliva often acid. There are two methods open to us for measuring the H-ion concentration in such cases : 1. The Hydrogen Electrode. — Place the fluid (e. g., blood serum or saliva) in a small closed vessel filled with hydrogen and with a platinum electrode dipping into it. Connect this hydro- gen electrode with a standard calomel electrode by wires in the course of which are suitably arranged electrical instruments for the measurement of electromotive force. From the difference in the electromotive force which is found to exist between the hydro- gen and the calomel electrodes, we can calculate the H-ion con- centration. This method is being employed for measuring the reaction of saliva in relationship to its influence on caries of the teeth. 2. The Use of Standardized Indicators. — It has been found that different indicators change color at different H-ion concen- trations. By taking solutions with variable known proportions of acid and alkaline salts such as NaH,P04 and Na2HP04 or NaHCO3 and measuring their actual acidity in terms of the H-ion concentration — by the electrical method — and then observ- ing their behavior with different indicators, it has been possible to evaluate the different indicators in terms of the H-ion concen- tration at which they change color. Expressing the results as the fraction of a normal solution of H-ion at which this change 32 PHYSIOLOGY FOR DENTAL STUDENTS. occurs, it has been found that paranitro-phenol turns at about .000,001 (or lxlO~7), which is the H-ion concentration of pure water, and is therefore the most practical point to choose as indi- cating neutrality. Methyl red and rosolic acid also change color about this point. Phenolphthalein, on the other hand, changes color at a H-ion concentration of 1 x 10~9, i. e., its is very sensitive towards acids, and methyl orange, at 1 x 10— 4, i. e., it is relatively insensitive towards acids. The indicators which change color at about the H-ion concen- trations found in animal fluids are rosolic acid, paranitrophenol and methyl red. By comparing the color produced by adding one of these indicators to the unknown fluid with those obtained by adding the same indicator to a series of solutions containing varying but known H-ion concentrations, we can accurately tell the H-ion concentration of the unknown solution, for the H-ion concentration of the solution whose tint matches with that of the unknown is the H-ion concentration of the latter. The series of standard solutions is made by mixing varying proportions of acid and alkaline phosphates. Before leaving this subject, it is important to point out that the blood has an H-ion concentration which is practically the same as that of water, i. e., is as nearly neutral as it could be. It also has the power of maintaining this neutrality practically con- stant even when large amounts of acid or alkali are added to it. Although saliva and some other body fluids are not so nearly neutral as blood, yet they can also lock away much acid or alkali without materially changing the H-ion concentration. This property is due to the fact that the body fluids contain such salts as phosphates and carbonates, which exist as neutral and acid salts, and can change from the one state to the other without greatly altering the H-ion concentration, and yet, in so changing, can lock away or liberate H- or OH-ions. This has been called the ' ' buffer ' ' action, and is a most important factor in maintain- ing constant the neutrality of the animal body. Colloids. — These are substances which do not diffuse through membranes when they are dissolved. Thus if blood serum be placed in a dialyser which is surrounded by distilled water, all COLLOIDS. 33 the crystalloids will diffuse out of it, leaving the colloids, which consist mainly of proteins. The physical reason for this failure to diffuse is the large size of the molecules, in comparison with the small size of those of the crystalloids. By causing a beam of light to pass through a colloidal solution and holding a micro- scope at right angles to this beam, the colloidal particles become evident, just as particles of dust become evident in the air of a room in a beam of daylight. In confirmation of this view of the cause of the indiffusibility of colloids is the fact that filters can be made of unglazed porcelain impregnated with gelatin, in which the pores are therefore very minute, through which col- loids cannot pass, though water and inorganic salts do so. When blood serum is filtered through such a filter, the filtrate contains no trace of protein. The colloidal molecules can also very readily be caused to fuse together, thus forming aggregates of molecules which become so large that they either confer an opacity on the solution or actually form a precipitate. Tli is fusing together of colloidal particles can be brought about either by adding certain neutral salts or by mixing with certain other colloids. The explanation of these results is as follows: colloidal molecules carry either a positive or a negative electrical charge, and when this is neutralized, the colloidal molecules fuse together, i. e., become aggregated. This neutralization of elec- trical charge can be brought about either by adding an electro- lyte, one of whose ions will supply the proper electrical charge, or by a colloid having an opposite charge. Thus the S04 anion of Na2S04, in virtue of charges of negative electricity which it carries, will very readily precipitate such a colloid as colloidal iron (ferrum dialysatum, U. S. P.), which is charged with posi- tive electricity ; or again, this colloid itself will readily precipitate arsenious sulphide, another colloid carrying a negative charge. The physiological importance of these reactions lies in the fact that they probably explain many of the peculiarities of behavior of mixtures of different animal fluids, such as toxins and anti- toxins (see p. 149). A property of colloids which is closely related to the above is that of adsorption. This means the tendency for dissolved sub- 34 PHYSIOLOGY FOR DENTAL STUDENTS. stances to become condensed or concentrated at the surface of colloidal molecules. An example is the well known action of charcoal when shaken with colored solutions. It removes the pig- ment by adsorbing it. Adsorption is due to surface tension, which is the tension created at the surface between a solid and a liquid, or between a liquid and a gas. It is in virtue of surface tension that a raindrop assumes more or less spherical shape. Since colloids exist as particles, there must be an enormous num- ber of surfaces throughout the solution, that is, an enormous sur- face tension. Now many substances, when in solution, have the power of decreasing the surface tension, and in doing so it has been found that they accumulate at the surface, that is to say, in a colloidal solution, at the surface of the colloidal molecules. The practical application of this is that it helps to explain the physical chemistry of the cell, the protoplasm of which is a col- loidal solution containing among other things proteins and lipoids. The latter depress the surface tension and therefore collect on the surface of the cell and form its supposed mem- brane, whilst the proteins exist in colloidal solution inside. It is possibly by their solvent action on lipoids that ether and chloro- form so disturb the condition of the nerve cells as to cause anes- thesia. General Nature of Enzymes or Ferments. To decompose proteins, fats or carbohydrates into simple mole- cules in the laboratory necessitates the use of powerful chemical or physico-chemical agencies. Thus, to decompose the protein molecule into amino bodies requires strong mineral acid and a high temperature. In the animal body similar processes occur readily at a comparatively low temperature and without the use of strong chemicals in the ordinary sense. The agencies which bring this about are the enzymes or ferments. These are all col- loidal substances (see p. 32), so that they are readily destroyed by heat and are precipitated by the same reqgents as proteins. They are capable of acting in extremely small quantities. Thus, a few drops of saliva can convert large quantities of starch solu- tion into sugar. During their action, the enzymes do not them- ENZYMES. 35 selves undergo any permanent change, for even after they have been acting for a long time, they can still go on doing their work if fresh material be supplied upon which to act. These proper- ties are explained by the fact that they act catalytically , just as the oxides of nitrogen do in the manufacture of sulphuric acid. That is to say, they do not really contribute anything to a chemi- cal reaction, but merely serve as accelerators of reactions, which however would occur, though very slowly, in their absence. Thus, to take our example of starch again, if this were left for several years in the presence of water, it would take up some of the water and split into several molecules of sugar (p. 34). The enzyme ptyalin in saliva merely acts by hurrying up or accelerating the reaction so that it occurs in a few minutes. Enzymes differ from inorganic catalysers in the remarkable specificity of their action, there being a special enzyme for prac- tically every chemical change that occurs in the animal body. Thus, if we act on any of the sugars called disaccharides (cane sugar, lactose and maltose) with an inorganic catylytic agent, such as hydrochloric acid, they will split up into their constitu- ent monosaccharide molecules, whereas in the body, each disac- charide requires a special or specific enzyme for itself. The en- zyme acting on one of them, in other words, will be absolutely inert towards the others. This specificity of action is explained by supposing that each substance to be acted on (called the sub- strat) is like a lock to open which the proper key (the enzyme) must be fitted. Enzymes are peculiarly sensitive towards the chemical condi- tion of the fluid in which they are acting, more particularly its reaction. Thus the enzyme of saliva acts best in neutral reaction, whereas the enzyme of gastric juice acts only in the presence of acid, and those of pancreatic juice in the presence of alkali. Enzymes may unfold this action either inside or outside of the cells which produce them. Thus, the enzymes produced in the digestive tract act outside the gland cells, but the enzyme of the yeast cell acts in the cell itself and is never secreted. The former are called extracellular enzymes and the latter intracellular. The activities of intracellular enzymes are much more liable to be 36 PHYSIOLOGY FOR DENTAL STUDENTS. interfered with by unfavorable conditions than those of extra- cellular enzymes. This is because the former become inactive whenever anything occurs to destroy the protoplasm of the cell in which they act. The living protoplasm is necessary to bring the substrat in contact with them. On this account enzymes used to be classified into organized and unorganized. We know that there really is no difference in the enzyme itself ; the only differ- ence is with regard to the place of activity. The cells that com- pose the tissues of animals perform their various chemical activi- ties in virtue of the intracellular enzymes which they contain. These are, therefore, the chemical reagents of the laboratory of life. After the animal dies, the intracellular enzymes may go on acting for a time and digest the cells from within. This is called autolysis. Enzymes are classified into groups according to the nature of the chemical action which they accelerate. Thus: Hydrolytic enzymes — cause large molecules to take up water and split into small molecules. (Most of the digestive enzymes belong to this class.) Oxidative enzymes (oxydases) — encourage oxidation. Deamidating — remove NH2 group. Coagulative — convert soluble into insoluble proteins. Each group is further subdivided according to the nature of the substrat on which the enzymes act ; e. g., hydrolytic enzymes are subdivided into amylolases — acting on starch; invertases — acting on disaccharides ; proteases — acting on proteins; ureases — acting on urea, etc. When enzymes are repeatedly injected into the blood, or under certain other conditions, they have the power, like toxines, of producing antienzymcs. As their name signifies, these are bodies which retard the action of enzymes. Thus, if some blood serum from an animal into which trypsin has been injected for some days previously be mixed with a trypsin solution, the mixture will digest protein very slowly, if at all, when compared with a mixture of the same amount of trypsiu and protein (see also p. 78). CHAPTER III. DIGESTION. Necessity and General Nature of Digestion: Digestion in the Mouth. The never-ceasing process of combustion that goes on in the animal body, as well as the constant wear and tear of the tissues, makes it necessary that the supply of fuel and of building mate- rial be frequently renewed. For this purpose food is taken. This food is composed of fats and carbohydrates, which are mainly fuel materials, of inorganic salts and water, which are neces- sary to repair the worn tissues and of proteins which are both fuel and repair materials, and are therefore the most important of the organic foodstuffs. The blood transports the foodstuffs from the digestive canal to the tissues. In the digestive canal the foodstuffs are digested by hydrolyzing enzymes (see p. 36), which are furnished partly in the secretions of the digestive glands and partly from the numerous micro-organisms that swarm in the intestinal contents. The enzymes, as we have seen, are very discriminative in their action, for not only is the enzyme for protein without action on a fat or carbohydrate, but each of the different stages in protein break-down requires its own pe- culiar enzyme. It becomes necessary therefore that the enzymes be mixed with the food in proper sequence, and to render this possible the digestive canal is found to be divided into special compartments, such as the mouth, the stomach, the small intes- tines, etc., each provided with its own assortment of enzymes and with some mechanism by which it can pass on the food to the next stage when it has been sufficiently digested. Such correlation between the different stages of digestion necessitates the existence, in the different levels of the gastro- intestinal tract, of mechanisms which are specially developed to 37 38 PHYSIOLOGY FOR DENTAL STUDENTS. bring about the right secretion at the right time. These mech- anisms are of two essentially different types, a nervous reflex control, and a chemical or "hormone" control. The nervous con- trol is exercised through a nerve center which is called into activ- ity by afferent stimuli which proceed from sensory nerve endings or receptors (see p. 244) that are especially sensitized so as to be stimulated by some property of food (its taste or smell, or some local action on the nerve endings). This type of control exists where prompt response of the glandular secretion is impor- tant, as in the mouth and in the early stages of digestion in the stomach. The hormone control consists in the action directly on the gland cells of substances which have been absorbed into the blood from the mucous membrane of the gastro-intestinal tract. The production of these substances depends upon the nature of the contents of the digestive tube. This is a more sluggish proc- ess of control than the nervous, but it is all sufficient for the cor- relation of most' of the disgestive functions. These considerations point the way to the scheme which we must adopt in studying the process of digestion ; we must explain how each digestive juice comes to be secreted, what action it has on the foodstuffs, and what it is, after each stage in digestion is completed, that controls the movement onwkrd of the food to the next stage. And when we have followed each foodstuff to its last stage in digestion, we may then proceed to study the means by which the digested foodstuffs are absorbed into the cir- culating fluids, and in what form they are carried to the tissues. On account of the varying nature of their food we find that the digestive system differs considerably in different groups of animals. In the omnivora, such as man, the digestive canal be- gins with the mouth cavity, in which the food is broken up me- chanically and is mixed with the saliva in sufficient amount to render it capable of being swallowed. The saliva, by containing starch-splitting ferment, also initiates the digestive process. The food is then carried by way of the oesophagus to the stomach, in the near or cardiac end of which it collects and becomes gradually permeated by the acid gastric juice. It is then caught up, portion by portion, by the peristaltic waves of the SALIVARY SECRETION. 39 further or pyloric end of the stomach and after being thor- oughly broken down by this movement and partially digested by the pepsin of gastric juice, is passed on in portions into the duodenum, where it meets with the secretions of the pancreas and liver. These secretions, acting along with auxiliary juices secreted by the intestine itself, ultimately bring most of it into a state suitable for absorption. What the digestive juices leave unacted on bacteria attack, especially in the caecum, so that by the time the food has gained the large intestine it has been di- gested as far as it can be. In its further slow movement along the large intestine the process of absorption of water proceeds rapidly. Disturbances in the digestive process may be due not only to possible inadequacy in the secretion of one or other of the diges- tive juices, but also to disturbances in the movements of the digestive canal. Such disturbances will not only prevent the forward movement of the food at the proper time, but, by failing to agitate the food, they will prevent its proper admixture with the digestive juices, for of course an enzyme acts more rapidly when the mixture is kept thoroughly agitated with the food than when it is stagnant. Digestion in the Mouth. Salivary Secretion. — In the mouth, besides its preparation for swallowing, by mastication, etc., the food, mainly on account of its taste and smell, stimulates sensory nerve endings which, by acting on nerve centres, set agoing several of the digestive secretions. The first of these is the secretion of the salivary glands. On account of their ready accessibility to experimental investigation, very extended studies have been made of the sali- vary glands, and from these studies some of the most important physiological truths, concerning the nature of the nervous con- trol of glands in general, have been drawn. Of the three salivary glands in man, the parotid secretes a watery saliva usually con- taining the enzyme, ptyalin, and the submaxillary and subling- ual secrete a sticky saliva containing mucin, usually along with some ptyalin. When the glands are not secreting, the cells that 40 PHYSIOLOGY FOR DENTAL STUDENTS. compose them are engaged in preparing material to be secreted. By microscopical examination, this material is seen in the proto- plasm of the cells (Fig. 2) as granules, which are extremely small in the serous gland cells, but much larger in the mucous. In both types of gland the granules so crowd the cell that the nucleus becomes indistinct and the cell itself much swollen. After the gland has been active, the granules disappear, being evidently discharged from the cell into the duct of the gland. The granules are believed to represent the precursors of the ptyalin or mucin of saliva — hence their name of "zymogen" or "mother of ferment" granules — rather than these substances A. Fig. 2. — Cells of parotid gland showing zymogen granules : A, after pro- longed rest ; B, after a moderate secretion ; C, after prolonged secretion. (Langley.) themselves. Watery or saline extracts of the glands contain neither mucin nor ptyalin, nor does the addition of acetic acid to a mucous gland cause any precipitate of mucin; indeed, it has an entirely opposite action, it causes the granules to swell. The Nerve Supply of the Salivary Glands. — The nerve fibers supplying the glands are of the autonomic or visceral type (see p. 277), and they include sympathetic and cerebro-spinal fibers. The sympathetic fibers are derived from cells in the lateral horns of the spinal cord, from which they emerge by the upper three or four thoracic roots, and after ascending as medullated fibers in the cervical sympathetic, terminate as synapses around the cells of the superior cervical ganglion. The axons of these cells proceed as non-medullated post-ganglionic fibers along the near- est vessels to the respective glands. The cerebral autonomic SALIVARY SECRETION. 41 fibers arise from a center in the medulla and proceed to the glands by various routes; those to the submaxillary and sub- lingual glands in the chorda tympani, and those to the partoid by way of the tympanic branch of the glosso-pharyngeal. The ganglion cells connected with the cerebral fibers are situated more or less peripherally; in the case of the submaxillary they are embedded in the substance of the gland ; in the case of the sublingual gland, in the connective tissue of the so-called submaxillary triangle, and in the case of the parotid, in the otic ganglion (Fig. 3). In both cerebral and sympathetic nerves there are two vari- eties of fibers, the one vasomotor, the other secretory. The for- Fig. 3. — The nerve supply of the submaxillary gland : Li, lingual nerve ; c. t., chorda tympani ; g. gland Wharton's duct is ligated and it will be noticed that the chorda leaves the lingual nerve, just before this crosses the duct, thus forming the submaxillary triangle. (Claude Bernard.) mer, in the case of the cerebral nerves, are dilator in their action, but in the sympathetic they are constrictor. On account of the association of secretory and vasodilator fibers, in the cerebral nerves, stimulation leads to the secretion of large quantities of saliva, the amount of which, as well as its percentage of organic and inorganic constituents, varies within certain limits, with the strength of the stimulus. Although secretory activities also be- come excited when the sympathetic nerve is stimulated, as is 42 PHYSIOLOGY FOR DENTAL STUDENTS. revealed by histological examination of the gland, there is only a slight flow of saliva from the duct because of the concomitant curtailment of the blood supply. In so far as actual secretion of saliva is concerned, the net result of stimulation of either nerve is therefore dependent upon whether dilatation or constriction of the blood vessels of the gland occurs, and this might lead us to conclude that the secretion is secondary to changes in the blood supply; in other words, that it is unnecessary to assume the independent existence of specific secretory nerve impulses. That such secretory fibers do exist, however, is established by many facts. Two of these are : ( 1 ) The vessels still dilate but no secretion occurs after a certain amount of atropin has been allowe'd to act on the gland. This alkaloid paralyzes the secre- tory nerve fibers, but has no action on those concerned in vaso- dilation. (2) If the secretions were merely the result of in- creased blood supply, in other words, were a filtrate from the blood, the pressure in the duct would at all times be less than that in the blood vessels, but this is not the case, for during stim- ulation of the cerebral nerves the duct pressure may rise far above that of the blood vessels. But it must never be lost sight of that although both kinds of fibers do exist, they are very closely associated in their action. The Reflex Nervous Control of Salivary Secretion. — The structural differences between the parotid and submaxillary glands suggest that their functions may not be the same; that their respective secretions must be required for different pur- poses. To put this supposition to the test, it becomes necessary to -adopt some means by which the conditions calling forth the secretion of each gland may be separately studied. This can be accomplished by a small surgical operation in which the ducts are transplanted so as to discharge through fistulae in the cheek, the secretion being easily collected, by allowing it to flow into a funnel which is tied in place. In general, two distinct types of stimuli may call forth secretion of one or other gland, namely: (1) direct stimulation of senxorii nerve endings in the mouth, and (2) psychological stimuli in- volving more or less of an association of ideas. SALIVARY SECRETION. 43 Of the stimuli which cause secretion by acting on sensory nerve endings in the mouth, some influence the parotid, others the sub- maxillary gland, and different stimuli produce different effects. Even for pure mechanical stimulation of the buccal mucosa, a marked degree of discrimination is shown; thus, smooth clean pebbles may be rolled around in the mouth and yet cause no saliva to be secreted, whereas dry sand will immediately cause the parotid to discharge enormous quantities of thin watery juice. Similarly dry bread crumbs invoke copious parotid secre- tion, bread itself having little effect; water, ice, etc., are inert, but if they contain a trace of acid an abundant secretion is in- stantly poured out. It is plain in all these cases that the pur- pose of the secretion is to assist in the removal or neutralization of the substance which is present in the mouth. The thick mucous secretion of the submaxillary and sublingual glands seems to depend more on the chemical nature of the food than on its mechanical state, boiled potatoes, hard boiled eggs, meat, etc., causing the secretion of a thick slimy saliva, which by coating the food assists swallowing. The relish for the food seems to be of little account in influencing the secretion of saliva, for noxious substances, or those that are acid, or very salty, call forth much more secretion than do savory morsels. Although mere mechani- cal stimulation is not in itself an adequate stimulus, yet move- ment of the lower jaw is quite effective, as for example in chew- ing, or when the mouth is kept open, as by a gag in a dental operation. The stimulus does not, however, require to be applied to the buccal mucosa itself; it may be psychic or associational, and here again a remarkable discrimination is evident, although the response is not so predictable as when the stimulus is local. Thus, when flry bread or sand is shown to a dog to whom previ- ously these substances have been given by mouth, salivation fol- lows, but this is not the . case when moist bread or pebbles are offered. Appetite plays an important part in this psychic reflex, for when dry food is shown to a fasting animal, salivation is marked, but may cause no secretion when it is offered to a well- fed animal. It is possible in this case, however, that there may 44 PHYSIOLOGY FOR DENTAL STUDENTS. -be inhibition of the glandular activities on account of the pres- ence of food products in the blood. Perhaps the most interesting fact of all is that even a fasting animal will after a time fail to salivate if he be repeatedly shown food which causes a secretion, but which he is not permitted to get. The response is immedi- ately established again, however, if some food, or indeed some other object, be placed in the mouth. A hungry animal will even salivate when he hears some sound which by previous experience he has learned to associate with feeding time. The psychic reflexes are evidently dependent upon an association of ideas (a nervous integration, see p. 242) ; they are conditioned reflexes, and are therefore the result of a certain degree of education. They are easily rendered ineffective by confusing the usual asso- ciations. General Functions of Saliva. — These observations indicate that a very important function of the saliva is what we may call a mechanical one, namely, either to flood the mouth cavity with fluid and so to wash away objectionable objects in it, or to lubri- cate the food with mucin and so facilitate swallowing. The sol- vent action of saliva is also important for the act of tasting (see p. 295). Its chemical activities in many animals seem to be lim- ited to the neutralizing properties of the alkali which is present in it, but in man and the herbivora it also contains a certain amount of a diastatic enzyme, ptyalin, which can quickly con- vert cooked starches into dextrines and maltose. Even when this action is most pronounced, however — for it varies considerably in different individuals — it cannot proceed to any extent in the mouth cavity, partly on account of the short time food remains here, and partly because many starches, as in biscuits, are taken more or less in a raw state. In some animals, such as the dog, the saliva has no diastatic action whatever. Although there can therefore be little diastatic digestion in the mouth, a good deal may go on in the stomach, for the saliva that is swallowed along with the food does not become destroyed by the gastric juice until some thirty minutes after the food has gained the stomach. Although mastication of the food and its preparation for swallowing are undoubtedly the main functions of the mouth cav- SALIVARY SECRETION. 45 ity, another exists which is of very great importance for proper digestion; this is the stimulation of the taste nerve endings, and, for foods with a flavor, of those of the olfactory nerve in the posterior nares. Such stimulation not only gratifies the appetite, but it serves as the adequate stimulus to set agoing the secretion of the gastric juice. Without any relish for food, digestion as a whole materially suffers, and for this reason unpalatable food is always more or less indigestible. CHAPTER IV. DIGESTION (Cont'd). The Chemistry of Saliva and the Relationship of Saliva to Dental Caries. A knowledge of the composition and chemical properties of saliva is of great importance because of the undoubted etiologi- cal relationship which exists between this secretion and dental caries. Mixed saliva when freshly secreted is a watery, more or less opalescent and sticky fluid, often containing small masses of mucin, but on standing it becomes cloudy because of precipi- tation of calcium carbonate. Its specific gravity is 1002-1006, and it contains about 0.05 per cent of solids. The saliva from the sublingual and submaxillary glands is very much richer in solids than that from the parotid. The parotid saliva also differs from that of the other glands in containing no mucin, although it is often rich in ferment. The solid constituents, with some of their properties, are as follows : Glycoprotein (mucin) : precipitated by acid. Other proteins: coagulated by heat. Organic. . .-\ Ptyalin: a starch-splitting enzyme. Potassium sulphocyanide : gives a red color with ferric chloride. Sodium chloride : ) give a precipitate with sil- Potassium chloride : | ver nitrate. Calcium bicarbonate : in fresh saliva. Calcium carbonate : precipitated in saliva after Inorganic.^ standing. Calcium and magnesium 1 Have an important re- phosphates: lationship to the neu- Sodium and potassium | tralizing properties phosphates: J of saliva. Organic Constituents. — Mucin is the substance to which saliva owes its stickiness. Being a glycoprotein, it yields reduc- 46 CHEMISTRY OP SALIVA. 47 ing sugar when it is hydrolyzed, as by boiling with acid. It was at one time suggested that sugar might sometimes appear in the saliva, as a result of bacterial action in the mouth, and be respon- sible for caries of the teeth. The amount is, however, so very small in comparison with the ingested carbohydrates that it can be entirely disregarded. Ptyalin. — This belongs to the class of diastatic or amylolytic enzymes, converting starch into sugar. It is not so powerful as the similar enzyme in pancreatic juice (see p. 74), for it has no action on uncooked starch, which the latter has. It acts best in neutral reaction and in the presence of sodium chloride, but is little affected by a small degree of akalinity. On the other hand, it is readily destroyed by acids and by higher degrees of alkalinity. These facts are of importance in connection with the continuance of action of saliva after it has been swallowed, for although the food remains in the mouth for much too brief a period to permit of more than a trace of sugar being formed here, yet, after the stomach is reached, ptyalin may continue to act for about half an hour. The ptyalin content, however, varies very considerably in different individuals. Ptyalin converts starch into the sugar maltose, so called be- cause it is also formed by the action of the diastase of malt. As intermediate substances are formed the dextrins, two of which are distinguishable on account of their behavior towards iodine ; the first dextrin, called erythrodextrin, gives a brown color, while the next gives no color and is called achroodextrin. It has been suggested that a deficiency of ptyalin may pre- dispose to caries of the teeth because, under such circumstances, a large amount of dextrin is formed, which being very sticky in character adheres to the teeth and becomes a suitable nidus for bacterial growth. Potassium Sulphocyanide (sulphocyanate) . — This salt has the formula KCNS, and is usually present in human saliva to the extent of about 0.01 per cent. It is produced in the blood whenever cyanides or organic nitrites make their appearance in the organism, one source for these being possibly protein meta- bolism (p. 108). It is excreted from the blood into the urine as 48 PHYSIOLOGY FOR DENTAL STUDENTS. well as the saliva. In contrast to cyanides it is non-poisonous, so that it represents the inocuous form into which these substances are converted. The chemical test used for its detection is the red color which it gives with a solution of ferric chloride (FeCl3). Sometimes, however, the reaction is not very definite, in which case the method of Bunting should be employed. This is performed as follows : Slowly evaporate 5 c. c. of saliva in a watch glass and while stirring with a glass rod add a few drops of a 26 per cent solution of FeCl3. Pour about 5 c. c. of a mixture of 5 parts amyl alcohol and 2 parts ether over the residue, and after stir- ring decant into a test tube. If sulphocyanide is present, the alcohol-ether will become red. Benzoate and aceto acetic acid may give a similar reaction, but most of the other substances which might interfere witii the test, as when it is done by merely adding FeCl3 to saliva, are eliminated by Bunting's method. All this care and interest in the testing for KCNS has arisen because of the supposition that the amount of this substance in saliva might have some relationship to caries of the teeth. It was suggested that it might confer on the saliva somewhat of an antiseptic action and thus destroy the bacteria that are the cause of caries. Careful work by Bunting, by Gies and others has. however, shown that this hypothesis is untenable. Inorganic Constituents. — Two important questions arise in connection with these, viz: (1) their relationship to the reaction of the saliva; (2) the conditions which control the precipitation of calcium carbonate and phosphate and the deposition of the precipitate on the teeth in the form of tartar. THE REACTION OF THE SALIVA. — Tested with litmus paper sa- liva is more or less alkaline and it is distinctly so towards lac- moid and Congo red, but it is acid when tested with phenolph- thalein. It is thus said to be amphoteric, like blood and urine Difficulty in deciding as to the reaction of saliva is partly due to the fact that it changes on standing because carbon-dioxide (CO2) is dissipated, thus making it more alkaline. To succeed in determining the reaction of saliva, we must therefore under- stand to what its amphoteric behavior is due and we must con- CHEMISTRY OP SALIVA. 49 stantly bear in mind that the real reaction of a fluid is the ratio between free H- and OH-ions (see p. 30). By analysis saliva has been found to contain phosphates and carbonates, both of which are capable of existing either as acid or alkaline salts, that is to say, as NaH2P04 and NaHC03 (acid salts) or Na2HP04 and Na2C03 (alkaline salts). Since the reaction given by solu- tions which contain such mixtures of acid and alkaline salts depends, first, on the relative proportions of these salts and, secondly, on the exact indicator employed to test the reaction (see p. 31), it is plain that the reaction of the saliva as ordi- narily tested must be very haphazard. To determine the H-ion concentration of saliva, some of this fluid is diluted about ten times with distilled water, which has been boiled and cooled so as to free it of carbon dioxide, and 0.5 c. c. of paranitrophenol solution is added. The resulting tint is then compared with that obtained by adding 0.5 c. c. of the same indicator to each of a series of test tubes containing vary- ing proportions of acid and alkaline phosphate solutions (yi5 normal). The tint of this series which matches with that of the saliva indicates the H-ion concentration of the latter because this is known in the standard from the proportion of the two phosphates present. THE METHOD OP MEASURING THE NEUTRALIZING POWER OP SA- LIVA.— Interesting though H-ion results may be, they do not ap- pear to be of any practical value in connection with the relation- ship between the saliva and caries of the teeth. To study this question it has been found to be of more value to determine the neutralizing power of saliva ; that is, to find out how much stand- ard acid or alkali we must add to a measured quantity of saliva in order to get a change with one or more of the above indicators. In doing this, however, we are immediately struck with the fact that the reaction does not change in proportion to the amount of acid or alkali added, but that the saliva under such conditions possesses the property of changing very slowly in reaction. This same property also exists in the blood, and it depends on a series of changes which the phosphates and carbonates can undergo, when acids or alkalies are added to solutions containing them, 50 PHYSIOLOGY FOR DEKTAL STUDENTS. without causing any considerable amount of free H- or OH-ion to be set free. This has been called the "buffer action" of such salts. It endows the saliva with the power of locking away con- siderable quantities of acid or alkali. In actually measuring the neutralizing power of saliva, it is best first of all to bring the saliva to a definite H-ion concentra- tion by adding standard acid and then to find out how much alkali is required to bring it to another definite H-ion concentra- tion. The methods for applying the above principles are as follows : 10 c.c. saliva is diluted in an evaporating dish with 20 c.c. water which has been boiled to expel CO, and then cooled to 20°C. About eight drops of an aqueous solution of paranitro- phenol is then added and N/200 HC1 run in from a burette, with constant stirring until the yellow color due to the indicator just disappears. The amount of N/200 HC1 is noted. N/200 NH4HO is then added till the yellow color just returns.1 The difference between the two readings gives the alkalinity in terms of c.c. of N/200 HC1. The acidity may be directly measured by adding four drops of an alcoholic solution of phenolphthalein to another 10 c.c. sample of saliva and running in N/200 NaOH until a definite pink color results. Addition of the acidity and alkalinity results gives the total neutralizing power of the saliva, or in other words the power of maintaining neutrality. This is a much more constant property of saliva than the acidity or alkalinity alone, and it has conse- quently been used, in the most recent work of Marshall,2 for the purpose of ascertaining whether the susceptibility to dental ca- ries bears any relationship to the reaction of the saliva. It \\.is found that it does not. On the other hand, this author has shown iThe reason for titrating back with N/200 NH«HO till a yellow color again reappears, when measuring the alkalinity, is to increase the accuracy of the titration, it being often difficult to decide the point at which the color disap- pears when N/200 acid is added, but easy to decide when it reappears when N/200 NH4HO is used. NaOH is employed in the acidity titration because phenolphthalein cannot be used with ammonia. 2Cf. J. A. Marshall, Amer. Jour, of Physiology, 1915, XXXVI, p. 260. CHEMISTRY OF SALIVA. 51 that the neutralizing power of saliva, collected without any ef- fort or artificial stimulation of the mouth (resting saliva), is very distinctly less than that of saliva collected whilst chewing on a piece of paraffin (activated saliva), and that this difference becomes -very much Jess in those with carious teeth. Marshall has suggested that we should express the ratio of the neutraliz- ing power of resting saliva to that of activated saliva as a per- centage ratio, which he calls the salivary factor. In persons im- mune from caries this factor amounted to 43-80; in those with caries it varied from 80-132. The following examples will illus- trate these points : NORMAL RESTING SALIVA ACTIVATED SALIVA Case c. c. N/200 HC1 c. c. N/200 NaOH Neutral- izing- Power c. c. • N/200 HC1 c. c. N/200 NaOH Neutral- izing Power Salivary Factor No. caries 22.22 7.60 29.82 57.55 0.90 58.45 51 Carious Without care 18.50 7.00 25.50 22.80 2.13 24.93 102 If these interesting observations should prove to be confirmed by other observers, it will supply us with a comparatively simple method for solving what has hitherto been a most puzzling ques- tion and which has prompted several observers, particularly Bunting and Price, to employ the very delicate physico-chemical methods of the concentration cell (p. 31) and electrical conduc- tivity to its elucidation. Before leaving the subject of the relationship between the character of the saliva and the occurrence of dental caries, it may be well to point out that other factors besides the neutral- izing power of the saliva must be taken into consideration, name- ly, its amount and the presence of phosphates. A large and free flow of saliva, besides mechanically cleansing the teeth, will offer more neutralizing fluid. An excess of phosphates, on the other hand, will encourage fermentation of any carbohydrate which may be adherent to the teeth and, by forming acids, thus tend to erode the teeth and predispose to caries. 52 PHYSIOLOGY FOR DENTAL STUDENTS. Tartar Formation and Salivary Calculi.— Under certain con- ditions a precipitate, varying in color from pale yellow to almost black, collects on the teeth, particularly on the lower incisors and molars. This precipitate is called tartar, and it may be either hard (as on the incisors) or soft (as on the molars). Its chemical composition varies considerably, but may be given as follows : I II Water and organic matter 32.24 per cent 31.48 per cent Magnesium phosphate 0.98 per cent 4.91 per cent Calcium phosphate 63.08 per cent 72.73 per cent Calcium carbonate 3.7 per cent (Talbot) The organic matter consists of epithelial scales, other extran- eous matter and leptothrix chains. The place and manner of deposition shows clearly that the tartar is largely derived from the saliva, the chemical explanation of the precipitation being probably as follows : Saliva, as it is produced in the gland, con- tains calcium bicarbonate, which is soluble in water, and is pre- vented from changing into the insoluble carbonate by the pres- ence of free carbon dioxide in solution. When the saliva is dis- charged into the mouth some of the carbon dioxide escapes from it so that the bicarbonate changes to carbonate and becomes pre- cipitated. The precipitate carries down with it phosphates as well as any organic debris or mico-organisms that may be present. The precipitation of calcium carbonate may even take place in the salivary ducts (Wharton's), thus forming salivary calculi, which may reach the size of a pea or larger. Such calculi may contain as much as 3.8 per cent of organic matter, the remainder being largely calcium carbonate. The following table gives the composition of three such calculi : I II III Calcium carbonate 81. 2 per cent 79.4 per cent 80.7 per cent Calcium phosphate 4.1 per cent 5.0 per cent 4.2 per cent Magnesium phosphate ... » present Organic matter and other soluble solids 13.3 per cent 13.3 per cent 13.4 per cent Water 1.3 per cent 2.3 per cent 1.7 per cent (Talbot) CHAPTER V. DIGESTION (Cont'd). Mastication : Deglutition : Vomiting. Mastication. — By the movements of the lower jaw on the upper, the two rows of teeth come together so as to serve for bit- ing or crushing the food. The resulting comminution of the food forms the first step in digestion. The manner of occlusion of the cusps of the teeth in the performance of this act is not a problem of Physiology, but rather of Anatomy and Orthodontics; never- theless, the other factors which contribute to the efficiency of the process and the condition into which the food is brought by it are subjects to which we must devote some attention. The up and down motion of the lower jaw results in biting by the in- cisors, and after the mouthful has been taken, the side to side movements enable the grinding teeth to crush and break it up into fragments of the proper size for swallowing. The most suit- able size of the mouthful is about five cubic centimetres, but this varies greatly with habit. After mastication, the mass weighs from 3.2 to 6.5 grammes, about one-fourth of this weight being due to saliva. The food is now a semi-fluid mush containing par- ticles which are usually less than 2 millimetres in diameter. Some, however, may measure 7 and even 12 millimetres. Determination of the proper degree of fineness of the food is a function of the tongue, gums and cheeks, for which purpose the mucous membrane covering them is supplied with very sensitive touch nerve endings (see p. 244). The sensitiveness of the tongue, etc., in this regard explains why an object which can scarcely be felt by the fingers seems to be quite large in the mouth. If some particles of food that are too large for swallow- ing happen to be carried backward in the mouth, the tongue re- turns them for further mastication. The saliva assists in mastication in several ways: (1) by dis- solving some of the food constituents; (2) by partially digesting 53 54 PHYSIOLOGY FOR DENTAL STUDENTS. some of the starch; (3) by softening the mass of food so that it is more readily crushed; (4) by covering the bolus with mucus so as to make it more readily transferable from place to place. The secretion of saliva is therefore stimulated by the chewing movements, and its composition varies according to the nature of the food (p. 43). In some animals, such as the cat and dog, there is no mastication, coating of the food with saliva being the only change which it undergoes in the mouth. In man the ability thus to bolt the food can readily be acquired, not however without some detriment to the efficiency of digestion as a whole. Soft starchy food is little chewed, the length of time required for the mastication of other foods depending mainly on their nature, but also to a certain degree on the appetite and on the size of the mouthful. The crushing force of the molars, as measured by a dyna- mometer, has been found to rise as high as 270 pounds, which is far in excess of the force required to crush the ordinary food stuffs. Thus cooked meats have a crushing point which varies between 15 and 80 pounds on direct thrust, but is considerably less when there is a side to side movement, as there is in chewing. Candies have a crushing point of 30 to 110 pounds, and nuts 55 to 170 pounds. Admixture of the food with saliva greatly lowers the crushing point, especially in the case of such foods as soft bread. Without such admixture this hardens into a solitl mass when it is crushed, whereas it readily breaks up into small particles in the presence of saliva. It cannot be too strongly insisted upon that the act of masti- cation is of far more importance than merely to break up and prepare the food for swallowing. It causes the food to be moved about in the mouth so as to develop its full effect on the taste buds; the crushing also releases odors which stimulates the ol- factory epithelium. On these stimuli depend the satisfaction and pleasure of eating, which in turn initiate the process of gas- tric digestion (see p. 60). Thus it has been observed in chil- dren with gastric fistula- that the chewing of agreeable fond caused the gastric juice to be actively secreted, which, however, was not the case when tasteless material was chewed. DEGLUTITION. 55 The benefit to digestion as a whole of a large secretion of sa- liva, brought about by persistent chewing, has been assumed by some to be much greater than it really is, and there has existed, and indeed may still exist, a school of faddists who, by deliber- ately chewing far beyond the necessary time, imagine themselves to thrive better on less food than those who occupy their time with other more profitable pursuits. Deglutition or Swallowing. — After being masticated the food is rolled up by the tongue acting against the palate into a bolus, and this, after being lubricated by saliva, is moved, by elevation Fig. 4. — The changes which take place in the position of the root of the tongue, the soft palate, the epiglottis and the larynx during the second stage of swallowing. The thick dotted line indicates the position during swal- lowing. of the front of the tongue, towards the back of the mouth. This constitutes the first stage of swallowing, and is, so far, a volun- tary act. About this time a slight inspiratory contraction of the diaphragm occurs — the so-called respiration of swallowing — and the mylohyoid (the muscles of the floor of the mouth) quickly contracts with the consequence that the bolus passes between the 56 PHYSIOLOGY FOR DENTAL STUDENTS. pillars of the fauces. This marks the beginning of the second stage, the first event of which is that the bolus, by stimulating sensory nerve endings, acts on nerve centers situated in the me- dulla oblongata so as to cause a coordinated series of movements of the muscles of the pharynx and larynx and an inhibition for a moment of the respiratory center (p. 219). The movements alter the shape of the pharynx and of the various openings into it in such a manner as to compel the bolus of food to pass into the oesophagus: (see Fig. 4) thus, (1) the soft palate becomes elevated and the posterior wall of the pharynx bulges forward so as to shut off the posterior nares, (2) the posterior pillars of the fauces approximate so as to shut off the mouth cavity, and (3) in about a tenth of a second after the mylohyoid has con- tracted, the larynx is pulled upwards and forwards under the. root of the tongue, which by being drawn backwards becomes banked up over the laryngeal opening. This pulling up of the larynx brings the opening into it near to the lower half of the dorsal side of the epiglottis, but the upper half of this structure projects beyond and serves as a ledge to guide the bolus safely past this critical part of its course. (4) To further safeguard any entry of food into the air passages, the laryngeal opening is narrowed by approximation of the true and false vocal cords. The force which propels the bolus, so far, is mainly the con- traction of the mylohyoid, assisted by the movements of the root of the tongue. When it has reached the lower end of the pharynx, however, the bolus readily falls into the oesophagus, which has become dilated on account of a reflex inhibition of the constrictor muscles of its upper end. This so-called second stage of swallowing is therefore a complex coordinated movement ini- tiated by afferent stimuli and involving reciprocal action of various groups of muscles : inhibition of the respiratory muscles and of those that constrict the oesophagus, and stimulation of those that elevate the palate, the root of the tongue yand the larynx. It is purely an involuntary process. The third stage of deglutition consists in the passage of the swallowed food along the oesophagus. The way in which this is done depends very much on the physical consistence of the food. DEGLUTITION. 57 A solid bolus, that more or less fills the oesophagus, excites a typical peristaltic wave which is characterized by a dilatation of the oesophagus immediately in front of, and a constriction over and behind the bolus. This wave travels down the cesopha- gus at such a rate that it reaches the cardiac sphincter in about five or six seconds. On arriving here the cardiac sphincter, ordinarily contracted, relaxes for a moment so that the bolus passes into the stomach. The peristaltic wave travels much more rapidly in the upper portion of the oesophagus than lower down because of differences in the nature of the muscular coat, this being of the striated variety above, and of the non-striated, be- low. The purpose of more rapid movement in the upper portion is no doubt that the bolus may be hurried past the regions, where, by distending the oesophagus, il might interfere with the function of neighboring structures, such as the heart. The peris- taltic wave of the oesophagus, unlike that of the intestines (see p. 79), is transmitted by nerves, namely, by the oesophageal branches of the vagus. If these be severed, but the muscular it- self left intact, the oesophagus becomes dilated above the level of the section and contracted below, and no peristaltic wave can pass along it ; on the other hand, the muscular coat may be sev- ered (by crushing, etc.) but the peristaltic wave will jump the breach provided no damage has been done to the nerves. The propagation of the wave by nerves indicates that the sec- ond and third stages of deglutition must be rehearsed, as it were, in the medullary nerve centers from which arise the fibers to the pharynx and the different levels of the oesophagus. The afferent stimuli which initiate this process proceed from the pharynx by the fifth, superior laryngeal and vagus nerves and not at all from the oesophagus itself; thus, a foreign body placed directly in the oesophagus remains stationary, but immediately begins to move if the pharynx be stimulated, as by touching it. The. af- ferent fibers in the glossopharyngeal nerve exercise a powerful inhibitory influence on the deglutition center as well as on that of respiration. Thus, if swallowing movements be excited by stimulating the central end of the superior laryngeal nerve, they can be instantly inhibited by simultaneously stimulating the 58 PHYSIOLOGY FOR DENTAL STUDENTS. glossopharyngeal, and the respiratory movements stop in what- ever position they may have been in at the time. This inhibition of the oesophagus is indeed a most important part of the process when liquid or semi-liquid food is swallowed By the contraction of the mylohyoid muscle, fluids are quickly shot down the distended oesophagus, at the lower end of which, on account of the cardiac sphincter being closed, they accumulate until the arrival of the peristaltic wave which has meanwhile been set up by stimulation of the pharynx. If the swallowing is immediately repeated, as is usually the case in drinking, the oesophagus remains dilated because peristalsis is inhibited, and the fluid lies outside the cardiac orifice until the last mouthful has been taken. These facts have been revealed by listening with a stethescope to the sounds produced by swallowing, and by observing with an X-ray lamp the shadows produced along the course of the oesophagus when food, impregnated with bismuth subnitrate, is taken. When a solid bolus is swallowed, one sound is usually heard, but with liquid food there are two, one at the upper end, due to the rush of the fluid and air and the other at the lower end (heard over the epigastrium) some four or six seconds later, due to the arrival here of the peristaltic wave with the accom- panying opening of the cardiac sphincter and the escape of the fluid and air into the stomach. Sometimes, as when the person is in the horizontal position, this second sound may be broken up into several, indicating that, unassisted by gravity, the fluid does not so readily pass through the sphincter. The X-ray shadows yield results in conformity with the above. After swallowing milk and bismuth, for example, the shadow falls quickly to the lower end of the oesophagus and then slowly into the stomach. When the passage of a solid bolus is watched by the X-ray method, its rate of descent will be found to depend on whether or not it is well lubricated with saliva ; if not so, it may take as long as fifteen minutes to reach the stomach ; if moist, but from eight to eighteen seconds. The Act of Vomiting. — This is usually preceded by a feeling of sickness or nausea and is initiated by a very active secretion VOMITING. 59 of saliva. The saliva, mixed with air, accumulates to a consider- able extent at the lower end of the oesophagus and thus distends it. A forced inspiration is now made, during the first stage of which the glottis is open so that the air enters the lungs, but later the glottis closes so that the in- spired air is sucked into the oesophagus, which, already somewhat distended by saliva, now becomes markedly so. The abdominal muscles then contract so as to compress the stomach against the diaphragm and, simultaneously, the cardiac sphincter relaxes, the head is held forward and the contents of the stomach are ejected through the previously distended oesophagus. The compression of the stomach by the contracting abdominal mus- cles is assisted by an actual contraction of the stomach itself, as has been clearly demonstrated by the X-ray method. (See p. 58.) After the contents of the stomach itself have been evac- uated, the pyloric sphincter may also relax and thus permit the contents (bile, etc.) of the duodenum to be vomited. The act of vomiting is controlled by a center located in the medulla, and the afferent fibers to this center may come from many different regions of the body. Perhaps the most potent of them come from the sensory nerve endings of the fauces and pharynx. This explains the tendency to vomit when the mucosa of this region is mechanically stimulated. Other afferent im- pulses come from the mucosa of the stomach itself, and these are stimulated by swallowing certain drugs called emetics, import- ant among which are strong salt solution, mustard water, zinc sulphate, etc. When some poisonous substance has been swal- lowed, the immediate treatment is to give one of these emetics and thus cause the poison to be vomited. Certain other emetics, particularly tartar emetic and apomorphine, act on the vomiting center itself, and can therefore act when given subcutaneously. Afferent vomiting impulses also arise from the abdominal vis- cera, thus explaining the vomiting which occurs in strangulated hernia, and in other irritative lesions involving this region. CHAPTER VI. DKiESTION (Cont'd). Digestion in the Stomach. The Secretion of Gastric Juice. — After passing the cardiac sphincter, the food collects in the fundus of the stomach. When it is solid in consistency it becomes disposed in definite layers, the first swallowed near the mucosa, the last swallowed in the center. When, as is usual in man, the food is more or less fluid, this layer formation is less evident and it collects in the most de- pendent part of the body of the stomach (see Fig. 5). Within a few minutes of the entry of the first portion of food, the glands of the gastric mucosa begin to secrete their digestive juices. The immediate exciting cause of this secretion is not the contact of food with the mucosa — although this acts later — but is a ner- vous stimulus transmitted to the stomach through the vagus nerve1 and coming from a nerve center situated in the medulla. The aetii'iti( s of Ihis y as trie ct nt< r arc called into operation by afferent impulses in the nerres that lirminate in the taste buds and olfactory epithelium. The process of gastric secretion is therefore initiated in the mouth, and the stimulus that is re- sponsible for it is the good taste and the flavor of the food. Just as in the case of the salivary glands, the food, in order to excite the secretion, need not actually enter the mouth for a psychologi- cal stimulus may also act on the gastric center. Thus the sight or smell of savory food, or even the hearing of some sound that is known by experience to be associated with the gratification of the appetite can call it forth. These important facts were first of all revealed by observations through a gastric fistula made in the case of a boy who. by swallowing strong alkali, was unable to take food by the mouth because of stricture of the (esophagus ; i After cuttiny the vuyi, this secretion of yastric juice does not occur. 60 DIGESTION IN THE STOMACH. 61 he had to be fed through the gastric fistula, but whence was al- lowed to chew food for which he had a relish and then spit it out, gastric secretion occurred. This observation suggested to Paw- low the establishment of analogous conditions in dogs, with the modification that, besides the fistula in the stomach, one was made of the oesophagus in the neck in such a way that swallowed food escaped by it. The animal could therefore swallow inter- minably without ever becoming satisfied, and it was observed Fig. 5. — Diagrams of outline and position of stomach as indicated by skia- grams taken on man in the erect position at intervals after swallowing food impregnated with bismuth subnitrate. A, moderately full ; B, practically empty. The clear space at the upper end of the stomach is due to gas, and it will be noticed that this "stomach bladder" lies close to the heart. (T. Wingate Todd.) that when it did so, gastric juice flowed, provided this "sham feeding" was with appetizing food. Stones, bread, acid or irri- tating substances, although they might cause much saliva to be secreted and swallowed (see p. 43), had no influence whatso- ever on the flow of gastric juice. The only adequate stimulus was gratification of the appetite. 62 PHYSIOLOGY FOR DENTAL STUDENTS. Iii passing, it may be well to call attention to the practical importance of these observations in connection with the feeding of debilitated persons ; by frequent feeding with appetizing food the nutritional condition is likely to improve much more rapidly than by occasional stuffing with uncongenial mixtures, however rich these may be in calories and nitrogen. The secretion is therefore well named the appetite juice, and. it lasts sometimes for nearly two hours after sham feeding has been discontinued. Yet this is only about one-half as long as the time during which gastric juice is secreted when the food is ac- Fig. 6. — Diagram of stomach showing miniature stomach (S) separated from the main stomach (V) by a double layer of mucous membrane. A. A. is the opening of the pouch on the abdominal wall. (Pawlow. ) tually permitted to enter the stomach. In order to investigate the cause of the continued secretion, it was necessary to devise some means by which the gastric juice could be collected, un- mixed with food, while normal digestion was in progress. Hav- ing no duct the only means by which this could be done was by isolating a portion of the stomach as a pouch with an opening exteriorly through which the secretions collecting in it could be removed. An operation for making such a pouch, or "miniature stomach," as it is called, without injuring any of the nerves of DIGESTION IN THE STOMACH. 63 the stomach has been devised by Pawlow (see Fig. 6). By sim- ultaneously collecting the secretions from the main stomach and the miniature stomach after sham feeding, it was found that they ran strictly parallel with one another, in amount as well as in strength of secretion. The secretion in the miniature stomach therefore accurately mirrors the secretion occurring in the main stomach, and so permits us to study this when food is actually being digested. . By introducing food directly into the main stomach through a fistula, it was found, by observations on the secretions from the miniature stomach, that very little secretion occurred until after some time, provided of course that precautions had been taken, as by experimenting on a sleeping animal, not to excite the appe- tite juice. There was found to be great discrimination in the nature of the adequate stimulus for this local secretion ; mechani- cal stimulation of the gastric mucosa, contact with alkaline fluids, such as saliva, or with white of egg, failed to produce any secre- tion ; water had a slight effect, milk still more, whereas a marked secretion occurred when a decoction of meat or meat extract, or a solution containing the half digested products of peptic diges- tion (such as Witte's peptone) was placed in the main stomach. It was further observed, when meat was directly placed in the stomach, that the juice which collected in the pouch increased, both in quantity and in strength, after the first hour, and that it continued to flow even after four hours, thus indicating that the primary stimulus had come from the extractives in the meat, but that, as the protein of the meat became digested, further stimulation occurred on account of the proteose and peptones liberated. This local stimulation is independent of the medullary nerve center that controls secretion of the appetite juice, for it still oc- curred after both vagi had been divided or even after destruc- tion of the sympathetic nerve pelxuses in the abdomen. It might, however, still be a nervous reflex involving the local nerve struc- tures (plexus of Auerbach) in the walls of the stomach, although this is not so probable as that it is dependent upon some chemical excitation of the gland cells by substances appearing in the blood 64 PHYSIOLOGY FOR DENTAL STUDENTS. as a result of absorption from the stomach. This "hormone" (see p. 124) is not merely absorbed food, for no gastric secretion occurred when solutions of meat extract, or of peptone were in- jected intravenously. It must therefore be some substance that is absorbed into the blood from the mucous membrane of the stomach, and which is produced in this as a result of the action of the gastric contents on its cells. In confirmation of this view it has been shown that boiled extracts of the mucous membrane of the pyloric region of the stomach (made with water or weak acid or solutions of peptone or dextrin) cause some gastric juice to be secreted when they are injected in small quantities every ten minutes into a vein, similar injections of the extracting fluids themselves being without effect. We are now provided with the necessary facts upon which to draw a completed picture of the mechanism of gastric secretion. The satisfaction of taking food causes appetite juice to flow and this soon digests some of the protein. The products of this diges- tion, along with the extractive substances of the food, after some time (which is probably quite short in the case of man), gain the pylorus, where they act on the mucosa to produce some hormone, which becomes absorbed into the blood and stimulates further secretion of the juice. As digestion proceeds juice therefore con- tinues to be secreted. The appetite juice sets the process agoing ; it ignites gastric digestion. The Active Constituents of Gastric Juice. — When there is no food in the stomach, a certain amount of the mucous secretion is present in it, and most of the gland cells are filled with zymo- gen granules (see p. 40). An extract (made with glycerine) of the mucosa in this resting condition exhibits no digestive powers; but if the mucosa be first of all macerated with weak hydrochloric acid, the extract becomes highly active, because it contains large amounts of the proteolytic ferment pepsin. Other cells in the stomach produce the necessary hydrochloric acid. It may be concluded therefore that during the process of secre- tion the zymogen granules in the cells are acted on by hydro- chloric acid and converted to pepsin. In conformity with this, it has been found that the secretion of a pouch of stomach pre- DIGESTION IN THE STOMACH. 65 pared from the pyloric region possesses no digestive activity, for in this region no hydrochloric acid is secreted. The activation of this pepsinogen can also be accomplished by tissue extracts and by the products of micro-organismal growth. Because of such growth in the stomach contents, it is often found, in dis- eased conditions in which there is no acid secretion, that active pepsin is present. Accompanying the pepsin, if indeed not iden- tical with it, the gastric juice contains the milk-curdling ferment, rcnnin. It also contains a fat-splitting ferment, lipase, whose activities are, however, limited to emulsified fats. The most remarkable constituent of the gastric secretion is hydrochloric acid, which in some animals, such as the dog, may attain a percentage of 0.6, being usually about 0.2 in the case of man. It is derived from the parietal cells of the glands in the cardiac region of the stomach, none being present in the secre- tion of the pyloric region, where there are no parietal cells. The source of the acid is of course the blood, for although this is practically neutral, yet it contains, on the one hand, substances such as sodium bicarbonate which readily yield hydrogen ions, and on the other, chlorides which, by dissociation, make chlorine ions readily available. Although it is thus possible, in the light of modern physico-chemical teaching, to formulate an equation for the reaction, yet we are at a loss to explain why just at this particular place (i. e., in the gland cells of the stomach) in the animal body and nowhere else the Cl- and H-ions should be picked out of the blood and secreted as HC1. Little as we know about the cause and mechanism of the secre- tion of hydrochloric acid, we do know something regarding its value and use in the process of digestion, and in general we may state that this is partly regulatory and partly digestive. It is regulatory in that it serves as the exciting cause of subsequent events in the digestive process, and digestive not Qnly in that it actually assists in the break-down of protein, but also because it may cause a certain amount of acid hydrolysis of sugar after it has neutralized all the alkali of the swallowed saliva. Its action on protein is, however, the most important, for it initiates pro- teolytic break-down by producing so-called acid protein on 66 PHYSIOLOGY FOR DENTAL STUDENTS. which the pepsin — itself also dependent, as we have seen, on a preliminary activation by acid — then unfolds its action. As the protein becomes progressively broken down into proteose and peptones, the acid becomes more and more absorbed, so that it is some considerable time after gastric digestion has started before any acid is allowed to exist in the free state. It is only after some of it is free that it can hydrolyse sugars or perform an- other important function, namely, act as an antiseptic. In this regard, however, it must be remembered that it is only towards certain organisms that such antiseptic action is displayed, for there may be bacteria in the gastric contents even in cases of ex- cessive secretion of hydrochloric acid. The undoubted tendency for intestinal putrefaction to increase when there is a deficient secretion of hydrochloric acid is probably dependent more upon the delay in digestion which this occasions, than upon any spe- cific antiseptic power of hydrochloric acid. During the time that elapses before a sufficiency of hydrochloric acid has accumulated to perform this function, bacterial fermentation occurs in the stomach contents. Carbohydrates are broken down by this pro- cess, at first into simple sugars and then into lactic acid, which may come to be present in considerable amount before the fer- mentation process is terminated. For these reasons we find that there is relatively much more lactic acid detectable in the gastric contents removed by the stomach tube at an early stage in gastric digestion than later. The so-called acid albumin which results from the action of the acid, becomes attacked by the pepsin, which still further breaks it down into so-called proteose and peptones, which do not coagulate by heat and which become progressively more dif- fusible through animal membranes. Although pepsin is capable of carrying the digestive process far beyond the stage of pep- tones, this does not occur in the comparatively short time (about six hours) during which the food remains in the stomach. Slight as is this action of pepsin in the stomach, it nevertheless appears to be of considerable importance for the subsequent digestion of protein by the other proteolytic ferments, trypsin and erepsin (see p. 75), which operate in the small intestine. Thus, a given DIGESTION IN THE STOMACH. 67 amount of blood serum becomes digested much further in a given time by a given amount of trypsin if it receives a prelim- inary digestion by means of pepsin, than when it is acted on by trypsin alone, and erepsin will cause no digestion at all unless the native protein is first of all acted on either by pepsin or trypsin. But peptic digestion is not essential for life, for sev- eral cases are now on record in which individuals have thrived after the stomach has been removed. The milk curdling action of gastric juice is due partly to the hydrochloric acid and partly to pepsin. Curiously enough the curdled milk undergoes little further change until the food has got to the small intestine. The lipase in gastric juice can act only on emulsified fat and in neutral or alkaline reaction. Fat digestion cannot therefore be an important gastric process. It has been supposed that there is a certain specific adaptation between the chemical nature of the food and the amount and strength of the gastric secretion. For example, it has been found, by observations on the juice flowing from a miniature stomach, that feeding in the ordinary way with bread causes a maximal secretion during the first hour, whereas with an equiva- lent amount of flesh the maximum occurs during the first and second hours, and with milk it is delayed till the third or fourth. In proteolytic power the bread juice is much the strongest of the three, but it contains a lower percentage of acid than the others. The Movements of the Stomach. — Solid food after being swallowed accumulates in the body of the stomach, where on ac- count of an absence of movements it is not uniformly acted on by the gastric juice, its outer layers only becoming digested. In the case of the man, however, some of the food, because of its semi-fluid nature, passes beyond the so-called transverse band and into the pyloric region, in which waves of contraction make their appearance. Starting very faintly at this point, these waves travel towards the pylorus and become gradually more marked until they may become so deep as practically to cut off a portion of the pyloric region from the rest of the stomach. This last portion of the pylorus, sometimes called the pyloric canal. 68 PHYSIOLOGY FOR DENTAL STUDENTS. gradually contracts on the food which has been forced into it, thus tending to eject it through the pyloric sphincter, or, if this is closed, to cause it to pass back again as an axial stream into the proximal part of the pylorus, which has been called the pyloric vestibule (see Fig. 5). These waves occur every fifteen to twenty seconds, three or four being present in the pyloric vestibule at the same time. They become more marked as diges- tion proceeds, and are accompanied by a gradual diminution in size of the body of the stomach. Their function, besides carrying the food towards the outlet of the stomach, is to keep it properly mixed with the gastric juice. The Opening of the Pyloric Sphincter. — The mere pressure with which the contents of the vestibule are thus driven, with each peristaltic wave, against the pyloric sphincter does not, however, in itself serve to open it; for half an hour after feed- ing with protein, for example, no food may pass the sphincter, although during this time there may have been' well over a hun- dred peristaltic waves. Nor is it the consistency of the food which controls the opening. It must therefore be some chemical property which the food acquires during its stay in the stomach. This has definitely been shown by Cannon to be the presence of free acid. By measuring the length of the skiagram shadow in the intestines after feeding cats with bismuth-impregnated foods rendered acid or alkaline, it could be clearly shown that acid hastened the initial discharge, whereas alkalies retarded it, and observations through a fistula in the vestibule showed that any delay in the appearance of acid in the contents was associated with a delay in the opening of the sphincter. But the sphincter does not remain open; it quickly closes after a little chyme, as the half digested food is called, has got through it. This clos- ure is due to the free acid acting on the duodenum, where it stimulates afferent nerve endings that cause the sphincter to close and to keep closed so long as any acid remains in the duo- denum. Whenever -this acidity has become neutralized by the alkali present in the bile and pancreatic juice, the acid on the stomach side again becomes operative and the sphincter opens. We must conclude that the pyloric sphincter is under the con- DIGESTION IN THE STOMACH. 69 trol of a nerve center which transmits influences that tend to re- lax the sphincter when the afferent fibers running to it from the stomach side are excited by acid, but which cause it still more powerfully to contract when the acid acts on afferent fibers hav- ing their terminations in the duodenum. When both afferent paths are simultaneously stimulated, the duodenal predominates over the gastric, so that the sphincter remains closed until the acidity of the chyme in the duodenum has all been neutralized, and this seems to be true however faint the acidity may be on the duodenal side and however strong on the stomach side. The reflex arc is situated in the walls of the pyloric region and duo- denum, for it operates after complete isolation from the central nervous system. It is a function of the plexus found present in the walls — the myenteric plexus. Rate of Discharge of Food from the Stomach. — The acidity of the gastric contents, as we have just seen, must attain a cer- tain degree before it becomes an adequate stimulus for the open- ing of the pyloric sphincter, and consequently the rate at which the different food stuffs leave the stomach is to a large extent proportional to their power of combination with the acid. Pro- teins, combine with large amounts of acid, so that their initial discharge is delayed and their subsequent passage slow. Car- bohydrates absorb but little acid, so that they begin to leave early and the stomach is soon emptied of them. The passage of fats is peculiar; when taken alone, which, however, is scarcely ever the case, they seem to bring about a partial relaxation of the pyloric' sphincter, so that bile and pancreatic juice regurgitate into the stomach and some fat may pass out, but the subsequent dis- charge into the intestines is very slow, so slow indeed that each discharged portion seems to become completely absorbed before any further discharge occurs. When fats are mixed with other foods, they materially delay the discharge. These effects are no doubt due in part to the inhibitory influence which fats have on gastric secretion ; and in part to the liberation of fatty acid in the duodenum by the action of pancreatic lipase. This fatty acid seems to be liberated more quickly than it becomes neutralized by alkali. 70 PHYSIOLOGY FOR DENTAL STUDENTS. Water alone begins to leave the stomach almost immediately after it is taken, because the sphincter opens before an acid reaction has been acquired, and remains open on account of there being no acid in the duodenum to effect its closure. Water stays for too short a time in the stomach to excite any gastric secretion, and consequently it readily carries infection into the intestine. The discharge of raw egg albumin is peculiar. Like water it begins to pass the pylorus immediately after ingestiou, its reaction for some time being alkaline ; it becomes acid later, so that the discharge becomes intermittent because of the duo- denal reflex. The consistency of food itself does not affect the rate of discharge unless hard particles are present in it, when a marked retardation occurs. It is well known that the gastric contents are but slowly dis- charged into the duodenum when there is excessive gas accu- mulation. This is due to the atony of the stomach which accom- panies pathological gas accumulation. CHAPTER VII. DIGESTION (Cont'd). Intestinal Digestion: The Movements of the Intestines: Absorption. The Secretion of Bile and Pancreatic Juice. — Besides caus- ing reflex closure of the pyloric sphincter, the contact of the chyme, which is the name given to the semi-digested food as it leaves the stomach, with the duodenal mucosa inaugurates the processes of intestinal digestion by exciting the secretion of bile and pancreatic juice. Neither of these juices is secreted into the intestine during fasting; but both begin to flow very soon after taking food, and they gradually increase in amount for about three hours, and then rapidly decline. The bile at first comes mainly from the gall bladder, in which it has accumulated dur- ing fasting. When the gall bladder supply is exhausted, the bile comes directly from the liver without entering the gall bladder, and this secretion becomes more and more marked as digestion proceeds. The storage of bile which occurs during fasting is necessitated by the fact that although it is not required in the intestine, bile is nevertheless being constantly produced by the liver, because it is an excretory product, as well as a digestive fluid: It must, therefore, be got rid of from the blood, but, be- ing also useful for digestion, it is stored until it is required to assist in this process. The sudden discharge of bile from the gall bladder is depen- dent upon a nerve reflex excited by the contact of the acid chyme with the duodenum. The increased secretion of bile from the liver, like the secretion of pancreatic juice, is however, inde- pendent of nerves, for it has been found that the application of weak hydrochloric acid to the duodenum causes the juices to flow after all the nerves, but not the blood vessels of the duodenum have been cut. The only way by which such a result can be ex- plained is by assuming that the acid causes some chemical sub- 71 I'l PHYSIOLOGY FOR DENTAL STUDENTS. stance to be added to the blood, which then carries it to the pan- creas and liver, upon the cells of which it exercises a stimulating influence. That this is the correct explanation was shown by studying the effect which is produced on the secretion of pan- creatic juice and bile by intravenous injections of decoctions of intestinal mucosa made with weak acid and subsequently neu- tralized. An immediate secretion resulted. The acid extract evi- dently contained some hormone whose production, in the normal process of digestion, is evidently occasioned by the contact of the acid chyme with the duodenal mucosa. This hormone is called secretin but we know very little of its exact chemical nature. It is not a ferment, for it withstands heat ; it is not a protein, for it can be extracted by boiling the mucous membrane with weak acids after treatment with alcohol. It is readily oxidized in the presence of alkalies, and is of the same nature in all animals. It is useless to give secretin as a drug with the hope that it will stimulate pancreatic secretion, for it is not absorbed from the lumen of the intestine. Although most abundant in the mucosa of the duodenum and jejunum, secretin is also present in the mucosa of the lower end of the small, and to a lesser degree, in that of the large intestine. Soap solutions act like acid in producing secretin. A fatty meal, therefore, excites the flow of much pancreatic juice and bile, be- cause the fatty acid which is split off unites with alkali and forms soap. It may be that the very first portion of pancreatic juice to be secreted after a meal is taken, is due, not to secretin formation, but to reflex nervous stimulation of the pancreas. In comparison with the hormone control the nervous control is, however, quite unimportant in pancreatic secretion, for there is no necessity in the intestine, as in the mouth, or to a less degree in the stomach, for a quick response to the stimulus produced by the presence of food. The histological changes produced in the gland cells of the pancreas by secretory activity are much the same as in the parotid glands. Functions of the Bile and Pancreatic Juice. — These 1\vo juices are very closely associated in their activities. This fact INTESTINAL DIGESTION. 7'} is perhaps most strikingly demonstrated in the digestion and ab- sorption of fat; for, in the absence of either secretion, large amounts of unabsorbed fat appear in the faeces. Both juices contain relatively large amounts of alkali, which neutralizes the acidity of the chyme. In the pancreatic juice alone, for example, there is a sufficient concentration of sodium carbonate to neu- tralize the acid in an equal volume of gastric juice. The action of pepsin disappears whenever the chyme becomes alkaline and conditions thus become suitable for the activities of the pan- creatic enzymes. Besides its neutralizing action, the bile causes the chyme to assume a somewhat greater consistency, by pre- cipitating incompletely peptonized protein, as well as pepsin. The precipitate becomes redissolved when excess of bile has be- come mixed with it, and the significance of the precipitation may be that it causes a temporary delay in the movement of the chyme along the duodenum, thus allowing it to become properly mixed with pancreatic juice before it moves further along the intes- tine. Composition, Properties and Functions of the Bile.— Water 85.9 Total Solids : 14.1 of which : Bile Salts 9.14 , Lecithin and Cholesterol 1.10 ^ Mucinoid Substance Pigment Inorganic Salts '. 0.78 The bile is a greenish-yellow fluid of sticky consistency and bitter taste. Its most interesting constituents are the bile salts, which are complex organic substances, having an important func- tion to perform in assisting the lipase and amylopsin of pan- creatic juice in their digestive activities. Otherwise the bile con- tains no digestive enzymes. The cholesterol is not a readily soluble substance, so that it is apt to become precipitated in the 1 2.98 74 PHYSIOLOGY FOR DENTAL STUDENTS. bile duct and cause gall stones. The distention of the ducts which these produce may cause great pain (biliary colic). The formation of gall stones is encouraged by inflammatory processes of the mucous membrane of the ducts. When bile fails to reach the intestine, because of blocking the ducts, either by gall stones or by inflammatory swelling of the mucous membrane, the di- gestion, especially of fats, is much interfered with, and the faeces become foul smelling and pale in color. The Composition and Properties of Pancreatic Juice. — The pancreatic juice contains three important enzymes: lipase (act- on fats), amylopsin (acting on starch), and trypsinogen ilflg on protein). Although the bile contains no enzymes, it is, as we have seen, a most important accelerator of the activities of the lipase and amylopsin of the pancreatic juice. Bile has no action on trypsinogen, which is nevertheless without any action until it has become changed into trypsin. This does not occur until the pancreatic juice has reached the intestine, when the activation is brought about by a ferment present in the intes- tinal juice (secretion of Lieberkiihn's follicles), called enter o- kinase. The intestinal juice contains this activator only when it is required ; it is absent, for example, in the juice that is se- creted as a result of mechanical stimulation of the intestinal mu- cosa, but it immediately appears when some pancreatic secretion is applied to the mucosa. Enterokinase is not the only substance which can activate trypsinogen, for the addition of calcium salts, the contact of the juice with leucocytes, as in granulation tissue, and even mere standing of the juice, have a similar effect. If the pancreatic juice in escaping from the duct should run over gran- ulation tissue, as occurs when a fistula of the duct is made, it be- comes activated and unless precautions are taken it will excoriate the wound. Should it escape into the peritoneum, as when a cyst bursts, it also becomes activated. By being secreted in an inactive state, the proteolytic enzyme develops no digestive ac- tion on the pancreatic ducts. It will be remembered that the amount of gastric juice secreted varies with different foods, being relatively more abundant on a diet of bread than on one of milk, or even meat (p. 63). Simi- INTESTINAL DIGESTION. 75 lar quantitative differences exist in the secretion of pancreatic juice and this is probably to be explained by the varying quanti- ties of acid chyme coming in contact with the duodenal mucosa. Chemical Changes Produced by Intestinal Digestion. — In the lower portion of the duodenum and in the jejunum, the digestive < tiii/mes of the pancreatic juice act on the food in full intensity. The trypsin rapidly hydrolyzes the proteins to peptone, which if it is not immediately absorbed may become further broken down to amino bodies and aromatic compounds. The lipase hydrolyses fat to glycerine and fatty acid, which are absorbed, the former as such, the latter, after combining with alkali to form soap, or, if no alkali be available, with bile salts to form compounds which like the soap are soluble in water. Amylopsin converts into mal- tose any starch or dextrines which the ptyalin of saliva has failed to act on. The maltose thus formed, and the other disaccharides, cane sugar and lactose, although soluble in water, do not become absorbed into the blood as such but become further hydrolyzed by the action of so-called inverting enzymes, of which there is one for each disaccharide (see p. 25). These inverting enzymes are more plentiful in extracts of the mucosa than in the intestinal juice itself, from which we conclude that it is only after they have been absorbed into the cells of the intestines that the disac- charides are inverted. The process, in other words, is an in- tracellular one. One other enzyme exists in the intestinal juice, namely, erepsin. It acts on partially hydrolyzed proteins and on caseinogen, so as to hydrolyze them completely into the amino compounds. Erepsin is a widely distributed enzyme in the animal body, be- ing present in practically every tissue, although it is absent from blood plasma. It is present in much greater concentration in ex- tracts of the intestinal mucosa than in succus entericus, so that, like the inverting enzymes, it possibly displays its action while the protein is being absorbed as proteoses and peptones. It serves as the last barrier against the entry into the blood of protein in any other form than as a mixture of amino bodies. Less com- pletely digested protein is poisonous when added to 'the blood (p. 152). 76 PHYSIOLOGY FOB DENTAL STUDENTS. Most of the food is now in a suitable condition for absorption. Before we proceed to study the nature of this process, however, there are one or two further digestive changes that we must con- sider. The Digestive Function of Intestinal Bacteria. — On account of the antiseptic action of free hydrochloric acid, there is, ordi- narily, no bacterial growth in the stomach, but the neutral i/a- tion of acid by pancreatic juice and bile in the intestine pro- vides a perfect medium for such growth. The extent and nature of the bacterial growth varies very greatly according to the na- ture of the diet. There can be no doubt that the micro-organisms are a valuable aid to digestion in the case of most animals, especially of those whose diet includes cellulose. Indeed, in such animals as the herbivora special provision is made to encourage bacterial growth by the grea^t length of the large intestine, for without bacteria, digestion of cellulose is impossible. Thus if newly-hatched chicks be fed with sterilized grain they succumb in about two weeks, but if a. small amount of the excrement of the fowl be mixed with the grain, they thrive, as ordinarily. On the other hand, if the food contains no cellulose, animals may develop and grow with sterile intestinal contents; thus guinea pigs have been re- moved from the uterus under aseptic conditions and kept in a sterile place on sterilized milk and have thrived and grown as normal guinea pigs. The organisms in the intestine of man are probably much more useful than harmful. No doubt they are parasites, but they are useful parasites; they work for their liv- ing, not only by assisting when necessary in the digestion of food but also by destroying certain substances which, if absorbed, would have a toxic action on the host. Thus cholin, a substance produced by the digestion of lecithin, is distinctly poisonous, but it really never gets into the blood because the bacteria destroy it. In the case of man bacterial digestion occurs both in the small and large intestines, and there are varieties of bacteria capable of acting on all the food stuffs. They may break up the sugars into lactic acid or even further so as to form C02 and H. It has been claimed that this formation of lactic acid in the intestine is INTESTINAL DIGESTION. 77 of benefit to the health of man because when it occurs other bac- teria which are more harmful than useful become destroyed. To encourage this growth of lactic acid bacteria, it has been recom- mended that large quantities of sour milk should be taken. It is undoubtedly true that such treatment is of benefit in many per- sons who suffer from excessive intestinal putrefaction, but that such treatment should prolong the life of otherwise healthy indi- viduals is visionary. As in herbivora, there are also bacteria in man which break up cellulose, producing methane and C02. After diets containing much vegetable matter, therefore, a large amount of gas is likely to accumulate in the intestines. From fats, the intestinal bacteria produce lower fatty acids, which tend to cause the contents in the lower portion of the small in- testines to become acid in reaction. Although capable of hydrolyzing native protein from the very start, bacteria act more readily on protein that has been partially digested by the proteolytic enzymes of the stomach and intes- tines. The products of this action are more or less characteristic because of the peculiar manner in which the aromatic groups of the protein molecule are attacked, producing from it such sub- stances as phenol, skatol, indol, etc., to which the characteristic odor of the fasces is due. "When protein has been adequately di- gested in the stomach, it is so rapidly acted on by the trypsin (and erepsin) of the small gut and is so quickly absorbed that bacteria have no chance to act on it. When protein has been in- adequately digested in the stomach, however, the trypsin fails to digest it quickly enough, so that bacterial putrefaction sets in which may be quite marked in the small intestine, although much more so in the colon. Even when they do not find a suitable sub- strat in the food, the bacteria attack the proteins of the intes- tinal secretions themselves, which accounts for the well-known occurrence of this process during starvation. The Immunity of the Walls of the Digestive Organs Toward the Enzymes Which Act within Them. — The immunity of the mucosa of the stomach and intestines seems to be due in main to the presence in the cells of the mucosa of anti-enzymes, that is of substances which can inhibit the action of the various enzymes 78 PHYSIOLOGY FOR DENTAL STUDENTS. (antipepsin, antitrypsin, etc.). As we should expect, very strong anti-enzymes can be prepared from tapeworms and other intes- tinal worms. It is in virtue of possessing these, that the worms are not digested. The immunity of the gland cells and ducts, as of the pancreas, to the proteolytic enzymes which they produce is possibly to be explained in another way, namely, by the ex- istence of the enzyme as an inactive precursor (e. g., trypsino- gen) until after the secretion has been carried to a region whose walls contain the specific anti-body. A certain degree of im- munity to a possible destructive action of the intestinal bacteria may be conferred by the mucin, which is quite abundant, at least in the empty stomach and in the large intestine. The relatively poor growth of bacteria which occurs on inoculating faecial mat- ter in culture media — although many bacteria can be seen by microscopic examination to be present — is probably to be ex- plained by their having been killed by the mucin. The Movements of the Intestines. The movements of the small intestine have two functions: (1) to macerate and mix up the food and "('2) to move it along to- wards the lower end of the gut. These two functions are sub- served by two different types of movement, the so-called pendular and the peristaltic. The pendular movements are rendered evi- dent by allowing the intestine to float out in a bath of isotonic saline, when the various loops sway from side to side like a pen- dulum. By closer examination it can be seen that the movements are produced by faint waves of contraction of both muscular coats which sweep with considerable rapidity along the gut. When the waves arrive at a part of the intestine containing any solid substance, they become accentuated, and this becomes most marked at the middle of the solid mass of food, thus tending, on account of the contraction of the circular fibers, to divide the mass into two. They are therefore sometimes called segmenting movements. Beyond the mass the contractions again fade away. Their function is evidently to break up the food masses and thus mix them with the digestive juices. This can be very well shown in skiagram shadows of the abdomen some time after taking food INTESTINAL DIGESTION. 79 mixed with bismuth. A column of food can be seen to divide into several segments, each of which in a few seconds breaks into two the neighboring halves then joining together, and the process repeating itself. Two varieties of peristaltic waves are usually described, both, of which are characterized by a marked constriction preceded by a distinct dilatation of the gut, which may extend for a consid- erable distance down it (two feet). The one variety of wave travels slowly (y2 cm. per minute), and has the function of car- rying along the food ; the other travels very rapidly (peristaltic rush), and is evidently for the purpose of hurrying along irri- tating substances. Besides being set up by the presence of food in the intestine, these waves may be influenced through the nervous system ; stim- ulation of the vagus excites them, whereas stimulation of the sympathetic brings about a marked inhibition, in which the whole gut becomes profoundly relaxed with the exception of the ileo- colic sphincter, which contracts. This influence of the splanch- nic may be excited reflexly, as by pain or fear. The movements of the large intestine are more difficult to study than those of the small intestine. They vary considerably in different animals, as indeed is to be expected when we remember that the function of this part of the alimentary tract depends upon the nature of the food. In herbivora, for example, food may lie in the capacious caecum for days, and even in carnivora, in which this part of the gut is rudimentary, it may remain for twenty-four hours. In man the conditions seem to be intermedi- ate between those in the herbivora and carnivora, and the move- ments are believed to be as follows: As the semi-fluid food en- ters the ca?cum through the ileo-caecal valve and collects in the caecum and proximal colon, it excites the occurrence of waves of constriction, which start probably about the hepatic flexure and travel back towards the caecum, thus forcing the food into this sac and tending to cause recurring axial currents to be set up. Occasionally the arrival of the wave at the caecum starts a true peristaltic wave, which travels distally getting feebler as it proceeds, and which may carry some of the contents into the so PHYSIOLOGY FOR DENTAL STUDENTS. transverse colon. Here the mass assumes more or less of the con- sistency of faeces, when more powerful peristaltic waves make their appearance and carry the solid masses on towards the rec- tum. These waves are sufficiently energetic to keep the descend- ing colon comparatively empty, and the fascal masses gradually accumulate in the sigmoid flexure and rectum until evacuated by the act of defaecation. Examination of the accompanying diagram (Fig. 7) will show how long food takes to pass along the various parts of the gastro- intestinal tract. Fig. 7. — Diagram of time it takes for a capsule containing bismuth to reach the various parts of the large intestine. The Absorption of Food. As has been explained, the whole object of digestion is to break up the large molecules of which food is composed into smaller ones so that they can be absorbed into the blood or lymph which circulates in the mucous membrane of the intestines. Unless un- der unusual circumstances, no absorption occurs until the small intestine is reached. Here sugars are absorbed as dextrose, and THE ABSORPTION OP FOOD. 81 proteins as amino bodies, into the blood, whilst fats are absorbed into the lymphatic vessels, as fatty acids and glycerine. These substances are absorbed in solution, which would lead us to ex- pect that, because of the water absorbed along with them, the contents of the small intestine would be more solid at its lower end than at its upper end ; but this is not the case, for the diges- tive juices which have been secreted make up for the loss of water. It is in the large intestine that the water is finally ab- sorbed. Attempts have been made to explain the process of absorption in terms of the known laws of filtration, osmosis, surface tension, and imbibition, but little further progress has been made than to establish the fact that although these processes may play a role, they do not explain the whole thing, for if blood serum be placed in an isolated loop of intestine, it will become entirely absorbed even although identical in all the above properties with the blood of the animal. That osmosis does have some influence, however, is evidenced by the well-known effect of a strong » saline solution in the intestine; it attracts water from the blood, * thus diluting the intestinal contents and stimulating peristaltic contractions. It is in this way that saline cathartics act. Regarding the absorption of fats, it is now definitely known that these first of all split into fatty acid and glycerine by the action of the lipase of pancreatic juice. The fatty acid then unites with alkali to form a soap, or with bile salts to form a sol- uble compound. In either case, the dissolved fatty acid passes into the intestinal epithelium, into which is also absorbed the glycerine, the two re-uniting after their absorption so as to form neutral fat again, which then passes into the central lacteal of the villus, whence it is transported by the abdominal lymphatics to the thoracic duct, which discharges it into the subclavian vein on the left side of the root of the neck. Hunger sensations coincide with stomach contractions which differ from those occurring during digestion. Thirst is due to dryness of the throat. It is temporarily relieved by moistening this, but unless liquid is swallowed permanent thirst develops because the tissues become dry. Resume of Actions of Digestive Enzymes. SECRETION ENZYME OB ADJUVANT AGENCY ACTION Saliva . . • Ptyttkn Converts boiled starch into maltose Gastric juice . Alkalies Pepsin Favors action of ptyalin. (1) Converts metaproteins (acid albu- HC1 min, etc.) into proteoses and pep- tones. (2) Clots milk. (1) Produces metaproteins Lipase (2) Acts as antiseptic. (3) Stops action of ptyalin. Pancreatic Trypsinogen . . Li past • Inactive until acted on by enterokinase. Splits neutral fat into fatty acid and Amylopsin . .. Alkali glycerine. Converts all starches into maltose. (1) Helps to neutralize HC1 of chyme. Bile Bile salts .... (2) Combines with fatty acid to form soaps. (1) Augment the action of lipase and Alkali . .1 and amylopsin. (2) Precipitate pepsin and peptones in chyme. (3) Combines with fatty acids. Intestinal juice Enterokinase . (2) Combines with fatty acid to form soaps. Converts trypsinogen into trypsin, Erepsin which splits proteins into amino bodies. Bacteria Inverting enzymes Acting on carbohydrates Acting on fats Converts caseinogen and peptones into simple amino bodies. One for each disaccharide, splitting them into monosaccharides. (Both the last two enzymes are more plentiful in the epithelium than in the intestinal juice.) (1) Digest cellulose. (2) Splits monosaccharides into lactic and lower acids. Acting on proteins . . . . Split higher, into lower fatty acids. Split off aromatic groups, as phenol, cresol, etc. (Besides these specific actions, bacteria may perform many of the diges- tive functions of the juices.) CHAPTER VIII. METABOLISM. The Energy Balance. Introductory. — The object of digestion, as we have seen, is to render the food capable of absorption into the circulatory fluids, the blood and lymph. The absorbed food products are then transported to the various organs and tissues of the body, where they may be either used or stored away against future requirements. After being used, certain substances are produced as waste products, and these pass back into the blood to be car- ried to the organs of excretion, by which they are expelled from the body. By comparison of the amount of these excretory prod- ucts with that of the constituents of food, we can tell how much of the latter has been retained in the body, or lost from it. This constitutes the subject of general metabolism. On the other hand, we may direct our attention, not to the balance between intake and output, but to the chemical changes through which each foodstuffs must pass between its absorption and excretion. This is the subject of special metabolism. In the one case we content ourselves with a comparison of the raw material which is acquired and the finished product which is produced by the animal factory ; in the other, we seek to learn something of the particular changes to which each crude product is subjected^ be- fore it can be used for the purpose of driving the machinery of life or of repairing the worn out parts of the body. In drawing up such a balance sheet of general metabolism, we must select for comparison substances which are common to both intake and output. In general the intake comprises, besides oxy- gen, the proteins, fats and carbohydrates, and the output, carbon dioxide, water and the various nitrogenous constituents of urine. This dissimilarity in chemical structure between the substances ingested and those excreted limits us, in balancing the one 83 84 PHYSIOLOGY FOR DENTAL STUDENTS. against the other, to a comparison of the smallest fragments into which each can be broken. These are the elements and of them carbon and nitrogen are the only ones which it is possible to measure with accuracy in both intake and output. From bal- ance sheets of intake and output of carbon and nitrogen and from information obtained by observing the ratio between the amounts of oxygen consumed by the animal and of carbonic acid (C02) excreted, we can draw far-reaching conclusions regarding the relative amounts of protein, fat and carbohydrate which have been involved in the metabolism. As has already been stated, the essential nature of the metabolic process in animals is one of oxidation, that is to say, one by which large unstable mole- cules are broken down to those that are simple and stable. Dur- ing this process of katdbdism, as it is called, the potential energy which is locked away in the large molecules becomes liberated as actual or kinetic energy, that is to say, as movement and heat. It therefore becomes of importance to compare the actual energy which an animal expends in a given time with the energy which has meanwhile been rendered available by metabolism. This is called the energy balance. We shall first of all consider this and then proceed to examine somewhat more in detail the material balance of the body. » Energy Balance. The unit of energy is the large calorie (written C), which is the amount of heat required to raise the temperature of one kilo- gramme of water through one degree (Centigrade) of tempera- ture.1 We can determine the calorie value by allowing a meas- ured quantity of a substance to burn in compressed oxygen in a steel bomb which is placed in a known volume of water at a certain temperature. Whenever combustion is completed, we find out through how many degrees the temperature of the water has become raised and multiply this by the volume of water in litres. Measured in such a calorimeter, as this apparatus is iThe distinction between a calorie and a degree of temperature must be clearly understood. The former expresses quantity of actual heat energy ; the latter merely tells us the intensity at which the heat energy is being given out. THE ENERGY BALANCE. 85 called, it has been found that the number of calories liberated by burning one gramme of each of the proximate principles of food is as follows : ( Starch ... .4.1 Carbohydrates ] . ( Sugar 4.0 Protein 5.0 Fat 9.3 The same number of calories will be liberated at whatever rate the combustion proceeds, provided it results in the same end products. When a substance, such as sugar or fat, is burned in the presence of oxygen, it yields carbon dioxide and water, which are also the end products of the metabolism of these foodstuffs in the animal body ; therefore, when a gramme of sugar or fat is quickly burned in a calorimeter, it releases the same amount of energy as when it is slowly oxidized in the animal body. But the case is different for proteins, because these yield less com- pletely oxidized end products in the animal body than they yield when burned in oxygen; so that, to ascertain the physiological energy value of protein, we must deduct from its physical heat value (calories) the physical heat value of the incompletely ox- idized end products of its metabolism. It is obvious that we can compute the total available energy of our diet by multiplying the quantity of each foodstuff by its calorie value. In order to measure the energy which is actually liberated in the animal body, we must also use a calorimeter, but of some- what different construction from that used by the chemist, for we have to provide for long continued observations and for an uninterrupted supply of oxygen to the animal. Animal calor- imeters are also usually provided with means for the measure- ment of the amounts of carbon dioxide (and water) discharged and of oxygen absorbed by the animal during the observation. Such respiration calorimeters have been made for all sorts of ani- mals, the most perfect for use on man having been constructed in America (see Fig. 8). As illustrating the extreme accuracy of even the largest of these, it is interesting to note that the act- ual heat given out when a definite amount of alcohol or ether is 86 PHYSIOLOGY FOR DENTAL STUDENTS. burned in one of them exactly corresponds to the amount as meas- ured by the smaller bomb calorimeter. All of the energy liber- ated in the body does not, however, take the form of heat. A variable amount appears as mechanical work, so that to measure in calories all of the energy which an animal expends, one must add to the actual calories given out, the calorie equivalent of Water to absorb heat Chamber for animol /" window H m Fig. 8. — Diagram of Atwater-Benedict Respiration Calorimeter. As the animal uses up the O«, the total volume of air shrinks. This shrinkage is indi- cated by the meter, and a corresponding amount of O3 is delivered from the weighed Oa-cylinder. The increase in weight of bottles II and III gives the C02. the muscular work which has been performed by the animal during the period of observation. This can be measured by means of an ergometer, a calorie corresponding to 425 kilo- gramme2 metres of work. That it has been possible to strike an accurate balance between the intake and the output of energy of the animal body, is one of the achievements of modern experi- mental biology. It can be done in the case of the human jini- 2A kilogrammemetre is the product of the load in kilogrammes by the dis- tance in metres through which it is lifted. THE ENERGY BALANCE. 87 mal ; thus, a man doing work on a bicycle ergometer in the Bene- dict calorimeter gave out as actual heat, 4,833 C., and did work equalling 602 C., giving a total of 5,435 C. By drawing up a balance sheet of his intake and output of food material during this period, it was found that the man had consumed an amount capable of yielding 5,459 C., which may be considered as ex- actly balancing the actual output. Having thus satisfied ourselves as to the extreme accuracy of the method for measuring energy output, we shall now consider some of the conditions which control it. To study these we must first of all determine the basal heat production, that is, the small- est energy output which is compatible with health. This is as- certained by allowing the man to sleep in the calorimeter and then measuring his calorie output while he is still resting in bed in the morning, and fifteen hours after the last meal. When the results thus obtained on a number of individuals are calcu- lated so as to represent the calorie output per kilogramme of body weight in each case, it will be found that 1 C. per kilo per hour is discharged. That is to say, the total energy expenditure in 24 hours in a man of 70 kilos, which is a good average weight, will be 70 X 24 = 1,680 C. When food is taken the heat production rises, the increase over the basal heat production amounting for an ordinary diet to about ten per cent. Besides being the ultimate source of all the body heat, food is therefore a direct stimulant of heat production. This specific dynamic action, as it is called, is not, however, the same for all groups of foodstuffs, being greatest for proteins and least for carbohydrates. Thus, if a starving animal is given an amount of protein which is equal in calorie value to the calorie output during starvation, the caloric output will increase by 30 per cent, whereas with carbohydrates it will increase only by 6 per cent. Evidently, then, protein liberates much free heat during its assimilation in the animal body ; it burns with a hot- ter flame than fats or carbohydrates, although as in the case of fats, at least, before it is completely burnt, it may not yield so much energy. This peculiar property of proteins accounts for their well-known heating qualities. It explains why protein com- 88 PHYSIOLOGY FOR DENTAL STUDENTS. poses so large a proportion of the diet of peoples living in cold regions, and why it is cut down in the diet of those who dwell near the tropics. Individuals maintained on a low protein diet may suffer intensely from the cold. If we add to the basal heat production of 1,680 C. another 168 C. (or 10 per cent) on account of food, the total 1,848 C. nevertheless falls far short of that which we know must be liber- ated when we calculate the available energy of the diet. What becomes of the extra fuel? The answer is that it is used for muscular work. Thus it has been found that if the observed person, instead of lying down in the calorimeter, is made to sit in a chair, the heat production is raised by 8 per cent, or if he performs such movements as would be necessary for ordinary work (writing at a desk), it may rise 29 per cent, that is to say, to 90 C. per hour. Allowing 8 hours for sleep and 16 hours for work, we can thus account for 2,168 C., the remaining 300 odd C. which is required to bring the total to that which we know, from statistical tables of the diets of such workers, to be the actual daily expenditure, being due to the exercise of walking. If the exercise be more strenuous, still more calories will be ex- pended; thus, to ascend a hill of 1,650 feet at the rate of 2.7 miles an hour requires 407 extra calories. Field workers may expend, in 24 hours, almost twice as many calories as those en- gaged in sedentary occupations. Another factor which controls the energy output is the cool- ing influence of the atmosphere. When this is marked, more heat must be liberated in order to maintain the body temperature (see p. 135). In other words, the necessary heat loss must be compensated by an increased heat production, just as we must burn more coal to keep the house at a given temperature on a cold, than on a warm, day. This adjustment of energy liberation to the rate of cooling at the surface of the body explains, among other things, why it should be that small animals give out much more energy, per unit of body weight, than those that aiv larger. The small animal has relatively the greater surface area, just as two cubes of equal weight when brought together have a com- bined weight which is double that of either cube, but a surface THE ENERGY BALANCE. 89 area which is less than double (two surfaces having been brought together). Its greater tendency to cool explains why small ani- mals ahouM so much more quickly succumb to cold than those that are larger, and why slim persons shrniM feel the cold more keenly than those that are stout. Other things, such as diet, external temperature, etc., being the same, it is therefore surface area and not body weight ivhich determines the energy production, a fact which is clearly dem- onstrated by finding that the calorie output for different animals is constant when it is calculated for each square metre of sur- face. Thus, a horse produces only 14.5 C. per kg. of body weight in 24 hours, whereas a mouse produces 452 C., but if we calculate according to square metre of surface the dif- ferences practically vanish. These facts, however, do not apply when the differences in size are due to age. This fact has been most strikingly demonstrated in the case of man, for it has been found that the calorie requirement per unit of surface is very distinctly greater in the early years of life than later. Thus, tak- ing the discharge of carbon dioxide as a criterion of the energy discharge, the following results have been obtained from indi- viduals sitting down : Carbon dioxide discharged, per Average age Average weight square meter of surface (years) "(kilogrammes) and hour (grammes) \Males 9 2/3 28 29.9 12 1/2 34 26.5 15 1/2 51 23.5 19 1/2 60 21.8 25 68 18.5 35 68 16.9 45 77 16.3 58 85 14.2 Females 8 22 26.6 12 36 20.1 15 49 16.0 17 2/3 54 14.8 30 54 16.3 45 67 17.9 90 PHYSIOLOGY FOR DENTAL STUDENTS. This table shows us clearly that over and above the greater combustion necessary on account of their relatively greater sur- face, children require calories for growth. They must be fed more liberally than adults, otherwise they starve. The table further shows that boys must be more liberally fed than girls of equal age and body weight, probably because of their greater restlessness. It is on account of these greater food requirements that children are the first to die in famine. CHAPTER IX. ' METABOLISM (Cont'd). The Material Balance of the Body. We must distinguish, between the balances of the organic and the inorganic foodstuffs. From a study of the former we shall gain information regarding the sources of the energy production whose behavior under various conditions we have just studied. From a study of the inorganic balance, although we shall learn nothing regarding energy exchange — for such substances can yield no energy — we shall become acquainted with several facts of extreme importance in the maintenance of nutrition and growth. ; • \ To draw up a balance sheet of organic intake and output re- quires an accurate chemical analysis of the food and of the excreta (urine and expired air). Furnished with such analyses we proceed to ascertain the total amount of nitrogen and carbon in the excreta in a given time and to calculate from the known percentage of nitrogen in protein how much protein must have undergone metabolism. We then compute how much carbon this quantity of protein would account for, and we deduct this from the total carbon excretion. The remainder of carbon must have come from the metabolism of fats and carbohydrates, and al- though we cannot tell exactly which, yet we can arrive at a close approximation by observing the respiratory quotient (R. Q.), which is the ratio of the volume of carbon dioxide exhaled to CO2 that of oxygen retained by the body in a given time, i. e., — 02 When carbohydrates are the only foodstuff undergoing metabol- ism, the quotient is one, that is to say, the C02 excretion and 02 intake are equal in volume. The reason for this is that a molecule of carbohydrates consists of C. along with II. and 0. in the same proportions as they exist in water ; therefore oxygen is required 91 92 PHYSIOLOGY FOR DENTAL STUDENTS. to oxidize the C., but not the H., and, since equimolecular quan- tities of all gases occupy equal volumes (at the same tempera- ture and pressure), the volume of C02 produced equals the vol- ume of C. required to produce it. The conditions are other- wise in the case of fats and proteins, for besides C. these mole- cules contain an excess of H., so that 0. is required to oxidize some of the H., as well as all of the C. A greater volume of 0, is therefore absorbed, during their combustion than the volume of CO2 that is produced, and R. Q. is about 0.7. By observing this quotient, therefore, we can approximately determine the source from which the non-protein carbon excretion is derived. Having in the above manner computed how much of each of the proximate principles has undergone metabolism, we next pro- ceed to compare intake and output with a view to finding whether there is an equilibrium between the two, or whether re- tention or loss is occurring. Starvation. — In order to furnish us with a standard condition with which we may compare others, we will first of all study the metabolism during starvation. When an animal is starved, it has to live on its own tissues, but in doing so, it saves its protein so that the excretion of nitrogen falls after a few days to a low level, the energy requirements being meanwhile supplied, as much as possible, from stored carbohydrate and fat. Although always small in comparison with fat, the stores of carbohydrate vary considerably in different animals. They are much larger in man and the herbivora than in the carnivora. During the first few days of starvation it is common, in the herbivora, to find that the excretion of nitrogen is actually greater than it was before starvation, because the custom has become established in the metabolism of these animals of using carbohydrates as the main fuel material, so that when this fuel is withheld, as in starvation, proteins are used more than before and the nitrogen excretion becomes greater. We may say that the herbivorous animal has become carnivorous. The same thing may occur in man when the previous diet was largely carbohydrate. During the greater part of starvation, however, most of the energy required to maintain life is derived from fat, as little STARVATION. 93 as possible being derived from protein. This type of metabolism lasts until all the available resources of fat have become ex- hausted, when a more extensive metabolism of protein sets in with the consequence that the nitrogen excretion rises. This is really the harbinger of death — it is often called the premortal rise in nitrogen excretion. It means that all the ordinary fuel of the animal economy has been used up, and that it has become necessary to burn the very tissues themselves in order to obtain sufficient energy to maintain life. Working capital being all exhausted, an attempt is made to keep things going for a little longer time by liquidation of permanent assets. But these assets, as represented by protein, are of little real value in yielding the desired energy because, as we have seen, only 4.1 calories are available against 9.3, obtainable from fats. These facts explain why during starvation a fat man excretes daily less nitrogen than a lean man, and why the fat man can stand the starvation for a longer time. Not only is there this general saving of protein during star- vation, but there is also a discriminate utilization of what has to be used by the different organs according to their relative activities. This is very clearly shown by comparison of the loss of weight which each organ undergoes during starvation. The heart and brain, which must be active if life is to be maintained, lose only about 3 per cent of their original weight, whereas the voluntary muscles, the liver and the spleen lose 31, 54 and 67 per cent, respectively. No doubt some of this. loss is to be ac- counted for as due to the disappearance of fat, but a sufficient remainder represents protein to make it plain that there must have been a mobilization of this substance from tissues where it was not absolutely necessary, such as the liver and voluntary muscles, to organs, such as the heart, in which energy transfor- mation is sine qua non of life. The vital organs live at the ex- pense of those whose functions are accessory. When we compare the excretion of carbon dioxide from day to day during starvation, it will be found to remain practically constant, when calculated for each kilogram of body weight. The same is true for the calorie output. Certain unusual substances 94 1^**'*' * PHYSIOLOGY FOR DENTAL STUDENTS. such as creatin also make their appearance in the urine, and there is an increase in the excretion of ammonia, indicating that larger quantities of free acid are being set free in the organism. Starvation ends in death in an adult man in somewhat over four weeks, but much sooner in children, because of their more active metabolism. At the time of death the body weight may be reduced by 50 per cent. The body temperature does not change until within a few days of death, when it begins to fall, and it is undoubtedly true that if means be taken to prevent cool- ing of the animal at this stage, life will be prolonged. Normal Metabolism. — Apart from the practical importance of knowing something about the behavior of an animal during starvation, such knowledge is of great value since it furnishes a standard with which to compare the metabolism of animals under normal conditions. Taking again the nitrogen balance as indi- cating the extent of protein tear and wear in the body, let us consider first of all the conditions under which equilibrium may be regained. It would be quite natural to suppose that if an amount of protein containing the same amount of nitrogen as is excreted during starvation were given to a starving animal, the intake and output of nitrogen would balance. We are led to make this assumption because we know that any business bal- ance sheet showing an excess of expenditure over income could be met by such an adjustment. But it is a very different matter with the nitrogen balance sheet of the body; for, if we give the starving animal just enough protein to cover the nitrogen loss, we shall cause the excretion to rise to a total which is practically equal to the starvation amount plus all that we have given as food, and although by daily giving this amount of protein there may be a slight decline in the excretion, it will never come near to being the same as that of the intake. The only effect of such feeding will be to prolong life for a few days. To strike equilibrium we must give an amount of protein whose nitrogen content is at least two and one-half times that of the starvation level. For a few days following the establishment of this more liberal diet, the nitrogen excretion will be far in ex- cess of the income, but it will gradually decline until it corre- NORMAL METABOLISM. 95 spoiids to the intake. Having once gained an equilibrium, we may raise its level by gradually increasing the protein intake. During this progressive raising of the protein intake, it will be found, at least in the carnivora (cat and dog) that a certain amount of nitrogen is retained by the body for a day or so imme- diately following each increase in protein intake. The excre- tion of nitrogen, in other words, does not immediately catch up on the intake. The amount of nitrogen thus retained is too great to be accounted as a retention of disintegration products of pro- tein; it must therefore be due to an actual building up of new protein tissue, that is, growth of muscles. Such results undoubtedly obtain in the cat, and less markedly in the dog. But they do not do so in man and the herbivorous animals. In these, we can never give a sufficiency of protein alone to maintain nitrogen equilibrium; there will always be an excess of excretion over intake. But indeed it scarcely requires any experiment to prove this, for it is self-evident when we con- sider that there are only 400 C. in a pound of lean meat, and there are few who could eat more than 4 pounds a day, an amount which however would only furnish about half of the required calories. A person fed exclusively on flesh is therefore being partly starved, even although he may think that he is eating abundantly and be quite comfortable and active. This fact has a practical application in the so-called Banting cure for obesity, which consists in almost limiting the diet to flesh and green vegetables, allowing only a very small quota of carbohydrates or fats. Very different results are obtained when carbohydrates or fats are freely given with the protein. Nitrogen equilibrium can then be regained on very much less protein, so we speak of fats and carbohydrates as being "protein sparers." Carbohydrates are much better protein sparers than fats ; indeed they are so effi- cient in this regard that it is now commonly believed that carbo- hydrates are essential for life, so that when the food contains no trace of carbohydrates, a part of the carbon of protein has to be converted into this substance. This important truth is supported by evidence derived from other fields of investigation (e. g., the 96 PHYSIOLOGY FOR DENTAL STUDENTS. behavior of diabetic patients, where the power to use carbohy- drates is much depressed). The marked protein-sparing action of carbohydrates is illustrated in another way, namely, by the fact that we can greatly diminish the protein break-down during starvation by giving carbohydrates. In this way we can indeed reduce the daily nitrogen excretion to about one-third what it is in complete starvation. In the case of man living on an average diet, although the daily nitrogen excretion is about 15 grammes, it can be lowered to about 6 grammes provided that in place of the protein that has been removed from the diet enough carbohydrate is given to bring the total calories up to the normal daily requirement. If an excess of carbohydrate over these energy requirements be given, the protein may be still further reduced and yet equilibrium main- tained. To do this, however, it is not the amount of carbohy- drate alone that determines the ease with which the irreducible protein minimum can be reached ; the kind of protein itself makes a very great difference. This has been very beautifully shown by one investigator, who first of all, determined his nitrogen ex- cretion while living on nothing but starch and sugar, and then proceeded to see how little of differnt kinds of protein he had to take in order to bring himself into nitrogenous equilibrium. He found that he had to take the following amounts : 30 gr. meat protein, 31 gr. milk protein, 34 gr. rice protein, 38 gr. potato protein, 54 gr. bean protein, 76 gr. bread protein, and 102 gr. Indian corn protein. The organism is evidently able to satisfy its protein demands when it takes meat protein much more readily than with vegetable proteins. To understand why proteins should vary so much in Uitir nutritive value, we must examine their ultimate structure very closely. When the protein molecule is disintegrated, as by diges- tion, it yields a great number of nitrogen-containing acids, the amino acids, as well as several bases and aromatic substance's. The most important of these acids are glycin, alanin, serin, valin, leucin, prolin, aspartic and glutamic acids, the bases being lysin, histidin and arginin and the aromatic bodies, phenylalanin, tyro- sin and tryptophan. These substances constitute the available NORMAL METABOLISM. 97 "units" or "building stones" of protein molecules, but in no two proteins are the materials used exactly in the same propor- tions, some proteins having a preponderance of one or more and an absence of others, just as in a row of houses there may be no two that are exactly alike, although for all of them the same building materials were available. Albumin and globulin are the most important proteins of blood and tissues, so that the food must contain the necessary units for their construction. If it fails in this regard, even to the extent of lacking only one of them, the organism will either be unable to construct that pro- tein, and will therefore suffer from partial starvation, or it will have to construct for itself this missing unit, a process which it can accomplish for some but not all of the above list. It is therefore apparent that those proteins are most valu- able as foods that contain an array of units which can be reunited to form all the varieties of protein entering into the structure of the body proteins. Naturally, the protein which most nearly meets the requirement is meat protein, so that we are not sur- prised to find that less of it than of any other protein has to be taken to gain nitrogen equilibrium. Casein, the protein of milk; although it does not contain one of the most important units, namely, glycin, is almost as good as meat protein, because the organism is itself able to manufacture glycin. When, on the contrary, proteins such as zein from corn are given, in which cer- tain units are missing, starvation inevitably ensues. But it does not do so if the missing unit, which in the case of zein is trypto- phan, is added to the diet. These most important facts have been ascertained by experi- ments carried out in New Haven by Osborne and Mendel. Young albino rats, just weaned, were fed on a basal diet con- sisting of the sugar, fat and salts of milk to which was added the protein whose nutrition value it was desired to study. The rats were weighed from day to day, and the results plotted as a curve — the curve of growth. A gradually rising curve was obtained when casein or the albumin of milk or eggs, or the edestin of hemp seed, or the glutenin of wheat was fed, but this was not the case with the gliadin of wheat or, as 98 PHYSIOLOGY FOR DENTAL STUDENTS. above mentioned, with zein of corn. It will be seen, there- fore, that of the two proteins in wheat one, glutenin, contains all the necessary units for building up the growing tissues, but that in the other protein, gliadin, some essential unit is absent ; by analysis this was found to be lysin. By adding lysin to gliadin a normal curve of growth resulted, thus showing that this was really the missing unit. The result was made even more spectacular by feeding a batch of young rats on gliadin alone, so that they remained undeveloped and stunted, and then adding lysin to their diet, when they very quickly made up for lost time, and soon reached, if not quite, yet almost as good a development as their more fortunate brothers who had been fed on glutenin or casein from the very start. The animal economy itself can therefore produce certain of the amino bodies — thus, as we have seen, it can produce glycin — this power being much more developed in the case of herbivor- ous as compared with carnivorous animals. In the vegetable food on which oxen live several of the prominent amino bodies of muscle protein are missing, but they are constructed in the or- ganism by altering the arrangement of the molecules of those amino bodies which are present, so that a protein is built up which is very like that present in the tissue of the carnivorous animals. Even in the case of the herbivora, however, there are limitations to the power of forming new amino bodies. Trypto- phan cannot be formed in this way, for example. CHAPTER X. THE SCIENCE OF DIETETICS. In order that a proper assortment of amino bodies may be assured in the diet, protein is taken in excess of the quan- tity necessary to repair the tissues. It has been thought by some that the surplus thus taken by the average indi- vidual is much more than need be, and that an unnecessary strain is thus thrown on the organs which have to dispose of the excess. It has been claimed by the adherents of this view that many of the obscure symptoms — headaches, muscular and back pains, sleepiness, etc. — that city folk are liable to suffer from, are due to the presence in the blood of unnecessary by-products of ex- cessive protein metabolism. Such opinions seemed to receive very weighty indorsement some years ago when Chittenden pub- lished a long series of observations showing that men in various callings in life, could perform their daily work quite satisfac- torily and apparently maintain their health after reducing the protein of their diets to less than half of the usual amount. No direct benefit could be claimed for this reduction except that some of the men believed that they felt better and fitter and more inclined for work, an improvement which admits of no quantitative measurement because of the psychological elements involved. Even although these observations were conducted with all the care and accuracy of the highly trained scientist, they have been considered quite inadequate to justify the claim that man takes too much protein, but the observations have been of immense value in compelling a careful review of the evidence that the proportion of protein which habit has prescribed, as being the proper one for us to take, is really the most suitable for our daily needs. There are, however, differences in the protein content of the diet according to the race and environment. This has been as- certained by compiling the stardard diet for a community, that 99 100 PHYSIOLOGY FOR DENTAL STUDENTS. is, measuring the exact quantities of protein and carbohydrate in the diets which the people are accustomed to live on, and aver- aging the results. One remarkable outcome of such statistical work has been to show that for peoples living under approxi- mately the same conditions as regards climate and amount of daily muscular work, the average daily requirement of calories, carbon and nitrogen works out pretty much the same, although there may be some diversity in the proportions of protein and carbohydrate. The following table shows this: Type of individuals. Protein Fat Carbo. Total Cal. C. N. gr. gr. gr. gr. gr. Average workman in Germany, 20 years age. 118 56 500 3,045 328 18.8 German soldier in the field 151 46 522 3,190 340 24 British soldier in peace... 133 115 429 3,400 ... 21.3 Russian soldier in war (Man- churian campaign) .... 187 27 775 4,900 ... 30 Professional man 100 100 240 2,324 230 16 Such figures can be compiled with tolerable accuracy because the diet is under control. It is of course more difficult to collect sufficiently accurate data regarding the diets of civilians, but it is safe to say that the average city dweller in temperate zones derives his daily requirement of 15 gr. nitrogen in 95 grammes of protein, which also yields 60 gr. of the required 250 gr. car- bon. This deficit he might supply either from fats or carbohy- drates, the actual proportion depending on availability and price. It should be particularly noted that the proportion of protein is very much increased whenever strenuous muscular work has to be performed. Now the question is, do such statistical studies substantiate Chittenden's claim that the protein which we are accustomed to consume could profitably be reduced? They cer- tainly do not. Let us for a moment consider the health condition and physical development of communities such as the Bengalis of Lower Bengal, who live largely on rice, and take only a little less in the way of protein than what Chittenden would have us take. The body weight, chest measurement and muscular devel- opment are distinctly inferior to those of the natives of Eastern DIETETICS. 101 Bengal, who however belong to the same race as the lower Ben- galis, but differ from them in taking more protein in their food. Not only this, but these people are in every sense of the word half starved, and they are very prone to disease, especially of the kidneys, the very type of disease which we are told excessive protein consumption must predispose to. Diabetes is also very prevalent amongst these people, probably because of the enorm- ous quantities of sugar-yielding food (carbohydrates) which they are compelled to eat in order to provide sufficient calories for life. They can not get fat, nor do they desire it. Mentally, they are a very inferior race. This then is an experiment on a much grander scale than Chittenden 's, and what of the results? It is fortunate that most of Chittenden 's subjects "through force of circumstances" have returned to their old dietetic habits. Exactly concordant results have been obtained when attempts have been made to reduce the protein in the dietaries of public institutions such as prisons, alms houses, etc. There has invari- ably been a distinct increase in the sick list, especially of such diseases as pneumonia, tuberculosis, etc. And if we seek for evidence of an opposite nature, we do not find that excessive protein ingestion is fraught with any evil consequences to the community. Thus the Eskimo takes five times more protein than the Bengali and two and one-half times more than the European, and yet he is peculiarly free from ' ' uric acid ' ' diseases ; and his physical endurance and his power of withstanding cold are ex- traordinary, and there is no quarreling! There are a great many secondary factors, such as availability, taste, etc., that determine the average diet of a community, but the main determining factors are instinct and experience. In the struggle for existence between human races, we may assume that adequacy of diet has played a role and that the average which is taken represents that which conduces to the greatest efficiency. We have dealt at some length on these questions because of their great practical importance, and because they show us that in the matter of the protein content of our diet, as in that of all other animal functions, there comes into play the principle of 102 PHYSIOLOGY FOR DENTAL STUDENTS. the ' ' factor of safety. ' ' "We have two lungs, although it is quite possible to live with one only, two kidneys, although one will usually suffice, and so with protein in food, we could get along for some time with about half of what we take, but at the con- stant risk of a deficiency, for should physical exhaustion occur, a reserve of building stones ought to be available to restore the tissue which has been consumed. Instead of the excess of pro- tein throwing a strain on the organism, the contrary is the caso, for it is indisputably a greater strain for the tissues to have to construct new building stones than to use these supplied ready made in the food. Another deduction which we may draw from these observa- tions is that more protein should be taken when its source is mainly vegetable food than when it is animal. On the other hand, there is nothing to indicate that one kind of animal pro- tein possesses any advantages over another; flesh protein, milk protein, egg protein are practically of equal dietetic value, and with regard to what varieties of meats — whether light or dark- are most nutritious, all we can say is that any differences that may be thought to exist are not due to differences in the chemical nature of the proteins which they contain, but depend on their flavor and digestibility. There are more fads and fancies about what meats are nutritious and what are not so than would fill a volume, but after all the whole question is one of flavor. Man digests best what he likes best, and he thrives best when digestion is good. Doctors and dentists must be ready to discuss questions of diet, for the public likes to be treated with something more than the hard facts of science; he demands something mystical and mysterious besides ; if he agrees to be fed according to calorie and protein values, he demands besides that he be told fairy tales about some peculiar virtues which this or that variety of foodstuff possesses. Very practical conclusions may be drawn from these observa- itons regarding the most suitable diet for the city dweller. It is evident that we are now-a-days in possession of a sufficient amount of scientific information regarding both the daily require- ments of the body and the ability of the various foodstuffs to DIETETICS. 103 fulfill these requirements, to compute, from the market prices of foods, how much it should take per diem for an individual, or a family of individuals, to live healthfully and economically. The day will surely come when, through the medium of schools and the press, everyone will know what we may call the fundamentals of dietetics, namely: (1) that a man of sedentary occupation (the ordinary city clerk) requires daily 2,600 calories, and a laboring man, at least 3,000 calories. (2) That at least 5 per cent of the calories should be provided in protein food of animal origin (meats, milk) with 10 per cent or more as other protein (bread, oatmeal, etc.). To enable the housewife to purvey the necessary food to meet these requirements, she must therefore become familiar with the calorie value and the percentage of protein in the different classes of protein foods, and of the calorie values of other great staples of diet. Canned foods will no doubt some day have printed on the label : ' ' This can contains .... calories, of which .... per cent are in proteins of grade " And this is no Utopian idea; it is practical common sense. The adoption of such a scheme is far more likely to be the solution of the problem of the high cost of living than anything else, for, indeed, it is not so much the high cost of living as it is the cost of high living that troubles us. We demand business efficiency in our manufac- turing organizations, and yet we are inclined to ridicule as im- practical any attempts at nutritive efficiency in the animal organ- ization, which is our own body. Not only the principles of dietetics, but the details as well are now so thoroughly under- stood that their application in the feeding of the masses is only a matter of education. Dietery impostures of the meanest de- scription, often hiding behind a "bluff" of scientific knowledge, are of course the most serious enemies we shall have to face in spreading the knowledge. It will be the duty of physicians, of dentists, and of the educated classes to offset this commercial brigandage by spreading the gospel of food efficiency. As illustrating the food efficiency, in relationship to cost we may take the following table from the menu of a well-known restaurant company: 104 PHYSIOLOGY FOR DENTAL STl'DKNTS. Cost in cents per portion Bread 5 Apple pie 5 Boston pork and beans 15 Ham sandwich ... 5 Corn beef hash ... 15 Beef stew 15 Club sandwich ... 25 Sliced pineapple .. 5 Mayonaise 20 Calories Total P % i irot< 933 12 337 5 828 12 170 20 507 14 461 25 409 20 36 46 53 16 Calories in for 5 cents 933 337 276 170 170 154 82 36 13 Cost in cents per 1000 calories 5 15 18 30 30 32 61 138 35 (Lusk) The above table is not by any means from a cheap restaurant. By economy and judicious purchasing it is possible even in New York to purchase 1,000 calories having the proper proportion of calories for 8 cents, so that a working man may easily cover his dietetic requirements for 25 cents a day, exclusive of the cost •-[' cooking. All he spends above this is for personal taste and relish. Chemistry of the Commoner Foodstuffs. The accompanying diagram (Fig. 9) indicates the composition of some of the commoner foods and is self-explanatory. There are certain foodstuffs concerning which a little more detail may however be advisable. Wheat Flour, besides a large amount of starch, contains two proteins, glutein and gliadin. When the flour is mixed with water and then kneaded, it forms dough, because the proteins change into a sticky substance called gluten. As dough the flour is not a suitable food, because the digestive juices cannot pene- trate it. To render it digestible the dough must be made porons and this is accomplished by causing bubbles of carbon dioxide gas to develop in it, either by mixing it with baking powder which is composed of a bicarbonate and an organic acid (tar- taric) or by keeping it in a warm place with yeast, which fer- ments the sugar that is present. The sugar is developed from the starch by the action of the diastase (see p. 44) present in the flour. 10 20 30 40 50 60 70 80 90 100 1020 Ash and water. Protein of 1st Quality. Carbohydrate. Whole milk. Skim milk. Cream. Cheese. Butter. Average meat (raw). Average mutton (raw). Average pork (raw). (Fish — flounder (raw). Bacon. Wheat bread. Oats. Rice. Protein of 2nd Quality. Fat. Calories. Fig. 9. — Dietetic chart, showing the percentage amounts of the various proximate principles (indicated by the shaded areas) and the calories (indi- cated in red) yielded by burning 1 Ib. of the commoner foodstuffs. The num- bers to the right represent the calorie values and the names to the left, the food in question. DIETETICS. 105 When the yeast has been allowed to act for some time, or if baking powder was used, when the gas formation has ceased, suit- able portions (loaves) of dough are placed in the oven. The heat causes the inclosed bubbles of gas to expand so that the whole mass becomes aerated and further increase of temperature acts on the proteins and starches on the surface coagulating the for- mer and converting the latter into dextrins. Thus is the crust formed. Brown bread is made from wheat from which all the husk has not been removed. There are two possible advantages of this over white bread, namely, the husks act as a mild laxative and they seem to contain traces of vitamines (see p. 121). Other Cereals. — These include maize or Indian corn, oatmeal and rice, and differ from wheat in that their proteins do not form gluten when mixed with water. They cannot therefore be formed into bread unless they be mixed with some wheat flour. They are relatively rich in ash and maize contains a large proportion of fat. When rice composes a large proportion of the diet, as is the case in tropical countries, the unpolished variety should be used to supply the vitamines. When the diet is a mixed one, however, danger of an insufficiency of vitamines cannot exist. As has been already explained, the protein of cereals is not of first qual- ity, because it does not contain all of the ammo acids (building stones) of tissue proteins. Milk and Milk Preparations. — Whole milk is as nearly as possible a perfect food, for its protein is of the first quality and it contains a sufficiency of fats and carbohydrates for the growth of the tissues. Where muscular exercise must also be performed, carbohydrates should be added to the milk, and this is best ac- complished by the use of cereals. Milk is an economical food, for one quart nearly equals in nutritive value a pound of steak or eight or nine eggs, and is easily digested and assimulated, but somewhat constipating. The chief protein of milk is caseinogen (phospho protein) and is characterized by being precipitated by weak acids and by the action of gastric juice. When milk soul's some of the milk sugar, or lactose, becomes converted by bacterial action into lactic acid and this precipitates caseinogen. When an extract of the mucous membrane of the stomach is added to 106 PHYSIOLOGY FOR DENTAL STUDENTS. milk and the mixture kept warm, the clot which forms is called casein. By separating the casein and allowing it to stand for some time ferments, derived from moulds and bacteria, act on it to produce cheese. The cheese, besides casein, contains much fat and mineral matter. Cheddar cheese is especially rich in fat. Cheese is a very concentrated article of diet and when taken in moderation is thoroughly digested and assimilated. Cream consists of the milk fats with some of the constituents of milk. It is the most easily assimilated of all the fats and is hence very nutritious. When sweetened, flavored and frozen it forms ice cream, which should not be regarded, as it usually is, as a luxury, but as a highly nutritious food. It should not there- fore surprise the indulgent parent when a child goes off its food after visiting the corner pharmacy. On standing, cream ripens (undergoes change due to bacterial growth) and if it be churned the fat separates as butter. There is no foodstuff that contains more calories and besides, the butter contains certain vitamines. The fluid from which the butter separates, buttermilk, contains practically no fat and is acid to the taste because of bacterial action on the lactose producing lactic acid. Its influence on the nature of bacterial growth in the intestines has already been referred to. Eggs. — The only point we need emphasize is the much greater percentage of fat substances (lipoids) in the yolk than in the white. One dozen eggs equals in food value two pounds of meat. Eggs are therefore more costly than milk. Meats. — The building stones of the protein molecule of meat, for reasons which are obvious, are more nearly identical with those of the tissues of man than are those of any other food. The carbohydrate is however insufficient in amount, for which rea- son we take potatoes with meat. The flavors of different meats depend largely on the extractive substances which they contain. These include creatin and purine substances. When a decoction of meat is evaporated to small bulk, after precipitating all of the protein, meat extract is prepared, which, like coffee or tea, has no nutritive value but acts as a mild stimulant (caff em and theine are chemically very closely related to the purine bodies of meat DIETETICS. 107 extract). Clear soups are mainly dilute solutions of meat ex- tractives, but in beef tea, ,if properly made, there is much meat protein. Other Foods and Condiments. — Although green vegetables and salads consist very largely of water, they are very important articles of diet, because they contain cellulose, which serves to increase the bulk of the intestinal contents — to serve as ballast, as it were — and prevent constipation by keeping the intestinal musculature active. Some vegetables, such as spinach, are especially important since they contain iron. Salads have a further importance because of the oil taken with them. The rel- ishes and the condiment flavors are by no means insignificant adjuncts of diet for they give the relish to food without which digestion is likely to be inefficient. This most important prop- erty of diet has been sufficiently insisted upon elsewhere. CHAPTER XI. SPECIAL METABOLISM. But we must now return to the more theoretical aspects of our subject. We will proceed to trace out very briefly the interme- diary stages in metabolism through which proteins, fats and car- bohydrates have to pass in order to yield the energy required to drive the animal machine and to supply material with which to repair the broken-down tissues. Metabolism of Proteins. — We must follow the amino bodies after their absorption into the blood until they ultimately reap- pear, the nitrogen among the nitrogenous constituents of urine and the carbon as part of the carbon dioxide of expired air. In order to do this it is necessary for us to become familiar with the nature and source of the urinary substances ivhich contain. nitrogen, and to consider some of the most important chemical relationships of these substances, so that we may understand how they become formed in the body. The substances in question are : urea, ammonia, creatinin, the purin bodies, and undetermined nitrogenous substances. Urea and ammonia may be considered together. UREA AND AMMONIA.-— There is no doubt that it is as ammonia that the nitrogen of the amino bodies is set free in the organism. The free ammonia would, however, be highly poisonous, so that it immediately becomes combined with acid substances to form harmless neutral salts. The acid which is ordinarily used for this purpose is carbonic, of which there is always plenty in the blood and tissue juices. The ammonium carbonate thus formed becomes changed into urea by removal of the elements of water from the molecule, thus: OH ONH4 NH, NH, / / / / 2NH., + CO = CO — H.,0 = CO — H,0 = (1() \ \ \ \ OH ONH4 ONI I, MI Ammonia Carbonic Ammonium Ammonium I'rcu acid carbonate carbamate 108 THE METABOLISM OF PROTEINS. 109 The conversion of ammonium carbonate occurs largely in the liver. Our evidence for this is: (1) If solutions containing ammonium carbonate be made to circulate through an excised liver, urea is formed. (2) If this organ be seriously damaged, either experimentally or by disease, less urea and more ammonia appears in the urine. We see therefore that urea is formed in order to prevent the poisonous action of ammonia. But the am- monia may be more usefully employed ; instead of being com- bined with carbonic acid in order that it may be got rid of, it may be employed to neutralize, and thus render harmless, any other acids that make their appearance. Thus, it may be em- ployed to neutralize the acids which sometimes result during the metabolism of fat, as in the disease, diabetes; or the lactic acid that appears in the muscles during strenuous muscular exercise ; or the acids produced on account of inadequate oxygenation. Taking acids by the mouth has a similar effect; thus the am- monia excretion rises after drinking solutions containing weak mineral acids. Ammonia is, of course, not the only alkali which is available in the organism for the purpose of neutralizing acids. The fixed alkalies, sodium and potassium are also used. Thus, when we greatly increase the proportion of these, as by taking alkaline drinks, or by eating vegetable foods, the ammonia excretion diminishes. Urea is an inert substance, capable of uniting with acids to form unstable salts (urea nitrate and oxalate), and like other amino bodies, being decomposed by nitrous acid so as to yield free nitrogen. This latter reaction is used for the quantitative estimation of urea, the evolved nitrogen being proportional to the amount of urea, thus : NH2 CO +2 HN02 = 2.C02 + 2 N2 -f 2 H2O NH2 Certain bacteria are capable of causing urea to take up 2 mole- cules of water so as to form ammonium carbonate, a process 110 PHYSIOLOGY FOR DENTAL STUDENTS. really the reverse of that which occurs in the organism and rep- resented by the above formulas. This change occurs in urine and accounts for the ammoniacal odor which develops when this fluid is allowed to stand. CREATININ. — This is very closely related to creatin, which is the most abundant extractive substance in muscle, and which yields urea when it is boiled with weak alkali. These chemical facts would lead us to expect that some relationship must exist be- tween the creatin of muscle and the creatinin and urea of urine, but, so far, it has been impossible to show what this relationship is. One very important fact has, however, been brought to light, namely, that creatin makes its appearance in the urine when carbohydrate substances are not being oxidized in the body, as in starvation, and in the disease diabetes. This is one reason for the growing belief that carbohydrates are something more than mere energy materials (see p. 113). The excretion of creatinin is so remarkably independent of the amount of protein in the food that it is believed to represent more especially the end prod- uct of the protein break-down of the tissues themselves, in con- trast to urea, which partly represents the cast-off nitrogen of the protein of the food. PURIN BODIES. — These are of particular interest because they include uric acid, about which more nonsense has been written than about any other product of animal metabolism. The so- called uric acid diathesis is very largely a medical myth — a cloak for ignorance. Uric acid is the end oxidation product of the purin bodies, which include the hypoxanthin and xanthin of muscle and their amino derivatives, the adenin and guanin of nuclein. These relationships are seen in the following formulas : Oxy purins of muscle . . . I Hypoxanthin C5H4N40 { Xanthin C5H4N40, Amino purins of nuclein. . 1 Adenin C5H4N4NH ( Guanin C5H4N4ONH Uric acid C5H4N402 There are therefore two sources for uric acid in the animal THE METABOLISM OF PROTEINS. Ill body, namely, the muscles and the nuclei of the cells. This ex- plains why the uric acid excretion increases after strenuous mus- cular work, and why it is much above the normal when cellular break-down is very excessive, as in the disease called leucocythe- mia, in which there is an excess of leucocytes in the blood (see p. 145). Another source of uric acid is the food when it con- tains either muscle (flesh) or glands (sweetbreads), for a large proportion (about half) of the ingested purins do not become destroyed in their passage through the organism; but become oxidized to uric acid, which is excreted in the urine. This is called the exogenous in contrast to purin produced in the tissues, which is called endogenous. There is only a trace of uric acid in the urine of mammals, but in birds and reptiles most of the nitrogen is present in this form. The reason is that in these animals it is important to have semi- solid, instead of fluid excreta, so that the urea which results from protein metabolism becomes converted into uric acid, which, either free or as salts, is relatively insoluble. Uric acid is chemi- cally a diureide, that is to say, it consists of two urea molecules linked together by a chain of carbon atoms. The chain of carbon atoms is furnished by substances not unlike lactic acid and the synthesis occurs in the liver. If this organ be removed from the circulation in birds, such as geese, in which the operation is comparatively easy, a very large part of the uric acid in the urine becomes replaced by ammonium lactate. The relative insolubility of uric acid and its salts, which we have already referred to, makes it apt to become precipitated in urine, especially on standing. It forms the orange reddish de- posit, so frequently observed in summer, when on account of per- spiration the urine does not contain as much water as usual. Such deposits do not therefore indicate that there is an excess of uric acid in the blood, but merely that enough water is not being excreted to dissolve the usual amount of urates. Sometimes the urate becomes deposited in the joint cartilages, particularly in those of the great toe, causing local swelling and redness and great pain. This is gout, and it may be most effectually treated by drinking large quantities of alkaline fluids, and eliminating 112 PHYSIOLOGY FOR DENTAL STUDENTS. from the dietary such foodstuffs as meats and sweetbreads, which yield exogenous purins. As we have said, there is no reason to believe that any other diseases besides gout are due to excess of uric acid in the blood. Besides the above there are traces of other nitrogenous sub- stances in the urine, such as : 1. Hippuric acid, which, as its name signifies, is very abun- dant in the urine of the horse and other herbivora, and which is the excretory product of the aromatic substances which the food of these animals contains. 2. Cystin, an amino acid containing sulphur. 3. Pigments and mucin. The exact significance of the end products of nitrogenous met- abolism has been very beautifully demonstrated by Folin, of Harvard. The observations were made on several men who lived for some days on a diet rich in protein (but containing no purin- containing foodstuffs), and then on one which was very poor in protein. The problem was to see how each of the nitrogenous constituents behaved during the two periods, both absolutely and in relation to the total amount of nitrogen excreted. In or- der to show the latter relationship the results are given, as in the following table, not as urea, etc., but as urea-nitrogen, etc. : On the protein-rich On the protein- diet poor diet Quantity of urine 1170 c. c. 385 c. c. Total nitrogen 16.8 gr. 3.6 gr. Urea-nitrogen 14.7 gr. (87.5) 2.2 gr. (61.7) Ammonia-nitrogen 0.49 gr. (3.0) 0.42 gr. (11.3) Uric acid-nitrogen 0.18 gr. (1.1) 0.09 gr. (2.5) Creatinin-nitrogen 0.58 gr. (3.6) 0.60 gr. (17.2) Undetermined nitrogen . . . 0.85 gr. (4.9) 0.27 gr. (7.3) The figures in parentheses represent the percentage which the nitrogen of, each substance furnishes of the total amount of nitro- gen excreted. It will be seen that urea decreases on the poor diet relatively more than total nitrogen, thus indicating that it comes partly from proteins in the food (exogenous) and partly THE METABOLISM OP PROTEINS. 113 from the organism itself (endogenous). This result leads us to infer that most of the amino substances of protein foods which are not required as building stones for the tissues are broken down so as to yield ammonia, which is excreted as exogenous urea in the urine, but that the amino bodies that are really appropri- ated by the tissues, although they may also produce some urea (endogenous), cause other end-products to be formed. The most important of these endogenous bodies is evidently Creatinin, for, as will be seen from the above table, this substance is excreted in the same absolute amount during both the starvation and the protein-rich periods. Direct evidence that this conclusion is correct has been ob- tained by examination of the blood and muscles for amino bodies, ammonia and urea. The results have shown that the ammo bodies absorbed from the intestine are carried through the liver into the systemic blood, which transports them to the muscles, where those that are not required for building up the tissues are broken down into ammonia and a carbonaceous residue, which is then burned just exactly as if it were carbohydrate or fat. The useless ammonia becomes converted into urea in the manner already described, either in the muscles themselves, or by being carried to the liver, which, as we have seen, possesses to a very high degree the power of producing urea. The Relative Importance of Proteins, Fats and Carbohy- drates in Metabolism. — The metabolism of fats and carbohy- drates, with regard both to their importance as builders of living tissues and the type of their metabolism, is very different from that of proteins. That carbohydrates and fats are less impor- tant in the animal economy than proteins is evidenced by the fact that we can live perfectly well on protein food alone, but not on either of the others. This does not, however, justify us in concluding that carbohydrates and fats are merely materials which are oxidized by the tissues, for the purpose of producing energy, fuel as it were, and which can be dispensed with. They •itfWH^^^M^tfHINMHHHHM^^^gB^^^^^^^^^^^ are more than this, for no cell, in however starved a condition it may be, is entirely free from either of them, thus indicating that they must have been produced out of protein itself. Pro- 114 PHYSIOLOGY FOR DENTAL STUDENTS. teins are no doubt the most important ingredients of cells, hut fats and carbohydrates are indispensable also. As reserve materials, striking differences exist between the three foodstuffs. Proteins are of little value in this regard for, as we have seen, very little, if any, can become laid down in the tissues when excess is taken as food; on the contrary, all that is not required is thrown out of the body, and when the food sup- ply is cut off, as in starvation, the protein is spared as much as possible (see p. 92). Carbohydrates are very readily depos- ited as a starch-like substance, called glycogen, and this reserve is the first to be called on, not only in starvation, but also when muscular work is performed. It may be considered as the most immediately available material for combustion in the organism, but the limits of its storage are restricted in man to some hun- dreds of grammes, which, as we have seen, soon becomes used up in starvation. Fat is pre-eminently the storage material, and the supply may serve in man to furnish, along with a little pro- tein, enough fuel for several weeks' existence. The relative importance of the three foodstuffs is shown in the extent to which each is used in the metabolism during muscular exercise. When there is an abundant store of glycogen, the energy is entirely derived from this source ; when there is little glycogen but much fat, it is fat that is burned, and when neither of these is abundant but much protein is being taken witli the food, or the animal is reduced to living on its own tissues, as in starvation, it is protein. In other words, the type of metabolism occurring during muscular work is the same as that which imme- diately preceded it ; the only change is in the extent of the com- bustion, not in the nature of the fuel employed. CHAPTER XII. SPECIAL METABOLISM (Cont'd). Metabolism of Fats. — Fats are absorbed into the lacteals and discharged into the blood of the left subclavian vein through the thoracic duct. They are carried to various parts of the body and gain entry into the cells, in the protoplasm of which they become deposited. This process occurs extensively in the sub- cutaneous connective tissues, between the muscles, and retroperi- toneally around the kidney (the suet). The fat which is thus deposited possesses more or less the same qualities as the fat of the food. Thus, when the only fat taken over a long period of time is one with a very low melting-point, such an oil, the fat deposited in the tissues is likely to be oily in character, whereas it is stiff after feeding with a high melting-point fat, such as mutton fat. This similarity between the tissue fat and that of the food becomes very striking when the animal has been sub- jected to a preliminary period of starvation and then fed for some weeks with a large excess of the particular fat and as little carbohydrate and protein as possible. Fat in the food is of course not the only source of the fat in the tissues. It also be- comes formed out of carbohydrates, a fact which is well known to farmers, who fatten their stock by feeding them with maize and other starchy grains, and to physicians, who reduce their corpulent patients by restricting carbohydrate foods. The fat thus deposited has the chemical characteristics of the fat which is peculiar to that animal. It is almost certain that there is ordi- narily no formation of fat out of protein in the higher animals. The fat thus deposited in the tissues may remain for a long time, but ultimately it is again taken up by the blood and car- ried to whatever active tissue requires it as fuel. Before being thus burnt, it splits into glycerine and fat acid (see p. 75). The fat acid possibly undergoes some preliminary change in the 115 116 PHYSIOLOGY FOR DENTAL STUDENTS. liver; iii any case, the long chain of carbon atoms of which we have seen fat acid molecule to be composed (see p. 24) becomes oxidized (burnt), not all at once but piece by piece, two carbon atoms being split off at a time. If the fat acid chain originally contained an even number of carbon atoms, the oxidation process may stop short when there are yet four carbon atoms in the chain, thus producing oxybutryic acid (CH3CHOHCH2COOH). This imperfect metabolism of fat oc- curs in severe cases of diabetes and often causes death. It also occurs in carbohydrate starvation, and indicates, more clearly than any thing else, that even carbohydrates are essential for life. Metabolism of Carbohydrates. — It will be remembered that these include the starches and the sugars, and that during diges- tion they are all hydrolyzed to dextrose or laevulose, as which they are absorbed into the blood of the portal vein. This ab- sorption is rapid, so that a striking increase in the percentage of sugar occurs in the blood of the portal vein shortly after the food has been taken. Most of this excess of sugar does not imme- diately gain entry to the blood of the systemic circulation, how- ever, because it is retained by the liver. For this purpose the liver cells convert the sugar into the starch-like substance, glyco- 'gen, which becomes deposited in their protoplasm as irregular colloidal masses, which stain with iodine and carmine. The liver does not manage in this way to remove all of the excess of sugar from the portal blood, so that, even in a healthy animal, there is a distinct postprandial increase of sugar, or hyperglycaemia, as it is called, in the systemic blood. If too much sugar passes the liver it causes so marked a postprandial hyperglycffimia that some sugar escapes into the urine, thus causing glycosuria, which is one of the early symptoms of diabetes, and whose occurrence furnishes us with a warning that less carbohydrates should be given in the food. If the warning be heeded, the severer form of the disease will very probably be staved off. The glycogen deposited in the liver stays there until the per- centage of sugar in the systemic blood begins to fall below its proper level (which in man is about 0.1 per cent), when it becomes reconverted into sugar, which is added to the blood. THE METABOLISM OF CARBOHYDRATES. 117 The reason why the sugar in the systemic blood tends to fall is that the tissues, especially the muscles, are using it up as fuel. If so much sugar is taken that the storage capacity of the liver is overstepped, the excess of sugar is carried by the systemic blood to the tissues, where much of it may be changed into fat. The glycogenic function of the liver, as the above process is called, is analogous to the starch-forming function of many plants, such as potatoes. Of the sugar which is formed in the green leaves, some is immediately used for building up other substances, the remainder being converted into starch, which be- comes deposited in the roots, etc., until it is required (as during the second year's growth), when it is gradually reconverted into sugar. Besides carbohydrates it is known that proteins form glyco- gen; fats, however, cannot form it. In severe cases of diabetes it is therefore usual to find that although carbohydrate foods are entirely withheld, dextrose continues to be eliminated in the urine. It may come partly from the protein of the food and partly from that of the tissues. The adjustment between the rate at which the glycogen of the liver becomes converted into dextrose and the percentage of sugar in the systemic blood is effected partly through the nervous system and partly by means of substances called chemical mes- sengers or hormones (see p. 124) secreted into the blood from the ductless glands, such as the pancreas and the adrenals. The very first symptoms of diabetes, which we have seen, consist in an excessive postprandial rise in the systemic blood-sugar and a consequent glycosuria, must therefore be due to defects in one or other of these regulatory mechanisms, so that it is of great interest to know that glycosuria can be induced in the lower animals by stimulation of the nerves of the liver or by interfer- ing with the function of the pancreas or the adrenal glands. The nerves of the liver may be stimulated either directly or through ;i nerve center located in the medulla oblongata (see p. 246). Complete removal of the pancreas is followed in a few hours by a very acute form of diabetes, which is invariably fatal in a few weeks, whatever the treatment may be. Injection of extract 118 PHYSIOLOGY FOR DENTAL STUDENTS. of the adrenal gland (adrenalin) causes a transient hyperglycae- mia and glycosuria. These laboratory discoveries have in their turn caused clinical investigators to pay close attention to the nature of the causes of diabetes. It has been found, as a result, that oft-repeated overstimulation of the nervous system — nerve strain, as it is called — greatly predisposes to this disease. For example, it has been found that a considerable proportion of students who un- derwent a severe examination for a university degree had glyco- suria in the urine, which was passed immediately after leaving the examination room. Even more interesting was an observa- tion on the urine of men waiting on the side lines as reserves in one of the large football games; about one-half of them passed sugar, due to nervous excitation of the glycogenic function. Be- sides these types of nerve strain, nervous glycosuria may also be brought on by fright and terror. This has perhaps been most definitely shown by frightening a tom-cat by allowing a dog to bark at it; the cat shortly afterward passed urine containing much sugar. Now, whereas occasional attacks of such nervous glycosuria are harmless, yet their repeated occurrence undoubt- edly weakens the ability of the liver properly to control the per- centage of sugar in the blood, with the consequence that post- prandial hyperglycaemia becomes more and more marked and takes longer to disappear, so that there comes to be a permanent increase in the percentage of sugar in the blood. This persistent excess of sugar acts as a poison and causes deterioration of many of the tissues, and if unchecked will lead to severe diabetes. It is for these reasons that diabetes is relatively common amongst locomotive engineers and ship captains; it is also said to be distinctly on the increase amongst business men. A most important element in the treatment of diabetes is therefore removal of the possible causes of nerve strain. Rest and quiet and freedom from worry, coupled with removal of sufficient amounts of carbohydrates from the diet so as to keep the urine free of sugar, is the correct treatment. One common symptom of diabetes is loosening of the teeth. When such is observed the urine passed an hour or so after lunch should be examined for THE METABOLISM OF INORGANIC SALTS. 119 sugar. Properly conducted treatment will often cause the teeth to tighten up again. A very common cause of death in diabetes is coma, which is due to the poisoning of the animal by acid substances (oxy- butyric acid) which result from the imperfect oxidation of fat (see p. 116). While these acid substances are gradually accumu- lating in the blood, the organism attempts to neutralize them by diverting ammonia from its normal course into urea (see p. 108) ; hence the ammonia content in the urine is very high in severe cases of diabetes. Along with these acids and ammonia, acetone also appears in the urine and breath, so that one can often diag nose a severe case of diabetes by the smell of these substances in the breath. Diabetes is therefore a disease which the dentist should always be on the lookout for. Metabolism of the Inorganic Salts. — Being already com- pletely oxidized, inorganic salts cannot yield any energy during their passage through the animal body but nevertheless they are essential to life. They are used not only for the building up of bones and teeth, but also for the proper carrying out of the metabolic processes. In this regard they are like the lubricant of a piece of machinery, the organic foodstuffs being like the fuel. Their indispensability is very clearly shown by the fact that animals die sooner when they are fed on food from which all traces of inorganic salts have been extracted than when they are deprived of food altogether. This result shows us that during the metabolism of organic foods substances must be produced which act as poisons in the absence of inorganic salts. Some of these poisonous substances are no doubt acid in reaction because life can be prolonged for some time by merely adding sodium carbonate to the salt-free food. But salts not having any neutralizing powers are also necessary to keep the animal alive. The chief salts which we take with our food are the chlorides, carbonates and organic acid salts (e. g., citrates, tartarates, etc.) of sodium and potassium and of calcium. We also take some iron and traces of iodine. All of these are already present in suffi- cient amount in the ordinary foodstuffs, except sodium chloride, 120 PHYSIOLOGY FOR DENTAL STUDENTS. or 'common salt. This we must add to our food. The extent to which the addition of common salt is made varies very strikingly according to the nature of the organic food taken. When this is mainly vegetable in origin, much common salt is required, the reason being apparently that vegetables contain large quantities of potassium salts which would be harmful unless a proper pro- portion of sodium is also taken. The demand for sodium by herbivorous animals often inclines these to wander for hundreds of miles from their feeding grounds to salt licks. Here they take enough sodium chloride to last them for some time. The carniv- orous animals do not visit salt licks unless it be for the purpose of preying on the herbivorous visitors. The salt hunger from which they suffer compels the the herbivora to the salt licks even in face of this danger of destruction by the carnivora. The same relationship between the desire for salt and the diet is seen in man, for the salt consumption per capita is much greater in rural communities than in those living in towns. Usually enough iron is taken either in meats or in certain vege- tables, as spinach. The body is very careful of its supply of iron (which is the most important constituent of haemoglobin), but if it loses it more quickly than the loss can be made good from the food, anemia results and it becomes necessary to pre- scribe iron salts as medicine. Similarly with calcium, there is usually enough in the food even of growing animals to meet the demands which bone and teeth formation entails. Rickets is not usually due to a defi- ciency of calcium in'the food, but to a depraved condition of the general nutrition, making it impossible for the available calcium to be properly used. Good food, air and exercise, rather than drugs, is the correct treatment for rickets. Our knowledge of just what each particular inorganic salt docs in the metabolism of an animal is not yet very far developed, but some most important discoveries have been made in this connec- tion during recent years. Thus, by observing the isolated beat- ing heart of the frog or turtle it has been found that a certain proportion of sodium, calcium and potassium salts is essential to the maintenance of a proper beat. With sodium chloride VITAMINES. 121 alone the beat soon stops, with excess of potassium an immediate paralysis occurs, and with excess of calcium an immediate rigor or permanent contraction. Analogous results are obtained with other muscles. Salts in certain proportions may even cause .processes of cell division to start in the ova of some of the lower animals. In other words, a process of embryo development may which is usually induced by impregnation by the male elements. Vitamines. — Equally remarkable as adjuncts of diet is a class of bodies called vitamines. Without them metabolism becomes upset, and serious symptoms make their appearance with per- haps death as the ultimate result ; and this happens even although the protein, fat, carbohydrate and inorganic salts of the diet be in proper proportion. The first indication of the importance of vitamines was furnished by observations on a disease called Beri-Beri, which occurs among peoples of tropical countries, and is characterized by severe neuralgic pains, muscular weakness and paralysis; symptoms which are due to inflammation of the nerves (neuritis). It was noted that it occurred most frequently in the case of people whose main article of diet was polished rice, but was infrequent in the case of those using the unpol- ished grain. The difference between these two grades of rice is that the one (the unpolished) still contains some of the brown- ish husk ; the other is free of it. This observation suggested the experiment of adding some of the ground-up rice husks to the polished rice diet of those suffering from the disease, with the result that the symptoms soon disappeared. Moreover, when unpolished rice was supplied, in place of polished rice, to natives among whom Beri-Beri was very prevalent, the disease disap- peared entirely. Other foodstuffs contain this vitamine, so that Beri-Beri does not occur with mixed diets. In order to learn something more about these remarkable sub- stances it was necessary to seek for some animal in which symp- toms similar to those of Beri-Beri could be induced by feeding with polished rice. Pigeons were found most suitable. When these birds are kept exclusively on such a diet, they develop the 122 PHYSIOLOGY FOR DENTAL STUDENTS. most alarming symptoms of neuritis (paralysis, weakness, etc.), which however disappear in a few hours, not only when unpol- ished rice or rice polishings (or husks) are given, but also when meat, or beans, or a small piece of yeast is mixed with the rice. Attempts have naturally been made to isolate the substance which is responsible for this remarkable action, and indeed some success can already be reported. For example, it has been pos- sible to separate from rice polishings and from yeast small traces of crystalline substances having a most powerful action in pre- venting neuritis. Even such success in investigating the cause of Beri-Beri in rice-feeders would scarcely warrant us in asserting that vita- mines are essential constituents of our own varied diets. To show that they are, however, has been no very difficult task. Thus, it is known that although young rats thrive admirably. on milk diet, they fail to do so on one of artificial milk, that is, of milk made in the laboratory by mixing together, in proper proportions, the same proteins, fats, carbohydrates and salts that occur in milk. In this chemical mixture, something is wanting which exists only when the ingredients of milk are compounded by the mammary glands. The addition to synthetic milk of desiccated milk from which most of the proteins had been removed bestowed on it full nutritive value. The practical importance of this observation in the feeding of infants, we need not insist on. Suffice it to say that it is quite possible that prolonged boiling of milk, as for its sterilization, may deprive it of vitamines and thus render the child liable to such diseases as rickets and infantile scurvy, or at least interfere materially with its proper development and growth. Among the symptoms thus produced, especially in the case of infantile scurvy, ulcers may develop on the gums, or the teeth may become loosened. Change of diet may in a few days restore perfect health, or even the addition of a few teaspoonfuls of orange or lemon juice to the original diet may suffice. It is often miracu- lous how quickly such treatment may change a fretful, pain- stricken child to one of perfect health and cheerfulness. Innumerable other examples of the wonderful influence of VITAMINES. 123 these mysterious vitamines in nutrition might be cited. The practical point to bear in mind is that, however correctly our diet may be composed with regard to calorie and chemical require- ments, it is likely to be unsuitable unless it contains a certain, though perhaps extremely minute, amount of the drug-like sub- stance called vitamines. CHAPTER XIII. THE DUCTLESS GLANDS. Introductory. — We have no more than touched the very fringe of the subject of metabolism, and yet we have learned enough to impress us with the fact that although it is extremely complicated, it is nevertheless under perfect control. It remains for us to learn something regarding the nature of this control. If we take such a metabolic process as that which carbohy- drates undergo, we should expect that the conditions which deter- mine whether glycogen shall be formed or broken down would be chemical in nature. We should expect, in other words, that some change in the chemical composition of the blood — either its reaction or the amount of sugar in it, or the appearance in it of some decomposition product of sugar — would determine whether or not glycogen should be mobilized as sugar. In muscular work, for example, sugar is required by the contracting muscles, and we find that the glycogen stores in the liver become very quickly depleted to meet the demand. The question is, how do the mus- cles transmit their requirements to the liver so as to cause this organ to mobilize the dextrose ? Our natural assumption would be that the active muscles cause some change to occur in the blood and that it is this change which excites the liver cells. Such a control of the metabolic activities of one tissue by prod- ucts of the activity of another, transmitted between them by way of the blood, is known as hormone control. We have already become acquainted with it in connection with the control of cer- tain of the digestive glands, particularly the pancreas (see p. 72), and it is no doubt very largely by such a mechanism that a given metabolic process becomes active or supressed, as occasion demands. The hormones in such cases are in part the interim-diary prod- ucts of metabolism, but besides these hormones others must exist 124 THE THYROID GLAND. 125 to call forth or regulate the activities of tissues which are not immediately concerned in general metabolism but rather with special processes, such as the excitability of the nervous system (e. g., adrenalin), the behavior of the reproductive glands (e. g., in the secretion of milk), the growth of certain tissues (e. g., of subcutaneous tissues, of hairs) or the atrophy of others, (e. g., of the uterus after pregnancy is terminated). For such hor- mones, special manufacturing centres are provided in the duct- less glands. The thyroid and thymus glands in the neck, the pituitary in the brain, the spleen and adrenal glands in the ab- domen are good examples. None of these has any duct, but they discharge the products of their activity — internal secretion — into the blood stream, by which it is carried to the tissue or organ on which it acts. Internal secretions may also be produced by certain cells of the digestive glands, as, for example, the so-called Isles of Langerhans of the pancreas (see p. 72), and likewise there are certain organs whose main functions are of quite a special nature, such as the ovaries and testes, that can produce very powerful internal secretions. We shall confine our attentions for the present, however, to the strictly ductless glands. Their function is ascertained ex- perimentally either by removing the gland by operation or by in- jecting an extract of it and then observing the behavior of the animal. Much can also be learned by observing patients in which the gland is diseased. The Thyroid and Parathyroid Glands. — The thyroid gland consists of two oval lobes situated one on either side of the trachea just below the larynx or voice box, -and connected to- gether over the trachea by an isthmus of thyroid tissue. Em- bedded in the substance of each lobe of the gland on the poste- rior surface are the two very small parathyroid glands. Minute examination shows the thyroid glands to be composed of vesicles lined by low columnar epithelium and filled with a clear glossy substance called colloid. The parathyroids have an entirely dif- ferent structure, being composed of elongated groups of poly- hedral cells with no colloid material. The functions of the two glands are probably essentially dif- 126 PHYSIOLOGY FOR DENTAL STUDENTS. ferent, the thyroid having to do with the general nutrition of the animal, and the parathyroid with the condition of the nervous system. They lie so close together, however, that it is very diffi- cult to study their separate functions. The importance of the glands is indicated by the relatively large blood supply. Fig. 10. — Cretin, 19 years old. The treatment with thyroid extract was started too late to be of benefit. (Patient of Dr. S. J. Webster.) When the thyroid is not properly developed in children, the condition is known as cretinism (Fig. 10). The child fails to grow in height, although its bones may thicken. It cranial bones soon fuse together, so that the growth of the brain is hindered THE THYROID GLAND. 127 and the mental powers fail to develop. It thus becomes idiotic, and although it may live for years, it will remain even at thirty years of age, a stunted, pot-bellied, ugly creature with the intel- ligence of an infant. The cause of this failure to develop is un- doubtedly bound up in some way with the deficiency of the thy- roid, for if the cretin be given extract of this gland, its condition will immediately improve, and indeed, if taken early enough, it may quickly make up for lost time and grow both physically and mentally as it ought to. Atrophy of the thyroid gland in older persons causes myxoe- dema. (Fig. 11). The symptoms of this are very characteris- Fig. 11. — A, Case of myxoedema ; B, Same after seven months' treatment. (Tigerstedt.) tic, being most commonly seen in women. The skin is dry and often of a yellowish color, the hair falls out, the subcutaneous tissues grow excessively, so that the hands, the feet and the face become large and puffy, and the speech indistinct, because of the thickening of the lips. The metabolism also becomes very slug- gish, so that the intake of food and the excretion of nitrogen in the urine become diminished, and the temperature subnormal. If 128 PHYSIOLOGY FOR DENTAL STUDENTS. unchecked, mental symptoms become apparent, first of all, a dulling of the intellect with sleepiness and lethargy, and later, muscular twitchings and tremors. Just as in cretinism, so in myxcedema, administration of thyroid extract causes these symp- toms to disappear, so that in a month or so the patient may have returned to his or her normal condition, to maintain which, how- ever, the thyroid extract must continue to be given. When the gland is removed surgically, either in lower animals or in man, very acute symptoms ending in death usually super- vene. These include a peculiar form of muscular tremor called tctany, passing into actual convulsions, which, by involving the respiratory muscles, ultimately cause dyspnoea and death. It is, however, probable that these nervous symptoms are due to the unavoidable removal of the parathyroid glands. The tetany is removed by giving calcium salts. These conditions associated with deficiency of the thyroid are grouped together as hypothy- roidism. Even in healthy individuals thyroid extract taken by mouth excites a more active metabolism, and may cause increased heart activity. One result' of this increased metabolism is disappear- ance of subcutaneous fat and increased appetite, thus rendering the administration of moderate doses of thyroid extract a not uncommon method of treatment for obesity. Such treatment should never be attempted except under the control of a physi- cian, for it is very easy to take too much of the extract and cause palpitation and nervous excitement. When the thyroid (and parathyroid) glands become excess- ively active in man, the condition is called hyper thy roidism, and the symptoms are very like those above described as produced by taking thyroid extract. To be exact, they are palpitation, wasting of the muscles and consequent weakness, extreme ner- vousness and protrusion of the eyeballs. On account of this last mentioned symptom the condition is usually called exophthalmic goitre. This acute and often fatal disease is to be distinguished from chronic goitre, in which there are very few general symp- toms, but great enlargement of the thyroid gland, indeed an en- largement which may be so pronounced as practically to obliter- THE ADRENAL GLANDS 129 ate the neck and sometimes so compress the trachea as to inter- fere with breathing. The cases of chronic goitre occur in the same districts in which the exophthalmic variety is common, these being, in this country, the shores of the great inland lakes and the river valleys, but not in districts bordering on the sea. They are also common in certain districts in Switzerland and Eng- land. It is of interest that in the lake and river districts in this country the thyroids of over ninety per cent of all dogs are more or less hypertrophied. The above remarkable influence of the thyroids on metabolism is in some way dependent upon the colloid material which fills the vesicles. This colloid contains a peculiar substance called iodothyrin, because it contains iodine, an element which is not found present in any other part of the animal body. The Adrenal Glands. — As their name signifies, these are situ- ated one on either side just above the kidneys. Each gland is yellowish in color, and is seen on microscopic examination to be composed of a medullary and a cortical portion. The medulla consists of irregular collections of cells containing granules which stain deeply brown with chronic acid and are therefore called chromophile granules. Similar chromophile granules may exist in other parts of the body. The great splanchnic nerve, which it will be remembered arises from the sympathetic chain in the thorax (see p. 278), makes very intimate connection with the adrenal medulla, for which reason and because of the fact that it is developed from the same embryonic tissue as the sym- pathetic system of nerves, the medulla of the adrenal gland is believed to be closely bound up with the functions of the sympa- thetic nervous system. The cortex is composed of rows of col- umnar cells which do not contain chromophile granules. Small though they be, the adrenal glands are essential to life, for their removal causes extreme muscular weakness and a fall in blood pressure followed by death within twenty-four hours. When they are the seat of disease (tubercular), symptoms of extreme muscular prostration, accompanied by vomiting and a peculiar bronzing of the skin, set in and grow steadily worse until at last the patient succumbs. This is called Addison's disease. 130 PHYSIOLOGY FOR DENTAL STUDENTS. The most striking proof of their importance is obtained by in- jecting an extract of the medulla of the adrenal gland into a vein. It causes an immediate rise in blood pressure, which is more or less proportional to the strength of the extract. The rise is accompanied by a slowing of the heart, due to the reflex stimulation of the vagus centre excited by the rising blood pres- sure. When this reflex slowing is rendered impossible by cutting the vagi, the rise in blood pressure following the injection may be enormous. The active substance in the extract is called adren- alin, suprarenin, adrenin or epinephrin. It is a comparatively simple chemical body, having the formula: (HO)C CH /\ CHCH (OH) CH2 — NHCHa CH \/ CH and existing in two varieties which differ from one another ac- cording to the direction to which the plane of polarized light is rotated. The variety rotating to the left is, by many times, stronger in its physiological actions than that which rotates to the right. The discovery of its chemical structure has made it possible for chemists to prepare suprarenin synthetically, and also to prepare a series of related substances having less marked properties of a similar kind. These are closely related to certain of the bodies which appear during the putrefaction of meat. By careful studies of the action of the suprarenin, or related substances, it has been found that the rise in blood pressure, above referred to, is due to stimulation of the muscle fibers in the walls of the blood vessels. It is on this account that a weak solution of suprarenin is used to stop haemorrhage, as after removing polypi from the nose, or in bleeding from the gums, as after tooth ex- traction. The muscle of arteries is by no means the only struc- ture on which adrenalin acts ; indeed it stimulates every structure which is capable of being stimulated by the sympathetic nervous system (see p. 277). Thus, it causes the pupil to dilate, saliva THE PITUITARY GLAND. 131 to be secreted (p. 41), the movements of the intestine to be in- hibited (p. 79), whereas it has no action on the blood vessels of the lungs or brain, which do not possess vasomotor nerves. This similarity between the results which follow suprarenin in- jection and stimulation of the sympathetic system is particularly significant when we call to mind the fact that the medulla of the adrenal gland is developed from the same embryonic tissue as the sympathetic system. The clotting power of the blood is diminished after injections of suprarenin. The Pituitary Gland. — This occupies the Sella Turcica of the base of the cranium and is composed of three portions or lobes. The anterior lobe consists of large epithelial cells and is really an isolated outgrowth from the epiblast of the upper end of the alimentary canal. Its complete excision causes death in a few days, but if only a part is removed, a condition called Jiypo- pituitarism develops, of which adiposity and sexual impotence are the main symptoms. When this lobe becomes excessively active in man (because of hypertrophy), it causes a peculiar growth of the bones, particularly of the lower jaw, thus making the person look as if he were very powerful. This disease is called acromegaly (Fig. 12), and besides the changes in the bones, there is frequently considerable metabolic disturbance, causing a mild form of diabetes. When the hypertrophy of the anterior lobe occurs in youth, most of the bones of the body may be affected, thus causing the condition known as giantism. The intermediary lobe is also composed of columns of epithe- lial cells, but there is often some colloidal material between the columns. This colloid differs from that of the thyroid in con- taining no iodine. The posterior lobe is really a downgrowth from the brain, and is composed of neuroglia mixed with some of the epithelial cells of the intermediary lobe. This lobe can be excised without caus- ing any evident change in the animal, but nevertheless it must have some important functions to perform, because extracts of it, when injected intravenously, have very pronounced effects, viz. : (1) a rise in blood pressure; (2) a very striking diuretic action (i. e., causes urine to be excreted) ; (3) secretion of milk. The 132 PHYSIOLOGY FOR DENTAL STUDENTS. active principle of these extracts has not as yet been isolated, although the extracts can be considerably concentrated, thus yielding the trade preparation called pituiirin. It is particularly interesting to note that although the anterior lobe does not yield any active extract, yet its excision is fatal. On the other hand, the posterior lobe can be removed with im- punity, although extracts of it have profound physiological effects when they are injected into normal animals. A. B. Fig. 12. — A, To show the appearance before the onset of acromegalis symp- toms: B, The appearance after seventeen years of the disease. (Aftei Campbell Geddes. ) The Spleen. — Notwithstanding the fact that this is the larg- est of the ductless glands, it is the one whose functions are the least well understood. It can be excised without causing any evident disturbance, and extracts of it when injected intraven- ously do not have any characteristic effects. It becomes very much enlarged in certain diseases, namely : ( 1 ) in leucocythe- mia, a form of anaemia, which is characterized by a great increase in the leucocytes of the blood (see p. 145) ; (2) in typhoid fever (enteric fever) ; (3) in malaria. It becomes contracted after THE THYMUS GLAND. 13,3 taking quinine. Under the microscope it is seen to be composed of a sponge of fibrous tissue, the spaces being filled with blood, which flows freely into them from arterioles in whose walls lymphoid tissue is abundant. Here and there, this lymphoid tissue becomes collected in nodules, which are large enough to be seen by the naked eye and are called Malpighian corpuscles. In the blood of the spleen, partly broken down erythrocytes are often visible. Sometimes, also, cells like those found in red bone marrow and having to do with the manufacture of new red corpuscles make their appearance. Taking all these facts together, it is believed that the spleen has the following functions: (1) manufacture of leucocytes; (2) manufacture of erythrocytes; (3) destruction of erythro- cytes; (4) removal from the blood of certain poisons. The Thymus Gland. — The thymus gland, situated at the root of the neck, is quite large at birth, but its size gradually dimin- ishes as the animal -grows. By the time that puberty is reached, it has almost disappeared. It is composed of peculiarly arranged lymphoid tissue*, having nests of epithelial cells embedded in it. It seems to bear some relationship to the generative glands, for its removal in young male animals hastens the growth of the testes. CHAPTER XIV. ANIMAL HEAT AND FEVER. In considering the problem of animal heat, it is essential to bear clearly in mind the distinction between amount and inten- sity of heat. The former is measured in calories (see p. 84), and the latter in degrees of temperature. To measure the tem- perature of a man a maximal thermometer with the Fahrenheit or Centigrade scale is placed in some protected part of the body, as the mouth, the axilla or the rectum. It is found by such meas- urement that the temperature varies according to the site of ob- servation and the time of day. It varies between 36.0° C. (96.8° F.) and 37.8° C. (100.0° F.) in the rectum ; between 36.3° C. (97.3° F.) and 37.5° C. (99.5° F.) in the axilla; and between 36.° C. (96.8° F.) and 37.25° C. (99.3° F.) in the mouth. These variations indicate that the temperature is higher in the deeper than in the superficial parts of the body ; in other words, that the visceral blood is warmer than that of the surface of the body. The variations of temperature, due to the time of day, are most evident when it is taken in the rectum, and they amount in health to a little over 1° C. or a little below 2° F., the highest tempera- ture occurring about 3 p. m., and the lowest about 3 a. m. This is called the diurnal variation and it may become much greater in febrile diseases. Animals whose temperature behaves as above described are called warm-blooded in contrast to other animals, called cold- blooded, in whom it is only a degree or two above that of the air, with which it runs parallel. Such animals include fishes, amphibians, snakes, etc. Between the cold and the warm-blooded animals is a group in which the animal is warm-blooded in sum- mer and cold-blooded in winter. These are the hib< muling ani- mals, such as the hedgehog, the marmot, the bat, etc. In this connection it is interesting to note that the human infant be- 134 ANIMAL HEAT AND FEVER. 135 haves more or less like a cold-blooded animal for some time im- mediately following birth, during which period it must there- fore be carefully protected from cooling, for, if its temperature be allowed to fall to any considerable extent, it is not likely to survive. It takes several months before the heat regulating mechanism becomes so developed that the infant can withstand any considerable degree of cold. Factors Concerned in Maintaining the Body Temperature.— The body temperature is a balance between heat production and heat loss. Heat is produced by combustion of the organic food- stuffs in the muscles, the amount which each foodstuff thus pro- duces being the same as when it is burned outside the body, except in the case of protein, where allowance must be made for the incomplete combustion of this substance in the animal body (see p. 85). The muscles are therefore the furnaces of the ani- mal body, the fuel being the organic foodstuffs. Heat is lost from the body mainly from the skin, but partly also from the lungs and in excreta. Heat loss from the skin is brought about by the utilization of several physical processes, namely: (1) by conduction along objects which are in contact with the skin or through the air; (2) by convection, that is, by being carried away in currents of air which move about the body ; (3) by radi- ation; (4) by evaporation of sweat. This last is the means by which most heat can be lost, because it takes a large amount of latent heat to vaporize the sweat (see p. 20). Heat loss from the lungs is mainly due to vaporization of water, with which the expired air is saturated. A small amount is also absorbed in warming the air itself. The heat lost in the urine and fasces is almost negligible. The Regulation of the Body Temperature. — It is plain that a very sensitive regulatory mechanism must exist in order that the production and loss of heat may be so adjusted as to keep the body temperature practically constant. When heat loss becomes excessive, then must heat production be increased to maintain the balance, and vice versa when heat loss is slight. The conditions are to a certain extent comparable with those obtaining in a house heated by a furnace and radiators and provided with a 136 PHYSIOLOGY FOR DENTAL STUDENTS. thermo-regulator, which, being activated by the temperature of the rooms, acts on the furnace so as to raise or lower its rate of combustion. In the animal body the thermo-regulator is the nervous sys- tem. Whenever the temperature of the blood changes from the normal, a nerve centre called the thcrmoycnic becomes acted on with the result that it transmits impulses to the muscles, which, by increasing or diminishing their tone (see p. 253), cause a greater or a less heat-production. But the centre does more than the thermo-regulator of a house, for it controls the agencies of heat-loss. Thus, when the blood temperature tends to rise, the thermogenic centre causes more heat to be lost from the skin and lungs in the following ways: (1) It acts on the blood vessels of the skin, causing them to dilate so that more blood is brought to the surface of the body to be cooled off. (2) It excites the sweat glands, so that more heat has to be utilized to evaporate the sweat. (3) -It quickens the respirations, so that more air has to be warmed and saturated with moisture. The degree to which these cooling processes are used varies in different animals. Thus in the dog, since there are no sweat glands over the surface of the body (they are confined to the pads of the paws), increase in the respiration is the chief method of cooling, hence the panting on warm days. In the case of man, civilization has stepped in to assist the reflex control of heat loss, as by the choice of clothing and the artificial heating of rooms. Desirable though this voluntary control of heat-loss from the body may be, there can be little doubt that it is often overdone to the detriment of good health. Living in overheated rooms during the cooler months of the year suppresses to a very low degree the heat loss from the body and thereby lowers the tone and heat production of the muscular system. The food is thereby incompletely metabolized and is stored away as fat ; the superficial capillaries are constricted and the skin becomes bloodless. But it is not looks alone that suffer, but health, as well, for, by having so little to do, the heat-regulat- ing mechanism gets out of gear so that when it is required to act, as when the person goes outside, it may not do so promptly ANIMAL HEAT AND FEVER. 137 enough, with the result that the body temperature falls some- what, and catarrhs, etc., are the result. There can be little doubt that much of the benefit of open-air sleeping is due to the con- stant stimulation of the metabolic processes which it brings about. The importance of the evaporation of sweat in bringing about loss of heat in man partly explains why climate should have so important an influence on his well-being. It is not so much the temperature of the air, as its relative humidity, that is of impor- tance; that is, the degree, expressed in percentage, to which the air is saturated with moisture at the temperature of observation. Thus, a relative humidity of 75 per cent at 15° C. means that the air contains 75 per cent of the total amount of moisture which it would contain if it were saturated with moisture at a tempera- ture of 15° C. A high relative humidity at a high temperature makes it impossible for much sweat to be evaporated, with the result that the body cannot cool properly, and the body tempera- ture is likely to rise unless muscular activity be reduced to a minimum. This explains why it is impossible to do much muscu- lar work in hot humid atmospheres. On the other hand, if the relative humidity is low, the temperature may rise to an extraor- dinary degree (even above that of the body itself) without caus- ing fever, provided always that the body is not so covered with clothing that evaporation of sweat is impossible. At low temperatures of the air, relative humidity has an effect which is exactly opposite to that which it has at high tempera- tures, for now it affects, not the evaporation of sweat, but the heat conductivity of the air itself. Cold moist air conducts away heat' much more rapidly than cold dry air. Hence, a tem- perature many degrees below zero on the dry plains of the West may be much more tolerable to man than a much higher tem- perature along the shores of the Great Lakes. Fever. — Any rise of temperature above the normal limits constitutes fever. When of slight degree, as it is in many semi- acute diseases, its detection demands l'iv<|iient observation, so as to allow for the normal diurnal variation of the body tempera- ture. For example, if the temperature were recorded in the 138 PHYSIOLOGY FOR DENTAL STUDENTS. morning in such a patient, a slight degree of fever might quite easily be missed, because at this time the normal temperature is low. In acute infectious diseases, the afternoon temperature may rise to 106° F. or 41° C., or even above this, without prov- ing fatal. A temperature of 113° F. or 45° C. has been observed, but lasting for only a short time. Fever is always higher in in- fants and young children than in adults. As to the causes of fever, two possibilities exist : either ( 1 ) that heat production has been increased, or (2) that heat loss has been diminished, or, of course, both factors may operate simul- taneously. To go into this unsolved problem is unnecessary here ; suffice it to say that there can be no doubt that disturbance in the thermogenic centre is the underlying cause of fever, and that it is the avenues of heat loss by the skin rather than the sources of heat supply in the muscles that are first of all acted on. The cold sensation down the back, the shivering, the goose skin, are the familiar initial symptoms of fever, and when the fever comes to an end, excessive sweating sets in and this, in part at least, explains the fall in temperature. Increased combustion in the muscles no doubt occurs during the height of the fever and accounts for the great wasting, but that this is not the only cause of the rise in temperature is evidenced by the fact that severe muscular exercise does not in itself cause fever, even although there may be much more combustion going on in the body (see p. 88). Certain drugs called antipyretics lower the temperature in fever. The most important of these are acetanilide, salicylates (aspirin), phenacetin, and quinine. The first three mentioned act on the thermogenic centre, whereas quinine seems to act directly on the combustion processes in the muscles. The body temperature is raised by cocaine and by the toxic products of bacterial growth. Even cultures which have been attenuated by keeping them for some time at high temperatures have this effect, and it is believed by many that fever is of the nature of a protective mechanism to destroy or attenuate the invading bacteria. There is bacteriological as well as clinical support for this view, thus, certain pathogenic organisms (such as the strep- ANIMAL HEAT AND FEVER. 139 tococcus of erysipelas) cannot live at a temperature above 41° C., and cholera patients are much more likely to survive if the dis- ease be accompanied by a moderate degree of fever. Heat stroke, or sun stroke, is due to an increase in body tem- perature that is above the limits of safety. "When sweating and the other processes by which heat is lost from the body are act- ing properly it is remarkable how high an air temperature may be borne without danger; for example, in dry air a man can sit for some minutes in an oven at 100° C. while his dinner cooks beside him (Leonard Hill). But if anything should interfere with heat loss, or if heat production be excessive, as during mus- cular exercise, there is always danger of heat stroke. Free move- ment of the air is probably the most important way for safe- guarding against deficient heat loss. It is almost certainly on account of the absence of such air movement, coupled with a high relative humidity, that discomfort is experienced in hot, stuffy atmospheres, for the faulty heat loss causes a slight rise in body temperature. This slight degree of hyperpyraxia low- ers the resistance of the organism to infection. CHAPTER XV. THE BLOOD. Introduction. — The individual cells forming the most simple types of life are nourished by substanees which they obtain directly from the water in which the animal lives. In exchange for this food, they excrete into the water the waste materials of their metabolism. As the organism becomes more and more complex this direct interchange of materials becomes impossible, and the blood and lymph assume the task of delivering food to the tissues and of removing the waste materials. To accomplish this, these fluids come into close relation with the absorbing, elimi- nating, and general tissue elements of the body, the lymph being in immediate contact with the cells and the blood moving quickly from place to place. Therefore all the elements found in the tissues and all the waste materials produced by the body ;nv present at some time or another in the blood. The blood may in- deed be compared to the wholesaler of commerce, who handles all the materials for the support of life, and the lymph to the retailer, who distributes to the tissue cells the materials which they need. In short, it may be said that the blood replenishes the lymph for the losses which it incurs in supplying the tissues. Physical Properties. — Ordinary mammalian blood is an opaque, somewhat viscid fluid, varying in color from a bright red in arterial blood to a dark red in venous blood. Contact witli air changes venous blood to arterial blood. Microscopical exami- nation showrs that the blood is not perfectly homogenous, but consists of a clear fluid in which cells called corpuscles are sus- pended. The Corpuscles. There are three varieties of these: the red corptischs (to which the color of blood is due), the wliite corpuscles and the Mood platelets. 140 THE BLOOD CORPUSCLES. 141 Erythrocytes. — :The red corpuscles, or eryfkrocytes, as they are called, are by far the most numerous, there being five mil- lion of them in a cubic millimetre of normal blood. Examined under the microscope, they are seen to be flattened, bi-concave, non-nucleated discs in man; but in the embryo, as well as in birds and reptiles, they have a nucleus. Each corpuscle consists of an envelope and a framework of protein and lipoid material containing a substance known as haemoglobin. HAEMOGLOBIN is a very complex body, belonging to the general class of conjugated proteins (see p. 21). Haemoglobin has the ability to unite with large amounts of oxygen, thus enabling the blood to carry the oxygen gathered in the lungs, to the dis- tant tissues. It consists of a combination of a simple protein, globin, and a pigment, haematin. Hcematin contains iron, which is responsible for the ability of oxygen to unite with the haemo- globin molecule. The combination of haemoglobin with oxygen is not very stable, and can be readily broken with the liberation of oxygen. It is for this reason that this molecule is adapted to carry oxygen to the tissues. The quantity of haemoglobin held by the corpuscle may vary and in some diseases, as in chloro- anaemia, for instance, it may be greatly diminished, so much so that the tissues may be unable to obtain the proper amount of oxygen. The amount of haemoglobin actually present in a sample of blood may be estimated by the intensity of the red color it gives to the blood. To estimate this intensity a drop of blood is received on blotting paper, the stain being then compared either with that produced by normal blood in various dilutions on the same paper, or with a standardized chart. From the con- centration of normal blood whose stain most nearly matches that of the unknown sample, we can determine the percentage of haemoglobin in the latter, or we can read this directly from the chart. ENUMERATION OF THE BLOOD CORPUSCLES. — The number of red or white cells present in a cubic millimetre of blood may be esti- mated by the use of a haemacytometer or blood-counter. This consists of two mixing capillary tubes, in one of which the blood is diluted one hundred times with saline solution, and in the 142 PHYSIOLOGY FOR DENTAL STUDENTS. other, ten times with 0.337% acetic acid. The former dilution is for counting red, and the latter, for counting white corpuscles. A drop of the diluted blood is then placed on a special glass slide which contains a counting chamber of such a depth that when a cover slip is put over a drop of fluid in the chamber, a column of fluid one-tenth of a millimetre deep is obtained (Fig. 13). The chamber is graduated with cross lines, so that each square represents a known fraction of a millimetre. The average number of corpuscles found in a number of squares, by actual count with a microscope, is multiplied by the factors of dilution employed, the product being the number of cells in a cubic milli- - ^ o - 0.100mm. 9 C. Zeiss Jena. v 2 ^J w- -j Fig. 13. — Thoma-Zeiss Haemocytometer ; M, mouthpiece of tube (G), by which blood is sucked into S; B, bead for mixing; a, view of slide from above ; b, in section ; c, squares in middle of B, as seen under microscope. metre of blood. The erythrocytes, which in health number about five million in a cubic millimetre, may decrease to less than a million in disease, such as pernicious anosmia, or after haemor- rhage. On the other hand, they may number six or seven million in people who live at high altitudes. The oxygen-carrying power of the blood is proportional to the percentage of haemoglobin, so that by estimating this and the number of corpuscles, a fair idea of the condition of the blood is obtained. THE ORIGIN OF ERYTHROCYTES. — It is interesting to inquire into the source of the blood cells, but although this has been the subject of many researches, it is by no means definitely settled THE BLOOD CORPUSCLES. 143 just what the process is or in what part of the body the cells origi- nate. Nor is it definitely known just where the worn out cells are dealt with. In the embryo certain cells are set apart to develop the vascular system. Some of these form the blood ves- sels and some the red corpuscles, but later in foetal life, the latter come from cells in the spleen, liver and red bone-marrow. At first the red corpuscles are nucleated, but towards the end of foetal life they begin to lose their nuclei, so that at birth there are very few nucleated red corpuscles remaining in the blood. After birth, the red corpuscles are formed in the red bone-mar- row of the flat bones. In these places special nucleated cells are found, which are called erythroblasts, and from these the ery- throcytes develop. After severe haemorrhage nucleated red cells may appear in the blood for a short time; the same is true in some forms of anaemia in which there occurs a Very rapid destruc- tion accompanied with a very rapid formation of red cells. Since the life of a erythrocyte is necessarily limited, provision must be made for the destruction and elimination of the sub- stances of which they are composed. In the pigments of the bile we find the remains of part of the haemoglobin. The bile is secreted by the liver into the intestine (see p. 71), and in case the free outflow of bile is interfered with, the blood absorbs the pigment and the individual becoir.es yellow or is said to be jaun- diced. The bile pigments do not, however, contain all the ele- ments of the haemoglobin, for the iron is not excreted by the bile. It is, on the contrary, stored up by the liver to be used again in the formation of fresh haemoglobin. Some have thought that the function of the spleen is to destroy the red blood cells, the waste products of which are sent to the liver through the splenic vein. The evidence for this is the presence of pigment and iron- containing substances in the blood of this vein. Iron is an essential constituent in the haemoglobin molecule, and it is necessary that some be constantly supplied to the body in the food. But this amount need not be large, since the iron- containing substance can be used time and again in the manu- facture of new haemoglobin, and once the body has the requisite amount, little more need be added (see p. 120). Indeed, it is 144 PHYSIOLOGY FOR DKNTAL STUDENTS. questionable if the inorganic forms of iron can be utilized by the body, the iron in our blood being probably derived from a con- jugated protein known as hsematogen, found in small quantities in the food. The White Blood Cells. — In normal human blood there are about ten thousand cells in a cubic millimetre of blood, or about one to every five hundred red cells. In many ways they resemble the unicellular amoeba, for like it they have the power of making independent movement by extending tiny processes called psi-u- dopodia in one direction and by retracting them in another. In virtue of this peculiar movement they are able to flow, as it were, between the endothelial cells of the capillaries and find their way into the tissue spaces. There are a number of forms of white cells differing from each other in size, in character of their nucleus, and in the granules they contain. In general, they are classified in two main groups on morphological grounds, viz., leucocytes and lymphocytes, The Leucocytes are the most numerous and compose about (>."> per cent of the total white cells. They are characterized by a lobed nucleus, the parts of which are connected by strands of chromatin material. To this class belong several sub-groups. The most important of these are the cells known as polymorpho- nuclear leucocytes. They comprise about 96 per cent of the leucocytes. Another type are known as eosinophyles, since they have granules with a marked affinity for acid stains. The Lymphocytes. — The second variety are so-called, since they are supposed to be formed in the lymph glands of the body. They possess a single large round nucleus surrounded by a clear layer of protoplasm. There are two sub-groups in this class; the large mononuclcar lymphocytes, which contain a rather abun- dant cytoplasm about the nucleus, and the small motion n< •!(•«>• lymphocytes, in which the amount of cytoplasm is very small. The former comprise about 4 per cent, and the latter about 30 per cent, of the white cells. ESTIMATION OF THE WHITE CELLS. — The number of white cells found in the blood is estimated by the same principle that is em- ployed in the counting of the red cells (see p. 142). In certain THE BLOOD PLASMA. 145 diseases their number may vary greatly. The number is also in- creased after meals. A marked increase over normal is known as a leucocytosis. THE FUNCTION OP THE LEUCOCYTES. — In acute infections, as in appendicitis, pneumonia, and localized or general septic con- ditions in which pus is formed, there is usually a great increase in the number of the polymorphonuclear leucocytes. In more chronic infections, as in tuberculosis, the lymphocytes are found in greater number. In the parasitic diseases of animal origin, as tapeworm and hookworm, in some skin diseases, and in scarlet fever, the eosinophile leucocytes are more abundant. In the disease leueocythsemia the lymphocytes may be present in such great numbers that they impede the movement of blood by in- creasing its viscosity or thickness. The above observations sug- gest that leucocytes play an important role in the protection of the body from infective processes. This function will be dis- cussed later. Another important function they may have is the preparation of the peculiar proteins which are found in the blood plasma. THE BLOOD PLATELETS. — These bodies are smaller than the erythrocytes, and number about 300,000 in a cubic millimetre of blood. When blood is shed they disintegrate very rapidly, and set free a substance which plays a part in the coagulation of the blood. Little is known concerning their chemical constitution or their physiological function. The Blood Plasma. The blood plasma is a very complex fluid containing all the va- ried substances associated with the function of the blood. Water composes 90 per cent of the plasma. The plasma proteins consti- tute the largest solid constituent (7 per cent), and include_S£OUiL _jy]jjbn1inj serum albumjn, and fibrinogen, There are a number of bodies which contain nitrogen which are not proteins. These may be grouped into two classes, the first, represented by the amino acids and other nitrogenous bodies derived from the pro- tein of the food and from which the tissue cells are built, and the second group, represented by waste materials given off by the 146 PHYSIOLOGY FOR DENTAL STUDENTS. tissue cells. These include substances such as urea, uric acid, creatinin, and ammonia. The non-nitrogenous organic bodies are dextrose, of which 0.1 per cent is present in normal plasma, and a small quantity of fat, About 1 per cent or inorganic salts are found, the chief of which is sodium chloride, which constitutes 60 per cent of the ash. Sodium carbonate is found in a little less degree. Besides these two we find small amounts of potassium, sodium and calcium chlorides and phosphates. An important group of substances known as hormones are excreted into the plasma by some of the glands of the body, and affect the meta- bolism of the tissues in a specific manner., Another group of bodies, the antitoxins, complements, and opsonins (see p. 124), are found in the blood. These are concerned in the protection of the body against infective organisms. CHAPTER XVI. THE BLOOD (Cont'd). The Defensive Mechanisms of the Blood. The Coagulation of the Blood. — Whenever a blood vessel is slightly cut, the blood, which at first comes very freely, soon ceases to flow because of the formation of a plug or clot of blood at the site of the injury. The process by which the blood spon- taneously forms the plug in the injured vessel is known as coagu- lation, or clot formation. It protects the body from fatal hem- orrhage in case of an ordinary wound. A clot is a semi-solid mass, which on microscopical examination is seen to consist of a meshwork of fibrils holding the blood corpuscles in their inter- spaces. If blood is collected in a basin and whipped with some twigs while it is clotting, the fibrils will collect on the twigs in stringy masses, and the blood will remain fluid. The stringy material is called fibrin. Obviously, fibrin cannot exist in the blood stream, else the blood would form a clot within the blood vessels; it is formed only when occasion demands, such as an in- jury to the blood vessel. There are a number of experiments which explain the process of coagulation. Thus, if blood is prevented from clotting by cooling it to 0.° centigrade, and is then mixed with a saturated solution of salt, a white precipitate forms, which may be filtered off and dissolved in 0.1 per cent salt water. This solution may be made to clot by the addition of a very little blood from which the fibrin has been removed. In other words, we have prepared a substance which under proper conditions forms the fibrin of the clot. This sub- stance is called fibrinogen, since it is the precurser of fibrin. Again, if blood be treated with sodium oxalate, it will not clot unless calcium salts be added in amount sufficient to precipitate 147 148 PHYSIOLOGY FOR DENTAL STUDENTS. completely all the oxalate and leave some in excess. In other words, the presence of a soluble calcium salt is necessary in order to have the blood clot. Defibrinated blood will, however, cause the clotting of pure fibrinogen solutions even though all the cal- cium be removed from both solutions. In order to explain the above facts, we must assume that three substances are present in solution in the blood: fihrinngfin, cal- _cium salts, and another substance, which has been called throrn-^ JwQcn. Under the proper conditions, thrombogen will combine with calcium salts to form thrombin, which in turn unites with fibrinogen to form fibrin, which is the substance forming the framework of the clot. The reason why the blood does not clot within the blood ves- sels is not definitely known. It is probable that the blood con- tains a substance which prevents the combination of thrombogen with calcium salts, and which we call anti-thrombin. Whenever a blood vessel is injured, the tissues and the blood platelets liber- ate a lipoid body called ' k< plmlin, which unites with the anti thrombin and thus allows the formation of thrombin to take place at the site of the wound. The whole process may be graphically shown in the following schema: Anti-thrombin -f- kephalin = inactive anti-thrombin. Thrombogen -(- calcium salts = thrombin. Thrombin -(- fibrinogen = fibrin. Fibrin -f- corpuscles = clot. Antibodies in the Blood. — The coagulation of the blood is only one of the measures which are developed in the blood for the protection of the animal. No less important in this regard are the destruction and removal of toxic and injurious substances from the body. All the infectious diseases are caused by the agency of micro- organisms. The greater number of these are microscopic plants known as bacteria and fungi ; some, however, are unicellular ani- mals known as protozoa. It is especially against the bacteria that a method of defense exists in the body ; the protozoal diseases, on THE DEFENSIVE MECHANISMS OF THE BLOOD. 149 the other hand — such as syphilis, malaria, sleeping sickness and those caused by amoeba in the mouth and alimentary tract — find relatively little resistance offered to the ingrowth in the body, and their destruction therefore must be for the most part brought about by drugs. The Process of Inflammation, which in a general way is known by the common symptoms of fever, pain, swelling and redness, is a sign of an increased activity on the part of the tis- sues in an effort to destroy some foreign body which is poisonous to the cells. Microscopical examination of a section of inflamed tissue will show that the blood vessels are dilated, and that the tissue spaces are infiltrated with leucocytes. It suggests that the blood elements must have a very important part in the process. The study of this function of the body is one of the most inter- esting chapters of physiological science, and includes the ques- tions of immunity from disease and the cure of infectious pro- cesses. Many pathogenic organisms can be cultivated on artificial media and the products of their metabolism can then be studied. It has been found that they may be divided into two groups ; the one group producing the soluble poisons, or true toxins, which are excreted from the cell ; and the other group producing toxic substances, the endo-toxins, which are not excreted from the cell. We will first take up the manner in which the body deals with the toxins. Toxins. — If a culture of diphtheria or tetanus bacilli be fil- tered through a porcelain filter, the bodies of the bacilli are re- moved and the filtrate contains the soluble toxic principles which the bacilli have produced and excreted into the nutrient fluid. Injections of a small amount of this filtrate into an animal will produce the same symptoms as are produced when a pure culture of the bacilli is injected. Each bacillus produces a specific kind of toxin. Diphtheria toxin acts primarily on the vascular sys- tem; tetanus toxin, on the central nervous system. The chemical nature of the toxin molecule is unknown, since it has been impos- sible to separate it in pure form. It is probably closely related to the protein molecule, and on the other hand resembles the 150 PHYSIOLOGY FOR DENTAL. STUDENTS. ferments in many of its actions (see p. 34). A peculiarity in the action of the toxins is that a relatively long period elapses between the injection of the toxin and the reaction of the body, whereas in the case of the alkaloids or vegetable poisons, the re- action appears very quickly. Antitoxin. — In spite of the very poisonous character of the toxin molecule, the body is provided with a means of defense against it, and is able to make itself still further immune to the action of the toxin. Thus, if somewhat less than the fatal dose of diphtheria or tetanus toxin be injected into the body, certain symptoms will follow, and the animal will react to the toxin in such a way that a subsequent injection can be made larger with- out proving fatal. If successively increasing doses are given, the animal after some weeks will be able to withstand very large doses of the toxin. In other words, the body develops an im- munity towards the toxic agent; it produces an antibody which neutralizes the poison of the toxin. To this body we give the name of antitoxin. Since these antibodies are found in solution in the blood, it is possible to withdraw the blood from such an immune animal, and inject it into a non-immune animal, thus rendering the latter immune to the toxin. It is this principle that is used in the preparation of diphtheria and tetanus anti- toxins. The exact nature of the combination of the toxin and the antitoxin cannot be learned from chemical studies, but Ehrlich has given to the phenomenon a biological explanation based on the various known reactions of the bodies. Ehrlich 's Side Chain Theory of Immunity. — Briefly summar- ized Ehrlich 's theory is as follows: Each toxin molecule is made up of a central nucleus of chemical radicles similar to those found in organic compounds. To the main body of this mole- cule are attached at least two other radicles, or side chains. One of these has a great affinity for certain chemical constituents of the tissues of susceptible animals, and unites the toxin molecule to the tissue cell. This chain is known as the haptophon f tho letters indicated. CHAPTER XXIV. THE FLUID EXCRETIONS. The Excretion of Urine. The Composition of the Urine. — The waste substance result- ing from the processes of metabolism in the tissues are eliminated from the body in a gaseous, fluid, or solid state. With the excep- tion of the carbon dioxide and water of the expired air, and cer- tain substances which are excreted into the intestines or appear in the secretions of the skin glands, the metabolic products are eliminated in the urine. The composition of the urine is therefore rather complex and varies greatly with the nature of the food and the amount of water taken. By careful analysis of the urine from a number of individuals on ordinary diet, the average amount of the various constituents in what may be considered a normal urine can be estimated. Fresh human urine is a clear yellow fluid, a little heavier than water, having a specific gravity of 1.016 to 1.02. If tested with litmus paper it usually shows an acid reaction, which is mainly due to the presence of acid salts, such as sodium dihy- drogen phosphates, but partly also to acid substances derived from proteins. Herbivorous animals secrete an alkaline urine, which is no doubt caused by the presence of the large amount of alkaline earths and the relatively small amount of protein mat- ter in their diet. The human urine becomes alkaline in reaction when vegetables are the main ingredients of the diet. The character of most of the urinary constituents and the man- ner by which they are derived from the foodstuffs have been de- scribed in the chapter on metabolism, and in the following ac- count only a brief review of their physical and chemical nature is necessary. THE ORGANIC SUBSTANCES OP THE URINE. — These comprise a number of nitrogenous compounds. The following figures, ob- 229 230 PHYSIOLOGY FOB DENTAL STUDENTS. tained from the results of the analysis of a number. of normal average urines, show how the nitrogen is distributed among these compounds. Urea 85 to 90'/ Ammonia 2 to 4% Creatinin 3% Uric acid 1 to 2% Unclassified nitrogen 5 to 6% Urea. — From the above figures it is seen that the greater part of the nitrogen eliminated by man appears as urea. The relative amount of urea eliminated depends very largely on the diet, be- ing 90 per cent or more of the total nitrogen excretion on a full protein diet, and 60 per cent or less during starvation. The total amount excreted is about 30 grams per 100 grams of protein in the diet7. Chemically urea has the following formula: NH., / OC NH2 If prepared pure it forms long colorless needles or four-sided prisms. It is very soluble in water. Hot alkalies, such as sodium hydoxide, decompose it into ammonia and carbon dioxide. The same reaction occurs in case of bacterial decomposition by the micrococcus urea, and accounts for the ammonical odor of urine after standing in the air. The significance of urea in regard to protein metabolism and the method of its formation are dis- cussed on page 108. Ammonia. — This, combined with chlorine or other acid radi- cles, is normally found in small amounts in the urine. It is one of the important agencies in maintaining the neutrality of the tissues, since with acids it forms ammonia salts, which are neu- tral in reaction and which are eliminated in the urine. Creatinin. — The amount of this substance found in the urine THE CHEMISTRY OF URINE. 231 is very constant from day to day, and is independent of the diet. It is largely a product of the metabolism of the body tissues. Uric Acid. — Uric acid is a purine body and its relationship to the other purines, and its mode of formation and significance are fully discussed in the chapter on metabolism (p. 110). It is relatively insoluble in water, and when allowed to crystalize it forms small' rhombic crystals. It can unite with an alkali, such as sodium hydroxide, to form two salts : a neutral or diurate of sodium (C5H,N403Na2) and the biurate or acid urate of sodium (C5H2N403HNa). The biurates are neutral in reaction and con- stitute the urates normally found in the blood and urine. They exist in two isomeric forms .(a and the &). The & is more solu- ble than the a form. It may be that the deposition of urate tar- tar on the teeth, and the deposits of urates in the joints of a pa- tient suffering with gout, are due to the change of the b form into the less soluble a type. There are a number of other nitrogenous bodies in the urine which are included in the item of unclassified nitrogen in the above analysis. The most important of these is urinary indican, which is derived from the indol produced in the intestines by the action of bacteria on the amino acid trytophane. The yellow color of the urine is produced by a pigment called urochrome, which is believed to be derived from the pigments in the blood. THE INORGANIC CONSTITUENTS OP THE URINE. — The urinary salts are chiefly the chlorides, sulphates and phosphates of so- dium, potassium, calcium and magnesium. The potassium and sodium salts are found in greatest abundance, since they form the main inorganic constituent of the food, and moreover the greater portion of the salts of the heavier metals, as calcium, iron, bismuth, mercury, etc., is excreted by the intestines. There is very little retention of salts by the body except during the for- nation of bone, so that the amount of the inorganic constituents of urine varies from day to day with the diet. The chlorides are formed for the most part from the inorganic chlorides of the food; the phosphates and the sulphates are derived from the sul- phur and phosphorus of the nucleo-protein molecules. If the urine is neutral or alkaline in reaction, there is apt to be a dc- 232 PHYSIOLOGY FOR DENTAL STUDENTS. posit of calcium or magnesium phosphate. This will dissolve when the urine is rendered faintly acid. ABNORMAL CONSTITUENTS OP THE URINE. — Many of tin- sub- stances found in the blood occur in minute traces in the urine. When any of these bodies are increased to an unusual amount in the urine, they become what we may term pathological con- stituents. The bodies most commonly affected are the proteins and sugars. The finding of a protein such as albumin, in more than the faintest trace, is an indication of nephritis or Bright 's disease. The presence of albumin may be detected by heating in a test tube a slightly acidulated sample of urine. Normal urine contains the faintest trace of the blood sugar dextrose, but in abnormal conditions, as in the disease dialxfis or after a meal rich in sugars, a large amount of dextrose ap- pears in the urine as a result of an increase in the sugar of the blood. The condition probably represents the inability of the tissues to make use of their carbohydrate food in the proper man- ner, and the kidney therefore excretes the sugar as if it were a waste material. The Organs of Excretion, The Kidneys. Projecting from the posterior wall of the abdominal cavity at the level of the lower ribs and on each side of the vertebral col- umn are the kidneys, the organs of urine excretion. Each kidney is of the nature of a tubular gland of a very complex structure, anatomically adapted to bring a large amount of blood at a high pressure in close relation with the excreting epithelial cells which line the walls of the gland tubules. The tubules empty into a pouch-shaped sac on the inner edge of the kidney, the pelvis of the kidney, and this is connected with the urinary bladder by means of a small tube, the ureter. A brief review of the essential parts of the uriniferous tubule and the organs of micturition is necessary in order to understand the mechanism of urine excretion, and the student is advised to consult his textbook of anatomy and histology for a more com- prehensive description than is here given. The uriniferous tu- bules may be divided into the excretory portion and the collect- ing portion. The tubules arise in the outer part of the kidney. Pig. 37. — Diagram of the uriniferous tubules (black), the arteries (red) and the veins (blue) of the kidney. THE EXCRETION OF URINE. 233 in the region called the cortex, as a body called the Malpighian corpuscle. This corpuscle consists of the dilated end of a tubule which is invaginated to form a cup-shaped vessel, within the cup of which lies a tuft of capillaries. The capillaries compose the structure known as the glomerulus, and the tubular part, the capsule of Bowman. From Bowman 's capsule a short neck leads into what is known as the convoluted tubule, which is a very tortuous vessel lined with very large epithelial cells. This structure lies in the cortex of the kidney and is nourished by the blood which has already been through the glomerular capillaries. A loop of the tubule leads down into the center or medullary portion of the kidney and back again to the cortex, where the cortex again becomes very tortuous. This finally empties, in company with many other similar vessels, into a common collecting tubule, which leads to the pelvis of the kidney. THE BLOOD SUPPLY OF THE KIDNEY is very large compared with that of the other organs of the same size. The renal artories come from the aorta and distribute their blood directly to the glomeruli and the inner medullary portions of the kidney. The vessels of the glomerulus are collected into an afferent vein, which again breaks up into capillaries to supply the remaining struc- tures of the cortical portions of the kidney (Fig. 37). THE NERVES OF THE KIDNEY. — The kidney is very richly sup- plied with vasomotor nerve fibers, which are carried to it in the splanchnic nerves. Whether there are nerve fibers in either the vagus or splanchnic nerves which have a secretory influence on the kidney cells, is at present an unsettled question. The Nature of Urine Excretion. — In spite of the many at- tempts to explain the nature of urine excretion, there remain many steps in the process which are not fully understood. The constituents of the urine are formed by other organs than the kidney, and are present in the blood plasma. Thq function of the kidney is to remove these substances from the blood. Many bodies are present in the blood plasma which are not found in the urine, and again some of the urinary constituents are found in far greater concentration in the urine than in the blood plasma. 234 PHYSIOLOGY FOB DENTAL STUDENTS. To explain these facts, Ludwig, a famous physiologist of the nineteenth century, formulated what is known as the mechanical theory of urine excretion. Impressed by the peculiar relation- ship of Bowman 's capsule and the glomerular capillaries, he con- cluded that the Malpighian corpuscle is a filtering apparatus which separates, in dilute solution, a portion of all the diffusible substances of the blood. The absence of such diffusible sub- stances as sugar in normal urine and its presence in the blood in a relatively large amount, he believed to be due to the ability of the epithelium of the tubules to reabsorb these substances from the dilute urine. Likewise, the high concentration of salts and nitrogenous bodies, such as urea, he explained by reabsorption of water through the tubules into the blood. In support of this theory Ludwig demonstrated that the urine excretion varied directly with the blood flow and the blood pressure of the kid- ney. In other words, the greater the supply of blood and the greater its pressure, the more rapidly will the watery solution of the urine be filtered from the blood. He was not able, how- ever to bring any satisfactory proof of the reabsorption of water or other substances by the epithelium of the urinary tubules. Indeed, most experiments show that this does not occur. It is impossible to explain all the facts of urinary excretion by simple physical laws. For example, urea and dextrose are both found in the blood and both obey the same physico-chemical laws; nevertheless the one is excreted in the urine and the other is retained in the blood. Furthermore, when certain pigments are injected into the blood, they are excreted by the kidney cells, but do not appear in those of other parts of the body. That an increase in the pressure of blood in the renal vessels has a very marked accelerating effect on the excretion of urine, is not necessarily evidence that the increased blood supply is the cause of the excretion. That other factors are concerned is demon- strated by the action of drugs which cause an increase in renal ex- cretion. For example, digitalis, a drug stimulating the circulatory apparatus, causes a marked diuresis in cases of a weak heart where the pressure has been totally inadequate to maintain a urine excretion, but has little or no action on the normal kidney. THE EXCRETION OF URINE. 235 On the other hand, sodium sulphate injected into the blood causes a diuresis without marked change in rate of blood flow or blood pressure by direct stimulation of the renal epithelium. In almost every case, moreover, an increase in the excretion of urine is followed by an increase in the amount of oxygen used up by the kidney. It is a general law that every increase in cell activity is accompanied by an increase in the amount of oxygen used by the organ, and the increased blood flow accompanying most forms of diuresis is readily explained on the basis of the physiological need of the tissue for water and oxygen. If physi- cal laws were sufficient to explain all the phenomena of excre- tion, there would be no need for oxygen in increased amounts during periods of increased urine formation. A conception of the actual amount of work which the cells must do to excrete the urine may be obtained by comparing the osmotic pressure of the urine with that of the blood. The osmotic pressure of the blood is only half that of the urine, and for each one thousand cubic centimetres excreted, it is sufficient to call for the expenditure, on the part of the renal cells, of a force capable of lifting a pound through one thousand feet. We may conclude that the nature of the excretory mechanism cannot be explained by the physico-chemical laws as we now know them, i. e., the phenomena of osmosis, filtration, absorption, etc., but rather that it must be due to a vital action on the part of the renal cells. It is this vital function of the cells which enables them to remove one substance from the blood and to leave another which is identically the same so far as physico-chemical properties are concerned. Micturition. — The urine discharged from the collecting tubules of the kidney into the pelvis, is carried to the urinary bladder through the ureters (Fig. 38). The muscular coats of the ureter have a movement similar to that of the digestive canal and by peristaltic waves force the urine down through the ureter into the bladder. The urine thus collected by the bladder is retained for a time and is at intervals ejected through the urethra by the act of micturition. This consists of strong contraction of the bladder walls, together with the contraction of the diaphrag- 236 PHYSIOLOGY FOR DENTAL STUDENTS. matic and abdominal muscles, the effect of which is to reduce the size of the bladder cavity and to expel the urine with pressure, through the urethra. The act is under nervous control, the motor nerves being de- rived from nerve cells found in the lumbar region of the cord. The stimuli here produced co-ordinate the muscular movements of the act. The afferent or sensory stimuli which initiate the act are excited by the distention of the bladder, or by the pass- age of a few drops of urine into the first portion of the urethra. These stimuli pass to the center in the cord and are returned to Vena cava Aorbe> U reWhro. Fig. 38. — Diagram of urinary system. the muscles of the bladder also causing the sphincter, which closes the bladder, to be relaxed. In the voluntary act the motor nerves are stimulated by impulses from the higher centers. The Function of the Skin. The skin serves a double function, that of protecting the body from the outside environment, and that of excreting essential THE FUNCTIONS OP THE SKIN. 237 fluids from its glands. Contrary to general belief, the glands of the skin do not excrete the waste substances of the body, or at least do so only to a very limited degree. Their functions are : to regulate the internal heat of the body (sweat glands) ; to lubri- cate its surface and hairs (sebaceous glands) ; and to provide the best form of nourishment for the newborn animal (mammary glands). The Sweat Glands. — These are simple coiled tubular struct- ures, found practically everywhere in the cutaneous tissue of the body, being especially numerous in certain parts, as in the palms of the hands and the soles of the feet. The excreting cells line the lower portions of the tubules, and are composed of granular, columnar epithelium. The glands are richly supplied with nerve fibers. The amount of sweat given off in a day varies greatly, since it is influenced by many things, as heat, moisture, exercise, cloth- ing, etc. (see p. 135). The perspiration of which we are uncon- scious amounts to a considerable number of grams (700 to 900 grams) in a day. Although it is very difficult to obtain pure sweat unmixed with the secretions of the other glands of the skin, we know that it consists for the most part of water, having a specific gravity of about 1.004. The salty taste is due to inor- ganic salts and to the impurities which the sweat dissolves on the surface of the skin. There is only a trace of urea and related substances, and probably the sweat glands never aid the kidneys in the excretion of these bodies. The most important function of the sweat glands is to control the temperature of the body by regulating the rate of its heat loss. Dry air is a poor conductor of heat, and to vaporize water requires a large amount of heat. As the water of the sweat is evaporated, the body loses heat rapidly. This principle is practi- cally applied by the housewives of tropical countries. The water is placed in porous pots and the rapid evaporation on the out- side of the pot cools the water within. The secretion of sweat, like the secretion of saliva, is under the control of the central nervous system, as can be demonstrated by electrically exciting the nerves supplying the paw of a cat or 238 PHYSIOLOGY FOR DENTAL STUDENTS. dog. Following such stimulation drops of sweat are found on the paw. The secretion is not due to an increased blood flow, as can be shown by stimulating the nerves in a limb severed from its blood supply, in which case a few drops of sweat will still appear. A center in the brain and subsidiary centers in the spinal cord have been found which, when stimulated, produce a secretion of sweat. Some drugs have the peculiar action of exciting the secretion of sweat, either reflexly through the nerve center or by stimula- tion of the nerve endings about the cells of the glands. To the former class belong such drugs as strychnine and picrotoxin, and to the latter, pilocarpin. Atropin, on the other hand, inhibits the secretion by paralyzing the secretory nerve mechanism. An increase in the external temperature will cause a secretion of sweat only when the sensory and motor nerves of the part are both functional. To stimulate the sweat nerves, heat therefore must act reflexly through the sensory nerves and the centers of the brain or spinal cord. THE SEBACEOUS GLANDS. — Besides the sweat glands there are numerous other glands in the skin. These are associated with the hairs, and are called sebaceous glands. They secrete an oily semiliquid material which affords protection to the hair and the skin. Its oily nature prevents the hair from becoming too brittle, and protects the skin from moisture. THE SECRETION OF MILK. — The mammary glands are modified sebaceous glands which secrete a nutrient fluid, milk. The glands are much better developed in the female than in the male, and are excited to physiological activity ait the birth of the child. Human milk is a white or yellowish fluid, without odor and with a peculiar sweet taste. It contains protein substances called caseinogen, lact-albumin, and lact-globulin ; also a sugar called lactose or milk sugar, and fats and inorganic matter, as the chlo- rides of sodium, potassium and calcium. Human milk is by far the best food for the infant, and should be replaced by other food only when absolutely necessary. CHAPTER XXV. THE NERVOUS SYSTEM. The General Functions and Structure of the Nervous System. —When a unicellular organism, such as the amoeba, is stimulated it responds by a movement because its protoplasm possesses among its other properties those of excitability, conductivity and contractility. In the case of multicellular organisms, some cells are set aside for the assimilation of food, others for movement, others to receive stimuli from the outside, others to compose tougher protective tissues on the surface, and still others, in many animals, to compose definite organs of offense. This loca- tion of specific functions in certain group of cells makes it neces- sary, for the welfare of the organism as a whole, that some means of communication be provided between the different parts of the animal, for otherwise the cells which are occupied, say, in ab- sorbing food, would be unable to move away when some destruc- tive agency approached them, and indeed the moving (muscle) cells could never know when they ought to become active. Tn some of the lower organisms these messages are carried by chemi- cal substances present in the fluids that bathe the cells. These belong to the group of hormones which we have already studied in connection with the ductless glands (see p. 124). The re- sponses mediated in this way are, however, too slow for the quick adaptation which it is necessary that the organism should un- dergo in its battle for life. If it had to depend on such a mech- anism alone, the organism would already be within the clutches of its enemy before it could make any attempt to defend itself. Some more sensitive mechanism, both for receiving and for transmitting impulses throughout the organism, becomes nec- essary. This is furnished by the nervous system, which, in its simpler form, consists of a cell on the surface of the animal so specialized that it responds to changes in the environment. This 239 240 1'IIYSIOLOGY FOR DENTAL STUDKNTS. receptor cell, as it is called, is prolonged inside the animal as a fiber, the nerve fiber, which passes to effector cells specialized either as muscle fibers or gland cells. When a stimulus acts on the receptor cell it therefore sets up a nerve impulse which causes effector cells to become active, so that the animal either moYes away or prepares to defend itself by secreting some poisonous substance or making some defensive movement. There are, how- ever, very few, even of the lowliest organisms, which have so simple a nervous system as this, for the nerve fibers from differ- ent receptors usually join together to form a nerve plexus and they do not run directly to the effector cell, but to another cell. Fig. 39. — Schema of simple reflex arc ; r, receptor in an epithelial mem- brane ; a, afferent fiber ; s, synapsis ; c, nerve cell of center ; e, efferent fiber ; in, effector organ. the central nerve cell, which is specialized as a junctional or dis- tributing center, and which then transmits the impulse by a fiber of its own to the proper effector organs. Thus we have the essential elements of the so-called rcfl< .r lx (Fig. 44). These crossed fibers run down in the lateral columns of the spinal cord as the crossed pyramidal tracts. The pyra- midal fibers which do not cross in the medulla form the direct pyramidal tracts of the cord, and they gradually cross in tin- cord itself. The pyramidal fibers end by synapsis around the cells of the anterior horn, so that all fibers from the cerebrum ultimately cross to the opposite side before they reach the anterior horn cells, for which reason it happens that a lesion involving the pyramidal tract anywhere above the decussation, such as the haemorrhage in the internal capsule above referred to. nhvays causes paralysis of the opposlit \/Vc of the body (hemiplegia). These facts regarding the course of the pyramidal fibers ha\v been ascertained by microscopic examination of sections from Fig. 43. — Reflex arc through the spinal cord, in which an intermediary neurone (in blue) exists between the afferent and efferent neurones. (From Howell's Physiology. ) Fig. 44. — Course of the pyramidal fibers from the cerebral cortex to tho spinal cord : 1, fibers to nuclei of cranial nerves ; 3. fibers which do not cross in the medulla (direct pyramidal tract) ; // and .7. fibers which cross in medulla (crossed pyramidal tract). (After Howell.) REFLEX ACTION. 249 various levels of the spinal cord some time after destruction of tht- Rolandic area of the cerebrum (see p. 270). The pyramidal fibers are degenerated and they occupy the areas indicated in Fig. 42. Since the degeneration occurs below the destruction, it is called descending degeneration, in contradistinction to as- cending degeneration, which we saw to follow section of the posterior roots between their ganglia and the cord (see p. 246). To sum lip, the sensory impulse on entering the spinal cord by the posterior root, by traversing a collateral, may take the shortest possible pathway to the efferent nerve cell of the an- terior horn, or it may avoid this and travel up the posterior columns of the cord to the medulla, thence by the fillet to the cerebral cortex of the opposite side, and thence down the pyra- midal tracts to the anterior horn cells. In this long cerebral route there are at least three places where the impulse must pass by means of a synapsis from nerve fibers on to nerve cells, and then along the nerve fibers arising from these. These three places are: (1) in the medulla, (2) in the cerebral cortex, (3) in the anterior horn. This long cerebral route, as it is called, is by no means the only one along which afferent impulses may travel to the brain. Some may be carried by collaterals to certain cells of the grey matter of the cord, and from these cells fibers may run up the cord to the cerebellum or lesser brain. These cerebellar tracts are located in the lateral columns of the cord outside the crossed pyramidal tracts (see Fig. 42). They do not degenerate when the posterior roots are cut, but do so after section of the cord itself (this distinguishing them from the fibers in the posterior columns). The impulses which they transmit to the cerebellum have to do with certain subconscious sensations concerned in the maintenance of the tone of the muscles. There are also certain pathways in the white matter of the cord which trans- mit descending impulses from the cerebellum. The main bundles of ascending and descending fibers in the spinal cord are charted in Fig. 42, which should be carefully studied. THE EFFERENT FIBER, OR NEURONE. — As already explained 250 PHYSIOLOGY FOR DENTAL STUDENTS. the cell of this neurone is located in the anterior horn of matter of the cord. These anterior horn cells are distinguished from the other nerve cells of the grey matter by their large si/c and angular shape, and they become greatly increased in num- ber in the portions of the cord from which the nerves going to the extremities originate. The fibers springing from them pass out in the anterior roots. If the cells are destroyed or the an- terior roots cut, degeneration occurs below the lesion, and para- lysis of the effector organs (muscles) to which they run results, but this paralysis is very slight in degree unless the lesion af- fects several roots, or the cells of several adjacent levels of the cord. The reason for this is that the nerve cells of one level of the cord only partially supply a given muscle or group of mus- cles with nerve fibers, thus showing that even the small muscles receive their nerve fibers from several adjacent levels of the cord. The anterior horn cells sometimes become destroyed by disease, namely, in infantile paralysis (poliomyelitis anter- ior). The resulting paralysis is never recovered from. Types of Reflexes. — Having traced the paths through which reflexes occur in the higher animals, we may now proceed to consider certain typical forms of reflex action and the condi- tions which may cause them to become altered. We must first of all confine our attention to the characteristic reflexes of the so-called spinal animal, for it is only after we have done so that it will be possible for us to determine what influence the brain has in modifying the spinal reflexes. The spinal animal (dog, for example) is prepared by cutting across the spinal cord some- where below the origin of the phrenic nerves. After the imme- diate effects of the operation have been recoverd from, the regions of the animal's body, lying below the level of the sec- tion of the cord, suffer from a condition called spinal shock. All reflex movements are absent, the sphincters are paralyzed so that incontinence of urine and faeces exists, and various "tro- phic" or nutritive changes occur in the skin (abscesses form, hair falls out, etc.). After some time, the length of which de- pends on the position of the animal in the animal scale, the sphincters regain their tone and the reflexes gradually reappear REFLEX ACTION. 251 in the paralyzed region, the first to do so being the protective reflexes, of which the flexion reflex is the type. The flexion reflex is elicited by any stimulus which would cause pain in an animal capable of feeling. Such stimuli are called nocuous and the reflex response is always of such a nature — usually flexion — as to cause the injured part to be removed from further damage. The return of the flexion reflex is soon followed by that of the knee jerk, which is elicited by tapping the.patellar tendon after putting it on the stretch by passively bending the knee joint. Somewhat later in many animals (e.g., dog) the scratch reflex appears, so-called because it consists of a scratching movement of the hind leg in response to mechanical irritation* of the flank of the animal! It is a reflex of very great interest because it illustrates to what a remarkable degree the spinal cord, unaided by the brain, is capable of bringing about complicated and purposeful co-ordinated movement. Later still, in the lower animals, practically all the reflex movements which a normal animal exhibits may reappear. When the cord becomes severed in man, as by spinal fracture, spinal shock is extremely profound, and in order to keep the patient alive great care must be taken, on account of the incon- tinence of urine, to prevent infection of the bladder and kidneys and to protect the skin from ulceration (bed sores). Even in such cases, however, many of the reflexes recover in the para- lyzed regions, but the recovery is slow and the limbs invariably atrophy. It is particularly important to note that the time of re- appearance of the reflexes bears a relationship to the degree of development of the cerebral hemispheres, thus rendering it evi- dent that spinal shock is due to a break in the nerve paths which lead to and from the brain. The higher the animal, the more frequently do all reflex acts involve a cerebral path instead of taking the short cuts available through the collaterals (see p. 243). From usage, as it were, the cerebral paths become so well developed that when they are suddenly severed, the reflex action becomes impossible until the entering afferent impulse has learned to use the hitherto unused short cuts available through collaterals. When completely recovered from spinal shock, an 252 PHYSIOLOGY FOR DENTAL STUDENTS. animal, say a dog, in so far as voluntary movement is con- cerned, is entirely paralyzed in all portions of the body below the level of the section of the cord. It cannot voluntarily move the affected parts, it cannot walk, it feels no pain or any other sensation below the lesion, and yet when appropriately stimu- lated, the paralyzed limbs may reflexly undergo various, often very complicated movements. The Essential Characteristics of Reflex Action. — As studied on a perfectly recovered spinal dog these are as follows : 1. For a certain interval after applying the stimulus then- is no response, the duration of this "latent period" depending partly on the nature of the reflex (short in the protective re- flexes, long in the scratch reflex) and partly on the strength of the stimulus. 2. The response may persist for some time after the stimulus is removed (after response). 3. The degree of the response is roughly proportional to the strength of the stimulus, except in certain of the protective re- flexes, such as the conjunctival, which consists in the closing of the eyelids when anything touches the eye. 4. The response is often rhythmical in character, even though the stimulus be continuously applied. This is well seen in the scratch reflex. 5. There are certain ways, apart from an alteration in the stimulus, by which we may cause a reflex movement to become increased or decreased. Thus, taking the flexion reflex as an example, the flexion may be diminished: (1) by stimulating some other reflex movement which involves the same muscles, but which is antagonistic to flexion, e.g., by stimulating the opposite limb and causing the so-called crossed extension reflex ; (2) by causing strong afferent impulses to pass through other levels of the spinal cord, e. g., pinching the tail. A similar "interference" is well illustrated in the case of man by stimulat- ing the fifth nerve by firm pressure on the upper lip at a time when there is an inclination to sneeze. The snee/ing, which is a reflex due to irritation of the mucosa of the nose, can usually be prevented. Expressing this phenomenon of reflex iiiterfer- REFLEX ACTION. 253 ence in popular language, we may say that when the attention of a segment of the cord, or its extension in the brain is taken up by some other stimulus, a reflex already in action, or about to act, is depressed. Pain, such for example as toothache, may likewise be lessened by applying counter-irritation such as a blister to some neighboring skin area. (3) By means of certain drugs known as anesthetics, which depress the excitability of the nerve cells. (4) By fatigue. The reflex movement may be increased: (1) by applying a second stimulus to some other area of skin of the same hind leg or by applying electrical stimulation to the central end of one of its sensory nerves; (2) by raising the excitability of the nerve centers by certain drugs, such as strychnine; (3) by first of all causing the movement to disappear, though the stimulation causing it is maintained, by exciting some other part of the body (see above). When the reflex reappears it is much more pronounced than formerly. Muscular Tone and Reciprocal Action of Muscles. — Having •learned some of the general characeristics of the reflex move- ments, we may now proceed to inquire into the method by which the spinal cord is enabled, by itself, so to direct the afferent im- pulses which enter it, that the nerve cells of the anterior horn discharge suitable impulses to bring about such complicated movements as have just been described. When a motor nerve or an anterior spinal root is stimulated, the muscles which con- tract are not grouped in such a way as to cause any purposeful or co-ordinated movement. Contractors, extensors, adductors and abductors are quite likely all to contract at once and by thus opposing one another to effect no definite movement. When such stimulation is extensive (e.g., involves a considerable num- ber of motor fibers), it is common to find that the extensor muscles predominate over the others, so that the limb becomes extended. Such is the case when some poisonous substance causes irritation of the nerve centers in the spinal cord. To cause a co-ordinated movement it is necessary that one group of muscles should become relaxed whilst their antagonistic group is undergoing contraction. Now, it might at first sight be 254 PHYSIOLOGY FOR DENTAL STUDENT.-. imagined that this relaxation is merely a passive act. that is to say, that the uncontracting group of muscles do nothing more than remain quiescent and permit themselves to be stretched. But such is not the case; on the contrary, they become actively extended. This they are enabled to do because of the fact that, even when apparently relaxed, • a muscle is really not so, but exists in a condition called tone, that is, in a slightly contracted state. This tone becomes greatly diminished during sleep, and it can be caused almost to disappear by deep anesthesia. It is for this purpose, as well as to abolish pain, that anesthetics are administered before attempting to reduce a dislocation. Tone is maintained by the nerve cells of the anterior horn oi the spinal cord. When therefore an afferent impulse brings about flexion at the knee joint, it does so by exercising two diametrically opposite influences on the anterior horn cells: it stimulates those which preside over the flexor muscles and de- presses the tonic influence of those supplying the extensors. This tone-depressing action recalls the inhibitory influence which the vagus nerve exercises over the heart beat (see p. 185), and since it always 'occurs along with a contraction of antagonistic muscles it is called reciprocal inhibition. Certain poisons, par- ticularly strychnine and tetanus toxin, cause this reciprocal action to break down so that all the muscles around a joint con- tract at the same time and produce an extension. Tetanus toxin is the poison produced in the blood by the tetanus bacillus, and its interference with the reciprocal inhibition of the muscles of the lower jaw causes lockjaw. Symptoms Due to Lesions Affecting the Reflexes. — From what we have learned regarding the functions of the spinal cord, it is easy for us to explain the following symptoms and conditions resulting from pathological destruction or stimula- tion of various parts of it : 1. In destruction of the continuity of the afferent or efferent fibers of the reflex arc, the reflexes are absent. This occurs in chronic inflammation of the nerves (neuritis) and in the disease called locomotor ataxia, in which the lesion consists of a de- structive pathological process involving the posterior columns REFLEX ACTION. 255 of the spinal cord. One of the first symptoms of loeomotor ataxia is absence of the knee jerk, which, it will be remembered, is elicited by tapping the patellar tendon after putting it pas- sively on the stretch, either by sitting with the feet swinging on the edge of a table, or by crossing one knee over the other. Pains, called crises, are also usual in various parts of the body. Later symptoms are inability to stand without falling when the eyes are shut, inco-ordinated walking, in which the foot is lifted too high and is brought down to the ground again too violently, loss of sensation of the skin of the foot and leg, and changes in the pupillary reflexes of the eye (see p. 284). The joints also be- come swollen and the articular surfaces roughened so that a grating sensation is experienced when the joint is bent (Char- cot's joint). The condition gradually gets worse, so that the patient becomes bedridden. Death is usually due to complica- tions. 2. Destruction of the anterior horn cells not only causes absence of reflex action, but is followed by marked atrophy of the affected muscles. It has been supposed that this points to a so-called trophic influence of these nerve cells, that is to say, a power of influencing nutrition. Such changes occur in infan- tile paralysis (poliomyelitis anterior). 3. Stimulation of the above fibers may cause exaggeration of the reflexes, as in the earlier irritative stages of neuritis, in tumors pressing on the nerve roots, or when the membranes of the cord become inflamed, as in meningitis. 4. Removal of impulses coming from the cerebrum by way of the pyramidal tracts causes exaggerated reflexes. Such occur in paralysis of both sides of the body in paraplegia, and on one side, the paralyzed, in hemiplegia. In a paraplegic patient the weakest stimulus applied to the skin of the paralyzed portion of the body will call forth a wide- spread and much exaggerated reflex contraction. CHAPTER XXVII. THE NERVOUS SYSTEM (Cont'd). The Brain Stem and the Cranial Nerves. The Brain Stem. — The medulla, the pons varolii, and the mid- brain (Figs. 45 and 46), compose the brain stem, which is n-ally an upward extension of the grey matter, and of certain of the columns of the spinal cord, into the base of the brain with special nerve centers and especially large bundles of inter-connecting nerve fibers superadded. It is because of the crossing in various directions of these bundles of fibers that the structure of the medulla, pons and mesencephalon is so difficult to understand. The grey matter, as in the spinal cord, lies deeply and the fibers superficially. Of the latter, the pyramids and fillet, already de- scribed, are the most important, and their direction is longi- tudinal. The most prominent of the connecting or commisural nerve bundles are the upper, middle and lower pedunchs of the cerebellum, or small brain, which, it will be rememltered, lies over and at the side of the pons varolii and midbrain. The lower peduncles spring from the medulla and connect the spinal cord with the cerebellum. They form the lower edges of the fourth ventricle. The middle peduncles enter the sids of the pons in which they cross at right angles with the pyramidal fibers (p. 248). They connect the cerebellum of one side with the cerebrum of the opposite side. The superior peduncles join the encephalon just under the posterior corpora quadrigemina. and the fibers composing them decussate to the other side to be- come connected with certain of the so-called basal ganglia. The basal ganglia are the optic thalamus and the corpora stri- ata, two large collections of nerve cells protruding into the third and lateral ventricles of the brain and having the internal capsule between them (see p. 248). The nerve cells composing these ganglia receive impulses from nerve fibers arriving at them both t 256 THE BRAIN STEM. 257 from below (coming from the spinal cord) or from above (com- ing from the cerebrum). They then transmit these impulses along their own nerve fibers, which may run to various other Fig. 45. — Under aspect of human brain. In the center line from below upwards are seen a section of the upper end of the spinal cord, and the medulla oblongata (m), with certain of the cranial nerves (as numbered). In front of this is the pons (p), with the large fifth nerve arising from it, and the middle peduncles of the cerebellum (M. Fed) running into the cere- bellum (A). The rounder bodies anterior to the pons are the corpora quad- rigemina (Cq), to the sides of which are the crura cerebri and the origins of the third and fourth nerves. The optic and olfactory nerves are in front. The under surfaces of the cerebrum (Cb) and cerebellum (A) constitute the remainder of the drawing. ( From a preparation by P; M. Spurney. ) PHYSIOLOGY FOR DENTAL STUDENTS. parts of the brain. The optic thalamus, as its name signifies, is intimately associated with the optic nerves. Another important collection of nerve cells occurs in the corpora quadrigcniina. These exist as four rounded swellings, two on either side, just where the superior peduncles of the cere- bellum come together. Their nerve cells serve as distributing centers for visual and auditory impulses, carried to them through tracts of nerve fibers connected with the optic and auditory — P Fig. 46. — Vertical transverse section of human brain. Below is a section of the pons (P) showing the fibers which connect the brain stem and cere- brum radiating up through the internal capsule (1C), which is bounded mesially by the optic thalmus (T), and laterally by the corpus striatum (L). The third (III-V) and lateral ventricles (LV) of the brain are seen in the center (black). The thickness of the grey matter and the infolding of the surfaces, as convolutions, should be noted. (From a preparation by 1'. M. Spurney. ) nerves. The corpora quadrigemina are usually more developed in the brain of the lower animals than in that of man. The Cranial Nerves. — On account of the introduction of the new structures described above there is no regularity in the THE CRANIAL NERVES. 259 arrangement of the grey matter in the brain stem as there is in the cord. Instead of forming horns, the grey matter is scat- tered in colonies or nuclei, many of which are centers for the fibers of the cranial nerves. Some of these fibers are, of course, afferent and some efferent. Since many of the cranial nerves are connected with the nose, mouth and teeth, it is im- portant for us to learn something concerning the location of their centers and the general function of the nerves. There are twelve pairs of cranial nerves, and the last ten of these originate from the grey matter of the medulla, pons or midbrain. The following list indicates the general functions of the nerves: 1. Olfactory. 2. Optic. 3. Oculo motor. 4. Trochlear. 6. Abducens. 5. Trigeminal. 7. Facial. 8. Auditory. 9. Glosso-pharyn- geal. 10. Vagus. 11. Spinal accessory. 12. Hypoglossal. It is important to the cranial nerves are nerve of smell, nerve of sight. nerves to the mus- cles of the eyeball. sensory nerve of face, main motor nerve of face muscles, nerve of hearing and of semicircular canals. motor nerve of phar- ynx, sensory nerve of taste, efferent and afferent nerve to various viscera, mainly blends with vagus motor nerve for tongue muscles arises from fore- brain. arises from fore- brain. arise from midbrain. arises mainly in pons. arises in pons and medulla, arises in pons. arises mainly in medulla. arises in medulla. arises with vagus except spinal por- tion, which extends down into spinal cord. arises in medulla. note that, like the spinal nerves, many of composed of two roots, motor and sensory, 260 I'lIYSIOLOGY FOR DENTAL STUDENTS. each having its own center. This fact justifies the statement which we have already made that the brain stem is really an up- ward prolongation of the spinal cord, and just as we saw thai each posterior root of the spinal cord is characterized by pos- sessing a ganglion, so also is there a ganglion in the senior n divisions of the cranial nerves. This ganglion, however, is often difficult to find. The nerve cells which compose it unite with the fibers of the sensory root by a T-shaped junction, and the fibers terminate by synapsis around the cells of the sensory nuclei. The ganglion of the fifth nerve is the Gasserian. Those for the eighth are the ganglia found in the cochlea and internal auditory meatus (Scarpa's ganglion). The ganglia of the ninth and tenth nerves are situated along the course of the nerves. The approximate position of the various ganglia will be best learned by consultation of the accompanying diagram (Fig. 47). In the brain stem there are three sensory or afferent nuclei, a long, combined one for the ninth, tenth and eleventh nerves, ex- tending practically from the upper to the lower limits of the medulla, one for the eighth in the center of the pons, and a very long one for the fifth, extending from near the upper limit of the pons down into the spinal cord. The motor or < studied by dental students : THE THIRD NERVE. — The third nerve controls: (1) the mus- cles of accommodation inside the eye; (2) all of those which are attached to the outside of the eyeball, except the muscle which moves it out (external rectus), and the one which rotates it down and out (the superior oblique) ; and (3) the elevator muscle of the eyelids (levator palpebras). When the third nerve is paralyzed, the symptoms are therefore: (1) drooping of the vvelid (ptosis) so that the chin is tilted upward when the pa- iient looks at anything; (2) inability to see clearly unless when V Fig. 47. — Diagram of the dorsal aspect of the medulla and pons showing: the floor of the fourth ventricle with the nuclei of origin of the cranial nerves. (After Sherrington. ) The sensory nuclei are colored red and are numbered on the left of the diagram, the motor, blue and numbered on the right. The peduncles of the cerebellum — 8. (superior), M. (middle), and /.. are shown cut across. C.O., corpora quidrigemina. The above nuclei are of course present on both sides. THE CRANIAL NERVES. 261 objects are at a distance (long sight) ; (3) squint of the eye so that it is directed outward and downward. Such a paralysis of the eye is sometimes accompanied by a partial hemiplegia (see p. 271) of the opposite side of the body, thus idicating that some destructive lesion (haemorrhage, de- structive tumour) exists on one side of the midbrain, so that it- involves the nucleus of origin of the third nerve and also the pyramidal fibers lying near. Since the fibers of the third nerve do not cross to the opposite side, but those of the pyramids do (see p. 243), we get a crossed or alternating paralysis. Some- times only one part of the third nerve may. be paralyzed, for example, that portion going to the muscles of accommodation. THE FOURTH AND SIXTH NERVES. — The fourth and sixth nerves supply the two extra-ocular muscles not supplied by the third, viz., the superior oblique (fourth) and the external rectus (sixth), respectively. THE FIFTH NERVE. — The fifth nerve is the largest, of the cranial nerves, and is a representative mixed nerve. It supplies the teeth. The motor branch runs to the muscles of mastica- tion, the tensor muscle of the palate, the rnylohyoid muscle (in the floor of the mouth) and the anterior belly of the digastric. These last two mentioned muscles pull the hyoid bone and there- fore the root of the tongue upward and forward during the act of swallowing. Both mastication and swallowing are seriously impaired when this nerve is paralyzed. The sensory fibers are connected with the receptors for all the common sensations of the head and face. As already explained, they are connected witli the nerve cells of the Gasserian ganglion, which is lodged in a depression near the apex of the petrous portion of the temporal bone. Shortly after leaving this ganglion, the nerve divides into three branches: (1) the upper or ophthalmic, carry- ing the sensory nerve fibers for the conjunctiva, the mucous membrane of the nasal fossae, and the skin of the eyebrow, fore- head and nose. (2) Middle or superior maxillary, supplying the meninges, the lower eyelid, the skin of the side of the nose and upper lip and all the teeth and gums of the upper jaw. (3) Inferior maxillary, supplying the teeth and gums of the lower 262 PHYSIOLOGY FOR DENTAL STUDENTS. jaw, the skin of the temple and external ear, the lower part of the face and the lower lip. RELATIONSHIP OP THE FIFTH NERVE TO THE TEETH. — In any in- flammatory condition of the teeth, the terminations of the sen- sory fibers become stimulated, causing extreme pain. This is toothache. The relationship of the fifth nerve to the teeth ex- plains why disturbance in the latter should often cause the pain to be referred not to the tooth that is involved, but to some skin area on the face. This is called referred pain. The skin areas corresponding to the different teeth have been worked out by Head, and are indicated in the accompanying diagrams (Figs. 48 and 49). Not only may the pain be referred to the skin area, but this itself may become hypersensitive. There is, moreover, in each area usually a maximal spot at which the pain and ten- derness are most marked. The sensory nerve endings in the teeth are all of the nature of pain receptors; there are no temperature or tactile receptors, these latter sensations being particularly developed in the tongue and lips (see p. 244). The pain receptors of the teeth, like those of the cornea, react practically in full intensity to every strength of stimulus. This explains why a small degree of irritation, as that due to caries, may cause as painful a toothache as an in- tense irritation. As we have already explained, the purpose of painful or nocuous sensation is protective, causing, for example, withdrawal of the irritated portion of the body or some move- ment of offense (see p. 251). In the case of the teeth it serves as a warning that something must be done to arrest whatever condition is causing it. The enamel and cement are devoid of nerve endings, which, however, are very abundant in the pulp, and probably also in the dental tubules (Mummery). An inert, sensationless exterior covering, a highly sensitive center, and between these a moderately sensitive tissue, describes the sensi- tiveness of a tooth. The sensitiveness of the pulp is so great as to suggest that it is partly of the nature of a highly specialized ncci-receptor, just as the taste buds and olfactory epithelium are specialized receptors for taste and smell. The sensitiveness of the teeth diminishes with advancing age. Fronto-nasal area lary incisors). (maxil- Naso-labial area (maxillary canine and first premolar). Maxillary area (maxillary second premolar and first molar). Mental area (mandibular incisors, canine and first premolar). The points of maximum intensity are ringed. Fig. 48. — Diagram to show areas of referred pain in distribution of fifth nerve due to affections of the various teeth (Front view). (From drawing by T. Wingate Todd.) THE CRANIAL NERVES. 263 The fifth nerve is very commonly the seat of neuralgia, which may affect one or all of its branches. This is called "iic douloureux" or tri-facial neuralgia. The attacks come in spasms, and besides the excruciating pain, there is often twitch- ing of the muscles or flushing of the skin of the face. Pressure at the points where the branches of the nerve come out of the skull, as at the supra or infra-orbital notches, is usually espe- cially painful in tic. An unhealthy condition of the teeth is often responsible for the symptoms, but if dental treatment and general medical care do not remove the neuralgia, it is usually advisable to cut out a portion of the nerve or even to remove the entire Gasserian ganglion. Sometimes the fifth nerve becomes paralyzed, causing anes- thesia involving the area of its distribution. Tingling, numb- ness or neuralgic pains often precede the anesthesia. Since the conjunctiva loses its sensitiveness, particles of dust, etc., are not removed from the eye by the tears so that they set up inflam- mation, which may develop and cause ulceration of the cornea. For the same reason, or perhaps because the nerve independently controls the nutrition of tissues, the gums and cheeks may be- come ulcerated and the teeth loosened. Partial loss of taste and inability to smell pungent vapors, which act on sensory nerves, are also common symptoms. THE SEVENTH^ NERVE. — The seventhnerve is purely motor in function. /^Tlthe facial muscles, except those TJOiMittflUid In" mastication, the platysma of the neck, the posterior belly of the digastric and one of the muscles of the middle ear (the sta- pedius) are supplied by it. On account of its tortuous course the seventh nerve is peculiarly liable to inflammation and com- pression. Thus tumors or inflammation located at the base of the brain may involve that portion running between the upper end of the medulla oblongata and the internal auditory meatus, where the nerve enters the aqueduct of Fallopius. In this region it is likely to become involved when there is disease of the internal ear or mastoid sinus (mastoiditis). After its exit from the skull (by the stylomastoid foramen) its close association with the parotid gland renders it liable to be involved in eel- 264 rV PHYSIOLOGY FOR DKNTAL STIDKNTS. lulitis of this gland, and on account of its superficial position, it may be injured by blows on the side of the head. Quite com- monly the seventh nerve becomes the seat of inflammation after exposure to a draught, as by sitting at an open window. The l>«r(i lysis is almost always one-sided. The eyelid on the affected side cannot be properly closed, a chink remains and the eyeball becomes rotated upward, thus showing the sclerotic. On smiling or showing the teeth the mouth is drawn up on the healthy side. causing a triangular opening because the lips do not become separated on the paralyzed side. Articulation is difficult and such acts as whistling and blowing are impossible. Because of paralysis of the buccinator muscle, food collects between the cheek and gums. The distortion of the face is much more pro- nounced in old, than in young persons; indeed in the case of the latter the paralysis may be overlooked until speaking or laughing is attempted. THE EIGHTH OR AUDITORY NERVE. — The eighth or auditory nerve is composed of two branches, the one called cachluir, con- nected with the organ of Corti (see p. 291), which collects sound waves, and the other, called vcstibular, with the semicircular canals which, by the movements of the fluid contained in them, record changes in the position of the head (see p. 276). Both branches, being sensory, are connected with ganglia situated in or near the internal ear (ganglion spirale for the cochlear di- vision and ganglion of Scarpa for the vestibular). Paralysis of the auditory nerve causes a degree of deafness which is more profound than that due to disease of the middle ear, for in the latter case a tuning fork can be heard when the end of it is applied to the skull or is held in the teeth, which is not the case when the nerve is diseased. When the eighth nerve becomes irritated (as by inflammation of the ear, or a general condition such as migraine, epilepsy, etc.), various kinds of sounds are heard. This is called tiiittitits. It is not infrequently followed by deafness. THE NINTH OR GLOSSO-PIIARYNGEAL NERVE. — The ninth or glosso-pharyngeal nerve is partly motor and partly sensory. The motor fibers supply the muscles of the pharynx and most of Temporal area (maxillary second premolar). Mandibular area (maxillary second and third premo- lars). Hyoid area (mandibular sec- ond premolar ; first and second molars). Superior laryngeal area (mandibular third molar). The points of maximum intensity are ringed. Pig. 49. — Diagram to show areas of referred pain in distribution of fifth nerve due to affections of the various teeth (Side view). (From drawing by T. Wingate Todd.) THE CRANIAL NERVES. 265 those of the soft palate. The sensory fibers carry impulses of common sensation and of taste from the root of the tongue, the neighboring portions of the pharnyx, the tonsils, the soft palate, and the pillars of the fauces. This nerve does not commonly become the seat of local lesions. THE TENTH OR VAGUS NERVE. — This is the main cerebrospinal nerve supplying the viscera and it is both motor and sensory in function. We shall see. later that the nerves to the viscera belong to the so-called autonomic system, which is distinguished from the somatic by two main facts, one anatomical and one functional. The anatomical difference is that every nerve fiber becomes connected through synapses with nerve cells located peripherally (i. e., near the end of the nerve), and the axons of the cells continue the impulse on to the structure ; the functional difference is that the autonomic fibers, as their name indicates, control automatically-acting or involuntary functions instead of voluntary movements, as is the case with the ordinary or somatic cerebrospinal nerve fibers. The most important of the vagus autonomic fibers run to the heart (see p. 185), the oesophagus (p. 57), the stomach (p. 60) and the intestines (p. 79). The vagus also contains afferent fibers which have their cell stations in ganglia situated in the trunk of the nerve. These fibers carry sensory impulses par- ticularly from the larynx and lungs (p. 219). Further details regarding the functions controlled by the vagus are fully given in the references indicated above. When the vagus nerve, or its center, is the seat of paralysis, swallowing is seriously in- terfered with, and food is liable to pass into the larynx and cause pneumonia. Various forms of paralysis of the vocal cords may also result from paralysis of the vagus. THE ELEVENTH OR SPINAL ACCESSORY NERVE. — The eleventh or spinal accessory is entirely an efferent nerve, one part of it, the accessory, being derived from the same column of nerve cells as the vagus and being really a part of this nerve; the other arises from the cells of the anterior horn of the spinal cord in the upper cervical region and supplies the trapr/ius and sterno-mastoid muscles. 266 PHYSIOLOGY FOR DENTAL STUDENTS. THE TWELFTH OR HYPOGLOSSAL NERVE. — The twelfth in-rvc or hypoglossal is entirely efferent, being the motor nerve of the tongue muscles and of most of the muscles attached to the hyoid bone. When it is paralyzed, as in bulbar paralysis, swallowing of food becomes impossible, the tongue cannot be protruded and soon atrophies because of the removal of the trophic in- fluence of the nerve cells. Rarely the paralysis is unilateral, but this is because of lesions higher up in the nervous system than the medulla and so situated that they destroy the con- nection of the fibers which run from the higher motor centers in the cerebrum to the hypoglossal nucleus. Such lesions neces- sarily involve fibers of the same type running to the nerve cells of the spinal cord, so that hemiplegia (p. 248) accompanies and is on the same side as the tongue paralysis. When a patient with such a lesion attempts to put out the tongue, it is directed towards the affected side but it shows no atrophy. CHAPTER XXVIII. THE NERVOUS SYSTEM (Cont'd). The Brain. The first question which naturally arises is, what influence does the brain have on the reflex movements produced through the spinal cord? These influences may be summarized as fol- lows : 1. The brain enables the animal to will that a particular movement shall or shall not take place, irrespective of the stimu- lation of spinal reflexes. Much of this influence of the brain is of course voluntary in nature, but some of it is subconscious or involuntary. In general it may be said that the cerebrum, through the pyramidal tracts, usually exercises a damping or inhibitory influence on the spinal reflexes. It is for this reason that the reflex response to a certain stimulus is usually much more pronounced in a spinal, as compared with a normal animal. For example, it is impossible to bring about the scratch reflex in many normal dogs, whereas it is always present in spinal animals. In man this restraining influence of the pyramidal tracts on spinal reflexes is .very evident in the case of the knee jerk, which, it will be remembered, is the extension of the leg which occurs when the stretched patellar tendon is tapped. Ordinarily the kick is moderate in degree, but in patients whose pyramidal tracts are diseased, as in spastic paraplegia, it becomes very pronounced. 2. The brain, being the receiving station for the projicient sensations (p. 279), sight, hearing and smell, adds greatly to the number of afferent pathways by which reflex actions can be excited. 3. Since in higher animals all the afferent impulses usually 267 268 PHYSIOLOGY FOR DENTAL STUDENTS. travel through the brain (p. 248), many nerve centers become more or less involved in the reflex actions, so that a much higher degree of co-ordination than that seen in a spinal animal attends the muscular response. For example, some of these afferent impulses reach the cerebellum, whose function, as we shall is to strengthen some impulses and weaken others, so that a more perfect movement results. 4. The animal becomes conscious not only of the nature and place of application of the sensory stimulus itself, but of the degree to which it has moved its muscles in response. The Functions of the Cerebrum. The complicated movements, such as those involved in the scratch reflex, which we have seen that a spinal animal can carry out in the paralyzed region after shock has passed away, become more and more numerous and complicated as the higher centers are left in connection with the spinal cord. That is to say, the higher up in the cerebrospinal axis that the section is made, the more capable does the part of the animal below the section be- come to peform complicated movements. The important centers in the medulla, pons and mesencephalon add their influence to those of the spinal cord itself, so that integration becomes more comprehensive. If the cut is made above the level of the pons. in other words, if the cerebral hemispheres alone be discon- nected from the rest of the cerebrospinal axis — f/rrm hrTU>F.XTS. ing part of the cranium and through this hole the tumor or blood clot is removed. III. These so-called motor areas are of course also *< nsm-ii areas in the sense that the afferent stimuli which come up from the spinal cord run to them. They are really sensori-motor centers. For some of the more highly specialized proficient sensations such as vision and hearing (see p. 279), there are. however, special centers. These along with an extensive liehl of associational or junctional grey matter constitute the third main division of the cerebral cortex and occupy the greater part of the parietal, the temporosphenoidal .and the occipital lobes. The visual is the most definite of these centers. Thus if the occipital lobe be removed or destroyed by disease on one side, the corresponding half of each retina becomes blind. It is by studying the exact nature of the involvement of vision in such cases that the physician is able to locate the position of a tumor, etc. The center for hearing is in the temporosphenoidal lobe, but its location is not very definite. It will be seen, however, that the visual and auditory centers take up but a small part of this third division of the cerebrum, the most of it being occupied by associational areas. The nerve cells of these areas do not, like those of the motor and sensory centers, send fibers which run as pyramidal or optic fibers to some lower nerve center, but only to other cerebral centers, which they serve to link together. They are specialized to serve as junction points for all the receiving and discharging centers of the cerebrum, so that all actions may be properly correlated or integrated. These junctional centers thus perform the great function of adapting every action of the entire animal to some definite purpose. Along with the nerve cells in the prefrontal areas, the associational cells represent the highest development of cerebral integration, so that we find the areas in which they lie to become more and more pronounced, the higher we ascend the animal scale. The Mental Process. — The impression received by the visual center when a young animal looks for the first time at, say a THE FUNCTIONS OF THE CEREBRUM. 273 bell, becomes stored away in nerve cells lying in or close to that center, and when the bell is moved sound memories are likewise stored in the auditory center. At first these remain as -isolated memory impressions and the animal is unable to associate the sight with the sound of the bell But later, with repetition, the visual and the auditory centers become linked together, through nerve cells and fibers which occupy the associational areas, so that the invocation of one memory is followed by association with others. It is evident that the intricacy of this interlace- ment of different centers will, in large part, determine the in- tellectual development of the animal, and the possibility of his learning to judge of all the consequences that must follow every impression which he receives or every act which he performs. In man these associational areas are very poorly developed at the time of birth, so that the human infant can perform but a few acts for itself. Everything has to be learned, and the learning process goes hand in hand with development of the associational areas, which proceeds through many years. On the other hand, most of the lower animals are born with the associational areas already laid down and capable of very little further increase, so that, although much more able, than the human infant, of fending for itself at birth, the lower animal does not afterwards, develop mentally to the same extent. The practical application of these facts concerning the func- tions of different areas of the cerebrum is in the study of mental diseases. To serve as an example we may take aphasia. This means inability to interpret sights or sounds or to express the thoughts in language. In the former variety — called sensory aphasia — the patient can see or hear perfectly well, but fails to recognize that he has seen or heard the object before. He fails to recognize a printed word (word blindness) or to in- terpret it when spoken (word deafness). The lesion responsible for this condition is located in the associational areas and not in the centers themselves. In the other variety, called motor aphasia, the patient understands the meaning of sounds or sights, of spoken or written words, but is unable to express his thoughts or impressions in language. The lesion in this case in- 274 PHYSIOLOGY FOR DENTAL STUDENTS. volves some of the centers concerned in the higher control of the muscles which are used in speech, and very commonly it is situated in the left side of the cerebrum. In all three forms of aphasia there is more or less decrease in the mental powers. Cerebellum. 'The afferent impulses set up by stimulation of the nerves of the skin in a spinal animal, and due therefore to changes in the environment, after entering the spinal cord travel to the various centers in the cord. Although complicated movements may result (e.g., the scratch reflex), there is an entire absence of the power of maintaining bodily equilibrium, and the animal cannot stand because the muscles are not kept in the degree of tone which is necessary to keep the joints properly stiffened A similar inability to maintain the center of gravity of the body results from removal of the cerebellum, or small brain, which it will be remembered is situated dorsal to the medulla and pons, with which it is connected by three peduncles. The cerebellum consists of two lateral hemispheres and a median lobe called the vermis. The remarkable infolding of the grey matter which composes its surface, and the large number of nuclei which lie embedded in its central white matter are struc- tural peculiarities of the cerebellum. The immediate results of removal of the cerebellum consist in extreme restlessness and inco-ordination of movements. The animal is constantly throwing itself about in so violent a man- ner that unless controlled it may dash itself to death. Gradually the excitement gets less until after several weeks all that is noticed is that there is a condition of muscular weakness and tremor, and difficulty in maintaining the body equilibrium. Quite similar symptoms occur when the cerebellum is diseased in man (as by the growth of a tumor), the condition being called cerebellar ataxia, and being characterized by the uncer- tain gait which is like that of a drunken man. These observations indicate that the function of the cerebellum is to harmonize the actions of the various muscular groups, so THE FUNCTIONS OP THE CEREBELLUM. 275 that any disturbance in the center of gravity of the body may be subconsciously rectified by appropriate action of the various muscular groups. It evidently represents the nerve center hav- ing supreme control over other nerve centers, so that these may not bring about such movements as would disturb the equili- brium of the animal. In order that the cerebellum may perform this function it must, however, be informed of two things. In the first place, it must know the existing state of contraction of the muscles and the tightness of the various tendons that pull upon the joints, and in the second, it must know the exact position of the center of gravity of the body. Information of the condition of the muscles and tendons is supplied through the nerves of muscle sense, which run in every muscular nerve and are connected in the muscles with peculiar sensory nerve terminations called muscle spindles. When the muscles contract, or the tendons are put on the stretch, these spindles are compressed and sensory or afferent stimuli pass up the nerves of muscle sense, enter the cord by the pos- terior roots and reach the cerebellum by way of the lateral col- umns (see p. 249). Information regarding the center of gravity of the body is supplied through the vestibular division of the eighth nerve, which, it will be recalled, is connected with the semicircular can- als and vestibule. In these structures are membranous tubes or sacs containing a sensory organ (called the crista or macula acoustica), which consists essentially of groups of columnar cells furnished with very fine hair-like processes at their free ends and connected at the other end with the fibers of the eighth nerve. The hair-like processes float in the fluid which is con- tained in the membranous canals or sacs. This fluid does not, however, completely fill these structures, so that it moves when- ever the head is moved. This movement affects the hair-like processes and thus sets up nerve impulses which are carried to the cerebellum. To make the hair cells of this receiving apparatus capable of responding to every possible movement of the head, it is, 276 PHYSIOLOGY FOR DENTAL STUDENTS. however, evident that there must be some definite arrangement of the tubes. This is provided for in the disposition of the semi circular canals in three planes, namely, a horizontal and two vertical (Fig. 51). Taken together the three canals form a struc- ture which looks somewhat like a chair, the horizontal canals being the seat of the chair and the two vertical canals joining together to form its back and arms. The back of each chair is directed inwards so that they are back to back. At one end of each canal is a swelling, the ampulla, in which the sensory nerve Fig. 51. — The semicircular canals of the ear, showing their arrangement in the three planes of space. (From Howell's Physiology.) apparatus above described is .located. It is evident that when the head is moved in any direction the fluid in some of these canals will be set in motion. It is this movement of the fluid which stimulates the hair cells. That this is really the function of the semicircular canals is proven by the fact that if they ;uv irritated or destroyed, grave disturbances occur in the bodily movements. This is what occurs in Meniere's disease, in which attacks of giddiness, often severe enough to cause the patient to fall, and accompanied by extreme nausea, are the chief symp- toms, the lesion being a chronic inflammation involving the THE SYMPATHETIC NERVOUS SYSTEM. 277 semicircular canals. It is believed by some that the constant movements of the fluid in the semicircular canals is the cause of sea sickness. The unusual nature of these movements causes confusion in the impressions transmitted to the cerebellum from the canals, but after a while the cerebellum becomes accustomed to them and the sea sickness passes away. The Sympathetic Nervous System. Along with the vagus and one or two less prominent cere- brospinal nerves, the sympathetic constitutes the autonomic nervous system, so called because it has to do with the innerva- tion of automatically acting structures, such as the viscera, the glands and the blood vessels. The characteristic structural fea- ture of the nerves of this system is that they are connected with nerve ganglia located outside the central nervous system. In these ganglia the nerve fibers run to nerve cells, around which they form synapses, thus permitting the nerve impulse to pass on to the cell, which then transmits it to its destination along its own axon (see p. 241). Before arriving at the ganglion in which the synapsis is formed, the 'fibers are called pregan- glionic; after they leave, they are called postganglionic. A preganglionic fiber .may run through several ganglia before it becomes changed to a postganglionic fiber. In the case of the vagus and other cerebral autonomic nerves, the ganglia are often situated, as in the heart (see p. 185), at the end of the nerve, but in the case of the sympathetic itself, they are more numerous, and are mainly situated at the sides of the vertebral column, where, along with the connecting fibers, they form a chain — the sympathetic chain — which can easily be seen on opening the thorax and displacing the heart and lungs. Two fine branches connect each of the spinal nerves with the corresponding sympathetic ganglion. It is through one of these branches that the sympathetic chain receives its fibers from the spinal cord. Through the other, fibers run from the ganglion to the spinal nerve. Some of the sympathetic ganglia are situated at a distance from the spinal cord ; the ganglia which compose the solar and hypogastric plexuses are examples. 278 PHYSIOLOGY FOR DENTAL STUDENTS. In the thorax, the uppermost ganglion is very large and is called the stellate ganglion. Its postganglionic fibers constitute the vasomotor nerves of the blood vessels of the anterior ex- tremity, and the sympathetic fibers to the heart. Some pregan- glionic fibers run through the stellate ganglion to pass up the neck as the c< rrical xi/)>i/> PHYSIOLOGY FOR DENTAL STUDENTS. occur in the eye, but the second is rendered possible by of tin ."> |. /////>, /•- »i< Iropia is due to the eyeball being too short so that the focus of the image is behind the retina. The error is corrected by prescribing convex glasses. Myopia is due to the opposite con- Fig. 55. — Errors in refraction : E shows the formation of the image on the retina in the normal or emmetropic eye ; H shows the condition in long- sight, or hypermetropia, where the eyeball is too short; M shows the condi- tion in short-sight, or myopia, where the eyeball is too long. dition, that is, the eyeball is too long, so that the focus occurs in front of it. Concave glasses correct it. AstiyvKttixm is due to the lens or cornea being of unequal curvature in its different VISION. 287 meridians. This causes the rays of light in one plane to be brought to a focus before those in other planes, so that the two hands of a clock, when they are at right angles to each other, cannot be seen distinctly at the same time, although they can be successively focused. A certain amount of astigmatism exists in every eye, but when it becomes extreme, it is necessary to correct it by prescribing glasses which are astigmatic in the opposite meridian to that of the eye. Such glasses are called cylindrical. Astigmatism may occur along with either myopia or hyper- metropia, and when any of these errors is only slight in degree, the patient may be able, by efforts of accommodation, to over- come the defect. The strain thus thrown on the ciliary muscle is, however, quite commonly the cause of severe headache. The correction of the errors should never be left to untrained per- sons, but a proper oculist should be consulted, since it is usually necessary to give atropin so that the accommodation may be paralyzed and the exact extent of the error measured. The use of improper glasses may aggravate the defect of vision and do much more harm than good. The Sensory Apparatus of the Eye. The Functions of the Retina. — The image which is formed on the retina by the optical system of the eye sets up nerve im- pulses which travel by the optic nerve to the visual center in the occipital lobes of the cerebrum (see p. 272), where they are interpreted. Microscopic examination of the retina has shown that it consists of several layers of structures, the innermost being of fine nerve fibers which arise from an adjacent layer of large nerve cells, and the outermost of peculiar rod or cone- shaped cells, called the rods and cones. Between the layer of large cells and the layer of rods and cones are several layers composed of other nerve cells and of interlacements of the pro- cesses of cells and nerve fibers. The rods and cones are the structures acted on by light, the other layers of the retina being for the purpose of connecting the rods and cones with the large nerve cells from which the fibers of the innermost laver arise. 288 PHYSIOLOGY FOR DENTAL STUDENTS. The fibers all converge to the optic disc, which is a little to the inside of the posterior pole of the eyeball. At this point the fibers of the nerve fiber layer bend backwards at right anglos and run into the optic nerve, thus crowding out the other layers and causing the existence of a blind spot, which can be readily demonstrated by closing one eye, say the left, and with the other regarding the letter B in the next line. Although the S is B S also distinctly visible in most positions, yet if the book be moved towards and away from the eye, the S will become in- visible at a certain distance corresponding to that at which the rays from it are impinging upon the blind spot. As we alter the distance of the book from the eye, the line of vision, or visual axis, being fixed on the B, the image of the S travels from side to side across the inner or nasal half of the retina. and at a certain position strikes the optic disc. Ordinarily we are unaware of the blind spot, partly because we have two eyes and, the blind spot being towards the nasal side of each side, the image of an object does not fall on it in both eyes at the same time; and partly because we have learned to disregard it. The area or extent of the blind spot may become so increased, as by excessive smoking, that it becomes noticeable. At another portion of the retina called the fovea centralis, all the layers become thinned out except that of the rods and cones, especially the cones. This, as we should expect, is by far the most sensitive portion of the retina, and is indeed the portion on which we cause the image to be focused when we desire to see an object clearly. The remainder of the retina is only suffi- ciently sensitive to give us a general impression of what we are looking at. Thus when we view a landscape, we can see only a small portion clearly at one time, although we have a general impression of the whole. The portion which we see clearly is that which is focused on the fovea, and we keep moving our eyes in all directions so that every part of the landscape may in turn be properly seen. We see with the fovea what the rest of the retina informs us there is to be seen. VISION. 289 The Movements of the Eyeballs. — In order that we may be enabled to move our eyes so as to see objects in different posi- tions in the visual field, the eyeballs are provided with six little muscles, four recti and two obliques. These muscles are in- nervated by the third, fourth and sixth nerves (see p. 259). The images in the two eyes cannot of course fall on anatomically identical parts of the retinae, but they fall on parts that are physiologically identical. Thus, an object, say on the right of the field of vision, will cause an image to fall on the. nasal side of the right retina and 011 the temporal side of the left retina. We do not, however, see two objects because by experience we have come to learn that these are corresponding points on the retinae. When an object is brought near to the eye, the two eyeballs must converge so as to bring the visual axes on to the corresponding points. This convergence of the eyeballs con- stitutes the third change occurring in the eyes during accom- modation for near vision, the other two being, as we have seen, bulging of the lens and contraction of the pupil. It is interest- ing that these three changes are controlled by the third nerve. If anything happens to throw one of the images on to some other portion of one retina, double vision is the result. This condition of diplopia, as it is called, can be brought about, vol- untarily, by pressing on one eyeball at the edge of the eye, or it may occur as a result of paralysis or incoordinate action of one or. more of the ocular muscles. This occurs in certain in- toxications, such for example, as in that produced by alcohol. Just as in the case of errors of refraction, e. g., astigmatism, slight degrees of diplopia may cause symptoms that are more distressing than where marked diplopia exists, because we try to correct for slight errors and the effort causes pain (headache) and fatigue, whereas with extreme errors we do not try to correct but, instead, we learn to disregard entirely the image in one eye. When the incoordination of ocular movement is permanent, as when it is due to shortening of one of the muscles it is called strabismus. This condition is usually congenital, and can often be rectified by surgical operation. Judgments of Vision. — Besides these purely physiological 290 1'IIYSloLOGY FOR DENTAL STUDENTS. problems of vision, there are many others of a physio-psycho- logical nature. Such for example are the visual judgments of size, distance, solidity, and color. Judgments of size and dis- Itnirc are dependent on: (1) the size of the retinal image, (2) the effort of accommodation necessary to obtain sharp defini- tion, and (3) the amount of haze which appears to surround tin- object. Judgment of solidity depends on the fact that the images produced on the two retina? are not exactly from the same point of view; they are like the two photographs of a stereoscopic picture. The brain on receiving these two slightly different pictures fuses them into one, but judges the solidity of the object from the differences in the two pictures. Judgments of color, or color vision, forms a subject of great complexity. It apparently depends on the existence in the re- tina of three varieties of cones, one variety for each of the three primary colors. The primary colors are red, green and violet; and by mixing them on the retina in equal proportions (as by rotating a disc or top on which they are painted as sectors) a sensation of white results; by using other proportions, any of the other colors of the spectrum may be produced. When one of these primary color receptors is absent from the retina, color blindness exists. Thus if the red or the green receptors are absent, the patient cannot distinguish between red and given lights. Such persons cannot be employed in railway or nauti'-al work. CHAPTER XXX. THE SPECIAL SENSES (Cont'd). Hearing1. Like light, sound travels in waves, but not as transverse waves of the ether that fills space, but as longitudinal waves of con- densation and rarefaction of the atmosphere itself. The magni- tude of these waves is much greater and their rate of trans- mission much slower than the waves of light; therefore we see the flash of a gun long before we hear its sound. The several qualities of sound, such as pitch, loudness and quality or timbre, depend respectively on the frequency, the magnitude and the contour of the waves. Sound waves are not appreciated by the ordinary nerve receptors but only by those of the cochlear division of the eighth nerve. These are connected, in the cochlea of the internal ear, with a highly specialized receptor capable of converting the sound waves into nerve impulses. The cochlea consists of a bony tube wound two and one-half times as a spiral around a central column, up the center of which runs the end of the cochlear nerve. A longitudinal section of the cochlea (Fig. 56), therefore shows us this spiral tube in sec- tion at several places, and it is noticed that there projects into it from the central column a ledge of bone having a C-shaped free margin. From the lower lip of the C a membrane, called the basilar membrane, stretches across the tube which it thus divides into two canals, of which the upper is again divided into two by another membrane running from the upper surface of the bony ledge. The basilar membrane is a very important part of the mechan- ism for reacting to sound waves. Resting on it is a peculiar struc- ture called the Organ of Corti (Fig. 57), which in transverse sec- tions of the cochlear canal is seen to be composed of two rows of long epithelial cells set up on end like the rafters of a roof, with 291 292 PHYSIOLOGY FOR DENTAL STfDENTS. shorter "hair"' cells leaning up against them, particularly on tin- side away from the central column. The sound waves which act on the basilar membrane are transmitted to the fluid which fills the uppermost of the three divisions of the cochlear tube (see Fig. 56) through a membrane covering an oval-shaped opening (the oval window) in the bony partition separating the internal from the middle ear. After reaching the apex of the cochlea they pass through a small aperture in the basilar membrane into the lowest Fig. 56. — Semidiagrammatic section through the right ear (Czermak) : G. external auditory meatus ; T, membrana tympani ; P, tympanic cavity or middle ear with the auditory ossicles stretching across it and the Eustachian tube (E) entering it; o, oval window; r, round window; B, semicircular canals; S, cochlea; Vt, upper canal of cochlea; Pt, lower canal of cochlea. (From Howell's Physiology.) canal, down which they travel to lose themselves against the mem- brane covering another opening (the round window) situated near the oval window in the same partition of bone. As they pass along these canals the waves cause the basilar membrane to move or vibrate. The vibration affects the cells of the Organ of Corti. and so sets up nerve impulses which are transmitted to the coch- lear nerve by means of nerve fibers which connect with each of the main cells of the Organ. A fine membrane (called Tec- Fig. 57. — Diagrammatic view of the organ of Corti (Testut) : D, basilar membrane ; A, B, inner and outer rods of Corti ; 6, 6". 6," hair cells ; 7, ?", supporting cells. (From Howell's Physiology.) HEARING. 293 torial) rests on the tops of the hair cells, and by rubbing on them when they move, this membrane augments the action of the basilar membrane. We must now consider how the sound waves are brought from the outside to the oval window. The pinna of the ear col- lects the sound waves from the outside and directs them into the external auditory canal, at the inner end of which they strike the drum of the ear or tympanic membrane. This membrane is stretched loosely in an oblique direction, across the canal and is composed partly of fibers which radiate to the edge of the membrane from the handle of the malleus, a process of one of the auditory ossicles, to which it is attached. Because of these properties, the tympanic membrane, unlike an ordinary drum, is capable of vibrating to a great variety of notes, and the vibrations cause the handle of the malleus to move in and out. Between the tympanic membrane and the cochlea is the middle ear or tympanum consisting of a cavity across which stretches the auditory ossicles composed of three small bones, the malleus, the incus and the stapes. Besides the long process or handle already described, the malleus consists of a rounded head sit- uated above and forming a saddle-shaped articulation with the head of the incus and a short process which runs from just be- low the head to the anterior wall of the tympanum. The incus is somewhat like a bicuspid tooth, the malleus articulating with the crown, and having two fangs, a short one passing backward and a long one vertically downwards. This process, at its lower end, suddenly bends inwards to form a ball and socket joint with a stirrup-shaped bone (the stapes), the foot piece of which is oval in shape and fits into the oval window already mentioned. The ossicles act together as a bent lever, the axis of rotation passing through the short process of the malleus in front and the short process of the incus behind. If perpendiculars be drawn from this axis to the tips of the handle of the malleus and the long process of the incus, it will be found that the latter is only two-thirds the length of the former (Fig. 58). The amplitude of movement at the stapes will therefore be only two-thirds of that at the center of the tympanic membrane, but one and one- 294 PHYSIOLOGY FOR DENTAL STI DKNTS. half times stronger. The increase in force with which the movements of the tympanic membrane arc conveyed to the oval window is still further magnified by the fact that the latter is only one-twentieth the size of the former. It is by these move- ments at the oval window that waves are set up in the fluid occupying the uppermost membraneous tube of the cochlea and thus acting on the basilar membrane. The tympanic cavity or Fig. 58. — Tympanum of right side with the auditory ossicles in place (.Mor- ris) : 1, incus (like bicuspid tooth) with one process (,,1) attached to wall of tympanum and the other running downwards to articulate at 9 and 8, the stapes ; 10, head of malleus attached to tympanic membrane. ( From How- ell's Physiology.) tympanum across which the chain of ossicles stretches is kept at atmospheric pressure by the Euxldcliian tub< , which connects it with the posterior nares. Deafness may be din to tin foll<>irin» & mi •: N TJi -P O! £