Southern Branch of the University of California Los Angeles Form L-l 2.16 This book is DUE on the last date stamped below. AUG WAY 3 1 193- ft 3 ^ APR 11 1941 EEB 1 ? 1944 JUN 20 1360 5m-8,'21 DISEASES OF NUTRITION AND INFANT FEEDING THE MACMILLAN COMPANY MEW YORK BOSTON CHICAGO DALLAS ATLANTA SAN FRANCISCO MACMILLAN & CO., LIMITED LONDON BOMBAY CALCUTTA MELBOURNE THE MACMILLAN CO. OF CANADA, LTD. TORONTO DISEASES OF NUTRITION AND INFANT FEEDING BY JOHN LOVETT MORSE, A.M., M.D. Professor of Pediatrics, Harvard Medical School; Visiting Physician at the Children's Hospital; Consulting Physician at the Infants' Hospital and the Floating Hospital, Boston AND FRITZ B. TALBOT, A.B., M.D. Instructor in Pediatrics, Harvard Medical School; Chief of Children's Medi- cal Department, Massachusetts General Hospital; Physician to Chil- dren, Charitable Eye and Ear Infirmary; Consulting Physician at the Lying-in Hospital and at the Floating Hospital, Boston SECOND EDITION REVISED Nrro fork THE MACMILLAN COMPANY 1920 AU rights reserved COPTKIOHT, 1915, 1920, BT THE MACMILLAN COMPANY Set up and electrotyped. Published September, IBIS Reprinted October, 1915. New Edition Completely Revised January, 1920 r 1MT PREFACE TO SECOND EDITION THE aim of the second edition remains the same as that of the first edition. New data have been added which brings the litera- ture up to April 1, 1918. The exigencies of the war have retarded investigation to such an extent that during the past year there have been very few workers who were able to do anything to ad- vance the science of Pediatrics. These recent publications have not been included in the literature. JOHN LOVETT MOBSE, FRITZ B. TALBOT. August 6, 1919. PREFACE THIS book was written to meet what seemed to the authors to be two distinct needs in American pediatric literature; a detailed description of the scientific basis of rational infant feeding and a description of the method of infant feeding taught in the Harvard H ^ Medical School. In it the authors have endeavored to meet these | needs. It is intended to satisfy the demands, on the one hand, of those students who wish to become acquainted in the original with the data on which the scientific basis of infant feeding rests i and, on the other, of the general practitioner who wishes to learn the clinical and practical sides of infant feeding. It is hoped that it will not only point the way to further investigations but also be of service to the clinician in his daily work. JOHN LOVETT MORSE. BOSTON, FRITZ B. TALBOT. September, 1915. TABLE OF CONTENTS SECTION I PHYSIOLOGY AND METABOLISM CHAPTER PAGE 1 PHYSIOLOGY OF DIGESTION 1 II. THE DIGESTION AND METABOLISM OP FAT 20 III. THE DIGESTION AND METABOLISM OP CARBOHYDRATES . . 32 IV. THE DIGESTION AND METABOLISM OP PROTEIN .... 43 V. THE METABOLISM OF THE MINERAL SALTS 58 VI. THE ENERGY METABOLISM OP INFANTS 64 VII. BACTERIOLOGY OF THE GASTROINTESTINAL CANAL ... 77 VIII. THE STOOLS m INFANCY 87 SECTION n BREAST FEEDING DC. GENERAL CONSIDERATIONS 99 X. HUMAN MILK: CHEMISTRY AND BIOLOGY 103 XI. CLINICAL CONSIDERATIONS AND TECHNIQUE 134 XII. WET-NURSES 163 SECTION m ARTIFICIAL FEEDING XIII. Cow's MILK: CHEMISTRY AND BIOLOGY 157 XIV. Cow's MILK: BACTERIOLOGY AND CHEMICAL TESTS . . . 175 XV. STERILIZATION, BOILING AND PASTEURIZATION OF MILK . . 179 XVI. CERTIFIED MILK 189 XVII. GENERAL PRINCIPLES OF ARTIFICIAL FEEDING .... 192 XVIII. THE PRESCRIBING OF MODIFIED MILK 225 XIX. THE FEEDING OF PREMATURE INFANTS . . 250 TABLE OF CONTENTS CHAPTER PAGE XX. SPASM OF THE PYLORUS 255 XXI. HYPERTROPHIC STENOSIS OP THE PYLORUS 259 XXII. NERVOUS DISTURBANCES OP THE DIGESTIVE TRACT . . . 267 XXIII. DISTURBANCES OP DIGESTION 269 XXIV. INDIGESTION WITH FERMENTATION 291 XXV. INFECTIOUS DIARRHEA 302 XXVI. CONSTIPATION 321 SECTION V DISEASES OF NUTRITION XXVII. RICKETS 329 XXVIII. INFANTILE SCURVY 341 XXIX. SPASMOPHILIA 354 XXX. ACIDOSIS 361 INDEX 369 DISEASES OF NUTRITION AND INFANT FEEDING SECTION I PHYSIOLOGY AND METABOLISM CHAPTER I PHYSIOLOGY OF DIGESTION MOUTH Food is drawn into the mouth of the infant by the negative pressure which results from the act of sucking. This nega- tive pressure is between five and fifteen centimeters of mer- cury or between ten and one hundred and forty centimeters of water. 1 Almost all the work on the reaction of the oral cavity has been done by older writers and, although their results have not been uniform, it seems to be established that the reaction of the mouth of the new-born infant is neutral or weakly alkaline before the first food is taken. The acid reaction of the mouths of older babies is probably due to the breaking down of food remains. Oshima 2 has recently demonstrated lactic acid, by Uffelmann's test, in the mouths of infants, most often between the ages of three and six months. He attributes the presence of this acid to the action of a leptothrix. It probably is not present in large enough amounts to be of any practical importance. Immediately after birth a baby's mouth is free from bacteria, but it very quickly becomes infected. The normal bacterial flora, therefore, quickly gain entrance into the infant's gastrointestinal canal a few hours after birth. The weight of the salivary glands at different ages, as given by Berger, 3 is as follows: 1 Gundobin: Die Besonderheiten des Kindesalters, Berlin, 1912, 248. * Oshima: Arch. f. Kinderh., 1907, xlv, 21. 1 Quoted by Gundobin: Die Besonderheiten des Kindesalters, Berlin, 1912, 258. 1 PHYSIOLOGY OF DIGESTION TABLE 1 Parotid Av. wt. Av. wt. Average Age body Av. wt. Max. wt. Min. wt. maxUlaries linguals weight gm. gm. gm. gm. gm. New born 3580 gm. 1.80 2.4 0.9 0.84 0.42 3 months 3600 gm. 3.18 4.8 1.4 1.53 0.84 6 months 4745 gm. 4.50 5.8 3.1 2.12 1.05 2 years 9100 gm. 8.60 9.6 8.2 4.89 2.00 These glands are heavier in healthy and well developed than in sickly and poorly developed infants, but considerable individual variations are often found. The glands begin to differentiate from the epithelium of the mouth in the second month of fetal lif e and can be dissected at the tenth week of fetal Me. Saliva is secreted during the first week of life and probably dur- ing the first day (Joerg, Bidder and Schmidt). It has the power of converting starch into sugar as soon as it is secreted. 1 ' 2> 3> 4 Ptyalin is present in both the parotid and submaxillary glands. 3 Ibrahim was able to demonstrate diastatic ferments in both the parotid and submaxillary glands of two fetuses. One of them weighed but 150 gm.; the other was in the sixth month of fetal life. He thought that there was about the same amount in each gland at birth. The diastase in the saliva is only able to digest starches as far as maltose and not into grape sugar. 6 ' 6> 7 Shaw 8 gave babies a test meal of barley water and washed out their stom- achs from fifteen to sixty minutes later. He found that it was possible for the diastatic action of saliva to continue in the stomach as long as two hours after feeding. It is difficult to say what r61e the saliva of infants plays in the physiology of digestion. Probably it plays a very small part. In general, it has been shown, 9 - 10> " 1 Schlossmann: Jahr. f. Kinderh., 1898, xlvii, 116. 2 Montague: Diss., 1899, Leiden; Montague: Centralbl. f. Inn. Med., 1900, xxi, 705. 3 Schilling: Jahrb. f. Kinderh., 1903, Neue Folge, Iviii, 518. 4 Moll: Monatsschr. f. Kinderh., 1905-06, iv, 307. 6 Musculus and Gruber: Zeitschr. f. Phys. Chem., 1878, ii, 177. 8 Musculus and Mering: Zeitschr. f. Phys. Chem., 1878, ii, 403. 7 Hamburger: Pfluger Arch., 1895, Ix, 543. 8 Shaw: Albany Med. Annals, Jan., 1904, xxv, 148. 9 Glinsky: Sitzung.d. Gesellsch. russ. Arzte zu. St. Petersburg, 1895. 10 Wulfson: Diss. St. Petersburg, 1898. "Snarsky: Diss. St. Petersburg, 1901. PHYSIOLOGY OF DIGESTION 1( 2 that the dryer the food, the greater the secretion of saliva. This rule, however, does not hold good with milk, 3 the food of babies, because considerably more saliva is secreted for a food containing milk than for that containing meat. It is admitted, 4 ' 5 however, that saliva may cause coagulation of milk and thus help stomach digestion. The amount of water, albumen, and mucus in saliva varies considerably. Finizio 6 induced infants to suck bits of cotton and then deter- mined the amylolytic power of the saliva. This was greatest about midday and was different in babies of the same age. When the babies were less than six months old, it did not vary after nursing or when starch was added to the food, but when they were over six months old, there was an increase in the amylolytic power im- mediately after a meal containing starchy foods. This increase was still noticeable an hour later. Beginning at about six months there seemed to be a gradual development of the specificity of function of the salivary glands. He tested the saliva of several babies monthly during the first year and found that the amylolytic power increased progressively from birth to the age of twelve months. At eight to ten months it was twice that at birth, and at one year a trifle less than that of children two to three years old. Allaria 7 found that, after the first weeks of life, the mouth reacted acid to litmus paper and phenolphthalein, and that the reaction was rarely neutral or alkaline. STOMACH The stomach of the fetus, with the exception of the pylorus, lies completely in the left hypochondrium. The pylorus is in the median line and is completely covered by the liver. These rela- tions change after birth so that at fifteen months the liver no longer overlaps the stomach. The position of the stomach of the fetus is nearly vertical. In the newly-born child, it lies some- what obliquely in the abdomen, and at the end of infancy, it has almost reached the transverse position. The growth of the fundus compared with that of the stomach as 1 Malloizel: Jour. d. Physiol. et Pathol., gener., 1902, 547. 2 Heymann: Diss. St. Petersburg, 1904. 'Sellheim: Diss. St. Petersburg, 1904. 4 Billard and Dieulate: Comptes rend, de la soc. de biol. a Paris, 1902. 5 Borissow: Russk. Wrat. 1903, Die, letzen 8 Arbeiten, quoted in Noth- nagel's Handbuch. 8 Finizio: Rev. Hyg. et Med. Infant, viii, No. 3, 224. 7 Allaria: Monatsschr. f. Kinderh., x, No. 4, 179. 4 PHYSIOLOGY OF DIGESTION a whole is relatively rapid during infancy. The length of the fundus of the fetus is one-fifth, of the infant one-quarter, and of the adult one-third of the total length of the stomach. 1 The stomach, as would be expected, grows rapidly in size during the first year. The greater curvature becomes longer, increasing 16 to 24 centimeters in length. Pisek and Lewald 2 conclude from their investigations with the Rrentgen ray that there is no charac- teristic normal type of stomach in the infant. It is horizontal rather than vertical when compared with the adult type, and fol- lows certain rather definite forms. They distinguished (a) the ovoid or Scotch bag-pipe type of Flesh and Peteri (b), the tobacco pouch (retort shape of Alwens and Husler), and (c) the pear- shaped stomach with base above and to the left. The shape of the stomach does not depend on the amount or character of the food ingested, but rather upon the quantity of gas which it con- tains or acquires. Major 3 showed that the shape of the Rcentgen ray picture of the stomach varied with the position of the infant and that the movements of the diaphragm could cause changes in its appearance. Alwens and Husler (quoted by Pisek 4 ) report, furthermore, that they have observed a change in the form from the tobacco pouch to the bag-pipe variety after the intestines have been emptied. Gastric Capacity. Recent investigations show that the ana- tomic gastric capacity, obtained by measuring the capacity of the stomach by water poured in post-mortem at a pressure of 15 cm. (the figures given in most text-books are based on such observa- tions), is considerably smaller than the physiologic capacity. The physiologic capacity of infants' stomachs is at such variance with the anatomic measurements that it is safe to say that a baby can digest more than the anatomic size of the stomach would seem to warrant. 6 The following figures were taken from Pfaundler, 6 and repre- sent the gastric capacity in cubic centimeters post-mortem with a pressure of 15 c. c. water. l Gundobin: loc. tit., 264. * Pisek and Lewald: Am. Jour. Dis. Children, 1913, vi, 232. Major: Zeitschr. f. Kinderh., 1913, viii, 340. 4 Pisek and Lewald: loc. tit. 6 Mosenthal: Arch. Ped., 1909, xxvi, 761. Pfaundler: Magencapacitat im Kindesalter: Stuttgart, 1898, quoted by Gundobin. PHYSIOLOGY OF DIGESTION TABLE 2 Age of infant Months 1 2 3 4 6 8 10 12 Systolic stomach 150 175 210 200 235 230 290 295 360 365 430 445 490 515 Diastolic stomach . . The gastric capacity, determined post-mortem by Holt, 1 is as shown by Table 3. Tables 2 and 3 represent the gastric capacity of infants with closed pyloric valves which allowed no food to escape into the intestine. Mosenthal investigated the gastric capacity of in- fants during life (physiological capacity) and post-mortem (ana- tomic capacity), and found that the former was always larger than the latter. TABLE 3 Age No. of cases Capacity oz. c. c. Age No. of cases Capacity oz. c. c. Birth 5 1.2 36 7-8 mos. 9 6.88 200 2 weeks 7 1.5 42 10-11 " 7 8.14 244 4 4 2.0 60 12-14 " 10 8.90 265 6 11 2.27 68 8 4 3.37 100 10 2 4.25 128 12 6 4.50 132 14-18 12 5.00 150 5-6 mos. 14 5.75 172 The following table is a summary of the results which he ob- tained in a study of twenty-four cases: TABLE 4 Amount of milk offered at each nursing 4.0 oz., Amount of milk ingested at each nursing 3.6 oz. Post mortem gastric capacity (Pfaundler's method) 2.6 oz., 120 c. c. 108 c. c. 78 c. c. "In every instance, excepting the diastolic stomachs, the in- fant ingested more fluid at a nursing than the volume of its stomach, as determined by careful measurements, can contain." This means that the figures for gastric capacity given above represent the ana- 6 Holt: Dis. Infancy and Childhood, N. Y. and London, 1911, 309. 6 PHYSIOLOGY OF DIGESTION tomic capacity of the stomach, and that the physiologic capacity, what an infant can take at a nursing, can be considerably larger than this. This can be explained by the fact that shortly after milk is swallowed the stomach shows signs of motor activity and the milk begins to pass almost immediately into the intestines. This is proven by fluoroscopic examination which shows the milk spurting through the pylorus into the intestine before the meal is finished. This happens more easily with human milk than it does with simple dilutions of cow's milk. Duration of Stomach Digestion. The duration of stomach diges- tion has been studied for a long time, at first with the stomach tube, 1 ' 2> 3> 4l 5 only, and recently with the Roentgen ray. 6 - 7 It can be said in general on the basis of these observations, that the stomach digestion lasts in the breast-fed baby from one and a half to two hours, and in the artificially-fed baby three hours. Pisek and Lewald believe that a large number of stomachs practi- cally empty themselves within an hour, while A. H. Meyer, 8 and Von Monrad think that it is three and one-half hours before the stomach is emptied. A large meal obviously requires a longer period for digestion than a smaller one, and cow's milk remains longer in the stomach than human milk. 9 Ladd's 10 extended series of observations on babies, and Cannon' 11 on animals, have done much to increase our knowledge of this complicated subject. The infant's stomach, as compared with the adult's, shows a "curious lack of peristalsis." Shortly after food is ingested some of it may be discharged into the duodenum, without undergoing stomach digestion. It has been found in animals that carbohydrates leave the stomach the most rapidly of the three food components, a large part of them being discharged within two hours, while proteins are discharged less rapidly, and fats the most slowly. These facts fit in with the economy of the body, since carbohydrates are not digested at all by the gastric juices, and are, therefore, passed along to the small intestine as 1 Epstein: Prager med. Wochenschr., 1880, 45, 450. 2 Epstein: Prager med. Wochenschr., 1881, 33-34. 8 Epstein: Jahr. f. Kinderh., 1887, xxvii, 113. 4 Czerny: Prager med. Wochenschr., 1893, 495, u. 510 . s Wohlmann: Jahr. f. Kinderh., 1891, xxxii, 297. Tobler and Bogen: Monat. f. Kinderh., 1908-09, vii, 12. 7 Leven and Barret: Presse Medicale, 1906, 63, 503. 9 Meyer, A. H. : Bibliothek f. Laeger, 8, R, III, 390-512. Kopenhagen, 1902. Ref. im Jahr. f. Kinderh., 1903, Neue Folge, Iviii, 275. Tobler and Bogen: Monat. f. Kinderh., 1908-09, vii, 12. 10 Ladd: Am. Jour. Dig. Children, 1913, v, 345. 11 Cannon: The Mechanical Factors of Digestion, London and N. Y., 1911. PHYSIOLOGY OF DIGESTION 7 quickly as possible; whereas the proteins, which are digested by the gastric juices, are retained for this action. The fats, on the other hand, are discharged from the stomach at such a slow rate that there is never any great accumulation of fat in the small intestine, the rate of the discharge from the stomach being ap- proximately the same as that of the departure of fat from the small intestine. The discharge of mixtures of food depends upon the relative proportions of fat, carbohydrate and protein which they contain (Cannon). These findings in animals have been partially confirmed in a few observations on infants. In one instance, how- ever, in which the infant received food containing no fat, 6.62% sugar, and 3.5% protein, the stomach was not empty at the end of iy 3> 4 In chronic diseases such as congenital syphilis and " enterocolitis " there may be an interstitial pancreatitis with a corresponding TABLE 5 Age Number of cases Wt. in grammes Average length in cm. Width in cm. Thickness in cm. 3 mos. fetus 1 0.07 1.1 0.4 -0.2 4 2 O.H5 1.65 0.75-0.27 0.33-0.17 5 3 0.38 3.2 0.8 -0.5 0.34-0.21 6 6 0.38 3.2 0.8 -0.48 0.38-O.25 7 2 0.76 4.35 1.0 -0.63 0.4 -0.25 8 2 1.18 4.32 1.2 -0.7 0.6 -0.35 9 4 1.63 5.7 1.5 -0.85 0.58-0.35 1-2 months 3 2.61 6.93 1.6 -0.9 0.66-0.56 2-3 3 2.64 7.54 1.6 -0.9 0.65-0.5 3-4 3 4.93 7.46 2.1 -1.5 0.8 -0.57 4-5 3 5.4 7.5 2.25-1.5 0.85-0.8 5-6 3 5.28 7.0 1.75-1.25 0.95-0.65 &-9 3 7.37 8.2 2.0 -1.6 1.0 -0.65 9-12 3 8.67 9.5 2.0 -1.2 0.9 -0.45 weakening of the pancreatic ferments (Gundobin). Hess 5 has shown that lipase (steapsin) may be deficient in acute intestinal indigestion while the two other pancreatic ferments are present in considerable amounts. The secretin of the intestinal mucous membrane stimulates the production of the pancreatic ferments. Bayliss and Starling 6 showed that when inorganic or organic acids were discharged from the stomach into the duodenum secretin was set free. When se- cretin is carried by the blood to the pancreas it starts the pan- creatic secretion. Secretin has been found in the fetus and in many new-born babies. The peptic ferment, trypsin, is present 1 Hess: Am. Jour. Dis. Children, 1912, ii, 205, Summary of Literature. 2 Moro: Jahrb. f. Kinderh., 1898, xlvii, 342. 3 Ibrahim and Gross: Ref. Deut. med. Wochenschr. Vereinsbeilage, 1908, xxv, 1128. 4 Hartge: loc. cit. 6 Hess: Am. Jour. Dis. Children, 1913, v, 268. 6 Bayiiss and Starling: Jour. Physiol., 1902, xxviii, 325-53, 1903, 174. 16 PHYSIOLOGY OF DIGESTION in the pancreas as the pro-ferment trypsinogen. Many fetuses have trypsinogen, but no trypsin. The secretion of enterokinase is called forth by the pancreatic juice and has been demonstrated in new-born and premature babies by Ibrahim. The pancreatic ferments, with the added action of erepsin, carry the digestion of proteins from albumoses and peptones into amino acids. The fat-splitting ferment, called lipase or steapsin, is active in acid, alkali, or neutral surroundings. This ferment is present in the pancreatic juice in part as a pro-enzyme, which is changed by the bile into steapsin. The bile in this way increases the fat- splitting power of the pancreatic ferments l and facilitates emul- sion. There is no work upon the sugar-splitting ferments in babies other than that of Ibrahim, 2 Miura, 3 neither of whom are able to find any in the new-born. LIVER The weight of the liver post-mortem depends upon whether or not it is full of blood. When the former weight is taken, it is known as the "physiological weight," and the latter as the "post- mortem weight." The physiological weight is obtained by filling the liver to its maximum with water, after it has been removed from the body. The following table of Kowalski's 4 gives the weights of the livers of fifty normal infants: 1 Furth and Schutz: Hofm. Beit. z. chem. Physiol. u. Path., 1907, ix, 28. 2 Ibrahim: Verhandl. d. Gesell. fur Kinderh. Koln., 1908, 21. 3 Miura: Zeitschr. f. Biologie. 32 Neue Folge, 1895, xiv, 266. 4 Kowalski: Die Leber des Kindes. Diss. St. Petersburg, 1900 (Russian), quoted by Gundobin. PHYSIOLOGY OF DIGESTION 17 TABLE 6 Age No. of cases Total wt. of Iwer in gram Body weight in gram 5 mos. fetus 1 39 650 j if 5 have demonstrated erepsin in the fetus and other ferments have been identified by other writers. Lang and Fenger, 6 studied the reaction of the small intestine in animals and man, employing an electrometric method. An alkaline reaction is less common than an acid one, even close to the duodenum, where a TABLE 8 Age Number of cases Length of trunk from the 7th cervical vertebra to the coccyx Length of the small intestine in cm. Length of the large intestine in cm. in cm. 1 month 4 21.5 296.4 63.3 1-2 mos. 6 21.1 319.1 65.1 2-3 14 22.2 358.1 70.6 3^ 5 23.1 379.4 71.2 4-5 4 25.5 383.4 72.3 5-6 5 25.1 380.3 69.2 7-9 2 27.0 412.4 80.5 6-12 6 27.0 419.8 83.9 Average 46 23.5 365.3 71.6 temporary alkalinity may be established by bile. The usual reac- tion is between 1 to 3 X 10 ~ 7 . 1 Uffenheimer: Ergebnisse d. inn. Med. et Kinderh., 1908, No. 2, 271. 2 Debele: Die Lange des Darmkanals im Kindesalter. Diss. St. Petersburg, 1900 (Russian), quoted by Gundobin. Langstein and Soldinr Jahrb. f. Kinderh., 1908, Neue Folge, Ixvii, 9. 4 Jaeggy: Zentralblatt f. Gynak., 1907, No. 35, 1060. 6 Foa: Munch, med. Wochenschr., 1907, 2201. 6 Science, 1917, xlvi, p. 000. PHYSIOLOGY OF DIGESTION 19 Carbohydrates are split into monosaccharides in the small intes- tines, where they are absorbed. The specific ferments, invertin, lactase, and maltase, convert the corresponding sugars into mono- saccharides and are either present in the digestive juices or in the mucous membrane. Food stays a relatively short time in the small intestine, but during that time is mixed with and acted upon by the digestive juices so that it is ready for absorption before it reaches the large intestine. There is nothing definitely known about the secretions of the large intestine. Digestion-Leucocytosis. The evidence on this point is con- flicting. Recent .work shows that it is only present hi 12% of the cases, while in the remainder there is no increase in the leucocytes after the ingestion of food but rather a decrease. The probable explanation being that they are drawn away from the peripheral circulation to the digestive tract. CHAPTER II THE DIGESTION AND METABOLISM OF FAT The fat in the infant's food is principally in the form of neutral fat. Saliva has no action upon it, and, although saponification begins in the stomach, it probably is not carried on to a point which influences to any degree the future digestion of the fat. The action of the fat-splitting ferment of the stomach is eventually stopped entirely by the acid reaction of the stomach contents. The action of the gastric secretions is of importance indirectly, because when milk is coagulated by rennin, most of the fat is ensnared in the meshes of the casein curds, and the casein coating must be first digested before the digestive juices can reach the fat. There is, therefore, very little opportunity for the absorption of fat in the stomach. This ensnaring of the fat by the casein may be of phys- iological importance in preventing the liberation of too large an amount of fat in the intestinal canal at one time. Fat has a definite influence on the emptying time of the stomach, large amounts tending to delay it. 2 Large amounts of fat in the food are, according to Tobler 3 of etiological significance in the pathogenesis of pyloric spasm. He found in the stomach of one infant more fat than had been given to it during the previous twenty-four hours. He also calculated that one liter of milk would cause one and a hah" liters of digestive juices to be secreted. The real digestion of fat commences when it reaches the small intestines, where it undergoes a physical change. The fat is first of all subdivided by the alkaline salts of the bile, and of the pancreatic and intestinal juices. Fatty acids, which are formed as the result of the action of the fat-splitting ferments, react with the alkaline carbonates present to form soaps. The soaps which result make the fat particles still smaller and form an emulsion. Absorption. There is considerable evidence to show that neu- tral fat (unsplit fat), is not absorbed as such into the intestinal 1 Tobler and Bessau: Allegemeine Fathologische Physiologie der Ernahrung und des Stoffwechsels im Kindesalter, Wiesbaden, 1914, has been consulted and quoted freely in this section. * Tobler and Bogen: Monatsschr. f. Kinderh., vii, 12. 1 Tobler: Verhandl. d. Gesellschaft f. Kinderh., 1907, 411. 20 DIGESTION OF FAT 21 wall: for example, hydrous wool fat and paraffin, which may be made into emulsions but cannot be split, are not absorbed. 1 It has also been shown by animal experimentation that the amount of fat in the chyme is directly proportional to the amount of fat which has been split. 2 It is also taught by some that fat is ab- sorbed both in the form of an emulsion and in the form of water- soluble soaps, neither view excluding the other. Langworthy and Holmes, 3 studied the digestibility of fat in the adult and found that its "coefficient of digestibility" was dependent on its melt- ing point; the lower the melting point the greater the digesti- bility. This is shown in the following table: Fat studied Coefficient of digestibility % Melting point degrees C. Butter fat Lard Beef fat Mutton fat 97 97 93 88 32 35 45 50 Bloor 4 found that substances similar to food fat in that they emulsified well, were soluble in fat solvents and were liquid at temperatures below that of the body, but could not be converted into a water soluble form, and were not absorbed at all in the intes- tinal canal. He concluded that the slow passage of fats from the stomach, the abundant provisions for hydrolysis and for the ab- sorption of fat-like substances which can be changed to a water soluble form, make it extremely probable that saponification is a necessary preliminary to absorption. The significance of the mech- anism involved is little understood, but one of its uses would appear to be to exclude undesirable fat-like substances which would otherwise be carried into the body with the fats. Kastle and Loevenhart 5 demonstrated the almost universal pres- ence of lipase in the tissues, and showed that this ferment could reverse its action. That is to say, it can synthetize or change soaps back into neutral fats as well as split neutral fats and form soaps. It is, therefore, possible that the soaps, which have been 1 Connstein, W.: Arch. f. Anat. u. Physiol., 1899, 30; Henriques and Han- sen: Zentralblt. f. Physiol., 1900, xiv, 313. 1 Levites: Ztschr. f. physiol. Chem., xlix, 273; liii, 349. 1 Bull. 136, Expt. Sta. U. S. Dep't Agric., 1903, p. 113. 4 Bloor: Jour. Biol. Chem., xv, 105, and Jour. Biol. Chem., 1914, xvi, 517. Kastle and Loevenhart: Am. Chem. Jour., 1900, xriv, 491. 22 DIGESTION OF FAT formed during the digestion, are changed during their passage through the intestinal epithelium by the reversible action of lipase into neutral fat, because neutral fat is found almost exclusively in the lymph stream. Whitehead's l experiments on cats seem to strengthen this statement because, he found that butter-fat stained with Sudan III lost the stain during absorption (soaps will not stain with Sudan III) ; Sudan-staining fat was seen in the lumen of the intestine; none was seen in the intestinal epithelium and a Sudan-staining fat was again found in the lacteals of the villi. The weight of evidence, therefore, is that fat must be converted into a water soluble form, soap, before it can be absorbed. The fate of glycerin, the other end product of fat-splitting is un- known. Noll 2 and Wilson 3 conclude from their studies with animals that the epithelium of the intestinal mucous membrane plays a part in the absorption of fat. The emulsified fat is taken up into the striated cells bordering the villi. These cells contain a con- siderable amount of fat before the fat can be detected in the lac- teals. A stage is then reached in which the fat content of the mu- cosa further increases and at the same time removal through the lacteals sets in. The fat is then found in the lacteals until all the fat has been removed from the epithelial cells. There is hardly any evidence to show that the fat can be carried from the epithelial cells to the lacteals by leucocytes. Samelson 4 has found a fat- splitting enzyme in the blood of infants. About two-thirds of the fat in the food enters the thoracic duct as chyle and may be accounted for in this way. The fate of the other third is not clear. It may find its way to the liver by way of the intestinal capillaries. The subsequent course and fate of fat was unknown until Bloor 5 added new light to the subject. He found that lecithin in the blood increased during the absorption of fats. This increase was mostly in the blood corpuscles and very little in the plasma. The fatty acids increased in both plasma and corpuscles, but to a greater extent in the latter; while cholesterol showed no change during digestion. Bloor con- cludes that the close connection between the fatty acids and lecithin can be interpreted to mean that all absorbed fat passes through the lecithin stage. 1 Whitehead: Am. Jour. Physiol., 1909, xxiv, 294. 2 Noll: Arch. ges. Physiol., cxxxvi, 208. 3 Wilson: Trans. Canadian Inst. Sept., 1906, viii, 241. 4 Samelson: Zeitschr. f. Kinderh., 1912, iv, 205. 6 Jour. Biol. Chem., 1916, xxiv, 447. DIGESTION OF FAT 23 When the fat has entered the blood stream it can be demon- strated by the ultra microscope. When fat is present in the blood after food has been taken, the condition is called digestion lipemia. It commences two to three hours after meals and disappears after seven to eight hours. 1 The height of the curve is dependent on the amount of fat hi the food, and also on the age and condition of the infant. The absorption of fat is extraordinarily good in health in babies fed on cow's milk as well as in those fed on human milk. It is usually over 90% and may be as high as 98% of the fat ingested; 2 8% to 11% of the ingested fat is absorbed hi the upper part of the small intestine 3 and the absorption of fat is nearly com- plete at the ileocecal valve. 3 The large intestine is capable of ab- sorbing fat in large amounts under special favorable conditions, 4 but under ordinary circumstances absorption here is probably very slight. The results of estimations of the amount of fat in the stools of babies in starvation and in health make it probable that the greater part of the fecal fat comes from the food and not from the intestinal secretions. 5 It is evident, therefore, that the study of the fat in the stools with the microscope will give valuable infor- mation about the digestion. It is necessary first to know how much fat may normally be found in a stool. There is a comparatively large amount of fat present in the first days of life, and this amount gradually becomes less as the babies grow older, 6 decreasing from 50% of the dried stools to between 14 and 25%. There is so much fat passed in the stools during the early weeks that it is practically impossible to ascertain by simple microscopic ex- amination whether there is an excess or not. In later infancy less fat is present and, therefore, microscopic examinations are of more value. In normal and in many pathologic conditions the greater part of the fat, 75% or more, is in the form of fatty acids and soaps. Neumann: Wien, klin. Wochenschr., 1907, 851; Schelble: Munchen med. Wochenschr., 1908, No. 10, p. 492; Bahrdt: Breslauer Tagung der Freien Ver- einigung fur wissenschaftliche Padiatrie, 1908; Monatschr. f. Kinderh., vii, 106. 2 Czerny and Keller: "Des Kindes Ernahrung, ErnahrungstSrungen und Emahrungstherapie," Leipzig u. Wien, 1906, I, 263; Freund: Ergebn. d. inn. Med. u. Kinderh., 1909, iii, 139. 3 Levites: loc. cit. * Hamburger, H. J.: Engelmann's Arch., 1900, 433. 6 Czerny and Keller: loc. tit. Talbot, F. B.: Boston Med. and Surg. Jour., 1909, vol. clx, No. 1, 13. 24 METABOLISM OF FAT METABOLISM Methods. Most of the earlier figures of the metabolism of fat were obtained by the Rosenfeld extraction method, 1 or one of its modifications. Later Kumagawa and Suto 2 criticised these meth- ods and devised a saponification method which goes under their name. These two methods are the ones most commonly used on the continent. The Folin-Wentworth method 3 (extraction) is now used in America almost to the exclusion of the other two methods. Gephart and Csonka 4 have recently shown the pres- ence of errors in all of the above methods and have described a method by which they have endeavored to overcome these errors. 5 Up to date there are no metabolism figures in infancy which were obtained by this method. When the methods are studied, it be- comes obvious that figures obtained by one method cannot fairly be compared with those obtained by another method, because they probably do not represent the same things. It is obvious also that slight differences in figures are of no significance and that only the most striking differences are of practical importance. Un- fortunately, the clinical status of the infant is not sufficiently con- trolled and recorded in most instances and the possibilities of error, both from errors in chemical technique, and in clinical ob- servation, are numerous. Despite these facts, it seems wise to summarize what we think we know about the digestion and ab- sorption of fat in health and disease. Fat Excretion on Fat-free Food. A careful analysis of the figures that are at present available shows that even when the quantity of fat in the food is very minute, an ether soluble sub- stance, which is recorded by investigators as fat, is found in the stools. In .most instances in infants the amount of this substance is smaller than the amount of fat in the food, and if it is fat it might very well originate in the food. 6 On the other hand, since fasting adults have had small quantities of fat in the stools, it is argued that this fat must come from the body. The amount of 1 Rosenfeld: Centralb. f. inn. Med., 1900, xxi, 833. 2 Kumagawa and Suto: Biochem. Zeitschr., 1908, viii, 212. 3 Folin and Wentworth: Jour. Biol. Chem., June, 1909-10, vii, 421. 4 Gephart and Csonka: Jour. Biol'. Chem., Dec., 1914. 5 A Rapid Nephelometric Method for the Determination of Fat in the Stools has been recently described by Laws and Bloor: Am. Jour. Dis. Chil- dren, 1916, xi, 229. 6 See expts. of Aschenheim (Kumagawa and Suto method), Jahrb. f. Kin- derh., 1913, Ixxvii, 505. METABOLISM OF FAT 25 fat in question is so small that the discussion is of more theoretical than practical importance. Fat Absorption in Health. It is generally agreed that the fat absorption of healthy infants is very high both in the breast-fed and in the artificially fed. Uffelmann * found that a breast-fed infant absorbed approximately 97.8% of the fat ingested. Shaw and Gilday 2 found the absorption 96%, while Nobe'court and Merklen 3 found the absorption of fat respectively 98.3, 99.7, 98.27, 98.23, and 98.62% in five healthy breast-fed infants. Fur- ther figures are given by Czerny and Kellar. 4 The absorption of fat in normal artificially-fed babies is also extraordinarily good and, according to Freund, it may remain ab- solutely normal even under abnormal conditions of nutrition. He records instances with "soap stools" in which the fat absorption reached as high as 97% of the intake (see Czerny and Kellar, 5 and Freund). 6 Freund gives 91.86% to 98.98% as the figures for the absorption of fat for healthy, breast-fed infants. The figures are somewhat lower in the babies he calls "apparently normal," but analyses of these figures show that these babies are considerably under the average weight for their age and can, therefore, not be considered "average normal." Nevertheless many of these infants show a very good absorption of fat. The significance of fatty acids and soaps is as yet unknown. Freund 7 has shown that an acid dyspeptic stool can be changed in many instances to a formed "soap stool" by a relative increase in the amount of casein, while an alkaline soap stool can be changed into an acid stool by a relative increase in the amount of carbohy- drates. Coincident with the change from an acid to an alkaline stool there is a change of the intestinal flora. Bahrdt 7 in contradis- tinction to Freund (see p. 22) has recently shown that babies passing "soap stools" may have diminished powers of absorption and that they may lose more than was formerly taught. He found the absorption of fat (Kumagawa and Suto method) as follows: 1 Uffelmann: quoted by Tobler and Bessau, loc. cit. *Shaw and Gilday: Brit. Med. Jour., 1906, ii, 932. 3 Nobe'court and Merklen: Rev. mens d. Mai. de 1'enfance, 1904, xxii, 337. 4 Czerny and Kellar: loc. cit. 6 Freund: Ergeb. d. inn. Med. u. Kinderh., 1909, iii, 158-159. 8 Freund: loc. cit. > Bahrdt, H.: Jahrb. f. Kinderh., 1910, bad, 249; Holt, Courtney & Fales: Am. Jour. Dis. Children, 1915, ix, 533. 26 METABOLISM OF FAT TABLE 9 Name of baby Age, months Body Weight, gm. Fat ab- sorbed, per cent Character of stools Schroder, 7 days. . . . 9 7470 82 4 "Soap stools" Schuler, 7 days .... 2 3945 83 2 Mostly "soap stools" Weiss la, 5 days 9/io 3750 81 9 "Soap stools" Weiss, Ib 9/K> 3750 86.0 "Soap stools" Weiss II, 8 days (Breast and skim milk) 10 3900 93.0 Normal stools The fat absorption in these babies with "soap stools" is, there- fore, considerably less than that of normal infants. There is, how- ever, not such a loss of fat as in diarrhea. The formation of "soap stools" may be prevented by the addition of whey to the diet. 1 It is very difficult to determine in the cases that have not been previously investigated how much their powers of digestion had been injured by previous poor feeding or disease. Conclusions as to the effect of the food on sick babies, on this account, must be very conservative. There seems to be little doubt, however, that increased peristalsis results in an increased loss of fat in the stools. Certain phases of this question will be considered in more detail later. Increased loss of fat in the stools may occur in any diarrhea, whether it be due for example, to an acute infection, or to chilling, or to an excess of sugar in the food. Birk's observations on Groe- ger III, during a period in which the temperature was elevated and there were frequent thin stools, showed an absorption of only 79%. Courtney 2 says that the lowest absorption in her cases, Janes 52.3% and Stoker 34.2%, was the result of increased peristal- sis and diarrhea. Usuki 3 found that when large amounts of malt extract were added to the food of an infant with alkaline stools the loss of fat in the stools increased from 10% to 15%. The same results were recorded for lactose by Talbot and Hill, 4 who found in their case that the absorption of fat while the digestion was good was 90% and that during a "sugar diarrhea" it dropped to 75%. The percentage of fat in the dried stool is higher in parenteral febrile infections than in health. Uffelmann 5 found, for example, 1 Giffhorn: Jahrb. f. Kinderh., 1913, Ixxviii, 531. 2 Courtney: Am. Jour. Dis. Children, 1911, i, 321. Usuki: Jahrb. f. Kinderh., 1910, Ixxii, 18. Talbot and Hill: Am. Jour. Dis. Children, 1914, viii, 218. B TJffelmann: quoted by Tobler and Bessau, loc. cit. METABOLISM OF FAT 27 that in an eight months' old infant with acute bronchitis and fever the fat excretion in the stools was as follows : TABLE 10 Fat 4th day 40.7% of dried stool 7th day 37.8% of dried stool 9th day 25.0% of dried stool 13th day 15.2% of dried stool Fat Diarrhea. Demme * and Biedert 2 described a condition which they called a fat diarrhea which was characterized by frequent, acid, diarrheal stools. Tobler thinks that, on account of their acidity, these stools are not characteristic of a primary fat indigestion, but that they may be secondary to some other form of indigestion which causes rapid peristalsis. He cites, as evi- dence in favor of this point of view, the fact that such a diarrhea will stop when the food is changed to "Eiweissmilch," even though the percentage of fat remains the same. It is a fact, nevertheless, that in certain instances, in which very large amounts of fat have been fed to young infants, they have passed three or four stools daily of the yellow color of Indian meal and the consistency of mush. Careful inspection of such stools shows drops of oil on the surface of and intermixed with the stool, while the microscope shows that the stool is composed almost entirely of fat. When the amount of fat is reduced in these cases without any other change in the food, the digestion becomes normal. Such cases are true fat diarrheas. Whether the fat in the stool is in the form of fatty acids or soaps depends chiefly upon the reaction of the stool, which in its turn depends upon the relation of the food components to each other. Talbot 3 has shown that "soft curds" or fatty curds, when al- kaline to litmus paper, are composed principally of soaps and, when acid to litmus paper, principally of fatty acids. The presence of a large amount of soaps presumably affects the absorption of the various salts. The technical difficulties in deter- mining the amount of calcium and other salts in the stools, make nearly all the figures very unreliable. 4 The usual conclusions from metabolism experiments are that in the normal infant, with 1 Demme: Jahrb. iiber die Thatigkeit des Jennerschen Kinderspitals in Berlin, 1874 and 1877; quoted by Hecht, Die Faeces des Sauglings, etc., p. 128. * Biedert: Jahrb. f. Kinderh., 1879, xiv, 336; ibid., 1888, xxviii, 21. * Talbot: Boston Med. and Surg. Jour., 1909, clx, 13. 4 According to Prof. Folin only those figures of the calcium metabolism obtained by McCrudden's methods are of any value. 28 METABOLISM OF FAT a normal fat absorption, a high fat intake does not change the mineral composition of the stools, while in chronic malnutrition the output of salts in the feces is considerably raised by increasing the fat in the diet. 1 Olive oil is considered by some authors to have a beneficial ac- tion on the absorption of fat. The metabolism experiments of Courtney 2 and Freund 3 apparently bear out this belief. Infantile Atrophy. "Alimentary decomposition" of Finkel- stein (" Marasmus"). When the literature of the metabolism of "infantile atrophy" is studied the first questions which arise in the student's mind are what is the clinical picture of "infantile atrophy," and are all the cases reported under that name suffering from the same disease. The summaries of the clinical histories are so meager that it is impossible to draw any definite conclusions from them and the statement of the investigator as to the clinical status of the given infant has to be accepted. This state of affairs is, of course, unfortunate, but with the present disagreement among authorities as to what the disease really is, it cannot be remedied. With modern improvements in the methods of di- agnosis it is possible to separate out chronic tuberculosis and hereditary syphilis as definite clinical entities. Prematurity should also be set aside by itself. This leaves, to be classed as "infantile atrophy," those cases which correspond to Holt's 4 definition, that "infantile atrophy is the extreme form of malnutrition seen in infancy, occurring so far as is known, without constitutional or local organic disease. It is a vice of nutrition only." There must be many stages of the disease if there is such a clinical entity. These facts must be borne in mind in considering the subse- quent remarks. The fat content of the body of an atrophic infant as compared with the normal is very much diminished. Ohlmiiller 5 found that the body of an atrophic infant contained only 3% fat as com- pared to 21% in a normal infant. Steinitz 6 analyzed the bodies of three atrophic infants, weighing 3190, 2625 and 1960 grams, and found that the total amount of fat was respectively 63.6, 37.9 and 35.9 grams, or from 1.45 to 1.99% of the total mass, as compared with from 12.3% to 13.1% in the normal. 1 Freund: Ergeb. d. inn. Med. u. Kinderh., 1909, iii, 139. 'Courtney: Am. Jour. Dis. Children, 1911, i, 321. 8 Freund: Biochem. Zeitschr., 1909, xvi, 453. 4 Holt: Dis. of Infancy and Childhood, N. Y. and London, 1911, p. 227. 6 Ohlmuller: Zeitschr. f. Biol. 1882, xviii, 78. Steinitz: Jahrb. f. Kinderh., 1904, lix, 447. METABOLISM OF FAT 29 A fatty liver is occasionally found at post-mortem examination, but, according to Holt, " This lesion is not more frequent in this condition than in infants dying of other diseases." Hayaslei l recently showed that in five out of eight cases of "infantile at- rophy" the liver contained neither fat nor lipoid substances. In two cases the livers were fatty. According to many authors 2 the digestive ferments are more or less diminished and weakened in infantile atrophy. This is especially true of the fat-splitting ferment. Hecht believes that there is a connection between the severity of the disturbance and the diminution in the amount of steapsin. Wentworth 3 found that secretin was either diminished or absent in these cases. The metabolism of fat varies. Freund 4 found that two atrophic infants with "milchnahrschaden" (soft curds) absorbed respec- tively 90% and 97% of the fat, except in one instance when one absorbed only 81.8%. Bahrdt, 5 on the other hand, found an absorption of only 81.9, 82.4, 83.2, 86.0 and 93%. L. F. Meyer 6 studied "infantile atrophy" in different stages and with different foods. He found in baby Kajitzki in periods I and II, in which whole milk, diluted one-half, was given, that the absorption of fat was respectively 74.2% and 24.9%. In the first period there was a slight gain in weight, and in the second period a marked loss in weight, with a corresponding loss of fat in the stool. In periods III, IV, and V, the absorption of fat was respectively 51.0, 68.3, and 78.6%, and during the last period there was a gain in weight. Baby Bentler did not show the same loss of fat, but there was a greater retention of fat when human milk was given than when cow's milk was given. Fife and Veeder 7 studied two cases which they considered to be "infantile atrophy" and found that the fat absorption (Brugsch method for fat) was less than in normal infants. Curiously enough, the per cent of fat absorbed was larger when large amounts of fat were given than when small amounts were given. They did not find that the carbohydrates in the food had any influence on the fat absorption, but their evidence in this respect is incom- plete. V-Hayaslei: Monatschr. f. Kinderh., 1913, xii, 221. 2 Tobler and Bessau: loc. cit. 130. 3 Wentworth: Jour. Am. Med. Assoc., 1907, xlix, 204. * Freund: Biochem. Zeitschr., 1909, xvi, 453. 6 Bahrdt: quoted by Tobler and Bessau, loc. cit. Meyer, L. F.: Jahrb f. Kinderh., 1910, Ixxi, 379. 7 Fife and Veeder: Am. Jour. Dis. Children, 1911, ii, 19. 30 METABOLISM OF FAT Wentworth l studied the fat metabolism (Folin-Wentworth method), of an atrophic infant and found that its tolerance for the fat in human milk was much greater than for that of cow's milk. His results were confirmed in the case of KajitzkL 2 He was un- able to determine whether this difference in the absorption of the two kinds of fat was due to a difference in the fats themselves or to some other ingredient in the milk. Hecht 3 and Reuss 4 have reported cases of congenital oblitera- tion of the bile duct with normal pancreas, hi which only one-half of the fat was split. In Niemann's case 5 of an infant with ad- vanced biliary cirrhosis and congenital absence of the bile ducts, the nitrogen absorption was from 80% to 93% and the fat absorp- tion from 28% to 39%. In Koplik and Crohn's case 6 the nitrogen absorption was 86.2% and the fat absorption 48.4%. Very much less than the normal amount of fat was split. Similar types of stools with large amounts of unsaponified fat have been observed by us clinically. 7 These figures show that in the infant as well as in the adult, bile is necessary for the normal splitting and absorp- tion of fat. Tubercular peritonitis in babies is primarily a disease of the lymphatic system and when the mesenteric glands become caseous they form a dam beyond which the fat cannot pass. It has been shown earlier that most of the fat is normally carried by the lym- phatics to the blood stream. If this road is blocked with tuber- culous tissue, it is reasonable that some of the fat should be lost from the body. Talbot 8 studied cases with tuberculosis of the mesenteric glands and found that in all cases in which a large proportion of these glands were involved there was a loss of fat through the intestines. Hecht 9 believes that 8% of the fat in the stool should be split, and considers that great divergence from this amount means either trouble with the bile or pancreatic juice. He reports the case of a seven months, premature baby which was able to split only 53% of the fat, and considers this to be due to 1 Wentworth: Boston Med. and Surg. Jour., 1910, clxii, 869, and Archives Int. Med., 1910, vi, 420. 2 Meyer, L. F. : loc. cit. 1 Hecht: "Die Faeces des Sauglings und des Kindes," Berlin- Wien, 1910, 128. 4 Reuss: Case of Obliterated Bile Duct (congenital) Reported in Discus- sion, Jahrb. f. Kinderh., Dec., 1908, 729. 6 Niemann: Zeitschr. f. Kinderh., 1912, iv, 152. 6 Koplik and Crohn: Am. Jour. Dis. Children, 1913, v. 36. 7 Morse, J. L.: Boston Med. and Surg. Jour., 1910, clxii, 238. 8 Talbot: Am. Jour. Dis. Children, 1912, iv, 49. (See literature.) Hecht: loc. cit. METABOLISM OF FAT 31 weak action of the pancreatic fat-splitting enzyme, which pre- sumably is not completely developed. Finizio l explains a large amount of fat in the stool of an eleven months' old baby ill with mumps by probable trouble hi the pancreas. In this case 75% of the dried stool was fat, and of this only 7% was soaps, while 11% was fatty acid and 82% neutral fat. Czerny 2 believes that babies with an exudative diathesis can be harmed by fat. He finds that an increase in the amount of fat in the food will bring out eruptions on the skin. Steinitz and Weigert 3 have apparently proved the correctness of this assum- tion by a metabolism experiment. Towle and Talbot 4 studied the digestion of infants ill with ec- zema and found that in a large number of cases the severity of the skin eruption bore a direct relation to the fat in the food. This was by no means the case in all instances, but there was a sufficient number to substantiate Czerny's findings. There is no doubt that large amounts of fat can do a great deal of harm to most babies. Such babies come under two classes, those which have a normal digestion and are unable to digest ex- cessive amounts of fat, and those which have diminished powers of digestion and are unable to digest normal amounts of fat. So much attention has been paid to the few babies that are unable to digest fat that we are apt to forget that most babies can digest fat within reasonable limits. L. F. Meyer 5 has shown in Finkel- stein's clinic that when fat is increased in the food of normal healthy babies there is no loss of fat or salts from the body. This dispels, in a very convincing way, the false impression that normal babies are unable to digest fat. Rowland has shown in a recent investigation (not yet published) that a baby can be fed on large quantities of fat without symptoms of indigestion and without acidosis. 1 Finizio: Pediat. Sept., 1909, 674; Rev. in Archiv. f. Kinderh., 1910, liv, 461. 1 Czerny: Part I, Monatschr. f. Kinderh., 1906, iv, 1; ibid., Part II, 1908, vi, 1; ibid., Part 3, 1909, vii, 1. 1 Steinitz and Weigert: Monatschr. f. Kinderh., 1910, ix, 385. < Towle and Talbot: Am. Jour. Dis. Children, 1912, iv, 219. Meyer, L. P.: Jahrb. f. Kinderh., April, 1910, 379. CHAPTER III THE DIGESTION AND METABOLISM OF CARBO- HYDRATES FERMENTS Saliva. Zweifel * found diastase in the parotid gland of the newly-born, but was unable to find it in the submaxillary. Ibra- him, 2 after prolonged investigations, found it in both the parotid and submaxillary glands, its action being stronger in the former than in the latter. Diastase was found much earlier in fetal life in the parotid than in the submaxillary, traces being found in the former at the fourth and in the latter at the sixth month of fetal life. The diastase of the parotid is the earliest digestive fer- ment found in the embryo. A diastatic ferment can always be found in the saliva of healthy infants. 3 The diastatic action of saliva may continue in the stomach as long as two hours after feeding. 4 Stomach. Ibrahim 5 is the only worker who has examined the gastric mucous membrane of the newly-born for the carbohydrate splitting ferments, and he has been unable to find either lactase, maltase or invertin. Pancreas. Moro 6 was able to demonstrate the presence of an amylolytic ferment in the pancreas of newly-born babies when the pancreas was thoroughly extracted, and thus disproved the earlier work of Zweifel and Korowin. Ibrahim 7 never failed to get the ferment in a six months' fetus when he tested the action of the 1 Zweifel: Untersuchungen iiber den Verdauungsapparat der Neugeborenen, Berlin, 1874. 2 Ibrahim: Verhandl. d. Gesell. fur Kinderh., Koln, 1908, p. 21. 'Schiffer: Berl. klin. Wochenschr., 1872, ix, 353; Korowin: Jahrb. f. Kin- derh., 1875, viii, 381; Zweifel: loc. tit.; Schlossmann: Jahrb. f. Kinderh., 1898, xlvii, 116; Montagne: Dissertation, Leyden, 1889, quoted in Czerny and Keller, "Des Kindes Ernahrung," etc.; Schilling! Jahrb. f. Kinderh., 1903, Iviii, 518. 4 Shaw: Albany Med. Ann., 1904, xxv, 148. 6 Ibrahim: loc. cit. Moro: Jahrb. f. Kinderh., 1898, xlvii, 342. 7 Ibrahim: loc. cit. 32 DIGESTION OF CARBOHYDRATES 33 ferment on starch meal. He was, however, unable to find it when he tested soluble (i. e., cooked) starch. Ibrahim was unable to demonstrate invertin and lactase in the pancreas of newly-born or older babies, but he was usually able to demonstrate maltase in the newly-born and always in older chil- dren. Maltase may also be found in the blood. Small Intestine. The mucous membrane of the small intes- tine contains amylolytic ferments. Lactase, the ferment which splits milk sugar, has been repeatedly found in the mucous membrane of the small intestine. 1 Ibrahim always found it in the small intestine and meconium of newly-born babies, but was unable to find it in premature infants. He says, however, that his method of determining lactase is not capable of demonstrating small amounts. Lactase is more abundant in young animals than in the adult. Pautz and Vogel found maltase, the ferment which splits malt sugar, in the small intestine of infants. Invertin, the ferment which splits cane sugar, was found in the secretions of the small intestine of the newly-born by Miura 2 and Ibrahim was always able to demonstrate its presence both hi the intestinal mucous membrane and in the intestinal contents of all fetuses. Large Intestine. It is difficult to wash the large intestine free from meconium, and the results of the examinations of its mucous membrane are variable, as the tables of Miura, Pautz and Vogel show. It is, therefore, impossible to say whether it contains fer- ments or not. Stools. Pottevin 3 found an amylolytic ferment in the me- conium. Kerley, Mason and Craig 4 were able to demonstrate the presence of a strong amylolytic ferment hi the stools of very young babies, the possibility of the bacterical fermentation of starch being excluded. There is a larger amount of diatase in the stools of breast-fed babies than in those of the bottle-fed, which Hecht 5 believes to be due to the fact that the intestinal contents of the breat-fed baby pass more quickly through the intestinal canal than do those of the bottle-fed baby. The power of digesting starch, while occasionally absent is, therefore, almost always pres- 1 Pautz and Vogel: Zeitschr. f. Biol., 1895, xxxii, 304; Weinland: ibid., 1899, xxxviii, 16; Orban: Prag. med. Wochenschr., 1899, xxiv, 427. 2 Miura: Zeitschr. f. Biol., 1895, xxxii, 266. Pottevin: Compt. rend, de la Soc. biol., 1900, Hi, 589. 4 Kerley, Mason and Craig: Arch. Pediat., 1906, xxiii, 489. 6 Hecht: "Die Faeces des Sauglings und des Kindes," Berlin, 1910. 34 DIGESTION OF CARBOHYDRATES ent both in the fetus and in the newly-born. Hess l always found it present during the first week of life, the amount of the ferment increasing with the age of the infant. Young babies are, neverthe- less, able to adapt themselves to a food rich in carbohydrates. There is according to Moro, 2 a rapid increase in the power of digesting starch during the first week of life. The baby, therefore, has a power of digesting starch at birth which gradually increases in strength as the baby grows older. It can digest twice as much at eight months as it can at birth, and at twelve months as much as a three year old child. 3 The digestibility of starch is obviously dependent on the way it is prepared and cooked. The question whether the carbohyrate-splitting ferments are affected by disease has been answered only in part. Orban 4 found by animal experimentation that an injured intestinal mucous mem- brane contained no lactase, and that the stools of babies ill with enteritis contained no lactase. Langstein and Steinitz 5 on the other hand, always found lactase in the stools of babies ill with enteritis, whether mild or severe, acute or chronic. Nothmann 6 was unable to demonstrate lactase in the stools of seven premature babies on the first day post partum, but found it always after milk had been fed. FORMS OF CARBOHYDRATES The forms of carbohydrates commonly used in infant feeding may be divided into the groups given in the following table (taken from Reuss 7 ). 1 Hess: Am. Jour. Dis. Children, 1912, iv, 205. 2 Moro: Jahrb. f. Kinderh., 1898, xlvii, 342. 3 Finizio: Rev. d. Hyg. et Med. Inf., 1909, viii, 224. 4 Orban: Prag. med. Wochenschr., 1899, xxiv, 427. 8 Langstein and Steinitz : Hoffmeister's Beitrage, 1909, vii, 575. 8 Nothmann: Monatsschr. f. Kinderh., 1909-10, viii, 377. 7 Reuss: Wien. med. Wochenschr., 1910, Ix, Nos. 28, 29, 30. DIGESTION OF CARBOHYDRATES TABLE 11 35 Milk sugar group Cane sugar group M alt sugar group Starch (Amylum) Dextrin (Amylo-dextrin) I Erythro & Achro-dextrin 1 Lactose (milk sugar) Saccharose (cane sugar) Maltose (malt sugar) I 1 1 Dextrose + Galactose Dextrose + Levulose Dextrose + Dextrose DIGESTION OF CARBOHYDRATES The carbohydrates are broken down during digestion into the simplest forms of sugar, the mono-saccharides, by the various fer- ments described above. According to Rohmann * a considerable amount of the di-saccharides may pass into the intestinal mucous membrane and there be split into mono-saccharides. The mono- saccharides are carried from the portal vein to the liver, where they are transformed into glycogen, the only difference being that dextrose is more easily converted than levulose or galactose. 2 Sugars may also be carried into the blood by way of the thoracic duct, 3 but ordinarily very little is absorbed in this manner. The pancreas has some influence on this process because extirpation of the pancreas in dogs results in sugar in the urine and interferes with the formation of glycogen in the liver. The liver actually has the property of forming glycogen from sugar. 4 The purpose of the splitting of the poly- and di-saccharides into mono-saccharides is to prepare them for use inside the body, be- cause the unsplit carbohydrates are not burned up in the body, but are excreted in the urine. The transformation of sugar into glyco- gen which is deposited in the liver and muscles, is of great impor- tance because this glycogen can be converted again into sugar according to the needs of the body. Rohmann: Pfluger's Arch. 1903, xcv, 533. 2 Alderhalden: Textbook of Physiological Chemistry, London, 1908. 1 Hendrix & Sweet: Jour. Biol. Chem., 1917, xxxii, 299. Grube: Pfluger's Arch., 1905, cvii, 490. 36 DIGESTION OF CARBOHYDRATES There is normally about 0.1 of dextrose in the blood. The slightest disturbance of the regulating apparatus will cause a hyperglycemia which results in glycosuria. A deficit of sugar in the blood is made up from the glycogen deposits. 1 ' The mono- saccharides are absorbed more quickly than the di-saccharides. 2 Niemann 3 found that a large proportion of infants respond to food with an alimentary glycemia but that the intensity varies within a wide range. The highest blood sugar (Bang's micro- method) is invariably found in infants thriving well on large amounts of carbohydrate. Other infants which show only a slight amount of alimentary glycemia, as a rule do not thrive on car- bohydrates. According to Bergmark 4 feeding cane sugar leads to a greater increase in blood sugar than does maltose or lactose, and maltose causes a greater increase than lactose. A large part of the digestion and absorption of the carbohydrates takes place in the upper part of the small intestine. 5 Splitting and absorption may also take place in the large intestine. 6 The bacteria of the stomach and intestines attack not only cellulose but other carbohydrates as well. The decomposition of the carbohydrates by means of bacteria, in general, is not very- extensive and depends very much on the external conditions. The products formed by their action are chiefly lactic acid, acetic acid, formic acid, butyric acid and alcohol with, in addition, the evolu- tion of carbon dioxide, hydrogen, and methane. 7 In abnormal conditions the bacteria probably play a much more important part in the breaking down of carbohydrates. Little or no sugar can be found in the stools under normal condi- tions, but when the food passes quickly through the intestinal canal, as it does when the peristalsis is increased as the result of disease or indigestion, sugar may be found in the stools (Hecht). Usually, only the products of the decomposition of sugar can be isolated. Hedenius 8 fed babies on milk mixed with wheat flour, oat 1 Langstein-Meyer: Sauglings Ernahrung und Sauglingsstoffwechsel, Wies- baden 1910. "He'don: Compt. rend, de k Soc. de Biol., 1900, 29; Nagano: Pfluger's Archiv., 1902, xc, 389; Rohmann: Chem. Bei., 1895, xxviii, 2506. 3 Jahrb. f. Kinderh., 1916, Ixxxiii, p. 1. 4 Bergmark: Jahrb. f. Kinderh., 1914, boot, 373. 5 London and Polowzowa: Zeitschr. f. physiol. Chem., 1906, xlix, 328. 8 Reach: Arch. f. exp. Path u. Pharm., 1902, xlvii, 230; SchOnborn: Diss. Wurzburg, 1897; Pehu and Porcher: Rev. d'Hyg. et de Med. Inf., 1910, ix, 1. 7 Tappeiner, H.: Zeitschr. f. Biol., 1883, xix, 228. 8 Hedenius: Ueber das Schicksal der Kohlehydrate im Sauglingsdarm. DIGESTION OF CARBOHYDRATES 37 gruel or Keller's malt extract and measured the amount of carbohydrate ingested, the amount found in the stools, and the acidity of the stools. He found less carbohydrate in the stools when simple cereals were used than when the more compli- cated mixtures were given. He also found that the more car- bohydrate there was in the stool, the greater was its acidity. He never found more than 3% of the ingested carbohydrate in the stools. Raczynski l has shown that in babies sick with what he calls "dyspepsia intestinalis acida lactorum," the acidity of the intestinal contents is increased and the utilization of fat diminished. Talbot and Hill 2 found in their case (J. P.), that an increasing amount of lactose in the food did not appreciably influence the titratable acidity of the stool until a diarrhea commenced. The acidity then increased 500% and lactic, acetic, succinic and butyric acids were found to be present. This fact seemed to indicate that the acid-forming bacteria played an important part in the breaking down of the sugar. This assumption finds support in the studies of Bahrdt and Bamberg, 3 who concluded that acetic acid was more effective in causing diarrhea than the other volatile fatty acids, and that it was undoubtedly formed in the small intestine through the agency of the intestinal bacteria. 4 Bahrdt and Mc- Lean b found that the volatile fatty acids in the stools of infants fed on breast milk increased when sugar was added to the milk. The same is true of bottle fed infants with acute digestive dis- turbances. They are not, however, always due to sugar but may also be due to the decomposition of fat. Keller 6 has shown that carbohydrates make the digestion of protein more complete. Talbot and Hill 2 have recently confirmed these findings. A possible explanation of the protein-sparing ac- tion of carbohydrates may be found in the work of Kendall and Farmer 7 on the metabolism of bacteria. They found that in the test-tube, when sugar was present in the food, less ammonia nitro- gen was formed than when sugar was absent. If the results ob- 1 Raczynski: Wien. klin. Wochenschr, 1903, xvi, 342. 2 Talbot and Hill: Am. Jour. Dis. Children, 1914, viii, 218; Weill & Du- fourt: La. Nourrisson, 1914, ii 65. 'Zeitschr. f. Kinderh., 1912, iii, 322. 4 Edelstein and Csonka: Biochem. Zeitschr., 1912, xlii, 372. 8 Bhardt and McLean: Zeitschr. f. Kinderh., 1914, xi, 143. 6 Keller: "Des Kindes Ernahrung," etc., loc. ell. 7 Kendall and Farmer: Jour. Biol. Chem., 1912, xii, 13; 1912, Nos. 1, 2 and 3; 1912-13, xiii, 63. 38 METABOLISM OF CARBOHYDRATES tained in the test-tube are applicable to the intestinal canal, the reason that more nitrogen is retained in the body when sugar is present is not because the sugar makes the nitrogen more easily absorbable, but because the intestinal bacteria use the sugar in preference to the protein and form less nitrogen to be carried away in the stools. In other words, the bacteria leave a larger amount of nitrogen for absorption than when they grow on a sugar-free pro- tein. Cathcart * and Janney 2 suggest that carbohydrates are es- sential to protein synthesis. Kocher 3 showed that lactic acid also spared protein. His work adds support to the possibility that the combination of ammonia, a product of protein metabolism with the dissociation products of glucose to form new proteins, is the mechanism by which this sparing action is effected. Albertoni 4 and He"don 5 found that sugars have a purgative action when they are given in large enough amounts. This action is more marked when they are taken in concentrated solution. All sugars have this action, the difference between them being only in degree. They found that glucose and cane sugar are much more quickly absorbed than lactose, and that glucose has less of a purgative action than the cane sugar. According to the extensive experiments of Rohmann and Nagano 6 saccharose is absorbed more quickly than maltose. Block 7 reports instances of infants fed on an exclusive carbo- hydrate diet, who seemed to be fat and well, but suddenly be- came ill and died. They had either sclerema or oedema. METABOLISM OF CARBOHYDRATES Numerous observations 8 have shown that when milk sugar is injected directly into the circulation it may be completely re- covered in the urine. Grosz 9 was never able to detect milk sugar in the urine of healthy babies, but found it in the urine of those suffering with gastrointestinal disease, in which there was pre- 1 Cathcart: The Physiology of Protein Metabolism, London, 1912, 121. 2 Janney: Jour. Biol. Chem., 1916, xxiv, 30. 3 Kocher: Jour. Biol. Chem., 1916, xxv, 571. 4 Albertoni: Arch. ital. de Biol., xv, xviii, xxx, xxxv, xxxviii, xl. 6 HMon: Compt. rend, de la Soc. de Biol., 1899, 884; ibid., 1900, 29 and 87. 6 Rohmann and Nagano: quoted by Hammarsten and Mandel, "Textbook of Physiological Chemistry," New York, 1912, 509. 7 Block: Ugeskrift f. Laeger, 1917, batix, no. 8, Abstr. Jour. A. M. A., 1917, Ixviii, 1444. 8 Voit: Deutsch. Arch, fur klin. Med., 1897, Iviii, 523. 9 Grosz: Jahrb. f. Kinderh., 1892, xxxiv, 83. METABOLISM OF CARBOHYDRATES 39 sumably an absence of lactase in the intestine. Langstein and Steinitz Repeated Grosz's experiments and in certain instances found lactase in the stools at the same time that sugar was being excreted in the urine. This sugar was, moreover, not always lac- tose, but sometimes galactose, one of the products of the splitting of lactose. They tried to explain this as follows: That some of the sugar passes through areas of the intestinal wall made abnormal by functional or anatomical lesions before it is completely broken up and it is excreted in the urine as an intermediary product of metabolism. Mendel and Keliner 2 have shown that when cane sugar is in- troduced subcutaneously into dogs or cats in doses of one to two grams per kilogram of body weight it is not completely recovered in the urine. The quantity excreted amounts as a rule to more than 65% of that introduced. The excretion begins within a few minutes and is usually completed within thirty-six hours. Fisher and Moore 3 draw attention to the possibility that the sugar thus introduced may be excreted through the walls of the alimentary tract and there be digested. These views are supported by Jappelli and D'Errico, 4 who conclude from their experiments on dogs that when cane sugar is introduced directly into the circulation the quantity eliminated in the urine is never equivalent to the amount injected. This causes both glycosuria and saccharosuria, the for- mer disappearing first. The blood has no power of converting cane sugar. According to these writers cane sugar introduced intravenously is eliminated into the alimentary tract through the gastric mucosa, the salivary glands and, to an insignificant degree, through the bile. The subsequent fate of this component is obvious. In the year 1906, Finkelstein published the first of a series of papers 5 which have caused much discussion as to the etiology of the digestive disturbances of infancy. In the first place he opposed Czerny's teachings as to the harmfulness of fat in infant feeding. He taught that bacteria played no part in the etiology of the 1 Langstein and Steinitz: Moffmeister's Beitrage, 1906, vii, 575. z Mendel and Keliner: Am. Jour. Physiol., 1910, xxvi, 396. 8 Fisher and Moore: Am. Jour. Physiol., 1907, xix, 314. " Jappelli: Ref. Maly's Jahresbericht fur Tierchemie, 1905, xxxv, 79. 6 Finkelstein: Verhandl. Gesellsch. f. Kinderh. (Stuttgart), 1906, xxiii, 117; Jahrb. f. Kinderh., 1907, Ixv, 1 and 263; Jahrb. f. Kinderh., 1908, Ixviii, 521; Deutsch. med. Wochenschr., 1909, xxxv, 191; Finkelstein and Meyer: Jahrb. f. Kinderh., 1910, Ixxi, 525 and Berliner klin. Woch., 1910, xlvii, 1165. For literature and an excellent discussion of the subject, see chapter on "Sugar in the Young " in Allen, "Glycosuria and Diabetes," Harv. Univ. Press, 1913. 40 METABOLISM OF CARBOHYDRATES digestive disturbances of infancy and that the sugars produced symptoms of intoxication. He also undertook to prove that the albumens were quite harmless. He considered that the most acute form of disease of the digestive tract, that accompanied by stupor, fever, and sugar in the urine, was the result of an intoxication caused by sugar. He blamed lactose for the poisoning of the system, and claimed that instantaneuos benefit and cure resulted from the complete withdrawal of sugar. Schaps 1 and Leopold and Reuss 2 also thought that lactose and other sugars were pyrogenic. In 1909, Finkelstein said, "It is possible, with the certainty of an experiment, by giving a dose of sugar (for example 100 grams of a 12.5% lactose solution), to an infant with bowel trouble to force up the previously afebrile temperature into fever, practically with the same certainty as if one should give it a dose of tubercu- lin." His " eiweissmilch " was prepared to cure sugar intoxications. He apparently overlooked the fact that it contained 1J^% or more of the lactose which he considered so poisonous in this con- dition. As his theories developed, he decided that the sugar in- toxication was not due to a sugar injury alone, but to the actions of salts, especially the chlorine-ion combination with sodium. Friberger, 3 Schloss, 4 Cobliner, 5 and Nothmann, 6 confirmed Meyer's statements concerning the pyrexial effects of sodium-halogen com- pounds, while Rosenthal 7 found that in animals neither salt nor sugar had any specific pyrogenic action. In 1910 Finkelstein and Meyer ascribed intestinal irritation to abnormal fermentations. They stated that casein was never harmful and that it prevented or diminished acid fermentation. They stated, on the other hand, that, as Czerny pointed out, fat was more dangerous, but claimed that it was only harmful in a bowel irritated by carbohydrate fermentation. They admitted, at this time, that human milk was the best food to give in these condi- tions, thus abandoning their earlier contention that lactose (which is present in large amounts in human milk) is poisonous. Helmholz 8 found that 5% solutions of sodium chloride, bromide, and iodide injected into rabbits subcutaneously in quantities of 1 Schaps: Verhandl. Gesellsch. f. Kinderh., 1906, xxiii, 153; Berliner klin. Wochenschr., 1907, xliv, 597. 2 Leopold and Reuss: Monatschr. f. Kinderh., 1909-10, viii, 1 and 453. 3 Friberger: Munch, med. Wochenschr., 1909, Ivi, 1946. 4 Schloss: Biochem. Zeitschr., 1909, xviii, 14. 5 Cobliner: Zeitschr. f. Kinderh., ii, 429. 8 Nothmann: Zeitschr. f. Kinderh., i, 73. 7 Rosenthal: Jahrb. f. Kinderh., 1909, Ixx, 123. 8 Helmholtz: Arch, of Internal Medicine, 1911, vii, 468. METABOLISM OF CARBOHYDRATES 41 from ten to twenty-five cubic centimeters caused no rise of temper- ature in the great majority of experiments. Sodium chloride pro- duced a slight rise in temperature when given intravenously in high concentration. A 1% solution of sodium chloride may, in excep- tional instances, produce a febrile rise in temperature when given by mouth. Schlutz * confirmed these findings; he found that lac- tose alone possesses no distinct pyrogenic action, but that it may affect the temperature if it is given in combination with a sodium salt when the intestinal tract is diseased. Allen 2 studied the effects of sugars in young, nursing animals and found that in no instance were there any symptoms of the intoxicating action of sugar, even when the animals received so much sugar by mouth that they had vomiting and diarrhea. He found, furthermore, that subcutaneous injections of glucose had a very beneficial action on animals, even when they had glycosuria and were doing badly. The evidence at hand is opposed to the be- lief that sugar has any specific intoxicating effect or acts as a food poison and is in favor of the theory 3 that it is a medium of growth for bacteria in which they can develop sufficiently to harm the body either by their own activity or by the products which result from then* activity. The limits of assimilation of the different sugars vary and are given as follows: Grape sugar: In babies, about 5 grams per kilogram (Langstein and Meyer). Grape sugar: In one month baby, 8.6 grams per kilogram (Greenfield). 4 Galactose: No accurate data. Levulose: (Lower for babies than adults), one gram per kilogram (Keller). Maltose: Over 7.7 grams per kilogram (Reuss). Lactose: From 3.1-3.6 grams per kilogram (Grosz). Porter and Dunn 5 state that as much as 120 gm. of lactose may be added to the food of infants with indigestion in twenty-four hours without appearing in the urine in sufficient quantities to be determined quantitatively. Cane sugar: Probably about the same as lactose (Reuss). The main facts which are apparently true about the metabolism 1 Schlutz: Am. Jour. Dis. Children, 1912, iii, 95. 8 Allen: "Glycosuria and Diabetes," Harvard Univ. Press, 1913. 3 Escherich: Deutsche Klinik, 1902, vii, 126. 4 Greenfield: Jahrb. f. Kinderh., 1903, Iviii, 666. 6 Porter and Dunn: Am. Jour. Dis. Ch., 1915, x, 77. 42 METABOLISM OF CARBOHYDRATES of carbohydrates in infancy are: carbohydrates are absorbed up to a certain point, lactose being absorbed more slowly than the other di-saccharides. Up to a certain point lactose and maltose increase the retention of nitrogen, but apparently have no or only slight beneficial effect on the retention of ash or the absorption of fats. Carbohydrates may increase the retention of sodium and water. The large pasty infant fed on a high carbohydrate mixture is an example of the effect of a large retention of water. Carbo- hydrates may also be deposited in the body in the form of fat. When too much sugar is given to an infant there is a marked in- crease in the acidity of the intestinal canal and an increased peristalsis, which washes the irritating food out of the bowels as quickly as possible. Large amounts of fat, protein and ash are carried out in the stools, resulting in a diminished absorption and retention of these food components. Some of the elements of ash are lost to a greater extent than others and then- loss may be so large that the output surpasses the intake. Under such circum- stances the organism is drained of part of its own mineral content. Starches act in the same manner as the other carbohydrates except that having a more complicated molecule, they go through one more step in the process of their conversion into a mono- saccharide. Marriott in a paper presented before the American Medical Association, June, 1919, shows conclusively that Finkelstein's theories have no scientific background. Marriott's conclusions should be consulted- on the publication of his paper. CHAPTER IV THE DIGESTION AND METABOLISM OF PROTEIN FERMENTS The saliva of man was shown to contain a proteolytic ferment by Ed. Muller, 1 but up to date such a ferment has not been found in infants. Pepsin was first demonstrated in the mucous membrane of the infant's stomach by Zweifel 2 and later Langendorff 3 extracted it with HC1 from the stomach of a fetus of four months, at which time there is microscopic evidence of glandular formation. The amount of pepsin increases with the age of the baby up to the third month, and from then on remains constant in amount; it is present in larger quantities in bottle-fed babies than in breast-fed babies. 4 Pechstein 5 examined the urines of babies at different ages and under different conditions and found that all babies excrete pepsin and rennin in their urine from the day of their birth onward. These ferments are present only in the form of then* pro-ferments. They are found in minute quantities in the early days of life and increase in amount up to the end of the first year, at which there is about time one-twentieth as much as in the adult. The urine of the artificially-fed baby contains more than does that of the breast-fed baby. During an acute disturbance of digestion they are as abundant as in health, but during chronic diseases they seem to be slightly diminished in amount. When pepsin and rennin are fed to a baby, no traces are found in the urine, and there is no increase in the amount of rennin in the stool. The ferments must, therefore, have been destroyed in the upper intestine or neutralized in the blood stream. If the intestinal mucous membrane is damaged, the ferments appear in the urine. Rennin, and hydrochloric acid are found in the first days of 1 Ed. Muller: Verhandl. d. Cong, fur inn. Med., 1908, 676. * Zweifel: Untersuchungen iiber den Verdauungsapparat der Neugeborenen, Berlin, 1874. 1 Langendorff: Arch, fur Anat. u. Physiol., 1879, 95. 4 Rosenstern: Berl. klin. Wochenschr., 1908, 542. 'Pechstein: Zeitschr. f. Kinderh., 1911, i, 365. 43 44 DIGESTION OF PROTEIN life. 1 Remain has been demonstrated in sterile meconium 2 and a rennin ferment which acts independently of the stomach and pancreas 3 has been found in the stool. Trypsin. Zweifel demonstrated trypsin in the pancreatic ex- tracts of new-born babies, and Langendorff found it at the be- ginning of the fifth month of fetal hie. Ibrahim 4 showed that when absolutely fresh material was used only the pro-ferment trypsinogen is present in the pancreas of the fetus, but that small amounts of trypsin may be present in the pancreas of older chil- dren. This can be markedly increased by activating it with enter- okinase. The pro-ferments are apparently activated by bacteria, which are, of course, not present in the intestinal canal of the fetus. He was able to demonstrate trypsinogen in a six-months-old fetus. Trypsin is found in the feces in small amounts in health and in large amounts during diarrhea caused either by drugs or disease. Sterile meconium has the property of dissolving gelatine. 5 Hecht 6 demonstrated trypsin in the stools of babies as early as the first day of life. Wienland 7 found anti-pepsin in the stomach and anti-trypsin in the intestinal mucous membranes; he believed that their func- tion was to prevent auto-digestion. Cohnheim 8 believes that anti- trypsin is identical with enterokinase and that in small amounts it activates trypsin, and in large amounts prevents its action. Enterokinase. The ferment which activates trypsinogen was first found by Ibrahim, who extracted it from the intestinal mu- cous membrane of new-born babies, and from meconium. It is most active in the lower third of the intestine in the majority of instances; it may also be obtained from the mucous membrane of the large intestine. It apparently first appears in embryonic life at the same time that trypsin is found in the pancreas. Secretin, according to Bayliss and Starling, 9 is necessary for the activation of the pancreas. It may be extracted from the intestinal mucous membrane; it is not destroyed by heat, and belongs to the group of hormones. When injected intravenously it causes a flow of pancreatic juice in about one minute. Ibrahim 1 Szydlowski: Jahrb. f. Kinderh., 1892, xxxiv, 411. 2 Pottevin: Compt. rend, de la Soc. de Biol., 1900, Hi, 589. 3 Th. Pfeiffer: Zeitschr. f. Exp. Path. u. Therap., 1906, iii, 381. 4 Ibrahim: Gesellschaft Deutscher Naturforscher und Artzte in Coin, 1908. 8 Pottevin: loc. cit. "Hecht: Wien. klin. Wochenschr., 1908, xxi, 1550. 'Wienland: Zeitschr. f. Biol., 1903, xliv, pt. I. 8 Cohnheim: Nagel's Handbuch d. Physiol., 1907, ii, 5-7. 9 Bayliss and Starling: Jour. Physiol., 1902, xxviii, 325. DIGESTION OF PROTEIN 45 and Gross * found it in babies who died at birth, but not in pre- mature babies. Wentworth 2 found it absent or present only in small amounts in newly-born babies. He found definite but weak action in a premature baby which had lived three weeks. Older babies, which had died of other diseases than those of the digestive tract, all showed a definitely active secretin. Hallion and Le- queux 3 found secretin in the upper part of the intestine of two newly-born babies, but were unable to find it in the lower part of the intestine. They obtained the same results in a five months' fetus. There is no record of secretin being found in the feces. Erepsin was first demonstrated in the intestinal mucous mem- brane by Cohnheim. 4 It changes albumoses and peptones very rapidly into amino- and diamino-acids, so that the Biuret reaction disappears. It has no action upon the native albumens with the exception of casein. It is present in all babies, including pre- mature infants. 5 Lust 6 found an anti-proteolytic ferment in the blood of an infant fourteen days old, which had the same anti-tryptic power as that in the blood of an infant of one year. There is no increased formation of this ferment in digestive disorders, while in some cases of alimentary intoxication, in which there is loss of protein from the body, there is an increased amount of the anti-ferment. Mitra 7 was unable to find nuclease or connectivase which could digest muscle fibre and connective tissue in the stomach of an infant twelve months old, but found both ferments in a child of fifteen months. Rossi 8 measured the stimulating effect of saliva on the pepsin digestion by the Mett method. He found it greatest in the early stages of digestion but it became almost imperceptible at the end of four hours. Wakabayashi and Wohlgemuth 9 found that the large intestine contains erepsin, nuclease, hemolysin and a fibrin enzyme. The changes which protein undergoes during digestion may be briefly enumerated as follows: When it is ingested it is split and hydrolyzed by the various 1 Ibrahim and Gross: Jahrb. f. Kinderh., 1908, Ixviii, 232. 2 Wentworth: Jour. Am. Med. Assoc., 1907, 119, 204. 3 Hallion and Lequeux: Compt. Rend, de la Soc. de Biol., Paris, 1906, Ixi, 33. 4 Cohnheim: Zeitschr. f. Physiol. Chemie. Mitteilungen uber das Erepsin, 1902, xxxv, 134. Notiz uber das Erepsin, 1906, xlvii, 286. 8 Langstein: Jahrb. f. Kinderh., 1908, Ixvii, 9. 6 Lust: Miinchen Med. Wochenschr., Ivi, 2047-2051. 7 Mitra: Folia clinica, iii, 274. 8 Rossi: Arch. Fisiol., viii, 484; from Zentralbl. Biochem. u. Biophys., ii, 436. Wakabayashi and Wohlgemuth: Internat. Beitr. Path. Therap., ii, 519. 46 DIGESTION OF PROTEIN ferments in a definite sequence. Pepsin reduces it into albumoses and peptones. Trypsin and erepsin then split these bodies further into amino acids, with an intermediary stage of polypeptides. The end products of protein digestion are amino acids and their combi- nations. Folin and Denis 1 and Van Slyke and Meyer 2 showed that the amino acids are absorbed as such from the alimentary tract. The evidence adduced by these observers that the amino acids reach the blood stream as amino acids and are carried to the tissues to be used in the formation of new tissue or to be disintegrated with the resultant production of the end product urea, has been strength- ened by the work of London. 3 Recent investigations on dogs seem to prove that the amino nitrogen is absorbed both through the blood vessels and the lymphatic system. 4 During digestion the amount of ammo-nitrogen increases not only in the portal blood but also in the peripheral circulation. CASEIN CURDS Twenty-eight years ago Biedert 5 published the first of a series of papers, in which he tried to show that many of the disturb- ances of digestion in infancy were due to difficulty in digesting casein. He believed that the bean-like masses which appeared in the stools of artificially-fed babies during disturbances of di- gestion were either casein or one of its derivatives. He found that their microscopic appearance was similar to that of coagulated casein and that they turned pink with Million's reagent. Weg- scheider, 6 Uffelmann, 7 Escherich, 8 and Fr. Miiller 9 were unable to confirm Biedert's assumption and concluded from their own ex- periments that the "so-called casein curds" were formed of cal- cium soaps, epithelium, bacteria, and intestinal secretions. It was shown, furthermore, that Biedert's methods of proving the 1 Folin and Denis: Jour, of Biol. Chem., 1912, xi, 87 and subsequent papers 2 Van Slyke and Meyer: Jour. Biol. Chem., 1912, xii, 399. 1 London: Zeitschr. f. Physiol. Chem., 1913, Ixxxvii, 313. 4 Hendrix and Sweet: Jour. Biol. Chem., 1917, xxxii, 299. 6 Biedert: Jahrb. f. Kinderh., 1888, xxviii, 21. ' Wegscheider: Ueber normale Verdauung bei Sauglingen. Innaug. Diss. Strassburg, 1875; cited by Blauberg: Experimentelle und kritische Studien iiber Sauglingsfeces bei naturliche u. kunstlicher Ernahrung, Berlin, 1897. 7 Uffelmann: Deutsch. Arch. f. klin. Med., 1881, xxviii, 437. 8 Escherich: Jahrb. fur Kinderh., 1888, xxvii, 100. 9 Fr. Miiller: Zeitschr. fur Biol., 1884, xx, 327. DIGESTION OF PROTEIN 47 presence of casein 1 were of no positive value since nucleo-protein and nucleo-albumen gave the same tests. 2 Talbot 3 showed that there are two kinds of curds, one of which is large and tough and contains a high percentage of protein, and the other which is small and soft and contains a low percentage of nitrogen and a high percentage of fat. The former are tough, bean-like masses of varying size and shape, weighing from % to \]/2 gEi-> the color varying from white to greenish-yellow according to how much" they are stained by the bile and intestinal secretions. They may be easily separated from the fecal material in which they are imbedded and become extremely hard when treated with 10% formaline solution. These curds are the ones examined by Biedert. The small, soft curds are either flat, white flakes (which look like undigested particles of milk) or pinhead elevations, which are stained green or yellow by the intestinal secretions. They are always associated with more or less mucus and are composed almost entirely of fat in the form of fatty acids or soaps. These curds are probably the ones examined by Biedert's opponents. Knopfelmacher 4 and Selter 5 examined the tough curds chem- ically and concluded that they were composed of casein. The chemical composition of casein curds is as follows: TABLE 12 Curds Neutral Fatty Soaps. Author Fat in food % Nitro- gen. % Total fat.% fat.% of dried acid, % of dried %of dried of dried of dried stool stool stool stool stool Talbot * 3 75 7.2 46.8 36.4 4.6 5.8 3.50 9.8 28. 21.4 1.2 5.6 Benjamin 5 " Eiweissmilch " 10.4 27. Courtney 8 2.3 10.6 22.3 1.8 10.6 19.0 Talbot 4 "Fat free milk" 12.0 8.4 2.2 0.8 5.4 4 Talbot: Boston Med. and Surg. Jour., 1908, clviii, 905. 5 Benjamin: Zeitschr. f. Kinderh., 1914, x, 185. 6 Courtney: Am. Jour. Dis. Children, 1912, iii, 1. 1 Biedert: Arch. f. Gynak., 1907, Ixxxi, 1. 2 See also Southworth and Schloss: Arch. Pediatrics, 1909, xxvi, 241. 3 Talbot : Boston Med. and Surg. Jour., 1908, clviii, 905 ; and ibid., Jan. 7, 1909. 4 Knopfelmacher: Wien. klin. Wochenschr., 1898, 1024; ibid., 1899, 1015; ibid., 1899, No. 52, 1038; and Jahrb. f. Kinderh., 1900, Iii, 545. 5 Selter: Verhandl. d. Gesellsch. f. Kinderh., Stuttgart, 1906, 177. 48 DIGESTION OF PROTEIN The foregoing table gives analyses of selected curds from three investigators and shows the general tendency for the amount of fat in the curd to increase with the amount of fat in the milk. Conversely the amount of nitrogen diminishes as the fat increases. This seems to indicate that fat, the accidental component of the curd, dilutes the nitrogen. These experiments were not considered conclusive by most pediatricians, especially those of the schools of Czerny, Finkelstein and Heubner, while Biedert and many American schools thought that they were casein. Wernstedt * compared under the micro- scope and microchemically the tough curds found in the stool with those found in the stomach and concluded that they were casein. Recently, Talbot, Bauer, Uffenheimer and Takeno 2 working at approximately the same time with different methods, showed by the precipitine method, by anaphylaxis, and by complement fixation that the protein in tough curds was cow casein. Liwschiz 3 repeated this work and found that casein could be differentiated from paracasein by complement fixation. When milk curdles in the infant's stomach it entangles a large proportion of the milk fat in its meshes and only such fat as lies near the surface of the curd can be reached by the digestive juices. The amount of fat in the curd depends upon the amount of fat in the milk. 4 Courtney 5 did not find any great variation in the percentage of fat in the curds examined by her. This is what would be expected, because there was no great variation in the percentage of fat in the food of the babies passing the curds. She went fur- ther, however, and examined the stool mass surrounding the curds and concluded that the casein curds are not pathognomonic of any pathological condition, and that the loss of food occasioned by their formation and the impairment of the general nutrition re- sulting from it is insignificant. Finally, that in attempting to cor- rect the state of digestion one should be guided by the general rules of infant feeding, paying only secondary attention to the appearance or disappearance of curds from the stools. Rowland 6 believes that the presence of casein curds in the stools 1 Wernstedt: Hygiea, 1907, No. 9, ref. Munchen Med. Wochenschr., 1907, 2543. 2 Talbot: Arch. Pediat., 1910, xxviii, 440; Uffenheimer and Takeno: Zeits. f. Kinderh., 1911, ii, 32; Bauer: Monatschr. f. Kinderh., 1911, x, 239. 'Liwschiz: Diss. Munchen 1913,Zeitschr. f. Kinderh., Ref., 1914, viii, 345. 4 Talbot: loc. tit. 5 Courtney: Am. Jour. Dis. Children, 1912, iii, 1. 6 Howland: Am. Jour. Dis. Children, 1913, v. 390. DIGESTION OF PROTEIN 49 is of " limited, if any, pathological importance, but rather depends on physical conditions in the gastrointestinal tract." Benjamin 1 notes that casein curds appear in the stools of healthy as well as of dyspeptic infants and that there is less gain in weight while these curds are being passed than when they are absent. There is no question, however, that the casein curds are relatively rare in in- fants' stools and that their presence is often associated with symptoms of indigestion. Ibrahim 2 and Brennemann 3 observed that the casein curds appeared in the stools of babies fed on raw milk and disappeared from the stools when the milk was boiled. They both suggest boil- ing as a therapeutic measure for preventing the formation of such curds. This fact explains why casern curds are seldom seen in Germany where the milk is almost universally boiled. Ibrahim observed that the curds seem to come more easily in babies with digestive disturbances, but that they may come in otherwise healthy babies who are fed on raw milk. He saw them in a two and one-half year old child which had a typical " digestion- insufficiency" as described by Heubner. 4 The most recent experi- ments of Uffenheimer 5 seem to indicate that casern is present in the stools more frequently than was formerly thought, as it has been found in the salve-like skimmed milk stools. Selter 6 described a picture of "intoxication" in which there is an excursion of temperature from 37 to 34 (i. e., subnormal), slow pulse and superficial respiration. The color of the skin is bluish-gray. The urine contains no reducing substance. The stools are curdy and grayish-yellow, with a cheesy odor. The urine contains a kenotoxine, which, when injected into mice, causes a condition similar to that described in the babies. The disease is cured by small amounts of breast milk, or by carbohy- drates, and is attributed to the proteins. Mellanby 7 believes that a substance known as ft imidozoly- ethylamine is accountable for the symptoms in the acute diar- rheas of infants. This substance may be derived from amino-acid histidin by the removal of C0 2 and is related to ptomaines. 1 Benjamin: Zeitschr. f. Kinderh., 1914, x, 185. 'Ibrahim: Monatschr. f. Kinderh., 1911, x, 55. 1 Brennemann: Am. Jour. Dis. Children, 1911, i, 341. 4 Heubner: Verhandl. d. Gesellsch. f. Kinderh. in Salzburg, 1909, xxvi, 169. 6 Uffenheimer: Sitzung der Mimchen Gesellsch. f. Kinderh., 1911; Munchen med. Wochenschr., 1911, 876. 6 Selter: Deutsch. med. Wochenschr., 1908, 512. 7 Quart. Jour. Med., 1915-16, ix, 164. 50 DIGESTION OF PROTEIN Schloss l found that in "intestinal intoxication" there was often acidosis and an increase of the non-protein nitrogen and urea of the blood. Although acidosis plays a definite part in the symptoma- tology, and the symptoms are essentially those of uremia, he con- cludes that the essential cause is probably some unknown toxic agent. The evidence at hand, therefore, strongly suggests that some product of protein decomposition is responsible for the symp- toms present in "intoxication." It is wise to bear in mind in this connection that "intestinal intoxication" is not a disease entity but is merely the term given for a group of clinical symptoms. Monrad 2 and Morse 3 do not believe with Finkelstein and his followers that casein is absolutely harmless, but think that it can cause dyspepsia. Holt and Levene 4 found that large quanti- ties of casein given by mouth could cause a rise in temperature. They observed a rise in temperature in five instances that con- tinued until the food was changed, and then subsided to normal. Fever occurred only when their "synthetic food" contained six per cent of casein. There was a retention of chlorides for three or four days preceding the rise in temperature. They call attention to the parallelism between this fever and that produced by Vaughan by the parenteral injection of protein. Their food contained a large amount of salts, however, and it is possible that the fever may have been caused by them. ANAPHYLAXIS The connection between anaphylaxis and the disturbances caused by cow's milk has always been a field for speculation. Ham- burger 5 believed that foreign protein (" artf remdes Eiweiss") was "an irritant to the especially sensitive cells of the infant's ali- mentary tract and that the necessity of breaking down the pro- tein molecule to such simple substances that they could not be injurious after absorption threw an added burden on the digestion and one which was unnecessary with milk of the same species." Rowland 6 has brought forward some evidence against this theory. Recent investigations, however, have added positive evidence. Moro and Bauer 7 found precipitines in the blood of marantic Schloss: Am. Jour. Dis. Ch., 1918, xv, 165. 2 Monrad: Monatsschr. f. Kinderh., 1911, x, 244. 3 Morse: New York Med. Jour., 1913, xcvii, 477. 4 Holt and Levene: Med. Klin., 1913, ix, 258. 5 Hamburger: quoted by Howland, Am. Jour. Dis. Children, 1913, v. 390. Howland: Am. Jour. Dis. Children, 1913, v. 390. 7 Moro and Bauer: quoted by Howland, Am. Jour. Dis. Children. 1913, v. 390. DIGESTION OF PROTEIN 51 infants in a few instances. There is not much doubt that during the first weeks of life a foreign protein can pass through the in- testinal wall. Schloss l and Berger 2 have given indirect, but sug- gestive evidence by differential counts of the blood, that when a foreign protein is introduced for the first time into the gastro- intestinal canal of infants, there is a similar reaction in the body to that obtained in active sensitization and immunity of the body. These two pieces of work suggest that the sequence of sensitiza- tion and immunity takes place when any foreign protein is intro- duced into the intestinal canal. Lust 3 fed different forms of for- eign protein to children with digestive disturbances and found by the precipitine reaction that egg albumen passed through the in- testinal wall in nine of sixteen cases of acute and chronic nutritional disturbances, while ox serum passed through in only one of seven- teen cases. Hahn 4 found that in five out of twenty-three infants with acute nutritional disturbances antitoxin passed from the in- testine into the blood. Modigliani and Benini 5 found by means of the precipitine reaction that the blood of infants fed on cow's milk showing symptoms of gastrointestinal disturbances, was al- ways positive for cow casein. Sick new-born babies gave a positive reaction, while older breast-fed babies were negative even when they were given a little cow's milk during an acute intestinal disturbance. No healthy infants gave positive reactions. These findings have been recently confirmed in a carefully controlled piece of work by Schloss and Worthen. 6 Vaughan 7 calls attention to the fact that peptone and other products of decomposition of protein may cause symptoms of disease and that "sensitization may result from the absorption of undigested or partially digested proteins from the alimentary tract." Differences in the Absorption of Human and Cow's Milk Ni- trogen. In most instances less nitrogen is taken in the food of naturally fed babies than in that of artificially-fed ones, but when approximately the same amounts of each are ingested there is less fecal nitrogen in the artificially-fed babies than in those fed natu- 1 Schloss: Paper read at the Am. Assoc. for the Study and Adv. of Clinical Investigation, May 11, 1914. 2 Berger: Paper read at the Thirty-fifth meeting of the New England Pedia- tric Society, held January 29, 1915. Lust: Jahrb. f. Kinderh., 1913, Ixxvii, 383. * Hahn: Jahrb. f. Kinderh., 1913, Ixxvii, 405. 6 Modigliani and Benini: Policlinico, Rome, Dec. med. Section, 1914, No. 12,533. 6 Schloss and Worthen: Am. Jour. Dis. Ch., 1916, xi, 342. 7 Vaughan: Jour. Am. Med. Assoc., 1913, hri, 1761. 52 DIGESTION OF PROTEIN rally. 1 The nitrogen in the feces of both naturally and artificially- fed babies increases, other things being equal, with an increase of nitrogen in the food. There may, however, be considerable varia- tions in the nitrogen excreted by the same child on the same food if the observation is continued over a long period of time, as is shown by the work of Cronheim and Miiller. 2 Starvation stools. Experiments on animals and man have shown that during starvation there are only small amounts of ni- trogen in the feces, that when a nitrogen-free food is given there is considerable increase in the fecal nitrogen 3 and that there may be more nitrogen in the stools on a nitrogen-free food than on one containing a large amount of nitrogen. It may be assumed, there- fore, that the animal albumins are probably completely or al- most entirely absorbed in health. It is evident also that the ni- trogen in the feces comes principally from the intestinal secretions and the intestinal bacteria. Keller 4 found that a baby excreted 0.74 gm. nitrogen per day in one experiment and 0.097 gm. in another, while undergoing starvation. It would be expected that when the amount of food is in- creased there would be an increased flow of digestive juices, but figures do not bear out this assumption. Vegetable nitrogen is digested and absorbed with greater difficulty than animal nitrogen. Wohlgemuth 5 found that he could cause an increased flow of pancreatic juices in a man with a pancreatic fistula by feeding carbohydrates and that protein caused a less profuse flow. Composition of Nitrogenous Bodies in Stools. It has already been shown that tough curds are formed from undigested casein. A large part of the remaining fecal material is due to the bodies of bacteria. The chemical composition of the nitrogenous com- ponents of the stools is as follows: 6 Proteins and amino acids 50-70% Free amino acids 2.4-24% Ammonia 3.0-37% 7 *See Tables in Keller: Phosphor, und Stickstoff im Sauglingsorganismus. Arch. f. Kinderh., 1900, xxix, 1; and Orgler: Ueber Harnsaureausscheidung im Sauglingsalter. Jahrb. f. Kinderh., 1908, Ixvii, 383. 2 Cronheim and Miiller: Biochem. Zeitschr., 1908, ix, 76. 3 Rubner: Zeitschr. f. Biol., 1879, xv, 115, and others. 4 Keller: Arch. f. Kinderh., 1900, xxix, 1. 6 Wohlgemuth: Berl. klin. Wochenschr., 1907, 47. 6 Van Slyke, Courtney and Fales: Am. Jour. Dis. Ch., 1915, ix, 533. 7 Gamble: Am. Jour. Dis. Ch., ix, 519. METABOLISM OF PROTEIN 53 THE METABOLISM OP PROTEIN Schlossmann and Murschhauser l investigated the fasting me- tabolism of infants. Their paper should be consulted in the origi- nal for the literature and the details of the investigations. They found that the nitrogen excretion in the urine during fasting de- pended upon the quality of the food ingested before fasting was commenced and that the greater the protein (nitrogen) content of the food, the greater was the excretion of nitrogen. For ex- ample, Baby 14: TABLE 13 Nitrogen content of urine per Nitrogen content of urine per hour, per kilogram hour per kilogram Grams Grams Feeding with human milk 0.00363 Modified cow's milk 0.0119 On first day of fast 0.00513 First day's fast 0.0160 On second day of fast 0.00686 Second day's fast 0.0151 On third day of fast 0.01083 Food again given 0.0080 On first day after fast 0.0068 On second day after fast 0.0042 When human milk had been used less body protein was broken down during starvation than when modified cow's milk was used. After eighteen hours of fasting the nitrogen in the urine represents the products of the katabolism of the body protein. The acetone bodies increase in the urine during fasting, and the evidence points to the absence of carbohydrate in the food as the cause. When the amount of protein in the food is increased there is increased retention of nitrogen. 2 Babies, unlike adults, are able to retain nitrogen even when they are not receiving the required number of food calories. They may continue to do so even under the most discouraging circumstances. In adults when the total carbohydrate of the food is replaced by fat of an equal caloric value there is a considerable albumin def- icit. 3 If only a part of the carbohydrate is replaced by fat, the body will eventually return to a nitrogenous equilibrium. Orgler believes that in normal babies, however, the amount of fat in the food influences the nitrogen metabolism to only a slight degree. Increasing the fat in the food of babies that do not digest fat well may, on the other hand, result in a negative nitrogen balance. It is not known whether the action of the fat of human milk and 1 Schlossmann and Murschhauser: Biochem. Zeitschr., 1913, Ivi, 355. * Meyer, L. F.: Biochem. Zeitschr., 1908, xii, 422. * Landergreen: Skandin. Arch. f. Physiol., 1903, riv, 112. 54 METABOLISM OF PROTEIN of cow's milk is the same or not. In Courtney's cases 1 the nitro- gen retention was higher in those babies which showed a very considerable gain in weight in the course of the experiment and were, therefore, in the stage of reconvalescence. Fat does not seem to have the property of sparing protein. Carbohydrates, on the other hand, have a marked property of sparing nitrogen. 2 Cane and milk sugar have the same action as malt sugar. When they are added to the food there is usually an increase in the nitrogen retention. When carbohydrates are given in excess, they cause increased peristalsis, frequent stools and a considerable loss of nitrogen from the body. 3 - 4 The growing body requires protein from which to build up the body tissues, muscles, etc., while carbohydrates and fats are used as fuel. It is obvious, therefore, that more protein or nitrogen must be ingested than is excreted in order that the needs of the growing tissues may be supplied. The osseous system, in the same way, requires mineral salts for its growth, and more salts must be ingested in the food than are lost in the excreta. These salts which are retained in the body are used to build up new bone. When the baby is gaining weight and strength, there is a retention of both nitrogen and salts and when the baby is not gaining, there may be a loss of both of these bodies. When one is retained in the body the other is apt to be retained, and vice versa, as shown by Orgler's Baby No. 9. 5 The metabolism of breast-fed babies can be compared more easily than of that bottle-fed babies because the food, i. e., breast milk, is essentially the same in all cases, while that of artificially- fed babies differs a great deal. Orgler found that in general there is more nitrogen retained per kilogram of body weight in young babies than in older babies; that is, the retention decreases as the baby grows older. Both the retention and the utilization of nitrogen must be taken into consideration when the various cases in literature are com- pared. Utilization represents the amount retained as compared with the amount in the food. The following table taken from Schwarz gives an idea of utilization : 1 Courtney: Am. Jour. Dis. Children, 1911, i, 321. 2 Keller: Maltsuppe, eine Nahrung fur magendannkrauke Sauglings. Jena, 1903. 3 Orgler: Jahrb. f. Kinderh., 1908, Ixvii, 383. 4 Talbot and Hill: Am. Jour. Dis. Children, 1914, viii, 218. 6 Meyer, L. F.: Ergebniss d. inn. Med. und Kinderh., 1908, i, 317. METABOLISM OF PROTEIN 55 TABLE 14 Age Up to 14 days 2-3 months 5 months Retention 0.351 0.153 0.048 Utilization 78.3% 40.8% 23.1% The foregoing table shows that the younger the baby is, the greater is the retention and utilization of nitrogen. This cor- responds with clinical observations of growth, for the very young baby grows very rapidly and, therefore, retains and reuses more nitrogen in building up new body tissues than the older baby which does not increase so rapidly in size. Under certain con- ditions of under-nourishment, an increase in the amount of nitro- gen in the food results in an increased retention of nitrogen and improvement in the general condition of the baby. Baby F. W. L. studied by Talbot and Gamble 1 gained weight rapidly and retained increasing amounts of nitrogen as the ni- trogen in the food was increased until period 5, when the greatest amount of protein was given in the food, and as a result casein curds appeared in the feces, and less nitrogen was retained. Coincidently symptoms of indigestion appeared and the baby refused to take all its food. These figures are the only ones which show that casein curds in the stools represent an increased excretion of nitrogen from the body. They are probably the only true record of the metabolism during protein indigestion. In other conditions an increase of the food nitrogen causes greater retention but not necessarily a gain in weight. There is no ex- planation of why this increase in the retention of nitrogen does not necessarily benefit the baby. Sick infants cannot retain as much nitrogen as well babies of the same age. Fife and Veeder 2 found that two cases of infantile atrophy had a greater retention of ni- trogen than normal babies of the "same age and weight." The question may be raised, however, as to whether the babies examined could have been atrophic if they were of the same weight as nor- mal babies of the same age. When the amount of carbohydrate in the food was increased there was increased retention of nitrogen but the nitrogen retention was not influenced by the amount of fat in the food. Czerny and Steinitz 3 have collected the figures of the nitrogen 1 Talbot and Gamble: Am. Jour. Dis. Ch., 1916, xii, 333. * Fife and Veeder: Am. Join-. Dis. Children, 1911, ii, 19. 3 Czerny and Steinitz: Stoffwechselpathologie des Kindes, Noorden's Hand- buch d. Path. d. Stoffwechsels, II, 391. 56 METABOLISM OF PROTEIN metabolism of infants with disturbances of digestion and found that the absorption was approximately normal except during diarrhea. Although the evidence all seems to show that there is a retention of nitrogen in practically all instances, yet this evidence is not sufficient to warrant its acceptance without reserve. Gam- ble, 1 has shown that in alkaline stools twenty per cent of the ni- trogen can be lost in the form of ammonia during the process of drying. This loss of nitrogen has not been taken into considera- tion in the metabolism experiments of other writers and might be sufficient to result in a negative balance of nitrogen in some of the instances in which the balance has been reported positive. Protein Needs of Infants. The increasing tendency to feed infants on dilutions of whole milk also necessitates giving larger amounts of protein in the food than is required by the body for growth. During metabolism the very process of digestion uses up energy. It has been shown repeatedly that the increase of metabolism due to fat or carbohydrate is very slight, but that the increase incident to protein hydrolysis may be 30%. 2 It, therefore, seems uneconomical to burden the digestion any more than is necessary with the food component which uses up so much energy in preparing itself for use. The figure commonly given as the caloric needs of infants is 2 grams of protein per kilogram of body weight. Hoobler 2 considers that the protein needs will be supplied for growth if 7% of the food calories are in the form of protein. 3 This figure is probably a little too low for the average infant. It has also the additional disadvantage that it requires a relatively high amount of fat and sugar to supply enough calories. It is, therefore, safer to figure that 2 grams of protein per kilogram of body weight is the lowest amount of protein on which an infant can thrive, that it is wise to keep the amount of protein relatively low, but never lower than this point, and that larger amounts may be given, if the digestion is such that sufficient calories cannot be supplied in fat and carbo- hydrate. Vitamines. Although the food may contain enough calories and protein to supply the requirements of an infant, it may not con- tain the proper "vitamines" necessary for growth. These are of two types and are described by McCollum as fat soluble A and water soluble B. Most of the knowledge on this subject is founded 1 Gamble: Am. Jour. Dis. of Children, 1915, ix, 519. 2 Lusk: Sc. of Nutrition: Phila. and London, 1917, 3rd Ed., p. 238. 3 Hoobler: Am. Jour. Dis. Ch., 1915, x, 153. METABOLISM OF PROTEIN 57 on animal feeding experiments 1 and need not necessarily apply to the human infant, but in all probability the fundamental principles will be the same in either case; "There is greater value in lactalbumen in promoting growth than in casein be- cause the amino acids are arranged in more suitable proportions. The protein of whey appears to be as perfect a material for use in the service of growth as any protein known." l The amino acids which play an essential role in growth are lysin, cystin, tryp- tophan, and glycocoll, while others may have a minor part. Their arrangement and relation to one another must fall within definite limits for the optimum results. 1 See Lusk: Science of Nutrition, 3rd Ed., 1917, Phila. and London, pp. 368 et seq. CHAPTER V THE METABOLISM OF THE MINERAL SALTS The metabolism of the mineral salts was first investigated by Liebig l in 1840. Very little information of value in relation to the problems of infant feeding and metabolism has been added since then, however, until recent years. Even such information as we now have is being continually modified or disproved by chemists, who find that the methods which were employed in ob- taining the figures gave erroneous results. Summaries of the pres- ent knowledge of the metabolism of the mineral salts are given by Albu-Neuberg, 2 L. F. Meyer, 3 Hoobler, 4 and Tobler and Bes- sau. 5 The body of the new-born infant is relatively richer in water and fat and poorer in nitrogen and ash than the body of the adult. The body of the fetus contains a very large proportion of water, the proportion diminishing as the fetus grows older. The com- position of the ash of the new-born infant is according to Soldner 6 as follows: In one hundred parts of the new-born infant there is K 2 0, 7.06; Na 2 O, 7.67; CaO, 38.08; MgO, 1.43; P 2 O 3 , 0.11; F 2 O 3 , 0.83; Mn 3 O 4 , 0.03; S 2 O 5 , 37.66; So 8 , 2.02; Cl, 6.61; SiO 2 , 0.06; Cos, 0.53. Human milk contains, with the exception of iron, much less of the mineral salts than cow's milk. More of the salts in human milk are in organic combination than in cow's milk and for that reason are supposed to be utilized more easily. Soldner 7 found that the sodium, potassium, and chlorine content of human milk decreased as lactation progressed, while the bone-forming con- 1 Liebig: Chemie in ihre anwendungs fur Agrikultur und Phys., 1876. 2 Albu-Neuberg: Mineralstoffwechsel, Berlin, 1906. J Meyer, L. F.: Ergebnisse d. inn. Med. u. Kinderh., 1908, i, 317. 4 Hoobler: Am. Jour. Die. Children, 1911, ii, 107. 5 Tobler and Bessau: Allgemeine Pathologische Physiologie der Ernahrung und des Stoffwechsels im Kindesalter, Wiesbaden. * Soldner: quoted in Pfaundler and Schlossmann: The Diseases of Children, Pbila. and London, 1908, i, 364. 7 Soldner: loc, cit. 58 METABOLISM OF SALTS 59 stituents, calcium, magnesium and phosphorus, remained fairly constant. The mineral salts play a very complicated part in digestion, because they are not only absorbed by the intestines, but also may be re-excreted into the digestive canal. There are also com- plicated reactions which take place between the organic and in- organic food components. The digestive juices contain salts. Bile contains from }/ to 1% of ash, which is especially rich in sodium and chlorides. 1 It also contains smaller amounts of potassium, calcium, and mag- nesium in combination with phosphoric acid. The pancreatic juices contain Y^/o of asn > the greater part of which is in the form of sodium carbonate. The intestinal secretions are also rich in carbonates. Metabolism of Ash. Cow's milk contains much more ash than human milk, and, therefore, much more salt is given to the in- fant taking an artificial food prepared with cow's milk than it requires. The breast-fed infant 2 absorbs about 80% of the ash in the food and retains between 40% and 50% while the artificially- fed infant absorbs from 43% to 78% and retains from 43% 3 to none at all or may even loose ash from the body. 4 Hoobler 3 found, in his experiments, that the retention of mineral salts as compared with the retention of nitrogen was relatively poor. The retention was poorest when the food contained but little fat, was better when it contained a medium amount of fat, and was best when it contained a large amount of fat (5.4%). Talbot and Hill 4 kept the fat and protein in the food approximately the same in seven periods, and found that when the carbohydrate was in- creased beyond the limit of tolerance and diarrhea resulted there was a loss of ash from the body. The increased excretion of ash was through the f eces. A careful study by Holt and his co-workers 5 showed that in loose stools as much as 84% of the intake may be lost, the principal loss being salts other than calcium phosphate. Chlorin, potassium and sodium are normally present in relatively small amounts in normal stools but in loose stools they are ex- creted in large enough amounts to result in a loss of sodium and potassium from the body. 5 Metabolism of Calcium. The metabolism of calcium is de- ir robler: toe. cti. * Blauberg: Zeitschr. f. Biol., 1900, xl, 1. Hoobler: Am. Jour. Dis. Children, 1911, ii, 107. Talbot and Hill: Am. Jour. Dis. Children, 1914, viii, 218. 6 Holt, Courtney and Fales: Am. Jour. Dis. Ch., 1915, ix, 533. 60 METABOLISM OF SALTS scribed in detail in the chapter on rickets. For that reason it is unnecessary to speak of it here except to say that some investiga- tors criticise the methods which were used to quantitate the amount of calcium and show that they are inaccurate. Metabolism of Iron. The amount of iron in both cow's milk and human milk is small and is insufficient for the needs of the growing infant. Nature has deposited enough iron in the liver l of the new-born infant, however, to last until it can digest foods which contain sufficient amounts of iron. The iron in human milk is apparently more easily retained than that in the milk of animals. The following table of Krasnorgorski 2 illustrates this point. TABLE 15 IRON METABOLISM OF THE SAME BABY IN TWO PERIODS Ab- Ab- Re- Re- Author Pood food Peces Urine sorbed mg. sorbed tained mg. tained Krasnor- Human milk 7.05mg. 0.84mg. 0.55mg. 6.21 88.09 5.66 80.28 gorski Krasnor- gorski Croat's milk 3.44 " 2.59 " 0.09 " 0.85 24.71 0.76 22.09 Metabolism of Magnesium. The absorption and retention of magnesium are higher in the breast-fed than in the artificially- fed infant. Hoobler 3 found that when an infant was taking an artificial food the retention was better when there was a low per- centage of fat in the food than when there was a high percentage of fat. Metabolism of Phosphorus. One liter of human milk contains from 0.31 to 0.45 gram of phosphorus and one liter of cow's milk about 1.81 grams. Three-quarters of the phosphorus in human milk is in organic combination, while only one-quarter of the phos- phorus in cow's milk is in organic combination; 41.5% of the total phosphorus in human milk is in the form of nucleon phos- phorus and only 6% in cow's milk. According to Blauberg 4 89.2% of the phosphorus in human milk and 53.2% of that in cow's milk is absorbed. Hoobler 3 found 1 Bunge: Zeitschr. f. Physiol. Chemie, 1889, xiii, 399. * Quoted by L. F. Meyer: Ergeb. d. inn. Med. u. Kinderh., 1908, i, 327. 1 Hoobler: loc. cit. 'Blauberg: see Hoobler, loc. tit. 61 that more was absorbed when the food contained a high per cent, than when it contained a low per cent, of fat. Knox and Tracy * confirmed the work of Keller showing that the bottle-fed baby excretes much more phosphorus in the urine than the breast-fed infant. The latter excretes very little or none. According to L. F. Meyer, 2 the retention of phosphorus is less in the artificially- fed than in the breast-fed infant, the former retaining about 30% of the intake and the latter 69.13%. Metabolism of Sodium and Potassium. There is more potas- sium than sodium in milk. Human milk contains less sodium and potassium than cow's milk. The absorption of these salts is good for both milks. The retention is better on human milk than on cow's milk, being 67% for sodium and 74% for potassium on human milk, while on cow's milk it is 15.27% for sodium and 16.12% for potassium. Both salts are eliminated in both the urine and feces, from 15% to 25% of the intake being eliminated in the feces. 3 Metabolism of Chlorides. Very little is known about the me- tabolism of the chlorides. Metabolism of Sulphur. Hoobler finds that the sulphur of both human and cow's milk is well absorbed, the absorption taking place principally in the small intestine. Sulphur is eliminated almost entirely through the urine, but a small part is eliminated into the large intestine. The retention of sulphur is better when human milk is taken than when cow's milk is taken. The Influence of the Various Food Components on the Metabolism of the Mineral Salts. There are very few in- vestigations which throw any light on the influence of the individual food components on the metabolism of the mineral salts. Rowland 4 found that carbohydrates increased the retention of calcium. L. F. Meyer found that the addition of casein to the food di- minished the absorption of all the mineral salts. Steinitz 5 Rothberg 6 and Birk 7 found that as the fat in the 1 Knox and Tracy: Am. Jour. Dis. Children, 1914, vii, 409. * Meyer, L. F.: Ergeb. d. inn. Med. u. Kinderh., 1908, i, 317. 3 Hoobler: Am. Jour. Dis. Children, 1911, ii, 107. See table and references. 4 Rowland (not yet published). Read before the Am. Fed. Soc'y, Wash., 1913. 6 Steinitz: Monatsschr. f. Kinderh., 1902-3, i, 225; Jahrb. f. Kinderh. 1903, Ivii, 689. Rothberg: Jahrb. f. Kinderh., 1907 Ixvi, 69. 7 Birk: Jahrb. f. Kinderh., 1907, Ixvi, 300. 62 METABOLISM OF SALTS food was increased the loss of mineral salts in the feces was also increased. This loss was especially of calcium and mag- nesium and sometimes resulted in a negative balance. Court- ney * on the other hand, did not find that fat had any marked influence on the retention of ash in infants with chronic in- digestion. L. F. Meyer 2 found that infants with "Bilanzstorung" lost from 34% to 60% of the ash in the food through the feces as com- pared with from 20% to 25% in normal cases. In the stage of in- toxication he found that more sodium, potassium, and chloride were lost in the feces but that there could still be a retention of calcium and phosphorus. There is always a loss of ash from the body 3 in acute diarrhea, although even under these circumstances a retention of calcium is possible. The reverse is apparently true when "soap stools" are passed. Relation of (Edema to Salts. (Edema is due to a retention of salts in the body. This connection between the two is shown by the analyses of Klose 4 who examined post-mortem the bodies of normal and O3dematous infants. He found that 29% of the water content of the body in a normal infant was in the muscles and 21% in the skin and subcutaneous tissue, while in infants with cedema there was slightly less fluid in the muscles and much more than the normal amount in the skin and subcutaneous tis- sue. Apparently there is much less subcutaneous fat in cedema- tous infants than in the normal but in its place there is an increase in the sodium chloride. Diarrhea. -(See page 33.) During many cases of diarrhea which are not of the ileocolitis type, Rowland and Marriott 5 have shown that there is a diminution of the alkali reserve in the blood and an acidosis (see chapter on Acidosis). Judell 6 finds that in diarrhea the ash retention is diminished, or in severe grades there is a negative balance, the loss being due especially to sodium and potassium. Holt 7 and his co-workers found that in diarrhea there is relatively a much greater amount of chlorin, sodium and potassium in the stool than of calcium and magnesium. There is two and a half times as much fat and protein in diarrheal stools 1 Courtney: Am. Jour. Dis. Children, 1911, i, 321. * Meyer, L. F.: Jahrb. f. Kinderh., 1910, Ixxi, 379. 3 Tobler and Bessau: loc. dt. * Klose: Jahrb. f. Kinderh., 1914, Ixxx, 154. 8 Howland and Marriott: Am. Jour. Dis. Ch., 1916, xi, 309. * Judell: Zeitschr. f. Kinderh., 1913, viii, 235. 7 Holt: Courtney and Fales, Am. Jour. Ch., 1915, ix, 213. METABOLISM OF SALTS 63 as there is in normal stools. The relation of excretion to intake is as follows: Fat: loss in normal stools 12.4% of intake very loose stools 40.5% " " Protein: loss in normal stools 7.7% loose stools 14.9% very loose stools 25 . 2% Ash: loss in normal stools 40.0% very loose stools 84.3% CHAPTER VI THE ENERGY METABOLISM OF INFANTS The earliest investigation of the gaseous metabolism of infancy is that reported by J. Forster, of Munich in 1877. 1 He found with the large Pettenkofer-Voit respiration chamber that the in- fant produces much more carbon dioxid per unit of weight than does the adult. In France Richet, Langlois, Variot and Saint- Albin, Bonnoit, Variot and Lavaille 2 and G. Weiss published a series of investigations on the metabolism of new-born infants and atrophic infants between the years 1885 and 1912. In 1898 the classical monograph of Rubner and Heubner 3 appeared. They studied the average daily requirement of food of a normal infant and in the following year 4 of an atrophic infant. They point out the fact that in human beings the carbon dioxid excre- tion is proportional to the body surface, whatever their size. In 1908 the first of a series of investigations by Schlossmann and Murschhauser 5 appeared, and this, with subsequent articles, the last of which was published in 1914 6 have added much to our knowledge of the metabolism of infancy. These authors emphasize the influence of muscular activity on metabolism and they studied the basal metabolism (Grundumsatz) during complete repose for the purpose of comparing the metabolism in health and disease. They conclude that slight changes in the temperature of the sur- rounding air are without influence on the metabolism. Their in- vestigations led them to study also the fasting metabolism in order to eliminate the influence of work done during digestion. Other investigators, whose names should be mentioned, are Mensi, Poppi, Scherer 7 Babak, and Hasselbach, Bahrdt, Birk, Edelstein and Niemann. 1 Forster: Amtl. Ber. d. 50 Versammlung deutsch. Naturforscher u. Aerzte in Miinchen, Munich, 1877, 355. 2 For synopsis of literature see Benedict and Talbot: Gaseous Metabolism of Infants, Carnegie Institution of Washington, Publication 201. 1 Rubner and Heubner: Zeitschr. f. Biol., 1898, xxxvi, 1. 4 Rubner and Heubner: Zeitschr. f. Biol., 1899, xxxviii, 315. 6 Schlossmann and Murschhauser: Biochem. Zeitschr., 1908, riv, 385. 'Schlossmann and Murschhauser: Biochem. Zeitschr., 1914, Iviii, 483. 7 See Benedict and Talbot: Am. Jour. Dis. Children, 1914, viii, 1. 64 ENERGY METABOLISM 65 In America, Carpenter and Murlin l studied the energy metab- olism of pregnant women before and after the birth of the child. Rowland 2 studied the direct calorimetry and compared it with the heat calculated from the carbon dioxid excretion and oxygen consumption. He found that the heat-production as directly meas- ured and as indirectly computed was strikingly close, the greatest difference being 2%. Benedict and Talbot 2 reported from the Nutrition Laboratory of the Carnegie Institution of Wash- ington in 1914, the results of three years' investigations with a respiratory chamber on about eighty babies, of which sixty-one were reported in detail. Murlin and Hoobler 4 reported the results of then* investigations with a respiratory chamber on a few in- fants in 1915. Methods of Computing the Energy Metabolism. There are several ways of computing the energy metabolism of infants: first, by measuring the heat lost by an infant in a calorimeter; second, by computing the heat production by collecting the carbon dioxid excreted and measuring the oxygen consumed by an infant in a respiratory chamber. Zuntz 5 has computed the calorific value of oxygen with different respiratory quotients and these figures may be considered today as the best data we have for the com- putation of the energy output from the measurement of the gaseous exchange. Knowing the respiratory quotient the calcula- tion of the calorific value of carbon dioxid is a simple one. (Bene- dict and Talbot, Carnegie Institution of Washington, Publication 201, Table fifteen, page twenty-nine, gives the calorific equiva- lents of carbon dioxid.) It is, therefore, possible to determine how many calories are used during a given period when the carbon dioxid and the respiratory quotient are known; thirdly, the energy metabolism has been com- puted by investigators who have measured the fat, carbohydrate and protein intake and the loss of fat, carbon and nitrogen in the excreta; and finally, the energy metabolism is roughly computed by clinicians who know the approximate or theoretical composi- tion of the elements in the food. The last method is of little or no 1 Carpenter and Murlin: Arch. Internal Med., 1911, vii, 184. 2 Trans. Fifteenth Internat. Cong. Hyg. and Demog., 1911, ii, 438. 3 Benedict and Talbot: Carnegie Institution of Washington, Publication 201; and Am. Jour. Dis. Children, 1914, viii, 1. . 4 Murlin and Hoobler: Am. Jour. Dis. Children, 1915, ix, 81. See also Bailey and Murlin, Am. Jour, of Obstetrics and Dis. of Women and Children, 1915, Ixxi, 526, for the Metabolism of New-born Babies. 6 Zuntz, quoted by Benedict and Talbot: Carnegie Publication of Washing- ton, No. 201, 1914. 66 ENERGY METABOLISM scientific value since the composition of the food varies even when the greatest precautions are taken to keep it uniform. It is of value only to the clinician in his practical work and may give false information. Howland, working in Professor Lusk's Laboratory at Cornell University Medical School, showed in a very brilliant way that the output of heat when measured directly and when computed from the carbon dioxid and oxygen, coincided very closely. The greatest difference was two per cent. Other investigations, in which the heat was computed from the carbon dioxid and oxygen, are, therefore, within very small limits of error. The Effect of Muscular Exercise on Metabolism. Schloss- mann appreciated the fact that muscular exercise caused a marked increase in the heat production of an infant. Howland found a difference of 17.6% and 39% hi the heat production between periods of quite sleep and active struggling and crying, while Murlin and Hoobler found that hard crying may increase the metabolism as much as 40%. Benedict and Talbot found that an increase of 60% was common and that there could be an increase of 100% (as in the case D Q Dec. 22 J ) from quiet sleep to active exercise. It is obvious, therefore, that a comparison of the metab- olism of an active healthy infant with that of a quiet sick infant is of no value, because in one the effect of muscular activity is added to the basal metabolism and in the other it is not. The basal metabolism, that is, the metabolism during complete mus- cular repose, should be always used when health and disease are compared. The Effect of Fasting on the Metabolism. There is evidence which seems to show that the metabolism of infants after taking food is always higher than it is in the same infant while fasting. 2 Rowland, 3 in commenting on one of his experiments says: "This experiment, so far as one can do so, brings additional proof to the view that insufficient food reduces the carbon dioxid excretion, but that after eighteen hours, a fasting metabolism is not reached with infants, as shown by the normal heat production and by the respiratory quotient of 0.81." Schlossmann and Murschhauser 2 found that after eighteen hours of fasting acetone soon appears in the urine in considerable quantities. The question can be raised, therefore, whether an infant, which has been starved more 1 Benedict and Talbot: Carnegie Institution of Washington, Pub. 201, p. 97. 2 Schlossmann and Murschhauser: See Murschhauser, Boston Med. and Surg. Jour., 1914, clxxi, 185. 3 Howland: Tr. Fifteenth Internat. Cong. Hyg. and Demog., 1912, ii, 438. ENERGY METABOLISM 67 than twenty-four hours and whose urine contains considerable quantities of acetone, can be considered normal. Benedict and Talbot * studied the fasting metabolism of several infants at periods from three to twenty-four hours after food had been given. They found that the respiratory quotient was markedly lowered after eighteen hours of fasting. The figures of heat production obtained were inconsistent, because it was almost impossible to obtain half hour periods for study in which the fasting infant was in complete muscular repose. If the metabolism is lower after eighteen or twenty-four hours' fast than it is directly after taking food, it must be only slightly diminished. Further investigations must be car- ried on to decide at which point the metabolism of a fasting infant changes from a physiological condition into a pathological condi- tion. For this reason recent investigations have been confined almost entirely to measuring the metabolism directly after food has been given. Comparison of Body Surface and Metabolism. For many years writers on metabolism have been wont to emphasize the sig- nificance of the relationship supposed to exist between the metab- olism and the body surface rather than that between the metab- olism and the body weight. The idea that there is an intimate relationship between body surface and heat production was first brought out by Bergmann 2 in 1847. The theory lay dormant for many years, but was finally resuscitated and put forth in a brilliant and highly stimulating manner by Rubner 3 in 1883, to- gether with experimental evidence. Based fundamentally on New- ton's law of cooling, it received great attention from practically all workers in physiology. The startling evidence which was brought forward to demonstrate that the heat production per square meter of body surface was about 1,000 calories for practically all species of animals lent further support to this hypothesis. The researches of Benedict and Talbot, 4 confirmed by Murlin and Hoobler, 5 show that such conclusions are not warranted in infancy since the relation between the basal metabolism of in- fants and the body surface is not uniform. 6 The following chart illustrates this point: 1 Benedict and Talbot: Carnegie Institution of Wash., Pub. 201. 1 Bergmann and Leuckart: Anatomisch-physiol. Uebersicht des Thierreichs, Stuttgart, 1852, 272; Bergmann: Warmeokonomie der Thiere, Gottingen, 1848, 9. s Rubner: Ztschr. f. Biol., 1883, xix, 545. * Benedict and Talbot: Am. Jour. Dis. Children, 1914, viii, 1. 8 Murlin and Hoobler: Am. Jour. Dis. Children, 1915, ix, 81. Lusk and others consider that there is a very definite relation between 68 ENERGY METABOLISM CHART I (Benedict and Talbot) * Chart showing actual body weight of infants and heat production per square meter of body-surface (Meeh formula) per twenty-four hours HEAT PER SQUARE METER (MEEH) PER 24 HOURS ACTUAL WEIGHT KILOS 4MiteiO->00<0 3 O O O O O 'o O HT EQ* RS EK EF RL PW. AS RA NO* PS* EM LL DO. RE. MA . FK .. BF JP DM A UH RC FR BO* ER- FD LB WP. JS TC FB TK< RD E% '{ OC MO* IR* OS KR > AD EC LO 3M* JV 8 1 /, < s. AC* EHS ES JV S V 2 HOB. 625 575 625 675 725 775 825 875 925 975 1025 1075 1125 1175 1225 1275 1325 1376. CALORIES This chart shows that the basal metabolism per square meter of body surface varies over 100%, when new-born infants, viz., those lying to the left on the line marked 675 calories are included. Benedict and Talbot l conclude, "that our evidence points strongly and conclusively to the fact that the active mass of protoplasmic tissue determines the fundamental metab- olism. The absence as yet of a direct mathematical measure of the proportion of active protoplasmic tissue does not, we believe, in any wise affect the convincing nature of our evidence." The total basal metabolism of an infant increases with its age and weight, as would be expected. On the following chart, taken from the paper by Benedict and Talbot, 1 the normal infants are indicated by crosses and the abnormal infants, including those that are under-weight, are indicated by dots. A hypothetical curve has been constructed for the normals that shows the tendency of the metabolism to increase with the weights of the infant. In general, those infants which weigh more than the average for the the metabolism of adults and their body surface. There is a much closer agreement between the figures when the body surface is measured by the Du Bois formula which is the most accurate. 1 Benedict and Talbot: Am. Jour. Dis. Children, 1914, viii, 1. ENERGY METABOLISM 69 age lie above the curve while those which weigh less than the aver- age fall below the curve. CHART II Chart showing the actual body weight of infants and the total heat produc- tion per twenty-four hours TOTAL HEAT PER 24 HOURS t'/j MOS 255 285 135 165 195 225 X = NORMAL INFANTS = ABNORMAL INFANTS INCLUDING THOSE UNDERWEIGHT 315 345 875 405 435 465 495 525 The comparison of the basal heat production per kilogram of body weight is of more practical interest to the clinician. Chart III on the nexi page is taken from the paper of Benedict and Talbot. In general, the babies weighing the average for the age and in all respects normal fall between the lines marked A and B or, roughly their basal metabolism is between 52 and 63 calories per kilogram of body weight. The normal infants, other than new-borns, that have a great deal of fat on their bodies in proportion to their muscu- lature, have a basal metabolism of between forty and a little more than fifty calories per kilogram of body weight. New-born infants are included in this class. Most of the infants that are under-weight 70 ENERGY METABOLISM CHART III Chart showing the actual body weight of infants and the heat production per kilogram per twenty-four hours HEAT PER KILOGRAM OF BODY-WEIGHT PER 24 HOURS B 9.0 8.0 7.0 :e.o 1 5.0 4.0 3.0 2.0 50 A B 65 have a basal metabolism of more than sixty-five calories per kilo- gram of body weight and, in general, the more they are under- weight, the greater is the basal metabolism. This chart shows that the basal metabolism per kilogram of body weight may vary 100% in different infants. There are some infants that are under-weight, whose vital functions are so depressed that their metabolism instead of being greater than the aver- age per kilogram of body weight, is less than the average. This is especially true of infants with subnormal temperatures, and may explain why some infants who have been very sick and as a result are weak, gain weight on surprisingly few calories. The Respiratory Quotient. The respiratory quotient is the ratio between the volume of carbon dioxid expired and the volume ENERGY METABOLISM 71 , . , , . ,. . vol. C0 2 _ of oxygen inspired during the same time, viz., : = R. Q. VOl. (J2 When carbohydrates are burned the respiratory quotient is unity, that is, for every hundred volumes of carbon dioxid excreted a hundred volumes of oxygen are absorbed. (The respiratory quo- tient for carbohydrates is 1.00.) The respiratory quotient for fat is 0.713 and for protein 0.801. The respiratory quotient, when carefully determined, throws considerable light on the character of the materials burned in the body. Caloric Values. Rubner's "standard values" have been widely used throughout the world in determining the average fuel value of a mixed diet. They are: 1 gram of protein 4.1 calories (large) 1 gram of fat 9.3 calories (large) 1 gram of carbohydrate 4.1 calories (large) The heats of combustion of the carbohydrates are as follows : Stohmann 1 Emery and Benedict * Dextrose 3.692 3.739 Lactose 3.877 3.737 Saccharose 3.959 3.957 Starch 4.116 Since the carbohydrates used in infant feeding are usually sugars rather than starch, the caloric value of the carbohydrate would be more accurate if a lower factor were used, for instance, 3.7 for lactose. Computed Metabolism. 3 The energy quotient is the term applied by Heubner 4 to the number of large calories per kilogram of body weight per day that are necessary for growth. The metab- olism of a large number of infants has been computed when the amount of fat, carbohydrate, or protein in the food was known, or in which averages of the various analyses of milk were taken. It has been shown by many investigators that the percentage com- position of human milk can vary within very wide limits, and ob- viously there must be a corresponding fluctuation in its caloric value. For this reason many of the computed energy quotients, based upon the average composition of human milk, are criti- 1 Quoted by Lusk: The Science of Nutrition, Phila. and London, 1909, 41. 2 Emery and Benedict: Am. Jour. Phys., 1911, xxviii, 301. Later they showed even a greater difference in the heat of combustion of lactose. 1 An excellent review of the Continental work may be found in Frank : Engergiequotient und Tempera tur im Saulingsalter. Inaug. Dissert. Miinchen, 1913. * Heubner: Kinderh., 3 auflage, Leipzig, 1911, vol. I. 72 ENERGY METABOLISM cised. Heubner * concluded that a breast-fed infant did not gain satisfactorily on human milk during the first three months when the energy quotient fell below one hundred calories, and that when the energy quotient fell below seventy calories there must be a loss of weight. Schlossman 2 on the other hand found the best gain on an energy quotient of one hundred and ten calories. Premature infants and artificially-fed infants, according to Heub- ner, should have an energy quotient of not less than one hundred and twenty calories during the first three months of life. Feer 3 found that the energy quotient of Baby Marianne, the composi- tion of whose food was known, during the thirty-third to the forty-sixth week of life was between eighty-six and one hundred and four calories. He believes that the reason artificially-fed infants require more calories than the breast-fed is that the work of digestion is greater in the former than in the latter. Cramer 4 studied the energy quotient of infants during the first nine days of life, and found a gain of from fifty to sixty grams with an en- ergy quotient of less than fifty calories. Gaus 5 confirmed these findings and it was concluded that there was a special metabolism for infants during the first two weeks of life. There is no doubt that the latter observations are true, and that during the first two weeks of life the caloric needs are very low. 6 The caloric requirements then increase up to the third or fourth month at which time they are close to those given by Heubner. After that they dimmish to the first year of life. Two infants, aged three and six months respectively, studied at the Nutrition Laboratory of the Carnegie Institution of Wash- ington by Talbot 7 showed a metabolism of 100 and 94 calories respectively per kilogram of body weight. The metabolism of these two infants was measured during the whole of twenty-four hour periods with the exception of short periods in which they were removed for feeding. Siegert 8 concluded that it was possible for the breast-fed in- fant to gain on eighty calories per kilogram of body weight dur- 1 Heubner: Jahrb. f. Kinderh., 1910, Ixxii, 121. 2 Schlossmann: Arch. f. Kinderh., 1902, xxxiii, 338. 3 Feer: Lehrbuch der Kinderh., 2nd Ed., 1912. 4 Cramer: Munch, med. Wochenschr., 1903, 2, L, 1153. 6 Gaus: Jahrb. f. Kinderh., 1902, N. F. Iv, 129. 6 Benedict and Talbot: Physiology of the New-Born Infant: Carnegie Ins., Wash., Publication No. 233. Murlin and Bailey: Amer. Jour. Obstetrics and Dis. Women and Children, 1915, Ixxi, No. 3. 7 Talbot. Trans. Am. Ped. Soc., 1917, xxix. 39. 8 Siegert: Versamml. d. Gesellsch., f. Kinderh., Stuttgart, 1906. ENERGY METABOLISM 73 ing the first three months of life. Czerny and Keller 1 consid- ered Heubner's figures too high and report an infant of average weight (Machill) which gained regularly on an average of seventy calories per kilogram of body weight. A daily examination of the milk was not made. Bundin 2 fed a number of infants on mix- tures of cow's milk which gave an energy quotient of seventy calories. These infants were of the average or of less than the average weight and gained weight consistently. Oppenheimer 3 gave an energy quotient of one hundred and eleven calories to a normally developed infant and as high as one hundred and forty-two calories to an infant which had previously been underfed. Beck, in 1904, 4 collected the literature up to date and gives the following figures as an average energy quotient for breast-fed infants: 1-12 weeks 107 calories 13-24 weeks 91 calories 25-36 weeks 83 calories 37-44 weeks 69 calories He concluded that artificially-fed and premature infants re- quired an energy quotient of from one hundred and twenty to one hundred and forty calories. Ladd 5 gave an energy quotient which varies between ninety-three and one hundred and fifty-nine cal- ories. Dennett 6 concluded that the average normal baby will do well on from one hundred and ten to one hundred and twenty cal- ories per kilogram and that very emaciated babies require from one hundred and sixty to one hundred and seventy calories, while those who are only moderately emaciated require from one hun- dred and thirty to one hundred and fifty calories. Finally, Fink- elstein, 7 Gittings, 8 and Mayerhofer and Roth 9 drew attention to the fact that infants who were under-weight required more calo- ries than well-developed infants and advanced the suggestion that they require as many calories as they would need if they had de- veloped in the normal manner. 1 Czerny and Keller: Des Kindes ErnUhrung, ErnShrungsstSrungen, und Erhahrungstherapie, Leipzig and Wien, 1906, vol. i, 396. 3 Bundin: See Czerny and Keller, p. 404. 3 Oppenheimer: Arch. f. Kinderh., 1909, L. 355. 4 Beck: Monatsschr. f. Kinderh., 1904-05, iii, 206. Ladd: Archives of Pediatrics, 1908, xxv, 178. 6 Dennett: Trans. Section on Dis. of Children, Amer. Med. Asso., 1912, 186. 7 Finkelstein: Lehrbuch der Sauglingskrankheiten, 1905, i, 54. 8 Gittings: Am. Pediatric Soc., Stockbridge, 1914, Reported in Jour. A. M. A., 1914, Ixiii, 55. 9 Mayerhofer and Roth: Zeitschr. f. Kinderh., 1914, xi, 117. 74 ENERGY METABOLISM The figures just given as to the clinical status of the caloric requirements of different infants show what a difference of opinion there is among the various authorities. There can be little doubt that in the main they are all correct, if one bears in mind the pos- sibility of error in such rough calculations of the energy metabo- lism of infants. Unfortunately, the accurate measurement of the energy metabolism in the calorimeter or by the respiratory ex- change is only for shorter or longer periods of the twenty-four hour day and does not give exact measurements of the twenty- four hour metabolism. It is necessary, therefore, to depend upon the knowledge of the basal metabolism of a large number of in- fants and to attempt to correlate this with the results of clinical experience. The metabolism of the new-born infant has been recently studied anew. 1 After birth there is a loss of weight which is due to two distinct causes : 1. Mechanical. 2. Physiological. The former is due to loss of meconium, urine and vomited ma- terial, while the latter is due to actual loss of body substance as a result of metabolism. The colostrum does not supply enough food for the infant in the first three days of life, before the breast milk "comes in"; the body substance, therefore, has to supply what is necessary for the infant's vital functions. The respiratory quotients show that during the first few hours of life the supply of glycogen and sugar in the body is quickly exhausted, and that the body must then subsist on its own fat. This it does until the body gets enough breast milk to supply the necessary food. There is also a distinct correlation be- tween the body temperature and the general metabolism, for when the temperature is subnormal, the metabolism is low, in- dicating that all the vital functions are below par. The usual cause of the subnormal temperature was chilling from the tub bath or exposure. This may be distinctly dangerous to life. The average basal metabolism of the new-born infant from !*/ to 6 days of life is 44 calories per kilogram of body weight, and it is estimated that the new-born infant requires 62 calories per kilo- gram of body weight in its food. These findings teach us that all precautions should be taken against exposure after birth, that the water cleansing bath may be dangerous to life and should, therefore, not be used, but in its place a warm oil bath may be 1 Bailey and Murlin: loc. tit. (6 infants); Benedict and Talbot, loc. tit. (104 infants). 75 given; that before the mother's milk "comes in" the baby does not get sufficient food, and, therefore, a sugar and water solution should be given to partly make up the deficit. A solution of 5% lactose proves very satisfactory. Metabolism During Starvation. Very few observations have been made on the metabolism during fasting, and nearly all of our knowledge comes from the work of Schlossmann and Mur- schhauser 1 in the Dusseldorf Clinic on normal infants. They found that there was always an increased nitrogen elimination from the body in both the infant that had been artificially fed or breast fed. The total amount lost was greater in the former than in the latter. Less nitrogen was lost if lactose were given the infant even in small quantities. The blood sugar remained nor- mal until near the end of a seventy-two hour fast when there was a slight fall. After twelve hours of fast, acetone bodies appeared in the urine and increased in amount in the same manner as during adult fasting. The excretion of acetone bodies was entirely pre- vented by giving 70 grams of lactose in the day. Summary. The basal metabolism of an infant is the metab- olism determined after the taking of food, with the infant in complete muscular repose. Comparison of infants in different states of nutrition shows that roughly the normal new-born infant has a basal metabolism of 44 calories per kilogram of body weight, while that of the older infant is about 55 to 60 calories per kilo- gram of body weight. This is the lowest amount of energy on which a baby can maintain its body functions. The habits of healthy infants vary with the individual. One is phlegmatic and sleeps most of the day and night, while another is moving, kick- ing or crying during most of its waking hours. It has been shown that the metabolism may be increased from forty to one hundred per cent above the basal metabolism by the change from complete muscular repose to active exercise. It seems probable, therefore, that the infants studied by Czerny, Budin and their followers were placid infants who conserved then- energy for development, and that Heubner and his followers dealt with more active infants. It is necessary to add certain factors to the calories found for the basal metabolism for muscular exercise, for loss of energy in the feces, and for growth. These can only be estimated by studying the habits of a given infant. The consensus of opinion seems to be that breast-fed infants require less energy than the artificially- fed, because less energy is required to make the food available for 1 Schlossmann and Murschhauser: Biochem. Zeitschr., 1913, Ivi, 335; Schlossmann: Biochem. Zeitschr., 1914, Iviii, 493. 76 ENERGY METABOLISM the body. This may be the sole explanation, or it may be that the difference in their requirements is due to the fact that the breast- fed infant is on the average a quieter infant and that it sleeps more than the artificially-fed infant. Babies that weigh more than the average weight for their age and new-born infants have usually a basal metabolism of between forty and fifty-two calories per kilogram of body weight. Both the new-born and fat infants are quieter than infants which have developed their muscles and as a result the energy required for muscular work, which must be added to their basal energy metab- olism, is less than it is in active, crying infants. The large fat babies which weigh more than the average will, therefore, gain more weight on a low energy quotient than babies of average weight. The new-born infant falls into this class as it has a rela- tively large proportion of fat and a small proportion of muscle. Moderately emaciated or atrophic infants have a higher basal metabolism than do the babies of average weight. It varies be- tween sixty-three and eighty-seven calories per kilogram of body weight. When the energy required for muscular work is added to this, the energy quotient is the result. It must be remembered, however, that infants of this type that have many loose undigested stools may lose twenty per cent 1 or more of the energy of the food. Some under-weight infants require many more than the 120 calories per kilogram of body weight, which is considered the high normal figure. If the infant is very weak and quiet, a small increase in the number of calories above the basal requirements will be suffi- cient to enable it to gain in weight. If, on the other hand, it is crying from morning to night because of either hunger or dis- comfort, a very much greater percentage of calories must be added to the basal requirements in order that it may grow. There laso can be little doubt that in weak babies energy, which would other- wise be used to keep the baby warm, can be conserved by increas- ing the temperature of the infant's surroundings. The infant that is under-weight requires, therefore, somewhere between one hun- dred and thirty and one hundred and sixty calories per kilogram of body weight. The normal new-born infant requires approxi- mately 62 calories per kilogram of body weight. The energy requirement increases in the first quarter year up to between 100 and 120 calories and then gradually falls so that at the end of the first year the normal infant needs between 70 and 80 cal- ories per kilogram of body weight. These figures are modified by the individual peculiarities of the infant. 1 Benedict and Talbot: Am. Join*. Dis. Children, 1914, viii, 1. CHAPTER VII BACTERIOLOGY OF THE GASTROINTESTINAL CANAL 1 BACTERIOLOGY OF THE MOUTH The infant's mouth is sterile before birth, but becomes infected from the mother's vagina during birth, 2 or from the air soon after birth. 3 The variety of organisms present at this time is relatively small, but as soon as the infant commences to take food the flora becomes more complicated. The number of bac- teria does not, however, increase materially. When the infant takes breast milk, there is an increase in the variety of the or- ganisms, and pathological bacteria even may be found in the mouths of healthy babies. 4 Because of the fact that even the purest cow's milk contains more bacteria than human milk it is reasonable to expect that the mouths of babies fed on the bottle will contain a greater variety of bacteria than those fed at the breast and that the dirtier the milk the greater will be the variety of the organisms. There are, however, no data as to whether this is true or not. After the eruption of teeth, i. e., after the infant is six months old, the number and variety of the bacteria increase 5 and certain microorganisms, such as the Leptothrix, 6 and fusiform bacteria, 7 which are apparently only able to obtain a foothold in the mouth when teeth are present, 8 appear. It is an open question as to how important a part the bacteria of 1 G. Bessau in Tobler, Allegemeine Pathologische Physiologic der Er- n'ahrung und des Stoffwechsels im Kindesalter, Wiesbaden, 1914, has been freely used in this chapter and many of the statements have been taken directly from it. It may be consulted by those who wish to go into the subject more deeply. 2 Kneise: Sittler quoted by Tobler. 3 Campo: La Pediatria, 1899, vii, 229. 4 Doernberger: Jahrb. f. Kinderh., 1893, xxxv, 395; Herzberg: Deutch. med. Woch., 1903, xxix, 17. 5 Noblccourt and Vicaris: Arch. gen. de Med., 1905, 2, 3201, ref. Monats- schr. f. Kinderh., 1905-6, iv, 640. Oshima: Arch. f. Kinderh., 1907, xlv, 21. 7 Uffenheimer: Munch, med. Woch., 1904, 1198, 1253; Ergebnisse d. inn. Med. u. Kinderh., 1908, ii, 304. 8 For a more detailed account of the flora of the mouth E. Kuster in Kolle Wasserman's Handbuch, II ed., Jena, 1913, vi, 435, may be consulted. 77 78 BACTERIOLOGY the mouth play in the digestion processes in the stomach. It is conceivable that these bacteria, especially when there is dental caries, may do harm. It has not been proven, however, that they do. BACTERIOLOGY OF THE STOMACH The same influences which modify the bacterial flora of the mouth modify that of the stomach. Under physiological con- ditions the bacteria in the stomach play an unimportant r61e. A description of the individual kinds may be found in the works of Escherich l who was a pioneer in this field of investigation. The smallest numbers are found in the stomachs of the breast- fed, 2 and they remain relatively scarce as long as the digestion is normal. When there is indigestion, there is an increase in their numbers. The greatest numbers are found in cholera in- fantum. 3 Bactericidal Powers of the Stomach. Free hydrochloric acid is able to destroy bacteria in the stomach. 4 There is no doubt that it is strongly attracted by the proteins of the food and quickly combines with them, thus becoming inert. Furthermore, the casein in the milk is rapidly coagulated into curds. The disinfecting action of the hydrochloric acid can only be effective on the sur- face of the curds, and the large numbers of bacteria which are present in the interior of the curds are not reached by it. 5 The number of bacteria in the stomach apparently depends also on the activity of the gastric motility, for the quicker the stomach is emptied, the fewer are the bacteria which it contains. The converse is also true. Lactic acid fermentation does not seem to play as important a part in the stomach of the infant as it does in that of the adult in which it occurs only when hydrochloric acid is absent. Lactic acid is seldom or never found in the stomach of the breast-fed, but is fre- quently found in small amounts in the stomachs of infants fed on cow's milk. 5 Butyric acid fermentation is more common, 6 and has been found to occur in the stomachs of atrophic infants in which the ex- cretion of hydrochloric acid and the motility are both diminished. 1 Escherich: Die Darmbakterien des Sauglings, Stuttgart, 1886. * Van Puteren: Ref. Zeitschr. f. mikroskopie, 1888, v, 539. 3 Seiffert: Jahrb. f. Kinderh., 1891, xxxii, 392. 4 Hamburger: Ueber die Wirkung des Magensaftes auf pathogene Bakterien. Inaug. Diss. Breslau, 1890, quoted by Tobler. 6 Tobler: Ergeb. d. inn. Med. u. Kinderh., 1908, i, 495. "Cassel: Arch. f. Kinderh., 1890, xii, 175. BACTERIOLOGY 79 The pasteurization or boiling of milk destroys the organisms which produce lactic acid but does not kill the spore-bearing bacilli, 1 which produce butyric acid. The latter causes the formation of butyric acid from carbohydrates and fat and possibly from protein. Whether butyric acid is formed or not depends, according to Tob- ler, not on the kind of food present, but on the type of bacteria. This may be in part true, because fermentation cannot take place without fermentative organisms. On the other hand, however, the food components necessary for fermentation must be present in sufficient quantity to supply the bacteria with fermentable material. The lactic acid bacilli and the butyric acid bacilli are the only organisms which usually play a part in the various proc- esses of acid production in the stomach. The other bacteria (B. bifidus, B. acidophilus, B. coli and B. lactis aerogenes), which form acid are usually found only in the lower intestinal canal. BACTERIOLOGY OF THE UPPER PART OF THE SMALL INTESTINE The upper part of the small intestine, in comparison with the rest of the digestive canal, is relatively free from bacteria, both in the breast and in the bottle-fed infant, especially during fasting. Hess 2 studied the bacteria of the duodenum during life by an ingeniously devised modification of his duodenal catheter. He found that in the new-born infants, who had received no food, the duodenum contained very few organisms, only from one to three growing on a plate. The organisms were staphylococci, Gram positive and Gram negative bacilli. Colon bacilli were not found. Infants in the first week of life also had very few bacteria in the duodenum and these were of the same varieties as those found soon after birth. There was more or less similarity between the bacteria of the stomach and the duodenum. The staphylococcus was the organism most frequently found at this age. Hess could not establish any relation between the amount of hydrochloric acid in the stomach, or of bile in the duodenum, and the number of bacteria. The presence or absence of icterus made no difference in the bacteriology of the duodenum in these babies. Cultures from the duodenal contents of older breast-fed babies showed from one hundred to two hundred colonies per plate. The plate method would not be satisfactory for an ae'ro- 1 (Bodkin's butyric acid bacillus appears to be relatively rare and it is possi- ble that the gas-bacillus, which also forms butyric acid, is the one that is ordinarily found.) 2 Hess: Ergebnisse der inn. Med. u. Kinderh., 1914, xiii, p. 530. 80 BACTERIOLOGY bic organism such as the bacillus bifidus, which may also be found in this region. It must be remembered, therefore, that these results may not represent the true condition. Those from bottle-fed infants showed many more. 1 There is evidence that, while the duodenum may be practically free from bacteria during the intervals between digestion, there is a relatively large population in the small intestine while the food is passing through it. 2 According to Ficker 3 and Moro 4 the flora of the upper small intestine is composed principally of short Gram negative rods (colon bacillus and bacillus lactis aerogenes) with an occasional isolated bacillus bifidus communis, bacillus acido- philus and butyric acid bacillus, and enterococci. Moro 5 believes that there can be an endogenous infection of the small intestine. Such an infection is probably present in most disturbances of nutrition, both acute and chronic. The epidemic of severe diarrhea, associated with the presence of inflammatory products in the stools (blood and pus), described by Escherich 6 has been used as evidence for this point of view. The infants attacked were all young, then* ages varying from four to ten months. The stools contained bacteria, which he called "blaue Bacillose" and which were proved to be, almost without question, "aciduric" 7 or acidophilic organisms. These organisms were probably identical with those which are normally present among the flora of the healthy nursling. Logan 8 on the other hand was unable to show that any colon-like organisms from cases with diarrhea showed any greater virulence to guinea pigs than the same organisms from babies not suffering from diarrhea. BACTERIOLOGY OF THE LOWER PART OF THE SMALL INTESTINE AND OF THE LARGE INTESTINE There are relatively fewer bacteria in the healthy small intes- tine down to the lower part of the ileum. There they begin to increase in number so that when the large intestine is reached 1 Moro; Jahrb. f. Kinderh., 1905, Ixi, 870, may be consulted for the litera- ture. 2 Moro: Arch. f. Kinderh., 1906, xliii, 340; Kohlbrugge: Cent. f. Bact., Orig. 1901, xxix, 571; Landsberger: Diss. Konigsberg, 1903, quoted by Kendall. 3 Ficker: Arch. f. Hyg., 1905, liv. 354. 4 Moro: Arch. f. Kinderh., 1906, xliii. 6 Moro: Munchen. Gesellsch. f. Kinderh., 1907, xi, 15. 6 Escherich: Jahrb. f. Kinderh., 1900, 52, 1. 7 Kendall: Jour. Med. Research, 1911, xx, 117. 8 Logan: Jour. Path, and Bact., 1914, xviii, 527. BACTERIOLOGY OF STOOLS 81 they are very numerous. The types of bacteria which are com- monly found, according to Kendall, are as follows: 1 The more commonly recognized bacteria are the B. bifidus (Tissier), the Mic. ovalis, the B. coli, the B. lactis aerogenes, and the B. acido- philus (Moro). These make up the fecal flora of the normal nurs- ling. The B. lactis aerogenes appears in the upper levels of the tract, that is, the duodenum and jejunum; the Mic. ovalis in the lower jejunum and in the ileum to the ileocaecal valve; the B. coli and the B. acidophilus in the region of the ileocsecal valve, while the B. bifidus appears to dominate the ascending and transverse colon. This cannot be accepted without reservation since intes- tinal bacteriology is by no means so simple as it would appear from the foregoing statement. The remainder of the tract to the anus is relatively poorly populated in relation to the ccecum so far as living bacteria are concerned. This is due in part to the consid- erable degree of desiccation of the fecal contents of the intestines and in part to the accumulation of waste products, which appear to inhibit the development of bacteria. The character of the bacteria in the large intestine depends largely upon the food, 2 and, since human milk is a relatively homo- geneous food, the tendency of the bacteriological flora of the breast- fed is toward uniformity. The bacteriological conditions in the artificially fed are, as would be expected, less consistent, because there is less uniformity in the food which they receive, and because cow's milk is rarely sterile. The distinctive features of the stools of the artificially fed are the relative increase of Gram negative bacilli of the colon-aerogenes type and of cecal forms of the Mic. ovah's types. Coincidently, there is a decrease in the number of organisms of the B. bifidus type. The B. acidophilus is relatively more numerous and the B. bifidus less numerous. BACTERIOLOGY OF THE STOOLS The first stools (meconium), of the new-born are sterile, but they become infected shortly after birth. Within eighteen to twenty-four hours after birth, bacteria make their appearance in the stools and the meconium begins to disappear. The kinds and the number of bacteria which are found depend largely upon the season and the environment of the infant. 3 This is a period of mixed infection. The following organisms have been found 1 Kendall: Jour. Med. Research, 1911-12, xx, 117. * Moro: loc. cit. * Kendall: Wisconsin Med. Jour., 1913, xii, No. 1. 82 BACTERIOLOGY OF STOOLS in meconium: B. subtilis, B. coli, 1 B. bifidus, B. putrificus (Bien- stock), butyric acid bacillus, 2 and enterococci. 3 These organisms undoubtedly gain entrance to the intestinal canal through both the mouth and the anus. Meconium is a poor culture medium, probably because of its small water content. The B. bifidus appears about the beginning of the third day and persists throughout the nursing period. It is an obligate anaerobe (Kendall), Gram positive, and is the most characteristic organism of the nursling's stool. It is apparently independent of the quality of the stool and is present in the classical golden-yellow, homog- eneous, pasty stool as well as in those which deviate from this character in consistency and color. 4 Although the B. bifidus dom- inates the typical field, other Gram positive bacteria can always be found. Other bacteria that have been described in the stools of the nursling are cocci, the B. lactis aerogenes, the B. coli, the B. acidophilus, butyric acid bacillus, the B. mesentericus and the B. aerogenes capsulatus (Welch). The bacteriology of the stools of the artificially-fed infant is much more complicated than that of the breast-fed. No charac- teristic type of bacteria predominates, but there is a mixture of bacterial types. Culturally, the same species are found as in the stools of the breast-fed infant. The general picture is, however, apt to be Gram negative in contradistinction to that of the stool of the breast-fed infant, which is usually Gram positive. The B. coli communis, and the B. lactis aerogenes are the most numer- ous of these predominating Gram negative bacteria. A peptoniz- ing bacillus, which is almost always absent from the stools of the breast-fed, has been recorded by Rodella. 5 Passini 6 found these types of butyric acid forming organisms, and isolated peptonizing organisms from the stools of apparently normal bottle-fed babies. The B. putrificus, the most typical example of a purely proteolytic organism, has been found in several cases. The discussion as to the causes which influence the appearance and disappearance of certain bacteria is of more than polemic in- terest, since it may lead to some conclusions which will have a practical application. Kendall's 7 view is given as follows: "The intestinal tract is sterile at birth, because the uterine cavity is 1 Escherich: loc. cit. 2 Moro: Jahrb. f. Kinderh., 1905, Ixi, 885. 3 Sittler: Habititationsschr., Wurzburg, 1909, quoted by Tobler.