i! {piiiic^;:iaiil(Sib^ \Ul> 1 H, I iKlvM^yHg'i nmrai H^Xt Q^oUcgc of AgrtcuUute atJiata. IN. % ffiibratg Library Burea Cal. No. 1137 ^1™iliEi^Slilfe,,l!lS.!??.!l?™/".?«on and a 3 1924 003 135 682 The original of tiiis book is in tine Cornell University Library. There are no known copyright restrictions in the United States on the use of the text. http://www.archive.org/details/cu31924003135682 BASAL METABOLISM ITS DETERMINATION AND APPLICATION BASAL METABOLISM ITS DETERMINATION AND APPLICATION FRANK B. SANBORN, M.S., Editor ORIGINAL PAPERS BY Charles G. Beall, M. D. Cabmen E. James, M. D. J. Eahl Else, M. D.. Lovell Langstroth, M. D. Edwin L. Gardner, M. D. Robert C. Lewis, Ph. D. Howard D. Haskins, M. D. Henry ElsnEr Marks, M. D. John Walker Moore, M. D. APPROVED ABSTRACTS OF PAPERS BY Cameron V. Bailey, M. D. Frank H. Lahet, M. D. Eugene F. Du Bois, M. D. George W. McCaskey, M. D. Charles H. Frazier, M. D. Stuart McGuire, M. D. James H. Hutton, M. D. Herman O. Mosenthal, M. D. Nelson W. Janney, M. D. Albert H. Rowe, M. D. John T. King, Jr., M. D. John L. Tiebney, M. D. First Edition SANBORN COMPANY, Publishers 1048 COMMONWEALTH AVENUE BOSTON, MASS., U. S. A. 1922 a?i7/ St Conyright, 1922 FRANK B. SANBORN All rights reserved "Health and good estate of body are above all gold, and a strong body above infinite wealth." To THE MEN AND WOMEN W'B.O APPLY SCIENCE IN DIAGNOSIS AND DILIGENTLY LABOR TO PREVENT THE ADVANCE OF DISEASE BAS.'VL METABOLISM .~X:: Pennsylvania Hospital, 8th and Spruce Streets, Philadelphia, Pennsylvania. The illustration shows the original building, the east wing of which was built in 1755. It was founded in 1751 and for the first four years occupied merely a dwell- ing house. Benjamin Franklin was largely instrumental in founding this, the oldest, hospital in America. HOSPITALS Front \ iew The buildings from left to right are: Superintendent's Cottage, Medical Pavil- ions, Administration Building, Surgical Building. Los Angeles County Hospital, Los Angeles, California Representative of a modem public hospital that has been expanded and developt to meet the needs of a rapidly-growing American city. Rear View From left to right: Tuberculosis Pavilion; Sen-ice Building; Power Plant; Laundry; Medical Pavilions; Garage and Morgue; Contagious Disease Pavilions; Psychopathic AVard. CONTRIBUTORS Bailey, Cameron V., b. '84; graduate of McGill University Faculty of Medicine, Montreal, '09. In charge of Metabolism Laboratory of New York Post-Graduate Hospital, New York, N. Y. Beall, Charles G., b. '81; graduate of Fort Wayne College of Medicine, Fort Wayne. Office, Lutheran Hospital, Fort Wayne, Ind. Du Bois, Eugene F., b. '82; graduate of Columbia University College of Physicians and Surgeons, New York, '06. Assistant Professor of Medicine, Cornell University Medical College, New York. In charge of Metabolism Laboratory of Bellevue Hospital, New York, N. Y. Else, J. Earl, b. '78; graduate of Northwestern University Medical School Chicago, '05. Assistant Professor of Surgery, University of Oregon Medical School, Portland. Office, Stevens Building, Portland, Ore. Frazier, Charles H., b. '70; graduate of University of Pennsylvania School of Medicine, Philadelphia, '92. Professor of Clinical Surgery at University of Pennsylvania School of Medicine, Philadelphia. Office, 1724 Spruce Street, Philadelphia, Pa. Gardner, Edwin L., b. '86; graduate of University of Minnesota Medical School, Minneapolis, '12. Office, LaSalle Building, Minneapolis, Minn. Haskins, Howard D., b. '71; graduate of Western Reserve University School of Medicine, Cleveland, '95. Professor of Biochemistry, University of Oregon Medical School, Portland. Office, Medical School, University of Oregon, Portland, Ore. Hutton, James H., b. '82; graduate of Hahnemann Medical College and Hospital, Chicago, '12. Office, 753 East 47th Street, Chicago, 111. James, Carmen E., b. '93; graduate of University of Tennessee College of Medicine, Memphis, '19. Resident Physician, U. S. P. H. S. Marine Hospital No. 13, Mobile, Ala. Jaimey, Nelson W. b. '81; graduate of University of Pennsylvania School of Medicine, Philadelphia, '06. Office, State Building, Los Angeles, Cal. King, John T. Jr. b. '89; graduate of John Hopkins University Medical Department, Baltimore, '14. In charge of Metabolism Laboratory at John Hopkins Hospital. Office, 1400 Eutaw Place, Baltimore, Md. Lahey, Frank H., b. '80; graduate of Medical School of Harvard Uni- versity, Boston, '04. Professor of Surgery at Tufts College Medical School. Office, 638 Beacon Street, Boston, Mass. CONTRIBUTORS 9 Langstroth, Lovell, b. '80; graduate of Cooper Medical College, San Francisco, '12. In charge of laboratories at University of California Hospital. Office, 240 Stockton Street, San Francisco, Cal. Lewis, Robert C. b. '88; graduate of Sheffield Scientific School of Yale University, '09, Ph. D. '12. Professor of Biochemistry, University of Colorado, Boulder. OfTice, Metropolitan Building, Denver, Col. McCaskey, George W., b. '53; graduate of Jefferson Medical College of Philadelphia, '77. Professor of Medicine, Indiana University School of Medicine, Indianapolis. Office, 409 West Main Street, Fort Wayne, Ind. McGuire, Stuart, b. '67; graduate of University of Virginia, Depart- ment of Medicine, Charlottesville, '91. Head of St. Luke's Hospital, Richmond, Va. Marks, Henry Eisner, b. '91; graduate of Syracuse University College of Medicine, '15. In charge of Metabolism Laboratory of Vanderbilt Clinic, New York. Office, 114 East 54th Street, New York, N. Y. Moore, John Walker, b. '84; graduate of University of Pennsylvania School of Medicine, Philadelphia, '12. Professor of Medical Research, University of Louisville, Louisville. Office, 1357 South Second Street, Louisville, Ky. Mosenthal, Herman C, b. '78; graduate of Columbia University College of Physicians and Surgeons, New York, '03. Office, 49 East 53rd Street, New York, N. Y. Rowe, Albert H., b. '89; graduate of University of California Medical School, Berkeley-San Francisco, '14. Office, Hutchinson Building, Oak- land, Cal. Sanborn, Frank B., Editor, b. '65; graduate of Dartmouth College, B. S., '87, C. E., '89. Harvard University, M. S., '98. Professor in Engineering at Tufts College, 1899-1918. Office, 1048 Commonwealth Avenue, Boston, Mass. Tiemey, John L., b. '90; graduate of St. Louis University School of Medicine, '14. Office, University Club Building, St. Louis, Mo. PREFACE This book is intended to supply the physician and the tech- nician with a treatise that will be a guide in making tests of metabolism and in interpreting the results of these tests. No longer is it possible for a single individual, or a small group of individuals, to have a comprehensive knowledge of the various forms of apparatus and different methods of interpreting results that have developt in this rapidly-expanding subject of Basal Metabolism. This volume presents the judgments of many competent authorities. It is the product of many minds. Ten chapters contain original articles. Each chapter has been prepared by a contributor whose views have been exprest with- out material curtailment, or regulation by the Editor or the Publishers. The Authors of the chapters on Determination of Metabolism were asked to make each chapter that describes a particular make or form of apparatus a scientific treatment and without criticism of other forms of apparatus, or methods. The Editor believes that this spirit of impartiality has been adhered to thruout the book. Nine forms of metabolism apparatus are described and information given of the best methods of using each apparatus so as to obtain the best results. The chapters that contain methods of Application embody the views and opinions of the physicians whose names appear on the chapters. Twelve chapters comprise abstracts which the Editor and his staff have prepared from important papers of recent date. These abstracts were submitted to the Authors and received their approval before being published in this volume. The chapters that have not an Author's name affixt have been prepared under the direction of the Editor. He is responsible for these chapters as well as for the grouping, headings, and cuts 12 BASAL METABOLISM in many of the remaining chapters. Miss Esther G. Price, A. B., collected and arranged most of the material in Chapters 1 and 2 on Normals. Miss Ruth A. Sanborn, B. S., has examined and made suggestions for many parts of the book, and prepared most of Chapter 27: A Conspectus of Recent Advances in Metabolism. Miss Mary A. Ruggles and Mr. V. R. Peterson, B. M. E.,have collected and correlated many parts and read and checked both manuscript and text. Frank B. Sanborn. Boston, Mass., U. S. A. February 25, 1922. TABLE OF CONTENTS CONTENTS CONTRIBUTORS 8-10 PREFACE 11-12 DEFINITIONS 16-17 NORMAL STANDARDS Chapter Page 1. Normal Standards of Basal Metabolism 19-39 2. Normal Standards and Methods of Computation 40-44 INITIAL PROCEDURE FOR ALL types' OF APPARATUS 3. Preparation of Patient 45-52 OPEN CIRCUIT METHODS Description — Procedure — Calculation 4. Gas Analysis Methods 53-64 5. Gas .-\^lysis Method of New York Post-Graduate Hosp^^ 65-72 6. King Meuisid: Determination of Carbon Dioxid EHmination : 73-79 \ CLOSED CIRCUIT METHODS Description — Procedure — Calculation 7. Sanborn-Benedict Apparatus 80-92 8. Benedict Universal Apparatus 93-103 9. Jones "Metabolimeter" 104-116 10. Collins-Benedict Apparatus 117-122 11. McKesson "Metabolor" 121-129 12. Sanborn-Handy Apparatus 130-135 CONTENTS 15 CLINICAL APPLICATIONS IN GENERAL 13. The Value of Metabolism Studies 136-141 14. Basal Metabolism and the General Practitioner 142-144 15. Basal Metabolism in Various Diseases 145-142 16. The Basal Metabolism in Endocrine Disturbances .... 149-158 17. Dysthyroidism 153-156 IN HYPERTHYROIDISM 18. Interpretation of Basal Metabolism in Hyperthyroidism 157-169- 19. Thyrotoxicosis 170-174 20. Treatment of Certain Types of Goiter 175-179 21. Diagnosis of Psychoneurosis and Hyperthyroidism 180-183- IN HYPOTHYROIDISM 22. Hypothyroidism: Physiological, Primary and Secondary 184-196 23. Therapy by Thyroid-Feeding 197-203 IN FEVER 24. The Basal Metabolism in Fever 204-214 IN SURGERY 25. Observations in Goiter Clinic of University Hospital . . 215-217 26. As an Index to Surgical Treatment 218-222' APPENDIX 27. A Conspectus of Recent Advances in Metabolism .... 223-237 28. Tables with Explanations 238-272 29. Selected References 273-275 30. Index 276 284 DEFINITIONS OF IMPORTANT TERMS IN METABOLISM TECHNIC A-nab'o-lism. — The process of food assimilation; constructive meta- bolism. Ba'sal Me-tab'o-lism. — The metabolism under basal conditions — after 14 hours of fasting and 12 hours of muscular repose — and unaffected by physical or mental exertion, or extraneous disturbance. Ba'sal Met"a-boI'ic Rate. — The percentage that the actual basal metabolism is above or below the normal standard for an individual of the same sex, age, weight, and height. Cal'i-brate. — To determine the caliber of; to establish graduations for an instrument, or to determine correct readings for a graduated instru- ment like a thermometer, or gasometer. Cal"o-rif'ic Val'ue. — Number of calories generated when 1 liter of oxygen combines with a combustible to form heat. The calorific value of 1 liter of oxygen when protein is burned is 4.485 ; when fat is burned, 4.686; when carbohydrate is burned, 5.047. Cal'o-ry, or Cal'o-rie. — The unit of quantity of heat is the small calorie, also called the gram calorie, written cal., the amount of heat required to raise one gram of water from 15° to 16 °C. Ca-tab'o-lism. — The series of changes by which living matter or pro- toplasm breaks down into less complex and more stable substances within a cell or organism; destructive metabolism. Closed Cir'cuit Ap"pa-ra'tus. — Designating the type of metabolism apparatus in which a person rebreathes the gases in a gasometer. Con-sump'tion of Ox'y-gen. — Volume of oxygen that is consumed and absorbed within the human system. Di-rect' Cal"o-rim'e-try. — The measurement of the heat eliminated by radiation and conduction together with the measurement of the heat ehminated by evaporation of water from the lungs and skin. Gas-om'e-ter. — A tank for storing, mixing, or measuring gas. In"di-rect' Cal"o-rini'e-try.— Method of determining the respiratory exchange; that is, the oxygen that is consumed and the carbon dioxid exhaled by a person in a known time. From these 2 factors it is possible to calculate not only the heat production, but also to apportion the amount of oxygen that was used for the burning of protein, fat, and carbohydrate in the body. Ky'mo-graf. — An instrument for recording various movements in the form of waves; used in metabolism tests to obtain grafic records of respirations. 16 DEFINITIONS 17 Me-tab'o-lism. — The act or process by which, on the one hand, the food is assimilated into living matter — which is called anabolism or building up; and by which, on the other hand, living matter is broken down within a cell or organism into simpler products — called catabolism or tearing down. (Originally MetaboHsm was strictly an ecclesiastical term.) Nor'mal Stand'ards. — The average basal metabolism for normal per- sons per unit of time: Normal Standards have been established from average results of extensive tests on normal persons. O'pen Cir'cuit. — Designating the type of metabolism apparatus in which a subject inhales fresh air. Re-sid'u-al Air. — The volume that is left in the lungs after a complete expiration. Res"pi-ra'tion Cal"o-riin'e-ter. — An apparatus designed for the measurement of the gaseous exchange between a living organism and the atmosphere which surrounds it, and the simultaneous measurement of the quantity of heat produced by that organism. A complete respiration calorimeter, therefore, combines within one apparatus two separate and entirely distinct methods: the one determining the heat production and the other the heat elimination, thus allowing a comparison of the two principles. Re-spir'a-tory Quo'tient. (R. Q.). — The ratio between the volume of carbon dioxid that is exhaled, and the volume of oxygen that is consumed in the same unit of time. Re-spir'a-tory Rate. — The number of respirations per minute. Spi-rom'e-ter. — An instrument for measuring the capacity of the lungs. Stand'ard Pres'sure. — Pressure of the atmosphere at sea level; it is equivalent to a column of mercury that is 760 millimeters high. Stand'ard Tem'per-a-ture. — Zero degrees Centigrade. Ti'dal Air. — The volume that is given out during each respiration. To'tal Ven"ti-la'tion. — Total volume of expired air. BASAL METABOLISM ITS DETERMINATION AND APPLICATION CHAPTER 1 NORMAL STANDARDS OF BASAL METABOLISM As the use of indirect calorimetry becomes more and more general as a routine aid to diagnosis in certain diseases, it becomes increasingly essential that accurate standards be available to clinicians by which they may judge of the normality or abnor- mality of the basal metabolism of their patients. It is, more- over, obviously desirable that in so far as possible, standards be uniform. "Basal metabolism has been defined as the condition of mini- mal or fundamental exchange, the irreducible minimimi of exchange of energy which is characteristic for the individual. It is the minimal activity of the body which maintains the func- tions of respiration, circulation, and secretion."^ It may also be considered as "the sum. total of all the Adtal activities of the quiet organism in the post-absorptive condition; i. e., the mini- mum of maintenance metabolism unaffected by extraneous factors. This may be expressed in terms of heat produced or of gaseous exchange incidental to heat production — carbon dioxid production and oxygen consumption. Using this basal metabolism as a standard, we may then measure definitely the superimposed factors."^ Normality of Subjects. — If standards are to be normal it is essential that the subjects used in establishing the standards be as near normal as is practicable. But one may well ask "What is normal?" Strictly speaking there is no such thing, because what is normal to one individual is not to another. Yet a person iLahey, F. H. and Jordan, S. M.: Basal Metabolism as an Index of Treat" ment in Diseases of the Thyroid — Boston Med. and Surg. Jour., 174: 348-358, April, 1921. 2 Benedict, F. G. and Talbot, F. B.^ Metabolism and Growth from Birth to Puberty — Carnegie Inst., Washington, Pub. No. 302, 1921. 20 BASAL METABOLISM who is in good health and has no abnormal physical character- istic has been generally accepted as meeting the requirements of the case. Uniformity of Conditions. — Granted that the subjects are nor- mal, we must next be assured of uniform conditions in the tests from which the standards are to be computed; in every instance the basal metabolic rate must be obtained. This point cannot be too strongly emphasized if the normals that are estabhshed are to be truly normal; and only strict adherence to it will make it possible to make comparisons between the findings of different researchists, both at present and in the future — a comparison which is highly desirable. Effect of Food, Posture, Sleep, Muscular Activity and Emotion. — The influence of all factors which are known to cause the metabolic rate to fluctuate should be eliminated during the tests. The effect of posture, food, sleep, mental anxiety or appre- hension, and muscular activity must all be reckoned with. In the words of Roth "the test is for the determination of the basal metabolic rate and not the metabolic rate as influenced by appre- hension, fear, fatigue, impatience, indignation, the tickling of a fly, discomfort, pain, or anything which increases muscular tension."^ It has been found that the metabolic rate in the sitting posture is higher than that in the reclining posture. Food in the stomach also raises the metabolism, and so in establishing normal rates it has been necessary, as in clinical tests, to have the patient in the post-absorptive condition. "The basal metabolism is al- ways measured fourteen hours or more after the last meal, because food stimulates the heat production. A meal containing 60 grams of protein can increase the metabohsm 10 or 12% for 6 or 7 hours. 100 grams of glucose may cause as great a rise, but for a shorter period. The stimulation from fat takes place much more slowly and does not reach its maximum until 6 hours after the meal. This stimulation caused by food is the specific dynamic action described by Rubner and studied in detail in the last few years by Lusk at the Cornell Medical College, New York City."" 'Roth, P.: Clinioal Observations with Benedict's New Portable Respiratioti Apparatus — Boston Med. and Surg. Jour., 184: 222-230, March, 1921. ■• Du Bois, E. F.: Basal Energy Requirement of Man — Jour. Wash. Acad. Sc, 6:347-357, June, 1916. NORMAL STANDARDS OF BASAL METABOLISM 21 The effect of sleep is slightly to lower the metabolism and in order that the accumulated tests may be strictly comparable it is advisable that all subjects be awake while tests are being made to establish normal standards. Any emotional disturbance, particularly fear and apprehension, will increase the metabolic rate and it is very important that such disturbances be obviated. "Muscular work affects metabolism to a far greater extent than all other factors combined. Even walking at a moderate gait may increase the energy consumption threefold, and riding on a bicycle ergostat may increase it sixfold."^ During severe, exhausting muscular work, almost at the limit of human endur- ance, the metabolism may be increased from 700 to 800 per cent. Bearing all these facts in mind in his endeavor to conduct uniform tests on normal subjects, still further problems await the researchist who would estabhsh normal standards. When the basal metabolism of an individual has been determined, shall it be considered in relation to his height, weight, body surface, or age? Relationship Between Age and Standards. — One would expect age to have a definite bearing on metabolism, and research has proved this to be true. "The level of the metabolism varies greatly with age. During the first few days of life it is very low, then rises rapidly during infancy, and reaches its highest level in the almost unexplored period between the ages of 2 and 6 years. After this it falls rapidly until about the 18th year when the curve flattens out. Between the ages of 20 and 40 there is com- paratively little change; but after this a slight fall, so that by the eightieth year the line is about 10 per cent, below the average level for the ages of 20 to 40. There seems to be a stimulation to the basal metabolism during the period of growth."* Body Surface and Metabolism. — The search for suitable standards has centered chiefly about the so-called body-surface law of Rubner who was the first to appreciate the relationship between metabolism and surface area. "Of course the heat pro- duction of a man depends largely on his size, but it is by no means proportional to the body weight. A large man gives off more heat than a small man; but for each kilogram of weight the small person has the higher metabolism. On the other hand the 5 Means, J. H. and Woodwell, M. N,: Remarks on Standards of Normal Basal Metabolism— Archiv. Int. Med., 27: 608-619, May, 1921. 22 BASAL METABOLISM metabolism of men of various sizes and shapes is rather closely proportional to the surface area of the body. Many years ago Rubner established this law of surface area and was able to show that mice, rabbits, dogs, men, and horses had almost the same metabolism per square meter of skin."^ The principle embodied in this law is that the basal metabolism is a simple function of the body surface. Even after the establishment of this principle, however, investigators were handicapt for years thru lack of an accurate method for measuring or calculating body surface. The formulas of Meeh and Lissauer, that determine body sur- face from body weight, are fairly accurate for persons of normal proportions. But for those who are tall and thin, or short and fat, it has been found that there is a considerable discrepancy between the actual area and the calculated area; this discrepancy at times amounts to 16 per cent. In 1914 Eugene F. Du Bois,® in collaboration with Delafield Du Bois, devised the so-called linear formula in which the body surface is computed from 19 measurements of the body. Casts were made of the bodies of 10 individuals who varied widely in form. "It was found that the area as calculated by theMinear formula varied on an average less than 1.7 per cent, from the areas as actually measured from the casts. It was with the advent of this formula that calorimetry became available to the clinician. In the linear formula, the clinical investigator is equipt with a method that will give him accurately the surface area of individuals of any shape. "^ "In 1916 the Du Boises brought out a still simpler formula: the so-called height- weight formula. This was worked out from the results obtained in a large series of persons by the linear formula, and enables one to obtain the surface area directly from the height and weight."^ The height-weight formula is ex- prest in the terms A = PF^^^^ X H°-^^^ X 71.84; 4 representing the surface area in square centimeters; W, the weight in kilo- grams; H, the height in centimeters; and 71.84 being a constant. By this formula Du Bois was able to calculate the true surface area within an average error of plus or minus 1.5 per cent, and a maximal variation of plus or minus 5 per cent. From this for- mula a chart has been plotted, as shown on page 245, which « Gephart, F. C. and Du Bois, E. F.: The Basal Metabolism of Normal Adults with Special Reference to Surface Area — Arch. Int. Med., 17: 902-914, June, 1916. NORMAL STANDARDS OF BASAL METABOLISM 23 makes it possible quickly to obtain the surface area of any individual whose height and weight are known. For very stout persons, however, it is still considered more accurate to use the linear formula. The criticism that there is no casual relationship between body- surface area and the metabolic rate has been brought forward by Benedict. Lusk meets this criticism in the following manner: "I believe that the Du Bois standards for basal metabolism can be relied upon, and I also believe that, tho one may doubt the casual relationship between surface area and heat elimination, such doubt will not iavalidate the arithmetic employed in the calculation. In making this statement I recall the words of Carl Voit, uttered regarding another matter: " 'I maintain this as an incontestable fact. It is so important that I question whether it is desirable to add a word of explana- tion. The results of a properly conducted and properly appre- ciated experiment can never be annulled, whereas a theory can change with the progress of science.' "The establishment of a predictable basal metabolism enabled those working with the Russell Sage calorimeter to interpret the variations from the normal in many diseased conditions and has offered a method now widely accepted thruout the world for a closer clinical diagnosis of several pathologic conditions."^ Having this formula to compute the body surface, the next step was the "establishment of accurate standards with which to compare the heat production in hyperthyroidism, for example, with the heat which the patient would presumably ha,ve produced had he been perfectly well."'^ Normal Standards for Adults. — Several well-known research- ists — notably Du Bois, Benedict, and Dreyer — have endeavored to establish normal standards with which to compare the basal metabolic rate in any individual pathologic case. Eugene F. Du Bois considered body-surface and age the most accurate physiological factors to which to refer the metabolic rate of individuals. After the Du Bois formula for computing body surface had been devised — a formula which is simple and much more accurate than the formulas of earlier researchists — he continued a series of tests on normals, and with the collaboration ' Lusk, G. : Fundamental Ideas Regarding Basal Metabolism — Jour. Am. Med. Ass., 77: 250-252, July, 1921. 24 BASAL METABOLISM of F. C. Gephart, published in 1916 a paper on "The Basal Meta- bolism of Normal Adults with Special Reference to Surface Area."® In this paper the authors state that the average meta- bohsm of fat and thin subjects is the same according to surface area when the surface area is correctly measured. Tentative normal standards were presented at that time but were later revised. Because of the paucity of data on the basal metabolism in old age, Aub and Du Bois undertook further study of basal meta- bolism of old men. It not being possible to find suitable subjects between 90 and 100 years of age, the age limits were reduced to between 75 and 85 years. Six men were obtained who fulfilled the requirements. Considering their ages they were in good health though they suffered from some of the pathologic condi- tions "which 'normally' accompany advanced years. "^ "The calorimeter findings on the group of old men can be com- pared directly with the findings on Boy Scouts and normal adults between the ages of 20 and 47. The experimental methods used with all of these subjects were the same in almost all par- ticulars. There was, however, one difference between the groups which could not be avoided. The younger subjects were active men on liberal diets, and almost all of them came to the calori- meter room from their homes on the mornings of the experi- ments. The old men were beyond the working age; they had been on rather meager fare, and they were all kept in the meta- bolism ward for several days before the tests were made. All of these factors tend to decrease the total metabolism in the same manner in which cage life affects a dog. Still they are part and parcel of old age. It would be difficult to find hard working men of 80 on large diets, or normal men in the prime of life leading the existence of octogenarians."^ It was necessary to exclude the findings for one of the six men tested because of the too great deviation from the mean. "The average basal heat production of the five men between the ages of 77 and 83 was 35.1 calories per square meter per hour, -which is about 12 per cent, below the average for men between the ages of 20 and 50. This depression in old age is about 7 per cent, less than had been assumed by one of us in a curve based on results ^ Aub, J. C. and Du Bois, E. F. : The Basal Metabolism of Old Men — Arch. Int. Med. 19: 823-831, May, 1917. NORMAL STANDARDS OF BASAL METABOLISM 25 obtained by other investigators. As one might expect, the depression of metabolism is somewhat proportional to the degree of senility . . . The methods of direct and indirect calorimetry agreed closely and the respiratory quotients were all within nor- mal limits."* At the suggestion of Drs. Means and Boothby, Du Bois, after considering the new data accumulated since 1916, revised his normal values for adults and in his paper on "The Basal Meta-. holism of Old Men"* published a new table of normal standards for the ages 14 to 80. CALOREES PER SQUARE METER OF BODY SURFACE PER HOUR HEIGHT-WEIGHT FORMULA — DUBOIS Age, Years Males Females 14-16 46.0 43.0 16-18 43.0 40.0 18-20 41.0 38.0 20-30 39.5 37.0 30-40 39.5 36.5 40-50 38.5 36.0 50-60 37.5 35.0 60-70 36.5 34.0 70-80 35.5 33.0 A further discussion of the normal values for individuals who are under 20 years of age will be found in the section on Normal Standards for the Age of Puberty. Benedict and Harris assert that the metabolism or heat output of the human body even at rest does not depend on Newton's law of cooling and, therefore, is not proportional to the body surface. They maintain that in predicting basal metabolism, "biologically, the most rational, and practically, the most satisfactory standard is that secured by taking into account the body weight, stature, and age of the subject."^ Each of these factors they believe has an independent influence upon metabolism. They have, there- fore, after a series of tests on normals, prepared two sets of tables, one of which shows the factor for a given body weight; the other, the factor for a given stature and age. After a factor ^ Harris, J. A. and Benedict, F. G. . A Biometric Study of Basal Metabolism in Man — Carnegie Inst., Washington Pub. No. 279, 1919. 26 BASAL METABOLISM is obtained from each table, the two are added together and the result is the normal total heat production of the individual per 24 hours. Example: For a man weighing 70.4 kilograms, 168 ren*-^- meters in height, and 42 years old, the weight factor is 1035 and the height-age factor is 557. The normal total metabolism is the sum of the two factors, or 1592 calories per 24 hours. A recent edition of the Harris-Benedict tables of normal values for adults may be found in "Tables, Factors, and Formulas for Computing Respiratory Exchange and Biological Transforma- tions of Energy," prepared by Thome M. Carpenter and pub- hshed by the Carnegie Institution of Washington in 1921. (Paper covered, 123 pages, price, $2.50). Dreyer^° has objected to the introduction of the standing height as a factor in the calculation of the surface area on the ground that it is not a physiologic measurement, and he regards the sitting height as a more normal expression. He has evolved a formula which is based on age and weight alone. He states that this formula indicates that basal metabolism is not a singrle function of body surface. FORMULAS FOR PREDICTING BASAL METABOLISM OF MALES AND FEMALES (DREYER) VW The formula for males is C= „.„,, , where C equals total 0.1015 X J°-^^^^ ^ calories per 24 hours, W equals body weight in grams, and J equals age in years. Example: Subject, 65 kilograms, 32 years. (1) Logarithm of W (63000) 2)4.81291 (2) vw 2.40646 (3) A X 0.1333 0.20064 (4) 0.1015 Sum of (3) and (4) 1.00647 (5) 1.20711 Subtracting (5) from (2) 3.19935 Calories per 24 hours 1583 f^vr. ,„io f„^ fo™oUo lo r — vw 0.1125 X ^0.1333 The terms and the method are the same as those used for males. '" Dreyer, G. : Normal Basal Metabolism in Man and Its Relation to the Size of the Body and Age. Exprest in simple Formulae — Lancet, 2: 289- 291, Aug. 1920. NORMAL STANDARDS OF BASAL METABOLISIVI 27 Normal Range of Variation. — "There is a normal range of variation amounting to plus or minus 10 per cent, from the average, and a few apparently normal individuals may depart as much as 15 per cent, from the mean. Curiously enough very fat people and very thin ones have almost exactly the same heat production, measured in this way, while there may be a difference of 30 to 40 per cent, between the two groups if we base the calculation on kilograms of bod}- weight . . . Women show an average basal metabolism about 7 per cent, lower than that of men of the same age. Athletes are about 7 per cent, higher than men of sedentary habits."* "Nearly every woman, whether normal or abnormal, has a menstrual history suggestive of a heightened metabolic rate before her menstrual period. Frequently there is emotional instability, excessive nervousness, some sensation of heat and even slight increase in perspiration."^^ The possibility of a periodic rise or fall in the metabolic rate of women, due to the influence of menstruation, has therefore been raised. Blunt and Dye have made 216 observations in the study of this question and reach .no definite conclusion. In the 17 sub- jects studied they found considerable fluctuation during the menstrual period; but this fluctuation was so irregular, bearing no apparent relation to the beginning or end of the period, and in several cases being no greater than the daily fluctuation found in many indi^"iduals during the intermenstrual period, that they consider it doubtful whether menstruation has am- appreciable effect upon metabolism. Rowe,'^ on the other hand, finds a rather definite relationship between changes in the metabolic rate of women and the men- strual period. He refers to a previous research by Snell, Ford, and Rowntree^' in which they find that "a rather constant rise occurs during menstruation or in the pre-menstrual period, the rise being followed by a post-menstrual fall." Of the 10 cases studied by them, 2 showed "practically constant rises and 6, constant rises var}-ing from 4 per cent, to 14 per cent., the average being 10 per cent., while in 2 a drop in rate was encountered. Values outside normal limits, + 10 per cent., were infrequent.' '' Rowe, A. H.: ^Monthly Fluctuations in the Normal iletaboUc Rate of Jlen and Women — Cal. State Jled. Jour., Aug., 1921. '^ Snell, A. il., Ford, F., and Rowntree, L. G.: Studies in Basal Jletabolism — Jour. Am. iled. Ass., 76: 515-523, Aug., 1920. 28 BASAL METABOLISM Kowe's study of the effect of menstruation on the metabolic rate of women up to the present time has been made with the modified Tissot apparatus on 6 subjects. His charts show "first, a uniform pre-menstrual rise occurring within the week preceding the onset of the period . . . ; secondly, that with the onset of menstruation or possibly a few hours before, the metabolic rate probably falls and may reach its lowest level during the men- strual period or within the following two weeks. "The rates in the cases observed fluctuate up to a maximum of from 13 to 18 points. "That menstruation influences the metabolic rates of women, therefore, seems quite probable. We feel that this menstrual influence should be recognized and taken into account in the establishing of a normal standard for women . . . Moreover, clinically, it is important for us to realize that the metabolic rate varies according to the menstrual cycles. No rate of a woman should be quoted without a record of the probable pre-menstrual and post-menstrual intervals. It is interesting to note that literature contains records of hyperthyroidism which is present only at menstruation. Such cases might have a post-menstrual rate of -j- 8 per cent, to -|- 12 per cent, and pre-menstrual rate of -1- 20 per cent to -j- 30 per cent., and unless the symptomatology were definite the diagnosis might be missed if only the post- menstrual rate were taken. A hypothyroid case might likewise be overlooked if a premenstrual rate of — 14 per cent, to — 10 per cent, were obtained. Of course the clinical manifestations are in all cases of the greatest importance."" From his rather limited observations Rowe concludes that "the menstrual cycle produces a definite metabohc curve in woman, the highest point being in the pre-menstrual week."" Relative Merits of Normal Standards. — The Du Bois height- weight chart with the Sage Institute standards has been very widely used for computing the normal metabolic rate for indi- viduals. The Harris-Benedict and Dreyer values have also a large number of advocates and the clinical calorimetrist may well be in doubt as to which of these, the Du Bois, the Harris-Benedict, or the Dreyer, he should use. Means and Woodwell,^ in a recent article, have presented a critical analysis of the variations between, and the relative accuracy of, these three current standards for the normal rate NORMAL STANDARDS OF BASAL METABOLISM 29 of basal metabolism. After a thoro study of the merits of the three standards they reach the conclusion that "in one sense it is really of small consequence which method the clinical calori- metrist uses, since the results obtained with the three are so similar. Uniformity, however, is always advantageous and it is best not to abandon an old method for a new one unless the new presents some material advantage over the old. The Du Bois method is the one in common use today. Since neither the Harris-Benedict nor the Dreyer methods have made any material improvement on it we believe it wise to continue with it, and especially in view of the fact that the existence of calorimetry in the clinic today is due in large measure to the work of Du Bois." Means and Woodwell in the same article suggest that a sub- traction of 1.8 calories from each of the Du Bois standards as the}' appear in the paper on "The Metabolism of Old Men" will render the difference between the Du Bois and the Harris-Benedict values so slight as to be almost negligible. Such a means would seem to present the most probable values and afford the highest degree of accuracy which is possible until further tests have been made. Accordingly, the following table has been prepared, the use of which is recommended. (The values for ages below 20 are probably more subject to change after further experiments than are the values for ages above 20). DU BOIS NORMAL STANDARDS OF BASAL METABOLISM WITH 1.8 CALORIES DEDUCTED (HEIGHT- WEIGHT FORMULA) Calories per Square Meier per Hour Age, Years Males Females 14-16 44.2 41.2 16-18 41.2 38.2 18-20 39.2 36.2 20-30 37.7 35.2 30-40 37.7 34.7 40-50 36.7 34.2 50-60 35.7 33.2 60-70 34.7 32.2 70-80 33.7 31.2 Normal Standards for Children. — The most extensive research on the metabohsm of children under 12 years of age, so far re- ported, is that made by Benedict and Talbot, the results of which 30 BASAL METABOLISM appear in a recent publication entitled "Metabolism and Growth from Birth to Puberty."^ In this research observations were made on 258 children from public and private schools and, in many instances, repeated observations were made on the same child in successive years. The research has been in progress nearly a decade. The general plan of study has been to make observations on the respiratory exchange of a large number of normal boys and girls that differ in age, height and weight and by a comparison of the average values thus obtained, to deter- mine the influence of age, height, weight and sex upon the heat production, to derive normal standards, and to establish the requirements of basal energy. Normality of Subjects. — For children as with adults in order to determine normal standards of basal metabolism the subjects should be normal. As to what factors govern the normal child it is customary to consider three factors: — height in relation to age, weight in relation to age, and height in relation to weight. In the past normality has been determined from height in rela- tion to age or, frequently from weight in relation to age. Altho the relations of age and height, or age and weight, cannot be ignored it is believed by Benedict and Talbot that these relations are not as important as height to weight. That is, in normal boys and girls the relation of first importance is not what is the age and the height, nor what is the age and the weight, but rather what is the height and the weight? Furthermore not one alone — age, height, or weight — is a sufficient index to use in selecting normal boys and girls, but rather height and weight together are recommended. After selecting a group of boys and girls who possess normal height and weight they may be classified as normal subjects and tests are then in order to determine normal standards of meta- bolism for these normal children. How shall the standards obtained from normals be exprest? In terms of age, body surface, or weight? Normal Standards Referred to Age. — Benedict and Talbot found that when the metabohsm of boys was referred to age and plotted in a chart, the points were widely scattered and there was "great irregularity in the grouping." The chart does, how- ever, show a rapid rise in the total metabohsm during the first year of hfe and, from the first to the thirteenth year, a somewhat NORMAL STANDARDS OF BASAL METABOLISM 31 slower but steady increase. The trend for girls from. 2 to 4 years seems to vary considerably from that of boys. Age does not appear to have a sufficiently definite or uniform influence upon the metabolism of children to render it advisable to express the normal values in terms of age. Normal Standards Referred to Body Surface. — When the total calories per 24 hours were referred to body surface and plotted on a chart, it was evident that the relationship between body surface and the metabolism of children was closer than the relationship between age and metabolism. In fact Benedict and Talbot feel that body surface affords a means of predicting the probable basal metabolism of a child with "reasonable accuracy" and that the total calories referred to body surface may be considered as distinctly helpful in indicating whether or not a given case has a great deviation from the general trend which is being tentatively established for children. In computing the body surface Benedict and Talbot believe that the Du Bois linear formula may properly be applied to children weighing 6.27 kilograms or under, but emphasize the superior accuracy of the old Lissauer formula for computing the surface areas of young children, as does Du Bois also. They recommend the use of a modified formula for computing the body surface area of children: Area=ii:v'lF In this formula W is the weight of the child in kilograms and K is a constant which varies with the weight of the child. There is also a slight difference in the constants suggested for boys and for girls as shown by the table: CONSTANTS FOR USE IN FORMULA FOR COMPUTING BODY SURFACE AREA OF CHILDREN.* Boys Constatit Girls Constant Upto6|kg. 10.0 Up to 6 kg. 10.1 6 to 15 kg. 10.6 6 to 10 kg. 10,6 15 to 25 kg. 11.2 10 to 20 kg. 10.8 25 to 40 kg. 11.5 20 to 40 kg. 11.1 * Prepared from Benedict and Talbot — Metabolism and Growth from Birth to Puberty. Having computed the body surface of a child, and having determined his basal metabolism in cubic centimeters of oxygen per minute, it becomes necessary to compute the total calories 32 BASAL METABOLISM produced by the child in 24 hours before comparing the figures with the curves on Benedict and Talbot's charts. No table, expressing the basal metabolism of children in terms of body surface, has been prepared since it was found that it was slightly more accurate to express it in terms of weight. Weight the Determining Factor in the Metabolism of Children. Altho body-surface area affords a useful medium for expressing the normal standards of basal metabolism for children and is a more accurate index than age, Benedict and Talbot consider the weight factor to be most influential in determining the metabohsm of a child, and their charts show that if the metab- bolism of children is referred to body weight the scatter of points is less. "With boys who have a body weight of 10 kilo- grams or above, more satisfactory results may be obtained in predicting the metabolism from a curve in which the calories are referred to surface." The same is true for girls. It should be remembered that during the period of growth "the factors of age, weight, and stature are intimately correlated, very much more so than is the case with adults. Adults weighing 70 kg. are much more likely to vary in stature than boys of 30 kg. Similarly, adults weighing 70 kg. may vary in age from early youth to old age, while the variation in age of boys weighing 30 kg. will be very much less. It is thus probable that the body weights of boys automatically include the variations in age and stature. For practical purposes, therefore, and until the meta- bolism of children is given biometric analysis, the prediction of the total basal metabolism of boys 10 kg. and above may be made with a reasonable degree of accuracy directly from the curve based upon body weight . . In every instance the prediction for boys is materially better than that for girls." Therefore, since it seems evident that weight is the most reliable factor to which to refer the metabolism of children, as well as being a very convenient one, Benedict and Talbot have prepared a table "giving the most probable heat production for each half kilogram of body weight for both boys and girls. They are not intended to be used for children above 12 years of age." If the weight of a child is known, the physician may read directly from the table on page 239 the predicted basal metabolism for a child of this weight and compare it with the heat production actually measured to note if the measured values are abnormal. NORMAL STANDARDS OF BASAL METABOLISM 33 It should of course be borne in mind that in physiology normal variations are so great as absolutely to preclude a mathematically established standard without deviations therefrom; and it is probable that variations within plus or minus 10 points in the metabolic rate may be considered as normal. Strictly Basal Standards Difficult to Obtain with Young Children. — The necessity for having patients in the post- absorptive condition — without food for 14 hours prior to the test — plainly cannot be applied to infants or very young children. It has in fact been proved that with infants the increase in the metabolic rate due to food in the stomach is extremely small when compared with the increase due to the cr3dng and restlessness which are attendant upon lack of food. Experiments on children under 2 years of age have, therefore, been run with food, and hence "the basal metabolism of children under 2 years of age can be compared with that of older children only on the distinct understanding that the values for the basal metabolism of the younger children are higher than they normally would be, owing to the influence of food." With children from 2 to 6 or 7 years of age the element of restlessness is greater than with older subjects, so that the standards for children up to 7 years of age are not strictly com- parable with those for adults. It is probable that all metabolism values established for children are higher than basal rather than lower than basal. However, the normal values established form a reliable basis for comparison with pathologic cases of the same age Then tested under similar conditions. Normal Standards for the Age of Puberty.— "During the later period of growth, from 12 to 17 years, one factor enters into the development of Ufe which produces pronounced psychological as well as physiological alterations in the body, namely, the influ- ence of puberty. ... It is quite clear, therefore, that serious consideration of the influence of puberty upon the metabolism of young children is a necessary accompaniment of any extended study of the vital activities of youth."'^ At present the age of puberty has not received sufficient attention to warrant the establishment of definite standards for 13 Benedict, F. G. and Hendry, M. F.: The Energy Requirements of Girls from 12 to 17 Years of Age — Boston lied, and Surg. Jour. Vol. 184, March and April, 1921. 34 BASAL METABOLISM basal metabolism, nor has it yet been determined how great an influence the establishment of puberty really has upon meta- bolism. An interesting study of the basal metabohsm of Girl Scouts between the ages of 12 and 17 years has recently been made by Benedict and Hendry.^^ They summarize their reasons for undertaking the research as follows: "Since the metabolism of girls has been considered experimentally very much less than that of boys, it seemed desirable, if possible, to begin our observa- tions with girls. A second incentive for studying girls was the lack of connection between the curve indicating the trend of metabolism of girls from birth to 12 years of age and the general slope of the line indicating that of women." The tests were made on groups of girls, not on individuals. Groups of 10 or 12 girls of nearly uniform age were selected from various troops of Girl Scouts. All the girls were selected on the basis that they were normal and in good health. It was difficult to avoid considerable variation in the height and weight of the individuals selected, but with the group system such variations play a relatively minor role. At the critical prepubertal and pubertal ages of 13 and 14 years groups were selected, as far as possible, in which the most decisive criterion of puberty in females, namely, menstruation, had or had not appeared. Each group received a light, uniform supper at the Carnegie Nutrition Laboratory and the girls engaged in no excessive muscular activity during the evening. Thruout the night they slept inside a respiration chamber and measurements of the carbon dioxid production were taken while they were in deep sleep. In this manner muscular repose and control of the factor of food ingestion were insured, and the computation of the probable heat production could therefore be made from the carbon dioxid output with a reasonably small error. At 10 o'clock the girls prepared for bed, and at this time record was made of their nude weight and height. They then entered the respiration chamber. The subjects were instructed to be quiet and to go to sleep as soon as possible. At the end of an hour ventilation was started, a sample of the residual air was taken for the calculation of the carbon dioxid in the chamber, and the first experimental period was begun. Periods of one half hour each were made from 11 p.m. to 2:30 NORMAL STANDARDS OF BASAL METABOLISM 35 a. m. They were then lengthened to an hour, and on the nights when the respiratory quotient was determined all ventilation was shut down for another hour and a half to allow the residual carbon dioxid to accumulate. Determination of the total carbon dioxid production during these periods with no ventilation was always made by analysis. During the last hour the ventilation was again started and the usual procedure followed. At 6:30 a. m. the cover of the respiration chamber was opened, the chamber rapidly ventilated with a high speed blower, and the resting pulse rate of each of the subjects was taken. After this the subjects were called, weighed carefully, and dismist. From the data which was accumulated from the tests, deter- mination of the actual minimum carbon dioxid production thruout the night was made; and since all the groups were studied under the same experimental conditions, we may compare the basal values that were determined for the different ages. The respiratory quotients ( — -^ ) for 4 of the 9 groups \ vol. O2 I observed were 0.81, 0.81, 0.78, and 0.79. The investigators were considerably surprised at these low respiratory quotients which were found 7 or 8 hours after a meal of approximately 500 calories. Yet one. can hardly question the accuracy of the Sonden apparatus for determining both carbon dioxid and oxygen, and all analyses were made by an experienced chemist. The deviations between the various quotients are so small as to justify the use of an average quotient, 0.79. From the practical standpoint this average quotient made it possible for the investi- gators to select the most accurate calorific value of carbon dioxid to be employed in the computation of the energy transformation. Accordingly, they used 3.086 calories as the calorific value of a gram of carbon dioxid and the heat production has been computed by multiplying the carbon dioxid by this factor. The essential findings in this research may be summarized as follows: The average basal heat production of groups of girls from 12 to 17 years of age was 1250 calories per individual for 24 hours. The heat production per kilogram of body weight decreases regularly with increasing age from 29.9 calories for 24 hours at 12 years, to 21.7 calories at 17 years. The results indicate that 36 BASAL METABOLISM the general metabolic trend is materially below the few scattered observations of earlier writers. The heat production per square meter of body surface like- wise decreases, but not so regularly, with increasing age, ranging from 928 calories for 24 hours at 14 years to 745 calories at 16 years. The prediction for the heat production per unit of body weight appears to be somewhat more accurate than that per unit of surface area. None of the results clearly prove any influence of puberty, or of the prepubescent stage on the heat production. BENEDICT-HENDRY NORMALS FOR GIRLS FROM 12 TO 17 YEARS PREPARED FROM TESTS ON GIRL SCOUTS Age of Girls Calories per kilo, per 24 Hours 12 30.9 121-^ 29.9 13 28.8 13K 27.7 14 26.7 143^ 25.7 15 24.6 153^ 23.6 16 22.6 l^Yo 21.7 17 21.2 The conclusions which Benedict and Hendry draw, and the tentative normal standards of basal metabolism which they present for girls from 12 to 17 years of age are of distinct value as a basis of comparison for investigators who have the facilities for performing tests under similar conditions. Since the differ- ence noted between the Benedict-Hendry standards and the Du Bois standards for girls of ages 12 to 17 is too great to be entirely accounted for by the difference in experimental con- ditions, it is evident that further investigation is necessary before we can know exactly what standards are normal for the age of puberty, and the extent to which the establishment of puberty influences basal metabolism. Perhaps the most pronounced effect of approaching puberty upon metabolism is that reported for boys by Du Bois. He found a high specific metabolism with boys at the age of 12 and NORMAL STANDARDS OF BASAL METABOLISM 37 13 years, while with the same boys 2 years later, after puberty was thoroly established, he found the metabohsm was consider- ably lowered. He made observations on boys of 12 and 13 and, after an interval of 2 years, repeated observations on these boys, as well as making further observations on boys of 12 and 13. In reporting this second set of experiments, he makes the follow- ing statement. "Altho the majority of the boys come a little below the line that was drawn 2 years ago, the change is not great enough to make it advisable to draw a new curve. The important fact remains that there is a rapid fall in metabolism during adolesence. The average decrease for the 7 satisfactory cases studied is 13 per cent. Their average metabolism at the ages of 14 and 15 years is 44.1 calories per square meter per hour, which is 11 per cent, above the average for adult men between the ages of 20 and 40 years. In the 3 youngest boys the meta- bolism during the 12th year was actually greater in calories pro- duced than during the 14th year, altho the boys showed a gain in weight of between 35 and 50 per cent."^* DU BOIS NORMAL STANDARDS FOR BOYS OF 12 TO 14 — TENTATIVE VALUES CALORIES PER SQUARE METER PER HOUR Age in Years Calories 12 to 13 50.7 14 to 15 44.1 Benedict and Talbot are at the present time studying the age of puberty in boys. From the limited data that has been obtained thus far they are inclined to disagree with Du Bois and they believe that, prior to puberty, there is no tendency for a change in the general trend of basal metabolism. The foregoing discussion clearly demonstrates that the physi- cian who attempts to compare the basal metabolism of patholo- gic cases between the ages of 12 and 19 with a definite normal standard will find it necessary to choose between the widely divergent values of Benedict and Hendry, and Du Bois, which have just been quoted. Pending further experiments, the con- tinued use of the Du Bois normal values is recommended with- the deduction of 1.8 calories, for the age of puberty, as for adults. These values are given on page 29. 1' Olmstead, W. H., Barr, David P., and Du Bois, E. F.: Metabolism of Boys 12 and 14 Years Old — Arch. Int. Med. 21: 621-626, May, 1918. 38 BASAL METABOLISM The Flexibility of Standards. The statement has been made that "there is no inflexible standard for normal metabolism for any given age, weight, height, and sex from which all normal individuals never vary."^^ This is of course true. "It would also be true if applied to other physiologic data of clinical value commonly determined, such as the temperature, the systolic and diastolic blood-pressure, the pulse rate, the acuity of hearing and vision, and the like."^® It does not hinder us from using normal standards for temperature and blood pressure. Neither should it prevent us from using approximately normal standards for normal basal metabolism as a guide in the study of pathologic conditions. However, care in the interpretation of metabohc findings cannot be overemphasized and Benedict has sounded a fitting word of caution: "The interpretation of metabolism results is not a simple rule of thiunb procedure. In fact, the interpretation of results now far exceeds in complexity the actual laboratory technic. The technical stumbling blocks to the advancement of metabolism studies in clinical medicine have, we believe, been overcome. The great intellectual stimibling block, namely, lack of education with regard to the significance of metabohsm measurements, cannot be overcome by the efforts of any one laboratory, one school, or one teacher. Before using gaseous metabolism measurements, it behooves every physician to familiarize himself thoroly with the fundamentals of gaseous metabolism and its significance."^® Greater Uniformity and More Permanent Value in Future Experiments on Normals.— Talbot has made a plea for uniform- ity in the experimental conditions under which future researches on basal metabolism are conducted. This is in order that the results may be of greater and more permanent value. "It is the duty of 20th century experimenters to make experiments of more than passing value. Each experiment should contribute to our fundamental knowledge. Each year sees an increase in the significance of normal values; an effort therefore should be made to secure normal values which will be of service not simply in the current year, but for a decade. In other words, experi- 15 Benedict, F. G. : The Measurement and Standards of Basal Meta- bolism—Jour. Am. Med. Ass. 77; 247-250, July, 1921. i^Boothby, W. M. and Sandiford, I. S.: — Basal Metabolic Rate Deter- minations, W. B. Saunders, 1920. NORMAL STANDARDS OF BASAL METABOLISM 39 ments on normals should serve not only their immediate purpose but should invariably contribute toward the sum of the knowl- edge of basal metabolism requirements of normal subjects."^ A brief summary of this chapter together with a full ex- planation of the method of computing the metabolic rate of individuals from the Du Bois, the Harris-Benedict, and the Dreyer standards will be found in the next chapter. CHAPTER 2. NORMAL STANDARDS AND METHODS OF COMPUTATIONS. Fundamentals of Basal Metabolism. — It should be emphasized at this point that the correct computation of the metabolic rate is comparatively simple, whereas the correct interpretation and application of the results demands a thoro understanding of the fundamentals that underlie basal metabolism. A careful reading of Chapter 1 is, therefore, advised in order to obtain a knowledge of the importance of normal standards of basal metabolism, the fundamentals underlying their establishment, and the modes of procedure which have been followed in determining these normal standards. Before discussing the methods of computing the metabolic rates of individuals from the values which have been determined as normal standards of basal metabohsm, it seems advisable to review briefly the salient points in the fore- going chapter. Definition of Basal Metabolism. — Basal metabolism is the irreducible minimum of exchange of energy which is character- istic for the individual; the sum total of all the vital activities of the quiet organism in the post-absorptive condition. It may be exprest in terms of heat produced or of gaseous exchange incidental to heat production — carbon dioxid production and oxygen consumption. Normal Standards of Basal Metabolism. — ^In establishing standards of basal metabolism which purport to be normal, care must be taken that the metabolic rate which is obtained is basal. It may be true that basal metabolism is not strictly pro- portional to, nor determined by surface area, but it appears to be more nearly proportion^ to area than to any other factor so far discovered. The standards for women are 7 per cent, lower than those 40 NORMAL STANDARDS AND COMPUTATIONS 41 for men, and it seems probable that in considering the meta- bolism of women the influence of menstruation should be con- sidered. In comparing the metabohsm of a pathologic case with the normal rate, it must always be borne in mind that the standards are not inflexible. The standards for adults, old age, and children may be con- sidered as approximately accurate. The standards for the age of puberty are tentative only. The Modified Du Bois Standards for Adults. — The normal standards as proposed by Du Bois, Benedict, and Dreyer each have unique m.erits, but it seems best, in the interests of uni- formity, to continue to use the standards established by Du Bois with 1.8 calories deducted from each value for ten year periods since Means, after a thoro study of the merits of the three standards concludes that neither those of Benedict nor of Dreyer have made definite improvements over tho^of Du Bois. Lusk confirms this opinion. The Du Bois standards as modified by recent suggestions may be found in the table on page 29. The Benedict-Talbot Standards for Children. — For children it seems best to use the standards recently established by Benedict and Talbot after 258 observations on children from one to twelve years of age. These values are given in the table on page 239. Normal Standards for the Age of Puberty. — For the age of puberty the use of the modified Du Bois standards is recom- mended. See table on page 29. As has been emphasized in the foregoing chapter, the values for the age of puberty are merely tentative. Moreover, the different researches have not been conducted under similar conditions, nor have the results been referred to the same factors. Until the results of further researches have been reported and the relative merits of these findings have been determined, it would be misleading to plot a continuous curve for normal values from infancy to old age. For the same reason it is inadvisable to present a continuous table of values. Methods of Computing Normal Basal Metabolism. — The fol- lowing examples illustrate methods of computing normal basal metabolism for adults, children, and the age of puberty by the modified Du Bois standards, the Sanborn tables, and the Bene- dict-Hendry standards. 42 BASAL METABOLISM Computations of Normal Standards for Adults (20 to 80 years). — Case No. 1: Male; age, 25; height, 175 cm.; weight, 70 kg. The method is in bri ef to multiply the number of cal- ories tha t are req uired for one sqiiare meter by the number of square meters in the body surface, thus to obtain the total calorieSj or normal FasaT metabolism of an individual. The calories required per hour per square meter are given in a table on page 25; for Case No. 1, 37.7 calories per square meter per hour. To find the number of square meters in the body surface of Case No. 1, refer to the Du Bois height-weight chart, page 245; follow the vertical line representing 70 kg. and the horizontal line representing 175 cm. until they intersect; the surface area may be read at the point of intersection as approximately 1.84 square meters. The above is the common method of finding surface area. A new method of finding surface area is presented by the table on page 246. Enter the table with the 175 cm. and 70 kg. of Case No. 1; the body surface is directly read as 1.85 square meters. This makes a simple and quick method of finding body surface area. The table has been computed by logarithms from the Du Bois height-weight formula. After the body surface area has been determined, whether by reference to the chart or the table, multiply by the calories per square meter. For Case No. 1 it would be 37.7 X 1.85, or 69.74 calories per hour, as the normal basal metabolism. Since by the indirect method the patient'sjnetabolism is usually measured in cubic centimeters of oxygen per minute, it is necessary for purposes of comparison to convert the calories of heat per hour into cubic centimeters of oxygen per minute. This is accomphshed by use of the formula cals. per hr. 1000 (c. c. in a liter) 4.83 (cals. per hter of oxygen) 60 (min. in an hr.) = c. c. of oxygen consumption per minute. A table of oxygen consumption equivalents has been prepared from this formula for 30 calories to 90.5 calories inclusive. By turning to this table (page 237) it is possible to read directly from the calories, the cubic centimeters of oxygen consumption per minute. For Case No. 1, the oxygen consimiption corre- NORMAL STANDARDS AND COMPUTATIONS 43 spending to 69.74 calories of heat poduction is found to be 241 c. c. per minute. Computation for Children (l to 12years). — Case No. 2: — Sex, female; age, 10; height, 132 cm.; weight, 29 kg. To compute the normal basal metabolism of this case from the Benedict and Talbot standards (see page 239) we find 29 kg. in the weight column and select the corresponding figure in the column for calories per 24 hours for girls — 1020 calories. Again, by the table on page 237 the equivalent of 1020 calories is 147 c. c. per minute — the normal basal metabolism of Case No. 2. Computation for the Age of Puberty (12 to 20 years). — Case No. 3: — Sex, male; age, 14; height, 148 cm.; weight, 40 kg. To compute the normal basal metabolism of this case by the modified Du Bois method, follow the procedure given for Case No. 1. Case No. 4: — Sex, female; age, 17; height, 160 cm.; weight, 52 kg. The basal metabolism of this case may be computed in three ways, i. e., by the modified Du Bois standards, by the Sanborn tables, or by the Benedict-Hendry standards. 1. By the Modified Du Bois Standards. — Turning to the table on page 29, we find the normal heat production per hour per square meter of body surface for a girl of 16-18 years to be 38.2 calories. Determining the surface area from the height- weight table on page 246, we find it to be 1.52 square meters. 'H Multiplying 38.2 calories by 1.52, we get 58.1 calories, the normal / basal metabolism per hour for this patient. Next we turn to the table of equivalents (page 237) and find opposite 58.0 calories — 200 c. c, the normal consumption of oxygen per minute for Case 4. 2. By the Sanborn Tables (based on the modified Du Bois standards). — Case 4: Sex, female; age, 17; height, 160 cm.; weight, 52 kg. We find 52 kg. and 160 cm. on the table. By following down the coliunn for 160 cm. to the point where the predictions for 52 kg. cross it, we find 196 c. c, the normal con- stimption of oxygen for a man of 20 of the same height and weight. Add 10 per cent, to obtain the basal metabolism of a boy of 17, and from this subtract 7 per cent, for sex, the final result being 201 c.c. ^3. By the Benedict-Hendry Standards. — Case 4: Sex, female; age, 17; height, 160 cm.; weight, 52 kg. In the Bene- dict-Hendry table we find that the normal standard of heat pro- 44 BASAL METABOLISM duction for a girl of 17 is 2L2 cals. per 24 hours per kg. There- fore, since this patient's weight is 52 kg., her normal heat pro- duction per 24 hours will be 2L2 cals. X 62 = Il021ijals7~per 24 Tiour sror 4 5.9 cals. per hour. KeSttce^lnrToT;. c. of oxygen pgf^inute (seerpage~2^T; ahar the normal consumption for Case No. 4 proves to be 159 c.c. per minute. The wide diSef ehce TJetween the results obtained by the Bene- dict-Hendry standards and those by the m.odified Du Bois- standards (or by the Sanborn tables) has been previously dis- cust in the Chapter 1, the section on "The Age of Puberty." Normal values for this Age have not been well estabhshed and further tests are now being made. CHAPTER 3 PREPARATION OF PATIENT By John Walker Moore, M. D. Interpretation of "Basal." — ^The rate of metabolism of an indi- vidual, in health and in disease, is subject to marked physiolo- gical fluctuations. The physiological variations must be re- duced to a minimum in order to establish a convenient basis for comparison of m.etabolism of different individuals, or of the same individual on different occasions. The term universally selected to designate this basis is known as Basal Metabohsm, and may be defined as the minimiun heat production of an organism at complete muscular rest and in a post-absorptive condition, or, as Harris and Benedict^ have exprest it, the cata- bolism in the absence of muscular activity and the stimulating influences of recently ingested food. It must be borne in mind that the modern conception of basal metabolism does not mean the lowest possible metabolism, for Benedict has shown that the metabolism during sleep sinks to a lower level than when the patient is awake and in complete muscular repose. Physiological Factors. — In order to prepare the patient so that the pathologic variations in metabolism can be correctly interpreted, it is essential to reduce to a minimum the fluctua- tions in metabolism that are physiologic in origin. The two main physiologic factors that influence the rate of metabolism in man are: first, muscular activity; and second, the ingestion of food. Muscular Activity. — Benedict^ has shown that a trained ath- lete was capable of increasing his basal metabolism eight-fold by doing severe muscular exercise in form of bicycle riding, and that the metabolism was maintained at a high level for a considerable period after the cessation of work. Zuntz^ and his associates found that walking on a level at a 1 Harris, J. A., and Benedict, F. G.: The Varialion and Slatistica Constants of Basal Metabolism in Men. — Journal Biol. Chem., 46, 257-279 1921. 2 Benedict, F. G., and Emmes, L. E.: A compaiison of Basal Metabolisml of Normal Men and Women.— Journal Biol. Chem., 20: 263-299, 1915. 3 Hewlett, A. W., Pathological Physiology. Appleton, 1917. 45 46 BASAL METABOLISM moderate pace increased the metabolism about 3 times, while walking rapidly on a level increased the metabolism about 5 times above the basal value. In attempting to produce a con- dition similar to that present in patients coming from their homes to an office or hospital for basal metabolic rate determina- tion, Snell et al.* found that immediately after walking 300 yards, or up 2 flights of stairs, the metabolic rate was increased on an average of 58 per cent. They conclude that these patients would revert to a basal condition in one-half to one hour, if allowed to rest. Slow periodic raising and lowering of the arms, repeated 2 to 3 times per minute, or even the regular movements of the fingers have been demonstrated by Speck®, Stuve® and others to raise the oxygen consumption 10 to 20 per cent. The work of mastication, such as would be involved in chewing gum con- tinuously, may increase the heat production 17 per cent. Muscular Activity — Result of Discomfort. — Emmes and Riche® found that the consxmiption of oxygen averaged 7.6 per cent, higher with the patient sitting upright in a chair with the head supported, than when lying flat in bed. Boothby and Sandiford,'^ using the gasometer method, found no constant variation in the metabolic rate when patient was either sitting in straight back chair or lying flat in bed. Of the 25 cases studied, 13 showed an average increase of 7 per cent., and 9 showed an average decrease of 5 per cent, when sitting, while 2 cases showed no change as the result of position. They believe the slight variation found to be due in all probability to a more complete muscular relaxation in one instance than in the other. Magnus-Levy® calls attention to the alterations of the body position as a whole, or of the limbs, or even an uncomfortable position which tends to keep muscles on the stretch, as causing a raise in the oxygen consumption 10 to 20 per cent, or higher. Soderstrom et al.* found the metabolism averages 3 per cent. ■• Snell, A. M., Ford, F., and Rowntree, L. G.. Studies in Basal Meta- bolism. Jour. Am. J\Ied. Ass., 75: 516, 1920. 5 Von Noorden's Metabolism and Practical iledicine, Vol. 1: The Physiology of Metabolism. Keener and Company, Chicago, 1907. * Emmes, L. E., and Riche, J. A.: The Respiratory Exchange as Affected by Body Position.— ?imer. Jour. Physiol. 27; 406-413, 1910-11. ' Boothby, W. M., and Sandiford, Irene. : Laboratory Manual of the Technic of Basal Metabolic Rate Determination. Saunders, 1920. 8 Soderstrom, G. F., Meyer, A. L., and Di Bois, E. F.:. Clinical Calori- metry Paper XI. A comparison of the Metabolism of Men Flat in Bed and sitting in a Steamer Chair. — Arch. Int. Med., 17: 872, 1916. PREPARATION OF PATIENT 47 lower with patients in the semi-rechning position than when lying flat at rest. Other conditions that may produce an increase in the rate as the result of discomfort may be enimierated. The desire to urinate; this may be so urgent that the rate is increased 20 per cent., as was found in one of the writer's series; particularly is this true in cases of diabetes insipidus. Women with hair arranged in a knot in back of head often suffer discomfort as the result of pressure of hair pins. Tight fitting articles of dress, as corsets, collars, coats, etc., as well as strong lights so arranged that their rays shine directly in patient's eyes, all produce a measureable increase in metabolism. The discomfort that is frequently complained of by patients as the result of using ill- applied or ill-arranged breathing appliances is a factor that must constantly be borne in mind as a potential cause of increased oxygen consumption. The extent to which ventilation or oxygen consumption re- turns to normal depends upon the amount of work done. A. Loewry® found the oxygen consumption returns to normal 4 to 9 minutes after medium work, and 20 minutes after fatiguing work. After severe work there was a slight rise after 20 minutes of rest. Benedict and Cathcart® report a case in which there was an increase in the basal metabolism for from 5 to 6 hours after the subject rode a bicycle for 70 minutes, doing work equivalent to 2.06 calories per minute. As has already been pointed out, Snell et al.* believe that the increased metabolism brought about by a patient coming to hospital or of&ce for a metabolic rate determination becomes basal as the result of complete rest for one-half to one hour. Boothby and Sandiford's'^ conclusion, based upon much experimental data, is that 20 minutes is a sufficiently long rest to insure a basal condition, provided no strenuous exercise precedes the rest period. Effect of Food, — Studies in metabolism have shown that there is liberation of heat after the ingestion of food and that this may last for 12 hours or more. The heat production is greater following the ingestion of protein than any other food stuff. In man, according to Gephart and Du Bois^°, the ingestion " Lusk, G. Science of Nutrition, Philadelphia, Saunders, 3rd Edition, 1917. 10 Gephart, F. C., and Du Bois, E. F. Clinical Calorimetry, Paper IV. The Determination of the Basal Metabolism of Normal Men and the Effect of Food. Arch. Int. 15: 835, 1915. 48 BASAL METABOLISM of 200 grams of glucose or 105 grams of nitrogen in form of casein increases the heat production about 12 per cent, over a period of from 3 to 6 hours. With a larger protein meal, con- sisting of 239 grams of nitrogen in the form of chopped beef and 100 grams of fat, these writers found the basal metabolism was much increased, showing a plus 26 per cent, at the end of 10 hours. Lusk found the heat production in man increased 46 per cent, after the ingestion of a large protein meal, and the increase did not disappear for about 12 hours. Soderstrom, Barr and Du Bois^^ studied the effects of a selected standard breakfast consisting of a shce of bread (20 grams), butter (8 grams), 200 c. c. of caffein-free coffee, contain- ing 10 gram.s cane sugar and 60 c. c. of milk. This breakfast contained protein, 4.7 grams, fat, 9 grams, and carbohydrates 28.9 grams. They found that in the first hour foUowing the ingestion of the food the average heat production was increased 7 per cent., in the second and third hours, 2 per cent., in the sixth and seventh the metabolism was slightly lower than basal. They believe a post-absorptive condition is reached 5 hours after the ingestion of the standard breakfast. Lusk" points out that the increase in metabolism following the ingestion of glucose dissolved in cold water, is the result of the effort of the individual to provide for the body heat lost to the fluid in the stomach. This author cites from Tangl's laboratory the findings of greater metabolism in man after the ingestion of a liter of cold milk than after taking the same amount when warm. It has been shown that after the ingestion of 500 c. c. of water at 20° C, the original temperature of the stomach is not regained for from 70 to 75 minutes. Miscellaneous Physiological Causes of Abnormal Oxygen Consumption. — Many patients, intelligent or otherwise, especially the latter, appearing for the first time to have their metabolic rate determined, are nervous and restless from appre- hension. Though in most instances they desire fully to co- operate, still there remains a secret fear which prevents a basal condition. 11. Soderstrom, G. F., Barr, D. P., and Du Bois, E. F.: Clinical Calori- metry, Paper XXVI. The Effect of a Small Breakfast on Heat Produclion. — Arch. Int. Med. 21: 613-620, 1918. PREPARATION OF PATIENT 49 A cold bath, especially when taken before breakfast, causes a great increase in metabolism. Lusk® quoting Rubner's experi- ments, showed that a tub bath at 16°C., taken before breakfast, increased the oxygen consumption 46.8 per cent.,whereas a douche at 16°C. increased the oxygen consimiption 110.1 per cent. The metabolism remains increased for about one and one-half hours. This author states that a bath of 35°C. has no effect on metabolism. It has been found that an imperceptible air current may have a profound influence upon metabolism. Rubner has show^n that wind, having a velocity of 0.18 meter per second, acting upon the exposed area of the arm, increased the heat loss between 19 and 75 per cent, depending upon the temperature of the wind. Snell et al.* found a rather constant rise in metabolism during menstruation, or in the premenstrual period, the rise being followed by a post-menstrual fall. The average rise in cases studied was 10 per cent. In the early weeks of pregnancy, there is little or no increase of metabolism above the normal; however, in Baer^s^^ series, the curve showed a gradual rise from a plus 26 per cent, in the thirty-fourth week to a plus 33 per cent, in the fortieth week. The rate became normal about the eleventh day of post-partum. Benedict found, in fasting or otherwise, that there is a diurnal variation in metabolism amounting, in a fasting subject, to an increase of 14 per cent, of the morning metabolism and 22 per cent, in the late afternoon over the metabolism during sleep. Smoking a cigarette up to within one and one-half hours of the test apparently has little effect upon metabolism. To determine the effect of smoking upon basal metabolism, six normal fourth year medical students were studied. In all the determinations, the subjects were allowed to smoke a cigarette one and one-half hours before the initial test. On the following morning the test was repeated without smoking. Four of the subjects smoked regularly, but not before breakfast. Their metabolic rates were increased after smoking on an average of 3.2 per cent, the highest being 5.9 per cent. One of the subjects had never acquired the habit, but usually smoked once or twice 12. Baer, J. L.: Basal Metabolism in Pregnancy and the Puerperium. — ■Am. Jour, of Obst. and t ynecology, 2: 249-25-5, 1921. 50 BASAL METABOLISM a month; in his case the rate was increased 1.3 per cent, after smoking. The other subject had been an inveterate smoker up to 2 years ago, since that time he has refrained entirely from the use of tobacco. His normal metabolic rate was plus 2.6 per cent., after smoking it was minus 1 per cent, a decrease of 1.6 per cent. Altho this series is too small to draw definite conclu- sions, the evidence shows that a cigarette smoked in a limited time before the test has little effect upon metabohsm. Routine Preparation of Patients for Obtaining a Basal Con- dition. — In order to obviate false metabolic rates as the results of the physiological factors that have been pointed out in the above, we recommend the following routine procedure to be carried out on all patients to be tested: 1. Patient is told to refrain from violent or fatiguing mus- cular exertion the day before the test, and to retire not later than 10 o'clock that evening. 2. He is directed to eat a light supper, preferably without meat, not later than 7 o'clock the evening before the test; water but no food may be taken before bed time. 3. No breakfast, drugs, and preferably no water are to be taken the morning of the test, however a glass of moderately cold water, an hour and one half before the test, will probably not alter the rate. 4. A cold bath should not be taken on the morning of the test. 5. Smoking should not be permitted the morning of the test, unless the patient is in the habit of indulging before breakfast, and then, not within one and one half hours of the determination. 6. The patient should present himself at the metabolic station at 8 or 8:30 A. m. If in hospital, he should be brought in a rolhng chair or on a litter; if ambulatory, he should refrain as far as possible from muscular exertion. 7. All stiff or constricting garments, as corsets, collar, belt, shoes, etc., should be removed, and women should take out all hair pins and combs. It is advisable that women should be pro- vided with kimona. 8. Patient is directed to empty bladder, and also the bowels if necessary. 9. Patient is taken to metabolic room, which should be done PREPARATION OF PATIENT 51 in cheerful but subdued colors with no unshaded lights; in addi- tion, it should be well ventilated, altho without perceptible air currents, and the temperature maintained between 65 and 70° F. 10. The operators should be kind, sympathetic, and, above all, gentle. One of them should show the apparatus and explain the harmlessness of the test to the patient, assuring him that he is to breathe pure air or oxygen, and that an operator will be on hand during the entire test period. 11. Patient is put to bed lying on his back and is made as comfortable as possible with one or two pillows as desired; chewing gum, etc., removed from mouth. 12. If patient appears restless or apprehensive a preliminary test lasting from 3 to 4 minutes is carried out. The breathing appliance is then removed and the rest begun. He should be instructed that at no time is he to assist in adjusting the breath- ing appliance. 13. The rest period for hospital patients should be maintained for from 20 to 30 minutes; for ambulatory cases, 30 to 60 min- utes, depending upon the extent of the previous muscular exer- tion. It is essential during this period to secure complete relaxation, and for this reason it is absolutely necessary to pre- vent anything that may tend to excite the patient, such as dis- comfort, noises, conversations, and friends or visitors. If the latter part of rest period is disturbed, as by movement, it should be extended 5 to 10 minutes longer, depending upon the degree of exertion. 14. To assure cooperation, and at the same time to allay any secret apprehension, with all patients a trial test should be carried out immediately before the actual test. 15. Temperature, pulse and respiration should be taken after patient is at rest in bed, but before the preliminary test. Pulse and respiration should be taken several minutes after this test, and again during the prelimimary and trial tests, as well as at 5 minute intervals during the actual test. 16. After the test has been completed the patient is weighed, nude, and height taken in bare or stocking feet. All restlessness and nervousness, irregularity in breathing, swallowing, etc., should be carefully noted and recorded. Shoxild 52 BASAL METABOLISM the patient appear extremely restless, enough so as to cause a pathologic change in the basal metabolic rate, he should be told to come back for another test at some future date. This has the preference over attempting to secure a normal rate in a nervous individual by repeating the test in the same day. CHAPTER 4 GAS ANALYSIS METHODS Gas Analysis Methods^ comprise theZuntz-Geppert Apparatus that was developt in Germany about 1890; the Atwater Calori- meter, in America, just before 1900; the Tissot Gasometer, in France, about 1900; the Douglas Bag, in England, about 1910; and various modifications of the Tissot Gasometer that have been developt in America since 1900. This chapter describes briefly the Douglas Bag Method, and the Gasometer Method, with special reference to details of Gas Analysis. The chapter that follows continues the Gas Analysis Method with special reference to the technic of the Gasometer that is used at the New York Post- Graduate Hospital; this technic is similar to that of the Mayo Clinic. Douglas Bag Method. — This method is used principally in England. In America it has been used but very little. The method may be briefly explained by stating that the subject breathes fresh air and exhales into a rubber bag that serves as a container, or gas bag. The exhaled gas is measured in volume, usually by passing it out of the bag thru a meter; the component parts of oxygen and carbon dioxid are then determined by chemical analysis. The illustration shows the way the apparatus is arranged for demonstration. When a patient is reclining or lying in bed, the gas bag may be suspended from a hook on the wall, from a bed post, or from the back of a chair. The bag should have a free chance to expand. The apparatus was developt by Dr. C. G. Douglas, and it was described by him in the Journal of Physiology, London, 1911. The subject breathes thru a mouthpiece or face mask that is connected with inspiratory and expiratory valves; fresh air enters thru the nose and the exhaled air passes out thru the mouth and into the bag, as shown by the arrangement in the cut. 1 A Comparison of Methods for Determining the Respiratory E.xchange of Man, by Thorne M. Carpenter, Carnegie Inst, of Washington, Pub. No. 216, 191.5. 53 54 BASAL METABOLISM Or, by placing a nose clip on the nose, and thus preventing nasal respiration fresh air will enter thru the inspiratory valve which opens during a inspiration and automatically closes during expira- tion, when the expiratory valve will open to allow passage of the expired air into the bag. This principle hkewise apphes when a face mask is used: namely, the inspiratory valve opens only during in- spiration, the expiratory valve only dur- ing expiration. In connection with the Douglas Bag, there is usually a three-way valve which permits the subject to breathe into the open for a few minutes before the test, and into the bag during the test period of 10 or 15 minutes. The three-way valve is then closed and the apparatus removed from the patient. The rubber pipe is disconnected from the expiratory valve and attached to a gas meter. The gas is thoroly mixt by repeated pressure on the bag, the three-way valve opened and, while the volume of gas is being measured thru the meter, a sample of gas is taken off for analysis. The Douglas Bag and the Gasometer Method, as described in the rest of this chapter and in the next chapter, both require some form of face mask or mouthpiece, inspiratory and expiratory valves, sampling tubes for gas, and a gas analysis apparatus. Face Mask or Mouthpiece. — One form of face mask is shown by illustration in the next chapter. This mask covers the whole face. A half-mask that covers the nose and mouth only has heretofore been used by many technicians both in America and in Europe. A form of mouthpiece and of nose clip are illustrated in Chapter 12. It is difficult to tell positively whether or not leakage is occurring around a face mask, or a mouthpiece. The patient can feel a current of cold air passing under a mask if there is undue leakage; or it may be observed by applying soap suds; or sometimes by listening closely. GAS ANALYSIS METHODS 55 Inspiratory and Expiratory Valves. — In gasometers, Douglas Bag or modified forms of apparatus, when the patient inhales, air enters thru the inspiratory valve, and when the patient exhales, air goes thru the ex- piratory valve into the gasometer or bag. These valves must open and close auto- matically and without leakage; they should be light weight so as to offer hardly any resistance to breathing; they should cause but a slight amount of noise, and it is most essential that no leakage occurs thru these valves when they are closed. The whole operation of these valves is a point for much emphasis. The valves as described by Dr. Tissot in Journal de Physiologie, 1911, were made of very thin brass, hinged on one edge. The valves have since been made with a mica seat. During the recent World War a very simple form of rubber valve was developt which at the present time is being more generally used than either the brass valves or mica valves. Under average conditions rubber valves are satisfactory. If there is excessive moisture, however, or if the valves are used in high temperatures, they will stick. Many authorities beheve that some form of valve should be devised which would be more nearly perfect than any hitherto developt. Sampling Tubes. — Samphng tubes may be of the new form that is described by Dr. Bailey in the following chapter, or of the common laboratory form that is shown in the accompanjdng cut. The glass parts are usually shipt unassembled, and the illustration will serve as a guide for assembling. The glass parts are connected by rubber tubing which should have heavy walls, inside diameter of 3 mm. and be about 40 cm. long. A set of 4 tubes requires 5 of the above lengths of tubing, or about 200 cm. in all, and about 1800 grams (or 4 pounds) of mercury. The process of collecting samples of the exhaled gas from the Douglas- Bag or from the Tissot Gasometer is described in Hal- dane's small volume on "Methods of Air Analysis," and briefly 56 BASAL METABOLISM in Boothby and Sandiford's "Basal Meta- bolic Rate Determinations." Care should be taken (1) that the sample is not altered while it is being collected or afterwards while in storage; (2) that the samphng tubes, or container, be air-tight. After the rubber tubing from the sampling tubes has been connected to the Douglas Bag, or Gasometer, a sample of gas may be drawn into one tube by lowering the mercury reservoir with the pet cock open and closing the pet cock when the sample has been taken. The process should be repeated once or twice, thus to wash the sampling tube. A sample should represent the average quality or mean composition of the total amount that is in the Bag or Gasometer; for that reason, before taking the sample the gas in the Douglas Bag should be thoroly mixt. In the gasometer method one sample is usually taken with the gasometer at the top, a second midway, and a third when the gasometer is near the bottom; a fourth is sometimes taken. Four sampling tubes are usually filled as described above. Two tubes are analyzed for oxygen and carbon dioxid, and two are held in reserve. The Haldane Gas Analysis Apparatus. — When assembled this apparatus corresponds to the illustration; when shipt an extra glass pet cock is left on the bottom of the buret. This pet cock may be used during calibration and afterwards broken off; usually there is a scratch around the glass tube where the break can easily be made, but if there is no scratch one may be made with a sharp, hard file. The calibrations on the buret should be tested. They may be tested by fihing the buret with mercury; drawing small portions, about 1 c. c. at a time, thru the extra glass pet cock into a weighed vessel, then computing the volume of these successive weighed portions and comparing with the gradua- tions on the buret. The buret should be kept perpendicular, free of air bubbles; drops of mercury should be wiped off the end of the pet cock after each portion is drawn out; a constant room tenperature should be maintained as 1 degree of change will cause an appreciable change of volume. GAS ANALYSIS METHODS 57 The process of analyzing samples of gas by the Haldane Method is explained in Haldane's "Methods of Air Analysis"^ and in Boothby and Sandiford's "Basal Metabolic Rate De- terminations." The essential steps in the analysis are given in Chapter 5 of this book by Dr. Bailey: "In principle, a volimie of air is drawn into a graduated buret where it is saturated with water vapor and measured; the air is then passed back and forth into a potash pipet where the carbon dioxid is removed; it is returned to the buret and again measured, the difference between this and the first reading representing the volume of carbon dioxid. The oxygen is removed in a similar manner by passing the air into a second pipet containing a potassium py- rogallate solution; after the oxygen is absorbed, the gas is re- turned to the buret and measured, this second loss in volume representing the oxygen in the sample of air." 58 BASAL METABOLISM The\gas in one of the tubes that contains the sample is ana- lyzed, a duplicate check being required upon the carbon dioxid and ox^en percentages. Thei-air that is breathed by a patient should not be room air, which "paries in its component parts, but should be outside air which, According to Haldane, contains 20.93 per cent, of oxygen, 0.03 per cent, of carbon dioxid; and according to Boothby, 20.93 per cent, of oxygen, and 0.04 per cent, of carbon dioxid. The analysis usually comprises the determinations of oxygen and carbon dioxid, and the rest of the 100 per cent, for the total is considered to be nitrogen (including argon). It is customary for a technician to analyze outdoor air once a week, thus to test the accuracy of the apparatus, the efficiency of the absorbing solutions, and his skill in making the tests. The limit of error is given by Haldane as 0.01 per cent., so that successive analyses of the same sample should not differ by more than 0.02 per cent. In routine testing 0.03 to 0.04 per cent, is a common variation to allow for duplicate tests. The Haldane Apparatus requires: 120 cm. of rubber tubing with heavy walls, inside diameter 3 mm. 120 cm. of special rubber tubing that is "sulfid-free" and will withstand chemical action. 300 c. c. of distilled water. 600 grams of stick potassium hydroxid (not purified by alcohol) . 10 grams of Merck's pyrogaUic acid. Henderson Gas Analysis Apparatus^. — The particular features of this type of apparatus are: (1) a 4-way glass stop-cock shown by cut; (2) the adjustment of the volume of the control tube by means of a screw pinch-cock on a bit of rubber tubing on the lower end of the tube; (3) two large test tubes in which the absorbents of potassium hydroxid or sodium hydroxid and potassium py- rogallate are placed. Buret graduations that are made by average glass blowers are far too rough and inaccurate for the Haldane or Henderson forms of gas analysis apparatus. Thus in some burets. Dr. Henderson states that he has "found the errors of graduation 10 or even 20 times as great as are allowable." He goes on 2 Applications of Gas Analysis, by Yandell Henderson. The Journal of Biological Chemistry, January, 1918. GAS ANALYSIS METHODS 59 Special 4-Way Stop Cock to say: "The absolute error of the instrument was only 0.1 c. c. and this is not greater than is quite common and is allowable for common purposes in an ordinary titration buret. For the calibration of the gas buret the glass blower must not use water but mercury. The standard buret against which he calibrates must be of at least as fine bore as that of the tube of the buret to be calibrated. The standard buret must have been calibrated with weighed amounts of mercury and no mark on the buret purchased should have an error greater than 0.005 c. c." "The purchaser of a buret should test it before assembling by inverting the buret, connecting it with a reservoir of mercury, filling to the 7, 8, 9 and 10 c. c. marks, respectively, pouring this mercury into a small tarred beaker, and weighing. One c. c. of mercury at room temperature (18°C.) weighs 13.55 gm. An allowance of 0.004 c. c. may be made for the reversal of the 60 BASAL METABOLISM convexity of the meniscus in the inverted buret." "The correctness of the gradua- tion of the tube of the buret is most easily checked by drawing in on top of the mercury about 0.5 c. c. of water. By raising and lowering the mercury and reading the air- water and water-mercury menisci at various levels (allowing time for the water to drain from the sides)., errors of graduation due to irregu- larities in the cahber of the tube are revealed. The difference in the volume between the two menisci should not vary more than 0.005 c. c. at any two levels." Chemicals for Henderson Appar- atus. — After the apparatus has been assembled and the buret cali- brated, chemicals are added. The apparatus requires: 350 grams of mercury. 100 c. c. of 10% sodium hydroxid. 100 c. c. pyrogallic solution, made up from 66 c. c. of 30% potassium hydroxid and 34 c. c. saj;u- rated aqueous pyrogallic solution. The potassium, hydroxid and the pyrogallic solution should be mixt out of contact with the air, and should make only a yellow or light brown solution, about the color of tea;. If exposed tO' the air during the m.ixing, the solution becomes darker than this and largely loses its oxygen-absorbing power. In the apparatus both of the absorbents, sodium, hydroxid and pyrogallic acid solution, are covered with layers of a few c. c. of liquid petrolatum. Assembling the Apparatus. — In most respects the apparatus^ the technic, and precautions for its use are the same as with the usual form of instrument. Dr. Henderson, however, calls atten- tion to certain features which are liable to be overlooked: "Red rubber should not be used on the connections where GAS ANALYSIS METHODS 61 alkali may touch it, as it gives off sulfur which may finally appear as hydrogen sulfid in the buret." "To make the rubber connections tight (in case of leakage) it is convenient to wrap them with elastic bands. Loop the band around the rubber tube, pull tight, and wrap the free end around the tube several times. Pass a small curved forceps under the wrapping, catch the end of the rubber band over the points of the forceps, and twist the end under the wrapping by withdrawing the forceps. This is a much better method of making joints tight than wrapping them with wire." "The walls of the buret should always be moistened with a fraction of a drop of 1 per cent, sulfuric acid, and 2 or 3 c. c. of this fluid should be placed in the control tube." "The analyst must remember that accuracy in the use of the instrument does not depend upon an extreme effort to read the buret as finely as possible, but rather upon making sure that the absorptions are complete. It is therefore common practice, after an analysis is supposedly complete, to pass the gas over again into the absorbent and make another reading to be sure • that no change occurs." "A check on calibration, tightness of joints, and efficiency of absorbents which should be used daily is to make an analysis of atmospheric air. If the apparatus is properly graduated and in good order the sum of the oxygen and carbon dioxid in uncon- taminated atmospheric air should be found 20.96 per cent., with an allowable error of +0.03 per cent." Use of Apparatus. — Dr. Henderson in a letter to the Editor, outlines the procedure as follows: "An unmeasured sample of air is drawn into the buret and past into the pyrogallic until no further absorption occurs. Pass into sodium hydroxid and again into pyrogallic. This leaves the tubes of the apparatus filled only with nitrogen. Proceed with analysis thus : 1. Draw pyrogallic solution and sodium hydroxid to lines marked on stems of absorbers by turning cock to the respective sides and raising or lowering mercury. 2. Turn cock and open buret to outside. Draw sm.all drop of 2% sulfuric acid into buret to moisten the walls. Run mercury to top of stem above cock and connect with sample to be analyzed. Draw sample into buret and bring mercury almost to the 10 c. c. mark. 62 BASAL METABOLISM 3. Turn cock to connect with sodium hydroxid absorber and move mercury reservoir until sodium hydroxid rests on line on stem of absorber. 4. Adjust air bulb control until sodium hydroxid in the stem lies on that line. 5. Read gas volume in buret accurately. 6. Pass gas back and forth into NaOH solution by raising and lowering mercury reservoir 5 or 6 times. 7. Bring NaOH to approxim.ately correct level in absorber stem. Bring NaOH in temperature control tube to line by moving NaOH absorber up or down. 8. Bring NaOH in absorber stem accurately to line on stem and take reading No. 2. 9. Turn cock to connect gas buret with pyrogallic absorber and pass gas back and forth slowly 10 or 15 times. 10. Turn cock and pass once into NaOH to take out oxygen in capillary tube. Pass 5 times more into pyrogallic and then draw gas into buret with pyrogallic to proper line on absorber stem. 11. Turn cock to NaOH absorber and take reading as de- scribed in (7) and (8). 12. Pass gas into pyrogallic 5 times more and take reading. Continue until no more decrease in volume occurs. Make final reading No. 3. (Repetition of the passage of gas into pyrogallic and repetition of reading No. 3 to constant volume is the chief element in accurate work) . 13. Calculate CO2 percentage of dry gas: Reading No. 1 minus Reading No. 2, divided by Reading No. 1. Calculate O2 percentage of dry gas: Reading No. 2 minus Reading No. 3, divided by Reading No. 1. The use of this apparatus requires some skill and experience in gas analysis. The beginner should be strongly advised to use at first merely the common Orsat gas analysis apparatus. Altho distinctly less accurate than the Haldane apparatus in its original form, or than my apparatus, the Orsat is capable, nevertheless, of giving sufficiently good results for ordinary clinical work and the beginner will not make nearly so many errors." GAS ANALYSIS METHODS 63 Calculation of the results of gas analysis and the intermediate steps for computing the metabolic rate are given in Chapter 27, Tables with Explanations. Qualifications of Analyst. — The person who makes the chem- ical analyses that are required in the Open Circuit Method, whether the apparatus is of the Gasometer type or the Douglas Bag, must be familiar with this particular phase of gas analysis. A special training is required. In explaining the method that is used at the Mayo Clinic, Boothby states in the Boston Medical and Surgical -Journal of September 22, 1921, that "We have not found it difficult to teach high school graduates, in from 4 to 8 weeks, to use a Haldane apparatus accurately." And he further points out that "The principle of a Haldane is very simple, altho it takes some time to acquire the manual dexterity necessary to use it properly." Benedict says, in the Boston Medical and Surgical Journal, May 16, 1918: "Although the cumbersome gas-analysis appara- tus of Zuntz-Geppert has been superseded by the more portable form of Haldane, gas analysis in all its intricacies still remains the bugbear of workers in gaseous metabolism. Furthermore, the gas analyst, to retain his skill, must analyze practically every day." It is commonly recommended that a technician should have at least a high school education; that to learn the gas analysis method, one month should be spent in some laboratory where daily tests are being made and where routine experience and competent instruction in details may be obtained. Summary of Apparatus required : A gasometer of some form, or bag and precise gas meter. Pipe or tube to outside air. Rubber tubing. Face mask, or mouthpiece and nose clip. Valves, inspiratory and expiratory. Sampling tubes. Gas analysis apparatus for determination of carbon dioxid and oxygen contents. Test tubes and beakers. Chemical balance weighing to hundredths of a gram and up to at least 100 grams. 64 BASAL METABOLISM Electrically driven shaft to raise and lower mercury reservoir (instead of raising and lowering repeatedly by hand) when several sets of tests are regularly required. Ground glass with electric lamp in back of it for illuminating the meniscus of the mercury in the buret. Magnifying glass to aid in taking accurate readings. CHAPTER 5 GAS ANALYSIS METHOD OF NEW YORK POST-GRADUATE HOSPITAL^ By Cameron V. Bailey, M. D. In equipping the respiration laboratory of the New York Post- Graduate Hospital, we were greatly influenced by the broad experience of Boothby and Sandiford in the clinical application of basal metabolism. Their arguments in favor of the open circuit or gasometer method for institutional work seem to be sound, and, despite the bugbear of gas-analysis, the method is eminently satisfactory. In this method the subject inspires atmospheric air and expires into a gasometer thru a series of tubes, mask and valves. The expired air, having been measured and its volume corrected, is analyzed for carbon dioxid and oxygen; the amount of oxygen absorbed is calculated on a basis of the ratio of expired nitrogen to atmospheric nitrogen. Dividing the volume of carbon dioxid produced by the oxygen absorbed gives the respiratory quotient, which has a known heat value for each liter of oxygen. In this manner the total calories produced per hour may be calculated. Accepting the heat production as practically proportionate to the surface area determined by the DuBois and DuBois formula, the calories produced may be exprest in terms of calories per square meter of body surface per hour. This result, the basal metabolism, is usually reported as the percentage above or below the average of the Du Bois normal standard. By the use of Boothby and Sandiford's calculation sheets, each step in the procedure can be checked by a second assistant, thereby greatly decreasing the chances of technical error. Logarithms, whose name alone has probably inspired dread in the minds of the uninitiated, is an invaluable means of accurately carrying out routine calculations. Employing a Haldane, or one of its modifications, the determination of the carbon dioxid is rapidly carried out before the oxygen analysis. ' Editor's abstract of "Apparatus Used in the Estimation of Basal Meta- bolism,'' by C. V. Bailey M.D., in the Journal of Lab. and Clinical Med., 6:657-679, Sept. 1921. 65 66 BASAL METABOLISM In the Gas Analysis Method (as used at the New York Post- Graduate Hospital, — Ed.) the expired air is collected under most favorable conditions. The subject reclines, the face mask is adjusted, and the test started after the gasometer has been completely washed out with expired air. The test is started and stopt during inspiration without the patient's knowledge, and without his undesirable cooperation. No especial skill is required in this part of the procedure, and, once the apparatus has been tested, the danger from leaks is negligible. Description of Mask. — The large mmiber of breathing ap- phances which have been introduced for use with respiration apparatus, is an evidence of the difficulty experienced in finding something suitable for this work. Some device is needed which can be rapidly fitted to any patient, which will permit of his normal type of respiration, which will accurately conduct the inspiratory and expiratory air without offering resistance, and which can be worn in comfort and without danger of leaks. The gas mask of the French army shown in cut below fulfills all of these requirements, when used with the rubber flutter valves introduced by the British during the late war. The mask is made of thick rubber, covers the whole face, and presents broad surfaces which closely engage the forehead, sides of the face and jaw. The tissues in these regions are well supported by the bony framework of the face and the mask readily adapts itself to these fixed surfaces. It is held in place by elastic straps passing around the head. With emaciated subjects, leaks may occur above or below the zygoma; in this area the pull of the straps is in the same plane as the surface of the face. In such instances the leaks are readily overcome by placing 5-inch rubber sponges over these areas of the mask and binding them in place with a 3-inch bandage. In this mask the incoming air is directed upward towards the windows, the opening of the expiratory tube being opposite the nose and mouth; this insures complete ventilation of the space and no discomfort results. When apphed to some individuals, the chin pad permits the mask to^ press on the throat; this can be readily overcome by drawing the mask away from the chin by means of a cord fastened to the tube connections on the mask, and tying the cord to a hook directly over the subject's head. With this cord the mask can be comfortably adjusted, and it has the added value of preventing GAS ANALYSIS METHODS 67 movement on the part of the patient. Following the test, the mask and attacht tubes are removed from the pipes and are readily cleansed with soap and water. K ^.-.^ Pipes, Valves and Connections 68 BASAL METABOLISM Procedure in Making Test. — The first consideration is the handling of the patient; this must be done expeditiously, and in such a way as to allay his fears and to permit of complete bodily rest for a period of at least half an hour before the test is started. During this period the respirations and pulse rate are closely observed and the mask is not applied until the patient appears to be mentally and physically at rest. At this time one also ascertains that the body temperature is normal. While the subject is resting one empties the gasometer by removing the lower portion of the counterweight and turning the valve (J) — see preceeding cut — to communicate with the room air; the bell sinks until it rests on the obturator and the pointer will stand at zero on the measuring tape. The valve (H) is now turned so as to connect the air-tube (G) with the gasometer. The rubber cap (A) is removed for a few minutes, permitting the large intake pipe to fill with fresh air from out doors; the cap is then replaced. When the patient is sufhciently rested, the ends of the tubes attacht to the mask are dipt in water and slipt over the brass pipes perforating the wall at (C) and (£), care being taken that the inspiratory pipe leads to the upper openings in the mask. The mask is then applied by holding the chin portion in position and pulling the straps over the top of the head. When accu- rately fitted, the mask-cord (D) is tied to the overhead hook, holding the mask and head in the most comfortable position for the patient. From the time the mask is applied, the inspira- tory air is drawn from outdoors thru the pipes to the flutter valve (B) and thence to the mask. The expiratory air passes from the mask thru the flutter valve (F) and along the tubing to the small space between the top of the bell and the obturator; from there it passes thru the outlet. pipe and escapes into the room thru the valve (7). In this way the entire dead space of the apparatus is flushed out with expired air. As an extra precaution, the lower portion of the counterweight is replaced, at the same time closing the valve (/). The expira- tions are now caught in the gasometer. When the bell has been elevated 6 or 8 cm., the valve (H) is turned during inspiration, cutting off the gasometer and permitting the expirations to escape thru the vent (/) . The bell is now dropt nearly to the zero mark by removing the lower counterweight and opening the GAS ANALYSIS METHODS 69 valve (J). This valve is then closed, the counterweight replaced, and the reading on the tape recorded to the nearest half-milli- meter. One is now ready to start the test. The respiratory phases can be readily followed by observing the flutter valves (B) and (F). During the inspiratory phase, the valve (H) is quickly turned to communicate with the gasometer and at the same time one presses the stop watch and the collection is begun. The attendant should watch the subject closely during these procedures and report any movements. While the air is being collected, the respiration and pulse rates are recorded at frequent intervals, and the patient is admonished to remain very still and encouraged by explanations that the test is nearing completion and that everything is very satisfactory. The duration of the test is determined by the subject's rate of ventilation. As a rule the gasometer is nearly filled at the end of 10 to 12 minutes, altho this period may vary from 5 to 15 minutes. Calculation is facilitated by stopping on the minute, the quarter, or the half minute. This is accomplished by holding the stop watch near the inspiratory valve (B) in such a way that both can be observed at the same time; the other hand grasps the valve lever (H); at the selected period of time, and during inspiration, the valve ( H) is quickly turned cutting the patient off from the gasometer. Should the subject be expiring, one waits until expiration is completed before closing the valve. The watch is stopt at this time. One must avoid shifting this valve during expiration as it is very disconcerting to the patient. The reading on the steel tape is now recorded to the nearest half -millimeter. The difference between this and the first reading tells the height in centimeters to which the bell has risen. As the bell is exactly counterbalanced in all positions, the inclosed air is under the prevailing atmospheric pressure. The lower portion of the counterweight is now removed leaving the air under positive pressure. Since volumes of gas vary directly with the temperature and inversely with the barometric pressure, it is necessary to record these factors which will be used later in the calculations. The temperature is determined by a Centigrade thermometer inserted in the bell. A brass-scale mercurial barometer is used in record- ing the atmospheric pressure. 70 BASAL METABOLISM Samples of the expired air can now be collected in gas sampling bottles. Gas-Sampling Bottles. — The gas-sampling bottle consists of parallel glass cylinders communicating at the bottom thru a small opening. The cylinders are hrmly cemented into a metal case which forms a base. The top of one of the cylinders has a funnel-shaped inversion; the other tapers off to a 2 mm. capillary tube to which a 3-way stop-cock is fused. The second open- ing in the stop-cock communicates with a capillary tube which bends over the inverted top of the first cylinder. The stop-cock terminates in a straight spout of capillary tubing 3 cm. long. The appliance is half filled with mer- cury, and before use is flushed out with 1 per cent, sulfuric acid. A 6 cm. length of j^ inch rubber tubing is permanently attacht to the spout. In preparation for use, one sets the stop-cock so that the spout communicates with the gas chamber. The bottle is now tilted forward over a small beaker containing 1 per cent, sulfuric acid, into which the rubber tube dips. The contained air is forced out by the mercury and when the bottle is tilted backward, acidulated water is drawn into the chamber. This position is maintained until mercury drops into the beaker (See A in cut). The stop-cock is immediately reversed; this leaves the gas chamber and the lower lead of the stop-cock filled with mercury (B), and the spout is in communication with the bent capillary tubing thru which the air to be sampled is blown. Enough acidulated water remains in the chamber to saturate the air when the bottle is filled. Collection of Air Samples from the Gasometer. — Having removed the lower portion of the counterweight following the final reading of the gasometer, the inclosed air is under positive pressure. The prepared samphng bottle is now placed on the shelf and connected with the sampling-cock. This cock is now GAS ANALYSIS METHODS 71 Procedure of Collecting Air Samples opened and the air blows thru the curved tube of the sampling bottle. Half the air in the gasometer is allowed to escape thru the outlet valve; this is to insure a fair sample, as recommended by Boothby. The stop-cock of the sampling bottle is now reversed, the bottle removed from its shelf, and tilted backward (C) and the compartment fills with the air from the gasometer. The stop-cock is returned to its original position and the sample is trapt under pressure in the bottle (D). Before trapping the sample, it is sometimes advisable to tilt the bottle backward and forward several times, at the same time allowing air to escape thru the outlet valve of the gasometer; in this way one is certain of securing a good sample of the inclosed air. Two or three bottles can be filled in this manner, each bottle holding enough air for six analyses. 72 BASAL METABOLISM Principles of Gas Analysis. — The Haldane method is used in determining the amount of carbon dioxid and oxygen in the expired air. In principle, a volume of air is drawn into a grad- uated buret, where it is saturated with water vapor and meas- ured; the air is then passed back and forth into a potash pipet, where the carbon dioxid is removed; it is returned to the buret and again measured, the difference between this and the first reading representing the volume of carbon dioxid. The oxygen is removed in a similar manner by passing the air into a second pipet containing a potassium pyrogallate solution; after the oxygen is absorbed, the gas is returned to the buret and meas- ured, this second loss in volume representing the oxygen in the sample of air. These analyses are made in duplicate or triplicate in order to obtain a check for accuracy. Details of Gas Analysis. — The details of gas analysis are fully covered by the treatises of: Haldane, J. S.; "Methods of Air Analysis", C. Griihn & Co., Ltd., London, 147 pp., $2.00, 1912; and Boothby and Sandiford, "Basal Metabolic Rate Determina- tions", W. B. Saunders Co., Philadelphia and London, 117 pp., $5.00, 1920. CHAPTER 6. KING METHOD: DETERMINATION OF CARBON DIOXID ELIMINATION \ By J. T. King, Jr., M. D. On account of the theoretical variable calorific value of a liter of carbon dioxid, so far it has not been suggested to make use of a simple measurement of the carbon dioxid elimination as an index to the basal metabolic rate. In order to determine this point, it seemed the best procedure to study the original chamber calorimetric work. By so doing we were able to compare the oxygen consumption with carbon dioxid elimination, and also to compare each of these factors with the heat production as measured directly. Analysis of Direct and Indirect Calorimetry Results. — For this purpose 27 experiments have been analyzed, 10 being taken from the publication of Benedict and Carpenter, and 17 from work by Sonderstrom, Meyer and Du Bois. Each experiment represents an hour's observation, tho in some cases repeated tests were made upon the same subject. The ten protocols of Benedict and Carpenter were analyzed by the writer as follows: A. The average carbon dioxid elimination per^ square meter per hour. B. The average oxygen consumption. C. The average heat production. On the basis of these averages the deviation of carbon dioxid from its average was calculated for each experiment. The deviations of oxygen consumption and heat production from their respective averages were also calculated for each experiment. 1 Editor's abstract, "Determination of the Basal Metabolism from the Car- bon Dioxid Elimination, with a Statistical Note by Raymond Pearl", The Bulletin of the John Hopkins Hospital, Sept., 1921. Approved by author. 73 74 BASAL METABOLISM The carbon dioxid deviation from its average was then compared directly with the deviation of heat production from its average in each experiment. A similar comparison was made between oxygen consmnption and heat production. It was found that the Average difference between carbon dioxid variations and calorie variations was 4.93% Average difference between oxygen variations and calorie variations was . . 8.39% An analysis was made in a corresponding manner of the data of Sonderstrom, Meyer and Du Bois. In this series the calories calculated by the indirect method are also published. It must be remembered that the technic of these early observations with the cham.ber calorimeter included not only the oxygen consumption and the carbon dioxid elimination but urinary nitrogen determination as well. By these means, the nitrogenous metabolism was estimated, and the oxygen and carbon dioxid figures were partitioned and calculated for protein and non- protein oxidation. The indirect method used in connection with the chamber calorimeter may, therefore, be taken as ideal. This analysis showed that the Average difference between the indirect and direct calorimetric figures was . 3.79% Average difference between the carbon dioxid and direct calorimetric figures was . 4.73% Average difference between oxygen and direct calori- metric figures was . , 5.70% A third series of protocols (Benedict, Emmes, Roth and Smith) was studied chiefly for the purpose of obtaining a scale of stand- ard figures for the carbon dioxid elimination in a large number of normal individuals. In this series we have not attempted to draw conclusions as to the correlation of the oxygen and carbon dioxid figures, respectively, with the calories, inasmuch as the calories are calculated calories (indirect method), and not measured calories (direct method). The calorie figures follow the oxygen figures more closely than they follow the carbon dioxid figures. It is, therefore, obvious that the practical result of the customary method of deriving calories from oxygen and KING METHOD 75 carbon dioxid figures is that the oxygen figure is more influential in determining the resultant calorie figures than the carbon dioxid figures. In the results of these analyses let letters have the following significance: A. Carbon Dioxid per square meter per hour in grams. B. Oxygen per square meter per hour in grams. C. Calories per square meter per hour. r. Coefficient of correlation between the two variables indicated by attacht letters. PE. Probable error. The significant comparisons are: Direct calorimetry (10 cases) Tac— rBc = -719— .488= +.231 + .192 Diff/P.E.„„^ = 1.2 Direct calorimetry (17 cases) Tac— rEc = -846— .836 = —.010 ± .068 Diff/P.E. diff=0.1 From these results it must be concluded that the oxygen intake is not significantly more highly correlated with directly measured calorie output than is carbon dioxid. The differences in the correlations are sensibly zero, having regard for these probable errors. In the longer series (17 cases) the correlation is actually shghtly (but not significantly) higher for the carbon dioxid with calories than for the oxygen with calories. Proposed Scale of Normal Figures. — In order to test the method which has just been described, a series of 17 observations was made upon normal subjects. Each observation included a preliminary period and 15 minutes of carbon dioxid collection. The results show that an average of 12.83 grams carbon dioxid per square meter of body surface per hour is eliminated by healthy men whose ages he between 20 and 40 years. On the basis of this standard figure, a prediction was made by the writer of carbon dioxid elimination for various ages and for both sexes. These results are based upon the curve con- structed by Aub and Du Bois, showing the heat production of healthy males at various ages. These predicted values were then compared with the actual values observed by Benedict and his associates — obtained by the analysis of Benedict's figures by decades. The correlation between the two sets of figures was close for the decades in which actual observations were 76 BASAL METABOLISM made: those of Benedict and others are 13.13 gram.s and 12.89 grams per square meter per hour for the third and fourth decades respectively. The author's figure for the third and fourth decades together is 12.83 grams. A satisfactory scale of normal ' figures may therefore be obtained by taking an average between Benedict's and the author's figures for the lower decades. For decades above the fourth it seems to the writer safer to allow the carbon dioxid figures predicated upon the curve of Aub and Du Bois. Such a proposed scale is as follows: GRAMS CARBON DIOXID ELIMINATED PER SQUARE METER PER HOUR Proposed Scale of Normal Figures Age Men Women 15-20 14.03 12.75 20-30 12.98 11.95 30-40 12.86 11.85 40-50 12.52 11.74 50-60 12.21 11.37 60-70 11.86 11.05 70-80 11.53 10.71 Description of the Apparatus. — The apparatus for collecting and measuring carbon dioxid elimination is quite simple. The method is open, the older U. S. Army gas-mask being used to deliver outside air to the subject and to carry expired air to the tubing leading to the 3 jars. The gas-mask canister, seen hanging from the horizontal bar, is emptied by removing the valve in the bottom, removing the contents and sealing the valve into place again. On the intake side, then, there is nothing between the patient and the outside air except a light rubber valve in the bottom of the canister, which rises and falls with respiration. Expired air passes thru the flutter-valve out of the gas-mask and is caught in a rubber cuff, that is sealed with paraffin about this outlet valve. The cuff tapers into rubber tubing and the expired air passes thru the 3 collecting jars. Resistance to the passage of air thru the jars has been measured by inserting a water manometer between the subject and the first jar. Observations upon 2 large men showed an average momentary rise of pressure of 6 to 8 millimeters of water. On KING METHOD 77 78 BASAL METABOLISM deep respiration the pressure rose occasionally with a quick ele- vation, such as one sees in a water hammer pulse, to 14 milli- meters of water. Such pressure changes, it was thought, made a fan superfluous. There is no inspiratory effort whatever. The 3 jars are identical in construction and are such as were part of the original portable apparatus. Incoming air is carried thru a tube almost to the bottom of the jar. Here it is scattered thru a cone with multiple perforations, filters upward thru the chemicals, and passes out at the top. The first jar contains 4-mesh calcium chlorid. This has been found to desiccate expired air completely. The second jar contains soda lime and absorbs the carbon dioxid from the dried air. To insure the efhcacy of soda lime it should be changed after it has taken up a total of 75 grams of carbon dioxid. The third jar contains calciiun chlorid of the same type as that used in the first jar. This third jar is necessary because the soda lime (jar 2) contains a rather high percentage of moisture, some of which is carried out of jar 2 during each test: jar 3 absorbs this vapor. The increase in weight in jar 3, therefore, must be added to the net increase in weight of jar 2 in order that the determination of carbon dioxid may be correct. Test for Leaks. — The test for leaks should be made frequently. While someone is breathing into the apparatus, go over the joints of the apparatus with a soft brush with soap suds. Formation of a bubble will indicate a leak. Ventilation Test. — The ventilation is practically always free with this method, the only difhculty being possible occasional adhesions of the moist valve. It is an advantage to have the flutter valve encased in some sort of glass chamber which can be opened, thus affording a means of drying the valve. Technic of the Test. — The patient is prepared in the usual way, as described on page 45. The room is well ventilated before and during the examination, the patient being carefully protected from the cold. After the mouthpiece and nose clip are adjusted, the patient is instructed to be quiet and to breathe naturally. For several minutes a preliminary period is carried out, the patient breathing thru the first jar only. This is done in-order to allow the patient to become used to the procedure, and the length of this preliminary period depends upon the KING METHOD 79 readiness with which he settles down to his task. It is found that most complaints arise during the very beginning of the test. If a new start must be made, it is, therefore, usually accomplished during this preliminary period, and it is not necessary to re-weigh jars 2 and 3. As soon as the patient is quiet and breathing smoothly, jars 2 and 3, which have been previously attacht to each other, are joined to jar 1, note being taken of the time to the second. The expired air is past thru all these jars for 10 minute periods, these 10 minute periods being repeated until 2 of the results agree reasonably closely. Calculating the Metabolic Rate. — The metabolic rate is cal- culated as follows: The sum of the increase in weight in jars 2 and 3 represents the carbon dioxid elimination. The carbon dioxid for 2 periods is added and multiplied by 3. This gives the carbon dioxid elimination per hour. This is divided by the body surface, (Du Bois height-weight chart). The resultant figure — grams carbon dioxid per square meter per hour — is our end result. This is compared with the standard normal figures and the percentage deviation from the average normal figure is calculated. CHAPTER 7. SANBORN BENEDICT APPARATUS By Hehry Elsner Marks, M. D. Indirect Calorimetry. — With the Benedict Portable apparatus the metabolic rate is calculated from measurements of oxygen consumption over a given period of time. This is the method of indirect calorimetry from one of the respiratory gases, and it is based upon the assumption that each Uter of oxygen used liberates a definite amount of energy from the food substances in the body; in other words, that the respiratory quotient is constant. Observation has shown that this assumption is justified when the subject is in the fasting state. Except in conditions in which the metabohsm of certain of the foodstuffs is interfered with, as in diabetes melUtus, the proportions of stored protein, fat, and carbohydrate metabolized by the fasting subject are quite constant. This fact permits us to assign a definite heat value to a given quantity of either oxygen or carbon dioxid, and, since Murlin and Lusk and others have shown that the values obtained by indirect calorimetry agree closely with those obtained by the direct measurement of heat elimination in the calorimeter chamber, we are justified in considering as accurate the calculated values obtained by this method. Description of Apparatus. — The apparatus gives accurate determinations of oxygen consumption by measuring the change in volimie of the gas in a closed circuit, the carbon dioxid pro- duced being absorbed by circulating the air through soda lime. A gasometer with an accurately balanced bell is included in the circuit; the rest of the circuit, with the exception of the lungs of the patient, is of fixed volume, so that a change in height of the gasometer bell indicates a change in total gas volume, provided the lungs are at the same phase of respira- tion when all measurements are made. The counter- weight of the gasometer bell bears an index and the height of the bell is read on a scale at the beginning and end of a measured period; from the readings of time and total change in volume 80 SANBORN BENEDICT APPARATUS 81 the oxygen^ consumption per minute is calculated. With the older machines the scale read in millimeters, and volume was found by multiplying the number of millimeters shrinkage by a factor representing the volume corresponding to one milli- meter on the scale; the more recent machines read directly in cubic centimeters. This volume is then corrected to standard con- ditions (0°C. and 760 mm. pressure) from the readings of tempfrature and barometric pressure, and then, using an assumed value of 4.825 calories per liter of oxygen (corres- ponding to a respiratory quotient of .82) the total calories per hour are calculated. The patient's body surface having been deter- mined from the height and weight mieasure- ments, in accordance withDu Boi^height- weight formula or his height-weight chart, the cal- ories per square meter per hour are found and compared with the stan- dards of average values, based upon age and sex. This then gives the basal metabolic rate in terms of percentage of the average normal value. Preparatio^: of the Apparatus. — The water-seal of the gasometer is first filled with water at about room temperature, to within 3 or 4 inches of the top of the tank. In order to prevent accidental spilling into the air chamber and circulation tubes when the machine is not in use, it is well to draw off a portion of the water after the completion of a test, and if this is kept in the vessel into which it is drawn it will be at room temperature when the machine is next used and can be poured back into the tank without disturbing the temperature of the gas. The fan motor and fan shaft bearings are now oiled, the motor started, and the test of ventilation rate is made. The fan should deliver approximately 30 liters of air per minute 82 BASAL METABOLISM past the mouthpiece, and its ability to do so should be tested each day that the machine is to be used. The test is best carried out by measuring the time required for the fan to empty the gasometer completely. The afferent tube (the smaller one) is first disconnected from the mouthpiece, the gasometer bell is raised to its highest point and the mouthpiece connection from which the tube was removed is closed with a cork. The motor is now started, the bell released, and its descent timed. It should empty itself in about 15 seconds. If more than 18 seconds are required, the fan or motor needs attention, or the absorber is packed too densely. When the ventilation test is completed, the machine is tested for leakage. A leakage test should be made each day that the machine is to be used as well as each timie any changes are made in the joints or connections of the air circuit. The test may be made with the motor running, or turned off; a 100-gram, weight is placed on the gasometer bell and volume and temperature read- ings are made over a period of several minutes, preferably at least 10 minutes or the length of a metaboUsm test period. With the temperature constant there should be no change in volume during this time, provided the gas has been well circulated and thoroughly mixed before making the first reading, so as to be of uniform temperature throughout. If the temperature changes during the test there will be a corresponding change in volume; this amounts to about 40 cc. for each degree Centigrade in the older form of apparatus with soda-Ume jar outside the gasometer, where the total volume with one jar in the circuit is about 10 liters. A complete leakage test should also include a test for negative leaks, especially with the form of apparatus in which the absorbing jar is placed before the circulating fan in the circuit, as here a higher degree of negative pressure may develop. The test is carried out in a manner similar to the ordinary test except that a weight is attached to the counterbalance cord of the gaso- meter instead of being placed upon the bell. This test need only be carried out occasionally, or when the connections between the gasometer and the fan have been changed. With the gasometer nearly empty, oxygen is now admitted until the bell is well filled. About 4000 cc, or 20 cm. on the scale, usually sufi&ce for a patient of mediumi size; with an ele- SANBORN BENEDICT APPARATUS 83 vated metabolic rate or a large patient, more should be allowed. The introduction of the compressed gas lowers the temperature and the gas should be circulated for several minutes and mixed thoroughly before making preliminary readings; time may be saved by making the leakage test after admitting the oxygen instead of before. Making the Metaboiism Test. — The test itself consists in making readings of the gas volume on the gasometer scale at the beginning and end of a measured period of time. Since the lung volume must be the same at the time of making each reading it is customary always to read the scale at the end of a normal expiration. Usually, with the patient at rest and comfortable, the lungs empty themselves to almost exactly the same point with each expiration; therefore the change in the scale reading with each successive descent of the index represents the oxygen absorbed during that respiration. Irregular expirations, however, deeper or shallower than the average or normal ones, are always more or less numerous, and if the scale is read at the end of one of these considerable error may be introduced. In order to avoid this, the scale is watched carefuUy over a series of expira- tions and from observation of these readings an idea is formed of the regularity of expiration and of the average shrinkage with each respiration. When a series of 3 or 4 expirations occurs which are apparently normal and show regular shrinkage the correct reading of the next expiration can be estimated from them; the time reading is taken at the moment of this next expiration and the estimated correct value is taken as the scale reading regardless of whether or not the index actually stopped at that point. The accuracy of this estimated reading may be further checked by watching one or two expirations immediately follow- ing the one taken. Readings both before and after the one taken can be made, of course, only when the patient is breathing into the circuit both before and after the reading; that is, with the so-called "flying start," or with inside readings by the Emmes method. With the outside readings, when the period is started or ended with the turning of the valve, the check readings are made only after or before the one recorded, as the case may be.. The period is started, then, by turning the valve at the end of a normal average expiration, and at the same moment starting the stopwatch. The next 2 or 3 expirations are watched and the 84 BASAL METABOLISM correct initial reading estimated from them and recorded on the data sheet, together with the temperature. At the end of the period readings are again made on each of several successive expirations, the reading for the next expiration is estimated from them, and when the index descends to that point, the valve is again turned and the watch stopped. If the operator is not successful in turning the valve at the point which he estimated as correct, the error is noted; after the gas is washed the final reading is corrected by the amount of this error. After turning the valve the gasometer continues to descend for a minute or two, usually shrinking from 80 to 200 c.c. before coming to rest. This is due to the washing out of carbon dioxid and water vapor, and since the period was started with dry air free from carbon dioxid the final reading is not made until the residual air is again dry and free from carbon dioxid. This reading is then corrected if necessary and recorded on the data sheet together with the final temperature reading. Readings are estimated to tenths of a millimeter, or to 10c. c. on the volume scale, for greater accuracy. Check values are obtained by determining the oxygen con- sumption over measured portions of the test period by the Emmes method. These are termed "inside readings", and it is customary to take two inside readings after the start of the period and two before the end, giving two inside periods, each from 6 to 8 minutes long. It must be remembered that atmospheric con- ditions inside the machine during the period are different from those found at the beginning or end, since both water-vapor and carbon dioxid are present to a degree depending upon the rates of their production and absorption. This point of equilibrium between production and absorption is reached only after an appreciable period of time, and since water-vapor and carbon dioxid content should be the same at both beginning and end of the inside periods, it is best to wait a minute or two after the start of the period before making the first inside reading. This reading is estimated in the manner described from the readings of the preceding and succeeding normal expirations, and the time noted at the instant of full expiration, without stopping the watch. Temperature is then noted, and the 3 readings recorded upon the data sheet. The initial reading of the second inside period is then made in the same way, and toward the end of the SANBORN BENEDICT APPARATUS 85 period the final readings of the inside periods are made. Thus 3 checks are obtained for each period. It is the practice of some operators to dispense with the outside reading and to make all 3 readings by the inside method. I believe, however, that if good checks can be obtained by 2 different methods the results are more reliable, and, therefore, prefer to follow Benedict's original technic, as here outlined. During the period the patient's pulse and respiration rates are noted, as well as the barometer reading. At least 2 periods, giving 6 check readings, should be obtained. Oxygen consumption per minute is calculated at once for each of the 6 readings and if the results show a variation of less than 3 per cent., no further readings are necessary. If not, another period should be run. It will then usually be found that the second and third periods give satisfactory checks, the higher value of the first period being due to nervousness, restlessness or irregular breathing at the beginning, and before the patient became accustomed to the procedure. Method of Calculation. — The first step in the calculation consists in the determination of the average oxygen consumption per minute. On the data sheet have been recorded for each period the figures of total shrinkage, duration of period, and temperature at start and end of the period. If the shrinkage is read in miillimeters on the gasometer scale it must be converted into cubic centimeters by multiplying by the factor suppHed with the apparatus which indicates the volume of gas correspond- ing to 1 mm. on the scale; if the scale reads directly in cubic centimeters this step is not required. Next, from the barometric pressure as observed the gas volume is corrected to 760 mm. by p multiplying by — . This volume is then corrected to 0°C. by temperature correction tables, or by multiplying by ^ , 00366^ t being the mean temperature during the period. This corrected volume is now divided by the number of minutes duration of the period (fractional parts of a minute being converted from seconds into decimal parts by a table) and the oxygen consiimption per minute is found. 86 BASAL METABOLISM A correction must be applied to this figure because of error in the method of making the temperature correction. This should properly be done by correcting the total volume of gas in the circuit at the beginning and at the end of the period to 0°C. and subtracting the two to obtain the total shrinkage. With the method used, however, we do not measure the total volume of gas in the circuit but only the change in volume, and then apply the temperature correction to the amount of shrinkage found. The error imposed by this procedure amounts to about 1.8 c.c. for each degree Centigrade of rise in temperature during the period, added to the oxygen consumption per minute. As mentioned above, the figures for oxygen consumption should show a maximum range of variation within 3 per cent.; that is, the extreme values should be within 10 c. c. of one another for an oxygen consumption in the neighborhood of 250 c. c. per minute. If a greater variation is present an effort should be miade to find the source of the discrepancy. The first 2 periods may show a considerable difference; as has been mentioned, this may be due to initial discomfort in breathing with the mouthpiece and nose-cUp, and a third period will give figures agreeing with the second. If the first 2 periods give good checks a third period is unnecessary. There will then be 2 periods, with 6 check values in all. If we have been fortunate enough to have had a patient who breathed regularly, or if, with irregular respiration, we have been able to estimate our scale readings correctly, it will be found that at least 4 of the 6 checks fall within an extreme variation of 4 or 5 c.c; one or two may fall wide of this group through error in observation or estimation and these are discarded in calculating the average. With less favorable conditions the values may all be more or less widely scattered. If at least four of them fall within the range of 3 per cent, variation they may be considered satisfactory, but with greater variation the relative value of the test must be considered impaired and the weight of the evidence which it is depended upon to contribute is correspondingly lessened. In such cases it is worth while to calculate 3 values of the metaboHc rate, one from the average oxygen consumption, and one each from the maximum and minimum values obtained. This procedure gives a clearer idea of what the test is worth in such cases. SANBORN BENEDICT APPARATUS 87 Having determined the average oxygen consumption per minute, the energy equivalent of this quantity is found by multi- plying by 4.825, the number of calories of energy liberated by 1 Uter of oxygen under the conditions of the test; that is, in the post-absorptive state, when the fuel burned gives a respiratory quotient of .82. Multiplying this product by 60 gives the total calories produced per hour. This is now divided by the nimiber of square meters of body surface to find the calories per square meter per hour, and finally, this quantity is divided by the normal average value for an individual of the same sex and age to determine the percentage variation from the normal standard. All these steps are performed most easily and simply by the use of logarithms. As illustrated in the accompanying figure, total oxygen consumption for each period is found by adding the logarithms for the spirometer factor (the constant supplied with the machine), the shrinkage factor (these two are combined when the scale reads in centimeters), the barometer factor, and the temperature factor. Tables are obtainable which give directly the logarithms for these last two factors. (See page 256) . The barometer reading is corrected first for temperature (of the barometer itself) ; this correction is taken from a table and sub- tracted from the observed reading. The corrected reading is then used to find on the barometer table the logarithm for the barometer factor. From the mean temperature for the period the logarithm for the temperature factor is similarly found on another table. The sum of these four (or three) gives the loga- rithm of the total oxygen used; from this is subtracted the loga- rithm of the duration of the period, and the antilogarithm of the difference is the oxygen per minute in cubic centimeters. To this is added the correction mentioned above of 1.8 c.c. for each degree Centigrade rise in temperature during the period, and the average oxygen per minute is then obtained. To convert this into calories the logarithm of average oxygen per minute is added to the logarithms of 60 and of 4.825; the antilogarithm of the siun is the number of calories produced per hour. Subtracting the logarithm of the number of square meters body surface gives the logarithm of calories per square meter per hour, and subtracting the logarithm of the standard value from this gives the logarithm of the percentage variation from 88 BASAL METABOLISM the standard. In all these operations the characteristic of the logarithm is omitted, only the mantissa being used. The body surface is found from the measurements of height and weight by Du Bois' height-weight chart, or calculated from these measurements by his height-weight formula, according to which: Log of body surface = 0.425 log weight + 0.725 log height +.85634 Location of Leakage. — -The importance of testing the machine frequently for leakage has already been mientioned. Error from an unsuspected leak is, of course, inexcusable and can only result from carelessness in technic. When the test shows that leakage is present it is often troublesome and dif&cult to find the source; we have found the following method to be most effective. The gasometer is first isolated from the rest of the circuit by removing the bell and closing the inlet and outlet tubes with rubber stoppers. If the inlet has wires soldered across it so that a stopper cannot be introduced, the inlet tube connection below the gasometer is unscrewed and the stopper used to close the tube at this point. A Y-tube connected with a blood-pressure bulb and manometer is then connected to the oxygen inlet or to a tube passed through one of the rubber stoppers, and the pressure in the circuit is raised to about 100 mm. of mercury. By listen- ing carefully now at all points of the circuit, the hiss of the escaping air can usually be heard, and the exact location of the leak is then found by painting the suspected area with soapsuds. If nothing can be heard the soapsuds must be used on one part of the circuit after another until the leak is found. The fault is usually found about one of the joints, especially those in which washers are used, and is then easily remedied. The fan is also apt to leak, especially about the gasket, as the pressure is greatest here when the motor is running, and it may also show either a positive or negative leak about the fan-shaft. This should fit well in its bushing and should be kept well oiled. Activity of Absorber. — The most convenient index of the activity of the soda Ume is the magnitude and rate of shrinkage at the end of the period after the patient has been cut off from the machine. With a normal ventilation rate and active soda SANBORN BENEDICT APPARATUS 8& lime the air in the gasometer should be washed free from carbon dioxid and water-vapor in not much more than 1 minute; the descent of the bell should have stopped in that time, and the total shrinkage during the washing period should not be much above 150 c.c, — with fresh sodalime it does not go above SOc.c. The special soda lime now obtainable, of the submarine type, is especially active. The ordinary soda lime is not active if too dry and should be moistened a little -when first used; with con- tinued use it may become so wet as to cake and retard the cir- culation of air, in which case, if the machine has outside absorber jars, a calcium chlorid jar may be introduced in the circuit before the soda hme. The dried air will then take up moisture from the soda Ume and so improve its efficiency. Irregular Respiration. — This is the commonest and most serious cause of error. The validity of the test depends funda- mentally upon accurate measurements of gasometer volume and accuracy of these measurements requires that all readings be made at the same point in the respiratory cycle. Consequently it is of the greatest importance that the scale be watched care- fully and the reading of each expiration made for at least half a dozen respirations before a reading is taken; in the case of the reading at the start of the period the expirations immediately following the initial reading should be noted carefully. The correct reading is then predicted from the preceding ones, and it may be checked by reading also 1 or 2 expirations following it. This procedure will give satisfactory results with regular breath- ing or with the usual case in which there is only slight irregularity. With the t3^e of case in which irregularity is extreme it may be impossible to determine or estimate any normal point of expira- tion, and in such cases a satisfactory determination of oxygen consumption is impossible. Several periods should be tried, however, before the attempt is given up, for not infrequently the respiration becomes more regular as the patient becomes accus- tomed to the machine. Variations in the Relspiratory Quotient. — The normal patient in the post-absorptive state shows a respiratory quotient close to- .82, which corresponds to a heat value of 4.825 calories for each liter of oxygen consumed. In this state the proportion of car- bohydrate, fat and protein utiUzed by the body is quite constant. During digestion and absorption, however, the proportions- 90 BASAL METABOLISM depend upon the previous food intake, and the heat value of a liter of oxygen may vary between the extremes of 4.686 calories and 5.047 calories, so that the importance of the preliminary fast is manifest, entirely aside from the effect of food in elevating the metabolic rate. In diabetes the normal ratio of utilization of the various foodstuffs is disturbed, and the respiratory quo- tient changes, so that in this condition determinations of the metabolic rate are not reliable unless they include the determina- tion of carbon dioxid elimination and the calculation of the respiratory quotient. Even then, if there is acidosis, with dis- turbance in the carbonate reserve of the body, and with incom- plete combustion of fat, and the elimination of ketones through the kidneys or lungs, the relationship between the respiratory oxygen and carbon dioxid cannot give accurate information of the food substances undergoing combustion or of the heat liberated by a definite quantity of oxygen. In such cases, therefore, indirect calorimetry is not to be relied upon. Length of Period.- — It should be remembered that each minute added to the period decreases the error due to inaccuracy in making the scale reading. It is best, therefore, to make the periods as long as possible. A duration of more than 15 minutes, however, is likely to make the patient restless, and if the oxygen consumption is high the capacity of the gasometer Umits the duration to about this length. In addition, there are a number of minor sources of error that must be guarded against. Restlessness and nervousness of the patient must be reduced to a minimum, and if present should be noted so that this circumstance may be taken into consideration in judging the result of the test. The pulse rate during the period should always be noted. The increased muscular work when tachycardia, tachypnea, or tremor is present may cause con- siderable elevation of the rate, so that these conditions should always be noted for the same reason. Error may be introduced by the swallowing of air. In order to estimate correctly the significance of these factors the patient should be watched constantly during the test. It is not necessary to correct the barometer reading for water vapor tension. If the air were saturated when one reading is made and dry when the other reading is made the error would amount to less than 3 per cent., but as a matter of fact the air is SANBORN BENEDICT APPARATUS 91 practically dry when the outside readings are taken, and is presumably at about the same percentage of saturation when all inside readings are taken. Under such conditions the difference between the readings represents oxygen consumption alone and water-vapor tension need not be considered. DATA SHEET Period Scale readings Time Temp. I. Start End End End Start Start Shr. Dur. ~ Diff. Aver. la. Start End End End Start Start Shr. Dur." Diff. ■ ■ - ■ - Aver. lb. Start End End End Start Start Shr. Dur." Diff Aver. Data sheet for a single period, with two inside periods. 92 BASAL METABOLISM u 4j -w m II >-. II Hj ^ pq <; PM p^i o U pq O s -^ > § bo o o M 0) O 5P > o s 5^ ri CO u ^ t^ M !h u bo bo c3 O ^ 3^ ^-^ «J d D nj o^ rf .2 D< tH " ■K ■" 01 3 n _ .3 a ■" s rf !3 1 bo &0 bo bo bo - - - o o 1-1 h-1 I h-1 1^ CHAPTER 8 BENEDICT UNIVERSAL APPARATUS By L0VE1.L Langstroth, M. D. [The Apparatus and Method here described are in use at the Hospital of the University of California, San Francisco, CaJ. It is a part of the service equipment, not for research. With it two to three patients are tested each day. The editor had opportunity at a recent visit there to see the thoroness and scope of the laboratory equipment of which this apparatus forms an integral part. It is modern equipment, well-kept, and systematically used. The chapter describes: Testing the Apparatus (before a patient is tested); Measuring the Oxygen (that a patient consumes); Measuring the Carbon Dioxid (that a patient exhales); Preparation of Patient; Making the Test; and Calculating the Results. — Editor.] Testing the Apparatus. — In setting up the apparatus (see illustrations on next page) the operator should first familiarize himself with the different parts and have clearly in mind the path which the current of air takes in going thru them. Begin- ning at the threeway valve near the mouthpiece the air passes by way of the large rubber tube directly into the spirometer. This allows for expansion and contraction of the volimie of the closed circuit and affords at the same time by means of the graduated scale a method of measuring the O2 (oxygen) con- sumed. From the spirometer outlet it passes to the blower which affords the positive pressure necessary to force the current thru the various acid and soda lime bottles. The air passes from right to left thru the Williams absorbers on the lower shelf of the apparatus where it is dried. The absorber bottle on the extreme right is kept empty to act as a guard against the entrance of acid into the pump in case of possible reversal of the direction of the current. The glass inlet tube should be turned to the left with the direction of the air current. The next two absorbers contain concentrated sulphuric acid and the inlet tubes should be turned to the right against the direction of the air current. They should not be filled more than one-half inch above the air 93 94 BASAL METABOLISM Front View of Universal Respiration Apparatus The Williams absorbers on the lower shelf contain sulphuric acid. The motor and blower are shown behind them. On the top of the table are the soda lime bottles, the sulphuric acid bottles to catch the moisture from them, the sodium carbonate can, and the spirometer. BENEDICT UNIVERSAL APPARATUS 95 holes. We have found it advisable to mark the level to which acid is added in the absorbers by means of a narrow strip of adhesive fastened on the wire basket container. This indicates the amount of water absorbed by the acid. The acid in the first absorber should be changed sufficiently often to keep that in the second at its maximum concentration. The dried air is now led through the soda lime container where the CO2 (carbon dioxid) is absorbed. Moisture taken up from the soda lime is caught by the concentrated sulphuric acid in the Williams absorber thru which the air then passes and any change in the weight of these two bottles will indicate the mass of CO2 absorbed from the circulating air. The air inlet of this absorber should point to the left against the air current. Any acid fumes in the , air are absorbed in the Sodium Carbonate can. A small piece of fine wire gauze is placed over the outlet tube at the bottom and the can then filled three-quarters full with alternate layers of cotton wool and sodium carbonate. From here the air is led thru the smaller rubber tube back to the three-way valve at the mouthpiece. The dried air can be led thru either of the two soda lime bottles by turning the double valve which connects the CO2 absorption bottles with the remainder of the apparatus. This is a matter of convenience when large amounts of work are being done with the machine. The spirometer should be filled with water to within 3 inches of the top and the bell should swing free of the sides. In setting up the two uprights which support the spirometer pulley the cross arm at the top should be adjusted so that they will be parallel when in position. Convergence or divergence of these supports will tend to throw the spirom.eter bell away from its center. The table itself should be carefully leveled as this, too, influences the position of the spirometer bell. When the apparatus has been set up with the bottles filled, attention should again be given to the direction of the inlet tubes in the Williams absorbers because an error in the position of these tubes will result in forcing acid out of the bottles into the metal or rubber parts of the apparatus. The three-way valve at the mouthpiece is then turned so as to close the circuit and the motor is started. During the first few minutes there will be a slight increase in the temperature of the air inside the circuit due to the addition of moisture to the concentrated sulphuric acid. A «6 BASAL METABOLISM Rear View of Universal Respiration Apparatus. BENEDICT UNIVERSAL APPARATUS 97 certain amount of this heat is lost by radiation to the surrounding air and soon the temperature of the air becomes quite constant and there is no volume change from this source. When the blower is started the spirometer bell is seen to jump downward a few millimeters and this indicates the development of a slight negative pressure in the spirometer which obtains until the pressure thruout the apparatus has been equalized. After a few minutes the pointer should indicate a constant volume in the spirometer for a period of 2 or 3 minutes before the apparatus can be considered tight. In case of leakage the pointer will indicate a steady loss of volume. If the apparatus be new it is well to test every possible source of leakage. The spirometer itseli can psobably b& conadeEed tight, tho. in case of doubt the inlet and outlet tubes can be plugged with rubber stoppers and pressure made on the bell with a 200 gram weight. Leakage will be indicated by a change in volume. The remainder of the connections can be easily tested by applying a lather made from soap and hot water with a shaving brush. After the apparatus has been thus carefully gone over one need only look at the couplings of the Williams absorbers and the soda lime bottles which are opened from time to time and occasionally develop leaks. Before filling the soda lime bottles, we have made it a practice to fasten the metal top, insert the rubber stopper, lather the joint around the rubber gasket and then test for leakage by stopping the outlet tube with the finger and blow- ing into the inlet tube. In case of leakage the top should be removed, given a quarter turn to the right, and the test repeated until the bottle is tight. In filling these bottles it is convenient to have a tin funnel made so that it will easily fit the opening in the top and reach an inch or more below it. Occasionally the wire with which the rubber hose is fastened to the couplings will cut thru and in case of difficulty it is well to test for leakage here. Sometimes a patient is found whose nose is not com- pletely closed by the nose chp. A little lather placed over the nostrils will determine leakage at this point. Measuring the O2 (Oxygen). — The O2 consumed by the patient may be measured in se^'eral ways. Because of the difficulty of beginning and ending a period at exactly the same phase of respiration any error inherent in one of these methods 98 BASAL METABOLISM is far exceeded by the mechanical or technical error common to all of them. The method of determining the exact beginning and end of each period is of such importance that it is worth while to go into some detail to make clear the sources of error. Theoreti- cally it should be possible to turn the three-way valve at the end of a normal expiration and start the stop-watch at the same moment for the beginning of the period. It is very easy how- ever, even after considerable experience, to turn the valve a little too soon. The timing of this valve can be checked by noting whether the spirometer level at the end of the first 2 or 3 expirations agrees approximately with the reading taken before the valve was turned. In case of failure to agree it is clear that had the watch been started with the valve an error would have been introduced. When the patient is excitable or nervous the expiratory volume will often suddenly increase when the valve is turned so that a true spirometer level for a normal expiration is not obtained. In such a case normal expiratory volumes might not be reached for several moments after turning the valve. As soon as the patient is connected with the closed circuit the addition of CO2 and water vapor will increase the volume be- tween the three-way valve and the absorption bottles. After 6 to 12 respiratory cycles this volume increment of from 40 to 80 c. c. remains constant except for variations introduced by the type of breathing which may amount to from 30 to 60 c. c. If the valve be turned off at any time the volume of circulating air will be diminished as the unabsorbed water vapor and carbon dioxid pass thru the absorption bottles. Because of the com- parative constancy of this volume increase while the patient is connected with the machine, and the accuracy with which the exact end of expiration can be determined from the spirometer pointer, we have adopted a method of marking the periods which eliminates the inaccuracy due to the three-way valve while introducing a maximum error of from 30 to 60 c. c. due to varia- tion in the type of breathing. The valve is closed at the end of expiration and a period of 12 or more respiratory cycles allowed to elapse. By this time the breathing will have become regular. The stop-watch is then started and the spirometer level read at the end of a normal BENEDICT UNIVERSAL APPARATUS 99 expiration to mark the beginning of the period. After 10 minutes the spirometer level is observed at the end of a normal expiration and the watch stopped at the same instant. This marks the end of the period. Oxygen is then added and the procedure repeated once or twice as may be desired. Ten minute periods will vary very little when the operator becomes skilled and the metabolism has reached the basal rate. The method of measuring the O2 will be somewhat different when the expired CO2 is to be weighed. This arises from the fact that the amounts of O2 and CO2 must be obtained for exactly the same period of time and will be discussed later under CO2 measurement. The simplest method of measuring the O2 is by difference in the spirometer readings. This limits the length of the period to 10 or 12 minutes in the average individual. Longer periods may be run by determining O2 differences by weight. The small type of O2 cylinders fitted with a reduction valve will weigh between 7 and 8 kilograms. A balance with a capacity of 10 kilograms and a sensitiveness of .02 grams will then determine O2 differences of 10 grams or more, with an error of much less than 1 per cent. The gas supplied to us has been found over 99 per cent, pure O2. A source of difficulty in this method is leakage at the point of attachment of the reduction valve. Gaskets of lead are probably most satisfactory but a fresh one must be used each time the valve is detached. In using this method the spirometer is filled to a mark, O2 is added from time to time and again at the end of the period until the bell has reached the first level. The O2 cylinder is first weighed after filling the spirometer and again at the end of the period when O2 has been added to the original level. Multiplying the difference in weights by the volume of 1 gram of O2, 0.699, gives the volume of O2 consumed. This volume does not have to be corrected for temperature or pressure. Oxygen may also be measured by means of a Bohr gas meter. In this case the bell is filled to the original level after the period by passing O2 slowly thru the meter and the volume corrected for temperature and pressure. It is well first to pass the gas under water in order that addition of water vapor in the meter may not influence the volume. The meter should be calibrated by weighing from a cylinder the amount of gas passed thru it. The rate of delivery should be kept about constant. 100 BASAL METABOLISM Measuring the CO2 (Carbon Dioxid). — In measuring the expired CO2 it is necessary to begin and end each period by turning the three-way valve at the end of an average expiration. When the valve has been opened the height to which the spiro- meter rises for the first 2 or 3 expirations should be averaged to get the reading. At the end of the period the valve is turned when the pointer indicates the end of an average expiration. The soda lime bottle and the Williams absorber next to it are weighed together before and after the completion of the test. The difference in weight multiplied by the volume of a gram of CO2 (Carbon Dioxid), 0.5087, gives the volume of CO2 expired. This need not be corrected for temperature or pressure. The weight can only be considered accurate if the air reaching the soda lime bottle be absolutely dry. Failure of the Williams absorbers to take up all the water vapor from the incoming air can be detected by weighing the soda lime bottle and the sul- phuric acid container next to it before and after running a 10 minute blank. Increase in weight indicates escape of moisture from the air drying system and is corrected by changing the sulphuric acid. Loss of weight after the same blank denotes failure of the sulphuric acid to take up all of the moisture given off by the soda lime and is corrected for in a similar manner. Preparation of Patient. — In order to obtain what is known as the basal rate the factors of food absorption and muscular activity must be eliminated. This is done by making the deter- mination before breakfast and after a preliminary half hour period of absolute quiet in the recumbent position. It is probably better to transfer the patient from his bed to the calorimeter bed with a minimum of muscular activity so that in general out- patient determinations are to be discouraged. Readings of consecutive periods, however, will very often check remarkably well even tho the patient has walked some little distance before- hand. A fall in the O2 consumption probably means that the basal rate has not yet been reached. In case the non-protein respiratory quotient is to be obtained the bladder should be emptied and a specimen of urine collected over a measured period of time from before the test is begun till after it is finished. The patient is weighed to tenths of a kilogram and the height taken to the nearest centimeter before lying down. BENEDICT UNIVERSAL APPARATUS 101 Making the Test. — The preliminary period of rest having passed, the bed on which the patient is lying is wheeled in posi- tion next to the calorimeter, the motor started and the spirometer filled with oxygen to about the 7 liter mark. The mouthpiece is adjusted and the nose clip apphed. When the spirometer level is constant and the temperature has been taken the valve is turned and a period of 12 to 15 respiratory cycles allowed to pass. Then at the end of an average expiration the watch is started and the reading taken. After 10 minutes the watch is stopped at the end of an average expiration, the spirometer level observed, and the temperature again noted. The time of the period, and the two volume and temperature readings are re- corded, the spirometer refilled and the same procedure repeated twice. At the end of the third period the valve is turned off for the first time and the test is finished. If the amounts of O2 con- sumed in 10 minutes do not check within about 100 c. c. it is advisable to run one or more extra periods. Calculating the Results. — The calculation of the results is much facilitated by the use of logarithms. The total volume of O2 consmned is obtained by adding the difference in the spiro- meter readings for each period. This volume is reduced to 760 mm. by multiplying by and to 0°C. by multiphing 273 bv Dividing by the total time of 273 + average temperature C. the three periods gives the O2 consumed per minute and from this the hour of the 24 hour amount is obtained by multiplying by 60 or 1440. This is converted into calories by multipljdng by the heat value of a liter of O2 at the respiratory quotient found, or by 4.825 if the R. Q. is assumed to be .82. The further cal- culation will depend on whether the Du Bois standard or the Benedict standard is to be used. In the former case the body surface is determined by the Du Bois formula from the height and weight and the number of calories per square meter per hour found by dividing the calories per hour by the body surface. Dividing by the expected number of calories per square meter for the age and sex gives the relation to the normal, which is multiplied by 100 to get the per cent, of normal. If over 100 this is written as per cent, higher than the theoretical value; 102 BASAL METABOLISM if less than 100 the figure is subtracted from 100 and the differ- ence written as per cent, below the theoretical value. A varia- tion of 10% above or below the normal is allowed but in general variations up to 15% below or 25% above are considered signi- ficant only when taken in conjunction with chnical findings. If the Benedict standard is used the number of calories per 24 hours is divided by the expected nximber of calories at the height, weight, age and sex of the patient and the result expressed in per cent, as above. Calculation of the respiratory quotient adds somewhat to the accuracy of the test as the heat value for 1 liter of oxygen varies slightly with it. The difference, however, is so slight that for clinical purposes it can be ignored and the heat value of a liter of O2 taken at the average respiratory quotient of .82. On theoretical grounds it is perhaps still more accurate to obtain the non-protein respiratory quotient as the heat values of O2 at the different respiratory quotients are calculated on this basis. This also allows a computation of the relative amounts of protein, fat and carbohydrate burned in the organism during the period of the test. The respiratory quotient is an expression of the relation of the CO carbon dioxid expired to the oxygen consumed ( — ^^ = R. Q.) O2 The weight of CO2 absorbed is multiplied by 0.5087, the voliune of a gram of CO2, and the volume thus obtained divided by the corrected volume of O2 consumed. A part of the energy of protein burned in the body is lost in the urine by the excretion of substance which may be still further oxidized. The O2 and the CO'2 values for these must then be subtracted from the theoretical amounts of O2 and CO2 for protein and the remainder considered available for respiratory exchange. It can be calculated that when protein is burned in the body, for every gram of N excreted in the urine 9.35 gms. of CO2 will be given off and 8.45 gms. of Oj absorbed for protein alone. The total N excreted in the urine during the period of the test having been calculated, the amounts of O2 and COj for protein are obtained by multiplying by 8.45 and 9.35 respectively and subtracted from the weight of O2 consumed and CO2 given off. The remaining O2 and CO2 are left for fat and carbohydrate BENEDICT UNIVERSAL APPARATUS 103 and after converting to voltime the relation between them is expressed as the non-protein respiratory quotient. ~r- = non-protein R. Q. U2 The computation on page 265 is one made on a patient with exophthalmic goiter. The heat value of Oj at the given respira- tory quotient and the volumes of 1 gm. of O2 and CO2 are taken from Luski where a full discussion of the principles involved may be found. When the respiratory quotient is not desired the calculation is simplified by the omission of the first and third portions. ^ Lusk, Graham: The Science of Nutrition, 641pp., $6.50, W. B. Saunders Co., Philadelphia, Pa. 1917. CHAPTER 9 THE JONES "METABOLIMETER"^ By Robert C. Lewis, Ph. D. Principle of the Method. — The determination of the basal metabolic rate is made with the Jones "Metabolimeter" by measuring the time required for the patient to consume exactly 1 liter of oxygen under standard conditions of pressure (760 mm. of mercury) and temperature (0°C.). The apparatus is the closed circuit tj^e in which it is necessary to measure only one gas, the oxygen, the assumption being made that the respiratory quotient of the patient is constant under conditions of the deter- mination. If a rigid adherence to the rules for preparation of the patient (see chapter 3) has been made, the R. Q. (respiratory quotient) will closely approximate 0.82. The heat value of oxygen varies to a small degree with the respiratory quotient; with an R. Q. of 0.82 it has been shown to be 4.825 calories per liter. Using this value and the time required to consume 1 liter of oxygen, it becomes a very simple matter to calculate the amount of heat produced per hour and, by estimating the surface area of the patient from a height-weight chart (after Du Bois), the amount of heat produced in calories per hour per square meter of body surface may be determined. This latter figure is the basal metabolism. Description of the Apparatus. — The metabolimeter consists essentially of (1) a CO2 absorption tower connected on the one hand directly with (2) a flexible rubber bag and on the other with the patient's lungs by means of rubber tubing and a special mouthpiece, the nose being closed by a suitable clip. Connection is also made with (3) a measuring cylinder and this in turn with (4) an oxygen tank. All connections between these different parts are rendered air tight by means of rubber or threaded connections, the latter being provided with rubber washers. 1 Designed and described (Jour. Am. Med. .'\.ss., 75: 538, 1920,) by Dr. Horry M. Jones of the University of Illinois College of Medicine. 104 THE METABOLIMETER 105 (1). The COj-absorption tower. — The C02-absorption tower is provided with a removable top which is held in place by a large hexagonal nut, and leakage at the cover is prevented by a rubber gasket. The tower is divided in the middle by a partition which runs from the top to within about 1 inch of the bottom. Near the top of this partition is a small opening pro- vided with a flutter valve, which per- mits the passage of air in one direction but not in the other. The tower is filled with broken charcoal var3nng from the size of a pea to that of a small chestnut. The charcoal is kept sat- urated with fresh, strong sodium hydroxide solution. The tower has 3 openings, 2 in the cover and 1 thru the bottom. As represented in the diagram the open- ings in the cover pass to the flexible rubber bag and the breathing tube, respectively. The opening in the bottom serves for the admission of oxygen from the measuring cylinder. This opening, instead of simply being tapped thru the bottom, is brought up to the center of one half of the tower by small metal tubing. This arrangement prevents sodiiun hydroxide solution from getting back into the measuring cylinder. As shown by the arrows in Fig. 2 (next page), air in passing from the patient's lungs is forced by the mechanical construction of the tower to pass down one side, under the partition, and up the other side, thus coming in contact with the large surface of sodium hydroxide on the pieces of charcoal and thereby losing its CO 2 before returning to the patient's lungs via the shorter route thru the flutter valve. (2). The measuring cylinder. — The measuring cylinder is considerably smaller than the C02-absorption tower. It is pro- vided with a pressure gage and is connected at the top by a needle valve with the C02-absorption tower, and at the side 106 BASAL METABOLISM with an oxygen tank. The gage is so standardized that the measuring cyhnder will deliver exactly 1 liter of dry oxygen tinder normal pressure (760 mm. of mercury) and normal temperature (0°C.), no matter what the room temperature may be. This is accomplished by having the gage marked in terms of degrees of temperature (Centigrade), the cyhnder being filled with oxygen until the gage records a pressure corresponding to the room temperature mark. In other words, when the room temperature is 25 °C. enough additional pressure is used over that provided for 15°C. to offset the expansion effect of the difference of 10 centigrade degrees in the volume of oxygen. In this way exactly 1 liter of gas measured directly in terms of 760mm. pressure and 0°C. is always used for a test. (3). Flexible rubber bag.— The patient breathes back and forth into a closed, air tight apparatus, all parts of which are of fixt volume except the flex- ible rubber bag. This bag is directly connected with the C02-absorption tow- er by means of its rubber tubing neck and, as the patient expires and inspires into the closed system, the bag expands and contracts. (4) . Oxygen tank. — A small size oxy- gen tank (about 16 inches long and of 40 gallons capacity, obtainable from a sup- ply house in any large city) fits in a clamp at the side of the measuring cylinder and has an air tight connection with it. No other kind than a round wheel-wrench (furnished with the metabolimeter) is satisfactory for use with this tank, for with it and with no other kind of wrench or key can one have perfect control over release of gas from the oxygen tank into the measuring cylinder. Overcharging the measuring cylinder will result in injury to the pressure gage, thereby ren- dering it inaccurate until re-caUbrated (see paragraf on recalibra- tion of pressure gage below). THE METABOLIMETER 107 Preparation of the Apparatus. — The apparatus is kept packed in a suitable carrying case, all parts except the oxygen tank l-eing contained therein. The oxygen tank is obtained from a local dealer or one in a nearby city. The various parts are removed from the box and the metabolimeter is assembled as shown, care being taken to see that all threaded connections are pro- vided with washers, thereby preventing leakage. The oxy- gen tank should hang directly over one foot of the tripod. If the apparatus is to be used for the first time, the charcoal is removed from the C02-absorption tower to a granite-ware or white enamel pan, covered with about 2 liters of 50 per cent, solution of sodium hydroxide, and allowed to stand over night. The excess of sodium hydroxide solution is then poured off and the C02-ab- sorption tower is filled with the wet charcoal. Thereafter this moistened charcoal is kept in the C02-absorption tower, ac- cumulated carbonates being washed out at the end of each series of tests by pouring 200 c. c. of water into the tower, allowing it to stand for a few minutes, and then replacing it with a second 200 c. c. of water. This water is allowed to remain in the tower until the apparatus is again needed, when it is poured off just before the metabolimeter is assembled. By this procedure the charcoal in the C02-absorption tower is kept moist and clean at all times. Just before a test is to be made all fluid is removed from the C02-absorption tower, as noted above, and 100 c. c. of 50 per cent, sodium hydroxide is poured over the charcoal, care being taken to distribute the alkali evenly to each half of the tower and not to pour it on the flutter valve. The cover is then put in place with the breathing tube outlet (the one with the three-way cock) on the flutter valve side of the tower. The apparatus is now ready for the metabolism determination, if a test shows it to be gas tight. To determine whether or not the apparatus leaks, the needle valve is closed and oxygen is cautiously admitted to the measur- ing cylinder by carefully turning the wheel wrench of the oxygen tank. When the indicator of the pressure gage is approximately at a point corresponding to the room temperature (in centigrade degrees), the outflow of gas from the oxygen tank is stopped and the needle valve of the measuring cylinder is opened. Gas escapes from the measuring cylinder into the C02-absorption tower and the rubber bag distends. When the side of the bag 108 BASAL METABOLISM almost touches the tower, the needle valve is closed and oxygen is again admitted to the measuring cylinder until the indicator of the pressure gage registers, after tapping the gage with a finger, exactly at the point corresponding to the centigrade temperature. If the indicator has gone beyond the desired point, the excess of gas may be discharged by opening the needle valve. The measuring cylinder now contains a supply of oxygen such that, when the needle valve is opened, exactly 1 standard liter (if measured at 0°C. and 760 mm. of mercury) of oxygen will be discharged into the closed system of the metabolimeter. The extent of space between the bag and the COa-absorption tower is now carefully noted and the stop watch (provided with the apparatus) is run for 1 or 2 minutes. If at the end of this time no increase in the space has occurred and the pressure gage still reads to correspond with the room temperature, all parts of the apparatus (closed system and measuring cylinder) are gas tight and ready for a metabolic rate determination. If a leak has occurred, it should be diagnosed by the procedure given below (see paragraf on Location of Leaks) . Before being used the mouthpiece, noseclip and breathing tube should be sterilized. This may be done by boiling in water or by immersing in 50 per cent, alcohol. At the end of each series of tests these parts should be removed and thoroly washed under a water faucet before being sterilized for the next patient. Preparation of the Patient. — The routine is given in Chapter 3. Above everything else, care must be taken to make the patient comfortable, raising the head on the bed by pillows if necessary. An explanation should be made to the patient that the only dis- comfort will be the slight inconvenience of breathing thru the mouth, and that all bad air is removed by the tower. The mouthpiece is connected with the apparatus in such a position that, when it is placed in the mouth, the breathing tube will not have to be rotated even to the shghtest degree. The mouth- piece is inserted into the mouth, and the upper and lower lips pulled well out and over the shield to make an air tight con- nection. The nose must be made air tight without causing the patient any discomfort. The Metabolism Test Proper. — After ascertaining again that the bag has not collapsed to an appreciable degree and that the indicator of the pressure gage still corresponds with the room THE METABOLIMETER 109 temperature, the three-way cock is turned at such a time during expiration as to allow the last one third of the volume of air expired to enter the apparatus. The bag expands so as to touch the side of the tower and then falls away during inspiration. With each respiration some of the oxygen is consumed and, as the carbon dioxid expired is absorbed by the alkali in the tower, the volume of gas in the closed system (lungs, breathing tube, C02-absorption tower, and bag) decreases slowly. Finally there comes a time when the bag fails to touch the side of the tower at the end of expiration. This may be determined with ease by the use of a white background and should occur after 5 to 10 respirations. If too much of the expired air is admitted, an unnecessarily long time may elapse before the beginning point is reached; if too little, the bag may fail to touch the tower, thereby necessitating an entirely new start (refiUing of bag and measuring cylinder). When the bag fails to touch the tower for the first time, the operator counts one; at the second failure, two; and finally, when the bag fails to touch for the third successive time, three. At this instant the stop watch is started and the measurement of the time required for the patient to consume 1 liter of oxygen has begun. The needle valve of the mieasuring cylinder is now opened slightly and the oxygen contained therein under pressure is allowed to escape slowly into the closed system. When the measuring cylinder has been completely discharged, as determined by the fact that the indicator of the pressure gage stands, after gentle tapping, at the zero pressure mark, the needle valve is again closed. Exactly 1 standard liter of oxygen has been admitted to the closed system and must be consumed before the rubber bag returns to its initial position.^ In the same way as the beginning point was chosen, so the end of the period is taken as that time when the bag fails to touch the tower at the end of expiration for the third successive time. At this instant the stop watch is stopped, the three-way cock is turned, the mouthpiece and noseclip are removed, and the patient is allowed to rest for a few minutes. The stop watch is then carefully read and the time noted (in minutes and hundredths thereof) . An error in reading of 1 minute is not unusual for one who is not thoroly accustomed to a stop watch; so that extreme ' Even if the oxygen used is not absolutely IOC per cent, pure, 1 standard liter of oxygen must be consumed before the rubber bag will return to the beginning point, oxygen previously present in the closed system being used in place of the inert gas which has been discharged. 110 BASAL METABOLISM care should be taken to prevent an erroneous conclusion as a result of inaccurate reading of the time. In our experience (at the Laboratories of the Medical and Surgical Group of Denver) it is not necessary to remove the tower and replace the alkali until 2 determinations have been made. Consequently, after the patient has rested for 5 minutes the mouthpiece and noseclip are again put in place and the test is repeated as described above. If the time required to consume 1 standard liter of oxygen checks the first test within 0.2 of a minute, it is not necessary to proceed further. However, the first test generally gives erroneous results, probably due to the nervousness of the patient, and must be discarded. In this event a third test must be made. Before doing this the CO2- absorption tower is removed and the alkali is poured off from the side opposite the flutter valve. A square of wire gauze with a hole punched in the center facilities removal of the alkli without loss of charcoal. A fresh 100 c. c. portion of 50 per cent, sodium hydroxide (sufficient for 2 additional determina- tions) is then poured over the charcoal, the apparatus is again assembled and a third test is made. If, as occasionally happens, checks are not obtained, additional determinations are made until it is established beyond the shadow of a doubt what time is required for consumption of a standard liter of oxygen under basal conditions. Unless close checks are obtained, entirely erroneous conclusions may be drawn as to the actual basal metabolic rate of the patient. Altho the data is not needed for calculation of results, valuable information for aid in diagnosis to be used along with the figure for basal metabolic rate, may be obtained by noting the pulse and respiration rates. The former should be taken between tests, the latter by counting the number of excursions of the flexible rubber bag during the third minute of the test. After the tests have been completed the patient's height (stocking feet) in inches should be measured and the weight in pounds taken. For the purpose of calculation, nude weight is required, and may be calculated sufficiently accurately by sub- tracting the approximate weight of the clothing from the weight of the patient as taken. The age of the patient must also be ascertained. Calculation of Results. — Having obtained checks on the THE METABOLIMETER 111 time required for the consumption of 1 liter of oxygen, the average of these figures is taken as a basis for the calculation of the basal metabolic rate. It should be remembered that the quantity of oxygen consumed during a test would equal exactly 1 hter measured under standard conditions (at a barometric pressure of 760 mm. of mercury and a temperature of 0°C.). Conse- quently, it is not necessary to correct the oxygen consumption to standard conditions, as would be required with any other type of apparatus; the oxygen consumed during each test is exactly 1 standard hter, no matter under what condition of atmospheric pressure and temperature the test may have been conducted. Knowing the time required to consume 1 standard liter of oxygen, the consumption per hour may be readily calculated. By dividing this figure by the body surface the oxygen require- ment per square meter of body surface is obtained. If the assumption is made that the respiratory quotient is 0.82, each liter of oxygen will yield 4.82.5 calories (see paragraf on Principle of the jVIethod) . By multiplying the figure for oxygen consump- tion per square meter of body surface by 4.825, the basal meta- bolism, i.e., the heat production in calories per hour per square meter of body surface, is obtained. In actual practice all figuring is eliminated by the use of charts provided with the apparatus. From the Body Surface Chart and Tables in Chapter 28 the body surface in square meters may be quickly obtained from the data of weight and height of the patient. The body surface area is used with the average time obtained for the consumption of 1 standard liter of oxygen for finding from Table 2 the basal metabolism of the patient. The intersection of the "body surface" and "time" lines is noted and its position between the oblique lines for basal metabolism is estimated to within 0.5 of a calorie. What the basal metabolic rate of a normal person of the age and sex of the patient should be is found in Table 3. The plus or minus per cent, rate is found by using the figures for the normal rate and observed rate in Table 4. The intersection of the lines for these two rates is noted and the plus or minus rate is read off from the oblique lines by interpolation, just as was done with the other charts. Thus the complete calculation of results is made by the reading of charts. To give a concrete example of a calculation: Female, age 32; E 3 in z z o >" u u >■ o X I- o □ u. u - n D Ul O I- TABLE 2 For Reducing Stop-wateh Time and Patient's Body Area to Calories per Hour per Square Meter. _ — ---—---__ M N) W ro t\i n \ \ \ ^ \ \ N Nl s^ s \ ^\ X \ \ y \^ \ \ \ ^ V \ \ -^ N \^ x\" \ ^•^ V V \ V, ^ \^ v\ \H ^4," \ ^ ^ "■ ■^ -~~, N^ <^^^^ ?N ^ ^ -^ ^ ^'^^ K ^ --- ^ -^ ■-^ :::::: ^ ^ ![^ — '^ ^ ;;^ -- 1 "^ :== ^ lODY AREA IN Curved lines = caloi QUARE METERS B per hr. per sq. meter TABLE 3 Average Rates of Persons in Health, in Calories per. Hour per Square Meter Body_ Area (From Aub and DuBois > Age Males Females 6-8 58.0 58.0 8-10 54.0 54.0 10-12 52.0 50.0 12-14 50.0 46.0 14-16 46.0 43.0 16-18 43.0 40.0 18-20 41.0 38.0 20-30 39.5 37.5 30-40 39.5 36.5 40-50 38.5 36.0 50-60 37.5 35.0 60-70 70-80 36.5 35.5 34.0 33.0 TABLE 4 For Reducing Patient's Calories per Hour per Square Meter to plus or minus Per Cent Rate of Metabolism 60 7S 70 JS 6S 60 SS SO -fS K) OBSERVED RATE BY TEST Radiating linea = plua or minus c000TtiOc0{N00C003CD -C'^i0i0cD<£>l>00C001CDOO'-HC4 'oocooo(X)oooqcocooqoqoiosaso\ ''OOCOOOoOoOoOOOoOOOOSOJOSOiO* ^OCD{N00CCOCD(N00C000lCrH — ^iOi0cDcDt>-C0C00i05OOTH(N00 ^OOCOOOODOOGOOOC<000010505C500 OOCOOOOOGOOOOOoOOiaiOSOSOlOO '^oooooooqcoooGOoocnasOiOiosoo WSlOCDlr-t-OOOOOSOOr-li-lO^COPO '^OOGOOOOOOOOOG001C5050S0105M ^ f_i-lt~C0C»lOCOi-lt-«) y M ^ooooooooooooooojoiooraicioo g Q r-h ^ S'Ot-t-OOOOOOO'-lrHlMWSS' Si>r-oooo0200rt.-i( v.-< 1;^ -vr vj' «ij cf "^^ i^ tf\ 00050503050505050505050505'" omoiooiooino (U O Qi pi '^000000000005030305030305051^ g< O g 8 b U Ml>(M001i5^t;C<3O5'Ort ^ ....•• '^ci000O5aiO5OiOiO5O5O5O3<35a3'*-' ^'<:HOl>C00ii0(NC0'^Ot^C0a>_, Soioo^rHCNcoco-^toiococor:^ ^^ n^ *T\ ^T^ f^^ l'^^ /T\ fT^ r^^ ^^K l'^^ j*^n /T^ *^\ CHAPTER 12 SANBORN HANDY APPARATUS By Charles G. Beall M.D. This apparatus has several advantages. It can be trans- ported in its case any distance and can be easily carried so that a metabolism determination can be made in the home. It does not get out of order as easily nor require as much attention as the larger types of apparatus. While the oxygen bell is not counterbalanced, patients generally take the test better with this apparatus than with our larger one. It may not be quite as Marker Clip Guide Arm with Cubic Centimeter Scale Set Screw to Adjust Guide Arm Mouth Piece Oxygen Bell. Capacity 6 Liters. Fill Tank witJi Water Here Soda Lime for Carbon Dloxid Absorption Inside: Breathing Tube Valve Breathing Tube 130 SANBORN HANDY APPARATUS 131 accurate as some of the older types of apparatus, but for clinical purposes it is very satisfactory. The table below gives the comparative readings of oxygen consumption of 10 individuals by the two types of apparatus that I am using. Normals Age Sex Benedict Handy Average St. J. 24 C. B. 40 E. 0. 30 J. R. 29 E. B. 19 M M F M F -13% — 19 + 9 — 5 + 14 - 2% — 14 + 5 + 2 + 15 — 8% — 17 + 7 — 2 + 14 C. M. 27 Chronic Appendicitis F — 0.5 — 7 — 4 M. S. 27 Simple Goiter F — 8 — 3 — 5 P. S. 29 Exophthalmic Goiter M + 98 + 89 + 94 I. R. 23 Adenoma of Thyroid F — 18 — 2 — 10 C. L. 50 Exophthalmic Goiter F + 61 + 49 + 55 The most probable values would be the average. Even with the same apparatus, different readings on the same individual will commonly vary 5 or 10 points in the metabolic rate. Several tests should be made on a patient and the average taken. Desscription of Apparatus. — (See illustration) . The spirometer bell contains oxygen and moves up and down in a water seal. The patient inhales from and exhales into this supply of oxygen thru a breathing tube entering thru the base of the oxygen chamber. The inhaled and exhaled gases pass thru a container of soda lime inside of the bell, thus removing carbon dioxid from the exhaled gas. The volume of oxygen consumed by the patient is shown by the scale in cubic centimeters. The scale automatically reduces the volume to zero degrees, Centigrade. The mouthpiece, metal connection and breathing tube should be sterilized by boiling before making the determination of the basal metabolic rate. 132 BASAL METABOLISM Testing the Apparatus. — It is of the utmost importance, in testing the metabolic rate of a patient, that there is no leak in the circuit, because the escape of oxygen from the tank, other than that being consumed by the patient, will mean an increase in the final reading, and, consequently, a misguiding result. The question of leakage should be looked after from two different angles, the patient and the machine. A mouthpiece improperly fitted, namely, one which is not overlapped by the lips, is liable to be the source of a leak at the least movement of the patient. Besides, it is very annoying to have a mouthpiece fitted wrongly causing undue discomfort in the mouth, annoying from the patient's standpoint, because he or she will have to stand it for 10 or 15 minutes, and annoying from the standpoint of the observer because the results will be modified. The nose clip is another factor that may modify the results. It will cause increased oxygen consumption, unless pains are taken to observe that there is no escape of gas. It is customary to fasten the nose clip before adjusting the mouthpiece. When this is done the patient is asked to close the lips tightly and make an expira- tory effort through the nose. If there is any leakage the nose clip is tightened and the patient asked to repeat the procedure until we have the certainty that the patient is not allowing the escape of air through the nostrils. In testing the apparatus itself proceed as follows: Open the breathing tube valve and allow air to enter by lifting the bell to the 4,000 or 5,000 c. c. mark. Close breathing tube valve. Place several small objects on the spirometer bell, not over half SANBORN HANDY APPARATUS 133 a pound, and distributed in such a fashion that the bell remains level. Read the scale again at the end of 10 minutes. Naturally, the second reading should be the same as the first. If it is not, there is a leak in the system. If a leak exists, push the ends of the rubber tubings further on the metal tube thus tightening the connections. Preparation of Patient. — It is essential that the patient be in the fasting state, i. e., without food for 14 hours. It is best to make the determination in the morning. The usual instructions given the patient are, that he must eat or drink nothing after the evening ineal and must not eat any breakfast, nor even drink a glass of water. This is important, as a patient will often take a cup of coffee and say, "that is no breakfast". A difference of 15% has been found in the metabolic rate before and after a cup of coffee. The patient's weight and height, without clothing, are taken, and he or she should then he down for at least 30 minutes before the test. Making the Test. — The apparatus is set up. The water seal of the gasometer is filled with water to within 2 inches of the top. The spirometer bell is then filled with oxygen by connecting the breathing tube with the oxygen tank and admitting 4,000 to 5,000 c. c. of oxygen. The breathing tube valve is now clamped tight. At this point it is well to explain to the patient as plainly as possible the object of the test and what is to be done, assuring him that he will have no pain or discomfort and will not be put to sleep, and that the object of the test is to determine how much "pure air" is consumed in 10 minutes. His confidence and co- operation is thus obtained. The nose chp is now adjusted and tested to see that no air escapes thru the nostrils by the pro- cedure above described. The mouthpiece is then handed to the patient, the technician showing him with another mouthpiece just how to introduce it into his mouth. After this is comfortably adjusted he is instructed to exhale and hold the breath until the breathing tube is connected to the mouthpiece and the breathing tube valve released. This takes only a few seconds. As explained in Chapter 7, care should be used in taking the readings on an apparatus of this sort, to obtain regular breathing. "Irregular expirations, however, deeper or shallower than the average or normal ones, are always more or less niomerous, and if the scale is read at the end of one of these considerable error 134 BASAL METABOLISM may be introduced." . . . When three or four regular expira- tions occur, note the height to which the bell rises, and the time. At the end of 5 minutes, again a reading should be taken. Two or three of the 5 minute periods should be run for each test of a patient. If there is a material difference between the 5 minute readings, it is best to repeat the test. (The test sheet shown below is a convenient form to use) . METABOLISM TEST SHEET Date Name Age . Height Weight Physician Technician Time Min. Min. H. H. H. H. M.. .. .. .. S.. .. . . c.c. M.. .. .. .. S.. .. . . c.c. M.. .. .. ,. S.. .. . . c.c. M.. .. Min. . . .. .. S.. . . . . c.c. c.c. Consumed in Min. Per Minute c.c. Consumption of Oxygen per Minute at 0°C. and 760 mm. Normal Consumption Plus or Minus Basal Metabolism in Percentage Remarks Volume SANBORN HANDY APPARATUS 135 The average amount of oxygen used per minute is now deter- mined. This figure is now corrected for temperature, the temperature being noted on the thermometer inside the oxygen chamber. With this apparatus corrections for temperature of the gas are easily made. There is a special scale for the volimie and "this scale is graduated so that the equivalent volume of gas at 0°C. is read directly from the scale at 19°, 20°, or 21° C." The cor- rections for volumes read at the temperatures commonly used are as follows: Degrees Centigrade Volume Corrections 16, 17, 18 Add 1% 19, 20, 21 No correction 22, 23, 24, 25 Subtract 1% This figure is then corrected for barometric pressure. When the barometer readings are near 760 mm. the corrections may be made by subtracting 1% for each 10 mm. below 760, or adding 1% for each 10 mm. above 760. This now gives the average amount of oxygen consumed per minute at 0° Centigrade and at 760 mm. barometric pressure. Now find what the normal consimiption is for this patient's weight and height by referring to the table on page 242 being sure to make the corrections of the figures in the table for age and sex on page 241. The differ- ence between this figure and the actual amount consumed by the patient shows whether the rate is above or below normal. The difference is divided by the normal consimiption and the result is the percentage above or below normal or the metabolic rate. The simplified method of computations that is used with this apparatus reduces the time of computations to less than 5 minutes, and, as I pointed out at the beginning of this article, the results found by use of this apparatus check within cUnical requirements. CHAPTER 13. VALUE OF BASAL METABOLISM STUDIES^ By Albert H. Rowe, M.D. Metabolism Studies. — -All investigators agree that basal metabolism depends largely upon thyroid activity and that an increase in the activity of this gland raises the metabolic rate above normal, while a decrease in thyroid secretion depresses the rate below its normal level. While other ductless glands, espe- cially the pituitary and ovary, control metabolism to a lesser degree, and while certain diseases such as fevers, lymphatic leucemia, hyperpituitarism, polychemia, severe diabetes, cancer and pernicious anemia increase the basal metabolic rate, and starvation, hypopituitarism and wasting diseases decrease it, — all these conditions can easily be ruled out in a careful diagnostic study. Thus, for proper investigation, basal metabolic rate determinations in thyroid disturbances are coming to be recog- nized as being as indispensable as is the Wasserman reaction in syphilis, or temperature determinations in fever. Studies made by the Author. — The author has been interested in basal metabolism in thyroid disease since 1915, when he came in intimate contact with the work of Means, Joslin and Du Bois in Boston and New York. This interest was intensified when in the fall of 1920 he watched the work of Boothby and Plummer at the Mayo Clinic, after which he estabhshed in his own office a metabohsm apparatus. Since then, he has made careful clin- ical and metaboUc studies of some 80 cases of actual and sus- pected thyroid disturbances and has become convinced of the value of basal metabolic rate determinations as a guide to both the diagnosis and treatment of these conditions. 'Editor's abstract of "The Value of Basal Metabolism Studies in the Diagnosis and Treatment of Thyroid Diseases" — Am. Jour. Med. Sc, 162: 187. August, 1921. Approved by Author. 136 VALUE OF BASAL METABOLISM STUDIES 137 An Aid to Differential Diagnosis. — Mild or definite cases of hyperthyroidism can be differentiated from neurosis and early tuberculosis by basal metabolic rate determinations. In a series of 49 cases referred to the author, with the diagnosis of actual or suspected hyperthyroidism, only 16, or 39 per cent., had rates above the approximate normal hmits of ±10 per cent. Clinically, all the cases showing rates higher than + 10 per cent, were definitely hyperthyroid. Moreover, with the exception of one, all the other cases that showed normal metabolic rates had one or more symptoms and signs which suggested hyper- thyroidism, tho a very careful scrutiny of their records in most cases would incline one to doubt the existence of too much thyroid secretion. It is especially in those cases where a decided ex- ophthahnos is present, where marked tachycardia, nervousness and sweating occurred, or where a tachycardia following a recent tuberculosis persisted, that a method of deciding on the re- sponsibility or harmlessness of the thyroid gland is of great importance. We all see tremulous, nervous, excitable, weak, and thin individuals who may or may not be hyperthyroid in type, the definite determination of which state is impossible without such a test as this one we are considering. Clinicians especially interested in heart diseases and in tuberculosis are beginning to see the advantages of these determinations in their diagnostic work. The basal rate determinations are being found of increased value in the analysis of tachycardia. Test of the Severity of Hyperthyroidism. — Again, the severity 'of an obvious case of h3rperthyroidism can be more accurately determined thru basal metabolic rate determina- tions than by any other method of analysis. Thus in our series, one case had symptoms which could easily suggest a very severe state of h^'perthyroidism, whereas her metabolic study placed her in the mild group of cases. Another case had encephalitis lethargica develop on top of her h5^othyroidism, and the problem of how much the thyroid was to blame for the prolonged con- valescence and weakness was greatly illuminated by the basal metabolic rate result. Another case which, one year ago, had a marked strmna with tachycardia, exaggerated tremor and loss of weight, and who had her septic mouth cleaned up at that time, still presented marked exophthalmos and some tremor. Tho we believed her hyperthyroidism to be considerably diminished, 138 BASAL METABOLISM it was a distinct surprise to find a normal rate. In other words, basal metabolism determinations have a definiteness which clinical signs have not. Guide to Roentgen-Ray Therapy. — As a guide to the amount of roentgen-ray therapy needed in a case of hyperthyroidism due to hyperplasia of the thyroid gland, basal metabolism studies are indispensable and are necessary for scientific work. One of our cases when first seen was a severe type of true hyperthyroidism, and at that time we were not ready to make metabolic rate determinations. Four rounds of roentgen-ray treatment had heen given when her first test was made, and in view of her increased weight, slower pulse, great improvement in her ner- vous condition and her increased strength, together with a rate of only + 7 per cent., we discontinued roentgen-ray therapy for one month. By that time her clinical condition was not quite so favorable and her rate had risen to + 12 per cent., because of which another round of roentgen-ray was given. . . . Another case, with a rate of + 10 per cent, after 11 roentgen-ray exposures, had marked hyperthyroidism before treatment. . . . Another has had definite amelioration of symptoms and reduction in rate by the use of roentgen-ray over, several months. . . . Our experience, therefore, indicates a definite beneficial effect of roentgen-ray treatment in cases of true exophthalmic goiter. The amount of therapy necessary to reduce the metabolic rate to normal limits certainly varies with the case. That there is danger of too much roentgen-ray is certain. Moreover, roentgen- ray will probably be found ineffective in fulminating cases. . . . With the increasingly low mortality after operative treatment in mind, we cannot at this time recommend roentgen-ray as a sub- stitute for surgery in all cases of hyperthyroidism. However, when it is used the effect must be carefully followed by metabolic rate determinations. This is especially emphasized by an ex- perience of a colleague in another city whose patient remained well for two years after a thyroidectomy. He then became weak and nervous, and as his condition suggested a return of the hyperthyroidism, he was sent for roentgen-ray therapy. Soon afterward a metabohsm test disclosed that he had a — 35 per cent, rate and, upon the administration of thyroid gland, his condition immediately improved. Here roentgen-ray was being administered where it was absolutely contraindicated and the VALUE OF BASAL METABOLISM STUDIES 139 error was discovered only thru metabolic rate studies. All ■doubtful cases of mild hyperthyroidism should have their rates determined before roentgen-ray therapy since many innocent thyroids are roentgen-rayed when they should be left entirely alone. An Index to Toxicity of Adenomas of the Thyroid. — Another use of the metabolic rate lies in the indication given as to the degree of toxicity of adenomas of the thyroid. It is weU known that adenomatous thyroids may produce no symptoms of liyperthryoidism or that all symptoms of Graves' disease may occur. Thus the finding of rapid pulse, nervousness and tremor in the individual with an adenoma of the thyroid calls for a •determination as to the responsibility of symptoms; whether the gland has taken on excessive secretory activity or whether a neurosis or sympathetic stimulation is causative. . . . One of •our cases, with a metabolic rate of + 53 per cent, after very exten- sive roentgen-ray therapy, illustrates the opinion of roentgenolo- gists today that hyperthyroidism due to adenomatous thyroids is not benefited by roentgen-ray treatment in the marked degree that hyperthyroidism due to hyperplasia of the gland is by such treatment. This woman, subjectively, feels a little better but Iter thyroid is still very active, as shown by her symptoms, and especially by her recent rate of -I- 57 per cent. Another case had been diagnosticated as having a toxic adenoma, and before metabolism determinations had received 3 rounds of roentgen- ray with no amelioration of symptoms. The normal rate recently obtained probably indicates that the symptoms for which she was being treated by roentgen-ray were neurotic in nature. Still another case had an intrathoracic adenoma and recently had been told that she was extremely toxic, as indicated by a marked tremor and subjective nervousness. Here again the rate was found to be normal, indicating a functional rather than a toxic nervousness. A Guide to Surgery. — As a guide for the surgical removal of hyperplastic, colloid and adenomatous thyroids, metabolic rate studies have gained recognition from the leading goiter men of the country. Means emphasizes the importance of these tests before surgery and, with Boothby, feels that when rates of over + 70 per cent, are found, rest or ligation should be resorted to before thyroid removal. ... It is generally conceded by sur- 140 BASAL METABOLISM geons, however, that the metabolic rate is not an inflexible guide, and that even when the rate is high, if the clinical condi- tion be favorable, it is probably safe to operate. ... As before stated, adenomatous thyroids must be treated surgically, since the metabolic rates are not easily reduced by roentgen-ray. A Method for Diagnosis of Hypothyroidism. — In diagnosing hypothyroidism and myxedema, metabolism tests hold as im- portant a position as in the diagnosis of hyperthyroid states. Clinicians are always presuming lack of thyroid secretion because of dry skin, thin hair, slow pulse and obesity. Analysis of such cases very often shows a perfectly normal rate and indicates that the responsibility of the symptoms can not be attributed to thy- roid activity. Thus in 25 cases recently referred, with the possi- bihty of hypothyroidism, only 10, or 40 per cent., had metabolic rates sufficiently low to indicate too little thyroid, or the possi- bihty of other ductless gland inactivity. Of these 25 cases, 10- were extremely obese and could easily suggest the lack of thyroid secretion; none of these, however, showed rates below normal limits. . . . One of the cases referred, when first seen a year ago, was a typical advanced case of myxedema with anemia, non- pitting edema and mental disturbances. At present she is taking thyroid very intermittently and feels well, altho her rate is still — 28 per cent. A Guide to Thyroid Therapy. — Finally, as a guide to correct thyroid administration, metabolic rate determinations are of the greatest value. As already stated, hypothyroidism with con- sequent thyroid therapy is undoubtedly often misdiagnosed. Metabohc studies, moreover, as pointed out by Means, usually show that it takes much less thyroid to keep that rate at normal than is usually administered; furthermore, it is found that the rate can be elevated considerably above normal without clinical symptoms of hyperthyroidism being evident. That such therapy does harm, even tho these symptoms are not present, is shown by a case recently s^en in which thyroid administration in rather large dosage for obesity suddenly produced a dilated thyrotoxic heart. This emphasizes the necessity for the use of the metabohc rate studies as a means first, of being sure of your clinical diag- nosis, and second, of gaging the amount of thyroid therapy. At present, in the use of the dry thyroid gland, we have little idea of the strength of the preparation, Kendall has shown that VALUE OF BASAL METABOLISM STUDIES 141 the amount of thyroxin in thyroids varies according to seasons. . . . Plummer has shown that 1 mg. of this thyroxin raises the metabolic rate about 2 per cent, and that it takes about 1 mg. per day to keep the rate of a myxedematous patient up to the normal. However, he determines his dosage by metabohc rate studies. . . . We feel that thyroid administration to children should be guided, if possible, by metabolic studies, and that these studies should be the basis for the diagnosis of mild hypo- thyroid states that are so often assumed by clinicians in their young patients. No child should receive thyroid simply because he looks "a little hypothyroid in type." Conclusions. — The importance of basal metabolism studies in the handling of thyroid diseases must be recognized. By metabolic rate determinations we are greatly aided in our diag- nosis of early and obscure cases of hyperthyroidism. Moreover, the degree of severity of an obvious hj^erthyroidism can be determined by this test. Again the presence or absence of toxicity of an adenomatous thyroid is made evident thru these metabolic studies. As a guide for surgical removal of goiters, surgeons are recognizing the value of this test. Finally, in the diagnosis of hypothyroidism and in directing and gauging thyroid administra- tion, metabolic rate determinations are of the greatest importance. CHAPTER 14. BASAL METABOLISM AND THE GENERAL PRACTITIONERi By James H. Hutton, M. D. Variations in Thyroid Activity. — In automobile language the thyroid is the ignition system of the body. Under certain con- ditions any increase or decrease in heat production is usually due to a corresponding change in thyroid activity. The two extremes of its activity are easily recognized. The picture of well-marked Graves' disease, and of the cretin, are ahnost as familiar to the laity as they are to the profession. It is the borderline case, where either a shght hypothyroidism or a slight hyperthyroidism exists that is hard to recognize. Up to date the best measure of the degree of thyroid activity is the determination of the basal metabolic rate. Certain con- ditions cause variations from the normal limits, hyperthyroidism probably being the most frequent cause of an increased rate. Febrile conditions, leucemia with large numbers of white cells, and acromegaly are also causes of an increased rate. Hypothy- roidism is the most frequent cause of a decrease in rate. Carbohydrate tolerance, which is another gross measure of metabolism, is usually decreased in the hyperthyroidic and increased in the hypothyroidic condition of the gland. Men who are doing a large amount of work with these tests feel that the determination of the basal metabolic rate is a much more accurate measure of the activity of the thyroid than any other test in use at this time. As a Differential Diagnostic Measure. — Incipient tubercu- losis is hard to differentiate from hyperthyroidism. Many cases are sent to sanatoria every year, only to be sent home when their rate is found to be 15 to 20 per cent, above normal. So far as 'Editor's abstract of "Basal Metabolism and the General Practitioner", 111. Med. Jour., June, 1921. Approved by author. 142 THE GENERAL PRACTITIONER 143 known, tuberculosis does not cause an increase. Organic heart disease, incipient tuberculosis and hyperthyroidism many times resemble each other very closely. A knowledge of the basal metabolic rate will enable one to decide with a great deal of certainty whether the thyroid is at fault. Case Reports. — Clinically it is often difficult to distinguish hyperthyroidism from hypothyroidism. As an example: Last winter Mr. W. had the flu. His recovery was slow and after a time he developed tachycardia, a tremor, loss of weight and other symptoms of hyperthyroidism. A number of physicians saw him and all were more or less agreed that his illness had precipitated an attack of hyperthyroidism. A surgeon advised operation as soon as the patient could stand it. Soon after this his basal metabolic rate was found to be 20 per cent, below normal. He recovered when given thyroid gr.i.t.i.d. Recently Janney and Henderson have called attention to "latent hypothyroidism." Most of us probably have such cases under observation. For instance, Mrs. G., 30 years of age, complained of various pains in her back, arms and hands. She had little "pep", but little appetite and no ambition; wanted more sleep than the average person and indulged in bad dreams while getting it. Her family and past history seemed to have no bearing on her present trouble. She had a negative Wasser- man and negative physical examination. She had a slight degree of anemia. Her blood pressure was 110-70-40 and her urine was low in specific gravity and urea. Her basal metabolism was 12 per cent, below normal. Her friend, who referred her to me, said that the patient's only trouble was that of many American women — too much money and time, too little responsibility, and a too active imagination — and yet under the influence of thyroid combined with a little ovarian substance and small doses of pituitary, she soon became able to take an interest in many things besides her own aches and pains. Value of Basal Metabolism Determinations. — The determina- tion of the basal metabolic rate in such cases may mean that many so-called neurasthenics can be changed from bores, for whom nothing can be done, to interesting cases for whom a great deal can be accomplished. This test for basal metabolism is a measure almost strictly diagnostic, and gives us exact and valuable information where formerly we had none. It in no 144 BASAL METABOLISM way relieves us of the responsibility of taking case histories and making the usual physical examination and laboratory tests. In fact, the finding of a basal metabolic rate outside the normal limits should, in many cases, stimulate us to make a more careful examination and a more detailed inquiry into the patient's history — especially the family history and the developmental period of the patient's life. The General Practitioner's Opportunity. — To us, as general practitioners, a knowledge of basal metabolism is of especial value. We see these cases early and if we can make a diagnosis promptly and institute proper treatment, they may never reach the stage where the specialist is called. If the specialist is called, and we have made the diagnosis, no one can complain that the patient's life might have been saved if only Dr. So-and-So had been alive to the situation. We probably overlook the hypothy- roidic condition more often than the hyperthyroidic; yet the former is the condition offering the greatest opportunity for brilliant cure. CHAPTER 15. BASAL METABOLISM IN VARIOUS DISEASES By H. 0. MosENTHAL, M. D. Facts of importance to clinical medicine have been obtained by the study of basal metabolism in obesity, cardiorenal disease, nephritis, pernicious anemia, leucemia, and diseases of the thyroid gland. The following table, taken largely from the writings of Du Bois and his collaborators (altho other sources have been consulted) indicates the variation in basal metabolism that has been observed in these diseases: BASAL METABOLISM AS REPORTED IN VARIOUS DISEASES Fer cent, basal metabolism above or below average normal Normal . —15 to +15 Obesity —14 to +10 Cardiorenal without dyspnea . — 10 to +10 Cardiorenal with dyspnea . . +25 to +50 Nephritis with edema. . . . — 40 to +14 Nephritis without edema . . . + 2 to +29 Pernicious Anemia , + 2 to +33 Leucemia . +21 to +123 Prolonged undernutrition — 30 to — 10 Exophthalmic Goiter: Very mild . . +15 to +30 Mild . . . +30 to +50 Severe . +50 to +75 Very severe . Over +75 Cretinism and Myxedema — 40 to — 15 ^ Editor's abstract of "The Clinical Value of Basal Metabolism. The Determination of Basal Metabolism by Means of the Benedict Portable Respiration Apparatus. Facts of Importance to Clinical Medicine that have been obtained by the Study of Basal Metabolism in Obesity, Diabetes Mellitus, Cardiorenal Disease, Nephritis, Pernicious Anemia, Leucemia, Typhoid Fever, and Diseases of the Thyroid Gland." Medical Clinics of No. Am. March 1921, 4: 103. Approved by Author. 145 146 BASAL METABOLISM Obesity. — There are some cases of obesity which are due to disturbances of the internal secretions. The t3^es brought on by the diminished activity of the thyroid and hypophysis are familiar to all, and may be diagnosed in large part by their clinical characteristics. In doubtful cases, however, a deter- mination of the basal metabolism will be of very great help. In the h3^othyroid cases the basal metabolic rate is below normal. In the more common form of obesity, due to overeating, physical inactivity, and a placid disposition, the metabolism, as measured by the surface area, is within normal limits. Evidently the increased body bulk, due to the "inert fat", has not the same effect in reducing metabolism as the "inert fluid" has in edema- tous patients. The former are up and about and the latter are usually bedridden and undernourished; these differences may be the determining factors in maintaining or lowering the basal metabolism. In treating obesity it is obvious, in view of the normal metabolic rate that exists in these individuals, that the addition of thyroid preparations to the subcaloric diet as an "accelerator" for the loss of weight, must be carefully watched. In these cases, symptoms of hyperthyroidism often follow even comparatively small doses; tachycardia, cardiac irregularities, headache, nervousness, restlessness, diarrhea are prone to develop and must be guarded against. In every case of obesity loss of weight does not ensue upon the use of thyroid medication, tho the drug is given to the point of mild intoxication. Nephritis and Heart Disease. — In cases of mild nephritis and compensated cardiac disease the basal metabolism ranges within normal limits. In some instances in cardiorenal patients the metabolism rises as high as 50 per cent, above the average. Dyspnea is the factor that produces this change; the muscular effort entailed by the increased respiratory rate is presumably responsible. On the other hand, in some cases the basal meta- bolism is considerably lowered; in patients who have much edema it may be as much as 40 per cent, less than the average. The edema increases the surface area by distention with an inert fluid, and it is probable that a lower metabohsm as measured by the surface area should be present under such circumstances. A rise in blood pressure, the presence of an acidosis or even the existence of marked impairment of renal function, as measured by the conventional tests, does not influence the plane at which meta- BASAI. METABOLISM IN VARIOUS DISEASES 147 holism proceeds. The abnormally high metabolism occurring in certain nephritics has been attributed to the dyspnea and rest- lessness characteristic of the severe types of the malady; previous fasting and undernutrition may be responsible for some of the low figures presented. Furthermore, a study of the respiratory quo- tients makes it evident that the metabolism of proteins, fats, and carbohydrates is not disturbed in the cases of heart and kidney disease thus far observed in the calorimeter. In isolated instances in very severe nephritis a determination of the nitrogen balance has shown that a toxic destruction of protein must exist at times at least. This apparently occurs most frequently when such patients are moribund and the phenomenon thus assumes a position of minor clinical impor- tance. From the physician's point of view some of these facts are of very great value. Dyspnea and edema in themselves demand immediate symptomatic treatment, and the determinations of basal metabolism are not of any aid in making either the diagnosis or therapy more precise. The knowledge that hypertension, acidosis, and renal insufficiency do not alter the metabolic rate or result in any change in the nephritic or cardiac patient that impairs his abihty to utilize proteins, fats, or carbohydrates, gives the clinician a very sound foundation upon which to proceed when the very important dietetic side of the treatment is deter- mined upon in this group of cases. Pernicious Anemia. — The increase of basal metabolism pre- sent in pernicious anemia may be somewhat unexpected. The languor of such patients certainly does not indicate it. The rapid regeneration of blood-cells, and the extra effort required from weakened and impaired muscles in carrying out the bodily functions, especially the respiration and circulation, with the increased frequency of the respiratory rate and the heart-beat, may explain the rather marked rise in basal metabolism occurring in anemia. These observations indicate why rest and a high caloric regime are efficacious in bringing about an amelioration of the condition. The high diet is generally acknowledged as being desirable, but it is carried out conscientiously in but few cases. This is partly due to the fact that many of these patients have poor appetites, and, in part, it may be attributed to the lack of care in administering such diets. It is a common experience 148 BASAL METABOLISM that "forced feeding", when it is actually analyzed, really provides a subcaloric ration. In those cases in which a high diet of 3000 to 5000 calories has been carried out the results have been re- markably good; the Ted blood-cells have increased and the general condition has been improved. Leucemia.— The very high basal metabolism characteristic of leucemia is extremely interesting. The rise is so great that the only theoretic explanation of this state of affairs does not seem to be entirely adequate; it is claimed that the process producing the great number of white blood-cells may be responsible for the increased metabolism; whether other factors also play a role remains to be determined. It is perfectly evident from the facts thus far obtained that these cases must have a diet of a caloric value considerably in excess of the normal if they are not to become weak and anemic. Further, from the above table it may be noted that cardiac disease, undernutrition, obesity, and certain nervous affections may lead to the suspicion that the thyroid gland is functioning too actively or too little. In the event of necessity of differential diagnosis under these circumstances, the determination of the basal metabolism is of very great help, inasmuch as all of the conditions mentioned vary much less from the average normal basal metabolism than do abnormal thyroid states. CHAPTER 16 THE BASAL METABOLIC RATE IN ENDOCRINE DISTURBANCES! By John L. Tierney, M. D. The value of the basal metabolic rate in the determination of the activity of other glands than the thyroid, for example, the pituitary and gonads, is less clear, and to venture in a small way to throw more light upon this phase has been the purpose of this paper, in the construction of which writer has studied: 40 Cases Hyperthyroidism 49 Cases Hypothyroidism 22 Cases Hypopituitarism 4 Cases Hyperpituitarism 6 Cases Diabetes Insipidus 22 Polyglandular Cases, involving disturbances of the Pituitary, Gonad and Thyroid Glands. Dualistic Function of the Hypophysis. — From fundamental, experimental, and clinical knowledge of the hypophysis, it is quite definite that this gland exerts a control upon metabolism, and it is logical to assxume that in disturbances of the hypophyseal function the basal metabolic rate should be modified, and, if this be true, should be an index to the physiological activity of the gland. A wealth of pathological, chnical, and experimental fact supports certain considerations concerning the hypophysis — i. e., that the anterior lobe regulates and controls: 1. The skeletal, cuticular and subcuticular growth; 2. The function and development of the gonads and the secondary sexual characters; and that the posterior lobe is concerned with: ' Editor's abstract, "The Basal Metabolic Rate in Endocrine Disturbances," Med. Clinics No. Am., 4:775, Nov. 1920. Approved by author. 149 150 BASAL METABOLISM 1. The regulation of carbohydrate metabolism, glycosuria, hyper-glycemia and obesity; 2. The contraction of the involuntary muscles, peristalsis, uterine contraction, etc., and 3. The renal secretion, polyuria, blood pressure and body temperature. Notwithstanding these facts there has been considerable argu- ment concerning the functions of the hypophysis cerebri and its effects upon metabolism, particularly carbohydrate tolerance and the basal metabolic rate. Means found a decreased basal metabolic rate in h)T)opituitarism with obesity; and Magnus- Levy an increased rate in acromegaly. Gushing maintains that when the posterior lobe is rendered inactive by disease or com- pression, metabolism procedures are checked and a high toler- ance is acquired for carbohydrates, which are promptly stored as fat. Robertson states that pathological conditions partially or totally destroying the function of the anterior lobe produce the clinical picture of adiposity, under-development of skin, bone, primary and secondary sexual characteristics, etc. Snell, Ford and Rowntree state — "Hyperactivity of the anterior lobe occurring in youth results in gigantism, and in adults, in acromeg- aly; functional hypoactivity results in infantilism." A marshalhng of the available facts regarding the physiologic action of the pituitary gland reveals that the function of the gland is dualistic. The component parts are embryologically, his- tologically, and physiologically distinct. These physiologic differences are manifest thru the hormonic signs, both subjective and objective, such as amenorrhea, dysmenorrhea, epileptiform attacks, somnolence, obesity, headaches, different changes in the osseous, genital and dermal symptoms, blood pressure, tempera- ture, involuntary muscle contraction, etc. Diagnosis of True Hyposecretion. — In studying the cases on record we note that certain cases may show physical evidence of hyperfunction and physiologic evidence of hypofunction. For instance, an acromegalic (or post-adolescent anterior lobe hj^er- secretion) may change into hypo-secretion, retaining the gross physical characteristics of acromegaly but exhibiting the func- tional features of hypoactivity, such as myasthenia, decreasing mentality, loss of libido, etc. In this type of case the determina- tion of the basal metabolic rate we believe is particularly valuable IN ENDOCRINE DISTURBANCES 151 because it serves as an index to the physiologic state at the time of observation, and to the proper procedure in a therapeutic way. Pluriglandular Syndromes. — Such combinations as thyroid and pituitary deficiency are exceedingly common. In our classi- fication this diagnosis has been based upon the associated hor- monic signs, and from the prominence of certain hormonic signs we believe it has been possible to distinguish the particular gland in which deficiency is mostmarked. The thyroid and pituitary insufficiency have showed most striking decreases in basal meta- bolism, but we have some cases showing absolutely no hormonic evidence of thyroid deficiency which have been classed as pit- uitary and gonadeal insufi&ciency showing very definite decreases in the basal metabolic rate. Gonadeal Deficiency. — In connection with deficiency of the gonads, we recognize certain gross metabolic effects such as changes in skeletal growth, development of dermal appendages and characteristic obesity. Whether these effects are primarily gonadeal or the results of secondary, reciprocal endocrine effects is a question. The writer has seen a decreased metabolic rate in a number of cases that have been deemed pure gonadeal insufficiencies and showing no clinical evidence of reciprocal thyroid or pituitary involvement. It must be admitted, however, that most testicular and ovarian insufficiencies have been defi- nitely associated in a clinical way with other glandular insuffi- ciency, to such an extent that it is difficult and ill-timed to attribute a decreased basal metabolism to a primary gonadeal deficiency. Conclusions. — In the case of polyglandular insufficiency, the basal metabolic rate has been consistently decreased. The most notable decreases have occurred in cases in which there was an associated hypothyroidism. We have come to the conclusion that the determinations of the basal metabolic rate are valuable in the study of endocrine disturbances, and that determinations of carbohydrate tolerance are of definitely lesser value. Despite the fact that the method is being severely criticized, and even discarded by some observers, we feel that the determinations of the basal metabolic rate are destined to become an integral part of diagnostic procedure, not only in the measurement of thyroid activity but in the determination of pluriglandular, pituitary and possibly gonadeal and adrenal activity as well. It must be 152 BASAL METABOLISM remembered that the physical characteristics and signs give evidence of certain endocrine states, but it must also be recalled, as Marie long ago pointed out, that hyperactivity can be trans- formed into a state of h3^oactivity retaining the physical characteristics of hyperactivity but possessing the physiologic functions of hypoactivity. The basal metabolic rate will help us, we believe, to determine the physiologic activities of certain glands at the time of observation, independently of what their previous activities may have been. This determination of the physiologic activities at the time of observation is of paramount importance because it is, we believe, the most logical index to diagnosis, prognosis, and, what is of greater importance, proper therapy. chapt£:r 17 dysthyroidism By J. Earl Else, M. D. A careful study of the clinical manifestations of hj^erthyroidism in conjunction with the basal metabolic rate shows that there is quite a group of cases in which the two do not coincide. Some patients with symptoms of mild hyperthyroidism have normal basal metabolic rates, while other patients who do not appear to have hyperthyroidism show increased metabolic rates. To this, group of cases, Janney has applied the term "dysthyroidism". Outline of Chapter. — This chapter is not intended to be an exhaustive study of dysthyroidism, but is, instead, a brief state- ment of the conclusions arrived at from a study of a group of cases, and is written with the hope that it may throw some light upon the problem. The cases were classified as follows: I. Basal metabolic rate lower than the symptoms would indicate. 1. Non- thyroid lesions. A. Chronic tonsil infection. B. Incipient tuberculosis. C. Asthenia with ptosis. D. Double oophorectomy. 2. Hyperthyroidism in the stage of remission. 3. Recurrent attacks of hyperthyroidism. 4. Permanent lesions after recovery from hyperthyroidism. A. Patients normal except for persistent symptoms. B. Mixed symptoms of hyper-and hypothyroidism. II. Basal metabolic rate higher than symptoms indicate. 1. Early cases of severe hyperthyroidism. Non-Thyroid Lesions. — The symptoms of other mild toxe- mias do not differ materially from the symptoms of mild hyper- thyroidism. The patients studied had goiters varying in size, which were either colloid or adolescent in type. In general, the 153 154 BASAL METABOLISM patients complained of tiring easily, tachycardia, and palpitation of the heart. Many were irritable, and complained of being "nervous". The majority of them were undernourished, al- though some were well nourished. The pulse rate varied from 80 to 120 in different cases. Tremor of varying degree was present in a considerable number, and in some the eyes were prominent, although the other signs found in exopthahnos were absent. (A) The majority of the cases were due to chronic tonsil infection, and the removal of the tonsils was followed by a satisfactory recovery, proving the diagnosis. In no case was the removal of the tonsils followed by a reduction in the size of the thyroid gland. However, this does occur sometimes, but it is, I believe, usually a coincident rather than a direct result, for it is very doubtful if there is any relationship between infected tonsils and goiter. In the Pacific Northwest, goiter is very frequent, as are also infected tonsils, so that of necessity the two lesions must frequently appear in the same patient. The tonsil infection appears to be about equal in the two sexes, while goiter occurs much more frequently in the female. If there were any direct- relationship between the tonsil infection and the goiter, then the goiter would be expected as frequently in tonsil cases in the male as in the female, which is not the case. Adolescent goiter is much more frequent in the female than in the male. (B) Incipient Tuberculosis. Very early cases of tuberculosis often give a history and findings similar to early hyperthy- roidism, with the exception that the basal metabolic rate is within normal limits. Later, as pointed out by McBrayer, the basal metabolic rate may rise, but it is always low as compared with the symptoms. (C) Asthenia with Ptosis. Asthenia with ptosis when com- bined with a small goiter is apt to be regarded as a case of hyper- thyroidism. The patients often complain of nervousness, being irritable, rapid heart, loss of strength and weight. Physical findings may show a rapid heart, and some' tremor, so that the picture will be suggestive of mild hyperthyroidism. The basal metabolic rate, however, will be within the normal limits. (D) Double Oophorectomy. The author has seen one patient who had had a dread of goiter since childhood. She gave a history of having had a double oophorectomy at the age of thirty. Following that there was some enlargement of the DYSTHYROIDISM 155 thyroid gland. This patient came complaining of a goiter, rapid heart, and "nervousness". Examination showed her to be fairly well nourished, pulse 96, coarse tremor, exaggerated reflexes, and a small goiter. Her palms were dry. The basal metabolic rate was between the average and the lower normal limit. Hyperth3nroidism in the Stage of Remission. — Exophthalmic or hyperplastic goiter runs a more or less definite course that can be divided into four stages: first, the stage of development, in which the basal metabolic rate runs higher than the symptoms would indicate; second, the stage of maximum intensity, in which the basal metabolic rate runs about parallel with the symptoms, third, the stage of retrogression, in which the basal metabolic rate falls more rapidly than the improvement of the symptoms would indicate; fourth, the stage of remission, in which the basal metabolic rate is around the normal although the symptoms of hyperthyroidism are still present. Some cases recover, but the majority have recurrences. During the stage of remission, the symptoms that were present in the attack will often persist. Thus, the patient will come complaining of tachycardia, nervousness, and tiring easily. In some of them, often upon exertion or excitement, the heart will become quite rapid. Examination shows a moderately en- larged heart, a tremor varying in degree, exophthalmos if exoph- thalmos was present in the attack. On determining the basal metabolic rate, it is found to be within the normal limits. The past history is of great importance in making a diagnosis. If the patients are kept under observation over a long period of time, exacerbations in which there is some rise of the basal metabolic rate will be observed. Recurrent Attacks of Hyperthyroidism. — Sometimes these patients appear to be quite sick, and yet the basal metabolic rate shows only a moderate increase. This can probably be best explained as follows: The administration of thyroxin over a long period of time or the rapid administration over a short period of time produces persistent lesions and a hypersusceptibility to thyroxin. An attack of hyperthyroidism lowers the resist- ance of the patient, so that exertion, fright, or worry often shows quite marked exacerbations, although the activity of the thyroid gland as measured by the basal rnetabolic rate is but little increased. 156 BASAL METABOLISM Permanent Lesions Following Recovery From Hyperthy- roidism. — Two groups of patients belonging to this type were seen: first, (A) those in which the patients were normal except for symptoms of hyperthyroidism. When thyroxin is adminis- tered over a long period of time or in large amounts, permanent lesions are produced in the heart muscle, central nervous system, behind the eyeball, and elsewhere. Although these patients may completely recover so far as the secretion of the thyroid gland, as indicated by the basal metabolic rate, is concerned, the heart may remain a damaged heart, with tachycardia and irregularity present. The tremor may persist, the patient may still be irritable, and a certain amount of exophthalmos remain because irreparable damage due to the excess of thyroxin. In the second group of patients, (B) there was a deficiency in thyroid secretion, so that the patient showed the evidence of hypothyroidism in addition to the persistent symptoms of hyperthyroidism. In mild cases, the hypothyroidism may be manifest only by a lower metabolic rate, but in the more severe cases the symptoms of hypothyroidism are present in varying degree. Early cases of Severe Hyperthyroidism. — In the beginning cases of hyperthyroidism, the basal metabolic rate appears in advance of the symptoms. It rises more rapidly than the symptoms develop. In severe cases, the rate may become very high before clinical manifestations become pronounced. A study of the group of atypical cases such as that upon which this chapter is based confirms the findings of those who have studied typical cases. The basal metabolic rate is the most accurate index of thyroid activity, but important as the basal metabolic rate is, the history and clinical picture can not be neglected. The synaptoms in hj^erthyroidism, as in other toxemias, vary with the susceptibility of the patient to the toxin as well as with the amount of toxin. In the more sus- ceptible patients, especially those having a recurrence after previous severe attacks, the patient may be in a precarious con- dition and have only a low rate, and in the stage of remission, the rate may be normal and yet there may be marked evidence of the recent attack present. Thyroid therapy should always be controlled by basal metabolic examinations. CHAPTER 18 INTERPRETATION OF BASAL METABOLISM IN HYPERTHYROIDISM By J. Earl Else, M. D. The influence of the thyroid gland upon the basal metabolic rate has been fairly well established, but its value to the clinician depends upon its interpretation. The estimation of the basal metabolic rate to the trained observer is not hard, but its inter- pretation is sometimes quite difficult, and to be made only in conjunction with a thoro knowledge of the patient's physical condition. Definition of Hyperthyroidism. — Hyperthyroidism is a clinical term used to include those diseases of the thyroid gland in wiiich there is an excessive secretion of thyroxin. It does not include non-toxic lesions. Some lesions, as the adenomata, may be non- toxic at first and later become toxic. As the term is a clinical one, these lesions can not be properly classified in the hyperthy- roid group until hypersecretion begins, for many patients have adenomas without ever becoming toxic. Classification of Hyperthyroidism. — In order to properly interpret the basal metabolic rate in hyperthyroidism, the patho- logy must be understood. Hyperthyroidism may be either functional or organic. Organic hyperthyroidism may be due either to hyperplasia and hypertrophy, or neoplastic growths, usually benign, but sometimes malignant. Excluding the functional hyperthyroidism and the hyperthyroidism from malig- nancy, toxic goiter may be divided into 2 types: first, exoph- thalmic or hyperplastic goiter ; and second, cardiovascular goiter. Exophthalmic or Hyperplastic Goiter. — This is a distinct chnical and pathologic entity running a more or less definite course, during which there is a fairly^definite relationship between the pathologic and clinical manifestations. The pathologic course may be divided into 4 stages. First, the stage of develop- ment. Microscopic examination shows that there is a diffuse hjperplasia and hypertrophy of the parenchyma. The acini are lined with tall columnar epithelium, contain but little or no 157 158 BASAL METABOLISM ■r3.::^M Fig. I. Exophthalmic or Hyperplastic Goiter. Stage of Development. Fig. 2. Exophthalmic or Hyperplastic Goiter. Stage of Maximum Intensity (early) HYPERTHYROIDISM 159 colloid, and have projecting into them papilloraatous-like masses. The absence of colloid in the acini is not to be taken as an indica- tion that the thyroid gland is not secreting. Colloid is not absorbed readily, its purpose apparently being to hold thyroxin and regulate its absorption. In hyperplastic goiter, the thy- roxin is not only secreted more rapidly than normal, but on account of the absence of colloid secretion, it is absorbed as rapidly as it is secreted (Fig. 1). Second, the stage of maximum intensity. As the hyperplasia increases, the acini may become completely filled with papillomatous-like masses. In the latter part of this stage, secretion begins to accumulate in the acini, distending them more or less. This secretion begins to take the eosin stain, indicating that colloid is again being secreted (Fig. 2). Third, stage of retrogression. The acini are distended with a deeper staining secretion and contain desquamated cells singly or in masses. The epithelial cells lining the acini approach the normal in size and arrangement, altho hj^erplasia and hyper- trophy are still present (Fig. 3). Fourth, stage of remission. Although the pathology in the first .3 stages is fairly constant, in the fourth stage there is considerable difference in the different cases. In some there is much h5qDerplasia and hypertrophy, and papillomatous masses are present. In others the acini appear quite normal, but here and there, rudimentary papillo- mata are seen. The microscopic picture may present a mixt appearance. In places there may be quite thick masses of con- nective tissue. Clinically, with the exception of the stage of remission, the sjTiiptoms correspond quite closely with the pathologic process, both as to course and intensity. Plummer has listed the symptoms in their usual order of occurrence as follows: Cerebral stimulation, vasomotor disturbance of the skin, tremor, mental irritabiUty, tachycardia, loss of strength, cardiac insufficiency, exophthalmos, diarrhoea, vomiting, mental depression. In the stage of remission there are persistent symptoms, the intensity of which varies with the intensity and frequency of the attacks. Basal Metabolic Rate and Clinical Manifestations. — Hyper- plastic goiter shows an increase in the basal metabolic rate before the appearance of symptoms. The length of time elapsing between the beginning of an increase in the rate and the approach of other clinical manifestations varies with the severity of the disease. In many cases formerly included under effort syn- 160 BASAL METABOLISM Fig. 3. Exophthalmic or Hyperplastic Goiter. Stage of Retrogression. MODERATE MIUD Fig. 4. Schematic Illustration of the Relationship, in cases of Hyper- thyroidism, OF the Basal Metabolic Rate to the Clinical Manifest- ations. HYPERTHYROIDISM 161 drome, but now recognized as early cases of hyperthyroidism, the condition improves, and the patient recovers without show- ing the symptoms generally looked upon as those of toxic goiter. As a rule, the usual clinical symptoms appear shortly after the basal metabolic rate appears, and rise with the rate (Fig. 4). When the disease reaches its height, both remain stationary, and then start downward. In mild cases, the sjrmptoms follow the rise and fall of the rate quite closely, but in severe cases, the symptoms do not develop as rapidly as the rate increases, and fall much more slowly in the third stage than does the rate. In the very severe cases, the s}miptoms may follow rather slowly. In the mild cases, the rate may return at once to normal, and remain there, but in the majority of cases, it fluctuates for a time at least. The lower limit may be below normal, while the upper limit varies mth the intensity of the recurrence or recru- descence. Patients with a fluctuating rate are rarely clinically normal. In some cases, the patients completely recover, and the rate and symptoms become normal, but many cases pass into the stage of remission which is followed by recrudescence. In the stage of remission, the rate is around the normal, often being slightly subnormal. In one case studied that was in the stage of remission, considerable damage had been done to the heart, so that while the patient was under observation previous to operation, she had cardiac manifestations following exertion or excitement, although the basal metabolic rate was persistently between the average and the lower normal limit. In general, it may be said that the rise of the basal metabolic rate is the first evidence of hyperthyroidism regardless of the type of lesion producing it. As the disease increases in intensity, the rise of the basal metabolic rate leads the clinical manifesta- tions. The more severe the onset, and the more severe the course, the higher the rate will be in proportion to the symptoms. In severe cases, the variation will be great, while in mild cases the rate and the symptoms will run almost parallel. When the disease reaches its height, there comes a time when the rate runs about parallel with the symptoms. As the disease begins to improve the rate drops more rapidly than do the symptoms'. In cases having frequent exacerbations, the rate may be -normal or below normal in the interval although the symptoms are present continuously. Results of Hyperplastic Goiter. — Following an attack of hy- 1( 1( 1( 162 BASAL METABOLISM Fig. 7. Colloid or Adult Adenoma. Fig. 8. Mixt Adenoma. HYPERTHYROIDISM 163 perplastic goiter, there are 6 possible tenninations: 1, Complete recovery, in which the rate becomes normal and the symptoms disappear. 2, Stage of remission, in which the symptoms per- sist, but the basal metabolic rate is usually within the normal limits or slightly below. 3, Partial remission in which there is not only a persistence of the symptoms, but also an increased rate, indicating that there is a continuous oversecretion. 4, Complete recovery so far as the thyroid gland and its secretions are concerned, as evidenced by a normal basal metabolic rate, but a persistence of certain of the symptoms, such as a rapid heart, exophthalmos, tremor, and mental irritability, because of permanent lesions produced by the action of the thyroxin. 5, Hypothyroidism, due to overdestruction of the secreting cells in the stage of retrogression. In this condition, the basal meta- bohc rate is below normal. 6, Hypothyroidism, with symptoms of hyperthyroidism. The former is due to overdestruction of epithelium or its inability to secrete sufficient thyroxin, and the latter is due to permanent lesions produced by the thyroxin in the height of the disease. Cardiovascular Goiter. — Cardiovascular goiter is a clinical but not a pathologic entity, as it may be due to at least 3 different pathologic processes, viz.. adenoma, adenomatosis, and regenera- tive or compensatory hyperplasia. The adenomata are new growths within a capsule, and may be single or multiple. There are 3 different varieties, the early or fetal, the late, called colloid or adult, and the intermediate or transitional stage, spoken of as the mixed. In the fetal adenomata, (Figs. 5 and 6) * the acini are at first small, without lumina, and lined with spheroidal epithelial cells. Later the cells become more cuboidal, begin to secrete colloid material, discharging it in a central direction, thus separating the cells and forming a Ivunen. The colloid secretion may continue until the acini become even larger than nor/nal. In this case, the epithelial cells become flattened out similar to those seen in colloid goiter. This latter condition is known as the colloid or adult adenoma (Fig. 7). In the mixt state, (Fig. 8) both fetal and adult acini are to be found in large numbers. In the colloid or adult adenoma, there are always some fetal acini present. In the adenomata producing toxic manifestations, the evidence of degeneration is often present. However, it is not always present, and degeneration may be present without symptoms being produced. * On page 166 li li li li li 11.64 BASAL METABOLISM Fig. 9. Adenomatosis. t,^ \'"-\, Fig. 10, Compensatory Hyperplasia. HYPERTHYROIDISM 165 Adenomatosis. — Adenomatosis (Fig. 9) is a diffuse growth without a capsule, which microscopically resembles the adeno- mata, particularly the mixt type. Like the adenomata, one can not tell from the microscopic appearance whether the condition was toxic or not. The regenerative or compensatory hyperplastic type (Fig. 10) is one in which the secretion has been below normal from any of the various causes, and a compensatory hyperplasia is set up in order to produce the needed secretion. The process does not stop when a sufficient nuinber of new acini to meet the needs of the body have been formed, but continues until there is an over- production, and the patient becomes toxic. Compensatory hyperplasia occurs more frequently in colloid goiter than in any other deficiency lesion, but it may occur after any lesion that causes a deficiency in the amount of thyroxin produced. Symptoms of Cardiovascular Goiter. — Altho cardiovascular goiter is not a pathologic entity, it is a clinical entity, as a similar clinical picture is produced by the various lesions. The sjonp- toms are slow in developing and resemble those produced by other slowly administered toxines. Exophthalmos and the acute toxic s3Tnptoms seen in exophthalmic goiter, are absent. Tremor, tachycardia, mental irritability, loss of strength, and cardiovascular changes are present, but develop rather slowly. Cardiac hypertrophy is often greater in the cardiovascular type than in the hyperplastic type. The blood pressure is often increased. Absorption of Thyroxin. — The work of Kendall would seem to show that the thyroxin produced in the normal gland, exoph- thalmic or hj^erplastic goiter, and in the group of lesions pro- ducing cardiovascular goiter is the same. The difference in symptoms between these two types of toxic goiter may possibly be due to the difference in the rate of absorption of thyroxin. Plummer and Wilson have shown that the time elapsing from the first evidence of hyperplastic goiter until the course has reached its height averages about 9 months, while in cardio- vascular goiter the time elapsing from the first appearance of the goiter until the height of the disease is reached, averages' about 14 years. This means that in the hyperplastic goiter there is a rapid absorption of thyroxin, while in the cardiovascular goiter the absorption is much slower. In poisoning by other toxic substances, the symptoms vary very much between the 166 BASAL METABOLISM './^^'"J'/i ■ it- 'M^ /*^ '^;i-4t:T Fig. 6. Fetal Ad HYPERTHYROIDISM 167 acute manifestation following a rapid administration of the poisonous substance, and the chronic manifestation following the slow adrr-inistration, so that by analogy the explanation as stated would appear reasonable. In cardiovascular goiter, the basal metabolic rate is an indica- tion of the amount of thyroxin absorbed, regardless of the tj^e of lesion. The curve rises much more slowly and usually does not reach so great a height as in the exophthalmic type. As a rule, cardiovascular goiter is not as severe as exophthalmic or hyperplastic goiter; but there are some very severe cases. Permanent Lesions. — Permanent lesions may be produced by the action of the thyroxin upon the central nervous system, heart muscle, tissue back of the eyeball, or elsewhere, and thus after the thyroid secretion has become normal as a result of operation or resolution, the patient may still be irritable, have a tremor, a defective heart, a protruding eye, or other persisting manifestations. A patient may , even develop myxedema, because of overdestruction of gland substance, and at the same time have some persisting symptoms of toxic goiter due to per- manent lesions. These persisting lesions may be likened to the final results after an arm has been badly mangled. The bone heals, the soft parts heal, but the function of the arm may remain below par; so in some cases of toxic goiter, after the goiter has been cured, the symptoms persist because of irreparable lesions. Basal Metabolism as an Indication to Diagnosis. — The diagnostic value of the basal metabolic rate may be summarized as follows: First, the basal metabolic rate is an indispensable index to the activity of the thyroid gland. Second, an increase in the secretion of thyroxin is followed by an early rise in the rate. This rise occurs before the clinical symptoms are manifest. Third, the height of the basal metabolic rate is not as important as is the course of the rate and the rapidity with which the rate is changing. Fourth, a rapidly rising rate or a rate that is higher than the symptoms would indicate usually means a rapidly secreting thyroid gland and greater severity than is seen with a slowly rising rate or a rate followed closely by the clinical mani- festations. Rapid absorption following massage or surgical in- tervention must be excluded. Fifth, a stationary rate after a rise usually means that the disease has reached its zenith, but not necessarily so. Sixth, a falling rate indicates a decrease in the activity of the thyroid gland. A faUing rate does not follow 168 BASAL METABOLISM the activity of the thyroid gland as closely as does the rising rate, and neither is it followed as closely by the symptoms. Seventh, the variation between the falling rate and the symptoms is indicative of the intensity of the disease through which the patient is passing. The more severe the disease, the greater the variation. Eighth, a normal or subnormal rate, after an attack of hyperthyroidism accompanied by symptoms of the disease, is indicative of injury produced by the thyroxin. Often the injury is permanent, and the symptoms persist for hfe, although the patient may recover from the goiter so far as excess secretion of thyroxin is concerned. Ninth, a fluctuating rate after an attack of hyperthyroidism is indicative of pathologic activity, and exacerbations of more or less severe grade are to be expected. Prognosis. — With a rising rate, a guarded prognosis should always be given. In general, with the first attack,when the rate is below 25 per cent, above the normal, the disease may be regarded as mild and the prognosis good; between 25 and 50% as moderate; between 50 and 75% as severe; and between 75 and 100% as very severe. The prognosis is grave if the rate is over 100%. A falhng rate gives a much better prognosis than 1 rising rate. Necessity for Correlation of Symptoms with Rate. — The character of the symptoms must always be considered in con- junction with the rate in determining the prognosis. In sub- sequent attacks, this is even more important than the primary attack. In permanent or persistent lesions, it requires but a small amount of thyroxin to produce a serious condition. Hence, the prognosis may be very grave even with a low rate. In other cases where there is a marked over-absorption of thyroxin as is evidenced by the high rate, the symptoms may be mild. It is not safe, however, to disregard the indication of the rate in the presence of mild symptoms, as these cases are apt to show very severe reactions. Neither is it safe to disregard the symptoms in cases where the symptoms are pronounced and the rate low, for fatal results may follow. The Basal Metabolic Rate as an Indication for Treatment. — As has been stated before, the basal metabolic rate must never be taken alone, but only in conjunction with the clinical mani- festations. In the onset of the disease with the rate below 25% medical treatment should be tried first. With a rate between HYPERTHYROIDISM 169 25 and 50"^ c , the rapidity of the development of the disease together with the relationship existing between the rate and the symptoms are important factors. The rapidly developing disease had better be regarded as surgical. In the cases where the disease is advancing slowly, and the symptoms are develop- ing as rapidly as the rate, medical treatment may be tried. In the developing disease with a rate not over 50%, the radical operation can usually be done without preliminary ligation. In cases seen in an exacerbation following the retrogressive stage, the symptoms of the patient are of great value in determining whether the preliminary ligation is necessary or not. Recurrent cases or cases in an exacerbation are always to be regarded as being surgical, altho the operation may need to be deferred. With a rate between 50 and 75%, it is usually best to ligate the superior thyroid arteries and wait for the rate to drop before doing radical work. With a rate between 75 and 100%, radical work should never be done until the superior thyroid arteries have been ligated. In the majority of cases only one artery should be ligated at a time. It must be remembered in doing any work on the thyroid gland that the manipulation forces , thyroxin into the blood stream. As a result there is usually an immediate rise in the rate followed by a fall in the rate. The interval that elapses between the operative procedures upon the gland should be great enough to permit the effect of the thyroxin thus forced into the blood stream to entirely pass away. For this reason the basal metabolic rate should always be observed after a ligation, and the next operation not done until the rate has ceased to drop. When the rate is over 100%, if the patient is in a precarious condition at all, no surgical work should be done, but the patient should be placed in bed, at absolute rest, and given sedatives and cardiac stimulants if indicated. With this procedure, the patient will usually improve and the rate drop to where a ligation is safe. Undue stress must not be placed upon the importance of the basal metabolic rate, but its determination in the study and treatment of thyroid lesions should be as routine as are blood counts in infections. If this were done and the indications for treatment, as shown by a study of the basal metabolic rate in its relationship to the clinical sjinptoms, were followed, the opera- tive death rate should be as low as that for the ordinary abdomi- nal operation. CHAPTER 19 THE METABOLIC RATE IN THYROTOXICOSIS^ By G. W. McCaskey, M.D. Value of Basal Metabolism Determinations. — It may fairly be said that the basal metabolism test rests on an established scientific basis. The general physiologic and clinical significance of fluctuations in the metabohc rate is now also well understood. The next step is for clinicians to work out the range and value of their clinical application in suitably selected cases in routine diagnostic work. This is really the "touchstone" of any diag- nostic method. Unless its clinical value can be shown to be commensurate with the time, labor and equipment required, it cannot and should not endure. As an Index of Thyroid Toxicity. — The important question bearing on this cHnical study is the dependabihty of fluctuations of the basal metabolic rate as an indication of thyroid activity; and this would obviously depend on whether the modified thyroxin molecule, if such exists, or possibly other unknown hormones, would retain the specific autocoid effect of the thyroxin molecule on cellular metabolism, or might possibly produce other toxic phenomena. Perhaps we cannot be too dogmatic on this point at present; but while recognizing the paramount position of the general clinical judgment in every case, variations in the metabolic rate as indirectly determined by the oxygen consump- tion must be regarded as the most scientific and practical index of thyroid toxicity. As to the question, in what group or groups of cases are the routine determinations of basal metabolism worth while, I believe: 1. In all cases of definite goiter, and especially if asso- ciated with health disturbances, to ascertain the degree, if any, of its toxicity. 1 Editor's abstract of "Basal Metabolism Determinations in General Internal Diagnosis", Jour. Am. Med. Ass., 74:927-931, Apr. 1920. .\bstract approved by author. 170 THE METABOLIC RATE IN THYROTOXICOSIS 171 2. In a large group of cases either with or without goiter, with symptoms resembling, either closely or remotely, those of thyrotoxicosis. In regard to the first group, whenever a patient has a goiter, large or small, and there is impairment of general health, whether the symptoms are typical of thyrotoxicosis or not, the toxicity of the goiter should be ascertained by the determination of the basal metabolism. This is especially true when considering the necessity for and character of therapeutic measures, surgical or medical. In any case with a goiter requiring a general diagnostic study, this accurate index of goiter toxicity should not be neglected. In judging of the operative risk in thyroidectomy, it is of the first importance. It appears to be true that this risk increases to an appalling degree when the metabolic rate attains an increase of around 100 per cent. Non-surgical measures should be exhausted in such cases in an effort to reduce the metabolic rate before operation, if the latter is decided on. The success of therapeutic measures can now for the first time be accurately gaged by basal metabolism determinations, instead of depending on the notoriously unreliable clinical data, such as pulse rate, or nervousness. Equally important, and presenting great diagnostic difi&culties, is the second group indicated. It does not matter much in the final judgment whether the patients have or have not a palpable thyroid. I have seen several cases in which the thyroid was very doubtfully palpable, with the metabolic rate increased more than 50 per cent. Clinical Symptoms Suggesting Toxicity. — Much more impor- tant than the goiter is the history of the case and the character of the symptoms. Among the symptoms suggesting investiga- tion along these lines may be mentioned: 1. Psychoneurotic disturbances. 2. Circulatory disturbances, (a) Tachycardia or brachycardia. (b) Cardiac myasthenias. (c) Certain arrhythmias. 3. Fine tremors. 4. Hyperhidrosis and hypohidrosis. 172 BASAL METABOLISM 5. General debility. 6. Loss of weight. 7. Slight temperature disturbances. Not one of the foregoing symptoms can be regarded as strongly diagnostic, much less pathognomonic, of hypothyroidism or hj^erthyroidism. In fact, it is perhaps not too much to say that if the majority or perhaps even all of these symptoms were present in an individual case, it would still be possible that the syndrome could be due to something entirely aside from thyroid disease. Signification of Goiter. — As a matter of fact, if with these symptoms there are found a goiter and exophthalmos, the diagnosis of thyroid disease should be considered established. With the goiter alone this would not be so obvious, because if these symptoms, singly or collectively, can be due to causes other than thyroid disease, the presence or absence of a goiter would really prove nothing, altho creating a strong presimiption in favor of hyperthyroidism or hypothyroidism to be verified by subsequent investigations. Clinical Symptoms Versus Basal Metabolism. — It is probably unnecessary to comment at length on the individual symptoms emmaerated above. Taking, for instance, such of the symptoms as psychoneurotic instability and tachycardia, which may be regarded as the most characteristic symptoms of the thyroid syndrome, it is perfectly obvious that they may be due to causes of the most diverse character. Nervous or mental overstrain, various chronic infections, but especially syphilis and tuber- culosis, and a great variety of pathologic conditions occurring in the various glandular organs of the body, malnutrition, from whatever cause, gastro-intestinal disturbances, and many other conditions must be kept in mind as possible explanations of such a symptom group. Their differentiation from thyrotoxicosis can usually be made with a certain degree of probability by the general clinical picture and the Usual diagnostic methods for the recognition of these pathologic conditions. The final court of appeal, however, so far as the thyroid problem is concerned, is the determination of the basal metabolism, which furnishes the most reliable proof either for or against the existence of thyroid disease. THE METABOLIC RATE IN THYROTOXICOSIS 173 Case Reports. — The following case reports have been selected because in them the metaboHc rate furnished a more or less decisive factor in the diagnosis, which could not have been ascertained in any other way, thus illustrating the practical clinical value of these methods: Case of H3rperthyroidism, with Chronic Hypertension. — History. — Mr. K., aged 43, complained of nocturnal asthmatic attacks. He had had an acute illness, diagnosed as pneumonia, one month before. One year before his health began to fail. He began to have some headache and to lose weight. He had lost 30 pounds during the last year. For the last two years, and probably for the last four years, he had had high blood pressure, ranging from 170 to 200, but he had been getting along fairly well until his acute illness one month before. The trouble began suddenly while he felt in good health. One evening he had a sensation of difficult breathing, with wheezing in the chest, which got so bad that medical aid had to be called. His physician found him with distressing asthmatic dyspnea, and this had recurred every night, becoming very severe at times. Physical Examination: The pulse was 135, and regular. The systolic blood pressure ranged from 185 to 200, the diastolic from 130 to 145, indicating rather low pulse pressure. A systolic murmur was heard at the apex. There was an area of dulness over the manubrium. The urine showed some hyaline and gran- ular casts, but the excretion of fluid and solids was within normal range. The blood was normal; the Wasserman test negative. June 23, 1919, the blood sugar, fasting, was 0.014; August 7,' 0.121; one hour after 100 gm. of glucose, 0.233; two hours after 100 gm. of glucose, 0.140. Roentgen-ray examination revealed definite dilatation of aotic arch, and enormous enlargement of the heart. June 3, six days after the first examination, the basal meta- , holism was +50 per cent; July 3, + 70 per cent..; August 5, + 97 per cent. There was a distinct gallop rhythm. The patient died October 13. This case is one of extraordinary scientific and clinical interest. Under rest and varied drug treatment the dyspneic attacks disappeared and the patient improved clinically in every respect. It will be noted that the basal metabolism at the outset indicated a moderate grade of thyrotoxicosis, which it was thought would 174 BASAL METABOLISM yield under treatment. No goiter could be detected by us or by the clinicians at the Mayo Clinic, where the patient went later for an examination. He had, however, a very short, thick neck, and a goiter of considerable size might have escaped detection, The subsequent marked increase in basal metabolism is thus best explained by increasing thyroid toxicity. The case was such a typical one of chronic hypertensive cardiovascular disease that the thyroid factor would be pushed entirely into the background unless forced to the front by the basal metabolism determinations. The etiologic relationship of the thyrotoxicosis to the cardio- vascular disease could not under the circumstances have been determined, but a careful study of the case suggested, on the one hand, the possibility just indicated, and, on the other hand, the desirability of carefully studying the basal metabolism in chronic hypertensive cases to determine the possible evolution of thyro- toxicosis. Case — Hyperthyroidism, Syphiliphobia. — History. Mr. S., aged 31, complained of being nervous and restless, and was always tired in the morning on rising. He had been "doctoring" for the past seven or eight years. He had had some palpitation and dyspnea, and was fully convinced that he had syphilis. Physical Examination. — This was iiegative, except for fine tremor. Repeated Wassernr.an tests (four) were negative. The blood sugar, fasting, was 0.079; it was 0.152 one hour after 100 gm. of glucose, and 0.162 two hours after 100 gm. of glucose. The basal metabolism was +41 per cent. In this case the determination of the basal metabolism con- verted a syphiliphobie patient into a thyrotoxic one, from the standpoint of diagnosis. In conclusion, I wish to say that so far as I am concerned, the procedure of establishing the metabolic rate in cases indicated has passed the experimental stage and has been assigned its place in my diagnostic armamentarium to be used as occasion requires. CHAPTER 20 TREATMENT OF CERTAIN TYPES OF GOITERi By Stuart McGuire, M. D. The Role of the Thyroid. — The thyroid is in many respects the most wonderful organ in the body. Thru its internal secretion it influences the physical development of the child and the mental activity of the adult. It regulates the growth of bone, the formation and distribution of fat, and the nutrition of the skin, teeth, hair and nails. It plays an important part in menstruation and parturition and has much to do with sexual desire and power. It influences the rate of the heart beat, the character of the peripheral circulation, and hence markedly affects the general blood pressure. It presides over the nitro- genous metabohsm of the body and in other, and perhaps unsuspected ways, plays an important part in the human economy. If thyroid secretion is excessive there are symptoms of meta- bolic riot. Heat production and gaseous interchange are rapid. The body tissues are stimulated to a course of wasting dissipation. There are seen tremors, sweating, tachycardia, muscular weak- ness, loss of weight and feverish mental activity. If thyroid secretion is deficient, the metabohsm of the body is depressed and heat production and gaseous interchange are at a low ebb. In the young, growth is lessened and the skeletal system is dwarfed. Connective tissue cells remain myxomatous. The skin is dry and thick and the hair coarse and shows deficient nourishment. The nervous system halts in developmient and mentalit}' does not rise above the level of the infant. Relation of Metabolic Rate to Thyroid Gland. — It has been learned that the thyroid regulates the general metabolism of the body and that an increase or decrease in its activity is accu- rately shown by corresponding changes in the patient's metabolic rate. Hence, by determining the degree of metabolism, we now ' Editor's abstract, "Treatment of Certain Types of Goiter,'' Virginia Med. Monthly, Jan., 1921. Approved by author. 175 176 BASAL METABOLISM have a scientific means by which we can estimate thyroid activity in an individual case, and can tabulate mathematically the effect of the various forms of treatment that are advocated for its abnormalities. The exact clinical value of the metabolic rate is yet to be determined. Like the thermometer, it promises to be a most valuable agent, but also like the thermometer, its record must be considered together with the patient's clinical symptoms. Types of Thyroid Disease. — Disease of the thyroid usually results in perversion of its function. If it causes diminished thyroid secretion the condition is known as hypothyroidism. If it causes increased secretion it is known as hyperthyroidism. Enlargement of the thyroid gland is termed goiter. If it be due to a general increase of tissue it is called a parenchymatous goiter. If due to the growth of a tumor it is called an adenoma- tous goiter. If due to the retention of secretion it is called a cystic or colloid goiter. Often two, or even all three of the above conditions may be found in the pathologic study of a single specimen. A goiter that causes no perversion of thyroid function and merely produces mechanical symptoms is called a simple goiter. This clinical division is not a hard and fast one, however, because a simple goiter may take on activity and cause general symptoms, and a toxic goiter may undergo degenerative changes and cease to produce constitutional disturbances. Treatment of Various Types of Goiter. — The treatment of simple goiter permits of little discussion. The parenchymatous type which causes the symmetrical enlargement of the thyroid, so frequently seen in girls about puberty, tends to spontaneous cure and is benefited by improving the patient's hygienic con- ditions and by the internal administration of thyroid extract and the external application of tincture of iodin. The adeno- matous and colloid types are not influenced by treatment. They may later develop toxic symptoms, or undergo malignant degeneration, but as a rule they simply cause deformity and pressure symptoms. The patient is often the best judge as to when the disfigurement or discomfort they produce is sufficient to justify an operation. Toxic goiters are much more serious and should be treated early and by efficient measures. While we do not know much about the etiology of exophthalmic goiter, it is a fact that the condition frequently follows some acute TREATMENT OF CERTAIN TYPES OF GOITER 177 disease and is maintained by a local focus of infection. Before beginning the systematic treatment of any case the tonsils and teeth should be examined and other possible sources of poison such as intestinal stasis should be determined, and if any diseased condition is discovered it should be corrected. Rest. — Rest is the first and most essential factor in the medical treatment of the disease. It should be absolute and complete and must be mental as well as physical. It is useless to try to secure it at home. The patient should be placed in a hospital where he can be under proper control. Means and Aub studied the effect of rest on a group of cases. These patients had an average metabolic rate of plus 81 per cent, and after one to three weeks the same group had an average of plus 67 per cent. In a few of the more toxic cases the curve rose in spite of rest. There was no case in the series whose metabolism was brought to within normal limits by rest alone. After a certain time a level was usually reached and rest alone did not cause a further drop. Drugs. — The administration of various drugs with a view to lessening metaboUsm has been advocated. Of these, hydro- bromate of quinine with ergotine, glycholate of soda and pan- creatic extract have the greatest number of advocates. Means and Aub have tested the action of hydrobromate of quinine on a group of patients and found that with these cases it had no apparent effect on the metabolic rate. X-Ray. — The use of X-Ray has long been advocated, and more recently the application of radium has been recommended, the theory being that a sclerosis is produced which lessens glandular activity. The relative merits of X-ray and radium have not yet been determined, but it seems that the choice is largely a question of the experience of the operator and the con- venience of the patient. Means and Aub tested the effect of X-ray on a group of cases. These patients had an average metabolic rate of plus 63 per cent. After one or two treatments at intervals of one month, there was a reduction to plus 52 per cent. After four or five treatments there was a reduction to plus 40 per cent., and after two or three years' treatment there was a reduction to plus 13 per cent, and the patients were able to lead normal lives. The advantages claimied for the X-ray method of treatment are that it avoids an operation and is 178 BASAL METABOLISM attended by less danger to life. The disadvantages are the increased length of invalidism, the greater difficulty of operating if surgery is ultimately necessary, the possibility of shrinkage of tissues of neck, danger of myxedema and of X-ray burns, and the liability of treating colloid and cystic goiters which are not benefited. Boiling Water Injections. — The injection of boiling « ater or a solution of quinine and urea into the body of the thyroid has been advised in the initial stages of hyperthyroidism, and as a preparatory measure to partial thyroidectomy in patients too ill to warrant any form of immediate operative procedure. The theory on which this practice is based is that the destruction of glandular cells and the obstruction of blood vessels will cut down the output of thyroid secretion. The method has many enthusiastic advocates who report good results. It is not -with- out immediate or remote disadvantages and dangers. Some patients are so sick that even this apparently simple procedure will cause an acute and perhaps a fatal hyperthyroidism; others will not be benefited, and a subsequent surgical operation will be made difficult by the adhesions it has caused, and finally the irritation miay eventually result in the development of ..cancer;. Surgery. — It is generally conceded that at present the safest, surest and most satisfactory treatment of hyperthyroidism is surgery. The practice of destroying a part of a gland in order to lessen its physiological activitv is certainly illogical, and only defensible on the ground that we are confronted with a condition and not a theory. Still it is a fact that a hile a patient is benefited by rest and drugs, and sometimes either makes a sppntaneous recovery or is cured by repeated and long-continued X-ray or radium treatment, he is given his best chance by an Qperation, and in order to economize time and avoid the possibility of serious complications, one should be advised as soon as the diagnosis of the disease can be established by the clinical symp- toms, the metabolic rate and the Goetsch test. Ligations. — The operations performed for hyperthyroidism are ligations and partial thyroidectomies. The benefits from ligations are marked but the results are rarely permanent. Observation in a series of cases at the Mayo Clinic showed that ligations reduced the metabolic rate from an average of plus 57 per cent, before operation to an average of plus 39 per cent, three TREATMENT OF CERTAIN TYPES OF GOITER 179 months after operation and there was also a corresponding improvement in clinical symptoms and an average gain of 21 pounds in weight. Experience has proved, however, that sooner or later there will almost invariably be a relapse and the patient's condition become worse than before. Ligations, therefore, are not relied on to effect a cure but are employed either as a test of a patient's reaction to trauma in cases where there is doubt of the individual's ability to stand a thyroidectomy, or as a means to get a patient in condition for a more radical operation when it is obvious that at the time a thyroidectomy could not be done without great hazard. Partial Thyroidectomies. — The results of partial thyroidecto- mies are prompt and permanent. If the operation does not effect a satisfactory cure it is because either not enough of the gland has been removed, or the' operation has been delayed until the patient's symptoms are no longer due to hyperthyroidism alone but to organic changes in the vital organs as well. Means and Aub found in a group of cases that the average metabolic rate was plus 46 per cent, before thyroidectomy and during the first two weeks after the operation there was a fall to plus 21 per cent. To get the best results it is necessary to remove the major portion of both lobes and the isthmus of the thyroid, leaving only a small amount of tissue cut from the posterior border of the lobes to carry on the function of the gland. This safeguards the para-thyroids and recurrent laryngeals and gives a symmetrical neck. Acute post-operative hyperthyroidism, which is the greatest danger of the operation, is not due as much to the amount of the gland taken out as it is to the amount of the gland left in. When it develops to a dangerous degree, the treatment advised by Crile of packing the patient in ice will be found most eflSca- cious. CHAPTER 21 DIAGNOSIS OF PSYCHO NEUROSIS AND TRUE HYPERTHYROIDISM IN THE EX-SERVICE MAN By Carmen F. James, M. D. Approved for publication by the Surgeon General of the U. S. Public Health Service. Prevalence of Neuro-Psychiatric Cases. — The recent war has brought to the attention of the Medical profession an alarming number of neuro-psychiatric cases. The Government agencies dealing with the ex-service men have announced that they need nearly as many beds for neuro-psychiatric cases as for tubercular, and far more than for all other classes of cases combined. This is a significant question and invites consideration. Is the War Responsible? — The war itself probably was not the primary causative factor in the production of more than a few neuro-psychiatric individuals. A few who were pronounced neurasthenics were taken into the Service under the stress of enlistm-ent or by the draft boards. In the greater number of cases, by far, the war was merely the immediate provocative cause, based on a congenital neuropathic or psychopathic per- sonality. The most of these men have had, practically all of their lives, an unstable nervous system. Some had had more or less symptoms before service. This did not materially interfere with their activity or usefulness. There were others who had had no recognizable trouble p-rior to the war. The excite- ment of going to camp, the change in the daily routine and habits of their life, and the new and unusual requirements of military life had a detrimental effect on this unstable nervous system. Som.e of these developed marked signs of "shell shock" without ever leaving the United States or hearing a gun fired. There were others that did not break until they were subjected to the strain of actual campaigning at the front. Some of these cases were very severe, and required removal from the lines and inten- sive treatment at the hands of specially trained workers. Others were mild and did not prevent the soldier from continuing his duties with his detachment. Problems of Differential Diagnosis. — With the close of the war and the return of these men to civil life, the physicians in civilian practice as well as the Public Health personnel have had 180 PSYCHONEUROSIS AND HYPERTHYROIDISM 181 to care for irany of these disabled men. Many problems of differential diagnosis present themselves to all of us. Some are easy of solution but others are very difficult. Some of these cases are at first confused with pulmonary tuberculosis, heart disease of various types, hyperthyroidism or goiter, gastro- intestinal conditions, organic disease of the central nervous system, and many other conditions not necessary to mention. On first thought it may seem strange that this confusion should occur, but most all of us can recall numbers of such mistakes in our own experience. We frequently have to call into play our highest skill in diagnosis and make use of the best methods of precision of the laboratory, and even then we will at times make mistakes. We are concerned mainly in this article with those cases of psychoneurosis that resemble hyperthyroidism, and more es- pecially the value of the study of the basal metabolic rate in differentiating these cases from true hyperthyroidism. The opinions expressed in this article are based on observations made on ex-service men while the writer was stationed at the U. S. P. H. Hospital No. 36, Boston, Mass. Ssrmptoms Common to Psychoneurosis and Hyperthyroidism. — Among the ex-service men, and it is equally true in civilian practice, we sometimes see a type of psychoneurosis that re- sembles, in many respects, hyperthyroidism, and occasionally even exophthalmic goiter. They present an unstable nervous system that reacts unduly to minor stimuli. There is usually a tremor of the outstretched fingers and protruded tongue, and even of the entire body in some cases. These tremors vary in degree from very mild to very severe. They are more often coarse in character, and usually accentuated by directing atten- tion to them. They can usually be lessened or made to disappear by diverting the patient's attention during the examination. These patients nearly always have an accelerated pulse rate, ranging around 100 per minute. The rate, however, is very variable, and the heart responds in a marked degree to very mild stimulation, such as slight amount of excitement, exercise, or emotional disturbance. The patients are conscious of this, and frequently complain a great deal of palpitation, shortness of breath, vague pains in the cardiac region, and even attacks resembling angina pectoris, as in one of my cases. The pulse 182 BASAL METABOLISM rate in these cases is influenced readily by complete rest, usually dropping to below 90, or even to normal. This drop is slight in cases of true hyperthyroidism. Some of these patients may show slight evidence of the other cardinal syrriptoms of exophthalmic goiter — exophthalmos and enlargement- of the thyroid gland. These are incidental and have no causation in the nervous condition. You may some- times see a rrild hyperthyroidism in a marked psychoneurotic. Some even contend that all the cases of the type under discussion have their origin in a disturbed thyroid secretion. Yet we see some cases in which there appear to be a slight exophthalmos and enlargement of the thyroid gland, along with a tachycardia and nervous manifestations when the basal metabolism rules out absolutely any hyperfunction of the gland. Quantitative Test for Thyroid Activity. — The basal meta- bolism determination is the only practical method of precision that the laboratory has developed that can be used as a measure of thyroid activity. It is of value in thyroid disturbances in that it is a measure of the basic metabolic activities taking place in the body. These activities are so closely linked with the thyroid secretion that it may be, for all practical purposes, con- sidered a measure of thyroid activity. It is the only quantita- tive test we have for thyroid hyperfunction. It has been con- clusively shown by many of the workers in metabolism^ that the basal metabolic rate fluctuates according to the degree of activity of the thyroid gland. When the symptoms in the hyperthyroid case increase in severity, the basal metabolism shows a corres- ponding rise in rate, and as the condition improves under treat- ment the metabolism rate drops accordingly. Consequently it is of great value in diagnosing disturbances of thyroid activity, and following accurately the patient's condition while under treatment. It is also especially valuable in differentiating from ■1 Means, J. H.: Hyperthyroidism (Toxic Goiter), Medical Clinics of North Apierica, January, 19 20, Du Bois, E. F. : The Basal Metabolism as a Guide in the Diagnosis and Treatment of Thyroid Disease, Medical Clinics of North America, 2: 1201, January, 1919. Boothby, W. M.: The Value of the Basal Metabolic Rate in theTreat- ment of Disease of the Thyroid, Medical Clinics of North America, November 1919. PSYCHONEUROSIS AND HYPERTHYROIDISM 183 srue hyperthyroidism many of those borderline cases that re- temble hyperthyroidism. This is its value in a neuro-psychiatric clinic. Goetsch Test. — A few years ago the Goetsch^ test was intro- duced as a simple diagnostic test for hyperthyroidism. This was soon shown not to be specific in nature, and the results not to be sufficiently uniform for practical use. A large percentage of neurasthenics show a marked positive adrenalin reaction. Peabody^ and his associates found a positive Goetsch test in 60 per cent, of cases of "irritable heart" in soldiers examined by them. O'Hare* found positive reactions in cases [of hypertension. Russell, Millet, and Bowen^, in a comparison of the functional tests for hyperthyroidism, found the adrenalin test positive in 55 per cent, of their cases of hy- pothyroidism, and negative in 2 cases with basal metabolic increase of over 50 per cent. Consequently this method has been discarded because it is unreliable. Conclusions. — The value of the basal metabolic rate in thyroid disturbances is too well established to be questioned. It is equally valuable in the study of those borderline cases re- sembling hyperthyroidism, such as certain cases of neurasthenia. The results are quite clear. The hyperthyroidism gives an increase in basal metabolic rate, the neurasthenia does not. Most of us have had the experience of diagnosing "irritable hearts" and neurasthenias as hyperthyroidism until the basal metabolism was determined and compelled us to change our diagnosis. Indirect calorimetry has been developed and sim- plified to such a point that it has become comparatively easy to obtain results sufficiently accurate for clinical purposes. With the increasing use of the apparatus for determining the metabolic rate, fewer errors in diagnosis will be made. 2 Goetsch, E.: Newer Methods in the Diagnosis of Thyroid Disorders, Pathological and Clinical, New York State Medical Journal, 18: 7, July, 1918. sPeabody, F. W., Clough, H. B., Sturgis, C. C, Wearn, J. T., and Tomp- kins, E. H. : Effects of the Injection of Epinephrin in Soldiers with "Irritable Heart", Jour. Am. Med. Ass., Dec. 7, 1918. * O'Hare, J. P. : Vascular Reaction in Vascular Hypertension, American Journal of the Medical Sciences, 159: 369, March, 1920. SRussel, N. G., Millet, J. A. P., Bowen, B. D.: Clinical Studies in Func- tional Disturbances. Study I. Functional Thyroid Tests as an aid to Differential Diagnosis, American Journal of the Medical Sciences, 162: 597, Dec, 1921. CHAPTER 22 HYPOTHYROIDISM — PHYSIOLOGICAL, PRIMARY, AND SECONDARY By Edwin L. Gardner, M. D. Definition. — Hypothyroidism is a condition produced by an impairment of the function of the thyroid gland and character- ized by a retardation of cellular metabolism and growth. Classification : — Physiological Hypothyroidism: a. Estimation of thyroid function. b. Effect of diet. c. Other physiological conditions. Primary or Congenital Hypothyroidism: a. Cretinism b. Minor Congenital Hypothyroidism Secondary Hypothyroidism: a. Following Hyperthyroidism b. Following surgery upon the thyroid gland c. Thyroid deficiency associated with disease of other endocrine glands d. Following removal of other endocrine glands e. Myxedema. Its Symptoms /. Minor thyroid deficiencies g. Following infections and toxemias Treatment of Hypothyroidism Physiological Hjrpothyroidism Estimation of Thyroid Function. — The cUnical estimation of thyroid function is often uncertain. The observations and experiments of Plummer and associates suggest an equihbrium between the "thyroxin" in the thyroid gland, the blood, and the tissues of the body. The thyroid principle is probably used as a catalase, acting as a stimulus which controls cellular metabohsm. It is not absolutely necessary for life, but in order to have the greatest efficiency, the total amount may vary 184 HYPOTHYROIDISM 185 within comparatively narrow limits. These facts afford some basis for studies of basal metabolism in thyroid disease. Much has been written and said about the technic and value of basal metaboUsm; unfortunately many good chnical men are doubting its accuracy and value. It is a procedure in which extreme care must be employed in controUing the technic and in the interpre- tation of the results. If the test is made by a trained technician and intelligently interpreted, it furnishes information which nothing else will. There are hmitations, such as urine analysis has in urinary disease or the Wasserman test in syphilis, but nobody would wish to discard either of these last well-known and ac- cepted laboratory examinations. Much error has arisen over the fact that other conditions than gross or microscopic thyroid disease may affect the basal metabolic rates. To assume that all cases coming within the limits of plus or minus 10% or any other figures, are normal, and that patients having a rate above or below are abnormal, can not be entirely supported by clinical observations. Repeated observations of the same patient, whether normal, hyperthyroid, or hypothyroid, will show con- siderable daily or even hourly variation, but the curve wiU be essentially a normal, hypothyroid or hyperthyroid type. Effect of Diet. — Many conditions have a tendency to cause slightly lowered basal metabolic rates and the borderline between the physiological and pathological states can be deter- mined only by the associated chnical symptoms and findings. Animals have shown lowered rates when on insufl&cient diets. Hibernating animals have a metabolism much below the normal and the iodin content of their thyroid glands is low in the spring months. Cattle, sheep and hogs killed early in the spring show a very low iodin content of their thyroid glands. It is uncertain whether this is due to seasonal or to dietary influences, but the latter is most probable. Pregnant sows fed upon iodin-poor food frequently abort or give birth to hairless pigs with brittle hoofs, and enlarged thyroids; an observation which has been most common in spring months. Other Physiologic Gondii ions. — It is a common observation of clinicians to note that patients are very susceptible to in- fections, if the diet is poor in those active principles called vitamines, altho the patient may be well nourished and ap- parently healthy. The basal metabolic rate may be lowered 186 BASAL METABOLISM 20% below normal in malnutrition cases; this has especialty been noted in the starvation treatment of diabetes. Heavy feeders, especially of meats, very commonly fall in a class slightly above normal. Pregnancy is not uncommonly associated with mild hypothyroidism; and following periods of nervous strain and excitement, when signs of "physiological hyperthyroidism" are present, the basal metabolic curve may temporarily drop below normal. Old age is usually associated with rates below normal, and often many of the symptom.s and findings of old age have been attributed to h3^othyroidism.. Symptoms of hypothy- roidism are very common in women following the menopause. These patients rapidly increase in weight and sometimes show signs of early myxedema. Primary or Congenital Hypothyroidism Cretinism. — True cretinism is always congenital, altho clinically, infantile myxedema developing before the end of the first year of life can not be differentiated from it. After the first year of life, infantile myxedema may usually be recognized when ossification has proceded to the stage of closure of the fontanelles. Infantile myxedema in the first years of life shows many of the same manifestations as true cretinism and for practical purposes the two conditions may be grouped together. The classical clinical picture is well known and is well described in most of the textbooks. Minor Congenital Hypothyroidism. — Altho tj^ical cretinism or myxedema in childhood once recognized can never be for- gotten, minor hypothyroidism may occur and escape detection. This condition usually occurs in backward or abnormal children and is often associated with other abnormalities. Delayed bony ossification, indicated by failure of closure of fontanelles; slow- ness in learning to walk; delayed eruption of teeth with mal- formation and early decay; malformation of bones of the face with high palate and poor development of the nasal cavity; spinal curvature and possibly the tendency to rickets may be associated with thyroid deficiency. Puffiness and dryness of the skin, large abdomen, small, weak muscles, tendency to lymphatic hypertrophy, poor growth of the hair, retardation of mentality, sleepiness, anorexia, lowered temperature, atonic con- stipation, enuresis and many other symptoms due to a slowing HYPOTHYROIDISM 187 up of cellular and nervous activity are suggestive when groups of symptoms appear together. No single symptom or even group of symptoms is pathognomonic, but should be investigated and checked by the therapeutic test with thyroid extract. Patients with other endocrine gland disturbances may show symptoms of abnormal thyroid function. Older children with persistent thjonus, tendency to lymphatic enlargement, suscep- tibihty to infections, and possibly findings referrable to pituitary and sexual glands, show mild thyroid deficiency. Many of these cases have a lowered basal metabolic rate, and improve considerably under prolonged feeding of small doses of thyroid extract, sufficient to maintain the rate nearly normal. Secondary Hypothyroidism Following H3rperthyroidism. — The hyperthyroid state very commonly passes gradually into one of lowered function. It can not, without reservations, be assumed that a thyroid disturbance is a quantitative one only. Dysfunction may play an active part. The studv of creatin and creatinin metabolism, the study of blood sugar, and many of the clinical signs suggest a quali- tative alteration of thyroid secretion. Much of the pathology resulting from the hyperthyroid condition remains permanent and confuses the picture. Following Surgery. — Myxedema or minor hypothyroid states often follow surgical procedures on the thyroid glands. Re- section, X-Ray, or injection of foreign substance, all may result in too low activity, due to reduction of thyroid substance. Associated with other Endocrine Diseases. — The thyroid syndrome is always complicated by those signs arising from other glands of internal secretion. Pituitary disease affects thyroid function. Activity of the gonads materially influences thyroid function and menopause is not uncommonly followed by minor thyroid deficiency or myxedema. Removal of a fibroid uterus or oophorectomy, may be followed by hypothyroidism. The largest number of cases arises from insidious or unknown causes. Infections and toxemias probably produce a large group of cases, due to atrophy or sclerosis. Vascular disease (old age) possibly is a factor in a small number of cases. Many of the 188 BASAL METABOLISM patients with hypothyroid disease, may have been "thyroid poor" at birth. Myxedema. — A case of true myxedema can not be mistaken, when once a few cases have been recognized. However, it is not uncommon to find myxedema patients who have been treated for nephritis, cardiac disease or other aihnents. The symptoms and signs of myxedema are varied, due to the altered cellular metabolism. Myxedema (Gull's disease) is more com- mon in women than men. It is more likely to occur in families who have thyroid or other endocrine gland disturbances, and is more common in goitrous communities. The disease may first appear in relation to pregnancy or menstruation, and after partial remissions become permanently established. The symp- toms may be referred to various organs: A characteristic infiltration of the skin is due to a substance resembling mucus, and a formation of new connective tissue. The skin of the entire body may be affected, but is more likely to appear in certain areas, as the face and neck, supraclavicular fossae, breasts, the wrists and back of hands, and about the ankles. The skin is often dry and scaley, and frequently tender upon pressure. The nails are dry, the hair coarse and has a tendency to fall out, especially the lateral portion of the eye- brows. The hands are often "spade-like" and movements are cliunsy. The face has a mask-like expression, the eyelids are swollen, and patches of pigmentation frequently occur about the face, forehead, or neck. The mucous membranes show a similar process. The tongue is thickened, the conjunctiva often inflamed, the gums are swollen and pyorrhea is very common. Thickening of the mucosa of the larynx causes a peculiar mono- tone to the voice. Tonsils and adenoids are common, and the patients often suffer from tinnitus and partial loss of hearing. Various symptoms may be produced from infiltration of the mucosa of the gastrointestinal, bronchial, urinary and genital tracts. Some symptoms are due to retardation of ossification if the disease appears early in life. This is especially noted in disease of dentition in young people. There is a tendency to early caries of the teeth. Fractures heal poorly. Infiltration of the cartilages may produce pain, stiffness and creaking about the joints, and especially so about the knee joints. The muscles HYPOTHYROIDISM 189 are flabby and weak; muscular movements are slow and fatigue quickly appears. The pulse is often slow, small and of low tension. Arterial degeneration may appear early. The heart dilates to the right and to the left and the electrocardiogram shows many signs of impaired myocardial function. A moderate anemia is the rule. The leucocyte count is usually reduced and there is a lymphocytosis. A tendency to hem- orrhage may exist, especially of the purpuric type. Anorexia is common and sensation of thirst is decreased. The general suppression of cellular activity is likely to produce atony, achylia and subsequent disturbances of motility and digestion. The liver may be enlarged and the function unpaired. The function of the kidneys is impaired, as shown by decreased urine output, albimiinuria, and often casts. Frequent urination or incontinence may be present either due to myxedematous infiltration or to infection. Enuresis in children sometimes responds to thyroid extract. Arrested development occurs if the thyroid deficiency develops early in life. Menorrhagia may appear, or there may be atrophy of the genitals with a premature climacteric. Some believe sterility may be associated with subthyroidism. Susceptibility to respiratory infections is common and dys- pnoea is often present. The dyspnoea may even be mistaken for bronchial asthma. The nervous symptoms are most marked in myxedema. All mental processes are slowed up and fatigue appears early. Memory is slow and less often markedly impaired. Sleepiness is the rule, but little relief is obtained from many hours of rest and sleep. Headache is common and the patients show signs of mental irritability and depression. Melancholic symptoms are not uncommon. Nervousness and tremor may appear and occasionally syncope or even convulsive seizures may be present. All movements are clumsy. Infiltration of the peripheral nerves may produce symptoms. Minor Thyroid Deficiency. — Minor thyroid deficiency is much harder to recognize and as a rule can only be suspected. The therapeutic test is usually employed. The estimation of basal metabolism has made the diagnosis much more certain, but not infalUble. Lowered m.etaboUc rates are common but 190 BASAL METABOLISM the statement that they run parallel with thyroid function probably is not justifiable. The greatest discrepancies appear through slight errors in technic, but other factors may materially affect the results. The majority of myxedematous patients have a rate of 20% to 40% below the normal, but some malnutrition cases will reach 20% below normal. Some patients with symp- toms and findings suggesting minor hypothyroidism will show a curve only by repeated examinations which is definitely below the normal limits. The writer has recently studied 275 cases who had a basal metabolic rate varying between and 40%. These were mostly ambulatory patients in whom some thyroid or other endocrine gland disturbance was suspected; about 40% of the cases were patients with malnutrition and a few were indefinite "neuras- thenic" individuals. A few normal people were included in the group but none of these had a rate below 5%. Females out- numbered males 6 to 1. Thirty-four patients were under 20 years of age. The majority of these 34 cases had goiters of adolescence, a few were girls with various nervous symptoms associated with delayed menstruation, and the others had mul- tiple endocrine gland disturbances. All showed improvement after the administration of iodides or thyroid extract, with the exception of some of the multiple endocrine gland cases. One child suffering from polycythemia associated with large spleen and cirrhotic liver showed marked improvement. Malnutrition caused a lowered metabolic rate in 40% of the cases studied. Of 53 patients in the third decade of life, all except five had to be placed in this group; two had had a pre- vious thyroid operation, two ovarectomy, and one a premature menopause of unknown cause. Myxedema and minor hypothy- roidism appear most commonly in the fourth, fifth, and less often in the sixth decades of life. Malnutrition is only one-half as common; but menstrual disturbances, pelvic operations multiple pregnancies, and disturbances near the menopause occur more often. Several cases first showed symptoms after ovarectomy or removal of fibroids. Only 14 cases were over 60 years of age and only six of these showed signs of diminished thyroid function, the others were undernourished. Only ten cases of entire series showed typical myxedema. The basal metabolism was determined frequently and — 10% seems as HYPOTHYROIDISM 191 good as any arbitrary figure as a dividing line between the normal and 0, even in definitely thyroid deficient cases when only one estimation is made. The condition of the thyroid was noted in the majority of the cases. In myxedema and definite thyroid deficiency the gland most often shows signs of atrophy or sclerosis. In many of the minor cases, especially in young people, there was shght or moderate enlargement. About 50% of the cases had thyroids which chnically could not be dififerentiated from the normal. Following Infections and Toxemias. — Experimentally hy- pothyroid animals are very susceptible to infections, in fact it is often hard to keep them alive long enough to carry out experi- ments. They show poor antibody formation. At least one investigator believes that the ability to produce antibodies may be exprest in terms of thyroid function; he claims to have increased the antibodies of the blood in poorly reacting animals by feeding thyroid extract. Cretins and myxedematous patients show very low resistance to infections. Following infectious diseases such as pneumonia, acute tonsillitis, typhoid fever, acute rheumatic feyer etc., we have repeatedly found lowered basal metabolic rates, and convalesence very often was tedious; improvement was apparently faster in those whose metabolism quickly returned to normal limits. Many of the symptoms of convalesence such as subnormal temperature, slow pulse, lack of endurance, susceptibility to cold, tendency to atony of striated and non-striated muscles, rapid gains in weight, etc., might be attributed to lowered thyroid function, as a result of a general- ized toxemia affecting all the cells of the body. Much of the old treatment of postinfective cases was directed towards in- creasing muscle tone and stimulating metabolism. No sharp line can be drawn between physiological depression of thyroid function and real pathological degeneration of the gland. Diagnosis of Hypothyroidism. — It is not possible in all cases to decide whether the thyroid depression is the cause of the symptoms or whether it is a part of the generally lowered meta- bolism. Malnutrition and postinfective cases probably belong to the latter group. The following symptoms and signs justify the suspicion that subthyroidism may exist and basal metabolic studies should be made.. 192 BASAL METABOLISM 1. Lack of endurance and sense of fatigue especially in the latter part of the day. 2. Mental depression and loss of power of concentration 3. Susceptibility to infections. 4. Secondary anemias without apparent cause. 5. Changes in the skin, especially increased sensitiveness to cold, formation of pads, tenderness upon pressure, and, less often, dryness or loss of hair. 6. Unexplained menstrual disorders. 7. Any of the symptoms associated with myxedema may appear singly or in groups but the above symptoms are most com- mon in the early cases. No one sign is infallible, and the thera- peutic test sometimes must be employed. Treatment ot Hypothyroidism. — Thyroid extract or thyroxin forms only a part of the treatrrent. It is needless to say that all possible causative factors should be corrected. Definitely infectious foci should be removed; the proper diet should be prescribed to build up the malnutrition (often visceroptosis) patients and the food should contain sufficient iodin and yita- mine principles. Thyroid extract often acts as a stimulant to the appetite, and to the glandular and muscular activities in this type of patient. Many of the cases showing vasomotor insta- bility react to very srrall doses of thyroid principle. Postinfective states have been studied in a separate group of cases. Following acute rheumatic fever, tonsillitis, influenza, and other infections, the rate is very often low, the muscles flabby and cellular activity lowered. Many of the symptoms disappear and convalescence apparently is shortened by thyroid stimulation. Whether these cases were subthyroid or normal before their infection, was not determined. A few cases of postinfluenzal melancholia were improved by thyroid feeding. We have had no opportunity to study worren in the puerperal state. In the above cases possibly the sarre results rray have wholly or partially been obtained by various "tonics" especially iodin. The older clinicians used iodin in some form very frequently as an "alterative" and the later metabolic studies are showing the accuracy of their clinical observations. Cretinism and myxedema should be treated continuously with thyroid extract. The most accurate method to determine when the optimum effect has been obtained is by allowing the HYPOTHYROIDISM 193 basal metabolic rate to determine the dosage. The first case of myxedema reported by Murray in 1891 recently died of heart disease at 74 years, having taken thyroid extract since 46 years of age. Thyroid Therapy. — Many conditions have been attributed to minor thyroid deficiency where the signs and results did not warrant such conclusions. This error has partly arisen from the ■ "therapeutic test." Basal metaboUc curves will give truer information,- but all conclusions must be guarded. Thyroid extract is a powerful agent "to fan up the fires when they are smoldering," until the body has a fresh chance. A few of the ■ conditions which may be helped by thyroid therapy are the following: — 1. Lo^yered metabolism with atonicity of muscles, striated and non-striated, producing a multitude of indefinite symptoms. Subnormal temperature is not constant in these cases. 2. Trophic condition of the skin, hair, nails, and teeth. There is no evidence to prove that any skin diseases are pri- marily due to subthyroidism. Subthyroid cases, upon con- tracting skin diseases may improve more rapidly if the subthyroid state is corrected. 3. Secondary anemia and occasionally hemorrhagic states. 4. Low blood pressure and low pulse pressure. Occasionally high blood pressure occurs in hypothyroid states and wiU respond nicely to iodines or thyroid extract. The viscosity of the blood is said to be increased in subthyroid states and iodin is supposed to decrease viscosity. 5. Heart disease. In myxedema the heart action is often slow and feeble, the heart is enlarged to the right and to left, and the electrocardiogram shows signs of myocardial disease. The same may be true in minor cases. We have repeatedly noted patients who clinically and by electrocardiograms showed evi- dence of serious myocardial degeneration, show rapid gains and improvement of the electrocardiogram, with thyroid : feeding, even after removal of focal infection, treatment of toxemias, and other procedures directed toward treatment of the heart muscle had already failed; and then again seen relapses when the thyroid therapy was discontinued. 6. Susceptibility, to respiratory infections. :;. - 7. Gastroiiitestinal. Suppression of . the.t.S)e.Qfe^onSi:>atony, 194 BASAL METABOLISM constipation and intestinal autointoxication n^ay be helped. Cases of achylia or hypoacidity are corrnion and may irrprove with the general condition of the patient. 8. Albuminuria and occasionally casts. 9. Enuresis in children is sometimes helped by thyroid thereapy. 10. Menorrhagia without other cause. 11. Early sterility, especially with premature menopause are said to be thyroidal in origin. We have had several rates which were low, but no definite imiprovement after thyroid extract, except in the occasional case. 12. Eye infections (and by one observer, cataracts in dogs) are coirmon in subthyroid animals. In man. Keratitis punctata and slowly healing corneal ulcers are said sometimes to heal more quickly. 13. Tinnitus and deafness due to subthyroidism. 14. Retardation of mental processes. 15. Irritability of temper. 16. Mental depression. There is no evidence that various nervous diseases and many psychoses are directly due to thyroid hypofunction. If such occur in a subthyroid patient, improve- ment may be noted. 17. Developm.ental abnonralities. 18. Pregnancy. Hypothyroidism may lengthen pregnancy, and foetal athyroidism or subthyroidism may result. 19. Chronic arthritis is occasionally helped. This condition m.ust be differentiated from myxedematous infiltration about the joints. Much conflicting evidence occurs iri the literature, but the above outline seems to be warranted from a review of the litera- ture and clinical observations. Pathology does not offer much help. Only gross anatomical changes such as atrophy and sclerosis can be observed. Degenerations and inflammations occur in the thyroid similar to other glandular tissue in the body but minor hypothyroid states do not as a rule show gross patho- logical changes. The clinician must determine when abnormal physiology exists. Dosage of Thyroid. — Thyroid dosage must be controlled and the basal metabolic rate should not be allowed to go above normal. Physiological hypothyroid cases are often very sensi- HYPOTHYROIDISM 195 tive to small doses. "Thyroxin" has a more constant potency, but is not necessary. The thyroid extract on the market is usually active, but is variable. A large number of tablets may be prescribed and the dosage determined for the patient. After a few months experience the patients very often can determine what their optimum dosage is by their sensations when the basal rate is within normal limits. When once the optimum amount of "thyroxin" is present in the body, small doses will in many cases maintain the desired effect, but in some patients the principle disappears (or its action) so that relatively large doses are necessary. One grain of the usual extract (we have used Armour's and Parke-Davis and Co.) per day is often sufficient in the minor cases. Some deterioration of the extract occurs when standing and exposed to the air. What are the Results of Thyroid Therapy. — Many of the most grateful patients are those who have been helped. They have been treated for first one symptom and then another, or not treated at all because they are "neurasthenic." The results sometimes are disappointing, but the attempt is always justifi- able. Patients with normal cellular activity are better candi- dates for good health than those with abnormal, but the patho- logical changes in the body are sometimes so permanent that nothing will do much good. All other methods for improving the patients' health should be employed, such as hygienic, dietary and corrective; thyroid principle is only an additional, although a very important, aid. CHAPTER 23. HYPOTHYROIDISM— THERAPY BY THYROID FEEDING' By N. W. Janney, M.D. Need for Precise Diagnostic Measure. — The results of a com- parative study of the dinical and laboratory data for determining thyroid deficiency are reported herewith. There is very little difficulty in recognizing the average well developed case of myxedema or cretinism, but our observations show that cases of mild thyroid deficiency are probably more numerous than has previously been supposed; also that some will remain unrecog- nized unless special methods are used in diagnosis and control of treatment. Examination of the thyroid may be quite misleading. Twenty- five per cent, of our cases exhibited thyroid glands normal to physical examination. It must likewise be remembered that involution of the thyroid takes place as age advances. A small thyroid in an elderly individual is per se no evidence of myxedema, unless the gland be scarcely palpable, which should arouse sus- picion. Family history suggestive of thyroid disease, fat padding, marked frailty and brittleness of the nails, growth anomalies, tho ' less frequent, are, when present, of diagnostic importance. Suf- ficient attention is not always given to examination of the hair and nails, which are very often anomalous in thyroid disease. Distrophies of hair and nails are nearly always present in myxedema, thus bespeaking their relative importance. Mental symptoms, as a result of latent hypothyroidism, are more common than usually accepted by the neurologist or intern- ist. Very few hypothyroid cases show, if carefully observed, a normal mentality. We look too often for mental lassitude, forgetting that symptoms of mental irritability are also very frequently met with. Sometimes the picture is only that of neurasthenia. It may, however, go on to insanity. In one of ^ Editor's abstract, N. W. Janney, M.D., and H. E. Henderson, M.D., "Concerning the Diagonsis and Treatment of Hypothyroidism," Archiv. Int. Med., 26:297-318, Sept. 1921. Approved by Dr. Janney. 197 198 BASAL METABOLISM our thyroid families, one individual had dementia praecox, another periodic insanity. Such cases may not be on a thyroid basis, but only accompanying degenerative phenomena. Simple failure of memory and the power of concentration are frequently met. A very interesting thyroid family of 62 members has recently been reported by Barrett^, marked anomalies of the hair and nails being present in many members, together with mental conditions and other signs of degeneration. In another paper^, I have emphasized the great value of basal metabolic rate determinations in diagnosis and treatment of hypothyroidism. The differentiation of cases of latent hypo- thyroidism from neurasthenia, chronic intestinal toxemia, and other debilitated states and conditions is materially assisted by this accurate physical means. Pathogenesis of Hypothyroidism. — The entire picture of hypothyroidism is that of impairment of tissue growth, regenera- tion and consequent degeneration due to hormone hunger. It may, indeed, be possible that the great depression of basal metabolism observed in cretinism is partly, at least, of compen- satory nature, energy being spared and all metabolic processes being inhibited on account of the inability to adequately utilize fuel and replacement materials. That such an explanation may apply seems likely from the results of basal metabolism deter- minations in inanition, in which the rates are quite as low as those of the most marked cases of hypothyroidism which have been recorded. All of these varying factors can be understood and correlated with the aid of acceptance of the view that the thyroid gland controls the metabolic processes, anabolic and catabolic, necessary for the required replacement and repair of the organ- ism's cells, together with the production of heat and energy. General Aspects of Metabolism in Hypothyroidism. — There still remains considerable confusion with regard to modern con- ceptions of thyroid function. This, to a great extent, has been due to the antithesis between hypothyroid and the so-called hyperthyroid symptoms, as originally drawn by Kocher. . . . Study of the metabolism of hypothyroidism is, however, a greater aid to a clearer conception of thyroid function than the perplexing ^Barrett, A. M.: Arch. Neurol, and Psychiat. 2:628, 1919. ^ Janney, N. W.: "Hypothyroidism." Barker's New System of Endoc- rinology and Metabolism. THERAPY BY THYROID FEEDING 199 picture of thyrotoxicosis. Since Magnus-Levy's discovery of the decreased metabolic rate exhibited by cretins and myxedematous individuals, little experimental data had been added for a number of years. A reinvestigation of this subject was therefore under- taken in 1915 by one of us (N. W. J.) and his co-workers. This has been continued recently in our Santa Barbara Clinic. Since the decreased basal metabolic rate of cretins was ac- counted for by Magnus-Levy and others as being caused by defective food absorption due primarily to alimentary tract slug- gishness, exact feeding experiments* were undertaken which demonstrated that absorption of food from the intestines of athyroid animals was just as active as in normal animals. This led to further work on cretins, bringing out the fact that thyroid deficient patients failed to absorb as much nutritive material from the intestinal tract as normals, not because the alimentary function was necessarily deficient, but because such subthyroid individuals could not utilize digestive products in the normal manner, whether for fuel, tissue repair, or replacement purposes, ajter this food was assimilated by the intestinal tract. As was clearly demonstrated in prolonged metabolic experiments, when thyroid extract or thyroxin was administered in proper doses to these cretins, there ensued increased intestinal absorption accom- panied by and probably required by increased ability to retain nutritive substances in the body and build them into new tissue. These data were obtained by following the nitrogen metabolism. With the demonstration that large amounts, even 100 per cent, more than previously, of nitrogen were retained on proper thyroid dosage, good, if indirect, evidence was secured that the thyroid synthetically controls the growth, probably also the constructive repair and replacement of tissue. The anabolic function of the thyroid gland on metabolism was thus experimentally demon- strated. Hitherto the thyroid was supposed to exert its effect on metabolism solely thru the stimulation of catabolic processes as shown by increased nitrogen loss following the ingestion of thyroid material. Further experiments were therefore carried out demonstrating that the loss of nitrogen in this latter instance is a toxic loss, due to over-great thyroid dosage. Cases of Decreased Metabolism. — Variations in the metabolic rate are not necessarily due to thyroid disease. Thus we have * Janney, N. W., and Isaacson, V. I.: Arch. Int. Med. 22:160, Aug. 1918. 200 BASAL METABOLISM observed rates of— 15 per cent, to— 30 per cent, in hypopituitarism. Depression of the metabohc rate from —20 per cent, to —40 per cent, is usually clearly indicative of thyroid deficiency. How- ever, it must be remembered that patients in lowered states of nutrition may show greatly deprest metabolic rates. Thus among diabetics without thyroid disease, we have observed rates as low as — 35 per cent. The metabolic rate may also fail to serve as an exact criterion in early cases of hyperthyroidism, and even exophthalmic goiter, altho in the vast majority of cases, it is a great aid to the appreciation of the severity of the case as well as to thferapy. Thus can be quoted a case of exophthalmic goiter recently observed by us showing thyroid hypertrophy, tremor of fingers and tongue, sympathicotonia, moist palms and soles, nervousness and excitability, exophthalmos, Stellwag's sign, the glistening eyeball, rapid pulse on slight provocation, loss of weight and strength, indeed, all the symptoms necessary for a diagnosis, yet the basal metabolism was 5 per cent, below normal. Sound clinical judgment should never be unduly influenced by labora- tory methods. m 5 O (5 3 -J 2 < J E O St a ° i z ■- +10 o s -lO -20 1 1 1 1 1 1 1 ^^^^^g^^g^g ^^^m^^^^i ^^^^^^^^^^^1 ^^M ^^^^^^■^^^■- A .. y ~~ -- -- -- y y y — - -- -- -- ^ rt ^ ■»=■ X y ^ / «- BEFC RE TR EATM .NT ARTE R 1 M JNT H'; AFTE R R ED JCTIO J F BASAL ^ 1 1 4ETAB0LISM 1 TREATMENT^ 5 GRS. T . E) T. DOSE TOJ 2 GRS. THY EX T. -I9 ?>0 \ ^?'\ \ V \ \ ^ X 30 40 WEIGHT 50 KG. 60 70 80 90 too H^Chart 1. — A comparison of the normal standards for men 30 years old. The solid curved lines give the calories per hour according to the surface area chart and standards of Aub and Du Bois. The dotted lines represent the figures according to the Harris-Benedict multiple prediction tables. For instance, a man 30 years old, 180 cm. tall and 60 kg. in weight would have a predicted normal basal metab- olism of 70 calories per hour according to the surface area curves, and about 67 calories per hour by the other method. The results according to the Harris- Benedict formula are lower, but the two sets of lines are almost parallel for this age group. subjects studied were between 20 and 40 years old, and the standard used for this age was 39.5 calories per square meter per hour.^" If we express the matter graphically on a chart (Chart l), we can show the curves for the predicted metabolism of normal individuals of different heights and weights. If meta- bolism were proportional to height, these lines would be horizontal; 8 Cecil, R. L.; Barr, D. P., and Du Bois, E. F.: Clinical Calorimetry, Thirty-First Paper, The Effect of the Injection of Foreign Protein on Meta- bolism to be published. 9 Du Bois, D., and Du Bois, E. F.: Clinical Calorimetry, Tenth Paper, A Formula to Estimate the Surface Area if Height and Weight be known, — Arch. Int. Med. 19: 863 June, 1916. W Aub, J. C, and Du Bois, E. F.: Clinical Calorimetry, Nineteenth Paper, The Basal Metabolism of Old Men, — Arch. Int. Med. 17: 823 May 1917. IN FEVER 207 if proportional to weight, they would be vertical. If propor- tional to surface area, they would have the slant shown in the curved solid lines of the chart, and our results do agree with these curved lines. A purely statistical study of the normal basal metabolism by Harris and Benedict'^ has resulted in a height-weight-age formula. With a little calculation we can show their results for men 30 years old on this chart. It is significant that the dotted lines for the Harris-Benedict formula are parallel to the surface area curves. The studies of large groups of normal controls show that about 90 per cent, of normal men come within 10 per cent, of this standard; but a few who are apparently normal may show figures as much as 16 per cent, above or below. Can we predict the metabolism as closely as this for any specified degree of fever? Discussion of Results Obtained. — Chart 2 shows the results in all the fevers studied in the calorimeter, expressed by the method used by McCann and Barr in tuberculosis. The ordi- nates show the rectal temperature in degrees Centigrade. The abscissas show the level of the metaboUsm in percentage of the average normal. The line 90 means 10 per cent, below the average; 150 means 50 per cent, above the average. Each dot denotes an experiment of from one to three hours at a given temperature level. The normal temperatures were obtained in afebrile periods or in the first eight days of convalescence The diagonals are sketched to represent the direction of the swarms of dots. It will be seen that in tuberculosis the diagonal crosses the 40°C. line at a level of about 32 per cent, above the normal. In many of these patients there was enough undernutrition to account for a certain diminution in metaboUsm. In erysipelas the metabolism is a little higher for the same temperature. In typhoid fever, the Une crosses the 40-degree level at 48 per cent, above the normal metaboUsm. In malaria and the fever follow- ing the intravenous injection of foreign protein, the metaboUsm is sUghtly higher. Of course, it is necessary to leave out the shivering periods in these two conditions. It is possible that some of the results in the high temperature following the chiU are sUghtly affected by the previous severe muscular exercise. 11 Harris, J. A., and Benedict, F. G.: A Biometric Study of Basal Meta- bolism in Man, Publication 279, Carnegie Institution of Washington, 1919. 208 BASAL METABOLISM ,r, N, 1- \ 1— < \ :\ * x szzz: \ -J \ ^ \ CC :==t \ X N, 5 .^ \ " > \ \, UJ N S ' \ \ >«. \ 3z it; \ \.- \ — iij o ■ ' k- -•\ ■. o x \ |3 ..\ \' • ■\ N . • •\ X J vs. > • . > - X o a. - X ;^ n •^ X. 2 to IN FEVER 209 Protein Metabolism. — Most of the patients whose metabolism is very high for the degree of temperature were typhoid or malaria patients with a high level of protein metabolism. Most of those with low basal metabolism were tuberculous patients with low protein metabolism. We know that protein increases the metabolism through its specific dynamic action, and this may explain the difference between the groups of patients. The ingestion of a large protein meal does not increase the heat production in typhoid fever, in which the protein metabolism is already high, but it does cause a striking increase in tuberculosis in which the protein metabolism is at a much lower level. Although the increased protein metabolism seems to be a factor of some mportance, we believe that it is outweighed by another and impler factor. Normal Metabolism for Given Temperature — We note par- ticularly the similarity betwen fevers of greatly different origins, such as typhoid and erysipelas, malaria and intravenous injec- tions. We are impressed by the importance of the nonspecific element in fevers. This is even more striking, if we group all the heterogeneous fevers in one chart (Chart 3). The continued diagonal line is here drawn from statistical calculations, and the dotted lines are placed to represent divergences of 10 per cent, from this average. Out of the total of 137 experiments in various fevers, 82 per cent, come within 10 per cent, of the average. In other words, the percentage variations in the metabolism for a given temperature are scarcely greater than in a similar group of normal individuals. Van't Hoff Law. — This surprising uniformity of results sug- gests at once that we are dealing with the law of physical chem- istry enunciated by van't Hoff.^^ For ordinary temperatures the van't Hoff law can be thus expressed: "With a rise in temperature of 10 degrees Centigrade, the velocity of chemical reactions increases between two and three times." In other words, the temperature coefficient is usually between 2 and 3. This mieans an increase of from 30 to 60 per cent, for the 3 degree rise from 37 to 40 C. Practically all of the fever experiments are within these limits, and the average line shows a temperature coefficient of 2.3. '^ Van't Hoff, J. H. : Studies in'Chemical Dynamics, Revised by E. Cohen, Translated by T. Ewan, Easton, Pa., Ciiemical Publishing Company, 1896. 210 BASAL METABOLISM Van't Hoff and Kanitz'^ give the temperature coefficients which show the rate of increase in a number of chemical reactions TEMP. C* 41 40 39° 36° 37' 36* o-V . • / • ."V • • ' • . • • • / • • • 90 100^ 110 120 139 140 ISO 160 170 Chart 3. — Results in six different fevers grouped in one chart. The continued line shows the average and the dotted lines are drawn to represent metabolism 10 per cent, above and 10 per cent, below the average. with an equal rise in temparature. If we plot these in exactly the style of the fever patients (Chart 4) we note that the lines TEMP C 4 ' 40 3a 37" 36' i- 1 TEH/ o R COE 1 Sj 1 FFICIENT S / ^ ^^^^^ -^^ .^ ^ ^ ^ .:■ ^ ^^ ^ w ■' 90 100 110 120 130 140 150 160 170 RATE OF CHEMICAL REACTIONS Chart 4. — The lines in this chart represent a number of typical chemical reactions taken from van't HoiT and Kanitz. The slant of the lines shows the increase in the rate of the reactions as the temperature is raised. Note that the lines corres- pond closely to those which represent the total oxidations in the human body. '^Kanitz, A.. Temp'eratur und Lebensvorgange in Biochemie in Einzel- darstellungen, Vol. 1, Berlin, Gebriider Borntraeger, 1915. IN FEVER 211 have approximately the same slope. In other words, the reac- tions in a fever patient respond to a rise in temperature in a manner which resembles closely the chemical reactions in a test tube suspended in a water bath. There is a tremendous gap between the simple reactions in the test tube and the complex oxidations in the diseased human body, and we should hesitate to compare them were it not for the large number of biologic reactions which show temperature coefficients between 2 and 3. Van't Hoff calls attention to the rate of carbon dioxid elimination in plants, which shows a coefficient of 2.5. Kanitz^ gives a long list of similar coefficients for plant respira- tion, rate of isolated hearts, contraction of smooth muscle and the metabolism in cold blooded animals. Malarial Chill. — We have seen that the gross results in different fevers are strikingly similar. It is interesting to note the simi- larity in the details of the mechanism of the rise and faU of temperature in the chills of malaria and those which follow the 41 Z i o CO i z i CM z 2 o z 2 o lO^ a: 1 o / 4d 9 Q '/ ,,.—-' aWMDYTCMR 3i 7^ / / — /^ / / / 250 37 CALSPffi flotm 200 IJO : INDIRECT CALS 1 INDIRECT CAL£ 100 50 '-'-■■-■ MEAT ELIM. VAPORIZATION CAIS n Chart 5. — Calorimeter results during a malarial paroxysm. The upper con- tinued curve shows the rectal temperature. 212 BASAL METABOLISM intravenous injection of foreign protein. The first curve (Chart 5) shows the results obtained in a malaria patient by Dr. David P. Barr and myself. Before the chill the metabolism and tem- perature were nomial. In the period of the thirty-four minute chill there was terrific shivering, and as a result the heat pro- duction rose to 216 per cent, above normal. After the chill the metabolism was increased by the hyperthermia, and then fell gradually as the temperature became lower. The chill was accompanied by no change in the heat elimination. The old idea that the rise in temperature is largely caused by a decreased elimination has been proved false. The rise is due to the in- • creased heat production, and this is caused in part by shivering and in part by some chemical regulation, the nature of which is still in doubt. After the temperature has reached its zenith, the elimination must, of course, exceed the heat production. Errors in Measurement. — The curve of the rectal temperature does not always parallel the curve for the changes in the average body temperature. We shall never know the exact level of the average body temperature, because we cannot place ther- ■^ RECTAL TEW f^ 39 36 37" 36° / AV.JODYJTEh IP ^ — ~ ~"~~ £HILU CAL. P 150 RHOL f- DIRECT C AL. - 100 ' r HEAT ELIM. -;- 50 ™_j 1 sidireEt "cal-: VAPOR IZAT ON CAL. Chart 6. — Calorimeter results following the intravenous injection of 35 million dead typhoid bacilli. The percentage rise in metabolism does not appear so great because the chill occupied only a portion of the period between 11 : 45 and 12: 45. IN FEVER 213 mometers all over the extremities and in the viscera; but if we know the differences between heat production and heat elimina- tion, we can calculate how many calories have been stored in or lost from the body, using the method devised by Barr.* If we start the average temperature curve half a degree below that of the rectal temperature, we can then follow its changes. Appar- ently the region whose temperature is measured by a thermometer deep in the rectum shows a more rapid rise than the whole body, with its large mass of tissue near the surface and in the extremities. The curve of the arthritic patient who was given an intravenous dose of 35 milUon dead typhoid bacilli is almost identical with that of the malaria patient (Chart 6). A Study of the Respiratory Quotient. — A study of the res- piratory quotients in various fevers indicates that there are no significant changes in the metaboHsm of fat and carbohydrate. Protein metabolism is high in fevers, and the protein minimum or "wear and tear quota" cannot be reduced to the normal level. This increase seems to be proportional to the toxemia, since it is excessive in patients seriously ill with typhoid and erysipelas, and comparatively insignificant in chronic tuberculous patients with the same degree of fever. Water Metabolism of Fever Patients. — Balcar, Sansum and Woodyatt have produced excessive fever in dogs by depleting the water reserves of the body, and they infer^* that an abnormal water metabolism may be the cause of fever in man. If this were the case, we should expect to find striking abnormalities in the total or percentage loss of heat through vaporization in febrile patients. A careful scrutiny of the calorimeter results shows no such phenomenon. The water metabolism of fever patients corresponds closely with that of patients with an equal percentage rise in metaboUsm caused by hyperthyroidism. Conclusions. — Let us now answer the original questions. We can say that it is possible to estimate the basal metabolism of a patient by calculating his normal according to surface area standards. To this we should add about 13 per cent, for each degree Centigrade above the normal temperature (7.2 per cent, for each degree Fahrenheit). This should be increased by 10 per cent, in the case of toxic patients with great destruction of i< Balcar, J. O.; Sansum, W. D., and Woodyatt, R. T.: Fever and the "Water Reserve of the Body, Arch. Int. Med. 24: 116 July, 1919. 214 BASAL METABOLISM body protein, and by approximately 10 per cent, in all other febrile patients who are receiving much food. A further allow- ance of from 10 to 30 per cent, for muscular activity may be necessary if the patients are restless. It is interesting to note that our practical calculations in the clinic are based on the law of the conservation of energy, on the surface area law of Rubner, on the laws of the specific d3Tiamic action of foods as formulated by Rubner and Lusk,^^and on the temperature law of van't Hofl. '^ Lusk, Graham: Science of Nutrition, Philadelphia, W. B. Saunders Company 1919. CHAPTER 25. OBSERVATIONS ON THE BASAL METABOLISM ESTI- MATES IN THE GOITER CLINIC OF THE UNIVERSITY HOSPITAL.' By Charles H. Frazier, M. D. Basal Metabolism as a Diagnostic Measure. — The metabolic rate is of special value in diagnosis in that it offers a ready means of distinguishing cases of true hyperthyroidism from those cases of neurasthenia, cardiovascular disease or tuberculosis, who present the clinical picture of toxicity and who happen to have a simple adenomatous enlargement of the thyroid. These cases are ofteii sent to the surgeon as a court of last resort. Such cases would naturally not be benefited by any operation and might be made a great deal worse. The metabolic rate enables us to decide for or against operation in cases in which there is little or no perceptible enlargement of the thyroid gland, and in which the only evidence of toxicity is tachycardia. Basal Metabolism as a Therapeutic Guide. — It has been our practice to take readings on all goiter cases before and after treatment, whether that consist in ligation or thyroidectomy. If the case comes to ligation as the initial step in treatment a second reading is taken either before leaving the hospital or when the patient returns for thyroidectomy several months later. The final reading, after all treatment is over, is usually made within a year from the last operation, when the patient returns for final observation. Classification of Cases. — For the convenience of study and analysis we have divided our cases into 4 groups, based on the metabolic rate. Group 1. Basal metabolic rate from 10 to 20% Group 2. Basal metabolic rate from 20 to 40% Group 3. Basal metabolic rate from 40 to 60% Group 4. Basal metabolic rate from 60 and up ^ Abstracted from article of same title in American Journal of the Medical Sciences, July 1921. Abstract approved by author. 215 216 BASAL METABOLISM At the same time we have graded our cases according to the s)anptomatic evidence of toxicity alone. This is done without a knowledge of the metabolic rate. In Group 1 we place the mildest cases, i. e., those with the lowest grade of toxicity; and in Goup 4 the severest cases, i. e., those with the highest grade of toxicity. Groups 2 and 3 are intermediate. We find that there is a certain conformity between the groups graded by the clinical picture and graded by the metabolic rate. In fact, the con- formity is sufficient to enable us to say that in the majority of cases we have in the basal metabolic rate a numerical index of the patient's toxicity. This gives us at once a means of classify- ing our patients, a guide to the treatment and a measure of the improvement under any particular treatment. Surgery. — In treatment we find that we may be guided by the metabolic rate in the choice of operations. Thus in Groups 1 and 2 we may proceed with a subtotal thyroidectomy at once. In Group 3, in the majority of cases, we first do a bipolar liga- tion; only occasionally a thyroidectomy as the initial procedure. In Group 4 we never do a thyroidectomy first but choose either unipolar or bipolar ligation. The Metabolic Rate as a Check on Therapy. — The metabolic rate is also useful in determining the amount of improvement which any course of treatment may have effected. It is inter- esting to note that after ligation the average reduction is greater than after thyroidectomy. That the two figures cannot be com- pared, and any deductions drawn, as to the relative value of these two procedures is evident when we consider the type of case which is selected for ligation. Those cases which have a prelim- inary ligation have the highest metabolic rates. In reducing the metabolic rate it is as tho we were reducing the height of a pyramid; much less effort is expended in taking away the top half, the labor increasing with each successive step. It is easier therefore, to cut down the top half of a high metabolic rate by ligation than to remove the remainder, this more difficult part of the work being accomplished by the thyroidectomy. The reduction in total points, therefore, is less after thyroidectomy than after ligation. Conclusions. — In conclusion, our experiences at the cUnic show that the estimations of basal metabolism are of value in the following cases: ESTIMATES IN GOITER CLINIC 217 1. Positive. — In eliminating those cases which will not be benefited, and might be made worse by operation. 2. Supplemental. — In offering confirmatory evidence of the degree of toxicity; and in offering a quantitative rather than a qualitative index for use in diagnosis, prognosis and treatment. 3. Problematical. — It may be possible by the metabolic rate to determine how much thyroid tissue may be removed. The reduction of the metabolic rate to points well (below that of the normal range (—10 per cent.) should imply that too much secreting substance had been removed. Such cases must be studied clinically for signs of hypothyroidism. CHAPTER 26 BASAL METABOLISM AS AN INDEX TO SURGICAL TREATMENT^ By Frank H. Lahey, M.D. and Sara M. Jordan, Ph.D. The Value of Metabolism Studies. — Basal metabolism as a diagnostic measure, altho subject to error in estimation and interpretation, is probably more constantly reliable than many of our other laboratory measures, both as to its qualitative and quantitative value. It is of the greatest value in hyperthyroidism since that disease is so distinctive in its course and symptoms, and so characteristically a disease of h3^ermetabolism. From our experience in metabolism studies in connection with thyroid disease, involving 304 metabolism estimations on 135 patients, it does not seem that active hyperthyroidism exists without an increase in the metabolic rate. Such a study is of value, further, in determining the presence of secondary hyperthyroidism in those cases of adenoma of the thyroid in which the symptoms of hj^erthyroidism are not markedly evident. It used to be a source of considerable surprise to us in the beginning of our thyroid experience, before we were accustomed to employ basal metabolism estimation, to find that many patients upon whom we operated merely to remove an adenoma which was either causing pressure or was unsightly, came back within a few months, having gained in weight, and stating that they felt a marked change in their general health. This we now know to have been an improvement from secondary hyperthyroidism which, when well marked, is — with the excep- tion of exophthalmos — similar in every way to primary hyper- ' Editor's abstract, "Basal Metabolism as an Index of Treatment in Diseases of the Thyroid," by Frank H. Lahey, M.D., and Sara Murray Jordan, Ph.D., Boston Med. and Surg. Jour. 184:348-358, April 7, 1921. Approved by Dr. Lahey. 218 INDEX TO SURGICAL TREATMENT 219 thyroidism, and no more difficult to demonstrate. Its presence, however, in mild or pre-states of clinical hyperthyroidism is not easily demonstrated clinically, but even slight degrees of secon- dary hyperthyroidism are demonstrable by increases in the rate of metabolic activity. Metabolism Determinations as an Index to Surgical Treat- ment. — Metabolism estimation, correlated with the clinical examination, is also of marked value in indicating the abilitj' of a patient to withstand surgical procedures of various magnitudes; for example, in deciding whether the ligation of a single thyroid pole should be employed, whether it would be wise to ligate both thyroid poles, or whether it would be safe to employ partial thyroidectomy as a primary procedure. It is of further value in deciding when to follow the preliminary pole ligation with the partial thyroidectomy. Until recently it has been our custom to ligate the superior thyroid poles and then to send the patient home for eight weeks, at the end of which time the patient returned to the hospital for the complete operation. As the result of our metabolism investigations, we have been finding that in some cases, by waiting eight weeks, we have passed the period of maximimi improvement, as indicated by a rise in the metabolic rate from the rate representing the maximum drop after pole hgation. We have, therefore, come to the conclusion that during the intervals between pole ligation and partial thy- roidectomy, metabolism estimations should be made every two weeks, and partial thyroidectomy employed as soon as the maximima gain indicated by a drop in metabolism and pulse rate is made. Necessity for Correlating Clinical Picture with Metabolism Estimations. — We feel that in hyperthyroidism the metabolic rate alone is not a true criterion of the seriousness of a patient's condition, and, considered alone, is unreliable as a guide to the extent of the surgical procedure to be employed. That thyroid toxicity is represented by increased basal metabolic rates, there can be little question. However, we feel very strongly that the level of the basal metabohc rate alone is quite undependable, and in fact often misleading as a means of prognosticating the seriousness of the patient's state and her ability to endure any surgical procedure. We have had surgical experiences with 220 BASAL METABOLISM patients showing metabolic rates at both extremes, in which the course and results of the operative procedure have been entirely out of accord with what might have been expected from the metabolic rate. It is, therefore, evident that it is impossible to make any fixed statement concerning the percentage figures in basal metabolism at which it is safe to perform partial thyroidectomy as a primary procedure. Neither is it possible to state at what level of the basal metabolic rate it is wise to ligate but one pole, nor is it further possible, from basal metabolism estimations alone, to weed out the cases too seriously afflicted to be submitted to any surgical procedure and to be relegated to the less satis- factory and more prolonged methods of treatment not surgical in nature, such as rest and X-ray treatment. Yet with the previous view clear in our minds, we are willing to make certain approximate groups which we believe, from our experience, work out satisfactorily in a majority of cases. Partial thyroidectomy may be employed as a primary measure, unpreceded by ligations, in most of the cases showing increases in metabolic rates of not over +35 per cent. In all such cases, however, careful consideration must be given to the apparent degree of toxicity of the disease, as evidenced by the clinical signs, and this consideration must not be biased by the degree of increase in the basal metabolic rate, however moderate it may be. Careful consideration must also be given resulting or associated lesions, such as myocarditis and renal lesions. Fine judgment, based largely upon an extensive experience as to how similar cases have acted under various surgical procedures, is necessary in deciding between pole hgation and primary partial thyroidectomy in the cases of hyperthyroidism showing increases in basal metabolic rates of between -|-35 per cent, and -|-oO per cent. Decision as to the type of operation should be. left until the patient is on the operating table and anaesthetized, and should then be made only when based upon the known basal metabolic rate, the pulse rate, its character and rhythm, and, with a consideration of the possible degree of post-operative thyroid reaction. When doubt exists even in the slightest degree as to the safety of primary partial thyroidectomy, we ligate. Most patients showing basal metabolic rates above -|-50 per AS AN INDEX TO SURGICAL TREATMENT 221 cent, are safest when submitted to primary ligation of one or both of the superior thyroid poles. It is our custom in these cases to reserve decision until the patient is anaesthetized (scopolamine, morphia, novocaine + gas oxygen), making use of the same measures as stated above. The decision is then made whether the patient shall be sent back to bed to observe the degree of reaction to the anaesthesia and visit to the operat- ing room, or whether ligation of the poles shall be proceeded with. If the latter procedure is decided upon, one superior pole is rapidly ligated and decision as to whether ligation of the other superior pole is to be carried out is based upon the immediate condition of the patient and how she has endured the ligation of a single pole. With patients showing metabolic rates of from +75 per cent, up, extreme caution must be exercised in the extent of the surgical treatment. In the doubtful cases, a visit to the operating room and the administration of gas oxygen anaesthesia with no opera- tive procedure gives valuable evidence as to the resulting degree of reaction. In the less doubtful cases, the ligation of a single pole with a wait of ten days to two weeks makes the ligation of the second pole very much more safe for the individual. Caution in Thyrotoxicosis. — It is our opinion that there is hardly a surgical disease in which caution is as necessary as in the cases of marked thyrotoxicosis. As they approach the higher levels of toxicity as indicated by clinical signs and increases in metabolic rates to a high level, each case should be individuahzed and no longer looked upon as being a member of a group. After such cases have reached the more intense stages of thyroid intoxication, they no longer conduct themselves by rule. This statement is more or less true of hyperthyroidism as a whole, but is particularly characteristic of the intensely toxic cases. After an extensive experience with thyroid cases, we feel able to prophesy with relative certainty the course and reaction of mild and moderate degrees of thyroid intoxication to various surgical procedures, but have by no means the same degree of assurance regarding the intensely toxic cases. It is because of this unknown capacity for unfavorable reaction on the part of severely toxic cases that extremely cautious advance should be made. First, the degree of reaction to the slight discomfort and apprehension which goes with the estimation of basal metabolism; next the 222 BASAL METABOLISM reaction to a visit to the operating room and short gas-oxygen anaesthesia, and finally, based upon this data, the ligation of a single thyroid pole. Having advanced so far, we have accu- mulated sufficient data upon which to base with reasonable certainty a decision as to the probable outcome with further surgical procedures. Clinical Complications. — Care must be taken, in thyroid cases, to ascertain the presence of complicating conditions which seriously affect the metabolic rate. For example, diabetes, in our experience, has not been a rare complication of hyperthy- roidism (or vice versa, if you choose), and in such a condition care must be taken to ascertain to what diet and to what treat- ment the patient has been subjected. Care must also be taken to ascertain possible renal lesions, marked examples of which are said to give increased metabolic rates. Seemingly simple infections giving but low degrees of tem- perature reaction must also be eUminated, as fever very promptly results in a marked increase in the metabolic rate. In thyroid cases, basal metabolism estimation should not be undertaken at a time too close to the period following the per- formance of the Goetsch or epinephrin test as injections of epinephrin have resulted in our experience in well marked rises in the metabolic rate. Apprehension, anxiety, and excitation play a considerable part in the production of unreliable data in metabolism estima- tion, and where even the possibility of such influence occurs the test should be repeated daily until an average is struck or the patient eliminated as a subject from whom a reliable result may not be obtained. Conclusions. — When all the factors, that are described in the paper, can be eliminated and the basal metabolic rate can be regarded as a true index of thyroid activity, it may be said in conclusion that, in our opinion, in a clinic for diseases of the thyroid, a test of the rate of bisa metabolism is an invaluable factor in the data necessary for diagnosis; second, that it aids greatly in prognosis; third, that it probably has its greatest value as an index of the results of treatment in any given case. CHAPTER 27 A CONSPECTUS OF RECENT ADVANCES IN METABOLISM For the purpose of presenting some of the new developments in the field of basal metabolism, recent papers by qualified authors have been reviewed. From them, relevant material that has not already been included in this book has been ex- tracted and is presented in summarized form as below: 1. Comparative Normals of Children. 2. Normal MetaboUsm After a Light Diet. 3. An Aid in Prognosis. 4. Classification of Goiter. 5. Effect of Menstruation. 6. Pregnancy and the Puerperium. 7. Chronic Pulmonary Tuberculosis. 8. Respiration in Tuberculosis. 9. Thyroxin. 10. Pituitary Extract. 11. Dysfunction of the Liver. 12. Myelogenous Leucemia. 13. Kymograf Records. Comparative Normals of Children. — Blimt^ made observa- tions on 28 children, chiefly underweight, ranging from 9 per cent, to 27 per cent, but revealing no clear symptoms of hyper- thyroidism or other organic disturbances. Three or four deter- minations of two 10 minute periods were made on the majority of the children, on an apparatus measuring only the oxygen consumption. The calories per square meter of body surface per 24 hours obtained for this series were in every case higher than the standards according to Benedict. Altho there was an excess metabolism as high as 40 per cent, no relation was observed between the percentages metabolism increase and the percentage underweight. ' Blunt, Nelson, and Oleson: The Basal Metabolism of Underweight Children — Jour. Bio. Chem. 49:.247-2o2, Nov., 1921. 223 224 BASAL METABOLISM Benedict^ studied 23 children, ranging from 2 to 15 years of age for periods of a few months to 3 or 4 years. A modified respiration chamber was used, in which the carbon dioxid con- tent was determined by weight of the absorbent bottles, and the oxygen content by a meter. The periods of 20 to 30 minutes were repeated as often as was advantageous. The conclusion drawn from this large series of tests is that the metabolism of the child is most dependent upon the body weight, girls manifesting, however, a constantly lower figure. Klein' propounds the belief that extensive determinations upon the same subject are more exhaustive and valuable than 1 or 2 tests upon many children. His figures are, therefore, the report of tests upon only 2 boys. Eight tests of 10 hours each were made in a respiration chamber, cautiously guarded for tightness. The heat exchange was calculated from the oxygen and carbon dioxid content of the expired air. For the meta- bolism the Lissauer and Meeh formulae are used. From each of these authors one case has been selected of approximately the same height and weight, and of the same sex, to compare the results: Height Weight Cdls -per sq. m. cm. kg. Age per 24 hrs. Blunt, Case John 125.8 23.2 8 y. 1 mo. 1213 Benedict, Case No. 215 116.5 20.8 8 y. 23^mo. 1165 Klein, Case Kurt 114.0 22.2 7 y.lO mo. 1079 Case John was 10 per cent, underweight, and determined in the post-absorptive condition. Case No. 215, "somewhat thin" but otherwise normal, was not allowed food before the test. Case Kurt, the normal figure for which is the lowest, was allowed a restricted diet on the day preceding the night of the test, dur- ing which it must be remembered that the boy was asleep, which factor alone might account for the lower figure. Normal Metabolism After a Light Diet. — Recently Baum- gart and Steuber conducted experiments in the pneumatic cabinet of the Physiological Institute in Beriin to determine the basal metabolism of 2 boys who were in the fasting state. After their ^ Benedict and Talbot: Metabolism and Growth from Birth to Puberty — Carnegie Inst., Washington, Pub. No. 302, 1921. 8 Klein, MuUer, and Steuber: Beitrag zur Kenntnis des energetischen Grundumsatzes bei Kindern — Archiv. fur Kinderheilkunde, Stuttgart, Oct. 29, 1921. CONSPECTUS OF RECENT ADVANCES 225 painstaking work, they found it to be 100 cals. lower than Rub- ner's constant for heat production, which decrease they attri- buted, judging from the R. Q., to the post-absorptive condition of the children. The authors^ believed that a more exact figure would be ob- tained if the subjects were allowed nourishment, preferably liquid, and of a definite amount. As subjects, two 8 year old boys were chosen who had always been in good health, and were well developt in regard to height and weight. All experiments were made at night during sleep, lasting 10 hours, with the fol- lowing preceding diet: Breakfast 7;00 A. u. SO g. rice, 25 g sugar, 50 c.c. milk Total about 350 cals. Noondaj lunch 30 g. sago cooked in water with one broth cube and salt. Total about 126 cals. Tea at 3:00 p.m. 250 c.c. tea with saccharin. Tea at 8:00 250 c.c. tea with saccharin. The experiment began about 9.00 p. m., after the boys had been taken for a walk to insure a good night's sleep. It was rather to the experimenter's amazement that the boys exper- ienced no hunger. Two reasons are given for performing the experiments on 2 boys at once: First, by one another's company to allay any fears that the closed chamber might arouse. Second, to rule out the personal factor: one of the boys was very phlegmatic; the other, Uvely. The tightness of the apparatus was checked bj' the nitrogen content, at the beginning and end of each experiment. Respira- tion quotients varied from .78 to .93. Altho the boys' height and weight were almost identical, 114 and 113 cm., and 22.2_and 21.6 kg., respectively, the individual body surface area was calculated and the average used. The heat production during rest and sleep by the Meeh for- mula was 1033.8 cal. per 24 hrs. per sq. m. of body surface; by the Lissauer formula, 1123.9 Cals.; and per kilo of body weight, 44.52 calories. An Aid in Prognosis. — Wilson* considers the determination * Wilson, C. M., and D.. The Determination of the Basal Metabolic Rate, and its value in Diseases of the Thyroid Gland. Lancet, Nov. 20, 1920. 226 BASAL METABOLISM of the basal metabolic rate helpful to bring out the value of rest and its limitations, to define the role of drugs, to separate the type of case the X-ray benefits from the larger group in which it is of no avail ; and with regard to surgery, to lay down precise rules for our guidance. We know now when nonsurgical meas- ures have done what they can do, when the choice rests between surgery and continued thyroid over-activity. We are told by this means not only under what conditions operation is necessary and beneficial, but also when the appearance of the surgeon is of evil omen. Finally, these measurements enable us to detect the malady, and the relapses of that malady after treatment at a stage when active measures will rapidly restore normal func- tion. In therapy, basal metaboUsm determinations mark off toxic from non-toxic goiter, establish or refute suspicions of hypo- or hyper-thyroidism, and furnish a grafic record of the results that follow the treatment of these conditions, so that the selec- tion of the line of treatment becomes less capricious and comes to rest upon exact methods. Classification of Goiter. — Mayo® has presented the mani- festations of various types of goiter at the onset of the disease, stressing the basal metabolism test as a diagnostic measure to differentiate particularly between toxic goiter and psycho- neurosis. Mayo mentions first, Basedow goiter, which may remain inactive for from 14 to 20 years with no exophthalmos, but with hyperthyroidism. This is not to be confused with Basedow's disease, the German term for exophthalmic goiter. In true exophthalmic goiter there is an hypertrophy of the epitheliimi causing crowding of the vesicles and no retention of secretion. Altho with this type of goiter hyperthyroidism ib not manifest until about 43 years of age, Mayo states that he has seen children under 10 with typical symptoms of exophthalmic goiter, such as tremor, tachycardia, nervousness and exophthal- mos. A small hard, symmetric gland, not exophthalmic goiter, may be tuberculous. All cystic goiters are the result of degeneration following failure of the blood supply of the encapsulated adenoma. The 5 Mayo, Chas.: The Thyroid. Medical Record, July 30, 1921. CONSPECTUS OF RECENT ADVANCES 227 cystic goiter is encapsulated and thus the thyroid is converted into an extra capsule. Toxic adenoma producing hyperthyroidism appears in the average case at 43 years, and yet the average age at which these patients are operated is 48 years. Carcinoma of the thyroid rarely produces symptoms early in the course of the disease. If there are irregular, hard nodules in the gland it is probably malignant, especially if the adjacent lymphatics are enlarged. Exploration, with examination of tissue is, however, necessary for diagnosis. Substernal goiter is more common than was supposed. Some- tim.es its presence is indicated by the veins on the neck extending down over the chest, showing the obstruction to the venous flow. This type of goiter is frequently well encapsulated and can be easily enucleated, especially if the patient cooperated by a little cough. In order to have the advantage of the cooperation of the patient, operations on goiters of this type should be per- formed under local anesthesia. Syphilitic goiter is not very common, and sarcoma is rarer than carcinoma. Effect of Menstruation. — No significant difference is noted for the pre- and intermenstrual periods of normal women, including a series of 216 observations® on 17 women, 14 of them covering 1 or more menstrual cycles, and 1 being observed for 26 almost consecutive days. The authors also note no regular, rhythmic, day by day variation. With a number of subjects a high meta- bolism day can be found just before or at the beginning of men- struation but so also can a low metabolism day. That there is no regularity of variation is corroborated by Zuntz, who in 1906, determined the carbon dioxid output and part of the time the oxygen consumption for 2 women for 97 days, almost without a break, including 3 menstrual periods with inter-, pre-, and postmenstrual observations. He noted no variation that he attributed to menstruation. Wiltshire^ has recently completed observations on 5 normal women during the menstrual period, with an average of from 25 6 Blunt, K. and Dye, M. : Basal Metabolism of Normal Women. Jour. Bio. Chem., June, 1621. ' Wiltshire, M. O. P. : Some Observations on Basal Metabolism in Men- struation. Lancet, Aug. 20, 1021, Op. 388. 228 BASAL METABOLISM to 58 tests upon each case, collecting the samples of air by the Douglas method and analyzing the expired air by the Brodie method. An average of 4 menstrual cycles of each case was covered, with tests each day of the period and 3 or 4 intermen- strual determinations. An average of 37.2 cal. per sq. m. per hr. was obtained, approximately normal according to Benedict, with little variation from the normal in pre-, post-, and intermenstrual periods Only in one case. No. 4, was there a perceptible drop, i.e. 6 per cent, between the premenstrual and menstrual periods; and only in one case, No. 3, was there a postmenstrual drop, of 5 per cent. Wiltshire's conclusions agree with those of Zuntz and Blunt: that no variation in metabolism can be noted as a result of menstruation, yet do not corroborate those of Snell* and Rowe" who have observed a specific deviation from the normal due to menstruation. Pregnancy and Puerperium. — Patients reported in the maternity ward of the Michael Reese Hospital, Chicago, the night previous to the test, thus insuring complete rest and re- stricted diet. Of 105 original cases^", only 44 completed the series of consecutive readings, due to complications of patho- logic conditions, tachycardia, lack of cooperation, and other factors which would of necessity make nil the value of their results. No increase could be noted in the early weeks. Be- ginning in the thirty-fourth week, there was a gradual rise from plus 26 per cent, to plus 33 per cent, in the fortieth week, fol- lowed by a drop to plus 15 per cent on the third day postpartum, reaching the normal level not later than the eleventh day. Fetal sex played no imiportant role, as an average rate in the fortieth week for the mothers bearing male fetuses was plus 37 per cent, in contrast to a plus 34 per cent, for those bearing female fetuses. The results are summarized: 1. The basal metabohc rate in 44 normal cases in late preg- nancy averaged 33 to 35 per cent, above the normal for non- pregnant women of a surface area equal to the pregnant woman. 8 Snell, A. M., Ford F., and Rowntree, L. G.: Studies in Basal Metabolism. Jour. Am. Med. Ass. 515-523, Aug., 1920. 9 Rowe, A. H. : Monthly Fluctuations in the Normal Metabolic Rate of Men and Women. Cal. State Med. Jour. Aug., 1921. M Baer, J. L.: Basal Metabolism in Pregnancy and the Puerperium. Am. Jour. Ob. and Gyne. Sept., 1921. CONSPECTUS OF RECENT ADVANCES 229 2. Three days after delivery the average basal metabolic rate is only 15 per cent, above normal. 3. Seven to ten days postpartum the average basal metabohc rate is approximately normal. 4. Death of the fetus in late pregnancy is detectable in a woman otherwise normal by a drop in the basal metabohc rate compared with the average in this series. Baer presents the following conclusions: 1. The increased basal metabolic rate in late pregnancy is due to the growing demands of the fetal organism and placenta. 2. The incomplete or delayed return to normal is due to involution of the uterus and the onset of lactation. 3. Twin pregnancy should show a rate above the average for single pregnancy when both twins are well developed. 4. Thyroid enlargement may occur in pregnancy without increasing the basal metabolic rate above the average obtained in this series 5. Differential diagnosis between uterine tumor and preg- nancy, will not be helped unless greater refinements in method show increased rates much earUer than in this series. The X-ray can be called on as early as the fifth month and with reasonable certainty in the sixth month. Chronic Pulmonary Tuberculosis and Hyperthyroidism. — Studies have been made of 23 incipient, 17 moderately advanced, and 4 far advanced cases of tuberculosis, with 6 known non- tuberculous cases. In about one-third of the cases of chronic pulmonary tuberculosis, the basal metabolic rate and the blood sugar are both increased; in about one- fifth of all such cases there may be an increased basal metabolic rate and a normal blood sugar, or just the reverse, while in a much smaller percentage of cases, no change in either basal metabolic rate or blood sugar may be present: very seldom, however, would both be decreased, or even one decreased and the other normal. McBrayer^^ advances the following theory to account for the increased basal metabolic rate and blood sugar in the tuberculous cases: Tuberculo toxins stimulate the suprarenal glands, resulting in an increased output of the secretion from these glands, which in turn would do three '1 McBrayer, R. A.: Blood Sugar and Basal Metabolism; Findings in Chronic Pulmonary Tuberculosis and Hyperthyroidism. Jour. Am. Med. Ass., Sept. 10, 1921. 230 BASAL METABOLISM things: (1) Inhibit the island of Langerhans; (2) stimulate glycolysis, and (3) stimulate the thyroid gland to greater activity, which would produce the hyperthyroid symptoms frequently encountered in incipient and chronic pulmonary tuberculosis. Thus, as hyperthyroidism will consistently manifest an increased basal metabolic rate and an increased blood sugar, McBr^iyer concludes that these tests can not be used for differential diag- nosis. Respiration in Pulmonary Tuberculosis. — For 5 normals McCann^^ finds the average minute volume to be 4.25 liters, average respirations were 11 per minute, and average tidal air, 397 c.c. For 5 tuberculosis patients, the average minute voliune was 8.25 liters, average respiration rate 25 per minute, and average tidal air, 350 c.c. Peabody has shown that a normal may increase his tidal air up to one-third of his vital capacity. If this obtains also with a tuberculosis patient, from the tidal air of 350 c.c. a vital capacity of only 1,000 c.c. would be indi- cated, diminished somewhat, to be sure, by the recimibent position of the patient at the time of the test. In comparing the average minute volumes, it will be noted that the total pulmo- nary ventilation of the 5 cases of advanced pulmonary tuber- culosis was about twice that of the normals. Yet for this in- crease in ventilation there was not a proportionate increase in amount of CO2 exhaled. For a ratio of 1.2 in total minute volume, there is a C02per minute production ratio of only 1:1.17. This would indicate a respiratory quotient deviating from the normal, 0.82. The respiration rate of the tuberculous was increased in each case, yet there was little rise in buccal tem- perature. The basal metabolic rates ranged from plus 30 per cent, to plus 3 per cent., with an average of plus 16 per cent. Thyroxin. — Recognizing the chief function of the thyroid gland to be the generation and storage of thyroxin, Plummer'^ has formulated the following deductions in regard to the func- tion of thyroxin: 1. Thyroxin is active directly or indirectly in the cells thru- out the tissues of the body. 12 McCann, W. S. : The Effect of the Ingestion of Foodstuffs on the Respira- tory Exchange in Pulmonary Ti berculosis. Arch. Int. Med. Dec. 15, 1921. ^5 Plummer, Henry.: Interrelationship of Function of the Thyroid Gland and of its Active Agent, Thyroxin, in the Tissues of the Body. Jour. Am. Med. Ass., July 23, 1921. CONSPECTUS OF RECENT ADVANCES 231 2. Thyroxin is an agent hastening the rate of formation of a quantum of potential energy available for transformation on excitation of the cell. The phenomena of hyper and hypo-activity of the thyroid gland are summarized thus: 1. Hj^erthyroidism is the physiologic status of an individual otherwise normal when the thyroxin in the tissues is sufficient to hold the basal metabolism above normal. 2. Hypothyroidism is the opposite of hyperthyroidism. 3. All the phenomena in pure hyperthyroidism are those that must attend a sustained elevation of the basal metabolism. 4. The status of the hyperfunctionating adenomatous goiter is the result of a pure hyperthyroidism. 5. The status of exophthalmic goiter is not accounted for by a pure hyperthyroidism. Experience with thyroxin administration to myxedematous patients at the Mayo Clinic has led Hummer to draw the fol- lowing conclusions : 1. After the administration of a single dose of thyroxin sufficient to bring the basal metabolism to normal, the physio- logic status of a thyroidless patient becomes normal in from 10 to 12 days, remains approximately normal for 10 days, and returns to the preexisting status in from 5 to 7 weeks. 2. The amount of thyroxin in the tissues (exclusive of the thyroid) of the average normal man is approximately 14 mg. Kendall, from an analysis of the iodin content in the tissues, recently estimated the amount to be 14 mg. 3. The average daily exhaustion of thyroxin in the tissues is between 0.50 and 1 mg. 4. A shift of 1 mg. of thyroxin in the tissues of the body is accompanied by a corresponding rise or fall of between 2 and 3 per cent, in the basal metabolism. 5. 14 mgs. of thyroxin given to a thyroidless person is not fully exhausted until from the end of the fifth to the eighth week. 6. 2 mgs. of thyroxin a day may hold the basal metabolism from 20 to 30 per cent, above normal; 3 mg. a day may hold the metabolism 50 per cent, above normal. An intravenous dose of more than 1 mg. of thyroxin will, with the exception of a case of exophthalmic goiter with a basal metabolism of plus 65 per cent, or colloidal goiter with bruit 232 BASAL METABOLISM cause a sustained elevation in the metabolic rate. It has been found, however, that daily doses of 1 w.g. of thyroxin for months to persons with an apparently normal thyroid have caused on deflection in the basal metabolism. The daily exhaustion of thyroxin of a thyroidless patient is from 0.2 to 0.4 mg., as compared with 0.5 to LO for the normal. The orar dose necessary to keep the basal metabolism of the myxedematous patient at the normal level is L6 mg., much in excess of the theoretical elimination of thyroxin. This is accounted for, possibly, by the incomplete absorption of thy- roxin from the gastrointestinal tract; thus the metabolic re- action is more intense and more constant with intravenous administration; a fact, incidentally, in favor of the use of thyroxin instead of desiccated thyroid. Pituitary Extract. — Experiments were performed'* upon 4 groups of individuals; normals, hypothyroids, those with pit- uitary disorders, and normal and hypothyroid cases who had received thyroxin. The object was to determine the effect that extract of the posterior lobe of the hypophysis, when used sub- cutaneously, had on the metabolism of the normal and of those with endocrine disturbances, chiefly of the thyroid and pituitary glands. Any relation between thyroxin, the active principle of the thyroid gland, and pituitary extract, was to be noted. Of 12 students, none manifesting signs of endocrine disturb- ance, with a normal basal metabolism, 11 responded with an increase after the use of pituitary extract. The percentile increase in basal metabolism varied from 2 to 16, and aver- aged 5. Physiological changes have been apparent; marked pallor, slight systolic elevation in the blood pressure, and subjectively abdominal cramps. In the group of 4 clearly defined cases of hypothyroidism, there was a decrease in the heat production after administration of the pituitary extract. There were fewer subjective symptoms in this group. A synergy between the thyroid and hypophysis would be evidenced by the comparison of results of pituitary treatment on the normals, on the one hand, in which there was an acceleration of heat production, and on the hypothyroids, 1-1 McKinlay, C. A. : The Effect of the Extract of the Posterior Lobe of the Pituitary on Basal Metabolism in Normal Individuals and in those with Endocrine Disturbances. Arch. Int. Med. 28; 703-710, Dec. IS, 1921. CONSPECTUS OF RECENT ADVANCES 233 on the other hand, in which there was a slight but consistent abatement of heat production. In the group of 3 cases with a normal thyroid, judged from the absence of myxedematous symptoms, there was a disturbed function of the hypophysis, evidenced by the development of obesity, increased sugar tolerance, subnormal temperature, and dysmenorrhea in one of them. Pituitary extract accelerated the heat production in each case. McKinlay suggests that if such a relationship, viz., that of an increase in metabolism with pituitary extract only if the thyroid is active, holds true in a larger series of cases, the determination of the effect of pituitary extract on basal metabolism may be used as a test to estimate in pluriglandular cases the extent, if any, of thyroid involvement. With the last group of 6 cases, 4 of whom were normals to which thyroxin had been administered, and 2 hypothyroids who had been receiving benefit from thyroxin, there was a corrobo- ration of the preceding hypothesis. The normals reacted with an increased heat production, slightly greater than the first group of normals who had had no thyroxin. The myxedematous patients showed no response to pituitary extract. McKinlay believes the experiment to give evidence that heat production of the body is due to a balance between endocrine glands, more specifically between the thyroid and hypophysis. The follow- ing conclusions are presented: 1. Normal persons responded quite constantly with in- creased basal metabolism following the subcutaneous injection of pituitary extract. 2. In a small series of cases with hypothyroidism, the basal metabolism was diminished rather than increased, which sug- gests that pituitary extract is effective in accelerating heat production only of a normally functioning thyroid gland. 3. In four cases with subnormal basal metabolism in which clinical evidence of myxedema was lacking and preponderance of influence of endocrine glands other than thyroid was suggested, the positive response to pituitary extract was present. 4. The increased acceleration of basal metabolism in a group of normal individuals following the subcutaneous injection of pituitary extract one week after an injection of thyroxin, is interpreted as suggesting a synergic action between thyroxin and pituitary extract. 234 BASAL METABOLISM Dysfunction of the Liver. — Aub and Means'^ report a normal basal metabolism on 12 patients with distinct involvement of the liver, representing varied types of disorders. The reaction to ingestion of protein food with the patients was much the same as with normals. Even in a case of portal obstruction with rapidly recurring ascites, and also a case with practically con- plete bile duct obstruction, the normal elevation of the meta- bolism was noted. Protein catabolism was more evident in cirrhosis in general, altho in two cases of cirrhosis and one of gallstones, there was no specific rise in metabolism. Aub and Means conclude: 1. That in these cases the basal metabohsm of liver disease was essentially within normal limits. The liver, is, therefore, either not an important regulator of the metabolic rate, or it is adequate for this purpose even when severely diseased. 2. The rate of absorption and utilization of protein in large quantities was usually normal. 3. The conclusion seems justified that either the liver is not the main seat of the specific dynamic action of protein or that it can adequately perform that function even in disease. 4. The observation of Du Bois that in exophthalmic goiter a normal increase in heat production, due to protein, is super- imposed on the high basal rate is confirmed. Myelogenous Leucemia. — Gunderson'® reports a consist- ently high metabolism on 19 cases of myelogenous leucemia with 62 observations. Altho he does not find that the increase in metabolism and the degree of leucocytosis vary in direct proportion, the former at least bears as close a relation to the number of immature white cells in the blood as it does to the total leucocyte count. The increase in metabolism above normal might be attributed to the anemia of varying degrees, present in all cases. Gunderson points out that at the most the anemia would be responsible for only a slight increase, and cites the following cases: On Jan. 11, the basal metabolism was plus 80 per cent, the hemoglobin 32 per cent., white count 240,000 per cu. mm., myelocytes 58 per cent., and the myeloblasts, '^ Aub, J. C, and Means, J. H. : The Basal Metabolism and the Specific Dynamic Action of Protein in Liver Disease. Arch. Int. Med., Aug. 15, 1921. '* Gunderson, A. H. : The Basal Metabolism in Myelogenous Leicemia and its Relation to the Blood Findings. Boston Sur. and Med. Jour., Dec. 25, 1921. CONSPECTUS OF RECENT ADVANCES 235 FIG. I NORMAL -Ap.neo'ic Rettntioti FIG. 2 HYPERPNEA Expiration Rate S\ope FIG. 3 .yvyv^MAAAAAAAAM, Saime Patient as F'ig.Z' Swallow— K--- Deep Sigh F\a. s 236 BASAL METABOLISM 30 per cent. On March 26, the basal metabolism was plus 34 per cent., hemoglobin 40 per cent., leucocyte 235,000, myelo- cytes 30 per cent., and the myeloblasts 3 per cent. The basal metabolism may then be used as an index of the activity of the leucopoetic tissue, as the results of these observations show that it bears a relation particularly to the number of immature white cells in the blood stream, regardless of the total leucocytosis. The highest values for the basal metabolism are usually found in cases with very high white counts and many myelocytes, or in cases showing high percentages of myeloblasts. Gunderson reports that in exactly half of the 62 determinations, the meta- bolic rate was over plus 20. The case stated above, however, had the maximimi rate, plus 80. Kymograf Records. — Records of respirations afford a grafic representation of respirations — a picture of respiratory pro- cesses from the beginning to the end of the test. These records may show the regularity, frequency and depth of respirations, and give a check on the rate of respiration and the rate of accu- mulation of expired air, or the rate of consumption of oxygen. The Kymograf records here shown have been obtained by a new form of recorder or kymograf that is directly attacht to an ordinary form of Benedict Metabolism Apparatus. The records are made in ink on a strip of paper 2^^" wide (ordinary adding machine paper) that is driven by a clock mechanism, and is wound on to one roll from another. A continuous record of a patient's respiration may thus be obtained covering many minutes, and extended on a strip of paper 10 to 20 feet long. The time mark is made every minute, or every fifth of a second. The marks are not shown in Figures 1 to 5 that are given on page 235, which illustrate the records of respirations for normal conditions as well as those resulting from certain irregularities. Figure 1 shows the record of a normal person in whom there was no element of fear of the apparatus, or apprehension of the test. In fact, a mechanic who had worked upon the apparatus for over a year was chosen for this test. It will be noted that there is a slight apneoic flatness of the curve at the base. The amphtude is, however, by no means exact, nor is the height. This is the usual type in records of composed patients. The frequency of respirations per minute, which is not shown by this portion of the curve, remains constant. The dotted hne has CONSPECTUS OF RECENT ADVANCES 237 been added to the record and represents the respiration rate slope and enables one to determine rate of oxygen consumption. Figure 2 shows the record of the respirations of a girl who has been familiar with metabolism apparatus for a year. Altho purposely no attempt was made to allay her fears, or to comfort her in any way, one would at least expect her curve to become more regular after she had been attacht to the apparatus for a few minutes. This portion of the curve represents the last of an 8 minute period. It is obvious that any reading taken dur- ing this period would be invalid, as not the slightest consistency is seen even at the expiration rate slope line. Figure 3 shows test on the same girl, made the following day. The respirations became more regular in every respect, altho there was a sUght increase in respiration rate. A wave at the expiration base Une is evident, which would indicate hyperpnea rather than dyspnea. Figure 4 illustrates the effect of swallowing. When meta- bolism tests are n:ade with closed circuit apparatus, many author- ities have stated that an error may occur in the amount of oxygen consumption if the patient swallows oxygen. They have also believed that carbon dioxid would be washed out of the respira- tory system as a result of the unnatural respirations that are brought about while the nose is clamped, as breathing into the closed circuit takes place thru the mouth only. Figure 4, however, show s that in the case of a deep swallow there is immediate return to the expiration rate slope line, and thus normal conditions resumed much more quickly than is generally supposed. Figure 5, illustrates the discrepancy of respiration that may be caused by a mental problem. A problem in oral arithmetic was given to the patient, such as — "Multiply 6 by 2, add 6, divide by 3, add 6, add 1, subtract 11, multiply by 5, etc." At the onset of the problem there was evidence of a distorted curve from the normal, due to the concentration of the subject upon the mathematics. The entire curve during the time of mental exertion was irregular in all respects, returning quickly to the normal at the end. Grafic records are a distinct aid in making metabolism de- terminations and analyzing the results of tests. It is probable that such records will come into more extended use in the future. CHAPTER 28 TABLES WITH EXPLANATIONS This chapter contains "Computations", which are the terror of many a successful physician and the joy of many a laboratory assistant. However, the average physician or technician need have little fear of having difficulty in understanding the re- quisite processes of computation if he will content himself with following the simplified methods that are given. Each section has both a simplified process and a more complete and accurate process. There are Normal Standards of Basal Metabolism; a simplified table of Normal Consumption of Oxygen; Values of Body Sur- face Area by direct readings from a table, a chart, and by computation; the Methods of correcting for Temperature, Baro- meter, and Saturation; and Tables of Equivalents. Determination of Normal Basal Metabolism. — The Du Bois Normal Standards of Basal Metabolism with 1.8 calories sub- tracted from each value are given below. (See Means, J. H. — Archives of Internal Medicine, May 1921.) AVERAGE CALORIES PER HOUR PER SQUARE METER OF BODY SURFACE, AND THE VOLUME OF OXYGEN PER MINUTE EQUIVALENT OF THE CALORIES Log. Oxygen Log. Cats. Log. Oxygen Log. Cals. «/ C. C. of Fe- of C. C. oi Age Males Cals. Per Minute C. C. males Cals. Per Minute C. C. 14-16 44.2 1 .6454 153 2.1847 41.2 1 .6149 142 2 .1523 16-18 41.2 .6149 142 .1523 38.2 .5821 132 .1206 18-20 39.2 .5933 135 .1303 36.2 .5587 125 .0969 20-30 37.7 .5763 130 .1139 35.2 .5465 122 .0864 30-40 37.7 .5763 130 .1139 34.7 .5403 120 .0792 40-50 36.7 .5647 127 .1038 34.2 .5340 118 .0719 50-60 35.7 .5527 123 .0899 33.2 .5211 115 .0607 60-70 34.7 .5403 120 .0792 32.2 .5079 HI .0453 70-80 33.7 .5276 116 .0645 238 31.2 .4942 108 .0334 PAGE 239 NORMAL STANDARDS OF BASAL METABOLISM FOR BOYS AND GIRLS OF WEIGHTS 20 TO 38 KILOS* (Ages 6 to 12 years approximately) Weight is determining factor for basal metabolism of boys and girls Oxygen Consumption in Cubic Centimeters per minute Body Weight Heat Production (without clothing) in Cal( ories per 24 hours Kilos Pounds Boys Girls 20,0 44 860 805 20.5 45 873 818 21.0 46 885 830 21.5 47 898 842 22.0 48 910 855 22.5 50 925 867 23.0 51 940 880 23.5 52 953 890 24.0 53 965 900 24.5 54 978 915 25.0 55 990 930 25.5 56 1005 940 26.0 57 1020 950 26.5 58 1033 962 27.0 59 1045 975 27.5 61 1058 987 28.0 62 1070 1000 28.5 63 1080 1010 29.0 64 1090 1020 29.5 65 1103 1032 30.0 66 1115 1045 30.5 67 1127 1058 31.0 68 1140 1070 31.5 69 1150 1080 32.0 70 1160 1090 32.5 72 1170 33.0 73 1180 33.5 74 1190 34.0 75 1200 34.5 76 1210 35.0 77 1220 35.5 78 1230 36.0 79 1240 36.5 80 1248 37.0 81 1255 37.5 83 1265 38.0 84 1275 Boys Girls 124 116 126 118 127 120 129 121 131 123 133 125 135 127 137 128 139 130 141 132 143 134 145 135 147 137 149 139 150 140 152 142 154 144 155 145 157 147 159 149 161 150 162 152 164 154 166 ..155 167 157 168 170 171 173 174 176 177 179 180 181 182 184 ♦ Predicted standards. Prepared by editor from Table 36 in Benedict and Talbot's "Metabolism from Birth to Puberty." Carnegie Institute of Washington, Washington, D. C, 1921. PAGE 240 Examples illustrating the method of using foregoing tables: Male, 32 years old; height, 160 cm.; weight, 67 kg. From the table on page 238 it is obvious that a man 32 years old would have a normal basal metabolism of 37.7 calories per hour for each square meter of his body surface. The method of computing the body surface of this particular patient is explained in the pages that fol- low. Itwill be seen that his body-surface area is 1 .70 square meters ; therefore his total basal metabohsm is 37.7 X 1.70 or 64.1 calories per hour. By referring to the table on page 272, the equivalent of 64.1 calories per hour is 221 c. c. of oxygen per minute. A girl weighing 50 lbs.: from the table it is readily seen that the normal heat production is 867 calories per 24 hours and the normal oxygen consumption is 125 c. c. per minute. For the Carbon Dioxid Method the following Standards for Normal Carbon Dioxid Elimination are proposed by Dr. J. T. King, Jr. CARBON DIOXID ELIMINATION PER HOUR PER SQUARE METER OF BODY SURFACE Age Males Females Years Grams Grams 15-20 14.03 12.75 20-30 12.98 11.95 30-40 12.86 11.85 40-50 12.52 11.74 50-60 12.21 11.37 60-70 11.86 11.05 70-80 11.53 10 .71 Normal consumption of oxygen may be determined by simply selecting the proper value from the table which follows and making minor corrections, or by accurate computations as explained later. The table and explanations of the simplified method are given on the following three pages. The values given in the table are based on Du Bois' Normal Standards with a slight modification: Instead of 37.7 calories and 36.7 for the ages of 20 to 50 as given in the preceding table, a mean value 'of 37.4 is used. For ages other than 20 to 50, the corrections are based on the Du Bois values and exprest in per cent, as shown on the next page. Table Shows NORMAL CONSUMPTION OF OXYGFN At Temperature and 760 mm. Barometer Pressure, in Cubic Centimeters per Minute under Basal Conditions. Sex and Age Corrections for Volumes in Tables. Males : Ages 20 to 50, no correction. 16 to 18, add 1 per cent, to volumes in table 18 to 20, add 5 per cent, to volumes in table 50 to 60, subtract 4 per cent, from volumes in table 60 to 70, subtract 7 per cent, from volumes in table Females: Compute for a Male of same age and subtract 7 per cent. Examples (To find Normal Consumption of Oxygen for) 1. Male, 32 years old, weight 67 kilograms, height 160 centimeters. From table volume is 220 cubic centimeters per minute. 2. Female, 28 years old, weight 147 pounds, height 65 inches. From table volume 221 cc. per minute. Subtract 7 per cent, for Sex Correction, 208 cc. per minute. 3. Female, 16 years old, weight 94 pounds, height 60 inches. From table, 185 cc. per minute. Add 10 per cent, for Age Correction, 193 cc. Subtract 7 per cent, for Sex Correction, 179 cc. normal consumption of oxygen per minute. Note: — The values given for the Normal Consumption of Oxygen have been prepared by Prof. Frank B. Sanborn. (1) From table of calories given by Drs. Aub and DuBois in "The Basal Metabolism of Old Men" (Archives of Internal Medicine, 1919.) with 1.8 calories subtracted. (See Means, J. H., Arch. Int. Med. May, 1921.) (2) Using an average value of 4.83 calories per liter of oxygen. (3) An average normal respiratory quotient of 0.82. (4) DuBois formula of Body Surface, which is: 0.725 0.425 Area (sq. cm.) equals 71.84 x (height in cm.) x (weight in kg.) PAGE 242 HEIGHT IN CENTIMETERS 140 145 150 155 160 165 170 175 180 185 190 30 142 145 149 152 156 159 163 166 170 173 177 66 1 144 147 151 154 158 161 165 168 172 175 179 68 2 145 149 153 156 160 163 167 170 174 177 181 70 3 147 151 155 158 162 165 169 173 177 180 184 73 4 149 153 157 160 164 167 171 175 179 182 186 75 5 151 155 159 162 166 170 174 177 181 184 188 77 6 153 157 161 164 168 172 176 179 183 187 191 79 7 155 159 163 166 170 174 178 182 185 189 1?3 81 8 156 161 164 168 172 176 180 184 188 191 K5 84 9 158 162 166 170 174 178 182 186 190 194 168 86 40 159 164 168 172 176 180 184 188 192 196 200 88 1 161 165 169 174 179 182 186 190 194 198 202 90 2 162 167 171 176 181 184 188 192 1£6 200 204 92 3 164 169 173 178 182 185 189 194 198 2C2 206 95 4 165 170 175 180 184 187 191 196 200 204 2C8 97 5 167 172 177 181 186 189 193 198 201 205 210 99 6 169 174 179 18.3 188 191 195 200 203 207 212 101 7 171 176 180 184 189 192 197 202 205 209 214 103 8 172 177 182 186 191 194 199 204 207 211 216 1C6 9 174 179 183 188 192 196 201 206 209 213 218 108 50 176 181 185 189 193 197 202 207 211 215 220 110 1 178 183 186 191 195 199 204 209 212 217 221 112 2 179 184 188 192 196 200 205 211 214 219 223 114 i' 181 186 189 194 198 202 207 212 216 220 225 117 182 187 191 195 199 203 2C8 214 217 222 227 119 9 5 184 188 193 197 201 2C5 210 216 219 224 228 121 ^ i? 185 189 194 199 203 207 212 218 221 226 230 123 a 186 191 196 200 205 209 213 219 222 228 232 128 g § 8 188 192 197 202 206 210 215 221 224 229 233 a 9 189 194 199 203 208 212 216 222 226 231 235 130 H geo 190 195 200 204 209 213 217 223 228 233 237 132 § H ^ 191 196 201 206 211 215 219 225 230 235 239 134^ g 3 192 198 202 207 212 216 220 226 231 236 240 136 g 193 199 203 209 214 218 222 228 233 238 242 139 n s ■^ 195 200 205 210 215 219 223 229 234 239 243 141 g S 5 196 201 206 212 217 221 225 231 236 241 245 143 O 6 .197 202 207 213 218 222 227 232 237 242 247 145"" 7 199 204 209 215 220 224 228 234 239 244 249 147 8 200 205 210 216 221 225 230 235 240 245 250 150 9 201 207 212 218 222 227 231 237 242 247 252 152 70 202 208 213 218 223 228 233 238 243 248 253 154 1 203 209 214 219 224 229 235 240 245 250 255 156 2 204 210 216 220 225 231 236 241 246 251 256 158 a 206 212 217 222 227 232 238 243 248 253 258 161 4 207 213 219 223 228 234 239 244 249 254 259 163 5 208 214 220 224 229 235 241 246 251 256 261 165 6 209 215 221 225 230 236 242 247 252 257 263 167 7 210 216 222 227 232 238 244 249 254 259 264 169 8 212 218 224 228 233 239 245 250 255 260 266 172 9 213 219 225 230 235 240 246 251 257 262 267 174 80 214 220 226 231 236 241 247 253 258 263 268 176 1 215 222 227 232 237 242 248 254 259 264 270 178 2 217 223 228 234 239 244 250 256 261 266 271 180 3 218 225 230 235 240 245 251 257 262 267 273 183 4 220 226 231 237 242 247 253 259 264 269 274 185 5 221 227 233 238 243 248 254 260 265 270 276 187 6 222 228 234 239 244 249 255 261 266 271 277 189 7 223 229 235 240 246 251 256 262 268 273 279 191 S 224 230 236 242 247 252 258 264 269 274 280 194 9 225 231 237 243 248 254 259 265 271 276 282 196 55 57 59 61 63 65 67 69 71 73 75 HEIGHT IN INCHES HEIGHT IN CENTIMETERS PAGE 243 150 155 160 165 170 175 180 185 190 195 200 90 238 244 249 255 260 266 271 276 282 287 292 198 1 239 245 250 256 261 267 272 277 283 288 253 200 2 240 246 251 257 262 268 273 278 284 289 294 202 3 241 247 252 258 264 269 275 280 286 291 2f6 205 4 242 248 253 259 265 270 276 281 287 292 297 207 5 243 249 254 260 266 271 277 282 288 293 298 209 6 244 250 255 261 267 272 278 283 289 294 299 211 7 245 251 256 263 269 274 279 284 290 295 300 213 8 246 252 258 264 270 275 281 286 292 297 3('2 216 9 247 253 259 266 271 277 282 287 293 298 303 218 100 248 254 260 267 272 278 284 289 294 299 304 220 1 249 255 261 268 273 279 285 290 295 300 305 222 2 250 256 262 269 274 280 286 292 297 302 307 224 3 251 257 263 270 275 281 288 293 298 303 308 227 4 252 258 264 271 276 282 289 294 299 304 309 229 5 253 260 266 272 278 284 290 296 301 306 311 231 6 254 261 267 273 279 285 291 297 302 307 312 233 7 255 262 268 274 280 286 293 298 303 308 313 235 8 256 263 269 275 281 287 294 300 305 310 315 238 9 257 264 270 276 282 288 295 301 306 311 316 240 110 258 265 271 277 283 289 296 302 307 312 317 242 308 313 318 244 309 315 320 246 310 316 321 249 312 317 322 251 313 319 324 253 ^ 314 320 325 255 S 315 321 326 257 2 317 323 328 260 3 318 324 329 262 ^ 294 301 307 313 319 325 330 264 ^ 295 302 308 314 320 326 331 266 V 296 303 309 315 321 327 332 268 2 297 304 310 316 322 328 333 271 § 298 305 311 317 323 329 335 273 O 299 306 312 319 325 331 336 275 ^ 300 307 313 320 326 332 337 277 301 308 314 321 327 333 339 279 302 309 315 322 328 334 340 282 303 310 316 323 329 335 341 284 290 297 304 311 317 324 330 336 342 286 291 298 305 312 318 325 331 337 343 288 286 292 299 306 313 319 326 332 338 344 290 287 293 300 307 314 320 327 333 339 345 293 288 294 301 308 315 321 328 334 340 346 295 281 288 294 302 309 316 323 329 335 341 347 297 282 289 295 303 310 317 324 330 336 342 348 299 7 283 290 296 304 311 318 325 331 337 343 349 301 8 284 291 297 305 312 • 319 326 332 338 344 350 304 9 285 292 298 306 313 320 327 333 339 345 351 306 140 286 293 299 307 314 321 328 334 340 346 352 308 1 287 294 300 308 315 322 329 335 341 347 353 310 2 288 294 301 309 315 323 329 336 342 348 354 312 3 289 295 302 310 316 324 330 337 343 349 355 315 4 289 296 303 311 317 325 331 338 344 350 356 317 5 290 297 304 312 318 326 332 339 345 351 357 319 6 291 298 305 313 319 327 333 339 346 352 358 321 7 291 299 306 314 320 328 334 340 346 353 359 323 8 292 300 307 315 321 329 335 341 347 354 360 326 9 293 301 307 315 322 329 336 342 348 355 361 328 59 61 63 65 67 69 71 73 75 77 79 HEIGHT IN INCHES 244 BASAL METABOLISM Body Surface Area affords another method of estimating the Normal Basal Metabolism of an individual. The tables given on the preceding pages include Body Surface Area as a factor which is fully taken into account when the tables are prepared, but in the pages that follow explanation is given of the inter- mediate steps by which Body Surface Area is determined and this combined with normal calories per unit of area gives the Normal Basal Metabolism. Body Surface Area may be found by the following table and chart that have been prepared from the Du Bois formula for Body Surface, which is ^=7L84XPF/. 0-425 xm. 0-725 A is the area in square centimeters; Ht., the height in centi- meters, and Wt., the weight in kilograms. Altho the formula gives the area in square ceijtimeters, in the table and chart it is exprest in square meters. (10,000 sq. cm. = 1 sq. m.)- Examples of Body Surface Area as obtained from the Tables: (Similar values may also be obtained from the chart on page 245) 1. A person 172 centimeters in height, weighing 62 kilo- grams. From the table the Body Surface Area is 1.74 square meters. 2. A person 70 inches in height, weighing 148 pounds. From the table the Body Surface Area is 1.84 square meters. 3. A person 74 inches in height, weighing 285 pounds. From the table the Body Surface Area is 2.53 square meters. The tables and also the Body Surface Chart, which are given on the pages that follow include values for all persons whose height or weight is not extreme. BODY SURFACE CHART o y m r- ^ y ,, y /> - 1 y X y y >v _ ^ \y y k y y y' y y o r^ ^ ^ y y ^ ^ \^ y n y y iC • y y y ^ ^ y CO k^ y c\l =0 A y y y J y y y U y ID :. ^ ^ PAGE 245 in ^ o Tti ^ ^ tXJ p: i> a c in rs o en t- m C o u ^ ■»-» ert o 3 o tM "S f/l 1-1 0) 03 9 'S 2^ f=i CT a " 10 .S S 0) 5 o< oq: o o _i ClJ 60 1- UJ .. en en OJ '% ^ "I ti to 3 n H 25 3.5 3.5 3.4 3.4 3.4 3.3 3.2 3.2 3,1 77 y ^ 26 3,7 3.7 3.6 3.6 3.5 3,5 3.4 3.4 3.3 79 g g 27 4.0 3.9 3.9 3.8 3.8 3.7 3.7 3.6 3.6 81 a g 28 42 4.2 4.1 4,1 4,0 3,9 3.9 3.8 3.8 82 g. g 29 4.5 4.4 4.4 4.3 4.2- 4.2 4.1 4.1 4.0 84 |^ 30 4.7 4.6 4.6 4.5 4.5 4.4 4.4 4.3 4.3 86 31 5.0 5.0 4.9 4.8 4.8 4.7 4.6 4.6 4,5 88 27.6 27.9 28.3 28.7 29.1 29.5 29.9 30.3 30.7 Barometer in Inches The Respiratory Quotient, that is, the ratio of the volume of carbon dioxid that is exhaled to the volume of oxygen that is consumed, should be determined for each test when for special reasons it is desired to obtain precise values of the basal metabolic rate. Various values of the respiratory quotient and the cor- responding calorific values for one liter of oxygen are given in the table below. The values that are commonly used as average values are printed in heavy face type, — respiratory quotient of 0.82 and corrresponding calorific value 4 83. PAGE 259 THE CALORIFIC VALUES OF ONE LITER OF OXYGEN FOR NON-PROTEIN RESPIRATORY QUOTIENTS ARE GIVEN IN THE TABLE BELOW (From Zuntz and Schumburg Physiologie des Marches Berlin 1901) R.Q. Cals. R.Q. Cals. R.Q. Cals. 0.71 4.69 0.81 4.81 0.91 4.94 .72 4.70 .82 4.83 .92 4.95 .73 4.71 .83 4.84 .93 4.96 .74 4.73 .84 4.85 .94 4.97 .75 4.74 .85 4.86 .95 4.99 .76 4.75 .86 4.88 .96 5.00 .77 4.76 .87 4.89 .97 5.01 .78 4.78 .88 4.90 .98 5.02 .79 4.79 .89 4.91 .99 5.03 .80 4.80 .90 4.92 1.00 5.05 In the Gas Analysis Method the actual basal metabolism is determined by the following procedure: Obtain the volume of expired air by test of patient as described in chapters 4 an 5. Correct for temperature, barometer and saturation of gas as explained in preceding pages of this chapter. Find the percentage of carbon dioxid by analyzing samples of the expired air as explained in chapters 4 and 5 ; then subtract the percentage of carbon dioxid in pure outside air (which is taken as 0.03 or 0.04 per cent.) ; multiply this percentage by the corrected volume per minute of expired air. Find the percentage of oxygen in the expired air by the methods referred to in chapters 4 and 5, and explained more fully in Haldane's "Methods of Air Analysis". To compute the voliune of oxygen even after knowing the percentage in the sample requires the consideration of several related facts. The per- centage of oxygen in pure outside air is generally taken as 20.93; and combining with this 0.04 per cent, for carbon dioxid gives 79.03 per cent, for nitrogen. Now the volume of dry air has diminished in the process of respiration because the volume of oxygen that has been taken up is greater than the volume of carbon dioxid that has been given off. Therefore, since nitrogen is neither taken up nor given off during respiration, it is evident that for every 100 volumes of air that is expired there are not 20.93 volumes of oxygen as in pure outside air, but a volume of 20.93 X Per cent, of nitrogen in sample 79.03 Subtract from the above volume the volume that would be indicated by the analysis of the samples of expired air to find the true volume of oxygen consumption. PAGE 260 OBSERVATION AND COMPUTATION SHEET FOR GAS ANALYSIS METHOD Form of data sheet that is used at the New York Post Graduate Medical School and Hospital. A similar form is also used at the Mayo Chnic (see form in Boston Med. and Surg. Jour., Sept., 1921.) METABOLISM LABORATORY CaseNo... mm. Log. Fact. Gasom "773^3 Temp. Gasom. ,2i3> "''■ ^°^' f^asom. diff /y_J- ^ 3 / Log. Fact. S. T. P. D "iSX^ . rEnd S"i^. cm. cm. Log. Time 01.1 I V Gasom, J Start .. C?. '.3 cm. cm. Log. Vent, per min (sub.) Q^hBS= l.l'?'^' ^ Diff. 6.f .• £> cm. cm. Log. % O2 absorbed 635'-Y8 Log. O2 absorbed (add) l^q J.03 =3l0,5'cc. Durationoftest/Om.3C^. = ^<3.J"min. Log. Cal. value02+Iog. 60 . ... JJS'St . j Log. Total Cal. per hr (add) 9V 7' 3 =»S(5'|Eal. Log. Surface Area / S 2. Z? CO2 Expired 3-3/% Log. Cal. per sq. m. hi. ..(sub) y ^ t^ j^/f=4,X3SCs.l. CO2 Inspired (h^^^o CO2 Produced (sub.) 3[aV% Cal. per sq. m. hr. (above nor.) c7 2.'3o ^ O2 Inspired 2./i|5'% Cal. per sq. m. hr. normal 3y O2 Expired _. . . . .ffo-83% Cal. per sq. m. hr. (below nor.) . O2 Absorbed '(sub.)^.3'J,% Difference (sub.) I.S. 3-i Log. difference '-Z O 3^ Log. % CO2 produced S.\ ^5S Log. normal SbJ^ ^ - Log. % O2 absorbed j22M:^Log. B. M. % (sub.) gSS"? Log.Resp. Quot (sub.) Q'J QOf ==0.1 b BASAL METABOLISM .^i?S..% - Gas Analysis n Gas Analysis ByQ.O.Q. Haldane No. ^ . . By Ot.6.V|,. Haldane No.S .. ?.7F(?-.C7(7Z = f.778 9.S-55't O = ^.56-5 . .3 '2. V. . ;^ / &_ l.^lO-\-.oo\ = 7. S\ I '^.i^1.S■^.oo■b ^'^jrST%_ Log.C02 diff. 5 1055" Log.02 diff. 14 ■£■ 6^Log.C02 diff. ¥\H^ Log.02 diff. "XOl I O Log.sample ^IfOlS Log. sample qi^O l5'L og.sample 48<3 2-3Log.sample ?ZO_l3_ Log.C02% £-10 30 Log.02 % Zl53^Log.C02 % J-iq4feLog.02% T-l-toTT C02% 32,, 02% i&,a C02% 3.3002% Ifo. Sfo Notes: Avg.C02 331% Readings by; ^ .A S;- T-it., 153 cm- Ave. O2 ib.«3,% checked by: '^CV,'^. Wr.. ;o* ib5, co2+02am% ^.tfchSSl^cv^e. ^lA/A^C^ Ih-^^ , 1.4-2. 5^-M. Second check by: 'Yi'& ?^ PAGE 261 OBSERVATION AND COMPUTATION SHEETS For Closed Circuit Method A convenient form (prepared by Editor) for recording observa- tions and computations by the Closed Circuit Method is shown on the following pages. BASAL METABOLISM Name of Patient Test No Date . Diagnosis before test Local Physician Technician for test . Make of Apparatus : Result of test : Unusually good, accepted, rejected. (Underline) BASAL METABOLIC RATE As determined by test . . . PAGE 262 To Find the Patient's Actual Consumption of Oxygen Barometer inches equals millimeters (Multiply by 25.4) Thermometer (Temperature in apparatus) Beginning of Test. C Time Start .h, .h. .m. End Duration . .mins Volume of Oxygen Start cc. End cc Consumption of Oxygen cc Per minute cc. Average Thermometer End of Test . . . . C Average beginning and end of Test C Correction for Temperature (Page 264) „ , . . Correction for Barometer (Page 264) Patient's actual consumption of oxygen per minute, corrected to temperature of degrees C. and barometer pressure of 760 mm. . cc. . cc. . cc. PAGE 263 To Find the Patient's Normal Consumption of Oxygen Age years. Male, Female (Underline) Weight (without clothing) pounds or kilograms Height (without shoes) inches or centimeters Normal Consumption of Oxygen For weight and height noted, ages 20 to 50 years (P. 242) . . . cc. Correction for other ages (Page 241) cc. Correction for females (Page 241) . . cc. Patient's Normal Consumption cc. Patient's Actual Consumption as found by tests cc. Consumption above normal (plus), below (minus) . . . .cc. (Underline) Per cent, above normal (plus), below (minus) (Divide the plus or minus cc. by normal) BASAL METABOLIC RATE (The percentage of oxygen consumed above or below normal is the plus or minus basal metabolic rate.) PAGE 264 Observations Auxiliary to Test, that may be Recorded as a Guide in Interpreting Results Pulse Rate (taken during, or at beginning and end of test) Respiration (taken during test) Blood Pressure (taken after test) Systolic Diastolic Buccal Temperature (taken after test) Temperature Corrections for Readings of Oxygen Scale. Degrees Ordinary Special Centigrade Scale Scale i6, 17, 18 Subtract 6% add 1% 19, 20, 21 "7% no correction 22, 23, 24, 25 " 8% subtract 1% Barometer Corrections for Readings of Oxygen Scale The correction for barometer pressure is found by the following formula: bar pressure in mm. Consumption of oxygen multiplied by or approximately : For each 10 mm. below 760 subtract 1 per cent. For each 10 ram. above 760 add 1 per cent. PAGE 265 COMPUTATION SHEET BENEDICT UNIVERSAL APPARATUS From page 103 J. D., Age 49 Ht., 185 cm. Wt, 67.2 kg. August 21, 1921 "A" Ward Period I Time 9.2 Period II Time 9.87 Period III Time 8.02 R 7160 T 21 R 7050 T 21 R 7050 T 22 R 3180 T 21 R 2700 T 22 R 3350 T 22 3980 21 4350 21.5 3700 22 No. Urine Collected 9.10 to 11.08 Total time of periods 27.09 Period of Urine Collection 118. Total N of Collected Urine Urinary N for time of period Total Readings Vol. reduced to 0°C. 273 -^- (t+ 273) Vol. reduced to 760 mm. (Bar. 4- 760) Corrected Vol. O2 C. C. per liter Liters O2 consumed Vol. 1 gm. O2 Wt. O2 consumed 1.4 .32 Urinary N O2 per gm. Ur. N O2 for Protein Wt. O2 Consumed Wt. O2 for Protein Wt. N. P. O2 Vol. 1 gm. O2 Vol. N. P. O2 11110 1000 11.110 0.699 15.90 .32 8.45 2.716 15.90 2.716 13.184 0.699 9.212 Log. 1.4328 2.0719 1.3609 0.1461 1.5070 4.0802 1.9672 1.9983 4.0457 3. 1.0457 1.8445 1.2012 1.5070 0.9269 0.4339 1.1199 1.8445 0.9644 Wt. Soda Lime and Acid (2) 4415.42 Wt. Soda Lime and Acid (1) 4398.15 Wt. CO2 Expired 17.27 Urinary N CO2 per gm. Ur. N. CO2 for Protein Wt. CO2 Expired Wt. CO2 for Protein Wt. N. P. CO2 Vol. 1 gm. CO2 Vol. N. P. CO2 Vol. N. P. O2 N. P. R. Q. No. .32 9.35 3.004 17.27 3.004 14.266 0.5087 7.259 9.212 .7879 Log. 1.5070 0.9708 0.4778 1.1544 1.7065 0.8609 0.9644 1.8965 Liters O2 Consumed 11.11 1.0467 Duration of Periods 27.09 L*32S O2 Consumed per min. .4102 1.6129 Min. per day 1440 3.1584 Cal. per Liter O2 4.789 .6802 Cal. per 24 hrs. 2828 3.4515 Theoretical 1586 3.2004 Basal Metabolism 1.778 .2511 Change to % 100 177.8% PAGE 266 LOGARITHMS OF NUMBERS FROM 1.000 TO 1.499 01 23456789 1.00 0,0000 0004 0009 0013 0017 0022 0026 0030 0035 0039 1.01 0043 0048 0052 0056 0060 0065 0069 0073 0077 0082 1.02 0086 0090 0095 0099 0103 0107 0111 0116 0120 0124 1.03 0128 0133 0137 0141 0145 '0149 0154 0158 0162 0166 1.04 0170 0175 0179 0183 0187 0191 0195 0199 0204 0208 1.05 0212 0216 0220 0224 0228 0233 0237 0241 0245 0249 1.06 0253 0257 0261 0265 0269 0273 0278 0282 0286 0290 1.07 0294 0298 0302 0306 0310 0314 0318 0322 0326 0330 1.08 0334 0338 0342 0346 0350 0354 0358 0362 0366 0370 1.09 0374 0378 0382 0386 0390 0394 0398 0402 0406 0410 1.10 0.0414 0418 0422 0426 0430 0434 0438 0441 0445 0449 1.11 0453 0457 0461 0465 0469 0473 0477 0481 0484 0488 1.12 0492 0496 0500 0504 0508 0512 0515 0519 0523 0527 1.13 0531 0535 0538 0542 0546 0550 0554 0558 0561 0565 1.14 0569 0573 0577 0580 0584 0588 0592 0596 0599 0603 1.15 0607 0611 0615 0618 0622 0626 0630 0633 0637 0641 1.16 0645 0648 0652 0656 C660 0663 0667 0671 0674 0678 1.17 0682 0686 0689 0693 0697 0700 0704 0708 0711 0715 1.18 0719 0722 0726 0730 0734 0737 0741 0745 0748 0752 1.19 0755 0759 0763 0766 0770 0774 0777 0781 0785 0788 1.20 0.0792 0795 0799 0803 0806 0810 0813 0817 0821 0824 1.21 0828 0831 0835 0839 0842 0846 0849 0853 0856 0860 1.22 0864 0867 0871 0874 0878 0881 0885 0888 0892 0896 1.23 0899 0903 0906 0910 0913 0917 0920 0924 0927 0S31 1.24 0934 0938 0941 0945 0948 0952 0S55 0959 0962 0966 1.25 0969 0973 0976 0980 0983 C986 0990 08S3 0997 1000 1.26 1004 1007 1011 1014 1017 1021 1024 1028 1031 1035 1.27 1038 1041 1045 1048 1052 1055 1059 1062 1065 1069 1.28 1072 1075 1079 1082 1086 1089 1092 1096 1099 1103 1.29 1106 1109 1113 1116 1119 1123 1126 1129 1133 1136 1.30 0.1139 1143 1146 1149 1153 1156 1159 1163 1166 1169 1.31 1173 1176 1179 1183 1186 1189 1193 1196 1199 1202 1.32 1206 1209 1212 1216 1219 1222 1225 1229 1232 1235 1.33 1239 1242 1245 1248 1252 1255 1258 1261 1265 1268 1.34 1271 1274 1278 1281 1284 1287 1290 1294 1297 1300 1 35 1303 1307 1310 1313 1316 1319 1323 1326 1329 1332 1.36 1335 1339 1342 1345 1348 1351 1355 1358 1361 1364 1.37 1367 1370 1374 1377 1380 1383 1386 1389 1392 1396 1.38 1399 1402 1405 1408 1411 1414 1418 1421 1424 1427 1.39 1430 1433 1436 1440 1443 1446 1449 1452 1455 1458 1.40 0,1461 1464 1467 1471 1474 1477 1480 1483 1486 1489 1.41 1492 1495 1498 1501 1504 1508 1511 1514 1517 1520 1.42 1523 1526 1529 1532 1535 1538 1541 1544 1547 1550 1.43 1553 1556 1559 1562 1565 1569 1572 1575 1578 1581 1.44 1584 1587 1590 1593 1596 1599 1602 1605 1608 1611 1.45 1614 1617 1620 1623 1626 1629 1632 1635 1638 1641 1.46 1644 1647 1649 1652 1655 1658 1661 1664 1667 1670 1.47 1673 1676 1679 1682 1685 16§8 1691 1694 1697 1700 1.48 1703 1706 1708 1711 1714 1717 1720 1723 1726 1729 1.49 1732 1735 1738 1741 1744 1746 1749 1752 1755 1758 PAGE 267 LOGARITHMS OF WITMBERS FROM 1,500 TO 1,999 1234567 89 1.50 0.1761 1764 1767 1770 1772 1775 1778 1781 1784 1787 1.51 1790 1773 1796 1798 1801 1804 1807 1810 1813 1816 1.52 1818 1821 1824 1827 1830 1833 1836 1838 1841 1844 1.53 1847 1850 1853 1855 1858 1861 1864 1867 1870 1872 1.54 1875 1878 1881 1884 1886 1889 1892 1895 1898 1901 1.55 1903 1906 1909 1912 1915 1917 1920 1923 1926 1928 i.56 1931 1934 1937 1940 1942 1945 1948 1951 1953 1956 1.67 1959 1962 1965 1967 1970 1973 1976 1978 1981 1984 1.58 1987 1989 1992 1995 1998 2000 2003 2006 2009 2011 1.59 2014 2017 2019 2022 2025 2028 2030 2033 2036 2038 1.60 0.2041 2044 2047 2049 2052 2055 2057 2060 2063 2C66 1.61 2068 2071 2074 2076 2079 2082 2084 2087 2090 2C92 1.62 2095 2098 2101 2103 2106 2109 2111 2114 2117 2119 1.63 2122 2125 2127 2130 2133 2135 2138 2140 2143 2146 1.64 2148 2151 2154 2156 2159 2162 2164 2167 2170 2172 1.65 2175 2177 2180 2183 2185 2188 2191 2193 21E6 2198 1.66 2201 2204 2206 2209 2212 2214 2217 2219 2222 2225 1.67 2227 2230 2232 2235 2238 2240 2243 2245 2248 2251 1.68 2253 2256 2258 2261 2263 2266 2269 2271 2274 2276 1.69 2279 2281 2284 2287 2289 2292 2294 2297 2299 2302 1.70 0.2304 2307 2310 2312 2315 2317 2320 2322 2325 2327 1.71 2330 2333 2335 2338 2340 2343 2345 2348 2350 2353 1.72 2355 2358 2360 2363 2365 2368 2370 2373 2375 2378 1.73 2380 2383 2385 2388 2390 2393 2395 2398 2400 2403 1.74 2405 2408 2410 2413 2415 2418 2420 2423 2425 2428 1 75 2430 2433 2435 2438 2440 2443 2445 2448 2450 2453 1 76 2455 2458 2460 2463 2465 2467 2470 2472 2475 2477 1 77 2480 2482 2485 2487 2490 2492 2494 2497 2499 2502 1 78 2504 2507 2509 2512 2514 2516 2519 2521 2524 2526 1.79 2529 2531 2533 2536 2538 2541 2543 2545 2548 2550 1 80 0.2553 2555 2558 2560 2562 2565 2567 2570 2572 2574 1 81 2577 2579 2582 2584 2586 2589 2591 2594 2596 2598 1 82 2601 2603 2605 2608 2610 2613 2615 2617 2620 2622 1 83 2625 2627 2629 2632 2634 2636 2639 2641 2643 2646 1.84 2648 2651 2653 2655 2658 2660 2662 2665 2667 2669 1 85 2672 2674 2676 2679 2681 2683 2686 2688 2690 2693 1 86 2695 2697 2700 2702 2704 2707 2709 2711 2714 2716 1 87 2718 2721 2723 2725 2728 2730 2732 2735 2737 2739 188 2742 2744 2746 2749 2751 2753 2755 2758 2760 2762 1.89 2765 2767 2769 2772 2774 2776 2778 2781 2783 2785 1 90 2788 2790 2792 2794 2797 2799 2801 2804 2806 2808 191 2810 2813 2815 2817 2819 2822 2824 2826 2828 2831 l'92 2833 2835 2838 2840 2842 2844 2847 2849 2851 2853 193 2856 2858 2860 2862 2865 2867 2869 2871 2874 2876 1^94 2878 2880 2882 2885 2887 2889 2891 2894 2896 2898 1 96 2900 2903 2905 2907 2909 2911 2914 2916 2918 2920 l'96 2923 2925 2927 2929 2931 293i 2936 2938 2940 2942 197 2945 2947 2949 2961 2953 2956 2958 2960 2962 2664 198 2967 2969 2971 2973 2975 2978 2980 2982 2984 2986 199 2989 2991 2993 2995 2997 2999 3002 3004 3006 3008 PAGE 268 LOGARITHMS OF NUMBERS FROM 2.00 TO 5.99 AND BY INTERPOLATION FROM 2.000 TO 5.999 Interpolation 1 2 3 4 5 6 7 8 912345 2.0 0.3010 3032 3054 3075 3096 3118 3139 3160 3181 3201 2 4 6 8 11 2.1 3222 3243 3263 3284 3304 3324 3345 3365 3385 3404 2 4 6 8 10 2.2 3424 3444 3^64 3483 3502 3522 3541 3560 3579 3598 2 4 6 8 10 2.3 3617 3636 3655 3674 3692 3711 3729 3747 3766 3784 2 4 5 7 9 2.4 3802 3820 3838 3856 3874 3892 3309 3927 3945 3962 2 4 5 7 9 2.5 3979 3997 4014 4031 4048 4065 4082 4099 4116 4133 2 3 5 7 9 2.6 4150 4166 4183 4200 4216 4232 4249 4265 4281 4298 2 3 5 7 8 2.7 4314 4330 4346 4362 4378 4393 4409 4425 4440 4456 2 3 5 6 8 2.8 4472 4487 4502 4518 4533 4548 4564 4579 4594 4609 23 56 8 2.9 4624 4639 4654 4669 4683 4698 4713 4728 4742 4757 13 4 6 7 3.0 0.4771 4786 4800 4814 4829 4843 4857 4871 4886 4900 13 4 6 7 3.1 4914 4928 4942 4955 4969 4983 4997 5011 5024 5038 1346 7 3.2 5051 5065 5079 5092 5105 5119 5132 5145 5159 5172 13 4 5 7 3.3 5185 5198 5211 5224 5237 5250 5263 5276 5289 5302 13 4 5 6 3.4 5315 5328 5340 5353 5366 5378 5391 5403 5416 5428 13 4 5 6 3.5 5441 5453 5465 5478 5490 5502 5514 5527 5539 5551 12 4 5 6 3.6 5563 5575 5587 5599 5811 5823 5835 5647 5658 5670 124 5 6 3.7 5682 5894 5705 5717 5729 5740 5752 5763 5775 5786 12 3 5 6 3.8 5798 5809 5821 5832 5843 5855 5866 5877 5888 5899 12 3 5 6 3.9 5911 5922 5933 5944 5955 5966 5977 5988 5999 6010 12 3 4 6 4.0 O.6021 6031 6042 6053 6061 6075 6085 6096 6107 6117 12 3 4 5 4. 1 6128 6138 6149 6160 6170 6180 6191 6201 6212 6222 12 3 4 5 4.2 6232 6243 6253 6263 6274 6284 6294 6304 6314 6325 12 3 4 5 4.3 6335 6345 6355 6365 6375 63S5 6395 6405 6415 6425 12 3 4 5 4.4 6435 6444 6454 6464 6474 6484 6493 6503 6513 6522 12 3 4 5 4.5 6532 6542 6551 6561 6571 6580 6590 6599 6609 6618 12 3 4 5 4.6 6628 6637 6646 6656 6665 6675 6684 6693 6702 6712 12 3 4 5 4.7 6721 6730 6739 6749 6758 6767 6776 6785 6794 6803 12 3 4 6 4.8 6812 6821 6830 6839 6848 6857 6866 6875 6884 6893 12 3 4 4 4.9 6902 6911 6920 6928 6937 6948 6955 6964 6972 6981 12 3 4 4 5.0 0.6990 6998 7007 7016 7024 7033 7042 7050 7059 7067 12 3 3 4 5.1 7078 7084 7093 7101 7110 7118 7126 7135 7143 7152 123 3 4 5.2 7160 7168 7177 7185 7193 7202 7210 7218 7226 7235 12 2 3 4 5.3 7243 7251 7259 7267 7275 7284 7292 7300 7308 7316 12 2 3 4 5.4 7324 7332 7340 7348 7356 7364 7372 7380 7388 7396 12 2 3 4 5.5 7404 7412 7419 7427 7435 7443 7451 7459 7466 7474 12 2 3 4 5.6 7482 7490 7497 7505 7513 7520 7528 7536 7543 7551 12 2 3 4 5.7 7559 7566 7574 7582 7589 7597 7604 7612 7619 7627 12 2 3 4 5.8 7634 7642 7649 7657 7664 7672 7679 7686 7694 7701 1123 4 5.9 7709 7716 7723 7731 7738 7745 7752 7760 7767 7774 112 3 4 PAGE 269 LOGARITHMS OF,t NUMBERS FROM 6.00 TO 9.99 AND BY INTERPOLATION FROM 6.000 TO 9.999 Interpolation 01 2 3 4 56 7 8 912345 6.0 0.7782 7789 7796 7803 7810 7818 7825 7832 7839 7846 112 3 4 6.1 7853 7860 7868 7875 7882 7889 7896 7903 7910 7917 112 3 4 6.2 7924 7931 7938 7945 7952 7959 7966 7973 7980 7987 112 3 3 6.3 7993 8000 8007 8014 8021 8028 8035 8041 8048 8055 112 3 3 6.4 8062 8069 8075 8082 8089 8096 8102 8109 8116 8122 112 3 3 6.5 8129 8136 8142 8149 8156 8162 8169 8176 8182 8189 112 3 3 6.6 8195 8202 8209 8215 8222 8228 8235 8241 8248 8254 112 3 3 6.7 8261 8267 8274 8280 8287 8293 8299 8306 8312 8319 112 3 3 6.8 8325 8331 8338 8344 8351 8357 8363 8370 8376 8382 112 3 3 6.9 .8388 8395 8401 8407 8414 8420 8426 8432 8439 8445 112 3 3 7.0 0.8451 8457 8463 8470 8476 8482 8488 8494 8500 8506 112 2 3 7.1 8513 8519 8525 8531 8537 8543 8549 8555 8561 8567 1122 3 7.2 8573 8579 8585 8591 8597 8603 8609 8615 8621 8627 112 2 3 7.3 8633 8639 8645 8651 8657 8663 8669 8675 8681 8686 112 2 3 7.4 8692 8698 8704 8710 8716 8722 8727 8733 8739 8745 112 2 3 7.5 8761 8756 8762 8768 8774 8779 8785 8791 8797 8802 112 2 3 7.6 8808 8814 8820 8825 8831 8837 8842 8848 8854 8859 112 2 3 7.7 8865 8871 8876 8882 8887 8893 8899 8904 8910 8915 112 2 3 7.8 8921 8927 8932 8938 8943 8949 8954 8960 8965 8971 112 2 3 7.9 8976 8982 8987 8993 8998 9004 9009 9015 9020 9025 112 2 3 8.0 0.9031 9036 9042 9047 9053 9058 9063 9069 9074 9079 112 2 3 8.1 9085 9090 9096 9101 9106 9112 9117 9122 9128 9133 1122 3 8.2 9138 9143 9149 9154 9159 9165 9170 9175 9180 9186 112 2 3 8.3 9191 9196 9201 9206 9212 9217 9222 9227 9232 9238 112 2 3 8.4 9243 924S 9253 9258 9263 9269 9274 9279 9284 9289 112 2 3 8.5 9294 9299 9304 9309 9315 9320 9325 9330 9335 9340 112 2 3 8.6 9345 9350 9355 9360 9365 9370 9375 9380 9385 9390 112 2 3 8.7 9395 9400 9405 9410 9415 9420 9425 9430 9435 9440 112 2 8.8 9445 9450 9455 9460 9465 9469 9474 9479 9484 9489 112 2 8.9 9494 9499 9504 9509 9513 9518 9523 9528 9533 9538 112 2 9.0 0.9542 9547 9552 9557 9562 9566 9571 9576 9581 9586 112 2 9.1 9590 9595 9600 9605 9609 9614 9619 9624 9628 9633 112 2 9.2 9638 9643 9647 9652 9657 9661 9666 9671 9675 9680 112 2 9.3 9685 9689 9694 9699 9703 9708 9713 9717 9722 9727 112 2 9.4 9731 9736 9741 9745 9750 9754 9759 9763 9768 9773 112 2 9.6 9777 9782 9786 9791 9795 9800 9805 9809 9814 9818 112 2 9.6 9823 9827 9832 9836 9841 9845 9850 9854 9859 9863 112 2 9.7 9868 9872 9877 9881 9886 9890 9894 9899 9903 9908 112 2 9.8 9912 9917 9921 9926 9930 9934 9939 9943 9948 9962 112 2 9.9 9956 9961 9965 9969 9974 9978 9983 9987 9991 9996 112 2 PAGE 270 INCHES TO CENTIMETERS, EQUIVALENTS Inches Centimeters SO 127 .Q 51 129.5 52 132.0 53 134.6 54 137.3 55 139.6 56 142.2 57 144.7 58 147.4 59 149.0 60 152.4 61 155.0 62 157.5 63 160.0 64 162.6 65 165.1 ches Centimeters 66 167.6 67 170.2 68 172.8 69 175.3 70 177.8 71 180.4 72 182.9 73 185.4 74 188.0 75 190.5 76 193.0 77 195.5 78 198.0 79 200.5 80 203.0 SECONDS TO DECIMAL PARTS OF A MINUTE, EQUIVALENTS ■>ecs. Mins 1 .02 2 .03 3 .05 4 .07 5 .08 6 .10 7 .12 8 .13 9 .15 10 .17 11 .18 12 .20 13 .22 14 .23 15 .25 16 .27 17 .28 18 .30 19 .32 20 .33 Sees. Mins. 21 .35 22 .37 23 .38 24 .40 25 .42 26 .43 27 .45 28 .47 29 .48 30 .50 31 .52 32 .53 33 .55 34 .57 35 .58 36 .60 37 .62 38 .63 39 .65 40 .67 Sees. Mins. 42 .UO .70 43 .72 44 .73 45 .75 46 .77 47 .78 48 .80 49 .82 50 .83 51 .85 52 .87 53 .88 54 .90 55 .92 56 .93 57 .95 58 .97 59 .98 60 1.00 PAGE 271 POUNDS TO KH.OGRAMS, : EQUIVALENTS Lbs. Kgs. Lbs. Kgs. Lbs. Kgs. Lbs. Kgs. 60 27.2 128 58.2 196 89.1 264 120.0 62 28.1 130 59.1 198 90.0 266 120.9 64 29.0 132 60.0 200 90.9 268 121.8 66 30.0 134 60.9 202 91.8 270 122.7 68 30.9 136 61.8 204 92.7 272 123.6 70 31.8 138 62.7 206 93.6 274 124.5 72 32.7 140 63.6 208 94.5 276 125.5 74 33.6 142 64.5 210 96.5 278 126.4 76 34.5 144 65.5 212 96.4 280 127.3 78 35.4 146 66.4 214 97.3 282 128.2 80 36.3 148 67.3 216 98.2 2S4 129.1 S2 37.2 150 68.2 218 99.1 286 130.0 84 38.1 152 69.1 220 100.0 288 130.9 86 39.0 154 70.0 222 100.9 290 131.8 88 40.0 156 70.9 224 101.8 292 132.7 90 40.9 158 71.8 226 102.7 294 133.6 92 41.8 160 72.7 228 103.6 296 134 .5 94 42.7 162 73.6 230 104.5 298 135 .5 96 43.6 164 74.5 232 105.5 300 136.4 98 44.5 166 75.5 234 106.4 302 137 .3 100 45.5 168 76.4 236 107.3 304 138.2 102 46.4 170 77.3 238 108.2 306 139.1 104 47.3 172 78.2 240 109.1 308 140.0 106 4S.2 174 79.1 242 110.0 310 140.9 108 49.1 176 80.0 244 110.9 312 141.8 110 50.0 178 80.9 246 111.8 314 142.7 112 50.9 180 81.8 248 112.7 316 143.6 114 51.8 182 82.7 250 113.6 318 144.5 116 52.7 1S4 83.6 252 114.5 320 145.5 118 53.6 186 84.5 254 115.5 322 146.4 120 54.5 188 85.5 256 116.4 324 147.3 122 55.5 190 86.4 258 117.3 326 148.2 124 56.4 192 87.3 260 118.2 328 149.1 126 57.3 194 88.2 262 119.1 330 150.0 CENTIGRADE TO FAHRENHEIT, EQUIVALENTS °C. v. "C. "F. "a °F. °C. V. 10 SO 16 61 22 72 28 83 11 62 17 63 23 74 29 84 12 54 18 65 24 75 30 86 13 55 19 66 25 77 31 88 14 57 20 68 26 79 32 90 15 59 21 70 27 81 33 92 CALORIES TO OXYGEN PER MINUTE, EQUIVALENTS Heat produced per hour, and per 24 hours, and the Equivalent Con- sumption of Oxygen per Minute for a Respiratory Quotient of 0.82 and a Calorific Value of Oxygen of 4.825 Calories per Liter. Heat Produced Oxygen Heat Produced Oxygen Heat Produced Oxygen Per Per Sk Per Per PerSlt Per Per Per Si Per Hour Hours Minute Hour Hours Minute Hour Hours Minute Cals. Cats. C. C. Cals. Cals. C. C. Cals. Cals. C. C. 31.0 744 107 51.0 1224 176 71.0 1704 245 31.5 756 109 51.5 1236 178 71.5 1716 247 32.0 768 111 52.0 1248 180 72.0 1728 249 32.5 780 112 52.5 1260 181 72.5 1740 250 33.0 792 114 53.0 1272 183 73.0 1752 252 33.5 804 116 53.5 1284 185 73.5 1764 254 34.0 816 117 54.0 1296 187 74.0 1776 256 34.5 828 119 54.5 1308 188 74.5 1788 257 35.0 840 121 55.0 1320 190 75.0 1800 259 35.5 852 123 55.5 1332 192 75.5 1812 261 36.0 864 124 56.0 1344 193 76.0. 1824 262 36.5 876 126 56.5 1356 ■ 195 76.5 1836 264 37.0 888 128 57.0 1368 197 77.0 1848 266 37.5 900 130 57.5 1380 199 77.5 1860 267 38.0 912 131 58.0 1392 200 78.0 1872 269 38.5 924 133 58.5 1404 202 78.5 1884 271 39.0 936 135 59.0 1416 204 79.0 1896 273 39.5 948 136 59.5 1428 206 79.5 1908 274 40.0 960 138 60.0 1440 207 80.0 1920 276 40.5 972 140 60.5 1452 209 80.5 1932 278 41.0 984 142 61.0 1464 211 81.0 1944 280 71.5 996 143 61.5 1476 212 81.5 1956 282 42.0 1008 145 62.0 1488 214 82.0 1968 283 42.5 1020 149 62.5 1500 216 82.5 1980 285 43.0 1032 149 63.0 1512 218 83.0 1992 286 43.5 1044 150 63.5 1524 219 83.5 2004 288 44.0 1056 152 64.0 1536 221 84.0 2016 290 44.5 1058 154 64.5 1548 223 84.5 2028 292 45.0 1080 155 65.0 1560 225 85.0 2040 294 45.5 1092 157 65.5 1572 226 85.5 2052 295 46.0 1104 159 66.0 1584 228 86.0 2064 297 46.5 1116 161 66.5 1596 230 86.5 2076 299 47.0 1128 162 67.0 1608 232 87.0 2088 301 47.5 1140 164 67.5 1620 233 87.5 2100 302 48.0 1152 166 68.0 1632 235 88.0 2112 304 48.5 1164 167 68.5 1644 237 88.5 2124 306 49.0 1176 169 69.0 1656 238 89.0 2136 308 49.5 1188 171 69.5 1668 240 89.5 2148 309 60.0 1200 173 70.0 1680 242 - 90.0 2160 311 50.5 1212 174 70.5 1692 244 90.5 2172 313 The above table is computed from the formula = C X 1000 - ^ nnr ^, ,'. ,r. where C is 4.825 X 1440 the heat per 24 hours in calories, and O is the oxygen per min. in c.c. CHAPTER 29 SELECTED REFERENCES Many of which have been used in this book on Basal Meta- bolism, are given below. These references have been taken from recent pubhcations and, with their bibliography, summarize the development of Basal Metabohsm thru its various stages. Normals Benedict, Francis G., and Hendry, Mary F.: Energy Require- ments of Girls from 12 to 17 years of age. Series, Boston Med. and Surg. Jour., March and April, Vol. 99, 1921. Benedict and Talbot: Metabolism and Growth from Birth to Puberty. (213 pp., $2.00). Carnegie Inst., Washington, Pub. No. 302, 1921. Blunt, Katherine, and Dye, Marie: The Basal Metabohsm of Normal Women. Jour. Bio. Chemistry, 47: 69, June, 1921. Blunt, Katherine, Nelson, Alta, and Oleson, Harriett Curry: The Basal Metabolism of Underweight Children. Jour. Bio. Chemistry, 49: 247-262, Nov., 1921. Lusk, Graham: Fundamental Ideas Regarding Basal Meta- bolism. Jour. Am. Med. Ass., 77: 250-252, July 23, 1921. Means, J. H., and Woodwell, N. M.: Remarks on Standards for Normal Basal Metabohsm. Arch. Int. Med., 27: 608-619, May, 1921. Rowe, Albert H., and Eakin, Margaret: Monthly Fluctua- tions in the Normal Metabolic Rates of Men and Women. Cal. State Med. Jour, of Med., August, 1921. Talbot, Fritz B.: Standards of Basal Metabolism in Normal Infants and Children. Am. Jour, of Diseases of Children, 21: 519-533, June, 1921. Methods of Metabolism Determinations Boothby, W. M., and Sandiford, Irene: (Open Circuit Gaso- meter Method) Basal Metabolic Rate Determinations. (117 pp., $5.00). W. B. Saunders Co., Philadelphia, 1920., 273 274 BASAL METABOLISM Boothby, W. M., and Sandiford, R. B.: Nomographic Charts for all the Calculation of the Metabolic Rate by the Gasometer Method. Boston Med. and Surg. Jour., 185: 337-354, Sept. 22, 192L Carpenter, Thorne M.: Tables, Factors, and Formulas for Computing Respiratory Exchange and Biological Transforma- tions of Energy. Carnegie Inst., Washington, Pub. No. 303, 1921. Jones, Horry M.: A Simple Device for Measuring Rate of Metabohsm. Arch. Int. Med., Jan. 15, 1921. Rowe, Albert H.: Basal Metabolism in Thyroid Disease as Aid to Diagnosis and Treatment, with Notes on the Utility Modified Tissot Apparatus Cal. State Jour, of Med., 18: 332, 1920. Application of Metabolism Determinations In General Aub, J. C, and Means, J. H.: The Basal Metabolism and Specific Dynamic Action of Protein in Liver Disease. Arch. Int. Med., 28: 173-191, Aug., 1921. Baer, Joseph L.: Basal Metabolism in Pregnancy and the Puerperium. Am.. Jour, of Obstetrics and Gynecology, Vol. 2, Sept., 1921. Means, J. H.: Determination of Basal Metabolism as a Method of Diagnosis, and as a Guide to Treatment. (Role of Calorimetry in Clinic.) Jour. Am. Med. Ass., 77: 347-352, July 30, 1921. McCann, W. S.: The Effect of the Ingestion of Foodstuffs on the Respiratory Exchange in Pulmonary Tuberculosis. Arch. Int. Med. Dec. 15, 1921. Plummer, H. S.: Interrelationship of Function of the Thy- roid Gland and its Active Agent, Thyroxin, in the Tissues of the Body. Jour. Am. Med. Ass., 77: 213-247, July 23, 1921. In Hyperthyroidism Boothby, W. M.: The Basal Metabolic Rate in Hyperthy- riodism. Jour. Am. Med. Ass., 77: 252-255, July 23, 1921. SELECTED REFERENCES 275 Eberts, E. M.: Hyperthyroidism. Diagnosis and Treat- ment. Can. Med. Ass. Jour., March, 1921. In Hypothyroidism Janney, N. W.: Hypothyroidism. Barker's New System of Endocrinology and Metabolism, 1921. Plummer, H. S.: Specific Dynamic Action of Thyroxin. Am.. Jour. Physiol. 55: 295-296, 1921. In Surgery Cheever, D.: Are there Reliable Criteria of Operability in Exophthalmic Goiter? Archives of Surgery, Vol. 2: Jan. 1921. Eberts, E. M.: Basal. Metabolism as a Guide in Surgical Treatment of Goiter with Hyperthyroidism. Can. Med. Ass. Jour., 11:641, Sept., 1921. Sistrunk, W. E.: Indications for Surgical Treatment of Different Types of Goiter. Surgery, Gynecology and Obstet- rics, 33:348, Oct. 1921. Speese, John, and Brown, H. P.: The Malignant Degenera- tion of Benign Tumors of the Thyroid Gland. Annals of Sur- gery, 74: 684-690, Dec, 1921. In Fever McCann, W. S., and Barr, D. P.: Chnical Calorimetry, Twenty-Ninth Paper, The Metabolism in Tuberculosis. Arch. Int. Med., 26: 663, Dec, 1920. Miscellaneous Articles Beebe, S. P.: lodin in the Treatment of Goiter. Med. Record, 99: 996, June 11, 1921. Boitel, M. M.: Notes on the Etiology of Goiter. Rec. Med. de la Suisse Rom., p. 717, Nov., 1920. Earle and Goodall: Kymograph Attachments for Benedict Metabolometer. Lancet, London, April 23, 1921. Kendall, E. C: Isolation of the lodin Compound which ■Occurs in the Thyroid. Jour. Biol. Chem.,39: 125-146, Aug., 1919. Landolt, Bornstein, and Roth: Tabellen, Berlin, Springer, 4 ed., 1912. Talbot, F. B.: The Metabolism of a Dwarf: Studies in Meta- bolism. Jour. Am. Med. Ass., 74: 1225, 1920. CHAPTER 30 INDEX This index includes references and cross references to chap- ter titles, paragraph headings, important subdivisions, authors, definitions, and tables. Acini of the Thyroid, 159 Adenoma, adult, 164 colloid, 164 fetal, 164 toxicity of, 139 with edema, 162 mixed, 164 toxic, 226 Adenomatosis, 165 Age, sex corrections and, 241 standards and, 21 Anabolism, 16 Analyst, qualifications of, 61 Anemia, pernicious, 147 Apparatus, description of, Collins Benedict, 117 Jones Metabolimeter, 104 King, 76 McKesson Metabolor, 124 Sanborn Benedict, 80 Sanborn Handy, 131 preparation of, Jones Metabolimeter, 107 McKesson Metabolor, 124 Sanborn Benedict, 81 testing the, Benedict Universal, 93 Collins Benedict, 118 King, 78 McKesson Metabolor, 125 Sanborn Handy, 132 Apparatus required for gas analysis. Appetite, effect of thyroid therapy on, 202 Bailey, Cameron V. 8„ 65 Barometer, corrections of, for temperature, 253 Basal, interpretation of, 45 Basal metabolic rate, 16 calculation of, 41 Basal metabolism, 16 actual, determination of, 248 definition of, 19, 40 fundamentals of, 40 in endocrine disturbances, 149 in fever, 204 in hyperthyroidism, 157 in hypothyroidism, 184 in thyrotoxicosis, 170 in various diseases, 145 normal standards of, 19, 40 Du Bois, modified, 37 for boys and girls, 239 Beall, Charles G., 8, 130 Benedict-Hendry normal standards for girls, 36 Benedict Universal apparatus, 93 calculating the results, 101 computation sheet, 265 making the test, 101 measuring the carbon dioxid, 100 measuring the oxygen, 97 testing, 93 61 Blood sugar, 228 277 278 BASAL METABOLISM Body surface area, and metabolism, 21 constants for computing, of children, 31 from chart, 245 from formula, 246 from table, 247 Boiling water injections, 78 Boyle's law, 251 Boys, experiments upon, 224 normal standards for, 37, 239, Calibrate, 16 Calorie, 16 Calories to oxygen per min., 272 Calorific value, 16 Calorimetry, direct, 16, 205 direct and indirect, 73 Carbon dioxid elimination, 73 table, 76 Carcinoma, of the thyroid, 226 Cardiovascular goiter, 163 symptoms of, 165 Catabolisra, 16 Centigrade to Fahrenheit, equivalents, 271 Charles' Law, 250 Children, Benedict-Talbot standards for, 239 comparative normals of, 223 constants for computing body surface, 31 weight and metabolism of, 32 Clinical manifestations in hyper- thyroidism, 159 Closed circuit apparatus, 16 Closed circuit method, computation sheet, 261 Collins Benedict apparatus, 117 calculating the rate, 121 description of, 117 making the test, 120 recording the data, 121 testing the, 118 Computations, 238 Conspectus, 223 Consumption of oxygen, 16 Contributors, 8 Cretinism, 199, 186 Definitions, 17 Determination of basal metabolism, actual, 248 normal, 238 Differential diagnosis, hyperthyroidism and, psychoneurosis, 180 pulmonary tuberculosis, 228 Direct calorimetry, 16 Douglas Bag method, '51 Dreyer, formula, 26 Drugs, effect of, 177 Du Bois, Eugene F., 8, 204 Du Bois, height-weight formula, 22 modified standards, table of, 29 normal standards, 41 for boys, 37 table of, 25 Dysfunction of the liver, 231 Dysthyroidism, 155 Else, J. Earl, 8, 153, 157 Emotion, effect of, 20 Endocrine disturbances, 149 Equivalents, tables of, 270 Estimates in the Goiter Clinic, 213 classification of, 213 Exophthalmic goiter, 157 Face mask, 52, 64 Fetal sex, 228 Fever, basal metabolism in, 204 protein metabolism in, 209 respiratory quotient in, 213 results of experiments, 207 summary of available data, 204 water metabolism, 213 Food, effect of, 20, 47 INDEX 279 Formula, Dreyer, 26 Du Bois, 22 Meeh, 31 Frazier, Charles H., 8, 215 Gardner, Edwin L., 8, 184 Gas analysis, collection of air samples, 68 Haldane apparatus, 54 Henderson apparatus, 56 assembling the, 58 chemicals for, 58 principles of, 70 sampling bottles, 68 sampling tubes, 53 Gas analysis methods, 51 Douglas bag, 51 of N. Y. Post Grad. Hosp., 63 calculation sheet, 260 making the test, 66 summary of apparatus required, 61 Gasometer, 16 Gas sampling bottles, 68 Girls, normal standards for, 239 Goetsch, 183 Goiter, Basedow, 226 classification of, 226 cystic, 226 hyperplastic, 157 substernal, 226 tuberculous, 226 treatment of certain types of, 175, 176 Gonadeal deficiency, 151 Haldane gas analysis apparatus, 54, 55 Haskins, Howard D., 8, 123 Heart disease, 146 Henderson gas analysis apparatus, 56, 58 assembling the, 58 chemicals for, 58 use of the, 59 Hutton, James H., 8, 142 Hyperplastic goiter, 157 results of, 163 Hyperthyroidism, 157 and psychoneurosis, 180 and pulmonary tuberculosis, 228 basal metabolism in, 157 classification of, 157 clinical manifestations in, 159 definition of, 157 recurrent attacks of, 155 Hypophysis, dualistic function of, 149 Hyposecretion, ISO Hypothyroidism, 184 cases of decreased metabolism in, 199 classification of, 184 congenital, 186 minor, 186 definition of, 184 diagnosis of, 193 effect of diet, 185 pathogenesis, 198 physiological, 184 primary, 186, 187 secondary, following, hyperthyroidism, 187 infections and toxemias, 191 surgery, 187 therapy by thyroid feeding, 197 treatment of, 201, 184 Indirect calorimetry, 16, 80 Intravenous administration, 229 James, Carmen E., 8, 180 Janney, Nelson W., 8, 197 Jordan, Sara, 218 King apparatus, 73 calculating the rate, 79 description of, 76 technic of the test, 78 test for leaks, 78 ventilation test, 78 280 BASAL METABOLISM King, John T., Jr., 8, 73 Kymograf, 16 records of, 235 Lahey, Frank H., 8, 218 Langstroth, Lovell, 9, 93 Lesions, permanent, 156, 167 non-thyroid, 153 Leucemia, 148 basal metabolism in, 235 blood count in, 235 myelogenous, 233 Lewis, Robert C, 9, 104 Ligations, 178 Liver, dysfunction of, 233 Logarithms, table of, 268 Malarial chill, 211 Malnutrition, 190 Marks, Henry Eisner, 9, 80 Mask, description of, 64, 52 McCaskey, George W., 9, 170 McGuire, Stuart, 9, 175 Meeh formula, 31 Menstruation, 226 Mental exertion, 234 Metabolimeter, the, 104 calculation of results. 111 description of, 104 location of leaks, 114 making the test, 108 preparation of, 107 preparation of patient, 108 principle of, 104 j-ecalibration of, 115 sources of error, 113 tables, 112 Metabolism, 17 effect of, air current, 49 cigarette smoking, 49 cold bath, 48 emotion, 20 food, 20 muscular activity, 20 from discomfort, 46 posture, 20 sleep, 20 Metabolor, the, 123 calculating the rate, 126 description of, 124 making the test with, 125 preparation of, 124 table for correction of volume 129 testing, 125 Moore, John Walker, 9, 45 Mosenthal, Herman 0., 9, 145 Mouthpiece, 52 Myelogenous leucemia, 233 Myxedema, 188 Nephritis, 146 New York Post Graduate Hosp. method used at, 63 Normal basal metabolism, methods of computing, 41 for adults, 20 to 80 yrs. 42 for age of puberty, 12 to 20 yrs., 44 for children, 1 to 12 yrs. 43 Normal consumption of oxygen, correction for age and sex, 241 tables of, 242, 243 Normality of subjects, 19, 30 Normal standards, 17, 19 and methods of computation, 40 basis of comparison of, 205 chart for comparison of, 206 for adults, 23 for boys and girls, 239 for boys, Du Bois, 37 for children, 29 for the age of pubert;y, 33, 41 of basal metabolism, 19, 37, 23a of Benedict-Talbot, 239 of Du Bois, 29, 41 referred to age, 30 referred to body surfaces, 31 relative merits of, 28 Obesity, 146 Oophorectomy, 154 INDEX 281 Open circuit, 17 Oral administration, 231 Oxygen, normal consumption of, correction for age and sex, 241 from body surface area, 127 table of, 242 Patient, preparation of, 45, 100 133, 108 routine, SO Physiological factors, 45 Pituitary extract, 230 effect of, 231 Pluriglandular, insufficiency, 151 syndromes, 151 Posture, effect of, 20 Pregnancy, 227 Principles of gas analysis, 70 Prognosis, 225 Protein metabolism, in fever, 209 in liver disease, 233. Psychoneurosis, 180 symptoms, 181 Puerperium, 227 Records, kymograf, 235 Residual air, 17 Respiration calorimeter, 17 Respirations irregular, 89 kymografic records of, 235 Respiratory quotient, 17 in fevers, 213 variation in, 89 Respiratory rate, 17 in pulmonary tuberculosis, 229 Rest, 177 Roentgen-ray therapy, 138 Rowe, Albert H., 9, 136 Rubber flutter valve, S3 Sampling bottles, 68 Sampling tubes, 53, 54 Sanborn Benedict apparatus, 80 calculation sheet, 92 data sheet, 91 description of, 80 location of leakage, 88 making the test, 83 method of calculation, 85 preparation of, 81 Sanborn, Frank B,, 9 Sanborn Handy apparatus, 130 calculating the rate, 135 description of, 131 making the test, 133 test sheet, 134 testing the, 132 Sex and age correction, 241 Sleep, effect of, 20 Spirometer, 17 Standard pressure, 17 Standard temperature, 17 Standards, flexibility of, 38 Surgery, 139, 178, 216, 217, 219 an index to, 219 Syphiliphobia, 174 Tables, body surface area, 246, 247 calorific values, 259 correction of barometer for temperature, 253 correction of dry gas for temperature and barometer 258 correction of saturated gas for temperature and barometer, 256, 257 correction of volume for, barometric pressure, 251 temperature, 249, 250 logarithms, 266 normal standards, for adults, 238 for boys and girls, 239 of carbon dioxid elimination 240 of consumption of oxygen, 242, 243 of equivalents, 270 calories to oxygen, 272 Centigrade to Fahrenheit, 271 inches to cms., 270 pounds to kilos, 271 282 BASAL METABOLISM seconds to decimal mins., 270 Therapy, 22S Roentgen-ray, 138 thyroid, 140, 197 X-ray, 177, 228 Thyroid activity, variation in, 142 Thyroid deficiency, minor, 189 Thyroid function, estimation of, 184 Tliyroid, role of the, 175 Thyroid therapy, 140, 197 Thyroidectomies, partial, 179 Thyrotoxicosis, 170, 221 clinical symptoms, 171, 222 Thyroxin, absorption of. 16S administration of, 230 exhaustion of, 230 Tidal air, 17 Tierney, John L., 9, 149 Tissot, S3 Tonsil infection, 154 Total ventilation, 17 Tuberculosis, chronic pulmonary, 228 incipient, 154 respiration in, 229 Underweight children, 223 Uniformity of conditions, 20 Valves, expiratory, S3 inspiratory, 53 rubber flutter, 53 Van't Hoff Law, 209 Variations in thyroid activity, 142 Variation, normal range of, 27 Volume, correction of, for change in temperature, pressure, 251 temperature, 249, 250 Water metabolism in fever, 21S X-Ray, 177, 228 I 1 It 'M •i\' '.'\^)\^^'i^j^^i,uVih\\X!rJWim^