Marine Biological Laboratory Library Woods Hole, Massachusetts Gift of F. R. Lillie estate - 1977 • • . . • . ^B • B A TEXT BOOK OF PHYSIOLOGY A TEXT BOOK OF PHYSIOLOGY BY M. FOSTER, M.A., M.D., LL.D., F.R.S., PROFESSOR OF PHYSIOLOGY IN THE UNIVERSITY OF CAMBRIDGE, AND FELLOW OF TRINITY COLLEGE, CAMBRIDGE. WITH ILLUSTRATIONS. FIFTH EDITION, LARGELY REVISED. PART II., COMPRISING BOOK II. The Tissues of Chemical Action with their respective Mechanisms. Nutrition. Hontron : MACMILLAN AND CO. AND NEW YORK. 1889 [The Eight of Translation is reserved.] CTambritigr : PRINTED BY C. 3. CLAY, M.A. AND SONS. AT TITK UNIVERSITY PRESS. Firtt Edition 1876. Second Edition 1877. y/x><7 Edition 1879. Fourth Edition 1883. Reprinted 1884, 1886. F(#7i Edition, 1880. CONTENTS OF PART II. BOOK II. THE TISSUES OF CHEMICAL ACTION WITH THEIR RESPECTIVE MECHANISMS. NUTRITION. CHAPTER I. THE TISSUES AND MECHANISMS OF DIGESTION. PAGE § 196. Food-stuffs. The several stages of Digestion 355 SECTION I. THE CHARACTERS AND PROPERTIES OP SALIVA AND GASTRIC JUICE. Saliva. § 197. The chemical characters of saliva. Muciii ..... 357 § 198. The properties of saliva. The action of saliva on starch. Characters of starch, dextrins, dextrose, maltose 358 § 199. The nature of the amylolytic action of saliva. The amylolytic ferment 361 § 200. The characters of parotid, submaxillary, sublingual and mixed saliva 362 Gastric juice. § 201. The chemical characters of gastric juice ...... 364 § 202. The action of gastric juice on proteids. Artificial gastric juice. The characters of the more important proteid bodies. Formation of acid-albumin .......... 365 § 203. Peptone and albumose. Parapeptone. Classification of proteids . 369 vi CONTENTS. PAGE §204. Circumstances affecting gastric digestion ; acidity, temporal un . 371 § 205. The nature of the action of gastric juice. Pepsin . . . 373 § 20(>. The action of gastric juice on gelatine, chondrin &c. . . . 374 § 207. The action of gastric juice on milk. Curdling of milk. Casein. Renniu 374 SECTION II. THE STRUCTURE OF THE SALIVARY GLANDS, THE GASTRIC Mucors MKM- BRANE, THE PANCREAS AND THE (Es< .ni.\< . § 208. The general plan of structure of the alimentary canal ; mucous, sub- mucous, and muscular coats . 377 § 209. The general nature of glands . . 379 Structure of the Stom/ '>lU'TI"N KUiiM Till; AlIMKNTAKY ( \\N\I. § 305. The main products of digestion, and the two paths of absorption open for them .......... 511 77,, ('"'//•.«•• t'lk'K )>ii (/>•• teveral § 306. The course taken l.y tlic futs . . . .512 §307. The oonrae taken by water and Balte ....... 513 S 308. The course taken liy sugar ........ 513 § 309. The course taken by proteids .... ... 514 ' § 310. The mechanism of the absorption of the fats ..... 516 S 311. The pumping action of the villi ....... 519 mechanism of the absorption of diffusible substances and of watiT. Illations of the process to diffusion. Action of the cells ............ 520 § 313. The two stages of the act of absorption ; their nature . . . 524 CHAPTER II. RESPIRATION. SECTION I. THE STRUCTURE OF THE LUNGS AND THE BRONCHIAL PASSAGES. § 314. The function of the lungs chiefly mechanical 526 § 315. The structure of the lung of the newt 527 § 316. The structure of the lung of the frog 528 § 317. The general structure of the mammalian lung : bronchia, bronchioles, infundibula and alveoli 529 § 318. The structure of an mfundibulum 530 j; 319. The structure of the trachea and bronchi 530 § 320. The structure of the bronchia and bronchioles .... 532 § 321. The structure of the alveoli . . 532 § 322. The lymphatics of the lungs 533 § 323. The nerves of the lungs 534 CONTENTS. xi SECTION II. THE MECHANICS OF PULMONARY KESPIRATION. PAGE | 324. The entrance and exit of air into and from the lungs ; tidal and stationary air 535 § 325. Complernental, reserve or supplemental and residual air. Eesults of an opening into the pleural chamber 536 § 326. The lungs before birth and the changes at birth .... 537 § 327. The pressure exerted in breathing and the quantity of air moved . 537 §328. The graphic records of the respiratory movements ; pneumatograph 538 § 329. The curve of respiratory movements ...... 542 The Respiratory Movements. § 330. The visible movements 543 § 331. The movements of inspiration. The movements of the diaphragm . 543 § 332. The elevation of the ribs 544 § 333. The muscles which move the ribs ....... 545 § 334. The muscles of laboured inspiration ....... 546 § 335. Expiration, The expiratory muscles 547 § 336. Facial and laryngeal respiration ..... . 548 SECTION III. THE CHANGES OF THE AIR IN RESPIRATION. § 337. The changes in temperature ........ 550 § 338. The aqueous vapour in expiration ....... 550 .§ 339. The gaseous changes .......... 550 § 340. The diminution in volume ........ 551 § 341. The organic impurities in expired air 552 SECTION IV. THE RESPIRATORY CHANGES IN THE BLOOD. § 342. The gases of arterial and venous blood. The mercurial gas pump . 553 The Relations of Oxygen in the Blood. § 343. The absorption of oxygen by blood is not according to ' the law of pressures' 557 § 344. The characters of haemoglobin 559 :§ 345. The spectroscopic features of haemoglobin . . . 560 § 346. The spectroseopie features of reduced haemoglobin . 563 § 347. The oxygenation and reduction of hamioglobin . . . 564 § 348. The colour of venous and arterial blood . . . 565 •j§ 349. Carbonic-oxide-hsemoglobiu .... 566 b 2 xii CONTENTS. 1'roducts of the Decomposition o PAOE § 350. Haemoglobin splits up into lufniatiii and a proteid .... 567 § 351. The features of hwmatiu. H;«iuin. Metlm aioglobiu . . . 568 The relations of the Carboni .!«•/ in tin IHood. § 353. The nitrogen simply absorbed ........ 571 SECTION V. TllK IJESl'IRATORY ('HANt.KS IN THE LUNGS. § 354. The relations of the oxygen of the blood to pressure. Association of oxygen with, and dissociation from hii-moglubin. The problem stated ....... ... 572 ji 355. The experimental evidence ........ 574 § 356. The relations of the oxygen in laboured breathing and asphyxia . 575 Tli>- K.'-it of Carbonic Acid. § 357. The exit of carbonic acid determined by the partial pressure in the pulmonary alveoli ......... 575 SECTION VI. THK Kl.M'IRATORY CHAN'.KS IN THK Tl>MK>. § 358. The oxidations of the body take place mainly in the tissues and not in the circulating blood. The respiration of muscle . . . 578' § 359. The respiration of other tissues. The taking in of oxygen separate from the giving out of carbonic acid ...... 580 § 360. A summary of respiration in its chemical aspects .... ~*2 SECTION VII. THE NERVOUS MECHANISM OF RESPIRATION. S 361. Respiration an involuntary act. The efferent nerves, the respiratory centre ............ 584 § 362. The complex nature of the medullary respiratory centre ; the sub- sidiary spinal mechanisms ........ 585' § 363. The action of the centre automatic ....... 5Hi; § 364. The centre influenced by afferent impulses. The respiratory action of the vagus nerve. Inhibitory and augmentor effects . . 587 § 365. The double action of the centre, inspirator? and expiratory. Antag- onism between the two . . . - •• . 591 CONTENTS. xiii PAGE § 366. The effects of inflation and suction. Double action of the vagus fibres. Self-regulating mechanism ...... 592 $ 367. The nature of the action of the centre 596 § 368. The influence on the respiratory centre of various afferent impulses . 596 § 369. The respiratory centre composed of two lateral halves . . . 598 g 370. The respiratory centre influenced by the condition of the blood brought to it. Eupncea, Hyperpncea and Dyspnoea . . . 598 § 371. The direct character of these influences. Effects of heat on the respiratory centre ......... 599 § 372. The relative shares taken by deficiency of oxygen and excess of carbonic acid in the above influences ...... 600 § 373. Changes in the blood other than differences in the gases influence the respiratory effect. The effects of muscular exercise . . 602 § 374. The phenomena and causes of apnoea 603 § 375. Secondary respiratory rhythm. The Cheyue-Stokes respiration . 605 SECTION VIII. THE EFFECTS OF CHANGES IN THE COMPOSITION AND PRESSURE OF THE AlR BREATHED. jg 376. The phenomena of asphyxia 60b § 377. The effects of breathing oxygen 609 .§ 378. The effects on respiration of breathing various foreign gases . . 609 J 379. The effects of a diminution of pressure in the air breathed . . 610 .§ 380. The effects of an increase of atmospheric pressure .... 611 SECTION IX. THE RELATIONS OF THE RESPIRATORY SYSTEM TO THE VASCULAR AND OTHER SYSTEMS. .§ 381. The respiratory movements influence the circulation. The respiratory undulations of the blood-pressure curve 613 § 382. The effects of the expansion of the thorax and its return on the flow of blood to and from the heart and so on the blood- pressure 615 § 383. The effects of the expansion and return of the thorax on the flow of blood through the lungs 618 .§ 384. The effects on the circulation of artificial respiration . . . 619 4; 385. An action of the cardio-iuhibitory centre synchronous with that of the respiratory centre 620 '.»!. The general features and arrangement of the tubuli uriniferi . . r.:{i; § 395. The structure of the Malpighian capsule and the special characters of a tubulus uriniferus in the several parts of its course . . »',:;:> § 396. The meaning of these characters, and the structure of the tubulus uriniferus in the amphibia (il.H §397. The vascular arrangements of the kidney. 644 § 3118. The connective tissue stroma of the kidiu y 646 §399. The nerves of the kidney . . . . . i;n; SECTION II. THE COMPOSITION AND CHAI;A«TKHS OF URINE. •5 400. The general characters of urine ill* § 401. The normal organic constituents of urine 649 § 402. The inorganic salts 650 •5 403. The non-nitrogenous constituents of the urine ..... 651 § 404. The pigments of the urine 651 ji 405. Ferments and other bodies present in urine 652 § 406. The relative quantities of the more important constituents of urine . 653 §407. The acidity of uriue ('>".] § 408. The abnormal constituents of urine 654 SECTION III. THE SECRETION OF URINE. § 409. The double nature of urinary secretion 656- § 410. The vaso-motor mechanisms of the kidney. The renal oncorneter and oncograph . 657 CONTENTS. xv PAGE § 411. The relation of the flow of blood through the kidney to variations in blood-pressure and to vaso-motor changes in general . . 660 § 412. The vaso-constrictor nerves of the kidney ..... 662 § 413. The vaso-dilator nerves of the kidney 663 § 414. The influence on the renal circulation of chemical substances in the blood 664 § 415. The connection between changes in the renal circulation and the secretion of urine 664 Secretion by the Renal Epithelium. § 416. The evidence of the secretory activity of the epithelium. Ex- periments on amphibia. The results of injecting sulphindigo- tate of sodium 665 §417. The nature of glomerular secretion; its relation to filtration and diffusion. Albuminous urine 668 § 418. The nature of the work of the epithelium as regards the secretion of urea 671 § 419. The formation of hippuric acid ....... 672 § 420. The relations of the secretory activity of the kidney to the secretory activity of the skin . 674 § 421. The relations of the secretion of urine to food and drink . . . 675 § 422. Diuretics 676 § 423. Direct action of the nervous system on the kidney .... 677 SECTION IV. THE DISCHARGE OP URINE. § 424. The structure of the ureter 678 § 425. The structure of the bladder 679 § 426. The movements of the ureter 679 Micturition, § 427. The muscles of the bladder, their action, the nerves governing them; the sphincter vesicaj ......... 680 § 428. The varying tone of the bladder 682 § 429. The general nervous mechanism of micturition .... 682 § 430. Involuntary and voluntary micturition 684 § 431. Changes of the urine during its stay in the bladder .... 685 SECTION V. THE STRUCTURE OF THE SKIN. § 432. The general structure of the skin. The features of the dermis . 6sC> § 433. The structure of the epidermis ; the Malpighian and the horny layer 687 § 434. The stratum granulosum and stratum lucidum .... 688 § 435. The characters and genesis of the cells of the horny layer; keratin . 689 § 436. The sweat glands 690 § 436. The sebaceous glands. The structure of hairs 691 xvi CONTENTS. SECTION VI. THE NATURE AND AMOUNT OF PERSPIRATION. PAGE i 13H. Sensible and insensible perspiration. Tlie characters and constituents of sweat ........... 694 ineotu i l.'VJ. The nature and amount of cutaneous respiration. The effects of varnishing the skin . . ....... (596 ; 1 10. Absorption by the skin . .697 | SECTION VII. THE MECHANISM OK THI; SECRETION OF SWEAT. ? 111. The relation of sweating to vascular changes. The nervous mechanism of the sweat-glands ......... 699 ?; 442. The sweat-nerves, their origin and course ..... 701 § 443. Inhibitory sweat-nerves ......... 702 CHAPTER IV. Tin: METABOLIC PROCESSES OF THE BODY. i. ill. The general characters of the metabolism of the body . . . 703 SECTION I. THE STRUCTURE OF THE LIVER. v 1 1.">. The general structure of the liver . 705 •j 1 Iti. The structure of a lobule of a liver . 706 S 447. Glissou's capsule ; the terminations of the hepatic artery 707 § 448. The structure of the bile ducts .708 ;; 449. The structure of the hepatic cells. Glycogen . . . 708 § 450. The arrangement of the cells. The bile capillaries . 709 § 451. The structure of the liver of the Frog .... . 711 s 152. The lymphatics of the liver .... 712 SECTION II. THE HISTORY OF GLYCOGEN. § 453. The characters of glycogen 714 § 454. The conversion of glycogen into sugar by the liver .... 715 •; 455. The influence of various foods in storing up glycogen. The storage of glycogen in the winter frog 716 § 456. The detailed characters of the hepatic cells in the frog . 719 § 457. The histological changes induced by food and circumstances in the hepatic cells of the frog 720 CONTENTS. xvii PAGE § 458. The corresponding changes in the mammal 720 § 459. The nature and meaning of these changes ..... 721 § 460. Views as to the manner in which glycogen is stored in the hepatic cells. By simple dehydration of sugar ..... 722 § 461. The glycogen formed by a product of the metabolism of the hepatic cells. Comparison of the two views ...... 723 § 462. The uses of glycogen. The formation of fat as a store of carbon - holding material 725 § 463. Glycogen in muscle 728 § 464. Glycogen in the placenta and in various tissues .... 729 Diabetes. § 465. Artificial diabetes 730 § 466. The nerves of the liver 731 § 467. The nervous mechanism of the diabetic puncture .... 731 § 468. Temporary diabetes from the use of drugs. Natural diabetes. The diminution of hepatic glycogen by arsenic and other agents . 732 SECTION III. THE SPLEEN. § 469. The general structure of the spleen 735 § 470. The reticulum of the spleen 736 § 471. The blood vessels of the spleen and their relation to the reticulum . 737 § 472. The lymphatics of the spleen. The Malpighian corpuscles . . 738 § 473. The nerves of the spleen 739 § 474. The spleen pulp ; the white and red corpuscles. Changes undergone by the latter 739 § 475. The movements of the spleen. The spleen curve .... 740 § 476. The chemical constituents of the spleen 742 SECTION IV. THE FORMATION OP THE CONSTITUENTS OF BILE. § 477. The formation of bilirubiu from haemoglobin ..... 744 § 478. The nature of and preparations towards this formation . . . 746 § 479. The formation of bile acids 747 § 480. The relations of the secretion of bilirubin to the secretion of bile acids 748 § 481. The relation of the secretion of bile to the formation of glycogen . 749 SECTION V. ON UREA AND ON NITROGENOUS METABOLISM IN GENERAL. § 482. Urea the end-product of the metabolism of proteid matter . . 750 § 483. Urea probably the result of a series of changes .... 751 § 484. The kreatin of muscle in its relations to urea 751 § 485. Difficulties presented by the normal presence of kreatin in urine . 752 § 486. The nitrogenous metabolism of the nervous tissues . 753 xviii CONTEXTS. PA i ;K The nitrogenous metabolism of the glandular structures. The increase of urea due directly to food ...... 7">l § 488. The formation of urea in the liver ....... 7", § 489. The synthesis of uiva . .... 756 S I'.lO. Uric acid ............ 757 > I'.il. Other nitrogenous crystalline bodies such as xanth in A.. . . . 7"-s §492. Kelations of urea to cyanogen compound- ..... 759 >i I'.m. A summary of nitrogenous metabolism ...... 759 SECTION VI. ON .SOMK STRUCTUHKS ANH l'u<" B8BBB <>F AN <>i:srru>: XATTKE. S I'.H. The structure of the thyroid body . 761 § 495. The functions of the thyroid body .... . . 7<'>H S J'.Ml. The pituitary body .... 7f>l i 1'.'7. The structure of the suprarenal bodies ...... 7i'>~> S I'.lH. The chemical constituents of the suprarenal bodies .... 7i>i'> •5 I'.i'.i. Tlie functions of the suprarenal bodies ...... 7i-i'' §500. The structure of thr thymus ... . 7»i7 § 501. The nature and functions of the thyinus ...... 7'N SECTION VII. Tm: ElSTOBl OF FAT. ADIPOSE Ti.— n . §502. Adipose tissue ; its changes ........ 7i'>'.i §503. The structure of adipose tissue . . 7i'.'.' § 504. The disappearance of fat from adipose tissue ... . 771 § 505. The nature of fat in adipose tissue ..... . . 772 §506. Fat is formed in the body ...... 772 § 507. Formation of fat from carbohydrates and from protcid- . . 773 § 508. Limits to the construction of fat ....... 775 SKCTIOX VIII. THK MA.MMAUY <}I.AM>. § 509. The general structure of the mammary gland ..... 777 § 510. The structure of the alveoli ; the varying appearances of the epithelial cells ............ 778 §511. The characters of the dormant mammary gland .... 780 § 512. The connective-tissue of the mammary gland ..... 780 §513. The nature of milk; its constituents; their relative quantities in different animals ......... 780 § 514. Colostrum, its chemical and microscopical characters . . . 783 § 515. The mammary gland at birth ........ 784 § 516. The nature of the act of secretion of milk ..... 784 § 517. The secretion of milk typical of metabolism in general . . 785 § 518. The relations of the gland to the nervous system .... 787 CONTENTS. xix CHAPTER V. NUTRITION. SECTION I. THE STATISTICS OF NUTRITION. PAGE § 519. The composition of the animal body ...... 788 § 520. The composition of the starving body and the general phenomena of starvation . . . . . . . . . 789 Comparison of income and output of material. § 521. The method of determining the income and output. The respiration chamber. The calculation of changes in the body based on a comparison of the income and output . . . . . 791 § 522. Nitrogenous metabolism. 'Tissue ' proteids and 'floating' proteids. Luxus consumption 794 § 523. The effects of fatty and carbohydrate food 797 § 524. The effects of gelatine as food 798 § 525. Peptone as food 799 § 526. The effects of salts as food 799 SECTION II. THE ENERGY OF THE BODY. The income of energy. § 527. The available potential energy of the several food-stuffs and of an ordinary diet 801 The expenditure of energy. § 528. The daily expenditure as heat and as work done. Calorimeters . 803 § 529. The energy of mechanical work does not arise exclusively from proteid metabolism ; urea and muscular exercise . . . 805 Animal Heat. § 530. The sources and distribution of Heat ; the muscles the chief source . 807 § 531. The temperature of the body; cold-blooded and warm-blooded animals 809 § 532. The regulation of the temperature of the body by variation in the loss of heat. The skin the great regulator .... 810 § 533. The production of heat, the circumstances determining it ; the effects of meals and of labour 812 § 534. The influence of the nervous mechanism in determining the pro- duction of heat ; the effects of heat and cold on the metabolism of the body are produced through the nervous system . . 814 § 535. The portions of the central nervous system concerned in this regu- lation of heat . . 816- NX CONTENTS. PAGE * •"•:<(>. The narrow limits within which the bodily temperature is main- tained 817 ?•">:-! 7. Abnormally high temperatures, pyrexia S17 ?. :.H8. The effects of great heat -H :• .Vi'J. The effects of great cold -1'.' i',10. Hibernation . . 820 SECTION III. ON NUTRITION IN I.KNKHAI.. ; ".(I. The general features of metabolism 822 i ". !•_'. The metabolism of muscle as typical of the metabolism of tissues; the nature of the food of muscle 823 ; "ilX The relations of metabolism to the structural features of muscle . s-j.'i ?, ."ill. The fate of the lactic acid produced by muscle 826 i "il"i. A comparison of the metabolism of muscular tissue with that of other tissues H27 * ".Hi. Proteid substance the pivot of metabolism 828 §511. Influences determining nutrition ; tin influence of food . . . s-js §548. The influence of nerves on metabolism; katabolic and anabolic nerves 829 § 549. The influence of the nervous system on the general nutrition of the tissues. The phenomena of disease itc. ; trophic nerves . . s'J'.i SKCTION IV. ON DIET. *: ~.">0. The normal diet, statistical and experimental 833 S V.I. The necessity for all three food-stuffs, proteids, fats and carbo- hydrates. The necessity and importance of salts including extractives; alcohol, tVc 835 § 552. The chemical value of articles of food to be corrected by their digestibility 838 § 553. The physiological value of a purely vegetable diet .... 839 § 554. The modifications of a normal diet needed to meet variations in size 842 § 555. The modifications of a normal diet needed to meet changes of climate 843 § 556. The modifications of a normal diet needed to promote or prevent fattening 844 § 557. The modifications of a normal diet needed to meet muscular and mental labour 845 LIST OF FIGURES IN PART II. pAGE 62. Diagrammatic representation of the submaxillary gland of the dog with its nerves and blood vessels ........ 397 63. Alveoli of the pancreas of a rabbit at rest and in activity . . . 405 64. Changes in the parotid gland during secretion ..... 407 65. Sections of the parotid gland of the rabbit at rest and after stimulation of the cervical sympathetic nerve ...... 408 66. Mucous cells from the fresh submaxillary gland of the dog . . . 409 67. Alveoli of dog's submaxillary gland in loaded and in discharged phases 410 68. Gastric gland of mammal (bat) during activity ..... 412 69. Diagram illustrating the influence of food on the secretion of the pancreatic juice .......... 433 70. Diagram to illustrate the nerves of the alimentary canal in the dog . 466 71. Apparatus for taking tracings of the movements of the column of air in respiration ..... . ..... 539 72. Tracing of respiratory movements . ..... . 542 73. Diagram of Ludwig's mercurial gas-pump ...... 554 74. Diagram of Alvergniat's pump ... ..... 556 75. The spectra of oxy-hsemoglobin in different grades of concentration, of (reduced) haemoglobin, and of carbonic-oxide-haemoglobin . . 562 76. Spectra of some derivatives of haemoglobin ..... . 569 77. Curve of the effect on respiration of section of one vagus . . . 588 78. Curve of the effect on respiration of section of both vagus nerves . . 589 79. Curve of the quickening of respiration by gentle stimulation of the central end of the vagus trunk ...... . 589 80. Curve of respiratory increase due to stimulation of vagus nerve . . 590 81. Curve of the inhibitory effects of stimulation of the superior laryngeal nerve ...... ...... 592 82. Curves illustrating the effects of distension and collapse of the lung . 593 83. Curve shewing the effects of repeated inflation of the lungs . . . 594 84. Curve shewing the effects of repeated suction of the lungs . . . 594 85. Curves of blood-pressure and intra-thoracic pressure taken together . 614 86. Curve of blood-pressure during a suspension of breathing . . . 623 \\ii LIST OF FIGURES IN PART II. i i... rv.r. 87. Gorve shewing Traube-Hering undulations ... . i;-ji 88. Renal oncometer . . t,.",s - I. Oncograph . . t'..v.i '.HI. Tracing from renal onoometer ........ i',i;n HI. Section of the liver of froK .... . .711 112. Three phases of the hepatic cells of the frog 718 '.iM. Section of mammalian liver ricli in ^Ivo- . . . . . 7-1 '.•I. Section of mammalian liver containing little or no glyoogen . . T'-'l 95. Xtninal spleen curve from dog 741 NOTE. The formula for Htematin given in § 351, p. 568, is the old one of Hoppe-Seyler ; that given in § 447, p. 744, is the more recent and probably more correct one of Nencki and Sieber. It was not observed until too late that in the diagram of the nerves of the alimentary canal in the dog § 276, p. 466, tivelve dorsal nerves had been represented. The figure, as stated, makes no pretence to anatomical exactness ; but it would have been better to represent either thirteen or fifteen (see § 412) dorsal nerves. EEBATA. p. 430, 1. 9, for § 237 read § 238. p. 434, 1. 23, „ § 232 „ § 233. p. 462, 1. 3, from bottom „ § 266 „ § 265. BOOK II. THE TISSUES OF CHEMICAL ACTION WITH THEIR RESPECTIVE MECHANISMS. NUTRITION. F. 23 CHAPTER I. THE TISSUES AND MECHANISMS OF DIGESTION. § 196. THE food in passing along the alimentary canal is subjected to the action of certain juices supplied by the secretory .activity of the epithelium cells which line the canal itself or which form part of its glandular appendages. These juices (viz. saliva, gastric juice, bile, pancreatic juice, and the secretions of the small and large intestines), poured upon and mingling with the food, produce in it such changes, that from being largely insoluble it becomes largely soluble, or otherwise modify it in such a way that the larger part of what is eaten passes into the blood, either directly by means of the capillaries of the alimentary canal or indirectly by means of the lacteal system, while the smaller part is discharged as excrement. Those parts of the food which are thus digested, absorbed and made use of by the body, are spoken of as food-stuffs (they have also been called alimentary principles) and may be conveniently divided into four great classes. 1. Proteids. We have previously (§ 15) spoken of the chief characters of this class, and have dealt with several members in treating of blood and muscle. We may here repeat that in general -composition they contain in 100 parts by weight "in round numbers" rather more than 15 parts of nitrogen, rather more than 50 parts of carbon, about 7 parts of hydrogen, and rather nmre than 20 parts of oxygen ; though essentially the nitrogenous bodies of food and of the body they are made up of carbon to the extent of more than half their weight. The nitrogenous body gelatin, which occurs largely in animal I'm id, and some other bodies of less importance, while more closely allied to proteid bodies than to any other class of organic sub- stances, differ considerably from proteids in composition and especially in their behaviour in the body ; they are not of sufficient importance to form a class by themselves. 23—2 356 FOOD-STUFFS. [BOOK IL. 2. Fats, frequently but erroneously called Hydrocarbons. These vary very widely in chemical composition, ranging from, such a comparatively simple fat as butyriu to the highly complex lecithin (§ 71); they all possess, in view of the oxidation of both their carbon and their hydrogen, a large amount of potential energy. 3. Carbo-hydrates, or sugars and starches. These possess weight for weight relatively less potential energy than do fats ; they already contain in themselves a large amount of combined oxygen and when completely oxidised give out, weight for weight, less heat than do fats. 4. Saline or Mineral Bodies, and Water. These salts are for the most part inorganic salts ; and this class differs from the three preceding classes in as much as the usefulness of its members to the body lies not so much in the amount of energy which may be given out by their oxidation, as in the various influences which, by their presence, they exercise on the metabolic events of the body. These several food-stuffs are variously acted upon in the several parts of the alimentary canal, and we may distinguish, as the food passes along the digestive tract three main stages : digestion in the mouth and stomach, digestion in the small intestine, and digestion in the large intestine. In many animals the first stage is, to a large extent, preparatory only to the second which in all animals is the stage in which the food undergoes the greatest change ; in the third stage the changes begun in the previous stages are completed, and this stage is especially charac- terised by the absorption of fluid from the interior of the alimen- tary canal. It will be convenient to study these stages, more or less apartr though not wholly so, and it will also be convenient to consider the whole subject of digestion under the following heads : — First, the characters and properties of the various juices, and the changes which they bring about in the food eaten. Secondly, the nature of the processes by means of which the epithelium cells of the various glands and various tracts of the canal are able to manufacture so many various juices out of the common source, the blood, and the manner in which the secretory activity of the cells is regulated and subjected to the needs of the economy. Thirdly, the mechanisms, here as elsewhere chiefly of a mus- cular nature, by which the food is passed along the canal, and most efficiently brought into contact with the several juices. Fourthly and lastly, the means by which the nutritious digested material is separated from the undigested or excremental material,, and absorbed into the blood. SEC. 1. THE CHARACTERS AND PROPERTIES OF SALIVA AND GASTRIC JUICE. Saliva. § 197. Mixed saliva, as it appears in the mouth, is a thick, glairy, generally frothy and turbid fluid. Under the microscope it is seen to contain, besides the molecular debris of food, bacteria and other organisms (frequently cryptogamic spores), epithelium-scales, mucus-corpuscles and granules, and the so-called salivary cor- puscles. Its reaction in a healthy subject is alkaline, especially when the secretion is abundant. When the saliva is scanty, or when the subject suffers from dyspepsia, the reaction of the mouth may be acid. Saliva contains but little solid matter, on an average probably about '5 p. c., the specific gravity varying from 1'002 to 1'OOG. Of these solids, rather less than half, about '2 p.c., are salts (including at times a minute quantity of potassium sulphocyanate). The organic bodies which can be recognised in it are globulin and serum-albumin (see §§ 16, 17) found in small quantities only, other obscure bodies occurring in minute quantity, and mucin ; the latter is by far the most conspicuous organic constituent, the glairiness or ropiness of mixed and other kinds of saliva being due to its presence. Mucin. If acetic acid be cautiously added to mixed saliva the viscidity of the saliva is increased, and on further addition of the acid a semi-opaque ropy mass separates out, leaving the rest of the saliva limpid. This ropy mass, which is mucin, if stirred care- fully with a glass rod, shrinks, becoming opaque, clings to the glass rod and may be thus removed from the fluid. If the quantity of mucin be small and the saliva be violently shaken or stirred while the acid is being added, the mucin is apt to be precipitated in flakes, and may then be separated by filtration. It may be added that the precipitation of mucin by acid is greatly influenced by the presence of sodium chloride and other salts ; thus after the addition of sodium chloride acetic acid even in considerable excess will not cause a precipitate of mucin. 358 MUCIN. [BOOK n, Mucin, thus prepared and purified by washing with acetic acid, swells out in water, without actually dissolving; it will however dissolve into a viscid fluid readily in dilute (01 p.c.) solutions of potassium hydrate, more slowly in solutions of alkaline salts. In order to filter a mucin solution, great dilution with water is necessary. Mucin is precipitated by strong alcohol and by various metallic salts ; it may also be precipitated by dilute mineral acids, but the precipitate is then soluble in excess of the acid. Mucin gives the three proteid reactions mentioned in § 15, but it is a very complex body, more complex even than proteids, for by treatment with dilute mineral acids, and in other ways, it may be converted into some form of proteid (acid-albumin when dilute mineral acid is used), while at the same time there is formed a body which appears to be a carbohydrate and resembles a sugar in having the power of reducing cupric sulphate solutions. Solutions of muein moreover on mere keeping are apt to lose their viscidity and to become converted into a proteid not unlike the body peptone, which as we shall see is the result of gastric diges- tion, and into a reducing body. Several kinds of mucin appear to exist in various animal bodies, but they seem all to agree in the character that they can by appropriate treatment be split up into a proteid of some kind and into a carbohydrate or allied body. § 198. The chief purpose served by the saliva in digestion is to moisten and soften the food, and to assist in mastication and deglutition. In some animals this is its only function. In other animals and in man it has a specific solvent action on some of the food-stuffs. Such minerals as are soluble in slightly alkaline fluids are dissolved by it. On fats it has no effect save that of" producing a very feeble emulsion. On proteids it has also no pecific action, though pieces of meat, cooked or uncooked, appear greatly altered after they have been masticated for some time ; the chief alteration however which thus takes place is a change in the haemoglobin, and a general softening of the muscular fibres by aid of the alkalinity of the saliva. Of course when particles of food are retained for a long time in the mouth, as in the interstices, or in cavities of the teeth, the bacteria or other organisms which are always present in the mouth may produce much more profound changes, but these are not the legitimate products of the action of saliva. The characteristic property of saliva is that of converting starch into some form of sugar. Action of Saliva on Starch. If to a quantity of boiled starch, which is always more or less viscid and somewhat opaque or turbid, a small quantity of saliva be added, it will be found after a short time that an important change has taken place, inasmuch as the mixture has lost its previous viscidity and become thinner and more transparent. In order to understand this change, the reader CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 359 must bear in mind the existence of the following bodies all belonging to the class of carbohydrates. 1. Starch, which forms with water not a true solution but a more or less viscid mixture, and gives a characteristic blue colour \vitli iodine. The formula is CfiH10O5 or more correctly (CBH10O5)n since the molecule of starch is some multiple (n being not less than 5) of the simpler formula. A kind of starch, known as fioluble starch, while giving a blue colour with iodine, forms, unlike ordinary starch, a clear solution. 2. Dextrins, differing from starch in forming a clear solution. Of these there are at least two ; one erythrodextrin, often spoken of simply as dextrin, giving a port-wine red colour with iodine, and a second, acliroodextrin, which gives no colour at all with iodine, The formula for dextrin is the same as that for starch, but has a smaller molecule and might be represented by (CfiH1005)n<. 3. Dextrose, also called glucose or grape-sugar, giving no colouration with iodine, but characterised by the power of re- ducing cupric and other metallic salts ; thus, when dextrose is boiled with a fluid known as Fehling's fluid, which is a solution of hydrated cupric oxide in an excess of caustic alkali and double tartrate of sodium and potassium, the cupric oxide is reduced and a red or yellow deposit of cuprous oxide is thrown down. This reaction serves with others as a convenient test for dextrose. Neither starch nor that commonest form of sugar known as caiie- sugar, give this reaction ; whether the dextrins do is doubtful. The formula for dextrose is C6H120B; it is more simple than that of starch or dextrin and contains an additional H2O for every C6. Unlike starch and dextrin it can be obtained in a crystalline form, either from aqueous solutions (it being readily soluble in water), in which case the crystals contain water of crystallisation, or from its solutions in alcohol (in which it is sparingly soluble), in which case the crystals have no such water of crystallisation. Solutions of dextrose have a marked dextrorotatory power over rays of light. 4. Maltose, very similar to dextrose, and like it capable of reducing cupric salts. The formula is somewhat different, being C12H220U. Besides this, it differs from dextrose chiefly in its smaller reducing power, i.e. a given weight will not convert so much cupric oxide into cuprous oxide as will the same weight of dextrose, and in having a stronger rotatory action on rays of light. Like dextrose it can be crystallised, the crystals from aqueous solutions containing water of crystallisation. Now when a quantity of starch is boiled with water we may recognise in the viscid imperfect solution, on the one hand the presence of starch, by the blue colour which the addition of iodine gives rise to, and on the other hand the absence of sugar (maltose, dextrose), by the fact that when boiled with Fehling's fluid no reduction takes place and no cuprous oxide is precipitated. If however the boiled starch be submitted for a while to the 360 ACTION OF SALIVA. [BOOK n. action of saliva, especially at a somewhat high temperature such as 35° or 40° C., it is found that the subsequent addition of iodine gives no blue colour at all, or very much less colour, shewing that the starch has disappeared or diminished ; on the other hand the mixture readily gives a precipitate of cuprous oxide when boiled with Fehling's fluid, shewing that maltose or dextrose is present. That is to say the saliva has converted the starch into maltose or dextrose. The presence of the previously absent sugar may also be shewn by fermentation and by the other tests for sugar. Moreover, if an adequately large quantity of starch be subjected to the charge, the sugar formed may be isolated, and its characters determined. When this is done it is found that while some dextrose is formed the greater part of the sugar which appears is in the form of maltose. As is well known starch may by the action of dilute acid be converted into dextrin, and by further action into sugar ; but the sugar thus formed is always wholly dextrose, and not maltose at all. The action of saliva in this respect differs from the action of dilute acid. While the conversion of the starch by the saliva is going on the addition of iodine frequently gives rise to a red or violet colour instead of a pure blue, but when the conversion is complete no coloration at all is observed. The appearance of this red colour indicates the pre-ener of dextrin (eiythrodeztrin) ; the violet colour is due to the red being mixed with the blue of still un- changed starch. The appearance of dextrin shews that the action of the saliva on the starch is somewhat complex ; and this is still further proved by the fact that even when the saliva has completed its work the whole of the starch does not reappear as maltose or dextrose. A considerable quantity of the other dextrin (achroo- dextrin) always appears and remains unchanged to the end; and there are probably several other bodies also formed out of the starch, the relative proportions varying according to circum- stances. The change therefore, though perhaps we may speak of it in a general way as one of hydration, cannot be exhibited under a simple formula, and we may rest content for the present with the statement that starch when subjected to the action of saliva is converted chiefly into the sugar known as maltose with a comparatively small quantity of dextrose and to some extent into achroodextrin (erythrodextrin appearing temporarily only in the process), other bodies on which we need not dwell being formed at the same time. Raw unboiled starch undergoes a similar change but at a much slower rate. This is due to the fact that in the curiously formed starch grain the true starch, or grannlose, is invested with coats of cellulose. This latter material, which requires previous treat- ment with sulphuric acid before it will give the blue reaction on the addition of iodine, is apparently not acted upon by saliva. €HAP. i.J TISSUES AND MECHANISMS OF DIGESTION. 361 Hence the saliva can only get at the granulosc by traversing the coats of cellulose, and the conversion of the former is thereby much hindered and delayed. § 199. The conversion of starch into sugar, and this we may speak of as the amylolytic action of saliva, will go on at the ordinary temperature of the atmosphere. The lower the temperature the; slower the change, and at about 0" C. the conversion is indefinitely prolonged. After exposure to this cold for even a considerable time the action recommences when the temperature is again raised. Increase of temperature up to about 35° — 40°, or even a little higher, favours the change, the greatest activity being said to be manifested at about 40°. Much beyond this point, however, increase of temperature becomes injurious, markedly so at 60° or 70° ; and saliva which has been boiled for a few minutes not only has no action on starch while at that temperature, but does not regain its powers on cooling. By being boiled, the amylolytic activity of saliva is permanently destroyed. The action of saliva on starch is most rapid when the reaction of the mixture is neutral or nearly so ; it is hindered or arrested by a distinctly acid reaction. Indeed the presence of even a very small quantity of free acid, at all events of hydrochloric acid, at the temperature of the body not only suspends the action but speedily leads to permanent abolition of the activity of the juice. The bearing of this will be seen later on. The action of saliva is hampered by the presence in a concen- trated state of the product of its own action, that is, of sugar. If a small quantity of saliva be added to a thick mass of boiled starch, the action will after a while slacken, and eventually come to almost a stand-still long before all the starch has been converted. On diluting the mixture with water, the action will recommence. If the products of action be removed as soon as they are formed, by dialysis for example, a small quantity of saliva will, if sufficient time be allowed, convert into sugar a very large, one might almost say an indefinite, quantity of starch. Whether the particular constituent on which the activity of saliva depends is at all consumed in its action has not at present been definitely settled. On what constituent do the amylolytic virtues of saliva depend ? If saliva, filtered and thus freed from much of its mucin and from other formed constituents, be treated with ten or fifteen times its bulk of alcohol, a precipitate is formed containing besides other substances all the proteid matters. Upon standing under the alcohol for some time (several days), the proteids thus precipitated become coagulated and insoluble in water. Hence, an aqueous extract of the precipitate, made after this interval, contains very little proteid material ; yet it is exceedingly active. Moreover by other more elaborate methods there may be obtained from saliva solutions which appear to be almost entirely free from proteids and yet are intensely amylolytic. But even these probably 362 THE AMYLOLYTIC FERMENT. [BOOK n. contain other bodies besides the really active constituent. Whatever the active substance be in itself, it exists in such extremely small quantities that it has never yet been satisfactorily isolated ; and indeed the only clear evidence we have of its existence is the manifestation of its peculiar powers. The salient features of this body, this amylolytic agent, which we may call ptyalin, are then : — 1st, its presence in minute and almost inappreciable quantity. 2nd, the close dependence of its activity on temperature. 3rd, its permanent and total destruction by a high temperature and by various chemical reagents. 4th, the \vant of any clear proof that it itself undergoes any change during the manifestation of its powers ; that is to say, the energy neces- sary for the transformation which it effects does not come out of itself; if it is at all used up in its' action, the loss is rather that of simple wear and tear of a machine than that of a substance expended to do work. 5th, the action which it induces is probably of such a kind (splitting up of a molecule with assumption of water) as is effected by that particular class of agents called " hydrolytic." These features mark out the amylolytic active body of saliva as belonging to the class of ferments , and we may henceforward speak of the amylolytic ferment of saliva. The fibrin-ferment (§ 20) is so called because its action in many ways resembles that of the ferment of which we are now- speaking. § 200. Mixed saliva, whose properties we have just discussed, is the result of the mingling in various proportions of saliva from the parotid, submaxillary, and sublingual glands with the secretion from the buccal glands. These constituent juices have their own special characters, and these are not the same in all animals. Moreover in the same individual the secretion differs in composition and properties according to circumstances ; thus, as we shall see in detail hereafter, the saliva from the submaxillary gland secreted under the influence of the chorda tympani nerve is different from that which is obtained from the same gland by stimulating the sympathetic nerve. In man pure parotid saliva may easily be obtained by introducing a fine cannula into the opening of the Stenonian duct, and submaxillary saliva, or rather a mixture of submaxillary and sublingual saliva, by 1 Ferments may, for the present at least, be divided into two classes, commonly called organised and iinorfjanised. Of the former, yeast may be taken as a well- known example. The fermentative activity of yeast which leads to the conversion of sugar into alcohol, is dependent on the life of the yeast-cell. Unless the yeast- cell be living and functional, fermentation does not take place; when the yeast- cell dies fermentation ceases ; and no substance obtained from the fluid parts of yeast, by precipitation with alcohol or otherwise, will give rise to alcoholic fermen- tation. The salivary ferment belongs to the latter class ; it is a substance, not a living organism like yeast. It may be added however that possibly the organised ferment, the yeast for instance, produces its effect by means of an ordinary unorganised ferment which it generates, but which is immediately made away with. CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 363 similar catheterisation of the Whartonian. duct. In animals the duct may be dissected out and a cannula introduced. Parotid saliva in man is clear and limpid, not viscid ; the reaction of the first drops secreted is often acid, the succeeding portions, at all events when the flow is at all copious, are alkaline ; that is to say the natural secretion is alkaline, but this may be obscured by acid changes taking place in the fluid which has been retained in the duct, possibly by the formation of an excess of carbonic acid. On standing, the clear fluid becomes turbid from a precipitate of calcic carbonate, due to an escape of carbonic acid. It contains globulin and some other forms of albumin, with little or no mucin. Potassium sulphocyanate may also sometimes be detected, but structural elements are absent. Submaxillary saliva, in man and in most animals, differs from parotid saliva in being more alkaline and, from the presence of mucin, more viscid ; it contains salivary corpuscles, that is bodies closely resembling if not identical with leucocytes, and, often in abundance, amorphous masses. The so-called chorda saliva in the dog, that is to say saliva obtained by stimulating the chorda tympani nerve, (of which we shall presently speak), is under ordinary circumstances thinner and less viscid, contains less mucin, and fewer structural elements, than the so-called sympa- thetic saliva, which is remarkable for its viscidity, its structural elements, and for its larger total of solids. Sublingual saliva is more viscid, and contains more salts (in the dog about 1 p.c.), than the submaxillary saliva. The action of saliva varies in intensity in different animals. Thus in man, the pig, the guinea-pig, and the rat, both parotid and submaxillary and mixed saliva are amylolytic ; the sub- maxillary saliva being in most cases more active than the parotid. In the rabbit, while the submaxillary saliva has scarcely any action, that of the parotid is energetic. The saliva of the cat is much less active than the above ; that of the dog is still less active, indeed is almost inert. In the horse, sheep, and ox, the amylolytic powers of either mixed saliva, or of any one of the con- stituent juices, are extremely feeble. Where the saliva of any gland is active, an aqueous infusion of the same gland is also active. The importance and bearing of this statement will be seen later on. From the aqueous infusion of the gland, as from saliva itself, the ferment may be approximately isolated. In some cases at least some ferment may be extracted from the gland even when the secretion is itself inactive. In fact a ready method of preparing a highly amylolytic liquid tolerably free from proteid and other impurities, is to mince finely a gland known to have an active secretion, such for instance as that of a rat, to dehydrate it by allowing it to stand under absolute alcohol for some days, and then, having poured off most of the alcohol, 364 «!ASTRIC JUICE. [BOOK n. and removed the remainder by evaporation at a low temperature to cover the pieces of gland with strong glycerine. Though some of the ferment appears to be destroyed by the alcohol a mere drop of such a glycerine extract rapidly converts starch into sugar. Gastric Juice. § 201. There is no difficulty in obtaining what may fairly be considered as a normal saliva ; but there are many obstacles in the way of determining the normal characters of the secretion of the stomach. When no food is taken the stomach is at rest and no secretion takes place. When food is taken, the characters of the gastric juice secreted are obscured by the food with which it is mingled. The gastric membrane may it is true be artificially stimulated, by touch for instance, and a secretion obtained. This we may speak of as gastric juice, but it may be doubted whether it ought to be considered as normal gastric juice. And indeed as we shall see even the juice, which is poured into the stomach during a meal, varies in composition as digestion is going on. Hence the characters which we shall give of gastric juice must be considered as having a general value only. Gastric juice, obtained in as normal a condition as possible from the healthy stomach of a fasting dog, by means of a gastric fistula, is a thin almost colourless fluid with a sour taste and odour. In the operation for gastric tistula, an incision is made through the abdominal walls, along the linea alba, the stomach is opened, and the lips of the gastric wound securely sewn to those of the incision in the abdominal walls. Union soon takes place, so that a permanent opening from the exterior into the inside of the stomach is established. A tube of proper construction, introduced at the time of the operation, becomes firmly secured in place by the contraction of healing. Through the tube the contents of the stomach can be received, and the mucous membrane stimulated at pleasure. When obtained from a n.-itnral fistula in man, its specific gravity has been found to differ little from that of water, varying from rOOl to I'OIO, and the amount of solids present to be correspondingly small. In animals, pure gastric juice seems to be equally poor in solids, the higher estimates which some observers have obtained being probably due to admixture with food, &c. Of the solid matters present about half are inorganic salts, chiefly alkaline (sodium) chlorides, with small quantities of phosphates. The organic material consists of pepsin, a body to be described immediately, mixed with other substances of undetermined nature. In a healthy stomach gastric juice contains a very small quantity only of mucin, unless some submaxillary saliva has been swallowed. CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 365 The reaction is distinctly acid, and the acidity is normally due to free hydrochloric acid. This is shewn by various proofs, among which we may mention the conclusive fact that the amount of chlorine present in gastric juice is more than would suffice to form chlorides with all the bases present, and that the excess if regarded as existing in the form of hydrochloric acid corresponds exactly to the quantity of free acid present. Lactic and butyric and other acids when present are secondary products, arising either by their respective fermentations from articles of food, or from the decomposition of their alkaline or other salts. In man the amount of free hydrochloric acid in healthy juice may be stated to be about "2 per cent., but in some animals it is probably higher. § 202. On starch gastric juice has no amylolytic action ; on the contrary when saliva is mixed with gastric juice any amylo- lytic ferment which may be present in the former is at once prevented from acting by the acidity of the mixture. Moreover in a very short time, especially at the temperature of the body, the amylolytic ferment is destroyed by the acid so that even on neutralisation the mixture is unable to convert starch into sugar. On dextrose healthy gastric juice has no effect. And its power of inverting cane-sugar seems to be less than that of hydrochloric acid diluted to the same degree of acidity as itself. In an un- healthy stomach however containing much mucus, the gastric juice is very active in converting cane-sugar into dextrose. This power seems to be due to the presence in the mucus of a special ferment, analogous to, but quite distinct from, the ptyalin of saliva. An excessive quantity of cane-sugar introduced into the stomach causes a secretion of mucus, and hence provides for its own conversion. On fats gastric juice has at most a limited action. When adipose tissue is eaten, the chief change which takes place in the stomach is that the proteid and gelatiniferous envelopes of the fat-cells are dissolved, and the fats set free. Though there is experimental evidence that emulsion of fats to a certain extent does take place in the stomach, the great mass of the fat of a meal is not so changed. Such minerals as are soluble in free hydrochloric acid are for the most part dissolved; though there is a difference in this and in some other respects between gastric juice and simple free hydro- chloric acid diluted with water to the same degree of acidity as the juice, the presence either of the pepsin or of other bodies apparently modifying the solvent action of the acid. The essential property of gastric juice is the power of dissolving proteid matters, and of converting them into a substance called peptone. Action of gastric juice on proteids. The results are essentially the same whether natural juice obtained by means of a fistula or 366 DIGESTION OF PROTEIDS. [BOOK n. artificial juice, i.e. an acid infusion of the mucous membrane of the stomach, be used. Artificial gastric juice may be prepared in any of the following ways. 1. The mucous membrane of a pig's or dog's stomach is removed from the muscular coat, finely minced, rubbed in a mortar with pounded glass and extracted with water. The aqueous extract filtered and acidulated (it is in itself somewhat acid), until it has a free acidity corresponding to '2 p.c. of hydrochloric acid, contains but little of the products of digestion such as peptone, but is fairly potent. 2. The mucous membrane similarly prepared and minced is allowed to digest at 35° C. in a large quantity of hydrochloric acid diluted to •2 p.c. The greater part of the membrane disappears, shreds only being left, and the somewhat opalescent liquid can be decanted and filtered. The filtrate has powerful digestive (peptic) properties, but contains a considerable amount of the products of digestion (peptone, ", its solvent powers are not only suspended but actually de.-troyed. Digestion is most rapid with dilute hydrochloric acid of "2 p.c. (the acidity of natural gastric juice). If the juice contains much more or much less free acid than this, its activity is distinctly impaired. Other acids, lactic, phosphoric, &c. may be substituted for hydrochloric ; but they are not so effectual, and tin- degree of acidity most useful vari>-- with the different acids. The presence of neutral salts, such as sodium chloride, in excess is injurious. The action of mammalian gastric juice is most rapid at 3o°— 40° C.; at the ordinary temperature it is much slower, and at about 0°C. ceases altogether. The juice may be kept however at 0°C. for an indefinite period without injury to its powers. The gastric juice of cold-blooded vertebrates is relatively more active at low temperatures than that of warm-blooded mammals or birds. At temperatures much above 40° or 45° the action of the juice is impaired. By boiling for a few minutes the activity of the most powerful juice is irrevocably destroyed. The presence in a concen- trated form of the products of digestion hinders the process of solu- tion. If a large quantity of fibrin be placed in a small quantity of juice, digestion is soon arrested ; on dilution with the normal hy- CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 37:5 drochloric acid ('2 p.c.), or if the mixture1 be submitted to dialysis to remove the peptones formed, and its acidity be kept up to the normal, the action recommences. By removing the products of digestion as fast as they are formed, and by keeping the acidity up to the normal, a given amount of gastric juice may be made to digest a very large quantity of proteid material. Whether the quantity is really unlimited is disputed ; but in any case the energies of the juice are not rapidly exhausted by the act of digestion. § 205. Nature of tlie action. All these facts go to shew that the digestive action of gastric juice on proteids, like that of saliva on si arch, is a ferment-action ; in other words, that the solvent action of gastric juice is essentially due to the presence in it of a ferment- body. To this ferment-body, which as yet has been only ap- proximately isolated, the name of pejisin has been given. It is present not only in gastric juice but also in the glands of the gastric mucous membrane, especially in certain parts and under certain conditions which we shall study presently. The glycerine extract of gastric mucous membrane, at any rate of that which has been dehydrated, contains a minimal quantity of proteid matter, and yet is intensely peptic. Other methods, such as the elaborate one of Briicke, give us a material which, though containing nitrogen, exhibits none of the ordinary proteid reactions, and yet in concert with normal dilute hydrochloric acid is peptic in a very high degree. We seem therefore justified in asserting that pepsin is not a proteid, but it would be hazardous to make any dogmatic state- ment concerning a substance, obtained in so small a quantity at a time that its exact chemical characters have not yet been ascertained. At present the manifestation of peptic powers is our only safe test of the presence of pepsin. In one important respect pepsin, the ferment of gastric juice, differs from ptyalin, the ferment of saliva. Saliva is active in a per- fectly neutral medium, and there seems to be no special connection between the ferment and any alkali or acid. In gastric juice, however, there is a strong tie between the acid and the ferment, so strong that some writers speak of pepsin and hydrochloric acid as forming together a compound, pepto-hydrochloric acid. In the absence of exact knowledge of the constitution of proteids, we cannot state distinctly what is the precise nature of the change into peptone ; the various proteids differ from each •other in elementary composition quite as widely as does peptone from any of them. Judging from the analogy with the action of saliva on starch, we may fairty suppose that the process is at bottom one of hydration ; and this view is further suggested by the fact that peptone closely resembling, if not identical with, that obtained by gastric digestion, may be obtained by the action of strong acids, by the prolonged action of dilute acids especially at a high temperature, or simply by digestion with super-heated DIGESTION OF MILK. [BOOK n. water in a Papiu's digester, that is to say by means of agents which, iu other cases produce their effects by bringing about hydrolytic changes ; beyond this we cannot at present go. We may add however, as supporting the same view, the statement of some observers that peptone when treated with dehydrating agents or when simply heated to 140° — 170° C. is in part recon- verted into a body or bodies resembling acid-albumin or globulin. § 206. All proteids, so far as we know, are converted by pepsin into peptone. Concerning the action of gastric juice on other nitrogenous substances more or less allied to proteids but not truly proteid in natiire our knowledge is at present imperfect. Mucin, nuclein, and the chemical basis of horny tissues are wholly unaffected by gastric juice. The gelatiniferous tissues are dissolved by it ; and the bundles and membranes of connective tissue are very speedily so far affected by it, that at a very early stage of digestion, the bundles and elementary fibres of muscle which are bound together by connective tissue fall asunder; moreover both prepared gelatine and the gelatiniferous basis of connective tissue in its natural condition, that is without being previously heated with water, are by it changed into a substance so far analogous with peptone, that the characteristic property of gelatinisation is entirely lost. Chondrin and the elastic tissues undergo a similar change. It is not clear however ho\v far this change is due simply to the acid of gastric juice independently of tin- pepsin. §207. Action of gastric juice on milk. It has long been known that an infusion of calves' stomach, called rennet, has a remarkable effect in rapidly curdling milk, and this property is made use of in the manufacture of cheese. Gastric juice has a similar effect ; milk when subjected to the action of gastric juice is first curdled and then digested. If a few drops of gastric juice be added to a little milk in a test tube, and the mixture exposed to a tempera- ture of 40°, the milk will curdle into a complete clot in a very short time. If the action be continued the curd or clot will be ultimately dissolved and digested. Milk contains, besides a peculiar form, or peculiar forms of albumin, fats, milk-sugar and various salines, the peculiar proteid casein. In natural milk casein is present in solution, and ' curdling ' consists essentially in the soluble casein being converted (or more probably as we shall see presently, split up) into an insoluble modification of casein, which as it is being precipitated carries down with it a great deal of the fat and so forms the ' curd '. Now casein is readily precipitated from milk upon the addition of a small quantity of acid, and it might be supposed that the curdling effect of gastric juice was due to its acid reaction. But this is not the case, for neutralized gastric juice, or neutral rennet, is equally efficacious. The curdling action of rennet is closely dependent on tempera- ture, being like the peptic action of gastric juice favoured by a rise of temperature up to about 40°. Moreover the curdling action CHAP, i.] TISSt'KS AND MECHANISMS OK DKJKsTloN. :i7') is destroyed by previous boiling of the juice or rennet. These tacts surest that a tenneiit is at the bottom of the matter; ;mF MILK. [BooK n. remain in solution; if calcic phosphate be present, the one, viz. tin- curd1, becomes insoluble. Rennin is abundant in the n-nstric juice and in the gastric mucous membrane of ruminants, but is also found in the gastric juice of other animals, and either it. or what we shall presently have occasion to spe.-ik of as the antecedent of the ferment or ciinini/t'ii H present also in the mucous membrane of the stomach of most animals. A very similar if not identical ferment has also been found in many plants. 1 It illicit he useful, in order to distinguish the curd from the natural soluble in, tu (Mil the former ti/i-cln (rcpos, cheese), and so reserve the name of casein for the latter. SEC. 2. THE STRUCTURE OF THE SALIVARY GLANDS, THE GASTRIC MUCOUS MEMBRANE, THE PANCREAS, AND THE (ESOPHAGUS. § 208. Before we study the nature of the processes by which the stomach and the salivary glands are able to secrete the gastric juice and saliva, whose remarkable properties we have just described, it will be desirable to say a few words on the structure of both the above organs. Throughout the greater part of its length, from the cardiac end of the oesophagus to near the anus, the alimentary canal is constructed on a certain general plan. This part of the alimentary canal is formed out of the mid-gut of the embryo^and the epithelium which lines it is of hypoblastic origin. The mouth and the anus have a different origin ; they are formed by involutions of the external skin, the epithelium of which is of epiblastic origin ; and the plan of structure of the mouth and terminal portion of the rectum is in some respects different from that of the rest of the alimentary canal. The transition from the epiblastic to the hypo- blastic canal occurs in the rectum at the anus, bu^yat the other end is at some distance from the mouth close to the junction of the oesophagus with the stomach. The plan of structure of the hypoblastic portion of the canal is somewhat as follows. A single layer of cylindrical, columnar, cubical or spheroidal "protoplasmic" cells, that is to say cells which are not transformed into flattened scales, forms the immediate lining of the cavity. The cells rest on a connective tissue basis, which is fine, delicate and often of a peculiar nature immediately under the epithelium, but becomes more open, loose and coarse at some little distance from the cells. This connective tissue basis is richly provided with blood vessels and lymphatics, and also contains a certain number of nerves. The' blood vessels reach up to, and fine capillary networks are especially abundant immediately beneath, the bases of the cells, but none pass between the cells themselves; 37S STRUCTURE OF ALIMKNTA11Y CANAL. [Boon n. the whole of the epithelium is extra-vascular. The connective tissue where it touches the cells forms a more or less continuous sheet; this is often spoken of a* the basement membrane and may be regarded as the demarcation between the extra- vascular epithelium and the vascular connective tissue basis. The two together, the epithelium and the connective tissue basis, form what is known as the i/mrous membrane. At the bases of the eylindrical cells, wed^-d in between them and the basement membrane, may be seen, in certain situations distinct Iv. in other situations less distinctly, small cells, that is to say cells the body <>f which is small relatively to the nucleus. These are supposed to be VollUg cells, held in reserve to replace any of the larger cylindrical cells which may from time to time disappear; if so the epithelium does not strictly consist always of a single layer, though practically it may be so regarded. Outside the mucous membrane or mucoii^ coat is placed the thick iinisriilar emit. This consists of two layers of plain muscular fibres, an inner thicker layer, in which the fibres and bundles of fibres are disposed circularly round the lumen of the alimentary canal, and an outer thinner one in which the fibres are disposed longitudinally. The bundles and sheets of fibres (see ij Sit) are bound together by connective ti-sue carrying blood vessels, lym- phatics and nerves, and a thin sheet of connective tissue more, or less distinctly separates the thicker inner circular muscular coat from the thinner outer longitudinal muscular coat. The lower or outer part of the mucous membrane where it becomes attached to the muscular coat is formed of very loose connective tissue, the interspaces of the bundles being large and open. This is spoken of as the submncous tissue or submucous coat. It is so loose that the mucous coat can easily move over the muscular coat, and along it the one can easily be torn away from the other, more easily in some parts of the canal than in others. It carries the larger arteries and veins, whose smaller branches and capillaries pass into and from the mucous membrane. Lying in the mucous membrane at some little distance from the epithelium is found a thin layer of plain muscular fibres, called the tunica muscularis mucosce. It is more conspicuous in some situations than in others, and when complete consists of an inner single layer of fibres disposed circularly and an outer single layer of fibres disposed longitudinally. The connective tissue on the inside of the muscularis mucosae, between it and the epithelium, is generally of a somewhat different character from that outside the muscularis mucosae, and many places is of the kind called adenoid or reticalar tissue ; of this we shall hereafter have to speak. Lastly, from the stomach to the rectum the muscular coat of the alimentary canal is covered by the visceral layer of the peri- toneum. This consists of a single layer of polygonal flattened nucleated epithelioid cells (belonging in reality as we shall see to CHAP, i.] TISSUES AND MECHANISMS OK DIGESTION. :',7!) the lymphatic system) resting on a thin connective tissue basis which separates them from the longitudinal muscular coat. The general plan of structure of the alimentary canal then, in its hypoblastic portion, is a compact muscular coat separated by a loose more or less moveable submucous coat from a fairly compact mucous coat. The mucous coat consists of a vascular connective tissue basis, in which is embedded a thin special muscular sheet, and of a single layer of special hypoblastic epithelial cells. The muscular coat consists of a thick inner circular and a thin outer longitudinal layer of plain muscular fibres; and the whole is covered with an epithelioid peritoneal layer. § 209. Glands. The surface of the mucous membrane however is not even and unbroken. It dips down at intervals, that is to say it is involuted to form pockets or depressions sunk into the under- lying connective tissue and differing in size and form in different parts of the alimentary canal. Such an involution is called a gland. The most simple kind of gland is a cylindrical depression with a blind end, somewhat of the form of a test-tube, lined with a single layer of epithelium cells, continuous at the mouth of the gland with the rest of the epithelium of the mucous membrane. The wall of the gland outside the epithelium is supplied by the connective tissue of the mucous membrane, which generally forms a distinct basement membrane, and is generally also richly supplied with capillary blood vessels. Hence when two such glands lie side by side, a certain quantity of connective tissue carrying blood vessels runs up between them to reach the epithelial cells which cover the surface of the mucous membrane between their mouths. Such a simple tubular gland may have the same diameter through- out, or may vary in diameter at different distances from the mouth, and the epithelium lining it may be of the same character throughout and similar to that on the surfaces between the mouths of the glands; very frequently however at the lower part of the gland the epithelium is modified and takes on certain special characters which we shall speak of presently as those of a ' secreting ' epithelium. When this occurs the upper part of the gland, where the epithelium is not so modified, is often spoken of as ' the duct ' of the gland. Very frequently the gland is not simple but branched, and the branching may be slight or excessive. Such branched glands, especially those in which the branching is considerable, are called compound glands ; and in these there is always a very marked distinction between the terminal portions of the several branchings where the epithelial cells have secreting characters, and the proximal portions or ducts where the cells have not these secreting characters. In such a compound gland a tubular main duct (whose mouth opens into the interior of the alimentary canal, and whose epithelial lining is continuous with the general epithelial lining of the canal) divides, dichotomously or otherwise, into secondary ducts, which again divide 380 STRUCTURE OF STOMACH. [BOOK n. into smaller ducts, and this division may be repeated again and again; ultimately however cadi duct ends in a part in which the epithelium takes mi secreting characters, and such terminal portions of ducts which are generally wider, more swollen as it were, than the ducts leading to them and not infrequently Mask-shaped are spoken of as alveoli. These alveoli, especially when flask-shaped, hear a certain, though l>y no means close, resemblance to the indi- vidual berries on a bunch of grapes, the ducts being the branching st.-ilks ; hence these compound glands are spoken of as "racemose." Sometimes the gland in dividing spreads out loosely over a wide Mil-face, that is to say. is 'diffuse'; sometimes the ducts ami alveoli with all the connective t issue, blood vessels, \-c., belonging to them are bound up tightly into a more or less globular mass, that is to say, form a 'compact' gland. ( Hands in fact vary widely in si/e, form and complexity, but they all have the one tea lure in common that they, 1 icing involutions of the mucous membrane, consist of a wall of vascular connective tissue lined by epithelium, and in the majority of glands there is a distinction in the characters of the epithelium bet \\een a terminal secreting portion and a proximal conducting portion. Where, as in the stomach and intestine, a number of com- paratively simple glands are closely packed together side by side, the whole mucous membrane acquires proportionately increased thickness; instead of being an attenuated sheet formed of a single la\er of cells on a thin connective tissue basis it becomes a mass whose thickness is determined by the length of the glands. It may be added that generally but not always the gland in its whole length lies above or outside the muscularis mucosie, so that when a vertical section is made of a mucous membrane the muscularis mucosa- is seen running in an even line at some little distance below the thick layer which is presented by the longitu- dinal sections of the glands. Bearing in mind these general characters of the alimentary canal and its glands we may now proceed to study some of its special characters, and it will be convenient to begin with the structure of the stomach. Structure of the Stomach. § 210. The stomach in its structure follows the general plan just described, and consists of a muscular coat and a mucous membrane separated from each other by loose submucous con- nective tissue. The muscular coat, which has considerable thick- ness, consists of an outer somewhat thick longitudinal coat and an inner still thicker circular coat, the innermost bundles of which take an oblique direction and form a more or less distinct thin oblique layer. As we shall see the movements of the stomach are more extensive and complex than those of the rest 'of the alimentary CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 3s 1 canal. Towards the pyloric end, in what is sometimes called the cmtrum pylori, the circular layer increases in thickness, and at the pylorus is developed into a, thick ring called the sphincter of the pylorus; a less marked circular sphincter is also present at the cardiac orifice. The size of the cavity of the stomach varies from time to time according to the bulk of contents present, and the condition of the muscular fibres. When the stomach is empty, the muscular fibres are in a state of tonic contraction, and the cavity is small ; when the stomach is full, the muscular fibres though carrying out as we shall see more or less rhythmical movements are as a whole relaxed and extended, so that the cavity is large. The mucous membrane in its natural condition so to speak is of such a size that it forms a smooth even lining to the muscular coat when this is extended and relaxed and the cavity of the stomach distended. Hence when the stomach is empty, and the muscular coat con- tracted, the mucous membrane is thrown into folds or rngw, which on account of the preponderance of the circular muscular coat take a longitudinal course, the loose submucous tissue allowing this movement of the mucous over the muscular coat. The mucous membrane is relatively very thick, the thickness being due to the fact that the membrane over its whole extent is thickly studded with glands ; it may in fact be said to be almost wholly composed of a number of short comparatively " simple " glands placed vertically side by side and bound together by just as much connective tissue as serves to carry the blood vessels and lymphatics. These glands vary in size, shape and character in different parts of the stomach, and the stomachs of different animals present in these respects very considerable differences : but, for present purposes, we may consider them as of two kinds, the glands at the cardiac end of the stomach or " cardiac glands " and the glands at the pyloric end, or "pyloric glands." $ 211. Cardiac glands. These are tubular glands, about "5 mm. to 2 mm. in length by 50 /j, to 100 // in width, whose course is not wholly straight but wavy or gently tortuous, and frequently curved or bent at the blind end. Some are simple or unbranched, but others divide into two, three or even more tubes. They are packed together side by side in a vertical position so closely that in sections of hardened and prepared stomachs in which the blood vessels are for the most part emptied of blood and the lymph spaces of lymph, each gland seems to be separated from its neighbours by nothing more than an extremely thin sheet of connective tissue seen in sections as almost a mere line. In the living stomach when the numerous blood vessels in this connective tissue are filled with blood, and the lymph spaces are distended with lymph, the glands are separated from each other by a considerable space equal probably to about their own diameter. ('AUDI AC : At the pyloric end of the stomach the glands are less r|ose!\ packed than at the cardiac end, and differ from the cardiac glands in si/.e, shape and structure. A typical pyloric gland possesses a mouth which is much longer and generally broader with a wider lumen than the mouth of a cardiac gland, though the walls are lined with mucous cells like those of the cardiac end. The body of the gland instead of being as in the cardiac gland often tubular and unbranched, frequently divides into two or more bram-he* close to the neck, and these branches which are relative! v shorter than the body of a cardiac i J I gland and have a much wider lumen, may again subdiviofcfclao that the whole gland is most distinctly branched. The whole- body with all its branches from the mouth to the several blind ends is lined throughout with one kind of cell only, which is very similar to the central cell of a pyloric gland, inasmuch as it is a polyhedral or short columnar cell with indistinct out- lines, a spherical nucleus, and a cell-body which in a specimen prepared in the ordinary way is faintly granular. The 'ovoid' cell so characteristic of the cardiac gland is absent. The arrangement of the connective tissue with its blood vessels and lymphatics and of the muscularis mucose is much the same as at the cardiac end. Thus the cardiac end of the stomach contains glands which are CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 385 tubular and often simple, which have a very narrow lumen, and which possess central and ovoid cells, while the pyloric end contains glands which are branched, which have a relatively deep mouth and wide lumen, and which possess one kind of cells only, central cells or cells very like these. In the middle region of the stomach the one kind of gland gradually merges into the other; in passing from the cardia to the pylorus the ovoid cells become less numerous and at last disappear, the mouth becomes longer, the lumen wider, and the body of the gland becomes more and more branched. The above supplies a general description of the gastric glands but these vary in minor characters and to a certain extent in distribution in different animals ; and as we shall presently see in all cases, the glands vary in condition and so in appearances according as digestion is or has been going on in the stomach. The Salivary Glands. § 215. The structural differences between the ' mucous ' cells lining the mouth and the 'central' and 'ovoid' cells lining the body of a gastric gland lead us to infer that the former differ from the latter in function ; and we have other evidence that this is so, that it is the central and ovoid cells which actually secrete the gastric juice, and that as far as the gastric juice is concerned, the mouths of the glands serve chiefly (though the mucous cells have a purpose of their own) to conduct to the interior of the stomach the juice secreted by the body of the gland. We may therefore speak of the body as the secreting portion and the mouth as the ' duct ' of the gland. This distinction between a secreting portion and a conducting portion, more or less obvious as we have said in most glands, is especially striking in the case of the salivary glands. These are involutions of the (epiblastic) mucous membrane of the mouth as the gastric glands are involutions of the (hypoblastic) mucous membrane of the stomach ; but instead of being comparatively simple they are exceedingly branched racemose glands, and the secreting portion of the gland is removed to a great distance from the epithelium of the mouth so that the conducting portion is of very great length. Moreover, not only the epithelium lining the secreting portion but also that lining the conducting portion differs so completely from the epiblastic epithelium lining the mouth that we may study the structure of the gland quite apart from the structure of the lining of the mouth, whose sensory functions, in the way of taste for instance, are so much more important than its digestive functions that we may reserve the study of its features until we come to deal with the senses. A salivary gland such as the submaxillary consists of a long main duct which pursues an undivided course backwards for several centimetres from its opening into the cavity of the mouth F. 25 386 STRUCTURE OF A SALIVARY GLAND. [BOOK n. until it reaches the body of the gland, when it rapidly divides and subdivides into a number of smaller ducts. Each of the ultimate divisions of the duct at last end- in a ' secreting' portion, \\hidi is lined by a 'secreting' epithelium different in character from the epithelium lining the ducts. Such a terminal secreting portion is called an alveolus. Sometimes a duct terminates in a single alveolus, which then appears as a swollen or somewhat flask-shaped termination of the duct distinguished from the duct by the size and character of its cells and by the narrow- ness of its lumen ; but more commonly a duct ends in several alveoli, which then appear as a number of short curved somewhat swollen tubes, branching off from the end of the duct. All the ducts and the alveoli in which they end are bound up by connec- tive tissue, carrying blood vessels, nerves and lymphatics, into a compact, rounded but somewhat lobulated mass, the gland proper. Each alveolus, or each group of alveoli, and the small duet of which it forms the blind end is surrounded and separated from its neigh lio ui-s by a certain amount of connective tissue. A number of alveoli with the ducts leading to them are humid together into a lobule by a father larger amount of connectivi ti— ue. Groups of these smaller lobules are bound together by connect ive tissue and enveloped by a more distinct coat of that ti-siie, and thus form larger or primary lobule-; and the-e larger lobules are bound up to form the -land itself by a tpiant ity of connect he t issue, which also forms a wrapping or sheath for the \\hole gland. Hence a thin section taken through the gland is seen, when examined under a low power, to be divided by septa of connective tissue (continuous with the sheath of the -land, and carrying blood vessels, &c.), into irregular areas, which are generally angular from compression. These areas are sections of the primary lobules, and each may be seen to be similarly but less distinctly subdivided into similar smaller areas, the smaller lobules. Each of these smaller lobules will in turn be seen to be for the most part made up of rounded bodies varying somewhat in size and shape but on the whole very much alike, bound together by a small amount of connective tissue; these are the alveoli which, being disposed in various direc- tions and being frequently more or less curved, are cut in various planes by the section. Where the section cuts the alveolus trans- versely the outline of the alveolus is circular, where obliquely the outline is more elliptical ; a section moreover may pass through the mere tip or side of the alveolus and so miss the lumen altogether ; and indeed many varied appearances may be presented. Among these alveoli are seen other bodies of a somewhat different aspect, circular, elliptical or cylindrical in outline, or hour-glass- shaped, or even irregular in form. These are the small tubular ducts cut in various planes. Sections of the larger ducts of various size may also be seen in the septa between the lobules. Even with quite a low power it is easy to distinguish between the alveoli or CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 387 secreting elements and the ducts, and when we come to examine them more closely we find that they differ markedly in structure. Moreover, when we examine the three glands, parotid, submaxillary and sublingual, and especially when we employ for the purpose different kinds of animals, we find that, while the ducts have nearly the same structure in all cases, two kinds of alveoli may be distinguished differing from each other in the characters of the cells lining them. In the one case the cells, for reasons which will presently appear, are called mucous cells, in the other serous cells, or perhaps better albuminous cells. In one gland all the alveoli may be lined with mucous cells, in which case it is called a ' mucous gland,' or with albuminous cells, in which case it is called an ' albuminous gland,' or some alveoli may be ' mucous ' and others ' albuminous,' the gland being a mixed one ; and this dis- tinction between mucous and albuminous obtains also in glands of the mucous membrane which are not distinctly salivary, for instance in the small ' buccal ' glands of the mouth, and in the glands of the pulmonary passages and of other structures. § 216. Mucous glands. -£The submaxillary gland of the dog is a fairly typical mucous gland. The alveoli of this gland vary a good deal in diameter, but are on an average about 35 /u-. The outline of each alveolus is defined by a distinct basement membrane formed of a number of flattened connective tissue cor- puscles fused together into a sheet ; in a section the long oval nuclei of the constituent cells may be seen here and there imbedded, as it were, in the membrane. Outside the basement membrane lie, as elsewhere in a mucous membrane, the lymph spaces of the fine connective tissue. The space defined by the basement membrane is nearly wholly filled, a very small central lumen only being left, by cells arranged for the most part in a single layer. The cells are large relatively to the alveolus, so that in a transverse section of an alveolus, about 5 or 6 cells will be seen. Each cell is more or less spherical or rather conical in form, with its broader base, which is sometimes irregular in outline, resting on the basement membrane and the narrower apex abutting on the lumen. The characters of the cell differ according to the condition of the gland. If the gland has, previous to its preparation for examination, not been actively secreting, the cells have certain characters and may be spoken of as ' loaded ' or ' charged.' If the gland has been actively secreting, these characters are replaced by others, and the cells may be spoken of as ' unloaded,' ' discharged.' In the ' loaded,' or as it is/ often called the ' resting ' phase, the cell, in hardened specimens, is as a whole transparent, and stains very slightly with the ordinary staining reagents. The nucleus, which in hardened specimens appears disc-shaped and sometimes curved or bent, but in the fresh living cell is seen to be spherical, lies at the base of the cell not far from the basement membrane. Around the nucleus is gathered a 25—2 :$ss MUCOUS GLANDS. [BOOK n. small quantity of ordinary protoplasmic cell-substance, staining ivuilily with the usual dyes; the rest of the cell-body consists of a transparent material, which does not stain readily, and which occu- pies the spacer or implies of a very delicate nieshwork continuous apparently with the staining protoplasmic cell-sul>stance around the nucleus, and with a thin sheet of similar material forming the wall of the cell. This transparent material is either mucin, which we have seen to be a conspicuous constituent of submaxillary saliva (in the dog) or a substance which can be easily comerted into actual mucin, that is to say an antecedent of muciu ; hence the name 'mucous cell.'^-A resting or loaded mucous cell thru consists largely of mucin , especially on the outer side, and sometimes the whole cell stains; the nucleus, now spherical even in hardened specimens, occupies a more central position. The transparent, non-staining mucin has in large part or wholly disappeared, its place has been taken by ordinary staining proto- plasmic cell-substance, and the distinction between the demilune cells and the proper cells of the alveolus is much less distinct. We shall presently have to discuss the nature and meaning of this change from the loaded to the discharged cell. § 217. A small duct of the submaxillary gland, even when cut transversely in the section so as to present like many alveoli a circular outline, has an appearance very different from that of an alveolus. -^The duct is lined by a single layer of epithelium, but these are slender, narrow, columnar cells leaving in the centre a relatively wide lumen, and the outside of the duct is not so sharply defined by a conspicuous basement membrane as is the case in an alveolus. Each cell, which bears an oval nucleus placed vertically in the cell at about the middle but rather nearer the base, consists of a protoplasmic cell-substance which on the inner CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 389 side of the nucleus towards the lumen has no special features, but on the outside, towards the basement membrane or connective tissue basis, has frequently a longitudinal striation as if made up of a number of rods or narrow prisms placed side by side. The larger ducts running between the lobules differ from such a small intralobular duct chiefly in the greater thickness of the connective tissue basis, which in these is developed into a distinct coat containing in the case of the larger branches and the main duct plain muscular fibres. In the main duct and its chief branches the single layer of columnar cells is replaced by two or three layers of cubical, or sometimes flattened cells not marked with the striation spoken of above. >When a small intralobular duct is about to end in an alveolus or a group of alveoli it becomes narrowed, the cells lose their striation, from being slender and cylindrical in form become short cubical, and at the very end of the duct change into flat spindle-shaped plates, the transition from which to the characteristic cells of the alveolus is in the case of most animals quite abrupt. Such a modified terminal portion of a duct is sometimes spoken of as a " ductule." § 218. Albuminous glands. These differ from the mucous glands in the constitution of the cells lining the alveoli, but the structure of the ducts and the general arrangements of the gland are the same in both ; indeed, as we have already said, in the same gland some alveoli may be albuminous and others mucous. : In an albuminous alveolus the cells are rather smaller than those in a loaded mucous gland, and their outlines are rather more angular.^ In each cell the nucleus, which is spherical, is placed near the centre of the cell but rather nearer the basement membrane, and the cell-substance, which has the general appear- ance, in an ordinary preparation, of somewhat densely granular protoplasm, stains readily and uniformly all over. J-No cells cor- responding to the demilunes of a mucous alveolus are present. In fact an albuminous cell does not at first sight appear to differ markedly from a discharged mucous cell, and does not shew the same marked differences between a loaded and a discharged con- dition as does a mucous cell. There are however differences between the loaded and the discharged albuminous cell, but to these we shall return presently. V" The parotid gland of man and indeed of all mammals is a Wholly albuminous gland, though in the dog a few cells are mucous ; the submaxillary of man is on the whole a mucous gland but some lobules in it are albuminous ; the submaxillary of the rabbit is an albuminous gland. The sublingual may perhaps in all mammals be regarded as a mucous gland, though it differs in several respects from other mucous glands ; the cells lining the ducts are much shorter and less distinctly striated, the alveoli are more obviously branched tubules, and the cells of some alveoli contain no mucin. 390 STRUCTURE OF THE PANCREAS. [BOOK n. The small buccal glands which lie in the substance of the mucous membrane of the mouth, and whose secretion contributes to " mixed " saliva, are formed, on a small scale, after the plan of a salivary gland, that is to say, they are composed of a duct (or ducts) and alveoli which in structure are similar to those of a salivary gland. They further resemble the salivary glands in that some of them ars ' albuminous ' and some ' mucous.' § 219. The salivary glands have each of them a special nervous supply of which we shall speak in detail in the following section, and will here simply say that the fibres passing into the glands are both medullated and non-medullated fibres, and that the terminations of the fibres have not been as yet exactly made out ; for, though it has been maintained by some observers that some of the nerve-fibres end in the secreting cells, this has not been satis- factorily proved. Numerous nerve-cells may be seen scattered along the nerve-fibres where they pass into the gland at the ' hilus ' whence the main duct issues. Of the nervous supply of the stomach, derived partly from both vagi nerves, and partly from the solar plexus, we shall also have to speak later on, we may here simply say that the fibres end for the most part in a peculiar plexus between the circular and longitu- dinal muscular layers, and in another peculiar plexus in the submucous coat, the two plexuses corresponding to what we shall describe in the small intestine as the plexus of Auerbach and the plexus of Meissner. The Pancreas. § 220. The structure of the pancreas is so similar to that of a salivary gland that though we shall not deal with the properties and characters of the pancreatic juice until later on, it will be convenient to consider the histology of the gland now. Whether as in man, in the dog and in most other animals it forms a compact mass, or as in the rabbit is spread out into a thin sheet, the pancreas is in all cases a compound racemose gland, con- sisting of ducts and alveoli arranged in lobes and lobules. In man the smaller ducts join one main duct, which running lengthwise through the gland pierces the coats of the duodenum in company with, and opens into the interior of the intestine by an orifice common to it and to the bile duct. Not infrequently a second but smaller main duct coming from the lower part of the head of the gland joins the intestine lower down ; in the dog such a second duct is a usual occurrence. In the rabbit the main duct does not join the intestine with the bile duct, but at a considerable distance, several centimetres, lower down, so that in this animal the bile and pancreatic juice are not poured together into the intestine, but CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 391 the food is for a distance exposed to the action of the former before it meets with the latter. The structure of the ducts is, in all essential points, similar to that of the ducts of a salivary gland, save that the striation of the epithelial cells is less distinct. «^c£s in the case of the salivary gland, the ductule, or narrow terminal portion of the duct, just as it joins the alveoli is lined by flat spindle-shaped cells. The alveoli also are similar to those of a salivary gland save perhaps that they are relatively longer and more tubular ; the lumen in all cases is very narrow. As compared with a salivary gland the alveoli are relatively more numerous than the ducts, so that in a section of the gland1 relatively fewer ducts are seen cut across. Each alveolus is lined with one kind of cell only, which is much more similar to an albuminous than to a mucous cell ; fthere are no demilune cells. The more minute features of the alveolus differ according as the gland has been ' resting ' and so is ' loaded,' or has been ' active ' and so is ' discharged.' The cells lining the alveolus are more or less polyhedral in form, and each cell consists of a clear transparent cell-body, in which occur a number of refractive discrete "granules;" a spherical nucleus lies at about the outer third of the cell. In a ' loaded ' cell these granules are very abundant, and reach from the narrow, inconspicuous lumen to near the outer margin of the cell, so as to leave only a narrow clear transparent zone immediately bordering on the basement membrane ; the cell-substance is so thickly studded with these ' granules ' that the nucleus is completely hidden, and the greater part of the cell appears quite dark. In a ' discharged ' cell these granules are far less numerous, and are largely confined to the inner part of the cell abutting on the lumen, so that there is established a clear distinction between a narrow inner " granular " zone and a clear transparent outer zone, free or nearly free from granules. The width of the granular zone varies in fact with the condition of the gland ; when the gland has been very active the granular zone is very narrow, when moderately active, it is broader, and when the gland has been for some time wholly at rest and is therefore loaded, the granular zone may encroach on nearly the whole cell. But we shall have to return to these matters presently. In the pancreas of the rabbit and some other animals groups of cells of a peculiar nature may be seen intercalated at intervals in the midst of the true glandular substance. These are rounded or polyhedral in form, and have a clear cell-substance with a relatively large nucleus ; they do not form alveoli and they have no ducts. Each of these groups is supplied with blood vessels forming a capillary network more close set than elsewhere. The exact nature of these cells is at present a matter of doubt. The pancreas is supplied with nerves coming from the solar plexus, and consisting partly of medullated and partly of non- 392 STRUCTURE OF THE (ESOPHAGUS. [BOOK n. medullatecl fibres. As in the case of the salivary glands nerve-cells are found in connection with the nerve-fibres as these pass into the gland. The Structure of the (Esophagus. § 221. In the general plan of its structure the oesophagus resembles the rest of the alimentary canal, for it consists of a mucous membrane, with a muscularis mucosse and glands, a loose submucous coat, and a muscular coat comprising an inner circular and an outer longitudinal layer.V But the epithelium, epiblastic in origin, is very different from that of the stomach or intestine, and both circular and longitudinal muscular layers are composed > to a large extent not of unstriated but of striated fibres like those of the skeletal muscles. In a vertical section of the oesophagus it will be seen that the epithelium is not arranged as a single layer of cells, but is several cells deep. The lower cells near the basement membrane, which is not very distinct, are cylindrical or spheroidal cells with granular ' protoplasmic ' cell-substance, but those nearer the surface are more flattened, and the uppermost cells are mere flattened nu- cleated scales, the bodies of which are no longer protoplasmic but have become changed into a peculiar material. Such an epithelium is called a ' stratified ' epithelium. A similar epithe- lium lines the greater part of the pharynx and the mouth, and is continuous with the corresponding epithelium of the skin or " epidermis " of which we shall have to speak later on. At the cardiac orifice there is a sudden transition from this stratified epithelium to the gastric epithelium previously described. The looseness of the submucous coat permits the mucous membrane to be thrown into temporary longitudinal folds which disappear when the canal is distended. But besides this, the line of the basement membrane, of the connective tissue basis of epithelium, ' dermis ' or ' corium ' as the corresponding part of the skin is called, is raised up into a number of permanent conical elevations or papillce, in which the connective tissue is especially fine and which are richly provided with blood vessels. The surface line of the epithelium does not follow the inequalities of the dermis produced by these papilla^, but remains fairly even. In the presence of these papillae the mucous membrane of the oesophagus also resembles the skin, but in the latter structure the papillae are more abundant and more regular in form and size. The dermis, or connective tissue basis of the epithelium, is a network of fibres and fine bundles of connective tissue, with connective tissue corpuscles and a considerable number of fine elastic fibres ; the number of leucocytes in the meshes of the network is relatively scanty. A few scattered masses of retiform or adenoid tissue, of which we shall speak later on, occur here and there. CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 393 The mucous membrane proper is defined from the underlying submucous tissue by a muscularis mucosae of plain unstriated muscular fibres, lying at some distance from the epithelium. These muscular fibres are absent at the upper part of the oesophagus, appear lower down in isolated longitudinal bundles, and eventually form a distinct layer, which however is not so regular as in the rest' of the alimentary canal, arid consists of longitudinal fibres only, circular fibres being absent. In man a few but in other animals a considerable number of small 'mucous' and 'albuminous' glands are found in the submucous tissue ; their ducts, penetrating the muscularis mucosa3 where present, open on to the surface of the mucous membrane." In man and mammalia these glands appear to serve only the purpose of keeping the internal surface of the oesophagus moist ; but in some animals, as in the frog, in which the epithelium of the oesophagus is not the many layered stratified epithelium just described, but a single layer of columnar ciliated cells mixed with mucous cells, of the kind which we shall later on describe as ' goblet ' cells, there is a large development of glands at the lower part of the oeso- phagus, and the cells of these glands manufacture pepsin. As in other parts of the alimentary canal the submucous tissue carries the larger blood vessels whose smaller branches supply the mucous membrane ; and lymphatics, beginning in the mucous membrane, form considerable plexuses in the submucous coat. § 222. In man both the thicker inner circular and the outer thinner longitudinal muscular layer consist in the upper part of the oesophagus exclusively of bundles of striated fibres, which in their main characters are identical with ordinary fibres of skeletal muscles. At about the end of the upper third or sooner, bundles of plain unstriated fibres make their appearance among the bundles of striated fibres, and a little lower down the striated fibres disappear, so that, in the lower half or more of the tube, both circular and longitudinal layers are composed almost exclu- sively of plain unstriated fibres, a few stray bundles of striated muscle being found here and there. The relation of the striated and unstriated fibres differs however in different animals ; in some the striated tissue reaches down nearly to the stomach. Above, both longitudinal and circular layers merge into the inferior constrictor of the pharynx ; below, the longitudinal bundles spread out in a radial fashion to join the corresponding longitudinal muscular coat of the stomach, and the circular fibres are also continuous with the circular and oblique layers of the stomach, more especially with the latter. Before the circular fibres thus spread out over the stomach, they undergo a somewhat increased development forming a sort of sphincter of the cardiac orifice. Outside the longitudinal muscular coat of the oesophagus there is a considerable development of connective tissue forming what is 394 STRUCTURE OF THE (ESOPHAGUS. [BOOK n. sometimes spoken of as a fibrous sheath. In, or rather perhaps on, this sheath in the lower part of the oesophagus run the two vagi nerves, with the oesophageal plexus which is formed by branches running from the one to the other. In it also run the larger blood vessels. § 223. It is obvious that the oesophagus is much more a muscular than a secreting structure, and further that a distinction is to be made between the upper part of the oesophagus where the muscular fibres are striated, and the lower part where they are unstriated. Corresponding more or less clearly to this distinction we find that though the whole oesophagus is supplied by nerve fibres from the trunk of the vagus (which however it must be remembered contains besides fibres of the vagus proper, fibres from the spinal accessory nerve and from other sources) the supply to the upper part takes a different course from the supply to the lower part. Thus in man the upper part is supplied by branches of the recurrent laryngeal nerve as it runs up between the trachea and oesophagus, while the lower part derives its nerve fibres from the oesophageal plexus formed by the two vagi. In various animals the supply of the upper part varies, coming in some cases chieHy from the pharyngeal branch of the vagus, and being in the rabbit a distinct branch of the vagus. In all cases however it would seem that the lower part of the oesophagus, the upper limit being placed higher or lower in different animals, is supplied from i lie oesophageal plexus. It may be remarked that the fibres in this plexus are for the most part non-medullated fibres, but we shall have to return to these nerves in speaking of the movements of the oesophagus. SEC. 3. THE ACT OF SECRETION OF SALIVA AND GASTRIC JUICE AND THE NERVOUS MECHANISMS WHICH REGULATE IT. § 224. The saliva and gastric juice whose properties we have studied, though so different from each other, are both drawn ultimately from one common source, the blood, and they are poured into the alimentary canal, not in a continuous flow, but intermit- tently as occasion may demand. The epithelium cells which supply them have their periods of rest and of activity, and the amount and quality of the fluids which these cells secrete are determined by the needs of the economy as the food passes along the canal. We have now to consider how the epithelium cell manufactures its special secretion out of the materials supplied to it by the blood, and how the cell is called into activity by the presence of food, it may be as in the case of saliva at some distance from itself, or by circumstances which do not bear directly on itself. In dealing with these matters in connection with the digestive juices, we shall have to enter at some length into the physiology of secretion in general. The question which presents itself first is : By what mechanism is the activity of the secreting cells brought into play ? While fasting, a small quantity only of saliva is poured into the mouth ; the buccal cavity is just moist and nothing more. When food is taken, or when any sapid or stimulating substance, or indeed a body of any kind, is introduced into the mouth, a flow is induced which may be very copious. Indeed the quantity secreted in ordinary life during 24 hours has been roughly calculated at as much as from 1 to 2 litres. An abundant secretion in the absence of food in the mouth may be called forth by an emotion, as when the mouth waters at the sight of food, or by a smell, or by events occurring in the stomach, as in some cases of nausea. Evidently in these instances some nervous mechanism is at work. In studying the action of this nervous mechanism, it will be of advantage to confine our attention at first to the submaxillary gland. 396 NERVES OF THE SUBMAXILLARY GLAND. [BOOK n. § 225. The submaxillary gland is supplied with two sets of nerves. These are represented in Fig. 62, which is a very diagram- matic rendering of the appearances presented when the submaxillary gland is prepared for an experiment in a dog, the animal being placed on its back and the gland exposed from the neck. The one set, and that the more important, belongs to the chorda tyinpani nerve (ch.t"}. This is a small nerve, which branches off from the facial or seventh cranial nerve in the Fallopian canal before the nerve issues from the skull. Whether it really belongs to the facial proper has been doubted ; in man the fibres which form it are either fibres coming not from the roots of the facial proper but from the portio intermedia Wrisbergi, or, according to some, fibres which though joining the facial in the Fallopian canal are ulti- mately derived from another (the fifth) cranial nerve. Leaving the facial nerve the chorda tympani passes through the tympanic cavity or drum of the ear (hence the name) and joins or rather runs in company (ch.t') with the lingual or gustatory7 branch of the fifth nerve. Some of the fibres run on with the lingual right down to the tongue (these are not shewn in the figure), but many leave the lingual as a slender nerve (ch.t), which reaching Wharton's duct or duct of the submaxillary gland (N//M/) runs along the duct to the gland. As the nerve courses along the duct nerve cells make their appearance among the fibres, and these are especially abun- dant just after the duct enters the hilus of the gland. The fibres may be traced into the gland for some distance, but as we have said their ultimate ending has not yet been definitely made out. Along its whole e»ur-e up to the gland, the fibres of the chorda are very fine medullated fibres, but they lose their medulla in the gland. The other set of nerve-fibres reaches the gland along the small arteries of the gland. These are non-medullated fibres mixed with a few medullated fibres and may be traced back to the superior cervical ganglion. From thence they may be traced still further back down the cervical sympathetic to the spinal cord, following apparently the same tract as the vaso-constrictor fibres, treated of in § 1G6. § 226. If a tube be placed in the duct, it is seen that when sapid substances are placed on the tongue, or the tongue is stimulated in any other way, or the lingual nerve is laid bare and stimulated with an interrupted current, a copious flow of saliva takes place. If the sympathetic be divided, stimulation of the tongue or lingual nerve still produces a flow. '^But if the small chorda nerve be divided, stimulation of the tongue or lingual nerve produces no flow. Evidently the flow of saliva is a nervous reflex action, the lingual nerve serving as the channel for the afferent and the small chorda nerve for the efferent impulses. If the trunk of the lingual be divided above the point where the chorda leaves it, as CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 397 at n.l', Fig. 62, stimulation of the (front part of) tongue produces, under ordinary circumstances, no flow. This shews that the centre of the reflex action is higher up than the point of section ; it lies in fact in the brain. FIG. 62. DIAGRAMMATIC BEPRESENTATION OF THE SUBMAXILLAKY GLAND OF THE DOG WITH ITS NERVES AND BLOOD VESSELS. (The dissection Las been made on an animal lying on its back, but since all the parts shewn in the figure cannot be seen from any one point of view, the figure does not give the exact anatomical relations of the several structures.) sm. gld. The subrnaxillary gland, into the duct (sm. d.) of which a cannula has been tied. The sublingual gland and duct are not shewn, n. L, n. I'. The lingual branch of the fifth nerve, the part >i. L is going to the tongue, ch. t., ch. t'., ch. t". The chorda tympani. The part ch. t". is proceeding from the facial nerve ; at ch. t'. it becomes conjoined with the lingual n. I' and afterwards diverging passes as ch. t. to the gland along the duct ; the continuation of the nerve in company with the lingual n. 1. is not shewn, sm. gld. The subrnaxillary ganglion with its several roots, a. car. The carotid artery, two small branches of which, a. sm. a. and r. sm. p. , pass to the anterior and posterior parts of the gland, v. s.m. The anterior and pos- terior veins from the gland, falling into v.j. the jugular vein, v.sym. The con- joined vagus and sympathetic trunks, g. cer.s. The upper cervical ganglion, two branches of which forming a plexus (a./.) over the facial artery, are distributed (n. sym. sm.) along the two glandular arteries to the anterior and posterior portions of the gland. The arrows indicate the direction taken by the nervous impulses during reflex stimulation of the gland. They ascend to the brain by the lingual and descend by the chorda tympani. In the angle between the lingual and the chorda, where the latter leaves the former to pass to the gland, lies the small submaxillary gan- glion (represented diagrammatic-ally in Fig. 62 sin. ///.). This consists of small masses of nerve cells lying on the small bundles of nerve-fibres which spread out like a fan from the lingual and chorda tympani 398 SECRETION OF SALIVA BY REFLEX ACTION. [BOOK n. nerves (ch. t.) towards the ducts of the submaxillary and sublingual glands. It has been much debated whether this ganglion can act as a centre of reflex action in connection with the submaxillary gland, but no conclusive evidence that it does so act has as yet been shewn ; it probably belongs in reality to the sublingual gland. Stimulation of the glossopharyngeal is even more effectual than that of the lingual. Probably this indeed is the chief afferent nerve in ordinary secretion. Stimulation of the mucous membrane of the stomach (as by food introduced through a gastric fistula) or of the vagus may also produce a flow of saliva, as indeed may stimulation of the sciatic, and probably of many other afferent nerves. All these cases are instances of reflex action, the cerebro-spinal system acting as a centre. We may further define the centre as a part of the medulla oblonguta, apparently not far removed from the vaso-motor centre. When the brain is removed down to the medulla oblougata, that organ being left intact, a flow of saliva may still be obtained by adequate stimulation of various afferent nerves ; when the medulla is destroyed no such action is possible. And a flow of saliva may be produced by direct stimu- lation of the medulla itself. \Yhen a flow of saliva is excited by ideas, or by emotions, the nervous processes begin in the higher parts of the brain, and descend thence to the medulla before they give rise to distinctly efferent impulses ; and it would appear that these higher parts of the brain are called into action when a flow of saliva is excited by distinct sensations of taste. Considering then the flow of saliva as a reflex act the centre of which lies in the medulla oblongata, we may imagine the efferent impulses passing from that centre to the gland either by the chorda tympani or by the sympathetic nerve. Although it would perhaps be rash to say that in this relation the sympathetic nerve never acts as an efferent channel, as a matter of fact we have no satisfactory experimental evidence that it does so ; and we 1 may therefore state that, practically, the chorda tympani is the sole efferent nerve.4- Section of that nerve, either where the fibres pass from the lingual nerve and the submaxillary ganglion to the gland, or where it runs in the same sheath as the lingual, or in any part of its course from the main facial trunk to the lingual, puts an end, as far as we know, to the possibility of any flow being excited by stimuli applied to the sensory nerves, or to the sentient surfaces of the mouth or of other parts of the body. The natural reflex act of secretion may be inhibited, like the reflex action of the vaso-motor nerves, at its centre. Thus when, as in the old rice ordeal, fear parches the mouth, it is probable that the afferent impulses caused by the presence of food in the mouth cease, through emotional inhibition of their reflex centre, to give rise to efferent impulses. § 227. In life, then, the flow of saliva is brought about by the CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 399 advent to the gland along the chorda tympani of efferent, impulses, started chiefly by reflex actions. The inquiry thus narrows itself to the question : In what manner do these efferent impulses cause the increase of How ? If in a dog a tube be introduced into Wharton's duct, and the chorda be divided, (lie flow, if any be going on, is from the lack of efferent impulses arrested. On passing an interrupted current through the peripheral portion of the chorda, a copious secretion at once takes place, and the saliva begins to rise rapidly in the tube ; a very short time after the application of the current the flow reaches a maximum which is maintained for some time, and then, if the current be long continued, gradually lessens. If the current be applied for a short time only, the secretion may last for some time after the current has been shut off. The saliva thus * obtained is but slightly viscid, and under the microscope a very few salivary corpuscles, and, occasionally only, amorphous lumps of peculiar material, probably mucous in nature, are seen. If the gland itself be watched, while its activity is thus roused, it will be seen (as we have already said, § 167) that its arteries are dilated, and its capillaries filled, and that the blood flows rapidly through the veins in a full stream and of bright arterial hue, frequently with pulsating movements. If a vein of the gland be opened, this large increase of flow, and the lessening of the ordinary deoxygenation of the blood consequent upon the rapid stream, will be still more evident. It is clear that excitation of the chorda largely dilates the arteries ; the nerve acts energetically as a vaso-dilator nerve. Thus stimulation of the chorda brings about two events : a dilation of the blood vessels of the gland, and a flow of saliva. The question at once arises, Is the latter simply the result of the former or is the flow caused by some direct action on the secreting cells, apart from the increased blood-supply ? In support of the former view we might argue that the activity of the epithelial secreting cell, like that of any other form of protoplasm, is dependent on blood-supply. When the small arteries of the gland dilate, while the pressure in the arteries on the side towards the heart is (as we have previously seen when treating generally of blood-pressure § 120) correspondingly diminished, the pressure on the far side in the capillaries and veins is increased ; hence the capillaries become fuller, and more blood passes through them in a given time. From this we might infer that a larger amount of nutritive material would pass away from the capillaries into the surrounding lymph-spaces, and so into the epithelium cells, the result of which would naturally be to quicken the processes going on in the cells, and to stir these up to greater activity. But even admitting all this it does not necessarily follow that the activity thus excited should take on the form of secretion. It is quite possible to conceive that the increased blood-supply should lead only to the accumulation in the cell of the constituents of the 400 SECRETION AND BLOOD SUPPLY. [BOOK n. saliva, or of the raw materials for their construction, and not to a discharge of the secretion. A man works better for being fed, but feeding does not make him work in the absence of any stimulus. The increased blood-supply therefore, while favourable to active secretion, need not necessarily bring it about. Moreover, the following facts distinctly shew that it need not. When a cannula is tied into the duct and the chorda is energetically stimulated, the pressure acquired by the saliva accumulated in the cannula and in the duct may exceed for the time being the arterial blood-pressure, even that of the carotid artery ; that is to say, the pressure of fluid in the gland outside the blood vessels is greater than that of the blood inside the blood vessels. This must, whatever be the exact mode of transit of nutritive material through the vascular \valls, tend to check that transit. Again, if the head of an animal be rapidly cut off, and the chorda immedi- ately stimulated, a rio\v of saliva takes place far too copious to be accounted for by the emptying of the salivary channels through any supposed contraction of their walls. In this case secretion is excited in the gland though the blood-supply is limited to the small quantity still remaining in the blood vessels. Lastly, if a small quantity of atropin be injected into the veins, stimulation of the chorda produces no secretion of saliva at all, though the dilation of the blood vessels takes place as usual ; in spite of the greatly increased blood-supply no secretion at all takes place. These facts prove that the secretory activity is not simply the result of vascular changes, but may be called forth independently ; they further lead us to suppose that the chorda contains two sets of h'bres, one which we may call secretory fibres, acting directly on the secreting structures only, and the other vaso-dilator fibres, acting on the blood vessels only, and further that atropin, while it has no effect on the latter, paralyses the former just as it paralyses the in- hibitory fibres of the vagus. Hence when the chorda is stimulated, there pass down the nerve, in addition to impulses affecting the blood-supply, impulses affecting directly the protoplasm of the se- creting cells, and calling it into action, just as similar impulses call into action the contractility of the substance of a muscular fibre. Indeed the two things, secreting activity and contracting activity, are very parallel. We know that when a muscle contracts, its blood vessels dilate ; and much in the same way as by atropin the secreting action of the gland may be isolated from the vascular dilation, so (in the frog at all events) by a proper dose of urari muscular contraction may be removed, and leave dilation of the blood vessels as the only effect of stimulating the muscular nerve. In both cases the greater flow of blood may be an adjuvant to, but is not the exciting cause of, the activity of the structures. Since the chorda acts thus directly on the secreting cells, we should expect to find an anatomical connection between the cells and the nerve ; and some authors have maintained that the nerve- CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 401 fibres may be traced into the cells. But, save perhaps in the case of certain glands of invertebrates (so-called salivary glands of Blatta), the evidence MS we have said is as yet not convincing. § 228. When the cervical sympathetic is stimulated, the \ vascular effects, as we have already said, § 1G8, are the exact I contrary of those seen when the chorda is stimulated. The small arteries are constricted, and a small quantity of dark venous blood escapes by the veins. Sometimes, indeed, the flow through the gland is almost arrested. The sympathetic therefore acts as a vasoconstrictor nerve, and in this sense is antagonistic to the chorda. As concerns the flow of saliva brought about by stimulation of the sympathetic, in the case of the submaxillary gland of the dog the effects are very peculiar. A slight flow results, and the saliva so secreted is remarkably viscid, of higher specific gravity, and richer in corpuscles and in the above-mentioned amorphous lumps than is the chorda saliva. This action of the sympathetic is little or not at all affected by atropin. In the submaxillary gland of the dog then the contrast between the effects of chorda stimulation and those of sympathetic stimu- lation are very marked : the former gives rise to vascular dilation with a copious flow of fairly limpid saliva poor in solids, the latter to vascular constriction with a scanty flow of viscid saliva richer in solids. And in other animals a similar contrast prevails, though with minor differences. Thus in the rabbit both chorda saliva and sympathetic saliva are limpid and free from mucus, though the latter contains more proteids ; in the cat, chorda saliva is more viscid than sympathetic saliva; but in both these cases, as in the dog, stimulation of the chorda causes a copious flow with dilated blood vessels, and stimulation of the sympathetic a scanty flow with vascular constriction. We shall return again presently to these different actions of the two nerves ; meanwhile we have seen enough of the history of the submaxillary gland to learn that secretion in this instance is a reflex action, the efferent impulses of which directly affect the secreting cells, and that the vascular phenomena may assist, but are not the direct cause of, the flow. § 229. We have dwelt long on this gland because it has been more fruitfully studied than any other. But the nervous mechanisms of the other salivary glands are in their main features similar. Thus the secretion of the parotid gland, like that of the submaxillary, is governed by two sets of fibres : one of cerebro- spinal origin, running along the auriculo-temporal branch the fifth nerve but originating possibly in the glossopharyugeal, and the other of sympathetic origin coming from the cervical sympathetic. Stimulation of the cerebro-spinal fibres produces a copious flow of limpid saliva, free from mucus, the secretion reaching in the dog a pressure of 118 mm. mercury; stimulation of the cervical sympathetic gives rise in the rabbit to a secretion F. 26 402 SECRETION OF GASTRIC JUICE. [BOOK n. also free from mucus but rich in proteids and of greater amylolytic power than the cerebro-spinal secretion ; in the dog little or no secretion is produced, though, as we shall see later on, certain changes are brought about in the gland itself. In both animals the cerebro-spinal fibres are vaso-dilator, and the sympathetic fibres vaso-constrictor in action. Stimulation of the central end of the glossopharyugeal produces by reflex action a secretion from the parotid gland, but that of the lingual is said to be without effect. § 230. The secretion of gastric juice. Though a certain amount of gastric juice may sometimes be found in the stomachs of fasting animals, it may be stated generally that the stomach, like the salivary glands, remains inactive, yielding no secretion, so long as it is not stimulated by food or otherwise. The advent of food into the stomach however at once causes a copious flow of gastric juice ; and the quantity secreted in the twenty-four hours is probably very considerable, but we have no trustworthy data for calculating the exact amount. So also when the gastric mucous membrane is stimulated mechanically, as with a feather, secretion is excited : but to a very small amount even when the whole interior surface of the stomach is thus repeatedly stimulated. The most efficient stimulus is the natural stimulus, viz. food ; though dilute alkalis seem to have unusually powerful stimulating effects ; thus the swallowing of saliva at once provokes a flow of gastric juice. During fasting the gastric membrane is of a pale grey colour, somewhat dry, covered with a thin layer of mucus, and thrown into folds ; during digestion it becomes red, flushed, and tumid, the folds disappear, and minute drops of fluid appearing at the mouths of the glands, speedily run together into small streams. When the secretion is very active, the blood flows from the capillaries into the veins in a rapid stream without losing its bright arterial hue. The secretion of gastric juice is in fact accompanied by vascular dilation in the same way as is the secretion of saliva. § 231. Seeing that, unlike the case of the salivary secretion, food is brought into the immediate neighbourhood of the secreting cells, it is exceedingly probable that a great deal of the secretion is the result of the working of a local mechanism ; and this view is supported by the fact that when a mechanical stimulus is applied to one spot of the gastric membrane the secretion is limited to the neighbourhood of that spot and is not excited in distant parts. This local mechanism may be nervous in nature or the effect of the stimulus may perhaps be conveyed directly from cell to cell, from the mouth of the gland to its extreme base, without the intervention of any nervous elements ; but the vascular changes at least would seem to imply the presence of a nervous mechanism. The stomach is supplied with nerve-fibres from the two vagi nerves and from the solar plexus of the splanchnic system. The CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 403 two vagi after forming the oesophageal plexus on the oesophagus are gathered together again as two main trunks which run along the oesophagus, the left in the front the right at the back, to the stomach. The left, or anterior nerve is distributed to the SHIM! lei- curvature and the front surface of the stomach, forming a plexus in which nerve-cells are present; and branches pass on to the liver and probably to the duodenum. The right, or posterior nerve is distributed to the hinder surface of the stomach, but only to the extent of about one-third of its fibres ; about two- thirds of the fibres pass on to the solar plexus. The fibres of the vagus nerves thus distributed to the stomach are for the most part non- medullated fibres ; by the time the vagus reaches the abdomen it consists almost exclusively of non-medullated fibres, medullated fibres being very few ; the large number of medullated fibres which the nerve contains in the upper part of the neck pass off into the laryngeal, cardiac and other branches. From the solar plexus nerves, arranged largely in plexuses, pass in company with the divisions of the coeliac artery, coronary artery of the stomach and branches of the hepatic artery, to the stomach. Though the two abdominal splanchnic nerves which join the solar plexus (semilunar ganglia) are chiefly composed of medullated fibres, the nerves which pass from the plexus to the stomach are to a large extent composed of non-medullated fibres. All these nerves, both the branches of the vagi and those from the solar plexus, lie at first in company with the arteries on the sur- face of the stomach beneath the peritoneum. From thence they pass inwards, still in company with arteries, and form on the one hand a plexus, containing nerve-cells, between the longitu- dinal and circular muscular coats corresponding to what in the intestine we shall have to speak of as the plexus of Auerbach, whence fibres are distributed to the two muscular coats, and on the other hand a plexus in the submucous coat, also containing nerve-cells, corresponding to what is known in the intestine as Mi 'issuer's plexus. From this latter plexus fibres pass to the mucous membrane; some of these end in the muscularis mucosa3 ; whether any are connected with the gastric glands, and if so how, is not at present known. There are 110 facts which afford satisfactory evidence that any part of this arrangement of nerves supplies such a local nervous mechanism as was suggested above. The importance however of such a local mechanism whatever its nature, and the subordinate value of any connection between the gastric membrane and the central nervous system, is further shewn by the fact that a secretion of quite normal gastric juice will go on after both vagi, or the nerves from the solar plexus going to the stomach have been divided, and indeed when all the nervous connections of the stomach are as far as possible severed. And all attempts to provoke or modify gastric secretion by the stimulation of the nerves going to the 26—2 404 SECRETION OF GASTRIC JUICE. [BOOK n. stomach, have hitherto failed. On the other hand, in cases of gastric fistula, where by complete occlusion of the oesophagus stimulation by the descent of saliva has been avoided, the mere sight or smell of food has been seen to provoke a lively secretion of gastric juice. This must have been due to some nervous action ; and the same may be said of the cases where emotions of grief or anger suddenly arrest the secretion going on or prevent the secretion which would otherwise have taken place as the result of the presence of food in the stomach. !So that much has yet to be learnt in this matter. § 232. The contrast presented between the scanty secretion resulting from mechanical stimulation and the copious flow which actual food induces is interesting because it" seems to shew that tin- secretory activity of the cells is heightened by the absorption of certain products derived from the portions of food first digested. This is well illustrated by the following experiment of Heidenhain. This observer, adopting the method employed for the intestine, of whirh we shall speak later on, succeeded in isolating a portion of the fimdus from the rest of the stomach; that is to say, he cut out a portion of the tundus, sewed together the cut edges of the main stomach, so as to form a smaller but otherwise complete organ, while by sutures he converted the excised piece of fundus into a small independent stomach opening on to the exterior by a fistulous orifice. \Yhen food was introduced into the main stomach secretion also took place in the isolated fundus. This at first sight might seem the result of a nervous reflex act ; but it was observed that the secondary secretion in the fundu^ was dependent on actual digestion taking place in the main stomach. If the material introduced into the main stomach were indigestible or digested with difficulty, so that little or no products of digestion were formed and absorbed into the blood, such ex. gr. as pieces of ligamentum nuchse, very little secretion took place in the isolated fundus. We quote this now as bearing on the question of a possible nervous mechanism of gastric secretion, but we shall have to return to it under another aspect. The changes in a gland constituting the act of secretion. § 233. We have now to consider what are the changes in the glandular cells and their surroundings which cause this flow of fluid possessing specific characters into the lumen of an alveolus, and so into a duct. It will be convenient to begin with the pancreas. The thin extended pancreas of a rabbit may, by means of special precautions, be spread out on the stage of a microscope and examined with even high powers, while the animal is not only alive but under such conditions that the gland remains in a nearly CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 405 normal state, capable of secreting vigorously. It is possible under these circumstances to observe even minutely the appearances presented by the gland when at rest and loaded, and to watch the changes which take place during secretion. When the animal has not been digesting for some little time, and the gland is therefore " loaded," the outlines of the individual cells, as we have already said, § 220, are very indistinct, the lumen of the alveolus is invisible or very inconspicuous, and each cell is crowded with small, refractive spherical granules, forming an irregular granular mass which hides the nucleus and leaves only a very narrow clear outer zone next to the basement membrane, or it may be hardly any such zone at all. Fig. 63 A. The blood-supply moreover is scanty, the small arteries being constricted and the capillaries imperfectly filled with corpuscles. If, however, the same pancreas be examined while it is in a state of activity, either from the presence of food in the stomach, or from the injection of some stimulating drug, such as pilocarpin, a very different state of things is seen. The individual cells (Fig. 63 B) have become smaller and much more distinct in E. FIG. 63. A PORTION OF THE PANCREAS OF THE RABBIT. (Kiihne and Sheridan Lea.) A at rest, B in a state of activity. a the inner granular zone, which in A is larger, and more closely studded with fine granules, than in B, in which the granules are fewer and coarser. b the outer transparent zone, small in A, larger in B, and in the latter marked with faint striae. c the lumen, very obvious in B, but indistinct in A. d an indentation at the junction of two cells, seen in B, but not occurring in A. outline, and the contour of the alveolus which previously was even is now wavy, the basement membrane being indented at the junctions of the cells; also the lumen of the alveolus is now wider and more conspicuous. In each cell the granules have become much fewer in number and as it were have retreated to the inner margin, so that the inner granular zone is much narrower and the outer transparent zone much broader than before ; the latter too is frequently marked at its inner part by delicate striae running into the inner zone. At the same time the blood vessels are 406 CHANGES IN PANCREATIC CELLS. [BOOK n. largely dilated and the stream of blood through the capillaries is full and rapid. With care the change from the one state of things to the other may be watched under the microscope. The vascular changes can of course be easily appreciated, but the granules may also be seen to diminish in number. Those at the inner margin seem to be discharged into the lumen, and those nearer the outer margin to travel inwards through the cell-substance towards the lumen, the faint stria? spoken of above, apparently at all events, being the marks of their paths. Obviously during secretion, the granules with which the cell-substance was ' loaded ' are ' discharged ' from the cell into the lumen of the alveolus. What changes these granules may undergo during the discharge we shall consider presently. Sections of the prepared and hardened pancreas of any animal tell nearly the same tale as that thus told by the living pancreas of the rabbit. In sections for instance of the pancreas of a dog which has not been fed, and therefore has not been digesting, for some hours (24 or 30), the cells are seen to be crowded with granules (which however are usually shrunken and irregular owing to the influence of the hardening agent), leaving a very narrow outer zone. In similar sections of the pancreas of a dog which has been recently fed, six hours before for example, and in which therefore the gland has been for some time actively secreting, the granules are far less numerous, and the clear outer zone accordingly much broader and more conspicuous. With osmic acid these granules stain well, and are preserved in their spherical form, so that the cell thus stained maintains much of the appearance of a living cell. But with carmine, hsematoxylin &c. the granules do not stain nearly so readily as does the cell-substance of the cells, so that a discharged cell stains more deeply than does a loaded cell because the staining of the ' protoplasmic ' cell-substance is not so much obscured by the unstained granules ; besides which however the actual cell-substance stains probably somewhat more deeply in the discharged cell. It may be added that in the discharged cell the nucleus is conspicuous and well formed ; in the loaded cell it is generally in prepared sections, more or less irregular, possibly because in these it is less dense and more watery than in the dis- charged cell, and so shrinks under the influence of the reagents employed. These several observations suggest the conclusion that in a gland at rest the cell is occupied in forming by means of the metabolism of its cell-substance and lodging in itself (§ 30) certain granules of peculiar substance intended to be a part and probably an important part of the secretion. This goes on until the cell is more or less completely ' loaded.' In such a cell the amount of actual living cell-substance is relatively small, its place is largely occupied by granules, and it itself has been partly CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 407 consumed in forming the granules. During the act of secretion the granules are discharged to form part of the secretion, other matters including water, ;is we slmll see, milking up (lie whole secretion ; and the cell would be proportionately reduced in size were it not that the act of the discharge seems to stimulate the cell- substance to a new activity of growth, so that new cell-substance is formed ; this however is in turn soon in part consumed in order to form new granules. And what is thus seen with considerable distinctness and ease in the pancreas, is seen with more or less distinctness in other glands. § 234. When we study an albuminous gland, the parotid gland for instance, in a living state, we find that the changes which take place during activity are quite comparable to those of the pan- creas. During rest (Fig. 64 A), the cells are large, their outlines very indistinct, in fact almost invisible, and the cell-substance is studded with granules. During activity (Fig. 64 B), the cells become smaller, their outlines more distinct, and the granules disappear, especially from the outer portions of each cell. After prolonged activity, as in Fig. 64 C, the cells are still smaller with A FIG. 64. CHANGES IN THE PAROTID DURING SECRETION. (Langley.) The figure, which is somewhat diagrammatic, represents the microscopic changes which may be observed in the lirii/;/ gland. A. During rest. The obscure outlines of the cells are introduced to shew the relative size of the cells, they could not be readily seen in the specimen itself. B. After moderate stimulation. C. After prolonged stimulation. The nuclei are diagrammatic, and introduced to shew their appearance and position. their outlines still more distinct, and the granules have disappeared almost entirely, a few only being left at the extreme inner margin of each cell, abutting upon the conspicuous, almost gaping lumen of the alveolus. And upon special examination it is found that the nuclei are large and round. In fact we might almost take the parotid, as thus studied, to be more truly typical of secretory changes than even the pancreas. For, the demarcation of an inner and outer zone is not a necessary feature of a secreting cell at rest. What is essential is that the cell-substance manufactures material, which for a while, that is during rest, is deposited in the cell, generally in the form of granules but not necessarily so, and that during activity this material is used up, the disappearance 408 CHANGES IN ALBUMINOUS CELLS. [BOOK 11. of the granules, when these are visible, being naturally earliest and most marked at the outer portions of each cell, and progressing inwards towards the lumen, the whole cell becoming smaller and as it were shrunken. In the cells of the parotid gland and other albuminous cells the granules seen in the living or fresh cell differ from the granules seen in the pancreatic cell, inasmuch as they are easily dissolved or broken up by the action of alcohol, chromic acid, and the other usual hardening reagents, and hence in hardened specimens have disappeared. In consequence, in sections of hardened and pre- pared albuminous glands the difference between resting or loaded and active or discharged cells may appear not very conspicuous ; and this is especially the case in the parotid gland of the rabbit when the activity has been called into play by stimulation of the auriculo-temporal nerve. When however, either in the rabbit or the dog, the cervical sympathetic is stimulated, though the stimulation gives rise in the rabbit to little secretion of saliva, and in the dog to none at all, a marked effect on the gland is produced, and changes, in the same direction as those already described, may be observed. During rest, the cells of the parotid as seen in sections of the gland hardened in alcohol (Fig. 05 A) are pale, transparent, staining with difficulty, and the nuclei possess irregular outlines as if shrunken by the reagents employed. After stimulation of the sympathetic, the protoplasm of the cells becomes turbid (Fig. 65 B), and stains much more readilv, while the nuclei FIG. 65. SECTIONS OF THE PAROTID OF THE RABBIT. A at rest, B after stimula- tion of the cervical sympathetic. Both sections are from hardened gland. (After Heidenhain.) are no longer irregular in outline but round and large, with conspicuous nucleoli, the whole cell at the same time, at least after prolonged stimulation, becoming distinctly smaller. § 235. In a mucous gland the changes which take place are of a like kind, though apparently somewhat more complicated, owing probably to the peculiar characters of the mucin which is so con- spicuous a constituent of the secretion. If a piece of resting, loaded submaxillary gland be teased out, while fresh and warm from the body, in normal saline solution, the CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 409 cell-substance of the mucous cells (Fig. 66 a) is seen to be crowded with granules or spherules which may fairly be compared with the granules of the pancreas, though perhaps less dense and solid than these. If a piece of a gland which has been secreting for some time, and is therefore a discharged gland, be examined in the same way (Fig. 66 b) the granules are far less numerous and largely confined FIG. 66. Mucous CELLS FROM A FRESH SUBM AXILLARY GLAND OF DOG. (Laugley.) (i and 1) isolated in 2 p.c. salt solution : a, from loaded gland, l> from discharged gland (the nuclei are usually more obscured by granules than is here repre- sented). (On teasing out a fragment of fresh in 2 to 5 p.c. salt solution, the cells usually become broken up so that isolated cells are rarely obtained entire ; isolated cells are common if the gland be left in the body for a day after death.) a', b', treated with dilute acid : a' from loaded, b' from discharged gland. to the part of the cell nearer the lumen, the outer part of the cell around the nucleus consisting of ordinary ' protoplasmic ' cell- substance. The distinction however between an inner 'granular zone ' next to the lumen and an outer ' clear zone ' next to the basement membrane is less distinct than in the pancreas, partly because the granules do not disappear in so regular a manner as in the pancreas and partly because the outer zone of the mucous cell, as it forms, is less homogeneous than that of the pancreatic cell. The ' granules ' or ' spherules ' of the mucous cell are moreover of a peculiar nature. If the fresh cell, shewing granules, (either many as in the case of a loaded or few as in the case of a discharged cell; be irrigated with water or with dilute acids or dilute alkalis the granules swell up (Fig. 66 a, b') into a transparent mass, giving the reactions of mucin, traversed by a network of ' protoplasmic ' cell-substance. In this way is produced an appearance very similar to that shewn in sections of mucous glands hardened and stained in the ordinary way. 410 CHANGES IN MUCOUS CELLS. [BOOK ii. As we have already said (§ 216) in the loaded mucous cell in such hardened and stained preparations (Fig. 67 a) there is seen a a FIG. 67. ALVEOLI OF DOG'S SVUMAXILLARY GLAND HAKDENKH IN ALCOHOL AND STAIXEH \\ixn CARMINK. (Langley. ) (The network is diagrammatic.) «, from a loaded glaud. b, from a discharged gland; the chorda tympaui having been stimulated at short intervals during five hours. small quantity of protoplasmic cell-substance gathered round the nucleus at the outer part of the cell next to the basement membrane ; the rest of the cell consists of a network of cell- substance, the interstices being filled with transparent material, which, unlike the network itself and the mass of cell-substance round the nucleus, does not stain with carmine or with certain other dyes. The discharged cell in similar preparations (Fig. 67 b) differs from the loaded cell in the amount of transparent non- staining material being much less and chiefly confined to the inner part of the cell, while the protoplasmic cell-substance around the now large and well-formed nucleus is not only, both relatively and absolutely, greater in amount, but stains still more deeply than in the loaded cell. It would appear therefore that in the mucous cell, as in the pancreatic cell, the cell-substance forms and deposits in itself certain material in the form of granules. During secretion these granules disappear and presumably form part of the secretion. But the granules of a mucous cell differ from those of the pancreatic cell in as much as they are apt under the influence of reagents to be transformed, while still within the cell, into the transparent viscid material which we call mucin ; hence the appearances presented by sections of hardened glands. It seems natural to infer that the granules consist not of mucin itself but of a forerunner of mucin, of some substance which can give CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 411 rise to muchi, and which we might call mucigen. And we might further infer that during the act of secretion the granules of mucigen are transformed into masses of mucin and so discharged from the cell. Under this view the appearances presented by the hardened glands, as distinguished from the living glands, might be interpreted as indicating that under the influence of the reagents employed, the mucigen of the loaded cells had undergone the transformation into mucin without being discharged from the cells. Up to the present however it has not been found possible to isolate from the gland any definite body, capable of being converted into mucin, and there are some reasons for thinking that not only the granules but part also of the substance between them contributes to the formation of mucin. Apart from this complication, however, the general course of events in the mucous cell seems to be the same as in the pancreatic cell ; the cell- substance manufactures and loads itself with a special product, (or special products) ; during the act of secretion, this product, undergoing at the time a certain amount of change, is discharged from the cell to form part of the secretion, and the cell-substance, stirred up to increased growth, subsequently manufactures a new supply of the product. § 236. The ' central ' or ' chief ' cells of the gastric glands also exhibit similar changes. In such an animal as the newt these cells may, though with difficulty, be examined in the living state. They are then found to be studded with granules when the stomach is at rest. During digestion these granules become much less numerous and are chiefly gathered near the lumen, leaving in each cell a clear outer zone. And in many mammals the same abundance of granules in the loaded cell, the same paucity of granules for the most part restricted to an inner zone in the discharged cell, may be demonstrated by the use of osmic acid, Fig. 68. When the stomach is hardened by alcohol these changes, like the similar changes in an albuminous cell, are obscured by the shrinking of the ' granules ' or by their swelling up and becoming diffused through the rest of the cell-substance ; so that though, in sections so prepared, very striking differences are seen between loaded and discharged cells, these are unlike those seen in living glands. In specimens taken from an animal which has not been fed for some time, the central cells of the gastric glands are pale, finely granular, and do not stain readily with carmine and other dyes. During the early stages of gastric digestion, the same cells are found somewhat swollen, but turbid and more coarsely granular ; they stain much more readily. At a later stage they become smaller and shrunken, but are even more turbid and granular than before, and stain still more deeply. This is true, not only of the central cells in the cardiac glands, but also of the cells of which the pyloric glands are built 412 CHANCKS IN CASTKK' CELLS. [Boon ii. n)i. In the loaded coll very little staining takes place, because the amount of living staining cell-substance is small relatively to the amount of material with which it is loaded and which does not FIG. 68. GASTRIC GLAND OF MAMMAL (Bat) DUHING ACTIVITY. (Langley.) c, the mouth of the glaml with its cylindrical cells. H, the neck, containing conspicuous ovoid cells, with their coarse protoplasmic network. /, the body of the gland. The granules are seen in the central cells to be limited to the inner portions of each cell, the round nucleus of which is conspicuous. stain readily. In the cell which after great activity has discharged itself, the cell is smaller, but what remains is largely living cell- substance, some of it new, and all staining readily. It would appear also that during the activity of the cell some substances, capable of being precipitated by alcohol, make their appearance, and the presence of this material adds to the turbid and granular aspect of the cell ; possibly also this material contributes to the staining. A similar material seems to make its appearance in the cells of albuminous glands. In the ovoid or border cells no very characteristic changes make their appearance. During digestion they become larger, more swollen as it were, and in consequence bulge out the CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 413 basement membrane, but no characteristic disappearance of gra- nules can be observed. In the living state, the cell-substance of these ovoid cells appears finely granular, but in hardened and prepared sections has a coarsely granular, " reticulate " look which is perhaps less marked in the swollen active cells than in the resting cells. § 237. All these various secreting cells then, pancreatic cell, mucous cell, albuminous cell, and central gastric cell, exhibit the same series of events, modified to a certain extent in the several cases. In each case the 'protoplasmic' cell-substance manufactures and lodges in itself material destined to form part of the juice secreted. In the fresh cell this material may generally be recog- nized under the microscope by its optical characters as granules ; these however are apt to become altered by reagents. But we must guard ourselves against the assumption that the material which can thus be recognized is the only material thus stored up ; we may, in future, by chemical or other means be able to differentiate other parts of the cell-body as being also material similarly stored up. During activity, while the gland is secreting, this material, either unchanged or after undergoing change, is wholly or partially discharged from the cell. The cell in consequence of having thus got rid of more or less of its load consists to a larger extent of actual living cell-substance, this being in many cases increased by rapid new growth, though the bulk of the discharged cell may be less than that of the loaded cell. This activity of growth continues after the act of secretion, but the discharged cell soon begins again the task of loading itself with new secretion material for the next act of secretion. Thus in most cases there is, corresponding to the intermittence of secretion, an alternation of discharge and loading ; but it must be borne in mind that such an alternation is not absolutely necessary even in the case of intermittent secretion. We can easily imagine that the discharge, say, of ' granules ' during secretion should stir up the cell to an increased activity in forming granules, and that the formative activity should cease when the secretory activity ceased. In such a case the number of new granules formed might always be equal to the number of old granules used up, and the active cell in spite of its discharge would possess as many granules, that is to say, as large a load, as the cell at rest. And in the central gastric cells of some animals it would appear that such a continued balancing of load and discharge does actually take place, so that no distinction in granules can be observed between resting and active cells. § 238. We spoke just now of the material stored up in the cell and destined to form part of the secretion as undergoing change before it was discharged. In the mucous cell we have seen that the material deposited in the living cell has at first the form of granules. These granules however are easily converted into a 411 TRYPSIN AND TRYPSINOGEN. [BOOK n. transparent material lodged in the spaces of the cell-substance, which material even if not exactly identical with at least closely resembles the inuciii found in the secret ion; and apparently, in the act of secretion the granules do undergo some such change. In the case of some other glands moreover we have chemical as well as optical evidence that the material stored up in the cell, is, in part at least, not the actual substance appearing in the secretion but an antecedent of that substance. An important constituent of pancreatic juice is, as we shall see later on, a body called trypsin, a ferment very similar to pepsin, acting on proteid bodies and o>n\ erting them into peptone and other substances. Though in many ivsprets alike, pepsin and trypsin are quite distinct bodies, and differ markedly in this, that while an acid medium is necessary tor the action of pepsin, an alkaline medium is necessary for the action of trypsin; and accordingly the pam-ivatic juice is alkaline in contrast to the acidity of gastric juice. Trypsin, can, like pepsin (§ 205), be extracted with gly- cerine from substances in which it occurs; glycerine extracts of trypsin however need for the manifestation of their powers the pn'-ence of a weak alkali, such as a 1 p.c. solution of sodium carbonate. Now trypsin is present in abundance in normal pancreatic juice; but a loaded pancreas, one \\hidi is ripe for secretion, and which if excited to secrete would immediately pour out a juice rich in trypsin, contains no trypsin or a mere trace of it; nay even a pancreas which is engaged in the act of secreting contains in its actual cells an insignificant quantity only of trypsin, as is shewn by the following experiment. If the panen a- of an animal, even of one in full digestion, be treated, while still warm from the body, with glycerine, the glycerine extract, as judged of by its action on fibrin in the presence of sodium carbonate, is inert or nearly so as regards proteid bodies. If, however, the same pancreas be kept for 24 hours before being treated with glycerine, the glycerine extract readily digests fibrin and other proteids in the presence of an alkali. If the pancreas, while still warm, be rubbed up in a mortar for a few minutes with dilute acetic acid, and then treated with glycerine, the glycerine extract is strongly proteolytic. If the glycerine extract obtained without acid from the warm pancreas, and therefore inert. be diluted largely with water, and kept at 35° C. for some time, it becomes active. If treated with acidulated insfead of distilled water, its activity is much sooner developed. If the inert glyce- rine extract of warm pancreas be precipitated with alcohol in excess, the precipitate, inert as a proteolytic ferment when fresh, becomes active when exposed for some time in an aqueous solution, rapidly so when treated with acidulated water. These facts shew that a pancreas taken fresh from the body, even during full digestion, contains but little ready-made ferment, though there is CIIAP. i.] TISSUES AND MECHANISMS OF DIGESTION. 415 present in it a body which, by some kind of decomposition, gives birth to tlie ferment. We may remark incidentally that though the presence of an alkali is essential to the proteolytic action of the actual fermentf>tfHe formation of the ferment out of its forerunner is favoured by the presence of a small quantity of acid ; the acid must be used with care, since the trypsin, once formed, is destroyed by acids. To this body, this mother of the ferment, which has not at present been satisfactorily isolated, but which appears to be a complex body, splitting up into the ferment, which as we have seen is at all events not certainly a proteid body, and into an un- deniably proteid body, the name of zymogen has been applied. But it is better to reserve the term zymogen as a generic name for all such bodies as not being themselves actual ferments, may by internal changes give rise to ferments, for all ' mothers of ferment ' in fact ; and to give to the particular mother of the pancreatic proteolytic ferment, the name trypsinogen. Evidence of a similar kind shews that the gastric glands, both the cardiac and the pyloric glands, while they contain compara- tively little actual pepsin, contain a considerable quantity of a zymogen of pepsin, or pepsinogen ; and there can be little doubt but that this pepsinogen is lodged in the central cells of the cardiac glands and in the somewhat similar cells which line the whole of the pyloric glands. It is further interesting to observe that, as a general rule, the amount of trypsinogen in a pancreas at any given time rises and sinks pari passu with the granular inner zone, i.e. with the amount of granules in the cell. The wider the inner zone and the more abundant the granules the larger the amount, the narrower the zone and the fewer the granules the smaller the amount, of trypsinogen ; and in the cases of old-established fistula, where the secretion is wholly inert on proteids, the inner granular zone is absent from the cells. And the same parallelism has been observed between the abundance of granules in the central cells and the quantity of pepsinogen present in the gastric glands. The parallelism however, at all events in the case of the pancreas, appears not to be absolute, for it is stated that in the pancreas of dogs after long starvation there is little or no trypsinogen in the gland and yet the cells exhibit a marked inner zone of granules. Moreover we should not, in any case, be justified in concluding that the granules of the pancreatic cell are wholly composed of trypsinogen ; for, as we shall presently see, the pan- creatic juice contains besides trypsin not only other important fer- ments but also certain proteid constituents ; and the granules, which are of a proteid nature, probably supply these proteids of the juice. Hence the parallelism between granules and trypsinogen is at best an incomplete one. But even such an incomplete paral- lelism is of value. The granules whatever their nature are pro- ducts of the metabolism of the cell, lodged for a while in the 416 NATURE OF THE ACT OF SECRETION. [BOOK n. cell-substance but eventually discharged ; and certain of the con- stituents of the several secretions, such as mucin, trypsin, pepsin and the like appear to be in a similar way products of the meta- bolism of the cell, lodged for a while in the cell-substance, not in all cases exactly in the condition in which they will be discharged from the cell, but in an antecedent phase such as zymogen or the like, and in all cases ultimately ejected from the cell, to supply part and generally the important part of the secretion. § 239. The act of secretion itself. The above discussion pre- pares us at once for the statement that the old view of secretion according to which the gland picks out, separates, secretes (hence the name secretion) and so niters as it were from the common store of the blood the several constituents of the juice, is untenable. According to that view the specific activity of any one gland was confined to the task of letting certain constituents of the blood pass from the capillaries surrounding the alveolus through the cells to the channels of the ducts, while refusing a passage to others. We now knt)\v that certain important constituents of each juice, the pepsin of gastric juice, the muciu of saliva arid the like are formed in the evil, and not obtained ready made from the blood. A minute quantity of pepsin does exist it is true in the blood, but there are reasons for thinking that this has made its \\av back into the blood, either being absorbed from the interior of the stomach or, as seems more probable, picked up directly from the gastric glands; and so with some of the other constituents of other juices. The chief or specific constituents of each juice are formed in the cell itself. But the juice secreted by any gland consists not only of the specific substances such as mucin, pepsin or other ferment, or other bodies, found in it alone, but also of a large quantity of water, and of various other substances, chiefly salines, common to it, to other juices and to the blood. And the question arises, Is the water, are the salts and other common substances furnished by the same act as that which supplies the specific constituents ? Certain facts suggest that they are not. For instance, as mentioned some time ago, in the submaxillary gland of the dog, stimulation of the chorda tympani produces a copious flow of saliva, which is usually thin and limpid, while stimulation of the cervical sympathetic produces a scanty flow of thick viscid saliva. That is to say, stimulation of the chorda has a marked effect in promoting the discharge of water, while stimulation of the sym- pathetic has a marked effect in promoting the discharge of mucin. To this we may add the case of the parotid of the dog. In this gland stimulation of a cerebro-spinal nerve, the auriculo-temporal, produces a copious flow of limpid saliva, while stimulation of the sympathetic produces itself little or no secretion at all ; but when the sympathetic and cerebro-spinal nerves are stimulated at the same time, the saliva which flows is much richer in solid and especially in organic matter than when the cerebro-spinal nerve CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 417 is stimulated alone. And we have already seen that in this gland the microscopic changes following upon sympathetic stimulation are more conspicuous than those which follow upon cerebro-spinal stimulation. These and other facts have led to the conception that the act of secretion consists of two parts, which in one case may coincide, in another may take place apart or in different propor- tions. On the one hand, there is the discharge of water carrying with it common soluble substances, chiefly salines, derived from the blood ; on the other hand, a metabolic activity of the cell- substance gives rise to the specific constituents of the juice. To put the matter broadly, the latter process produces the specific constituents, the former washes these and other matters into the duct. It has been further supposed that two kinds of nerve fibres exist : one governing the former process and, in the case of the submaxillary gland for instance, preponderating, though not to the total exclusion of the other kind, in the chorda tympani ; the other governing the latter process and preponderating in the branches of the cervical sympathetic. These have been called respectively ' secretory ' and ' trophic ' fibres ; but these terms are not desirable. It may be here remarked that even the former process is a distinct activity of the gland, and not a mere filtra- tion. For, as we have seen in the case of the salivary glands, when atropin is given, not only do the specific constituents cease to be ejected as a consequence of stimulation of the chorda, but the discharge of water, in spite of the blood vessels becoming dilated, is also arrested : no saliva at all leaves the gland. And what is true of the salivary glands as regards the dependence of the flow of water on something else besides the mere pressure of the blood in the blood vessels, appears to hold good with other glands also. Indeed it has been suggested that the very discharge of water is due to an activity of the cell ; the hypothesis has been put forward that changes in the cell give rise to the formation in the cell of substances which absorb water from the blood or lymph on the one side and give it up on the other side into the lumen of the alveolus. Such an hypothesis cannot be regarded as proved ; but the mere putting it forward raises doubts as to the validity of the distinction on which we have been dwelling ; and other considerations point in the same direction. For instance, if the common soluble salts present in a juice, as distinguished from the specific constituents, were merely carried into the juice by the rush so to speak of water, we should expect to find the percentage of these salts either remaining the same or perhaps decreasing when the juice was secreted more rapidly and in fuller volume. But under these circumstances the percentage very frequently increases; and in general we find that under various circumstances the proportion of salts secreted to the quantity of water secreted may vary considerably. Obviously, while something determines F. 27 418 THE ACT OF SECRETION. [BOOK 11. the quantity of water passing into the alveolus, something else de- termines how much of common soluble salts that water contains, and still something else determines to what extent that water is also laden with specific constituents and other organic bodies. The whole action is too complicated to be described as consisting merely of the two processes mentioned above, but the time has not yet come for clear and definite statements. Everything however tends to shew that the cell is the prime agent in the whole business, though we cannot at present define the nature of the several changes in the cell, nor can we say how those changes are exactly related to each other, to changes of the blood- pressure in the blood vessels, or, we may add, to changes taking place in the lymph-spaces which lie between the blood and the cell. We may perhaps add that, since in certain cutaneous se- creting glands the alveolus, or what corresponds to the alveolus, is wrapped round with plain muscular fibres, the contraction of which appears to force the secretion outwards, the idea has been suggested that in glands, such as we are now considering, the cell- substance making use of " protoplasmic " contraction instead of actual muscular contraction, may force part of the cell contents into the lumen of the alveolus. Such a mode of secretion would be comparable to the ejection of undigested material, or " excre- tion," by an amceba. But we have no satisfactory evidence in favour of this view. § 240. Throughout the above we have spoken as if the secretion were furnished exclusively by the cells of the alveoli or secreting portion of the gland, as if the epithelium cells lining the ducts, or conducting portion of the gland, contributed nothing to the act. In the gastric glands the slender cells lining the mouths of the glands (which correspond to ducts) and covering the ridges between, are mucous cells secreting into the stomach generally a small, but under abnormal conditions a large amount, of mucus, which has its uses but is not an essential part of the gastric juice. In the salivary glands we can hardly suppose that the long stretch of characteristic columnar epithelium which reaches from the alveoli to the mouth of the long main duct serves simply to furnish a smooth lining to the conducting passages ; but we have as yet no clear indications of what the function of this epithelium can be. § 241. Before we leave the mechanism of secretion there are one or more accessory points which deserve attention. In treating just now of the gastric glands we spoke as if pepsin were the only important constituent of gastric juice, whereas, as we have previously seen, the acid is equally essential. The formation of the free acid of the gastric juice is very obscure, and many ingenious but unsatisfactory views have been put forward to explain it. It seems natural to suppose that it arises in some way from the decomposition of sodium chloride drawn from the blood ; CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 419 and this is supported by the fact that when the secretion of gastric juice is actively going on, the amount of chlorides leaving the blood by the kidney is proportionately diminished ; but nothing definite can at present be stated as to the mechanism of that decomposition. And even admitting that the sodium chloride of the body at large is the ultimate source of the chlorine element of the acid, it appears more likely that that element should be set free in the stomach by the decomposition of some highly complex and unstable chlorine compound previously generated, than that it should arise by the direct splitting-up of so stable a body as sodium chloride at the very time when the acid is secreted. In the frog, while pepsin free from acid is secreted by the glands in the lower portion of the O3sophagus, an acid juice is afforded by glands in the stomach itself, which have accordingly been called oxyntic (c^vvetv to sharpen, acidulate) glands ; but these oxyntic glands appear also to secrete pepsin. In the mammal the isolated pylorus secretes an alkaline juice ; in fact, the appearance of an acid juice is limited to those portions of the stomach in which the glands contain both 'chief or 'central/ and 'ovoid' or 'border' cells. Now from what has been previously said there can be no doubt that the chief cells do secrete pepsin. On the other hand there is no evidence whatever of the formation of pepsin by the ' border ' or ' ovoid ' cells, though this was once supposed to be the case and these cells were unfortunately formerly called 'peptic' cells. Hence it has been inferred that the border cells secrete acid ; but the argument is at present one of exclusion only, there being no direct proof that these cells actually manufacture the acid. The rennin appears to be formed by the same cells which manufacture the pepsin, that is, by the chief cells of the fundus generally and to some extent by the cells of the pyloric glands. We may add that we have evidence of the existence of a zymogen of rennin analogous to the zymogen of pepsin or of trypsin. The mucus which is present as a thin layer over the surface of the fasting stomach, and which especially in herbivorous animals is increased during digestion, comes as we have said from the mucous cells which line the mouths of the several glands and cover the intervening surfaces. § 242. We previously called attention to the fact that in the case of the stomach the absorption of the products of digestion largely increased the activity of the secreting cells. This has led to the idea that one effect of food is to ' charge ' the gastric cells with pepsinogen, and that certain articles of food might be considered as especially peptogenous, i.e. conducive to the formation of pepsin. Such a view is tempting, but needs as yet to be more fully sup- ported by facts. § 243. Seeing the great solvent power of both gastric and pancreatic juice, the question is naturally suggested, Why does 27—2 420 SELF-DIGESTION. [BOOK n. not the stomach digest itself ? After death, the stomach is frequently found partially digested, viz. in cases when death has taken place suddenly on a full stomach. In an ordinary death, the membrane ceases to secrete before the circulation is at an end. That there is no special virtue in living things which prevents their being digested is shewn by the fact, that the leg of a living frog or the ear of a living rabbit introduced into the stomach of a dog through a gastric fistula is readily digested. It has been suggested that the blood-current keeps up an alkalinity sufficient to neutralize the acidity of the juice in the region of the glands themselves ; but this will not explain why the pancreatic^ juice, which is active in an alkaline medium, does not digest the proteids of the pancreas itself, or why the digestive cells of the bloodless actinozoon or hydrozoon do not digest themselves. We might add, it does not explain why the amoeba, while dissolving the protoplasm of the swallowed diatom, does not dissolve its own protoplasm. \Vc cannot answer this question at all at present, any more than the similar one, why the delicate proto- plasm of the amosba resists during life the entrance into itself by osmosis of more water than it requires to carry on its work, while a few moments after it is dead water enters freely by osmosis, and the effects of that entrance become abundantly evident by the formation of bullae and the breaking up of the protoplasm. SEC. 4. THE PROPERTIES AND CHARACTERS OF BILE, PANCREATIC JUICE AND SUCCUS ENTERICUS. § 244. In the living body the food, subjected to the action first of the saliva and then of the gastric juice, undergoes in the stomach changes which we shall presently consider in detail, and the food so changed is passed on into the small intestine, where it is further subjected to the action of the bile secreted by the liver, of pancreatic j nice secreted by the pancreas, and possibly to some extent, though this is by no means certain, of a juice secreted by the intestine itself, and called succus entericus. It will be convenient to study the minute structure of the liver in connection with other functions of the liver more important perhaps than that of the secretion of bile, namely the formation of glycogen, and other metabolic events occurring in the hepatic cells ; we have already studied the structure of the pancreas ; and the structure of the intestine will best be considered by itself. We therefore turn at once to the properties and characters of the above-named juices. Bile. Though bile, after secretion in the lobules of the liver, is passed on along the hepatic duct, it is in the case of most animals not poured at once into the duodenum but taken by the cystic duct to the reservoir of the gall-bladder. Here it remains, until such time as it is needed, when a quantity is poured along the common bile duct into the intestine. The quality of bile varies much, not only in different animals, but in the same animal at different times. It is moreover affected by the length of the sojourn in the gall-bladder; bile taken direct from the hepatic duct, especially when secreted rapidly, contains little or no mucus ; that taken from the gall-bladder, as of slaughtered oxen or sheep, is loaded with mucus. The colour of the bile of carnivorous and omnivorous animals, and of man, is generally a bright golden red : of herbivorous animals, a yellowish 422 BILE. [BOOK n. green, or a bright green, or a dirty green, according to circum- stances, being much modified by retention in the gall-bladder. The reaction is neutral or alkaline. The following may be taken as the average composition of human bile taken from the gall-bladder, and therefore containing much more mucus as well as, relatively to the solids, more water than bile from the hepatic duct. In 1000 parts. Water 859'2 Solids :— Bile Salts 91'4 Fats, &c. 9'2 Oholesterin 2'6 Mucus and Pigment ... ... ... 29-8 Inorganic Salts ... ... ... ... 7'8 140-8 The entire absence of proteids is a marked feature of bile ; pancreatic juice, as we shall see, contains a considerable quantity, saliva, as we have seen, a small quantity, normal gastric juice probably still less and bile none at all. Even the bile which has been retained some time in the gall-bladder, though rich in mucus, contains no proteids. The constituents which form, apart from the mucus, the great bulk of the solids of bile ami \vhich deserve chief attention, are the pigments and the bile-salts ; of these we shall speak immediately. With regard to the inorganic salts actually present as such sodium salts are conspicuous, sodium chloride amounting to '2 or more per cent., sodium phosphate to nearly as much, the rest being earthy phosphates and other matters in small quantity. The presence of iron, to the extent of about '006 p. c., is interesting, since, as we shall see, there are reasons for thinking that the pigment of bile, itself free from iron, is derived from iron-holding haemoglobin ; some, at least, of the iron set free during the conversion of haemo- globin into bile pigment, which probably takes place in the liver, finds its way into the bile. Bile also appears to contain a small quantity, at all events occasionally, of other metals, such as man- ganese and copper ; metals introduced into the body are apt to be retained in the liver and eventually leave it by the bile. The small quantity of fat present consists in part of the complex body lecithin. The peculiar body cJiolesterin, which though fatty looking (hence the name 'bile fat') is really an alcohol with the composition C^H^O, is conspicuous by its quantity and constancy. It forms the greater part of most gall-stones, though some are composed chiefly of pigment. Insoluble in water and cold alcohol, though soluble in hot alcohol and readily soluble in ether, chloroform &c., it is dissolved by the bile-salts in aqueous solution and hence is present in solution in bile. Its physiological functions are obscure. CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 423 The ash of bile consists largely of soda, derived partly from the sodium chloride and partly from the bile-salts, of sulphates derived chiefly if not wholly from the latter, and of phosphates partly ready formed, and in part derived from the lecithin. § 245. Pigments of Bile. The natural golden red colour of normal human or carnivorous bile, is due to the presence of Bili- rubin. This, which is also the chief pigmentary constituent of gall- stones, and occurs largely in the urine of jaundice, may be obtained in the form either of an orange-coloured amorphous powder, or of well-formed rhombic tablets and prisms. Insoluble in water, and but little soluble in ether and alcohol, it is readily soluble in chloro- form, and in alkaline fluids. Its composition is C16H18N2O3. Treated with oxidizing agents, such as nitric acid yellow with nitrous acid, it displays a succession of colours in the order of the spectrum. The yellowish golden red becomes green, this a greenish blue, then blue, next violet, afterwards a dirty red, and finally a pale yellow. This characteristic reaction of bilirubin is the basis of the so-called Gmelin's test for bile-pigments. Each of these stages represents a distinct pigmentary substance. An alkaline solution of bilirubin, exposed in a shallow vessel to the action of the air, turns green, becoming converted into Biliverdin (C16H20N205 or C16H18N2O4 Maly), the green pigment of herbivorous bile. Biliverdin is also found at times in the urine of jaundice, and is probably the body which gives to bile which has been exposed to the action of gastric juice, as in biliary vomits, its characteristic green hue. It is the first stage of the oxidation of bilirubin in Gmelin's test. Treated with oxidizing agents biliverdin runs through the same series of colours as bilirubin, with the exception of the initial golden red. § 246. The Bile-salts. These consist, in man and many animals, of sodium glj/cocholate and taurocholate, the proportion of the two varying in different animals. In man both the total quantity of bile-salts and the proportion of the one bile-salt to the other seem to vary a good deal, but the glycocholate is said to be always the more abundant. In ox -gall, sodium glycocholate is abundant, and taurocholate scanty. The bile-salts of the dog, cat, bear, and other carnivora, consist exclusively of the latter. Insoluble in ether but soluble in alcohol and in water, the aqueous solutions having a decided alkaline reaction, both salts may be obtained by crystallisation in fine acicular needles. They are exceedingly deliquescent. The solutions of both acids have a dextro-rotatory action on polarized light. Preparation. Bile, mixed with animal charcoal, is evaporated to dryness and extracted with alcohol. If not colourless, the alcoholic filtrate must be further decolorized with animal charcoal, and the alcohol distilled off. The dry residue is treated with absolute alcohol, and to the alcoholic nitrate anhydrous ether is added as long as any precipitate is formed. On standing the cloudy precipitate becomes 424 BILE-SALTS. [BOOK n. transformed into a crystalline mass at the bottom of the vessel. If the alcohol be not absolute, the crystals are very apt to be changed into a thick syrupy fluid. This mass of crystals has been often spoken of as bilin. Both salts are thus precipitated, so that in such a bile as that of the ox or man bilin consists both of sodium glycocholate and sodium taurocholate. The two may be separated by precipitation from their aqueous solutions with sugar of lead, which throws down the former much more readily than the latter. The acids may be separated from their respective salts by dilute sulphuric acid, or by the action of lead- acetate and sulphydric acid. On boiling with dilute acids (sulphuric, hydrochloric), or caustic potash, or baryta water, glycocholic acid is split up into cholalic (cholic) acid and glycin. Taurocholic acid may similarly be split up into cholalic acid and taurin. Thus glycocholic acid cholalic acid C26H43N06 + H20 = C24H4005 + CH2 . NH2 (CO . OH) taui'ocholic acid cholalic acid taurin C26H45NS07 + H20 = C24H4005 + C2H4 . NH2 . S03H. Both acids contain the same non-nitrogenous acid, cholalic acid ; but this acid is in the first case associated or conjugated with the important nitrogenous body glycin, or amido-acetic acid, which is a compound formed from ammonia and one of the "fatty acid" series, viz. acetic ; and in the second case with taurin, or amido-isethionic acid, that is a compound into which representatives of ammonia, of the ethyl group, and of sulphuric acid enter. The decom- position of the bile acids into cholalic acid and taurin or glycin respectively takes place naturally in the intestine, the glycin and taurin being probably absorbed, so that from the two acids, after they have served their purpose in digestion, the two ammonia com- pounds are returned into the blood. Each of the two acids, or cholalic acid alone, when treated with sulphuric acid and cane-sugar, gives a magnificent purple colour (Pettenkofer's test) with a char- acteristic spectrum. A similar colour may however often be pro- duced by the action of the same bodies on albumin, amyl alcohol, and some other organic bodies. § 247. Action of Bile on Food. In some animals at least bile contains a ferment capable of converting starch into sugar ; but its action in this respect is wholly subordinate. On proteids bile has no direct digestive action whatever, but being, generally at least, alkaline, and often strongly so, tends to neutralise the acid contents of the stomach as they pass into the duodenum and as we shall see so prepares the way for the action of the pancreatic juice. To peptic action it is distinctly antagonistic; the presence of a sufficient quantity of bile renders gastric juice inert towards proteids. Moreover when bile, or a solution of bile- salts, is added to a fluid containing the products of gastric diges- tion, a precipitate takes place, consisting of parapeptone (when CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 425 present), peptone, pepsin and bile salts. Tin- precipitate is redis- solved in an 6X0688 of bile Or Solution of bile-salts ; but the pepsin though redisso|\ed remains inert towards proteids. This precipi- tation actually does take place in the duodenum, and we shall speak of it again later on. With regard to the action of bile on fats, the following state- ments may be made : r.ile has a slight solvent action on fats, as seen in its use by painters. It has by itself a slight but only slight emulsifying power : a mixture of oil and bile separate after shaking rather less rapidly than a mixture of oil and water. With fatty acids bile forms soaps. It is moreover a solvent of solid soaps, and it would appear that the emulsion of fats is under certain circum- stances at all events facilitated by the presence of soaps in solution. Hence bile is probably of much greater use as an emulsion agent when mixed with pancreatic juice than when acting by itself alone. To this point we shall return, j' Lastly, the passage of fats through membranes is assisted by wetting the membranes with bile, or with a solution of bile-salts. Oil will pass to a certain extent through a niter-paper kept wet with a solution of bile-salts, where- as it will not pass or passes with extreme difficulty through one kept constantly wet with distilled water. \ Bile possesses some antiseptic qualities. Out of the body its presence hinders various putrefactive processes ; and when it is prevented from flowing into the alimentary canal, the contents of the intestine undergo changes different from those which take place under normal conditions, and leading to the appearance of various products, especially of ill-smelling gases. These various actions of bile seem to be dependent on the bile salts and not on the pigmentary or other constituents. Pancreatic Juice. § 248. Natural healthy pancreatic juice obtained by means of a temporary pancreatic fistula differs from the digestive juices of which we have already spoken, in the comparatively large quantity of proteids which it contains. Its composition varies according to the rate of secretion, for, with the more rapid flow, the increase of total solids does not keep pace with that of the water, though the ash remains remarkably constant. By an incision through the linea alba the pancreatic duct (or ducts) can easily be found either in the rabbit or in the dog, and a cannula secured in it. There is no difficulty about a temporary fistula; hut with permanent n'stuhe the secretion is apt to become altered in nature, and to lose many of its characteristic properties. Some, however, have succeeded in obtaining permanent fistuliu without any impairment of the secretion. 426 PANCREATIC JUICE. [Booic n. Healthy pancreatic juice is a clear, somewhat viscid fluid, frothing when shaken. It has a very decided alkaline reaction, and contains few or no structural constituents. The average amount of solids in the pancreatic juice (of the dog) obtained from a temporary fistula is about 8 to 10 p. c. ; but in even thoroughly active juice obtained from a permanent fistula, is not more than about 2 to 5 p.c., '8 being inorganic matter; and this is probably the normal amount.^xThe important con- stituents of quite fresh juice are albumin, /a peculiar form of proteid allied to myosin, giving rise to a sort of clotting, a small amount of fats and soaps, and a comparatively large quantity of sodium carbonate, to which the alkaline reaction of the juice is due, and which seems to be peculiarly associated with the proteids. Since, as we shall presently see, pancreatic juice contains a ferment acting energetically on proteid matters in an alkaline medium, it rapidly digests its own proteid constituents, and, when kept, speedily changes in character. The myosin-like clot is dissolved, and the juice soon contains a peculiar form of alkali- albumin (precipitable by saturation with magnesium sulphate) as well as small quantities of leucin, tyrosin and peptone, which seem to be the products of self-digestion and are entirely absent from the perfectly fresh juice. § 249. Action on Food-stuffs. On starch, pancreatic juice acts with great energy, rapidly converting it into sugar (chiefly maltose). All that has been said in this respect concerning saliva might be repeated in the case of pancreatic juice, except that the activity of the latter is far greater than that of the former. Pancreatic juice and the aqueous infusion of the gland are always capable of converting starch into sugar, whether the animal from which they were taken be starving or well fed. From the juice, or, by the glycerine method, from the gland itself, an amylolytic ferment may be approximately isolated. On proteids pancreatic juice also exercises a solvent action, so far similar to that of gastric juice that by it proteids are converted into peptone. If a few shreds of fibrin are thrown into a small quantity of pancreatic juice, they speedily disappear, especially at a temperature of 35° C., and the mixture is found to contain peptone. The activity of the juice in thus converting proteids into peptone is favoured by increase of temperature up to 40° or thereabouts, and hindered by low temperatures ; it is permanently destroyed by boiling. ^AThe digestive powers of the juice in fact depend, like those of gastric juice, on the presence of a ferment which, as we have already said, may be isolated much in the same way as pepsin is isolated, and to which the name trypsin has been given. The appearance of fibrin undergoing pancreatic digestion is however different from that undergoing peptic digestion. In the CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 4:>7 former case the fibrin docs not swell up, but remains as opaque as before, and appears to suffer corrosion rather than solution. But there is a still more important distinction between pancreatic and peptie digestion of proteids. Peptic digestion is essentially an acid digestion ; we have seen that the action only takes place in the presence of an acid, and is arrested by neutralisation. Pan- creatic digestion, on the other hand, may be regarded as an alkaline digestion ; the action is most energetic when some alkali is present ; and the activity of an alkaline juice is hindered or delayed by neutralisation and arrested by acidification at least with mineral acids. The glycerine extract of pancreas is under all circumstances as inert in the presence of free mineral acid as that of the stomach in the presence of alkalis. If the digestive mixture be supplied with sodium carbonate to the extent of 1 p.c., digestion proceeds rapidly, just as does a peptic mixture when acidulated with hydro- chloric acid to the extent of "2 p.c. Sodium carbonate of !_ ]3.c. seems in fact to play in tryptic digestion a part altogether comparable to that of hydrochloric acid of ;2 p.c. in gastric di- gestion. And just as pepsin is rapidly destroyedHby being heated to about 40° with a 1 p.c. solution of sodium carbonate, so trypsin is rapidly destroyed by being similarly heated with dilute hydro- chloric acid of '2 p.c. Alkaline bile, which arrests peptic digestion, seems, if anything, favourable to tryptic digestion. Corresponding to this difference in the helpmate of the ferment, there is in the two cases a difference in the nature of the products. In both cases peptone is produced, and such differences as can be detected between pancreatic and gastric peptones are relatively small ; but in pancreatic digestion the bye-product is not, as in gastric digestion, a kind of acid-albumin, but, as might be ex- pected, a body having more analogy with alkali-albumin. More- over, before the alkali-albumin is actually formed, the fibrin becomes altered and takes on characters intermediate between those of alkali-albumin and of ordinary albumin ; and when fresh raw, i.e. unboiled, fibrin is acted upon by pancreatic juice, one or more globulins appear as initial products. Further, there are evidences that differences, of even a more profound nature than the above, exist between pancreatic and gastric digestion. One of these is the appearance, in the pan- creatic digestion of proteids, of two remarkable nitrogenous crys- talline bodies, leucin and ty rosin. When fibrin (or other proteid) is submitted to the action of pancreatic juice, the amount of peptone which can be recovered from the mixture falls far short of the original amount of proteids, much more so than in the case of gastric juice ; and the longer the digestive action, the greater is this apparent loss. If a pancreatic digestion mixture be freed from the alkali-albumin by neutralisation and filtration, the filtrate yields, when concentrated by evaporation, a crop of crystals of tyrosin. If these be removed the peptone may be precipitated 428 TRYPTIC DIGESTION. [BOOK n. from the concentrated filtrate by the addition of a large excess of alcohol and separated by filtration. The second filtrate upon being concentrated by evaporation yields abundant crystals of leucin and traces of tyrosin. Thus by the action of the pancreatic juice a considerable amount of the proteid, which is being di- gested, is so broken up as to give rise to products which are no longer proteid in nature. From this breaking up of the proteid there arise leucin, tyrosin, and probably several other bodies, such as fatty acids and volatile substances. As is well known, leucin and tyrosin are the bodies which make their appearance when proteids or gelatin are acted on by dilute acids, alkalis, or various oxidising agents. Leucin is a body, which in an impure state crystallizes in minute round lumps with an obscure radiate striation, but when pure, forms thin glittering flat crystals. It has the formula C6H13NO2 or CSH10.NH2 (CO. OH) and is amido-caproic acid. Now caproic acid is one of the " fatty acid " series, so that leucin may be regarded as a compound of ammonia with a fatty acid. Tyrosin, C9HUNO3, on the other hand, belongs to the "aromatic" series; it is a phenyl compound, and hence allied to benzoic acid and hippuric acid. So that in pancreatic digestion the large complex proteid molecule is split up into fatty acid and aromatic molecules, some other bodies of less importance making their appearance at the same time. \Vc infer that the proteid molecules are in some way built up out of "fatty acid" and "aromatic" molecules, together with other components, and we shall later on see additional reasons for this view. Among the supplementary products of pancreatic digestion may be mentioned the body indol (C8H7N), to which apparently the strong and peculiarly faecal odour which sometimes makes its appearance during pancreatic digestion is due. Indol, however, unlike the leucin and tyrosin, is not a product of pure pancreatic digestion, but of an accompanying decomposition due to the action of organised ferments. A pancreatic digestive mixture soon be- comes swarming with bacteria, in spite of ordinary precautions, when natural juice or an infusion of the gland is used. When isolated ferment is used, and atmospheric germs are excluded, or when pancreatic digestion is carried on in the presence of salicylic acid, or thymol, which prevent the development of bacteria and like organisms but permit the action of the trypsin, no odour is perceived, and no indol is produced. After long-continued digestion, especially when accompanied by putrefactive decomposition, the amount of proteids which are carried beyond the peptone stage and broken up, may be very great. In gastric digestion such a profound destruction of proteid material occurs to a much less extent or not at all ; neither leucin nor tyrosin can at present be considered as natural products of the action of pepsin. CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 429 On the gelatiniferous elements of the tissues as they actually exist in the tissue previous to any treat incut pancreatic juice appears to have no solvent action. The fibrilla3 and bundles of fibrillre of ordinary untouched connective-tissue are not digested by pancreatic juice, which in this respect affords a striking contrast to gastric juice. But when they have been previously t reated with acid or boiled so as to become converted into actual gelatine, trypsin is able to dissolve them, apparently changing them much in the same way as does pepsin. Trypsin unlike pepsin, will dissolve mucin. Like pepsin, it is inert towards nuclein, horny tissues, and the so-called amyloid matter. On fats pancreatic juice has a twofold action. In the first "•p'lace it emulsifies fats. If hog's lard be gently heated until it melts and be then mixed with pancreatic juice before it solidifies on cooling, a creamy emulsion, lasting for almost an indefinite time, is formed. So also when olive oil is shaken up with pancreatic juice, the separation of the two fluids takes place very slowly, and a drop of the mixture under the microscope shews that the division of the fat is very minute. An alkaline aqueous infusion of the gland has similar emulsifying powers. In the second place pan- creatic juice splits up neutral fats into their respective acids and glycerine. Thus palmitin (or tripalmitin) (C]5H31 . CO . O)3 . C3H5 is with the assumption of 3H20 split up into three molecules of palmitic acid 3(C15H31.CO.OH) and one of glycerine (C3H5)(OH)3 ; and so with the other neutral fats. If perfectly neutral fat be treated with pancreatic juice, especially at the body-temperature, the emulsion which is formed speedily takes on an acid reaction, and by appropriate means not only the corresponding fatty acids but glycerine may be obtained from the mixture. When alkali is present, the fatty acids thus set free form their corresponding soaps. Pancreatic juice contains fats, and is consequently apt after collection to have its alkalinity reduced ; and an aqueous infusion of a pancreatic gland (which always contains a considerable amount of fat) very speedily becomes acid. Thus pancreatic juice is remarkable for the power it possesses of acting on all the food-stuffs, on starch, fats and proteids. The action on starch, the action on proteids, and the splitting up of neutral fats appear to be due to the presence of three distinct ferments, and methods have been suggested for isolating them. The emulsifying power, on the other hand, is connected with the general composition of the juice (or of the aqueous infusion of the gland), being probably in large measure dependent on the alkali and the alkali-albumin present. The proteolytic ferment trypsin as ordinarily prepared seems to be proteid in nature and capable of giving rise, by digestion, to peptone ; but it may be doubted, as in the case of pepsin and other ferments, whether the pure ferment has yet been isolated. There are no means of distinguishing the amylolytic ferment of the pancreas from ptyalin. The term pan- 430 SUCCUS ENTERICUS. [BOOK n. creatin has been variously applied to many different preparations from the gland, and its use had perhaps better be avoided. The action of pancreatic juice, or of the infusion or extract of the gland, on starch, is seen under all circumstances, whether the animal be fasting or not. The same may probably be said of the action on fats. On proteids the natural juice, when secreted in a normal state, is always active. The glycerine extract or aqueous infusion of the gland, on the contrary, as we have already explained, § 237, is active in proportion as the trypsinogen has been converted into trypsin. Succus Entericus. § 250. When, in a living animal, a portion of the small intestine is ligatured, so that the secretions coming down from above cannot enter its canal, while yet the blood-supply is maintained as usual, a small amount of secretion collects in its interior. This is spoken of as the succus entericus, and is supposed to be furnished by the glands of Lieberkiihn, of which we shall presently speak. Succus entericus may be obtained by the following method, known as that of Thiry modified by Vella. The small intestine is divided in two places at some distance (30 to 50 cm.) apart. By fine sutures the lower end of the upper section is carefully united with the upper end of the lower section, thus as it were cutting out a whole piece of the small intestine from the alimentary tract. In successful cases, union between the cut surfaces takes place, and a shortened but otherwise satisfactory canal is re-established. Of the isolated piece the two ends are separately brought through incisions in the abdominal wall and their mouths carefully fastened in such a manner that each mouth of the piece opens on to the exterior. During the process of healing two fistula? are thus established, one leading to the beginning of and the other to the end of a short piece of intestine quite isolated from the rest of the alimentary canal ; by means of these openings a small quantity of fluid can be obtained. The quantity secreted is said to be considerably increased by the administration of pilocarpin. Succus entericus obtained from the dog by the above method is a clear yellowish fluid having a faintly alkaline reaction and containing a certain quantity of mucus. It is said to convert starch into sugar, and proteids into peptone (the action being very similar to that of pancreatic juice), to split up neutral fats, to emulsify fats and to curdle milk. It is also said to convert rapidly cane-sugar into grape-sugar, and by a fermentative action to convert cane-sugar into lactic acid, and this again into butyric acid with the evolution of carbonic acid and free hydrogen. According to the above results, succus entericus is to be re- garded as an important secretion acting on all kinds of food. CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 431 But even at the best, its actions are slow and feeble. Moreover many observers have obtained negative results, so that the various statements are conflicting. Besides, we have no exact knowledge as to the amount to which such a secretion takes place under normal circumstances in the living body. We may therefore conclude that, at present at all events, we have no satisfactory reasons for supposing that the actual digestion of food in the intestine is, to any great extent, aided by such a juice. Of the possible action of other secretions of the alimentary canal, as of the csecum and large intestine, we shall speak when we come to consider the changes in the alimentary canal. § 251. Gallstones. Concretions, often of considerable size, known as gallstones are not unfrequently formed in the gall bladder, and smaller concretions are sometimes formed in the bile passages. In man two kinds of gallstones are common. One kind consists almost entirely of cholesterin, sometimes nearly free from any admixture with pigment, sometimes more or less dis- coloured with pigment. Gallstones of this kind have a crystalline structure, and when broken or cut shew frequently radiate and concentric markings. The other kind consists chiefly of bilirubin in combination with calcium. Gallstones of this kind are dark coloured and amorphous. Less common than the above are small dark coloured stones, having often a mulberry shape, consisting not of bilirubin itself, but of one or other derivative of bilirubin. Gallstones consisting almost entirely of inorganic salts, calcic carbonates and phosphates, are also occasionally met with. In the lower animals, in oxen for instance, bilirubin gallstones are not uncommon, but eholesterin gallstones are rare. A gallstone appears always to contain a more or less obvious ' nucleus,' around which the material of the stone has been de- posited, and which may be regarded as the origin of the stone ; the real cause of the formation of the stone lies however in certain changes in the bile, by which the cholesterin, or bilirubin, or other constituent ceases to remain dissolved in the bile. But we cannot discuss this matter here. SEC. 5. THE SECRETION OF PANCREATIC JUICE AND OF BILE. § 252. The Secretion of Pancreatic Juice. Although in some cases, as that of the parotid of the sheep, the flow of saliva is continuous or nearly so, in most animals, as in man, the inter- mittence of the secretion is very nearly absolute. While food is in the mouth saliva flows freely, but between meals only just sufficient is secreted to keep the mouth moist, and probably the greater part of this is supplied not by the larger salivary but by the small buccal glands. The flow of pancreatic juice, on the other hand, is much more prolonged, being in the rabbit continuous, and in the dog lasting for twenty hours after -food. But this contrast between the secretion of saliva and that of pancreatic juice is natural, since the stay of food in the mouth even during a protracted feast is relatively short, whereas the time during which the material of a meal is able in some way or other to affect the pancreas is very prolonged. The flow though continuous, or nearly so, is not uniform. In the dog the flow of pancreatic juice begins immediately after food has been taken, and rises to a maximum which may be reached within the first, or as in the case furnishing the diagram given in Fig. 69 the second hour, but which more commonly is not reached until the third or fourth hour. This rise is then followed by a fall, after which there is a secondary rise, reaching a second maximum at a very variable time but generally between the fifth and seventh hours. This second maximum, however, is never so high as the first. The second rise may be due to material absorbed from the intestines being carried in the circulation to the pancreas and so directly exciting the gland to activity, much in the same way as, in the case of the stomach, the absorption of digested material promotes the flow of gastric juice, see § 232 ; and a similar ab- CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 433 sorption may contribute to the first rise also, but it is more probable that so marked and sudden a rise as this is carried 2|3|4|5|6|7|8|9|lO|ll|l2|l3|l4lj5,l6l I I 2 I 3 \A-\ 5 j 6| 7\8 \ Q ||0 FIG. 69. DIAGRAM ILLUSTRATING THE INFLUENCE OF FOOD ON THE SECEETION OF PANCREATIC JUICE. (N. 0. Bernstein.) The abscissae represent hours after taking food ; the ordiuates represent in c.c. the amount of secretion in 10 min. A marked rise is seen at B immediately after food was taken, with a secondary rise between the 4th and 5th hours afterwards, Where the line is dotted the observation was interrupted. On food being again given at C, another rise is seen, followed in turn by a depression and a secondary rise at the 5th hour. A very similar curve would represent the secretion of bile. out by some nervous mechanism. The details of this mechanism have however not as yet been satisfactorily worked out. The pancreas derives its nerves, which reach it along its blood vessels, from the solar plexus of the splanchnic system, but the ultimate origins of the fibres have not been traced outr^lsome of them however certainly come through the plexus from the right vagus. Stimulation of the medulla oblongata, or of the spinal cord, will call forth secretion in a quiescent gland, or increase a secretion already going on. From this we may infer the existence of a reflex mechanism, though we cannot as yet trace out satisfactorily the exact path of either the afferent or the efferent impulses ; all we can say is that the latter do not reach the pancreas by the vagus, since stimulation of the medulla is effective after section of both vagi. A secretion already going on may be arrested by stimulation of the central end of the vagus, and the stoppage of the secretion which has been observed as occurring during and after vomiting p. 28 434 SECRETION OF PANCREATIC JUICE. [BOOK n. is probably brought about in this way. This effect, which however is not confined to the vagus, stimulation of other afferent nerves, such as the sciatic, producing the same effect, may be regarded (in the absence of any proof that the result is due to reflex constriction of the pancreatic blood vessels unduly checking the blood-supply) as an inhibition of a reflex mechanism at its centre in the medulla or in some other part of the central nervous system, much in the same way as fear inhibits at the central nervous system the secretion of saliva following food in the mouth, § 226. But if so, then we must regard the secretion of pancreatic juice as closely resembling that of saliva in as much as it is called forth by a reflex act. Yet it is stated that, unlike the case of saliva, the secretion of pancreatic juice continues after all the nerves going to the gland have been divided, an operation which would do away with the possibility of reflex action. Such an experiment however cannot be regarded as decisive, since it is almost impossible to be sure of dividing all the nerves. No evidence has yet been brought forward to prove the exist- ence of any double nervous mechanism similar to that of chorda fibres and sympathetic fibres in the salivary gland. All that can be said is that, when the gland is stimulated to secrete, the blood vessels are dilated as in the salivary gland ; and we have already, § 232, dwelt on the histological changes which accompany secre- tion. We may add that when the gland is stimulated to increased secretion the increase is not merely an increase of water, the discharge of solids is increased even more than the discharge of water, so that the percentage of solids in the juice increases. The quantity of pancreatic juice secreted, in the case of man, in 24 hours has been calculated at 300 c.c., but such a calculation is of very uncertain value. We have seen, § 227, that in the salivary glands the pressure which may be exerted by the fluid in the ducts is very considerable, exceeding it may be even the blood-pressure in the carotid artery. In this respect the pancreas differs from the salivary glands. When, in a rabbit, a cannula connected with a vertical tube or a manometer is placed in the pancreatic duct, the column of fluid does not rise above a height corresponding to a pressure of about 17 mm. of mercury. But at this pressure the gland becomes cedematous on account of the juice secreted passing back through the walls of the ducts and alveoli into the connective tissue ; a much higher pressure is needed to render a salivary gland cedematous ; and whether the low pressure observed in the pan- creas is due to the ease with which cedema takes place or to the actual secretion not being able to reach a higher pressure cannot be stated with certainty. § 252* The Secretion of Bile, The act of secretion of bile by the liver must not be confounded with the discharge of bile from the bile-duct into the duodenum. When the acid contents of the CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 435 stomach are poured over the orifice of the biliary duct, a gush of bile takes place. Indeed, stimulation of this region of the duo- denum with a dilute acid at once calls forth a flow, though alkaline thuds so applied have little or no effect. When no such acid fluid is passing into the duodenum no bile is, under normal circumstances, discharged into the intestine. The discharge is due to a contraction of the muscular walls of the gall-bladder and ducts, accompanied by a relaxation of the sphincter of the orifice ; both acts are probably of a reflex nature, but the details of the mechanism have not been worked out. The secretion of bile on the other hand, as shewn by the results of biliary fistula?, is continuous ; it appears never to cease. When no food is taken the bile passes from the liver along the hepatic and then back along the cystic duct (the flow being aided probably by peristaltic contractions of the muscular fibres of the duct) to the gall-bladder, where it is temporarily stored ; hence in starving animals, when no discharge is excited by food, the gall- bladder becomes greatly distended with bile. But the secretion, though continuous, is not uniform. The rate of secretion varies, and. is especially influenced by food ; it is seen to rise rapidly after meals, reaching its maximum, in dogs, in from four to eight hours. There seems to be an immediate, sudden rise when food is taken, then a fall, followed subsequently by a more gradual rise up to the maximum, and ending in a final fall to the lowest point. The curve of secretion, in fact, resembles that of the secretion of pancreatic juice in having a double rise ; and as in that case so in this, it is very probable that the first rise is in part the result of nervous action, and it is also possible that nervous influences intervene in the second more lasting rise ; but, as we shall see presently, even nervous influences may affect the liver in a very indirect manner, and our knowledge as to any direct action of the nervous system on the liver is at present very imperfect. The liver receives its chief nervous supply from the solar plexus, and to a great extent through that part of the solar plexus called the hepatic plexus which embraces the portal vein, hepatic artery and bile duct, as these plunge into the liver at the porta. The solar plexus is fed by the two abdominal splanchnic nerves, major and minor, by other smaller nerves from the lower parts of the splanchnic (sympathetic) chain, and by the terminal portion of the right vagus nerve. Small branches from the left vagus, rami hepatici, also pass directly to the liver from the terminations of that nerve on the stomach, finding their way also through the porta. The fibres thus entering the liver from the several sources are, for the most part, non-medullated fibres ; with these, however, are mixed a certain number of medullated fibres. As to the functions of these nerves in reference to the secretion of bile, we may say at once that no satisfactory or exact statement can at present be made. 28—2 436 BLOOD-SUPPLY OF LIVER. [Boon n. § 253. It must be remembered, however, that the liver is so peculiarly related to the other organs of digestion, and its vascular arrangements so special that, with regard to it, as compared with many other organs, an intrinsic nervous mechanism must occupy a more or less subordinate position. The blood-supply of the pancreas for instance is dependent chiefly on the width for the time being of the pancreatic. arteries; it will be affected of course by the general arterial pressure and by any circumstances which affect the outflow by the pancreatic veins, and therefore by the condition of the portal venous system of which those veins form a part ; but in the main, the amount of blood bathing the alveoli of the pancreas will depend on whether the pancreatic arteries are constricted or dilated. The quality of the blood reaching the pancreas, being arterial blood drawn direct from the arterial foundation, will be modified only by such circumstances as modify the general mass of the blood. Very different is the case of the liver. The supply of arterial blood coming direct through the hepatic artery is small compared with the mass pouring through the vena portae ; it moreover, as we shall see, is distributed in capillaries among the small inter- lobular branches of the vena portss and has become venous, indeed merged with the portal blood, before it reaches the actual lobules. The supply of blood for the liver is mainly that through the vena portae ; and this supply is not, like an arterial supply, a fairly uniform one, modified chiefly by the vaso-motor events of the organ itself, but is dependent on what happens to be taking place in the alimentary canal and in abdominal organs other than the liver itself. When no food is being digested and the alimentary canal is at rest, the vessels of that canal, as we have already said in speaking of the stomach, are like those of the pancreas and 'salivary glands, in a state of tonic constriction ; a relatively small quantity of blood passes through them ; hence the flow through the vena portse is relatively inconsiderable, and the pressure in that vessel is low. When digestion is going on all the minute arteries of the stomach, intestine, spleen and pancreas are dilated, and general arterial pressure being by some means or other maintained (see § 194), a relatively large quantity of blood rushes into the vena porta? and the pressure in that vessel becomes much increased, though of course remaining lower than the general arterial • pressure. Moreover during digestion, peristaltic movements of the muscular coats of the alimentary canal are, as we have seen, active ; and these movements, serving as aids to the circulation (see § 121), help to increase the portal flow. Further the spleen, as we shall see in speaking of that organ, is in many animals richly provided with plain muscular fibres, and in such cases seems, especially during digestion, to act as a muscular pump driving the blood onwards, with increased vigour, along the splenic veins to the liver. So that even were the liver not connected with CHAP, i.] TISSUES AND ^IKCHANISMS OF DKJESTTON. 437 the central nervous system by a single nervous tic, (lie tide of blood through the liver would ebb and Mow according to the ' absence or presence of food in the :ilinicnt;iry canal. Au increase of blood-supply does not of course necessarily mean an increase of secretory activity. As \vc have seen, § 227, in the presence of atropine, the secretion of saliva may stand still in spite of dilated bloodvessels and the consequent rush of blood; but we may safely assert that, other things being equal, a fuller blood-supply is favourable to activity. Apparently a mere change in the quantity of blood bathing an alveolus will not start in the cells the changes which constitute the act of secretion, any more than an increase in the blood bathing a muscular fibre will neces- sarily set going a contraction ; but unless there be some counter- acting influence at work, a fuller and richer lymph around a cell will naturally lead to the cell taking up more material from the lymph, and so will increase the cell's store of energy. Hence, especially in the hepatic cell, which appears to be always at Avork, always undergoing metabolism of such a kind as to give rise to bile, we might fairly expect the greater flow through the portal vein to quicken the flow through the bile duct. And as a matter of fact we do find vaso-constrictor action dominant over the secretion. In the various experiments which have been made to ascertain the action of the nervous system on the secretion of bile, it has always been found that stimulation of the medulla oblongata, or of the spinal cord, or of the abdominal splanchnic nerves, stops or at least checks the flow of bile. Now the effect of these stimulations is, as we have already seen more than once, a powerful constricting action on the abdominal blood vessels ; by such stimulation the blood-supply of the liver is materially diminished, and in consequence the secretory activity is slackened or arrested. But there is something besides the mere quantity of blood to be considered in this relation. The blood which passes from the alimentary canal at rest is ordinary venous blood, laden simply with carbonic acid and the ordinary products of the metabolism of the muscular and mucous coats of the canal. When digestion is going on the portal blood is laden, as we shall see, with some at all events of the products of digestion, with sugar probably and with various proteid bodies. And it is quite possible or even probable that some of these bodies in the portal blood reaching the hepatic cells stir them up to secretory activity ; indeed this view may be regarded as supported by the facts that proteid food increases the quantity of bile secreted, whereas fatty food, which as we shall see passes, chie-fly if not wholly, not by the portal vein but by the lymphatics and which is probably largely disposed of in some way or other before it can reach the liver, has no such effect. Hence we may infer that at all events the second increase of 438 BLOOD SUPPLY OF LIVER. [BOOK n. the flow of bile which occurs during the later stages of digestion may be to a large extent the direct effect of blood, laden with digestive products, passing from the stomach and intestines, especially the latter, to the liver by the portal vein, quite independent of any direct nervous action on the liver itself; and indeed it is possible that the first rise also may be partly due to the increased flow of blood from the stomach, aided by the absorption from that organ of a certain amount of digested material. Since, however, there is no evidence of any decrease in blood-sugply, or in the rate of absorption, corresponding to the fall between the two rises, some influences other than those which we are discussing must be at work in the mattfv. § 254. The blood-supply of the liver being thus, quite apart from any nervous supply of its own, so closely dependent on what is going on in the alimentary canal, it will be convenient to say a few words more concerning the vaso-motor nerves of that canal. As we have already said in speaking of the vascular system (§ 169), the vaso-constrictor fibres for the stomach and intestines, large and small, issuing from what we may call the vaso-constrictor region of the cord pass for the most part through the two abdominal splanchnic nerves, major and minor, a small number only passing out below the roots of those nerves. When these splanchnic nerves are divided the vessels of the canal are dilated, when they are centrifugally stimulated the vessels are constricted. Whether there be any distinct vaso-dilator fibres for all or any part of the canal, and if so what course they take, is not known. When no food has for some time been taken, the mucous membrane of the stomach as seen through a gastric fistula is pale ; the blood vessels are constricted. And as far as we know a similar condition obtains throughout the small and large intestines. When food is taken the mucous membrane of the stomach becomes flushed ; its vessels become dilated. This appears to be the result of an inhibition of the previously existing tonic constriction ; at least we have no evidence supporting any other explanation. Apparently the presence of food in the stomach starts in the mucous membrane influences which, ascending to the central nervous system, inhibit the vaso-motor centre for the abdominal splanchnic nerves or such part of that centre as governs the vaso-constrictor fibres of the stomach. By what path such afferent impulses reach the central nervous system is not as yet definitely settled ; but possibly by the vagus nerve, if it be true, as stated, that centripetal stimu- lation of that nerve, while it raises the general blood-pressure by increasing, in a reflex manner, vase-constriction in other regions, leads to a dilation of the gastric vessels. So also it is probable that as the food reaches succeeding sections of the alimentary canal, these in turn in a similar manner become flushed with blood. In the frog there is some evidence that vaso-constrictors leaving the spinal cord by consecutive spinal CIIAP. i.] TISSUES AND MECHANISMS OF DIGESTION. 439 nerves govern the blood vessels of consecutive sections of the alimentary canal. All this Hushing of the canal with blood leads, we repeat, to an increased How of blood at a higher pressure through the portal vein. Whether besides this there be any additional mechanism set to work, such as, for instance, which some observations suggest, a rhythmical peristaltic contraction of the portal vein, by which the blood is still more rapidly hurried to the liver, and whether the increased venous supply through the portal vein is accompanied by a corresponding increase of the lesser supply of arterial blood through the hepatic artery, is not known. It may perhaps be here remarked that there is no need for any increase of arterial blood, since the blood from the alimentary canal, owing to its more rapid passage through the minute vessels, is probably like the corresponding blood in the veins of an active salivary gland, (though probably also not to the same extent) less venous than usual during digestion in spite of the extra quantity of carbonic acid thrown into it by the increased metabolism of the muscular coat during the peristaltic movements. § 255. It is interesting to observe that the pressure under which the bile is secreted is relatively low like that of the pancreatic juice, not high like that of the saliva ; it is much lower than the arterial pressure in the same animal, whereas in the case of saliva (§ 227) the pressure is greater than the blood-pressure in the carotid artery. But, in the case of bile, since the blood which Hows through the hepatic lobules is, mainly, venous portal blood, we have to compare the pressure of the secretion not with arterial pressure but with the venous pressure in the portal system ; and in the dog it has been found that while the pressure of the bile secreted stood at about 200 mm. of a solution of sodium carbonate, that is, about 15 mm. mercury, the blood-pressure in a branch of the superior mesenteric vein stood only at about 90 mm. of the same solution, that is, about 7 mm. mercury. Now the venous pressure in the mesenteric veins is higher, though only slightly higher, than that in the portal vein into which these pour their blood (the difference of pressure being the main cause why the blood flows from the one into the other), and is therefore certainly higher than the pressure in the portal capillaries of the hepatic lobules. So that what is true of the salivary gland is also true, on a different scale, of the liver, viz. that the pressure exerted by the secretion is higher than the pressure of the blood in the vessels feeding the secreting cells. § 256. If the pressure in the bile duct be artificially increased, as by pouring fluid into the glass tube or manometer with which the cannula in the duct is connected, a resorption of the secreted bile takes place ; and resorption will also take place within the body, when the pressure generated by the act of secretion itself reaches and is maintained at a sufficiently high level. Thus 440 RESORPTION OF BILE. [Boon n. when in the living body the bile duct is ligatured, or becomes obstructed by gallstones or otherwise, fluid is accumulated on the near side of the ligature at a pressure which goes on increasing until resorption of bile takes place, bile salts and biliary pigments are thrown back upon the system, and "jaundice" results. It would appear that in these cases resorption takes place through the interlobular bile ducts and not through the hepatic cells or other structures within the lobules. The high pressure in the ducts does not lead to a reversal of the current in the hepatic cells (at most it slackens or possibly stops the current) but the bile secreted into the interlobular ducts escapes from these. It further appears that the escape is not into the blood vessels but into the lymphatics ; the bile salts, pigments and other constituents are carried into the thoracic duct, and in an indirect manner only find their way into the blood stream. To complete the history of the secretion of bile we ought now to turn to the manufacture of the biliary constituents within the cells. But since the hepatic cells are also engaged in labours other and more important perhaps than that of secreting bile, it will be convenient to defer what we have to say on this point until we come to speak of the formation of glycogen and of the general metabolic events taking place in the liver. SEC. 6. THE STRUCTURE OF THE INTESTINES. The Small Intestine. § 257. The intestine, small and large, throughout its length from the pylorus to close upon the rectum, follows in its structure the general plan previously described § 208. A thin outer longi- tudinal muscular layer, covered by peritoneum, is succeeded by a thicker inner circular muscular layer, and this double muscular coat is separated by a submucous layer of loose connective-tissue, carrying the larger blood vessels, from the mucous membrane which consists of an epithelium lying upon a connective-tissue basis of peculiar nature, a well-developed muscularis mucosse of longitudinal and circular fibres marking off the mucous membrane proper from the underlying submucous tissue. In the small intestine the outer longitudinal muscular layer is evenly distributed over the whole circumference of the tube and is everywhere much thinner than the inner circular layer, which is the more important layer of the two. The individual fibre- cells of these muscular layers of the intestine are large and well developedr '"In the thin sheet of connective-tissue which separates indistinctly the two layers lies the plexus of Auerbach, a plexus of nerve-fibres, for the most part non-medu Hated, at the nodes of which are gathered groups of very small nerve-cells, the substance of each cell being especially scanty. This plexus supplies the two muscular layers with nerve-fibres. The submucous coat contains besides blood vessels and lymphatics, a somewhat similar plexus of nerve-fibres, called the plexus of Meissner ; from this plexus fine nerve-fibres proceed to the blood vessels, to the muscularis mun.s.-i', and possibly to other structures. § 258. The Mucous Membrane. This is thrown into folds which are not as in the case of the stomach temporary longi- 442 STRUCTURE OF INTESTINE. [BOOK n. tudinal folds, rugae, but permanent transverse folds, the valvulae conniventes, reaching half-way or two-thirds of the way round the tube. Each fold is a fold of the whole mucous membrane carrying with it a part of the submucous tissue, the latter thus forming a middle sheet between the mucous membrane on the upper surface and that on the lower surface of the fold. The folds, which vary in size, large and small frequently alternately, begin to appear at a little distance from the pylorus ; they are especially well developed just below the opening of the bile and pancreatic ducts, and are continued down to about the middle of the ileum, where, becoming smaller and irregular, they gradually disappear. They serve to increase the inner surface of the intestine and present an obstacle to the too rapid transit of material along the tube. Over and above the coai'ser inequalities of surface caused by these folds, the level of the mucous membrane is broken on the one hand by tongue-like projections, the villi, and on the other hand by tubular depressions, the glands or crypts of Lieberktihn. The latter are very much smaller and are more numerous than the former, several crypts being placed in the interval between two villi."Y~iBoth are found on the projecting valvulae as well as in the valleys between, and both extend along the whole length of the intestine from the pylorus to the ileocaecal valve ; but while the villi vary a good deal, being short and few immediately next to the pylorus, very numerous and large in the duodenum and upper part of the intestine, less numerous, smaller, and more irregular in the lower part, the crypts have nearly the same characters and are uniformly distributed throughout. Very much as in the case of the stomach, the muscularis mucosse runs in an even line (except for the sweeps of the valvulae couniventes) at a little distance from the bases of the closely packed crypts, and at a greater distance (viz. the length of the crypts) from the bases of the villi ; as we shall see, however, the muscularis mucosoe sends up muscular fibres into each villus. § 259. Before proceeding to describe the villi and crypts it will be convenient to study the characters of the peculiar connective- tissue lying between the epithelium above and the muscularis mucosae below. The upper surface of this tissue is defined by what may be spoken of as a basement membrane, which however appears not to be here (at least over the villi) as in the stomach a continuous sheet composed of flat connective-tissue corpuscles fused together, but to have a structure which we shall presently describe. The muscularis mucosae consists of an outer longitu- dinal and an inner circular sheet of plain muscular fibres, in some places the one, and in other places the other being pre- dominant ; each sheet consists in most cases of a single layer of fibres, the constituent fibres being cemented into flat bundles and the bundles united by fine connective-tissue. Between the flat bundles vessels pass to and from the submucous tissue below and CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 443 the rest of the mucous membrane above, the muscle itself being also well provided with blood vessels. The connective tissue which occupies the whole of the narrow irregular zone between the basement membrane above and the muscularis nmcosa> below, except for the space taken up by the blood vessels and definite lymphatic vessels (of which we shall presently speak), is of a kind, which, though it is not quite the same in the villi as elsewhere, is on the whole closely allied to the kind known under the various names of retiform or reticular connective tissue, adenoid tissue or li/ntpliuid tissue, and indeed is often called by one or other of these names. Typical adenoid tissue such as is met with in the lymphatic follicles of the intestine, of which we shall presently have to speak, in lymphatic glands and elsewhere, presents the appearance of a fine close-set and fairly regular network with meshes so small as not to afford room for more than one or two leucocytes in each mesh. The bars of the network are delicate fibres composed of material which is similar to, if not identical with, that of the fibrillse of ordinary connective tissue. At the nodal points of the network thickenings are frequently but not always present, and some of the more conspicuous of these thickenings may contain nuclei either spherical in form or more or less misshapen ; but such nuclei are not tiumerous.4£Adenoid tissue in fact is composed of anastomosing branched cells, the greater part of the cell in most cases, and indeed the whole of the cell in some cases, having been transformed into filamentous processes, of a differen- tiated nature, which join freely with each other and with the like processes of other cells to form a fine regular network, a portion only of the cell, sometimes with and sometimes without its nucleus (this having disappeared), being left to form a nodal thickening. It may be regarded as a less developed form of connective- tissue than the white fibrous or the ordinary areolar connective- tissue. In the earlier stage of its development in the embryo connective-tissue of all kinds is represented by a number of nu- cleated granular protoplasmic cells, lying in a fluid or nearly fluid matrix. The cell-bodies are branched, the branches joining together at intervals to form a network. In the development of ordinary connective-tissue the outer portion of the cell-body of some of the cells is converted in,to or at least gives rise to fibrillar gelatinife- rous material, or the whole of it may be so converted, the rest of the cell, or other cells, being left as connective-tissue corpuscles. In adenoid tissue the cells remain as branched cells, joining into a network, and the cell- substance is not in any part transformed into bundles of fibrilte, though it has undergone, besides an increase in its branching, in part at all events, a chemical trans- formation, since the material forming the bars of the network is in a large measure no longer ordinary ' protoplasmic ' cell-sub- 444 RETICULAR TISSUE. [BOOK n. stance. The meshes of typical adenoid tissue are always crowded with, and practically filled up by, leucocytes of various sizes ; it is only with very great difficulty that the network can be obtained free from them. The connective-tissue occupying the spaces between and below the glands of Lieberkiihn is very similar to adenoid tissue in as much as it presents a network of delicate fibres; but the meshes are somewhat larger and more irregular than those of true adenoid tissue, and though they contain, are not crowded with, leucocytes ; the amount of cell-substance left at some of the nodal points is greater, nuclei are more abundant, and some of the processes of the cells forming the bars of the network are flat expansions rather than fibres. It is on the whole therefore somewhat different from the typical adenoid tissue of lymphatic structures, and though it is often spoken of under the same name as that tissue, it will be convenient to distinguish it by some term ; it might be called reticular tissue. The tissue which fills up the body of a villus differs still more from true adenoid tissue; it is formed of branching cells which have for the most part retained their nuclei and a larger amount of cell-substance round each nucleus ; the processes are partly membranous, partly fibres, and some of them exhibit a tendency to form minute bundles of fibril hv. It is intermediate between adenoid-tissue and ordinary connective-tissue, and may perhaps be desc-ribed as forming a loose somewhat open sponge-work rather than a network. Lying loose in the meshes of this peculiar reticular connective- tissue, both in the villi and elsewhere, are seen bodies having the general characters of white blood corpuscles (see § 31), which, though they are probably not all of the same kind, we may speak of under the term of leucocytes. Sometimes these are scanty but often are very numerous. This reticular connective-tissue «/ forms in fact a labyrinth of irregular passages which are occupied by fluid but through which leucocytes can wander to and fro. We shall later on point out that this labyrinth of passages is associated in a particular manner with the lymphatic vessels and that the fluid occupying the spaces is in reality lymph. Indeed this tissue ought perhaps to be regarded as part of the lymphatic system. The basement membrane spoken of above appears to be formed largely, at least over the villi, by the expanded ends of fibres of the reticulum which reaching the surface from below spread out laterally beneath the epithelium, and being joined by a certain number of cells lying flat on the surface, form together a sheet which is not continuous but discontinuous, being broken by openings through which the bases of the cells of the epithelium are brought into contact with the fluid occupying the spaces of the reticulum below. CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 445 § 260. The Villi. The villi vary in size and form in different animals, and in different parts of the intestine in the same animal ; each villas moreover varies in form at different times ; they may be generally described as having the shape of a flattened finger but are frequently broader at the free end than at the base ; they have, in man, a length of about 1 mm. and a breadth of from "2 mm. to "5 mm. Each villus consists of a body of reticular tissue, the outer surface forming, as explained above, a basement membrane, which is covered by a single layer of epithelium cells. Two kinds of cells, that is cells presenting two sets of characters, make up this single layer of epithelium. One kind is a columnar or conical cell, with its broader end forming part of the free surface of the villas, and its narrower end resting on or filling up a gap in the basement membrane. The greater part of the cell-body is formed of the kind of 'granular' cell substance spoken of as protoplasmic, but differs in appearance and condition according to circumstances ; these variations we shall study separately. An oval nucleus is placed vertically at about the lower third of the cell. At the free border of each cell the granular cell-substance changes to a narrow band of clear hyaline refractive material marked, in many prepared specimens and often even in the fresh state, with fine vertical lines so as to appear striated vertically or rather radially ; in a section of a villus, optical or actual, the whole villus seems to be surrounded by a baud of this clear refractive material. A ciliated epithelium bears, as we have seen (§ 93), a similar hyaline refractive border from which the cilia project and with which they are connected, but which does not share in the movements of the cilia belonging to it, remaining unchanged in form while these are moving ; its exact nature is at present uncertain. The refractive border of a columnar cell of a villus differs from the similar border of a ciliated cell in that on the one hand it never, in vertebrates, bears cilia, and on the other hand does under certain circumstances change its form. The striation spoken of above appears to be due to the fact that the border is composed of a number of rods imbedded side by side in a substance which is sometimes of the same refractive power as the rods, in which case the whole border appears homogeneous, but which is sometimes of different refractive power, in which case the striation is distinct. The rods, which are thought by some to be hyaline processes of the underlying cell-substance projecting into the above-mentioned cement-substance, are sometimes long and thin, sometimes short and thick, the whole border being in the former case narrow, in tin • latter broad. Under the influence of reagents or of circumstances the one condition may change into the other, and the change seems to be an active not a passive process, since it will only take place so long as the cells are alive. This refractive border of the 44G GOBLET CELLS. [BOOK n. columnar cell of a villus is obviously a peculiar and presumably an important structure. § 261. Mixed in varying proportion with the columnar cells possessing this characteristic hyaline border, are cells of another kind, the goblet cells. These are essentially mucous cells; in all their important characters they resemble the mucous cells previously described (§ 235), but receive their special name because in shape they usually resemble a goblet or flask. In a hardened and prepared specimen of a villus numerous goblet cells may be seen scattered among and surrounded by columnar cells. Each goblet cell has a base, often irregular and sometimes branched, lying on or near the basement membrane, and a top which reaches the surface of the villus between the refractive borders of the neighbouring columnar cells. Near the base is placed a nucleus, generally disc-shaped, owing to the action of the reagent, surrounded by a small quantity of staining protoplasmic cell-substance. Above this the cell consists of a mass of transparent mucin, lying in the meshes of a delicate reticulum, and surrounded by a thin layer or envelope which is prolonged upwards from the cell-substance below, and which on the top or free surface of the cell usually bears a distinct round orifice or mouth. The upper part of the cell is consequently a sort of cup filled with mucin (and reticulum) and opening into the interior of the intestine by .a somewhat narrow mouth, through which the mucin in due time escapes. In a villus examined quite fresh in normal saline solution some of these goblet cells may be observed in a condition which has been described, § 235, as the normal condition of a mucous cell. The cell is then cylindrical or oval rather than distinctly flask- shaped, and the upper part of the cell consists of cell-substance studded with granules and spherules, the transparent mucin being absent and the mouth not visible. But in perfectly fresh villi, studied under even the most favourable conditions, many if not most of the goblet cells will be seen to have become goblet shaped, to have already undergone the transformation into transparent mucin and reticulum, and to have acquired a mouth. In such cases the clear transparent body of a goblet cell stands out in strong contrast with the more dim granular bodies of the columnar cells which surround it, both when they are seen on their side and when they are looked at from above. In the latter case when the microscope is focussed for a point a little below the free surface of the villus, the goblet cells look like round clear droplets scattered in the dim ground formed by the columnar cells. A similar contrast is afforded by prepared specimens stained with carmine and certain other dyes, which leave the transparent mucin unstained. Under certain methods or conditions of hardening however and with certain dyes, as with haematoxylin, the mucin may stain as deeply or even more deeply than its surroundings. Obviously these goblet cells are simply mucous cells somewhat CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 447 modified by reason of their position. They are not hidden in the recesses of an alveolus like salivary mucous cells, (hey do not form a layer by themselves like the gastric mucous cells, but are scat- tered among other cells carrying on important functions. Hence apparently their shape of a goblet and their well-defined mouth. A goblet cell to start with is a cell of a more or less columnar form and ordinary protoplasmic cell-substance. The cell-substance manufactures and becomes studded with granules or spherules which very speedily give rise to mucin, the cell swollen with its load assumes a goblet shape, and the formation of a mouth in the space between the converging refractive borders of neighbouring columnar cells assists in the discharge of the load. The columnar cells of the villus are, as we shall see, chiefly occupied in the reception of material from the intestine into the body of the villus ; the goblet cells are chiefly occupied in secreting into the interior of the intestine mucin and possibly some of the constituents of the succus entericus. Below this layer of columnar and goblet cells extends the thin basement membrane, above which, between the bases of the other cells, may be seen small cells, that is to say, cells with a relatively small quantity of cell-substance round the nucleus ; these have been taken to be reserve or replacement cells. But at times clearly recognizable leucocytes may be seen between the columnar cells ; these have probably wandered into the epithelium from the body of the villus ; and it may be that some of the small cells in question are of an allied nature. § 262. The centre or rather the axis of the body of the villus is occupied by a club-shaped space, sometimes bifurcate or even branched at. the distal end, varying indeed a great deal in different animalsr^This is the central lymphatic space or ' lacteal radicle,' as it has been called, which may be filled with fatty or other material, or, as more frequently is seen in hardened preparations, may be empty and collapsed. It is lined with epithelioid plates, and is at the base of the villus continuous with the lymphatic passages and vessels of the mucous membrane. It will be con- venient to defer the further study of this lymphatic space until we come to deal with the lymphatics generally. Between this lymph-space, and the basement membrane, generally close underneath the latter, lies a fairly close-set net- work of capillary vessels, especially well developed towards the upper part of the villus. This network is fed by generally one small artery which springing from the arteries of the submucous tissue splits up into capillaries towards the middle of the villus ; and the blood of the capillaries passes into veins, generally two, which in a similar manner pass down to the veins of the submucous tissue. Between the basement membrane and the central lymph-space, are also found a number of plain muscular fibres, some running 448 STRUCTURE OF VILLUS. [BOOK n. singly, others forming small bundles of two or three fibres abreast. These vary much in number and disposition in different animals. Some of them lie close under and end in the basement membrane ; others lie nearer the lymph-space, to which in some animals they form a sort of muscular sheath. These fibres belong to the muscularis mucosa.- ; at the base of the villus the fibres of the muscularis mucosae take an upward course, passing between the adjacent crypts of Lieberkiihn, and run into the villus, following most commonly a longitudinal but sometimes a more or less oblique or even a transverse direction. By the contraction of these fibres the form of the villus can be changed; but we shall return to this point when we come to speak of the absorption of digested material by means of the villi. All the space intervening between the basement membrane and the central lymph-space which is not taken up by the blood vessels and the muscular fibres, is occupied by the special kind of reticular connective-tissue described above (§ 259), the meshes of which are to a greater or less extent occupied by leucocytes. On the outer surface of the body of the villus this reticular tissue is connected with, and indeed as we have seen forms the basement membrane; in the centre it forms around the epithelioid plates of the lymph-space the walls of that cavity, and supplies a similar bed for the blood capillaries; the fine connective tissue belonging to the small bundles of muscular fibres is continuous with it, and some of the muscular fibres seem to end in it; to it also is attached the connective-tissue of the outer walls of the small artery and veins. The body of the villus is in fact a sponge work of reticular tissue in which are excavated the lymph-space and the blood channels with their respective linings, into which the plain muscular fibres plunge, and which is condensed on the outside into a basement mem- brane. The meshes of the sponge work are further occupied, as we have said, with leucocytes or with nucleated cells of an allied but different nature; hence in ordinary stained specimens, not specially prepared, the lymph-space and blood channels being collapsed, the whole body of the villus appears a confused mass of nuclei ; there are the nuclei of the muscular fibres, the nuclei of the epithelioid plates of the lymph-space and capillaries and of the other coats of the artery and veins, the nuclei of the leucocytes in the meshes, and lastly the nuclei belonging to the reticular tissue itself. The thickness of the body of the villus, that is to say the amount of reticular and of the other tissues lying between the bases of the epithelium cells and the central lymph-space, varies in different animals, being for instance considerable in the dog and small in the rabbit ; in the latter animal the muscular fibres are very scanty. § 263. The Crypts or Glands of LieberkuJin. These are found everywhere along the whole length of the small intestine from the CIIAIM.] TISSUES AND MECHANISMS OF DIGESTION. 4-IU immediate vicinity of the pylorus to the ileocsecal valve, except immediately underneath each villus, and in the spots occupied by the lymphatic follicles of which we shall presently speak. The mucous membrane of the small intestine is in fact to a very large extent made up of a number of these short tubular glands placed side by side and packed closely together, though not so closely as the somewhat similarly arranged cardiac glands of the stomach ; these glands form the greater part of the thickness of the intes- tinal mucous membrane, and the muscularis mucosa? runs in a fairly even line at some little distance below them, that is outside their blind ends. Each gland is a straight or nearly straight tube, rarely dividing, about 400 /j, long and 70 p broad. The outline is furnished by a very distinct basement membrane, in which nuclei are imbedded at intervals, and this basement membrane is lined with a single layer of short cubical cells, leaving a small but distinct lumen; the cells should perhaps be rather described as somewhat conical, with a broader base at the basement membrane and a narrower apex abutting on the lumen. The cell-body, surrounding a somewhat spherical nucleus, is faintly granular except for a hyaline free border, which however is not so conspicuous or so constant as in the columnar cells of the villi. Similar cells cover the ridges intervening between adjacent glands, and where a villus comes next to a gland the short cubical cells of the gland may be traced into the columnar cells of the villus, the hyaline border becoming more marked and the nucleus becoming oval. Among the cubical cells of the gland are to be found, in varying numbers, goblet cells quite similar to those of the villi. It sometimes happens that (hiring the preparation of a specimen the whole epithelium is shed en masse, the cells being much more adherent to each other than to the basement membrane ; in such a case the features of the basement membrane are well seen. Outside the basement membrane, between adjacent glands and between the blind ends of the glands and the underlying muscu- laris mucosse, is reticular connective-tissue, finer and more truly reticular than that of the villi ; it is perhaps less crowded with leucocytes. In this reticular tissue run, encircling the glands, capillary blood vessels supplied by small arteries coming from the submucous tissue, and pouring their blood into corre- sponding veins, and with this reticular tissue lymphatics are con- nected. These glands of Lieberkiihn are supposed to furnish the succus entericus. The reasons for this view lie in their tubular form, which is that of many secreting glands, in their lumen being too narrow for the passage of food into it, and in the fact that, as we shall see, they unlike the columnar cells of the villi are not concerned in the absorption of fat ; otherwise there are no definite facts to prove that the cubical cells are concerned in secretion only or that thev may not absorb matter other than fat. The goblet F. 29 450 THE LARGE INTESTINE. [BOOK n. cells in these glands as in the villi certainly secrete mucus, and may secrete also some of the constituents of the succus entericus. Besides these glands properly so called, that is to say involu- tions of the epithelial (hypoblastic) mucous membrane, there are found in the mucous membrane bodies belonging to the lymphatic system also often called glands, viz. the solitary glands and the agminated glands or patches of Peyer. We shall speak of these as lymphatic follicles, and it will be convenient to study them separately in connection with the lymphatic system. § 264. Immediately below the pylorus in man, but varying somewhat in position in different animals, are the glands of Brunner. These may be regarded as modifications of the pyloric glands of the stomach. In each gland a duct, lined with short columnar epithelium cells leaving a distinct lumen, extends single for some distance, and piercing the muscularis mucosae divides in the submucous tissue into a number of tubes, which subdividing take a twisted course and end in slight enlargements or alveoli. The cells lining both the branching tubes and the alveoli are short cubical cells with an indistinct outline, similar to but, in a fresh condition, more distinctly granular than the cells of the gastric pyloric glands. Bundles of plain muscular fibres, stragglers from the muscularis mucosoe, are scattered among the tubes. These glands of Brunner when traced back to the stomach are found to pass gradually into the pyloric glands; traced along the intestine they soon disappear, the ducts of those glands which reach into the duodenum so far as to be found in company with the glands of Lieberkuhn and villi, open into the lumina of the former. It is not clear that any special purpose is served by these glands of Brunner ; an extract of the glands is said to digest fibrin in the presence of acid. The Large Intestine. § 265. The general plan of structure of the large intestine is the same as that of the small intestine, the salient points of distinction being the absence of villi, and a peculiar arrangement of the longitudinal coat. Instead of being uniformly distributed as a thin layer over the whole circumference of the tube as in the small intestine, the longitudinal coat is in the large intestine chiefly gathered up into hree thickened bands or bundles, being very thin elsewhere. These bands moreover are shorter than what may be called the natural length of the intestine, so that the tube instead of being as in the small intestine of fairly uniform bore, is puckered up into 'sacculi' more or less divided by the three bands into groups of three. This sacculated arrangement answers much the same purpose as the arrangement of valvulae conniventes in the small ,v te CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 451 intestine. The circular muscular layer is thicker in the middle or bellies of the sacculi than at the puckers, where it is very thin. The villi as we have just said are wholly absent. In the lower part of the small intestine they become fewer and smaller, and none at all are found beyond the ileocaecal valve. An increase of surface is provided by longitudinal ridges, but these like the corre- sponding ruga; of the stomach involve the whole mucous mem- brane, including part of the submucous tissue. The glands of Lieberkiihn in the large intestine are in the main like those of the small intestine but larger and better developed, being both deeper and broader, and owing to the absence of villi are more easily studied. The cells of the glands have the same characters as in the small intestine except that the hyaline border is rarely present ; goblet cells are perhaps more abundant than even in the small intestine, especially in some animals. On the ridges between the glands the cells become longer and thinner, and the hyaline border, frequently striated, makes its appearance. . The marked development of these glands in the large intestine is noteworthy since, as we shall see, absorp- tion of material and not the secretion of digestive juice is the characteristic work of the large intestine. It can scarcely be imagined that absorption takes place only at the ridges between the glands and not by the immensely larger amount of surface which is presented by the interiors of all the glands together; but if these glands absorb in the large intestine, they probably act in the same way in the small intestine. Lymphatic follicles are abundant in the large intestine, the caecum and especially the appendix vermiformis being crowded with solitary follicles. The patches of Peyer are absent. § 266. The Rectum. As the sigmoid flexure passes into the rectum the three bands of the longitudinal muscular coat spread out and become once more a uniform layer ; and with this change the sacculation disappears. This longitudinal coat is continued to the anus, where it ends abruptly. The circular coat at its termi- nation at the anus is developed into a distinct ring, the internal sphincter. The mucous membrane is thrown into numerous folds or ridges which below are longitudinal but higher up oblique or even trans- verse in direction ; to permit the formation of these folds, which are obliterated when the rectum is fully distended, the submucous tissue is more abundant and more loosely developed than in the rest of the intestine. Down to the margin of the anus the mucous membrane retains the characters of the large intestine, glands being still present ; it then abruptly puts on the epiblastic characters of the epi- dermis. The rectum has a special nervous supply, but of this we shall speak in connection with the movements of the alimentary canal. 29—2 SEC. 7. THE MUSCULAR MECHANISMS OF DIGESTION. § 267. From its entrance into the mouth until such remnant, of it as is undigested leaves the body, the food is continually subjected to movements having for their object the trituration of the food as in must i<-;it inn, <»• its more complete mixture with the digestive juices, or its forward progress through the alimentary canal. These various movements may briefly be considered in detail. Mastication. This in man consists chiefly of an up and down movement of the lower jaw, combined, in the grinding action of the molar teeth, with a certain amount of lateral and fore-and-aft movement. The lower jaw is raised by mean.- of the temporal, masseter, and internal pterygoid muscles. The slighter effort of depression brings into action chiefly the digastric muscle, though the mylohyoid and geniohyoid probably share in the matter. Contraction of the external pterygoids pulls forward the coudyles, and thrusts the lower teeth in front of the upper. Contraction of the pterygoids on one side will also throw the teeth on to the opposite side. The lower horizontally placed fibres of the temporal serve to retract the jaw. During mastication the food is moved to and fro, and rolled about by the movements of the tongue. These are effected by the muscles of that organ governed by the hypoglossal nerve. The act of mastication is a voluntary one, guided, as are so> many voluntary acts, not only by muscular sense but also by contact sensations. The motor fibres of the fifth cranial nerve convey motor impulses from the brain to the above-mentioned muscles ; but paralysis of the sensory fibres of the same nerve renders mastication difficult by depriving the will of the aid of the usual sensations. § 268. Deglutition. The food when sufficiently masticated is, by the movements of the tongue, gathered up into a bolus on the middle of the upper surface of that organ. The front of the tongue being raised — partly by its intrinsic muscles, and partly by CIIAI-..I.] TISSUES AND MECHANISMS OF DIGESTION. 453 the styloglossus — the bolus is thrust back between the tongue and the palate through the anterior pillars of the fauces or isthmus faucium. Immediately before it arrives there, the soft palate is raised by the levator palati, and so brought to touch the posterior wall of the pharynx, which, by the contraction of the upper margin of the superior constrictor of the pharynx, bulges some- what forward. The elevation of the soft palate causes a distinct rise of pressure in the nasal chambers ; this can be shewn by introducing a water manometer into one nostril, and closing the other just previous to swallowing. By the contraction of the palato-pharyngeal muscles which lie in the posterior pillars of the fauces, the curved edges of those pillars are made straight, and thus tend to meet in the middle line, the small gap between them being filled up by the uvula. Through these manoeuvres, the entrance into the posterior nares is blocked, while the soft palate is formed into a sloping roof, guiding the bolus down the pharynx. By the contraction of the stylo-pharyngeus and palato-pharyngeus, the funnel-shaped bag of the pharynx is brought up to meet the descending morsel, very much as a glove may be drawn up over the finger. Meanwhile in the larynx, as shewn by the laryngoscope, the arytenoid cartilages and vocal cords are approximated, the latter being also raised so that they come very near to the false vocal cords ; and the cushion at the base of the epiglottis covers the rima flottidis, while the epiglottis itself is depressed over the larynx, he thyroid cartilage is now, by the action of the laryngeal muscles, suddenly raised up behind the hyoid bone, and thus assists the epiglottis to cover the glottis. This movement of the thyroid can •easily be felt on the outside. Thus, both the entrance into the posterior nares and that into the larynx being closed, the impulse given to the bolus by the tongue can have no other effect than to propel it beneath the sloping soft palate, over the incline formed by the root of the tongue and the epiglottis. The palato-glossi or constrictores isthmi faucium, which lie in the anterior pillars of the fauces, by contracting, close the door behind the food which has passed them. When the bolus of food is large, it is received by the middle and lower constrictors of the pharynx, which, contracting in sequence from above downwards, thrust it into the oesophagus, along which it is driven by a similar series of successive con- tractions which we shall speak of immediately as peristaltic action. This comparatively slow descent of the food from the pharynx into the stomach, may be readily seen if animals with long necks such as horses and dogs be watched while swallowing. When however the morsel is not large or when the substance swallowed is liquid, the movement of the back part of the tongue may be sufficient not merely to introduce the food into the grasp of the constrictors of the pharynx, but even to propel it rapidly, to 4:>4 DEGLUTITION. [BOOK n. shoot it in fact, along the lax oesophagus before the muscles of that organ have time to contract. In such a mode of swallowing' lli«' middle and lower constrictors take little or no part in driving the food onward, though they and the oesophagus appear to contract from above downwards after the food has passed by them, as if to complete the act and to ensure that nothing has been left behind. Deglutition in this fashion still remains possible after these con- strictors have become paralysed by section of their motor nerves. When a second act of deglutition succeeds a first with suffi- cient rapidity, the nervous changes which start the pharyngeal movements of the second act appear to inhibit the cesophageal movements of the first act; and when swallowing is repeated rapidly several times in succession, the oesophagus remains quiet and lax during the whole time, until immediately after the last- swallow, when a peristaltic movement closes the series. When the stethoscope is applied over the oesophagus, at different regions a sound is heard during deglutition ; sometimes two sounds are heard. The first and most constant is coincident with tin- passage of the boln-, and is due to this and to the muscular sound of the contracting muscles. The later and less constant sound appeal's to be caused by a quantity of air-bubbles with which the bolus was entangled, lodged at the cardiac end of the oesophagus, being forced into the stomach by the sequent peristaltic contraction of the oesophagus. It will be seen, from what has been said, that deglutition, though a continuous act, may be regarded as divided into three stages. The first stage is the thrusting of the food through the isthmus faucium ; this may be either of long or short duration. The second stage is the passage through the upper part of the pharynx. Here the food traverses a region common both to the food and to respiration, and in consequence the movement is a& rapid as possible. The third stage is the descent through tin- grasp of the constrictors. Here the food has passed the respi- ratory orifice, and in consequence its passage again becomes com- paratively slow, except in case of fluids and small morsels, when, as we have seen, it may continue to be rapid. The passage along the oesophagus may perhaps be regarded as constituting a fourth stage ; but it will be more convenient to consider the cesophageal movements by themselves. The first stage in this complicated process is undoubtedly a voluntary act. The raising of the soft palate and the approxi- mation of the posterior pillars may also be, at times, voluntary, since they have been seen, in a case where the pharynx was laid bare by an operation, to take place before the food had touched these parts ; but the movement may take place without -any exercise of the will and in the absence of consciousness. Indeed the second stage taken as a whole, though some of the earlier com- ponent movements are, as it were, on the borderland between the CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 455 voluntary and involuntary kingdoms, must bo regarded as a. reflex act. The third and last stage, whatever be the exact form which it takes, is undoubtedly reflex ; the will has no power whatever over it, and can neither originate, stop, nor modify it. Deglutition in fact as a whole is a reflex act ; it cannot take place unless some stimulus be applied to the mucous membrane of the fauces. When we voluntarily bring about swallowing move- ments with the mouth empty, we supply the necessary stimulus by forcing with the tongue a small quantity of saliva into the fauces, or by touching the fauces with the tongue itself. In the reflex act of deglutition, caused in the ordinary way by the food coming in contact with the fauces, the afferent impulses originated in the fauces are carried up to the nervous centre by the glosso-pharyngeal nerve, by branches of the fifth, and by the pharyngeal branches of the superior laryngeal division of the vagus. The latter seem of special importance, since the act of swallowing, quite apart from the presence of food in the mouth, may be brought out by centripetal stimulation of the superior laryngeal nerve. The efferent impulses descend the hypoglossal to the muscles of the tongue, and pass down the glosso-pharyngeal, the vagus through the pharyngeal plexus, the fifth, and the spinal accessory, to the muscles of the fauces and pharynx : their exact paths being as yet not fully known, and probably varying in different animals. The laryngeal muscles are governed by the laryngeal branches of the vagus. The centre of the reflex act lies in the medulla oblongata. Deglutition can be excited, by tickling the fauces, in an animal rendered unconscious by removal of the brain, provided the medulla be left. If the medulla be destroyed, deglutition is impossible. The centre for deglutition lies higher up than that of respiration, so that in diseases or injuries involving the upper part of the medulla oblongata the former act may be impaired or rendered impossible while the latter remains untouched. It has been said to form part of the superior olivary bodies, but this view is based on anatomical grounds only. We shall have to deal with this and similar matters in treating of the central nervous system. It is probable that, as is the case in so many other reflex acts, the whole movement can be called forth by stimuli affecting the centre directly, and not acting on the usual afferent nerves. § 269. Peristaltic movements. Putting aside the somewhat complicated pharyngeal part of deglutition, and taking the ceso- phageal movements by themselves we find that these, together with the movements of the stomach, and of the small and large intestines right down to the anus are more or less alike, and may be described under the general name of ' peristaltic ' movements. We have already in § 92, spoken of these, but it may be well to consider them briefly again under a general aspect, before dwelling 4f)G PERISTALTIC MO\7EMENTS. [BOOK n. on the special movements of the several parts of the alimentary canal. The muscular coat of the alinu'iitarv canal consists as we have •/ seen of two layers, separated more or less distinctly by a sheet of connective tissue, an outer thinner longitudinal layer, and an inner thicker circular layer; and a similar arrangement obtains in nearly all the muscular hollow tubes of the body, except the arteries, in which the muscular elements are present not so much for the purpose of driving the blood onward as for the sake of regulating the irrigation. The action of the circular coat is fairly simple. A contraction starting at any part travels onwards in the same direction, generally downwards, that is to say from a part nearer the mouth to a part nearer the rectum, for a greater or less distance, the circularly disposed bundle's cont raeting in sequence. The result is a narrowing or constriction of the tube which, travelling more or less slowly along the tube, drives the contents onwards; when a butcher empties the intestine of a slaughtered animal by squeezing it high up with his hand or with his thumb and linger, and carrying the squeezing action downwards along the length of the intestine, he makes the passive intestine do very much what the circular coat does actively, by contraction, in the living animal. The action of the longitudinal coat is perhaps not so clear; but a contraction of the longitudinal coat taking place in any segment of the tube would tend to draw the tube over the contents lying immediately above, or below, the segment, very much as a glove is drawn over a finger. And a succession of such contractions travelling along the tube would lead to a movement of the contents in the same direction. Were the circular coat absent a longitudinal coat might by itself possibly suffice to propel the contents along the tube. In the presence of the circular coat, the action of the longi- tudinal coat in any segment of the tube, if taking place immediately before the circular contraction would, by filling the segment with contents, render the squeezing action of the circular coat more efficient ; if taking place immediately after the circular contraction, it would help in quickening the return of the tube to its normal calibre, for the contraction of the longitudinal coat tends to shorten and widen the segment, and thus would prepare it for new con- tents. We can hardly imagine that the two coats would contract at the same time, since they would tend to neutralize each other's action. Indeed we may probably go farther and assume that in each segment of the canal first the longitudinal coat contracts while the circular coat is relaxed, and that then the circular coat contracts while the longitudinal relaxes. When we come to deal with respiration we shall meet with a similar double antagonistic and successive action between inspiratory and expiratory muscles ; we shall further see reason to think that the processes which start the expiratory act tend to check or inhibit the inspiratory act CIIAIM.] TISSUES AND MECHANISMS OF DIGESTION. 457 and vice versa,; and very possibly a like see-saw of stimulation and inhibition obtains in the muscles of the alimentary canal. It must be remembered that the circular coat is always much thicker than the longitudinal coat; and we may infer that while the chief work of driving the contents onward falls on the former the latter assists the work, either in the way which we have suggested or in some other way. In the small intestine the tube is hung loosely and much twisted so that many loops are formed ; the contents moreover are largely fluid. Hence the steady onward movement, such as is seen when more. solid contents pass along the straight and somewhat firmly attached oesophagus, is complicated by movements due to a loop being projected forward by the entrance of fluid from above, or being dragged down by the weight of its new contents, or, on the other hand, due to a loop being retracted by the driving onward of its contents and the emptying of itself, and the like. In this way a peculiar writhing movement of the bowel is brought about, and the phrase ' peristaltic movement ' is generally used to denote this total effect of the contraction of the muscular coats ; it will however be best to restrict the meaning to the progressive contraction of the circular coat assisted, in most cases, by a similar progressive contraction of the longitudinal coat. § 270. Movements of the (Esophagus. These as we have just said are fairly simple. The circular contraction begun by the constrictors of the pharynx is continued along the circular coat of the oesophagus and assisted by an accompanying contraction of the longitudinal coat, the direction being always, save in the abnormal action of vomiting, from above downwards. It will be remembered (§ 222) that the muscular bundles of the oesophagus are composed of striated fibres in the upper part, and of plain unstriated fibre-cells in the lower part, the transition occupying a different level in different animals. Nevertheless, as far as the peristaltic movement is concerned, the two kinds of fibres behave in the same way except that the peristaltic wave if we may so call it travels more rapidly in the striated region. These peristaltic movements of the oesophagus may, like those of the intestine, be seen after removal of the organ from the body ; and indeed may continue to appear upon stimulation, for an unusual length of time. They may therefore be carried out by the muscular elements, with or without the help of the nervous elements embedded in them, apart from any action of the central nervous system. Nevertheless, in the living body, the move- ments of the oesophagus seem to be in a special way dependent on the central nervous system ; the contractions are not started and carried out by the walls of the tube alone and so transmitted from section to section in the walls of the tube itself; but afferent impulses started in the pharynx and passing to the medulla oblongata, give rise to reflex efferent impulses which descend along 458 MOVEMENTS OF (ESOPHAGUS. [BOOK n. nervous tracts to successive portions of the organ. If the oesophagus be cut across some way down, or if a portion of the middle region be excised, stimulation of the pharynx will produce a peristaltic contraction, which travelling downwards will not stop at the cut or excision but will be continued on into the lower disconnected portion by means of the central nervous system. And it is stated that ordinary peristaltic contractions of the lower part of the oesophagus can be readily excited by stimulation of the pharynx, but not by stimuli applied to its own mucous membrane. In the reflex act which thus brings about the- peristaltic contraction of the oesophagus the afferent nerves are those of the pharynx, vix. the superior laryngeal nerve and pharyngeal branches of the vagus, branches of the fifth, and in some animals at least branches of the glossopharyngeal, but chiefly the first; and cesophageal movements can easily be excited by centripetal stimulation of the superior laryngeal. The centre lies in the medulla oMongata, being a part of the gem-nil deglutition centre ; and the efferent impulses pass along fibres of the vagus, reaching the upper part of the oesophagus by the recurrent laryngeal nerves and the lower part through the cesophageal plexuses of the vagus (Fig. 70). Section of the trunk of the vagus renders difficult the passage of food along the oesophagus, and sti- mulation of the peripheral stump causes cesophageal contractions. The force of this movement in the oesophagus is considerable ; thus in the dog a ball pulling by means of a pulley against a weight of 250 grammes has been found to be readily carried down from the pharynx to the stomach. At the junction of the oesophagus with the stomach the circular fibres usually remain in a more or less permanent condition of tonic or obscurely rhythmic contraction, more particularly when the stomach is full of food, and thus serve as a sphincter to prevent the return of food from the stomach into the oesophagus. Upon the arrival of the bolus of food at the end of the oesophagus, the centre for this sphincter is inhibited and the orifice is thus opened up. Possibly the patency of the orifice is still further secured by a contraction of the longitudinal muscular fibres which radiate from the end of the oesophagus over the stomach. § 271. Movements of the Stomach. While the object of the cesophageal movement is simply to carry the swallowed bolus with all due speed to the stomach, and while the intestinal movement has, in like manner, simply to carry the intestinal contents onward, the twisted course of the looped path ensuring all the mixing of t>he constituents of the contents that may be necessary, the movements of the stomach have a double object : on the one hand to provide an adequate exposure of the contents of the dilated chamber to the influence of the gastric juice, and on the other to propel the partially digested food, when ready, into the duodenum. We may accordingly distinguish between what we CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 459 may call the " churning " and the " propulsive " movements of the stomach. When the stomach is empty all the muscular fibres as we have said, longitudinal, circular and oblique, fall into a condition which we may perhaps speak of as an obscure tonic contraction. The whole stomach is small and contracted, its cavity is nearly obli- terated, and the mucous membrane, owing to the predominance of the circular coat, is like the lining membrane of an empty artery, thrown into longitudinal folds. As more and more food enters the stomach all the coats become relaxed, with the exception of the pyloric sphincter, which remains at first permanently closed, and the less marked cardiac sphincter, which merely relaxes from time to time at each act of swallowing. No sooner however do the coats thus become relaxed than they set up obscure rhythmical peristaltic contractions, giving rise to the " churning " movements. These movements have been described as of such a kind that the contents flow in a main current from the cardia along the greater curvature to the pylorus, and back to the cardia along the lesser curvature, subsidiary currents mixing the peripheral portions of the contents with the more central ; it may be doubted however whether any such regularity of flow is marked or constant, and it is not easy to see by what combination and sequence of contractions in the three coats, longitudinal, circular and oblique, such a regular flow can be produced. But in any case, by such rhythmical contractions the food and gastric juice are rolled about and mixed together. These churning movements are feeble at first, even though the stomach be filled and distended by a large meal rapidly eaten; they become more and more pronounced as digestion proceeds. Before digestion has proceeded very far the ' propulsive ' movements begin. These occur at intervals, and are repeated at first slowly but afterwards more rapidly. Each movement consists in a contraction of the circular muscular fibres more powerful than any taking part in the churning movements, and leading to a circular constriction which, beginning apparently at about the obscurely defined groove which marks the beginning of the antrum pylori, travels down towards the pylorus, propelling the food onward. This movement is accompanied or rather preceded by a relaxation of, that is to say in all probability an inhibition of the permanent contraction of, the sphincter pylori itself, in order that the gastric contents may pass into the duodenum. But the occurrence of this relaxation is determined by the nature of the gastric contents; for if the propulsive movement drives large undigested pieces towards the pylorus, the sphincter is apt to close again, the result of which is that the undigested morsels are carried back into the main body of the stomach. The combined effect then of the churning and of the propulsive movements is, after a certain part of the meal has been reduced to 4\ impulses reaching it from parts of the l>rain higher up than itself, as in cases of vomiting produced by smells, tastes or emotions, or by the recollection of past events, and in some cases of vomiting due to cerebral disease. Manx emetics, snch as tartar emetic, appear to act directly on the centre, since, introduced into the blood, they will produce vomiting after a bladder has been substituted for the whole stomach. Others again, such as mustard and water, act in a re- flex manner l>y irritation of the gastric mucous membrane. With others, a^ain, which cause vomiting by developing a nauseous taste, the action involves parts of the brain higher than the centre itself. § 273. Movements of the Small Intent inc. These, as we have already said, are the typical peristaltic movements, simple except in so far as they are complicated by the existence of the pendent loops, the peculiar oscillating movements of which appear to be produced chiefly by the longitudinal filuvs. The peristaltic movements, as a rule, take place from above downwards, and a wave beginning at the pylorus may be traced a long way down. But contractions may, and in all probability occasionally do, begin at various points along the length of the intestine. A movement started by artificial stimulation some way down the intestine, may travel not only downwards but also upwards ; it has been disputed however, whether in the living body any natural backward peristaltic movement really takes place. In the living body the intestines have periods of rest, alternating with periods of activity, the occurrence of the periods depending on various circumstances ; the intensity of the move- ments also varies very considerably. § 274. Movements of the Large Intestine. These are funda- mentally the same as those of the small intestine, but distinct in so far as the latter cease at the ileo-caecal valve, at which spot the former normally begin ; they are simpler, in as much as the pendent loops are absent, and not so vigorous, since relatively to the diameter of the tube, the amount of muscular fibre is less. Along the colon where the sacculi are well developed (§ 266) the movement may perhaps be described as almost intermittent from sacculus to sacculus, the contents of one sacculus being driven CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 463 by the peristaltic contractions of its circular fibres into the next sacculus, which prepares to receive them by a relaxation of its circular and a contraction of its longitudinal fibres. Since the lips of the ileo-csecal valve are placed transversely across the caecum, not only does distension of the caecum, by stretching the valve along the line of the lips, bring them into apposition, but the pressure exerted by the peristaltic movement has the same effect. In this way any return of the contents from the large to the small intestine is prevented. Arrived at the sigmoid flexure, the contents, now more or less solid fasces, are supported by the bladder and the sacrum, so that they do not press on the sphincter ani. § 275. Defalcation. This is a mixed act, being superficially the result of an effort of the will, and yet carried out by means of an involuntary mechanism. Part of the voluntary effort consists in producing a pressure-effect, by means of the abdominal muscles. These are contracted forcibly as in expiration, but the glottis being closed and the escape of air from the lungs prevented, the whole force of the pressure is brought to bear on the abdomen itself, and so drives the contents of the descending colon onward towards the rectum. The sigmoid flexure is by its position sheltered from this pressure ; a body introduced per anum into the empty rectum is not affected by even forcible contractions of the abdominal walls. The anus is guarded by the sphincter ani, which is habitually in a state of normal tonic contraction, capable of being increased or diminished by a stimulus applied, either internally or externally, to the anus. The tonic contraction is in part at least due to the action of a nervous centre situated in the lumbar spinal cord. If the nervous connection of the sphincter with the spinal cord be broken, relaxation takes place. If the spinal cord be divided somewhat higher up, for instance in the dorsal region, the sphincter, after the depressing effect of the operation, which may last several days, has passed off, regains and subsequently main- tains its tonicity, shewing that the centre is not placed higher up than the lumbar region of the cord. The increased or diminished contraction following on local stimulation is probably due to reflex augmentation or inhibition of the action of this centre. The centre is also subject to influences proceeding from higher regions of the cord, and from the brain. By the action of the will, by emotions, or by other nervous events, the lumbar sphincter centre may be inhibited, and thus the sphincter itself relaxed ; or augmented, and thus the sphincter tightened. A second item therefore of the voluntary process in defsecation is the inhibition of the lumbar sphincter centre, and consequent relaxation of the sphincter muscle. Since the lumbar centre may remain wholly efficient when separated from the brain, the paralysis of the sphincter which occurs in certain cerebral diseases is probably due 464 DEFECATION. [BOOK 11. to inhibition of this lumbar centre, and not to paralysis of any cerebral centre. Thus a voluntary contraction of the abdominal walls, accom- panied by a relaxation of the sphincter, might press the contents of the descending colon into the rectum and out at the anus. Since however, as we have seen, the pressure of the abdominal walls is warded off the sigmoid flexure, such a mode of defecation would always end in leaving the sigmoid flexure full. Hence the necessity for these more or less voluntary acts being accompanied by an involuntary augmentation of the peristaltic action of the large- intestine, sigmoid flexure and rectum. In the movements of the rectum we can trace out more distinctly than in other regions of the alimentary canal the separate actions of the longitudinal and circular fibres. The former, by means of contractions travelling from above downwards, shorten the rectum, and since the anus affords a more or less fixed support pull the reetum and its contents down; the latter, by means of contractions travelling from above downwards but taking plaee somewhat later, narrow the rectum and so squeeze the contents onwards and "inwards. Defecation then appears to take place in the following manner. The large intestine and sigmoid flexure becoming more and more full, stronger and stronger peristaltic action is excited in their walls. By this means the feces are driven into the rectum and so, by a continuance of the movements increasing in vigour, against the sphincter. Through a voluntary act, or sometimes at least by a simple reflex action, the lumbar sphincter centre is inhibited and the sphincter relaxed. At the same time the contraction of the abdominal muscles presses firmly on the descend- ing colon, and thus, contractions of the levator ani assisting, the contents of the rectum are ejected. It must however be remembered that, while in appealing to our own consciousness, the contraction of the abdominal walls and the relaxation of the sphincter seem purely voluntary efforts, the whole act of defecation, including both of these seemingly so voluntary components, may take place in the absence of conscious- ness, and indeed, in the case of the dog at least, after the complete severance of the lumbar from the dorsal cord. In such cases the whole act must be purely reflex, excited by the presence of feces in the rectum. § 276. TJte nervous mechanisms of gastric and intestinal movements. Both the stomach and intestines when removed from the body and thus wholly separated from the central nervous system may, by direct stimulation, be readily excited to move- ments; and indeed in the absence of all obvious stimuli, movements which seem to be spontaneous may at times be observed. The movements of which we are speaking are orderly movements of a peristaltic nature, not mere local contractions of a few bundles of CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 465 plain muscular fibres. The alimentary canal therefore, like the heart, though to a less degree, possesses within itself such mechanisms as are requisite for carrying out its own movements ; and, as in the case of the heart, there is no adequate evidence that the ganglia scattered in its muscular walls, those namely forming the plexus of Auerbach, play any prime part in developing these movements. On the other hand, powerful movements of a peristaltic kind may be induced, not only as we have already seen in the oesophagus but also in the stomach, in the small intestine, and even in the large intestine by stimulation of the vagus nerve. The chief and usual cause of the movements of the stomach and intestines is the presence of food in their interior. But we do not know definitely the exact manner in which the food produces the movement. It may be that the food, by stimulating the mucous membrane, sends up afferent impulses, and that these give rise by reflex action to efferent impulses which descend the vagus fibres to successive portions of the canal, in a manner similar to that already described in reference to the oesophagus. If this be so the efferent impulses reach the stomach and upper part of the duodenum by the terminal portions of the two vagi, Fig. 70, R.V. L.V., and reach the intestines by the portion of the right or posterior vagus, Fig. 70, R'. V'., which passes into the solar plexus and thence by the mesenteric nerves. The afferent im- pulses from the stomach travel also apparently by the vagus ; the paths of those from the intestines have not yet been determined. But that such a reflex action through vagus fibres is not the only means by which the presence of food brings about the move- ments in question, is shewn by the fact that these continue to be developed after section of both vagus nerves. Probably the whole action is a mixed one which we may picture to ourselves some- what as follows. The alimentary canal possesses a power of spontaneous movement, feeble it is true, very inferior to that of the heart, and very apt to be latent, but still existing. The presence of food in some way or other, by some direct action quite apart from the central nervous system, is able to increase this power so that, without any aid from the central nervous system, as after section of the vagi, adequate peristaltic movements can, under favourable circumstances, be carried out. Nevertheless in the normal course of events satisfactory movements are still further secured by the reflex action through vagus fibres just described. Thus, in the dog, the act of swallowing food or even the mere smell of food has been observed to increase the move- ments of a piece of intestine isolated from the rest of the alimen- tary canal but retaining its connections with the central nervous system. Under this view the peristaltic movements produced by centrifugal stimulation of the vagus in the neck are comparable not so much with the contraction of a skeletal muscle when its F. 30 466 NERVES OF ALIMENTARY CANAL. [BOOK n. motor nerve is stimulated as with the beats which may be called forth in an inhibited or otherwise quiescent heart by stimulation of the cardiac augmentor fibres. RV Ret. FIG. 70. DIAGRAM TO ILLUSTRATE THE NERVES OF THE ALIMENTARY CANAL IN THE DOG. The figure is for the sake of simplicity made as diagrammatic as possible, and does not represent t]i<- /inntoinical relation*. Oe to Ret. — The alimentary canal, oesophagus, stomach, small intestine, large intestine, rectum. LV. Left vagus nerve, ending on front of stomach, r.l. recurrent laryngeal nerve supplying upper part of oesophagus. E.V. right vagus, joining left vagus in cesophageal plexus, oe. pi., supplying the posterior part of stomach and con- tinued as R'.V. to join the solar plexus, here represented by a single ganglion and connected with the inferior rnesenteric ganglion (or plexus) in. gl. — a. branches from the solar plexus to stomach and small intestine, and from the mesenteric ganglion to the large intestine. Spl. maj. Large splanchnic nerve arising from the thoracic ganglia and rami communicantes r.c. belonging to dorsal nerves from the 6th to the 9th (or 10th). S})!. min. Small splanchnic nerve similarly arising from 10th and llth dorsal nerves. These both join the solar plexus and thence make their way to the alimentary canal. C.r. Nerves from the ganglia &c. belonging to llth and 12th dorsal and 1st and 2nd lumbar nerves, proceeding to the inferior mesenteric ganglia (or plexus) m. gl. and thence by the hypogastric nerve n. hyp. and the hypogastric plexus pi. hyp. to the circular muscles of the rectum. l.r. Nerves from the 2nd and 3rd sacral nerves, S2, S3 (nervi erigentes), proceed- ing by the hypogastric plexus to the longitudinal muscles of the rectum. CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 467 Indeed we may perhaps call the vagus fibres which pass to the stomach and intestines (and these we may remark are, like the cardiac angmentor fibres, uon-medullated fibres along the greater part of their course) angmentor fibres rather than motor fibres. We have all the more reason to do so since there exist companion but antagonistic inhibitory fibres. If while lively peristaltic action is going on in the bowels, the splanchnic nerves be stimulated the bowels are brought to rest, often in a very abrupt and marked manner. Inhibitory fibres therefore run in the splanchnic nerves, Fig. 70, Spl. maj. and min., passing along them from the spinal cord to the abdominal plexuses, and thence to the alimentary canal ; probably some of the fine medullated fibres which may be observed along this track are of this nature. It will be noticed that the splanchnic nerves while containing vaso-constrictor i.e. augmentor fibres for the blood vessels of the intestines, carry inhibitory fibres for the muscular coat; and probably the vagus while containing augmentor fibres for the muscular coat carries inhibitory dilator fibres for the blood vessels. It may further be remarked that the vagus while supplying aug- mentor fibres for the muscular mechanisms of the alimentary canal carries, as we so well know, inhibitory fibres for the cardiac muscular mechanism. In the above statement we have purposely used the general term peristaltic movement, but as we have seen, in the movements of the alimentary canal, two sets of muscles are concerned, the circular and the longitudinal. Now in the rectum we are able to recognise that the two sets of muscles have quite distinct nervous supplies. The longitudinal coat is governed by nerve-fibres which, in the dog, leave the spinal cord in the anterior roots of the second and third sacral nerves, Fig. 70, $2, S3, pass along the branches of those nerves, frequently spoken of as the nervi eri- gentes, L r., to the hypogastric plexus, pi. hyp., and thence to the rectum. Stimulation of these nerves causes contractions of the rectum which are confined to the longitudinal coat and as we have said pull the rectum down. The circular coat is governed by fibres which leave the spinal cord by the anterior roots of the lower dorsal and first two lumbar nerves, Fig. 70 (coming from the lower part of that spinal region from which as we have seen § 169 the vaso-constrictor fibres take origin), and, early losing their medulla, pass to the rectum by the inferior mesenteric ganglia, the hypogastric nerves and hypogastric plexus, Fig. 70, in. gl., ft. hyp. pi., hyp. Stimulation of these fibres gives rise to con- tractions which are confined to the circular coat, and squeeze out the contents of the rectum. A similar double nervous supply probably governs the longitudinal and circular coats along the whole alimentary canal; but the details of such a supply are at present unknown. Our knowledge moreover concerning the details of any special 30—2 468 MOVEMENTS OF ALIMENTARY CANAL. [BOOK 11. nervous mechanisms, by means of which the more complicated movements of the stomach, including the closing and opening of the sphincters, are carried out, is at present very imperfect. We cannot add to what we have incidentally said in speaking of vomiting. The movements of the rectum, including the sigmoid flexure, appear to be much more closely dependent on the central nervous system than are those of the rest of the alimentary canal. As we have said the movements of both large and small intestine are rather assisted and augmented than primarily called forth by impulses descending from the central nervous system along the vagus fibres. As the large intestine however passes into the rectum government by the vagus is replaced by government through the lumbar cord and the nerves just previously mentioned ; and this government appears to be not so much mere augmen- tation as the actual carrying out of the movements through reflex action. Hence this is the part of intestinal movement which fails in diseases of the central nervous system; the failure leading to obstinate constipation if not to actual difficulty of defecation. The presence of faeces in the sigmoid flexure no longer stirs up the reflex mechanism for their discharge ; meanwhile the more in- dependent movements of the higher parts of the canal continue to drive the contents onward ; and hence the fseces accumulate in the sigmoid flexure and colon awaiting the delayed action of the imperfect reflex mechanism. With regard to the exact manner in which the presence of food acts as a stimulus it may be worth while to remark, that, though in the stomach as we have seen mere fulness is not the efficient cause of the movements, since these become more active as digestion proceeds and the bulk of the contents diminishes, yet in the intestine distension of the bowel up to certain limits most distinctly increases the vigour of the movements just as distension of the cardiac cavities within certain limits improves the cardiac stroke. This is well seen in obstruction of the bowels in which cases the bowel distended above the obstruction is frequently thrown into violent peristaltic movements. This effect is in part at least due to the distension extending the muscular fibres and so in a direct manner promoting their contraction (see § 81), but may be in part due to augmentor impulses excited in a reflex manner. Probably in an intestine isolated from the central nervous system, food provokes peristaltic movements much more by causing distension and so stretching the muscular coats than by acting as a stimulus to the mucous membrane either through chemical action or in any similar way. § 277. Next to the presence of food in the interior of the alimentary canal, a deficient oxygenation of the blood supplied to the walls of the canal or the sudden cutting off of the supply of blood, may be regarded as the most powerful provocatives of peristaltic action. When the aorta is clamped or when the CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 469 respiration is seriously interfered with, peristaltic movements become very pronounced. Thus, in death by asphyxia or suffoca- tion, an involuntary discharge of fasces, which is in part at least the result of increased peristaltic action, is not an unfrequent result ; and the marked peristaltic movements which are so frequently seen in an animal when the abdomen is laid open immediately after death, appear to be due to the cessation of the circulation and the consequent failure in the supply of blood to the walls of the alimentary canal and not, as has been suggested, to the contact with air of the peritoneal surface. Since it is blood which brings oxygen to the tissues, failure in the supply of blood is tantamount to failure in the supply of oxygen ; but the blood current brings other things besides oxygen and also takes things away ; and the failure of this action also probably, as well as failure in the supply of oxygen, provokes the movements in question. The movements thus produced are to some extent the result of the deficient supply of blood acting directly on the walls of the canal, though in asphyxia at all events this effect may be increased by the too venous blood stimulating the central nervous system and thus sending augmentor impulses down the vagus. With regard to the mode of action of the drugs which promote peristaltic action it will be sufficient here to say that while some such as nicotin appear to act directly on the walls of the canal, others such as strychnia produce their effect chiefly by acting through the central nervous system. SEC. 8. THE CHANGES WHICH THE FOOD UNDERGOES IN THE ALIMENTARY CANAL. § 278. Having studied the properties of the digestive juices as exhibited outside the body, and the v'arious mechanisms by means of which the food introduced into the body is brought under the influence of those juices, we have now to consider what, as matters of fact, are the actual changes which the food does undergo in passing along the alimentary canal, what are the steps by which the contents of the canal are gradually converted into faeces. The events which lead to this conversion are two-fold. On the one hand the digestive juices do bring about, inside the alimen- tary canal, changes which in the main are the same as those observed in laboratory experiments outside the body and described in previous sections, though the results are somewhat modified by the special conditions which obtain within the body. On the other hand absorption, that is to say, the passage from the interior of the canal into the blood vessels and lymphatics, of digested material in com- pany with water, is going on along the whole length of the canal, and especially in the small and large intestines. It will be con- venient to confine ourselves at present to the study of the first class of events, the changes effected in the canal, merely noting the disappearance of this or that product, and deferring the difficult problem of how absorption takes place to a subsequent and separate discussion. In the mouth the presence of the food, assisted by the move- ments of the jaw, causes, as we have seen, a flow of saliva. By mastication, and by the addition of mucous saliva, the food is broken into small pieces, moistened, and gathered into a convenient bolus for deglutition. In man some of the starch is, even during the short stay of the food in the mouth, converted into sugar ; for if boiled starch free from sugar be even momentarily held in the mouth, and then ejected into water (kept boiling to destroy the ferment) it will be found to contain a decided amount of sugar. In many animals no such change takes place. The viscid saliva of the dog serves almost solely to assist in deglutition ; and even the longer stay which food makes in the mouth of the horse is CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 471 insufficient to produce any marked conversion of the starch it may contain. During the rapid transit through the wsophayus no appreciable change takes place. The amount, of absorption of digested material, or even of simple water from the mouth or oesophagus, must always be insignificant. The Changes in the Stomach. § 279. The arrival of the food, the reaction of which is either naturally alkaline, or is made alkaline, or at least is reduced in acidity, by the addition of saliva, causes a flow of gastric juice. This, already commencing while the food is as yet in the mouth, increases as the food accumulates in the stomach, and as, by the churning gastric movements, one part after another of the food is brought into contact with the mucous membrane. The characters of the juice appear to change somewhat as the act of digestion proceeds. The amount of pepsin in the gastric contents increases for some time after food is taken, and probably the actual secretion increases also. The acidity of the gastric contents is at first very feeble ; indeed in man, in some cases at least, for some little time after the beginning of a meal no free acid is present, and during this period the conversion of starch into sugar may continue. This condition however is temporary only ; very soon the contents become acid, arresting the action of and ultimately destroying the amylolytic ferment ; and, since the rate of the secretion of acid appears to be fairly constant, the contents of the stomach, unless fresh alkaline food be taken, become more acid as digestion goes on. The gross effect of gastric digestion is to break up and partly to dissolve the larger lumps of masticated food into a thick greyish soup- like liquid called chyme, with which are still mixed in variable quantity larger and smaller masses of less changed food. This is the result, partly of the solution of proteid matters, partly of the solution of the gelatiniferous connective-tissue holding the proteid elements together. In a fragment of meat, for instance, the muscular fibres, through the solution of the connective-tissue binding them together, fall asunder, the sarco- lemma is dissolved, and the fibres themselves split up sometimes longitudinally but most frequently by transverse cleavage into discs, and are ultimately more or less reduced partly into a granular mass, partly to actual solution. In a piece of tissue con- taining fat, the connective-tissue binding the fat cells together and the envelopes of the fat cells are dissolved, so that the fat, fluid at the temperature of the body, is set free from the individual cells and runs together into larger and smaller masses. In vegetable tissue the proteid elements are in part dissolved and, though there is no evidence that in man cellulose is dissolved in the stomach, 472 CHANGES IN THE STOMACH. [BOOK n. the whole tissue is softened and to a certain extent disintegrated. Milk is curdled and the curd subsequently more or less dissolved. The thick soup-like acid chyme consists accordingly partly of substances which have entered into actual solution, partly of mere particles or droplets of proteid, fatty or other nature and partly of masses small or great, which may be recognized under the micro- scope as more or less changed portions of animal or vegetable tissue. The amount of material actually dissolved is in most specimens of chyme exceedingly small. When the solid parts are removed by nitration the clear nitrate contains besides salts, pepsin and free hydrochloric acid (the constituents of the gastric juice), a small amount of sugar, of parapeptone and of peptone. The sugar is often absent, the parapeptone is not always present, and the amount of peptone (or albumose) is always small. During gastric digestion the chyme thus formed is from time to time ejected through the pylorus, accompanied by even large morsels of solid less-digrstrd matter. This may occur within a few minutes of food having been taken ; but the larger escape from the stomach probably does not in man begin till from one to two, and lasts from four to five hours, after the meal, becoming more rapid towards the end, and such pieces as are the least broken up by the gastric juice and movements being the last to leave the stomach. The time taken up in gastric digestion probably varies in the same animal not only with different articles of food but also with varying conditions of the stomach and of the body at large. In different animals it varies very considerably, being from 12 to 24 hours in the dog after a full meal, while the stomachs of rabbits are never empty but always remain largely rilled with food, even during starvation. In man the stomach probably becomes empty between the usual meals. The total amount of change which the food undergoes in the stomach, that is the share taken by the stomach in the whole work of digestion, seems to vary largely in different animals, and in the same animal differs according to the nature of the meal. In a dog fed on an exclusively meat diet, a very large part of the digestion is said to be carried out by the stomach, very little work apparently being left for the intestines ; that is to say, the larger part of the meal is reduced in the stomach to actual solution and a considerable quantity is probably absorbed directly from the stomach. In such cases the amount of peptone found in the stomach during the digestion of the meal is found to be fairly constant, from which it may be inferred that the peptone is absorbed as soon as it is formed. There is also evidence that fat may to a certain extent undergo in the stomach changes leading to emulsion, similar to those which, as we shall see, are carried out in the small intestine. But such cases as these cannot be regarded as typical cases of CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 473 gastric digestion, and in man, at all events, living on a mixed diet the work of the stomach appears to be to a large extent preparatory only to the subsequent labours of the intestine. It is true that our information on this matter is imperfect, being chiefly drawn from the study of cases of gastric or duodenal fistula, in which probably the order of things is not normal, or being in large measure deductions from experiments on animals, whose economy in this respect must be largely different from our own ; but we are probably safe in concluding that, in ourselves, the chief effect of gastric digestion is by means of the disintegration spoken of above to reduce the lumps of food to the more uniform chyme and so to facilitate the changes which take place in the small intestine. During that disintegration some of the proteid in the meal is converted into peptone ; and the peptone so formed is probably absorbed at once ; but much proteid remains unchanged or at least is not converted into peptone, and the fats and starches undergo in themselves very little change indeed. In the act of swallowing, no inconsiderable quantity of air is carried down into the stomach, entangled in the saliva, or in the food. This is returned in eructations. When the gas of eructation or that obtained directly from the stomach is examined, it is found to consist chiefly of nitrogen and carbonic acid, the oxygen of the atmospheric air having been largely absorbed. In most cases the carbonic acid is derived by simple diffusion from the blood, or from the tissues of the stomach, which similarly take up the oxygen. In many cases of flatulency, however, it may arise from a fermentative decomposition of the sugar which has been taken as such in food or which has been produced from the starch, the gas being either formed in the stomach or passing upwards from the intestine through the pylorus. The enormous quantity of gas which is discharged through the mouth in cases of hysterical flatulency, even on a perfectly empty stomach, and which seems to consist largely of carbonic acid, presents difficulties in the way of explanation ; it is possible that it may be simply diffused from the blood, but it is also possible that in many cases it is derived from air which the patient has hysterically swallowed, the oxygen having been removed, in the stomach, by absorption and replaced by carbonic acid. In the Small Intestine. § 280. The semi-digested acid food, or chyme, as it passes over the biliary orifice, causes as we have seen (§ 253) gushes of bile, and at the same time the pancreatic juice flows into the intestine freely. These two alkaline fluids, especially the more strongly and constantly alkaline pancreatic j nice, tend to neutralize the acidity of the chyme, but the contents of the duodenum do not become distinctly alkaline until some distance from the pylorus is 474 CHANGES IN THE SMALL INTESTINE. [BOOK n. reached. The rapidity with which the change in the reaction is completed is not the same in all animals, and in the same animal appears to vary according to the nature of the food, and various circumstances. In man, living on a mixed diet, the contents have probably become distinctly alkaline before they have passed far down the duodenum. On the other hand in dogs, the contents of the small intestine have been observed to be acid throughout, and that, not only when fed on starch and fat, which might, by an acid fermentation of which we shall presently speak, give rise to an acid reaction, but even when fed on meat. The conversion of starch into sugar, which as we have seen is sooner or later arrested in the stomach, is resumed with great activity and indeed completed by the pancreatic juice, possibly assisted by the succus entericus, the presence of bile being said to increase the activity of the pancreatic amylolytic ferment. The converMon begins as soon as the acidity of the chyme is sufficiently reduced and continues along the intestine; portions however of still undigested starch may be found in the large intestine, and even at times in the fseces. The pancreatic juice, as we have seen, emulsifies fats, and also splits them into their respective fatty acids and glycerine. The fatty acids thus set tree become comer! ed by means of the alkaline contents of the intestine into soaps ; but to what extent sapouifica- tion thus takes place is not exactly known. Undoubtedly soaps have to a small extent b^-u found both in portal blood and in the thoracic duct after a meal; but there is no proof that any large quantity of fat is introduced in this form into the circulation. On the other hand, the presence of neutral fats in the lacteals, and to a slight extent in portal blood, is a conspicuous result of the diges- tion of fatty matters ; and in all probability saponirication in the intestine is a subsidiary process, the effect of which is rather to facilitate the emulsion of neutral fats than to introduce soaps as such into the blood, v For the presence of soluble soaps favours the emulsion of neutral fats. Hence a rancid fat, i.e. a fat containing a certain amount of free fatty acid, forms an emulsion with an alkaline fluid more readily than does a quite neutral fat. A drop of rancid oil let fall on the surface of an alkaline fluid, such as a solution of sodium carbonate of suitable strength, rapidly forms a broad ring of emulsion, and that even without the least agitation. As saponification takes place at the junction of the oil and alkaline fluid currents are set up, by Avhich globules of oil are detached from the main drop and driven out in a centrifugal direction ; the intensity of the currents and the consequent amount of emulsion depend on the concentration of the alkaline medium and on the solubility of the soaps which are formed. Now the bile and pancreatic juice supply just such conditions as the above for emulsionizing fats : they both together afford an alkaline medium, the pancreatic juice gives rise to an adequate amount of free fatty CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 475 acid, and the bile in addition brings into solution the soaps as they are formed. So that we may speak of the emulsion of fats in the small intestine as being carried on by the bile and pancreatic juice acting in conjunction ; and as a matter of fact the bile and pancreatic juice do largely emulsify the contents of the small intestine, so that the greyish turbid chyme is changed into a creamy-looking fluid, which has been sometimes called chyle. It is advisable however to reserve this name for the contents of the lacteals. Many of the fats present in food, for instance, butter, already contain some fatty acids when eaten ; for these fats the initial action of the pancreatic juice is less necessary. This mutual help of bile and pancreatic juice in producing an emulsion explains to a certain extent the controversy which long existed between those who maintained that the bile and those who maintained that the pancreatic juice was necessary for the diges- tion and absorption of fatty food. That the pancreatic juice does produce in the intestine such a change as favours the transference of neutral fats from the intestine into the lacteals, is shewn by the fact that in diseases affecting the pancreas, much fatty food frequently passes through the intestine undigested, and great wasting ensues ; but it cannot be maintained that the pancreatic juice is the sole agent in this matter, since in animals in which the pancreatic ducts have been successfully ligatured chyle is still found in the lacteals. On the other hand, that the bile is of use in the digestion of fat is shewn by the prevalence of fatty stools in cases of obstruction of the bile-ducts ; and though the operation of ligaturing the bile-ducts, and leading all the bile externally through a fistula of the gall bladder, is open to objection, since it, in some way or other, so exhausts the animal as indirectly to affect digestion, still the results of experiments in which the resorption of fat was distinctly lessened (the quantity of fat in the lacteals falling from 3'2 to "02 p.c.) by the ligature and fistula, obviously point to the same conclusion. That in man the succus entericus possesses a wholly insufficient emulsifying power is shewn by the observation of a case in which the duodenum opened on the surface by a fistula in such a way that the lower part of the intestine could be kept free from the contents of the upper part containing the bile arid pancreatic juice and matters proceeding from the stomach. Fats introduced into the lower part, where they could not be acted upon either by the bile or by the pancreatic juice were but slightly digested. Without denying the possible assist- ance of the succus entericus, or even of gastric juice, we may conclude that the digestion of fat is in the main carried out by the conjoint action of bile and pancreatic juice. § 281. We have seen, § 247, that the addition of bile to a digesting mixture gives rise to a precipitate. This is partly a coarse flocculent precipitate, consisting of parapeptone with sonic amount of bile acids, and partly of a finer more granular pre- 476 CHANGES IN THE SMALL INTESTINE. [BOOK n. cipitate, which is longer in falling down, and consists chiefly of bile acids with a variable amount of peptone; the latter is re-dissolved on the further addition of bile even though the reaction of the mixture remain acid. In the upper part of the duodenum the inner surface, if examined while digestion is going on, is found to be lined by a coloured flocculeut and granular material, which is probably a precipitate thus formed ; the purpose of this precipitation is probably to delay the passage of the un- digested parapeptone along the duodenum. Moreover, apart from this precipitation, bile arrests the action of pepsin, even while the reaction of the mixture still remains acid; and as soon as an alkaline reaction is established the pepsin is apparently destroyed by the trypsin, so that with the flow of bile and pancreatic juice into the duodenum the processes which have been going on in the stomach come to an end. In fact it would seem that the juices of the various districts of the alimentary canal are mutually destruc- tive; thus, while prpsin in an acid solution destroys the active constituents of saliva and of pancreatic juice (probably also those of the succus entericus), it is in its turn antagonized or destroyed by the bile and the other alkaline juices of the intestine. Hence pancreatic juice introduced through the mouth must lose its powers in the stomach and can only be of use as an alkaline medium containing certain proteid matters. On the other hand if, as we have reason to believe, the contents of the stomach as they issue from the pylorus still contain a large quantity of undigested proteids, these must be digested by the pancreatic juice (with or without the assistance of the succus entericus), the action of which seems to be assisted or at least not hindered by bile. And in dogs fed through a duodenal fistula, so that all gastric digestion is excluded, proteids are completely digested and give rise to quite normal faeces. To what stage the pancreatic digestion is carried, whether peptone is, practically, the only product, or whether the pancreatic juice in the body, as out of the body, carries on its work in the more destructive form, whereby the proteid material subjected to it is so broken down as to give rise to appreciable quantities of leucin and tyrosin, is at present not exactly known. Leucin and tyrosin have been found in the intestinal contents, and may therefore be formed during normal digestion, but whether an insignificant quantity or a considerable quantity of the proteid material of food is thus hurried into a crystal- line form cannot be definitely stated. The extent to which the action is carried is probably different in different animals, and probably varies also according to the nature of the meal and the condition of the body. Possibly when a large and unnecessary quantity of proteid material is taken at a meal together with other substances, no inconsiderable amount of the proteids undergo this profound change, and, as we shall see, rapidly leave the body as urea, without having been used by the tissues, their contribution CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 477 to the energy of the body being limited to the heat given out during the changes by which they are converted into urea. To this apparently wasteful use of proteids we shall return in speaking of what is called the ' luxus consumption' of food. § 282. In dealing with the action of pancreatic juice we drew attention, § 249, to the difference between the results of pure tryptic digestion and those obtained when bacteria or other micro-organisms were allowed to be present. We saw that indol, for example, was the product of the action of these organisms, not of trypsin. Now indol is formed, in varying quantity, during the digestion which actually takes place in the intestine, some of it at times appearing in the urine as indigo-yielding substance (indican). Moreover bacteria and other micro-organisms are present in the intestinal contents. Hence we must regard the changes taking place in the intestine not as the pure results of the action of the several digestive juices, but as these results modified by or mixed with the results of the action of micro-organisms. We spoke above, § 247, of bile as being antiseptic, but this must be under- stood as meaning not that the presence of bile arrests the action of all micro-organisms within the intestine, but that it modifies their action, keeping it within certain limits and along certain lines. Concerning the exact nature and extent of the changes thus due to micro-organisms our knowledge is at present very imperfect. The proteids and the carbohydrates seem to be the food stuffs on which these organisms produce their chief effect. Out of the proteids they give rise not only to indol but to several other compounds, among which may be mentioned phenol (C6H60), of which a small quantity may be recognized in the faeces, the rest being absorbed and appearing in the urine in the form of certain phenol- compounds, such as phenyl-sulphuric acid. Out of proteids they may also form the peculiar poisonous bodies called ptomaines, which appear in the ordinary putrefaction of proteids. But their most conspicuous effects are those on the carbohydrates. As the food descends the intestine, the presence of lactic acid becomes more and more obvious ; indeed in some cases the naturally alkaline reaction of the intestinal contents may in the lower part of the intestine be changed into an acid one by the presence of lactic acid. Now lactic acid may be formed out of sugar by means of a special organism inducing what is spoken of as the lactic acid fermentation. And we have every reason to believe that in even normal digestion, a certain quantity of sugar, either eaten as such, or arising from the amylolytic conversion of starch, does not pass away from the intestine into the blood as sugar, but undergoes this fermentation into lactic acid. To what extent this change takes place we do not know ; the amount probably varies according to the amount of carbohydrates eaten, the condition of the alimentary canal, and other circumstances. It may be under 478 CHANGES IN THE LARGE INTESTINE. [BOOK n. certain circumstances simply a part of normal digestion ; under other circumstances it may be excessive and give rise to troubles. That fermentative changes may occur in the small intestine is further indicated by the facts that the gas there present may contain free hydrogen, and that chyme after removal from the intestine continues at the temperature of the body to produce carbonic acid and hydrogen in equal volumes. This suggests the possibility of the sugar of the intestinal contents undergoing the butyric acid fermentation during which, as is well known, carbonic anhydride and hydrogen are evolved. By this change the sugar is removed from the carbohydrate group into the fatty acid group ; it is thus, so to speak, put on its way to become fat. We shall see hereafter that sugar may be somewhere in the body con- verted into fat ; this conversion however takes place chiefly if not wholly in the tissues, and such change as may take place in the alimentary canal is to be regarded as suggestive rather than as important. The hydrogen thus occurring in the intestine may also arise from the proteid decompositions spoken nf above. However arising it may act as a reducing agent, reducing sulphates for instance, and thus giving rise to sulphides and to sulphuretted hydrogen; as a reducing agent it assists in the formation of the faecal and urinary pigments. Thus during the transit of the food through the small intestine, by the action of the bile and pancreatic juice, and possibly to some extent of the succus entericus, assisted by various micro-organisms, the proteids are largely dissolved and converted into peptone and other products, the starch is changed into sugar, the sugar possibly being in part further converted into lactic or other acids, and the fats are largely emulsified, and to some extent saponified. These products, as they are formed, pass into either the lacteals or the portal blood vessels, so that the contents of the small intestine, by the time they reach the ileo-caecal valve, are largely but by no means wholly deprived of their nutritious constituents. So far as water is concerned, the secretion of water into the small intestine maintains such a relation to the absorption from it that the intestinal contents at the end of the ileum, though much changed, are about as fluid as in the duodenum. In the Large Intestine. § 283. The contents, whether alkaline or not in the ileum now become once more distinctly acid. This, however, is not caused by any acid secretion from the mucous membrane : the reaction of the intestinal walls in the large as in the small intestine is alkaline. It must therefore arise from acid fermenta- tions going on in the contents themselves; and that fermentations do go on is shewn by the appearance of marsh gas as well as CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 479 hydrogen in this portion of the alimentary canal. The character and amount of fermentation probably depend largely on the nature of the food, and probably also vary in different animals. Of the particular changes which take place in the large in- testine we have no very definite knowledge ; but it is exceedingly probable that in the voluminous caecum of the herbivora a large amount of digestion of a peculiar kind goes on. We know that in herbivora a considerable quantity of cellulose disappears in passing through the alimentary canal, and even in man some is digested. It seems probable that this cellulose digestion takes place in the large intestine, and is the result of fermentative changes carried out by means of micro-organisms, marsh gas being one of the products formed at the same time. Be this as it may, whether digestion, properly so called, is all but complete at the ileo-csecal valve, or whether important changes still await the chyme in the large intestine, one great characteristic of the work done in the colon is absorption. By the abstraction of all the soluble constituents, and especially by the withdrawal of water, the liquid chyme becomes as it approaches the rectum con- verted into the firm solid faeces, and the colour shifts from the bright orange, which the grey chyme gradually assumes after admixture with bile, into a darker and dirtier brown. The Faeces. § 284. These consist in the first place of the indigestible and undigested constituents of the meal : shreds of elastic tissue, hairs and other horny elements, much cellulose and chlorophyll from vegetable, and some connective tissue from animal food, fragments of disintegrated muscular fibre, fat-cells, and not unfrequently undigested starch-corpuscles. The amount of each must of course vary very largely according to the nature of the food, and the digestive powers, temporary or permanent, of the individual. In the second place, to these must be added substances not distinctly recognisable as parts of the food but derived for the most part from the secretions of the alimentary canal. The faeces contain mucus in variable amount, sometimes albumin, cholesterin, butyric and other fatty acids, lime and magnesia soaps, colouring matters, and inorganic salts, especially earthy phosphates, crystals of ammonio-magnesia phosphates being very conspicuous. The reaction is generally but not always acid. They also contain a ferment similar in its action to pepsin, and an amylolytic ferment similar to that of saliva or pancreatic juice. The bile salts are represented by a small quantity of cholalic acid, or some product of that body, and sometimes a very small quantity of taurin. The glycin and most or all of the taurin have been absorbed from the intestine, and the cholalic acid has been partly absorbed and partly decomposed. The fact that the fasces become ' clay-coloured ' 480 FJECES. [BOOK n. when the bile is cut off from the intestine shews that the bile- pigment is at least the mother of the faecal pigment ; and a special pigment, which has been isolated and called stercobilin, is said to be identical with the substance called urobilin, which may be formed from bilirubin. As other special constituents of the faeces may be mentioned excretin, a somewhat complex nitrogenous body, whose exact chemical nature is at present uncertain, and skatol (C9H9N), a nitrogenous body which like indol is derived from the decomposition of proteids by means of micro-organisms, and which is the chief cause of the faecal odour, since only a small quantity of indol remains in the faeces. These odoriferous bodies are derived directly from the food; at the same time it is quite possible that other specific odoriferous substances may be secreted directly from the intestinal wall, especially from that of the large intestine. SEC. 9. THE LACTEALS AND THE LYMPHATIC SYSTEM. § 285. We have seen that absorption does, or at least may, take place from the stomach. We have also stated that a large absorption, especially of water, occurs along the whole large intes- tine. Nevertheless it is during the transit of food along the small intestine that the largest and most important part of the digested material passes away from the canal, partly into the lacteals, partly into the portal vessels. The portal vessels are simply parts of the general vascular system ; the lacteals, into which we may at once say the greater part of the fat passes, are similarly parts of the general lymphatic system, being in fact the lymphatic vessels of the alimentary canal, and especially of the small intestine. The only reason for the special name of lacteals is that, unlike the lymphatic vessels of other parts of the body, the lymphatics of the intestine contain at times a fluid of a milky white appearance. Hence for the better understanding of absorption by the lacteals it will be desirable to study at some length the whole subject of the lymphatic system. The lymphatic vessels may be said to begin in minute passages, possessing special characters, known as lymph-capil- laries. Broadly speaking these lymph-capillaries are found, in the mammal, in all parts of the body in which connective tissue is found ; and they have special connections with those minute spaces in connective tissue which we have already more than once spoken of as lymph-spaces. Of all the varied functions of connective tissue perhaps the most important is this relation to the lymphatic system ; in nearly every part of the body connective tissue serves as the bed or origin of lymphatic vessels. These lymph-capillaries, which, as we shall see, are frequently arranged in plexuses, are continuous with other passages also minute but of a different and more regular structure, the lymphatic vessels proper, which are gathered into larger and larger vessels, all running like the blood vessels in a bed of connective tissue, until at last all the lymphatic vessels of the F. 31 482 THE LYMPHATIC VESSELS. [BOOK n. body join either the great thoracic duct which opens by a valvular orifice into the venous system at the junction of the left jugular and subclavian veins, or the small right lymphatic trunk which similarly opens into the junction of the right jugular and sub- clavian veins. The latter course is taken by the lymphatics of the right side of the head and neck, the right arm, the right side of the chest, the right lung and the right side of the heart, as well as by some vessels coming from part of the upper surface of the liver ; all the rest of the lymphatics including the lacteals fall into the thoracic duct. The lymphatic vessels, while like the veins they join in their course into larger and larger trunks, do not increase in calibre so rapidly or so regularly as do the veins ; they may run for some distance without greatly increasing in size ; and further they, unlike the veins, freely anastomose, forming plexuses. Moreover during their course they enter into peculiar relations with struc- tures known as lymphatic glands. It will be advantageous to consider separately the lymphatic vessels other than the lymph-capillaries, the lymph-capillaries themselves, and the lymphatic glands. The Lymphatic Vessels. § 286. On these we need not dwell at length since their structure-, in all essential respects, resembles that of the veins. The thoracic duct, which in man has at its lower end where it is widened into what is sometimes called the receptaculum chyli a diameter of six or seven millimetres, but is narrower higher up, may be said to possess three coats. The inner coat consists of a layer of fusiform epithelioid cells, not unlike those in a vein but more elongate and with a tendency to be sinuous in outline, and of a slender elastic lamina on which these rest. The middle coat consists of fine bundles of plain muscular fibres, which are for the most part disposed circularly but also to a certain extent obliquely and even longitudinally. The spaces between the bundles of muscu- lar fibres are occupied by connective tissue and networks of elastic fibres. The outer coat, which is not well defined either from the middle coat on the one side or the connective tissue surrounding the duct on the other side, consists chiefly of connective tissue with elastic elements, a few muscular fibres being sometimes present. The wall of the thoracic duct is essentially muscular, and from the scantiness of connective tissue and of elastic elements is more tender, more apt to be torn than the wall of a vein of corresponding size. Numerous valves are present, these like the valves of the veins being foldings of the inner coat. The smaller vessels resemble in structure the thoracic duct, the coats being of course more slender. In the majority of even smaller lymphatic vessels the muscular fibres are abundant. CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 483 Valves are especially numerous, and in many of the vessels, as for instance in those of the mesentery, just above each valve, where the tube is somewhat swollen, the muscular fibres, which elsewhere are chiefly disposed circularly, run in various directions so as to form a contractile network. The smallest vessels, springing from the distinct lymph- capillaries to be immediately described, consist of hardly more than an epithelioid lining resting on a scanty connective tissue basis. The epithelioid cells are still fusiform and regular in shape, and the calibre of each vessel is fairly uniform though, owing to the valves which are exceedingly numerous, there is a great tendency to become beaded. These smaller vessels like the others also anastomose freely. Lymph- Capillaries. § 287. The smallest lymphatic vessels just described might, from analogy with the blood vessels, almost be considered as capillary vessels ; but the name lymph-capillaries is given to vessels which joining and feeding those just described possess very different characters. They are 011 the whole larger in calibre than these, and distinctly larger than blood capillaries ; they are exceedingly irregular in shape, and in their junctions with each other form irregular labyrinths rather than formal plexuses; they possess no valves and their only coat is an epithelium of a very striking character. Like the blood capillaries their structure is revealed by the action of silver nitrate. When a piece of tissue containing lymph-capillaries, ex. gr. one taken from the tendinous portion of the diaphragm, is examined after proper treatment with silver nitrate, numerous spaces, on the whole tubular but highly irregular in form, joining into an irregular labyrinth, are seen to be lined with a layer of epithelioid plates of a peculiar kind. Each plate or cell, which is more or less polygonal or at least not dis- tinctly fusiform, is marked out by lines which are not straight and even, but very markedly sinuous, the several bulgings of one cell dove-tailing into the depressions of its neighbours and vice versa. Such epithelioid plates of sinuous outline, or such a sinuous epithelium, as we may for brevity's sake say, is characteristic of the lymph-capillaries. A lymph-capillary is in fact merely a space or areola of connective tissue, sometimes more or less tubular but frequently irregular in form, lined by a single layer of flat, transparent, nucleated epithelioid plates, each of which possesses a remarkably sinuous outline. The lymph-capillaries anastomose freely with each other and open into or join the smallest regular lymphatic canals, which, many of them smaller than the lymph-capillaries, are distinguished from these by their more regular disposition, by their epithelioid plates being fusiform with very little sinuosity of outline, and by the presence of valves. 31—2 484 LYMPH-CAPILLARIES. [BOOK n. The lacteal radicle of a villus (§ 262) is such a lymph- capillary, more or less tubular in form, or perhaps club-shaped and sometimes bifurcate or branched, placed by itself in the midst of the reticular tissue of the villus, ending, or as we should perhaps say beginning, blindly near the apex of the villus and joining below by a valvular mouth a regular lymphatic canal forming part of the network of regular lymphatic vessels with which as well as with lymph-capillaries the connective tissue of the mucous mem- brane is furnished. In other parts of the body where connective tissue runs, lymph-capillaries are more or less abundant, all passing their contents on to the more regular lymphatic canals. In certain parts, as for instance in the central nervous system, the smaller blood vessels are surrounded by large lymph-capillaries, or by regular lymphatic vessels, in the shape of tubular sheaths. In these cases the lymph-capillary forms a sort of hollow jacket around the artery or vein which, covered with a layer of sinuous epithelioid plates, lies in the middle of a tubular space lined with similar sinuous plates. The plasma which exudes through the walls of the blood vessel passes accordingly at once into the tubular space or interior of the lymph-capillary, whence it is carried away into the regular lymphatic canals. Such an arrange- ment is spoken of as a " perivascular lymphatic." § 288. The lymph-capillaries may in one sense be regarded as the beginnings of the lymphatic system ; they are the first lymphatic passages definitely lined with a continuous epithelium. But lymph exists outside these capillaries. In treating of connec- tive tissue § 105 we more than once spoke of the spaces between the interlacing bundles of fibrilL-E as lymph-spaces ; and indeed they are during life occupied by fluid which may be spoken of as lymph. It is fluid which has in some way or other passed into them from the blood stream, through the walls of the capillaries and other minute blood vessels. We shall speak of this passage as a process of transudation and shall consider its nature later on. Many of the larger of these spaces, the areolse of areolar connec- tive tissue, are completely lined by epithelioid plates with sinuous outlines; these are in fact lymph-capillaries. But many spaces, especially the smaller ones, are not so lined ; these lie outside the lymph-capillaries. Nevertheless they contain lymph, which reaching them by transudation through the walls of the blood vessels, streams from them in some way or other into the lymph - capillaries and so into the other lymphatic vessels. Coloured fluid injected by means of a fine syringe into these spaces soon finds its way into the lymphatics; and besides, in the vast majority of cases, a certain number of these spaces always intervene between the wall of the capillary or other small blood vessel from whence the lymph comes and the lymph-capillary to which the lymph goes ; the lymph must have some means or other of passing from CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 485 the spaces into the lymph-capillary. It is of course possible that the lymph transudes from the lymph-space into the lymph- capillary through the continuous sheet of epithelioid plates, in the same manner that it transudes from the blood-capillary into the lymph-space through the similarly continuous wall of the capillary ; but there are some reasons for thinking that, at places, the epithelioid lining of a lymphatic capillary may be imperfect and so allow the interior of the lymph-capillary to open out into a connective-tissue space. It will be remembered that, in the case of some of these spaces, a connective-tissue corpuscle may be found lying on the face of, or partly imbedded in, one of the bundles which form the walls of the s] >ace ; and in some cases the space appears as it were imperfectly lined with scattered flat cells, which may perhaps be regarded as transitional forms between an ordinary branched connective-tissue corpuscle and a sinuous epithelioid plate. We may perhaps regard the epithelioid plate as a differentiated connective-tissue corpuscle, whose sinuosities of outline are the remains of its previously branched condition. If this be so we may consider the lymph-capillary as a differentiated connective-tissue space, and consequently may fairly expect that the one, if it does not as suggested actually open into, should be at all events in easy communication with the other. We seem justified at least in 7 concluding that the completely lined lymph-capillaries draw their supply of lymph from the incompletely lined connective-tissue spaces. We may probably go a step still further. Many of the con- nective-tissue corpuscles are imbedded in, lie in cavities excavated out of, the cement substance which unites the fibrillas into bundles and sometimes joins the bundles together ; in some situations the corpuscles are similarly imbedded in a homogeneous ground sub- stance which has not become differentiated into fibrillae. The cavities in which these corpuscles lie are, like the corpuscles them- selves, branched and generally flattened ; they appear moreover to be generally larger than the corpuscles so as to leave a small space which can be occupied by fluid. Where two corpuscles lie near each other their spaces may, by means of the branches, communi- cate ; and in some situations, as in the body of the cornea where a number of flattened corpuscles are imbedded in the lamina of ground substance which unites each two adjacent parallel (or rather concentric) lamina? of fibrillated bundles, the series of cavities, uniting by their branches may be regarded as con- stituting a labyrinth of passages, largely but not entirely filled by the corpuscles, space being left for some amount of fluid. That fluid we need hardly say is lymph. And though the view is not one admitted on all hands, there are reasons of some weight for thinking that these cavities belonging to the corpuscles open out into the connective-tissue spaces just treated of or even more 48G ORIGIN OF LYMPHATICS. [BOOK n. directly into the lymph-capillaries. When a piece of connective- tissue, such for instance as that lying between the radiating bundles of the tendon of the diaphragm on the pleura! side is treated in a particular way, the result is what is called a "negative staining"; the matrix is stained brown but the corpuscles and ra\ities are left unstained, and appear as irregularly branched clear patches standing out in contrast with the brown matrix. In such a preparation many of these clear spaces are seen to abut upon and apparently to lose themselves in a neighbouring lymph-capillary, which also always stands out in contrast to the matrix, appearing as a clear space marked with the sinuous outlines of its plates. Without insisting too much on the argument drawn from this negative staining, and resting rather on the facts previously mentioned and on general considerations, we may probably conclude that all the spaces of connective-tissue, including the cavities of the corpuscles, form a labyrinth of passages Avhich is to be con- sidered as the real beginning of the lymphatics, and that this irregular labyrinth is in some way or other in fairly free communi- cation with the more regular but still labyrinthine lymph-capillaries, lined by a definite epithelioid lining, and that from thence the lymph passes on to the regular and valved lymphatic canals. All over the body wherever blood vessels go connective-tissue and lymph-spaces go too. Certain parts of the plasma of the blood passing through the walls of the blood vessels become lymph in these lymph-spaces. As such it soaks through not only the bundles of gelatiniferous fibrillse of the connective-tissue itself, but also the basement membrane and so the epithelium of the mucous membrane and its glands, the unstriated muscular fibre, the sarco- lemma and muscle substance of the striated fibre, the neurilemma and contents of the nerve-fibre of nerves, in fact the elements of all the tissues which are supplied with blood vessels. More than this, lymph goes where blood vessels do not go, and in these situations the value as lymph-passages of the cavities of the corpuscles seems most striking. In the cornea for instance blood vessels and definitely constituted lymphatic vessels cease near the periphery, and the greater part of the nutrition of the cornea (beyond that effected by what we may call mere imbibition, that is by the passage of fluid between the molecules of the actual substance of the tissue) is carried on by the stream of lymph through the cor- puscular cavities. In a similar way in bone lymph finds its way from the blood vessels of the periosteum, marrow and Haversian canals through the very substance of the bone by means of the labyrinth of lacunas and canaliculi. And in cartilage we have reason to think that minute passages in the matrix facilitate the transmission of lymph from the perichondrium through the body of the cartilage from cartilage cell to cartilage cell, far more efficiently than if its progress were left to mere imbibition. The CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 487 somewhat peculiar relations of the lymphatics in the central nervous system we shall consider when we come to treat of that system. Meanwhile we have said enough to form a general idea of the arrangements by means of which the very elements of all the tissues are bathed with lymph, and by means of which that lymph is carried back from the elements of the tissues along irregular and regular lymphatic channels back to the blood from whence it originally came. § 289. The Serous Cavities. In the mammal lymph-spaces are for the most part minute and microscopic ; but in some other animals they may attain considerable size; in the frog for instance in Avhich lymph-capillaries and lymphatic vessels are scanty, the large subcutaneous spaces which are disclosed when the skin of the back is cut through are in reality lymph-spaces lined by sinuous epithelioid plates. Both in the mammal and other animals certain large cavities, known as serous cavities, such as the peritoneal, pericardial, pleural and other cavities, must be considered as parts of the general lymphatic system, and indeed the ' serous fluid ' which they contain is in reality lymph. The subarachnoid space surrounding the brain and spinal cord may also perhaps be regarded as a part of the lymphatic system, but this and the contained cerebro-spinal fluid we shall consider in connection with the central nervous system. In the abdomen of the frog, on each side of the vertebral column, behind or above, i.e. dorsal to the peritoneal cavity, lies a large lymph-space spoken of as the cisterna mag no, lympliatica, the cavity of which is separated from the peritoneal cavity by a thin membranous sheet consisting of a median basis of connective-tissue covered on the peritoneal side by peritoneal epithelium and on the cisterna side by lymphatic epithelium. The latter consists, as in a lymphatic capillary, of flat epithelioid plates with sinuous outlines; the former is made up also of flat epithelioid plates but these are more or less polygonal in shape and have outlines which are not distinctly sinuous. If a piece of this partition, after being stained with silver nitrate, be spread out and examined either with the peritoneal or with the cisterna side uppermost, it will be seen that in each case here and there a group of cells assuming a triangular form appear to converge to or radiate from a centre which some- times, especially on the lymphatic side, is a mere point but some- times is a larger or smaller hole, which in other words is an orifice or stoma, sometimes closed but sometimes more or less open. On the peritoneal surface the stoma is surrounded and guarded by a crown of what appear to be small granular cells placed at the apices of the converging epithelioid plates, but which are held by some to be the displaced nuclei of the epithelioid plates themselves. Around each stoma which is in reality a perforation leading from the peritoneal cavity into the cisterna, the connective-tissue basis between the two epithelioid layers is arranged in a concentric 488 SEROUS CAVITIES. [BOOK 11. manner ; the whole arrangement serves as a communication from the peritoneal cavity into the cisterna, and by these stomata the peritoneal fluid passes into the cisterna and so into the general lymphatic system. Owing to causes which we shall study presently the contents of the small lymphatic vessels and such spaces as the cisterna are continually being drained by the vascular system ; the cisterna is continually tending to empty itself and so to draw fluid from the peritoneal cavity through the stomata. In the female frog the small granular cells encircling the stomata are, during the breeding season provided with cilia, the action of which increases the current from the peritoneum through the stoma into the cisterna. In the mammal similar stomata place the serous cavities in connection with the lymphatics of the walls of those cavities. They may be readily seen in the tendon of the diaphragm. The peritoneal membrane of the mammal as of the frog consists of a single layer of flat epithelioid plates lying on a connective- tissue basis; the plates, smaller than those in the frog, are polygonal in form, and their outline is not sinuous. On the tendon of the diaphragm the epithelioid plates over the radiating spaces, or clefts between the radiating bundles of the tendon, are smaller than over the bundles themselves, and along the lines of these radi- ating intertendinous spaces may be seen stomata, orifices guarded by small cells, similar to but smaller than and less conspicuous than those just described as seen in the frog. These stomata open into the lymphatics which are abundant in the connective tissue lying between the radiating bundles of the tendon of the diaphragm, and through them the fluid of the peritoneal cavity passes away into the lymphatics of the diaphragm and so into the general lymphatic system. The movements of the diaphragm in breathing, of which we shall have to speak presently, greatly assist the flow through the stomata; and even passive movements of the diaphragm are effectual for this purpose. If a quantity of injection material, such as a solution of Berlin blue, be injected into the peritoneal cavity of a living animal it soon enters into and injects the lymphatics of the diaphragm, and a similar injection may be obtained in a dead but recently killed animal by placing the animal with its head downwards, injecting the colouring matter into the abdomen, or even pouring it into the hollow of the diaphragm, and then producing movements of the diaphragm by a rhythmically repeated artificial respiration. Not only coloured fluids but coloured material merely suspended in fluid and such things as the globules of fat in milk, or even red blood corpuscles may thus find their way from the peritoneal cavity into the lymphatics of the diaphragm. Indeed if a piece of the diaphragm of a recently killed animal be stretched out and milk poured upon it, the fat globules of milk may be seen with the aid of a lens or microscope to disappear through the stomata in a number of minute vortices. CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 489 By similar stomata the pleural cavity is put into communica- tion with the lymphatics not only of the diaphragm (on its pleural surface) but also of the lungs, and to a smaller extent of the thoracic walls, and during the movements of the chest in breathing the contents of the pleural cavity are continually being pumped away, partly into the lymphatics of the lungs partly into those of the diaphragm and chest walls. In a similar manner pericardia! fluid passes away from the pericardial cavity, and the fluid in other smaller serous cavities such as that surrounding the testis, passes away from the respective cavities into the general lymphatics. The quantity of fluid in even the largest of these cavities is at any one time in normal conditions very small, but that fluid appears to be continually renewed, old fluid passing away to the lymphatic system, and new fluid taking its place. The serous cavities therefore are to be regarded as expanded initial reservoirs from which as well as from the lymph-capillaries and lymph-spaces of the tissues the lymph stream is continually being fed. The Structure of Lymphatic Glands. § 290. Solitary Follicles and Peyers Patches. All along the small intestine and at various points of the circumference are found, partly in the submucous tissue but reaching up to the surface of the mucous membrane, small rounded bodies, of the size of a small pin's head, more numerous perhaps in the lower than in the upper part of the bowel, often called ' solitary glands.' They are not glands however in the sense (§ 209) of being involutions of the mucous membrane, and it is better perhaps to speak of them as solitary follicles. At the free border of the small intestine, opposite to the attachment of the mesentery, the mucous membrane contains long oval patches, Peyer's patches, placed lengthways, there being some twenty or thirty of these ; they are most numerous in the ileum and disappear towards the duodenum. Each patch is practically a group of solitary follicles, and indeed these patches are sometimes spoken of as agminated follicles. In the large intestine especially at the caecum, and in man particularly in the vermiform appendix, solitary follicles are abundant, but here they lie wholly in the submucous tissue below the muscularis mucosse. In the stomach also, in young people, there occur in the mucous membrane, generally between the mouths of the glands, structures which are very similar to solitary follicles and which are sometimes called "lenticular glands." A solitary follicle consists essentially of a spherical mass of tine adenoid tissue the meshes of which are crowded with leucocytes. In the intestine as we have seen (§ 259) the con- nective tissue lying between the epithelium above and the muscularis mucosa? below has a reticular arrangement and 490 SOLITARY FOLLICLES. [BOOK n. contains leucocytes ; but in the follicle the network is finer, closer and more regular than elsewhere, the meshes are almost com- pletely filled with leucocytes, and the spherical mass breaking through the muscularis mucosse reaches some way down into the submucous tissue. Over the surface of the follicle, which bulges somewhat into the interior of the intestine, villi may be present, but the glands of Liebcrkuhn are pushed aside and are found only at its circumference. Into this mass of adenoid tissue one or more small arteries enter and break up into a capillary network the blood from which is carried away by one or more small veins. i Around the mass there is placed a more or less well developed ( spherical lymph space, lined with sinuous epithelioid plates and continuous with the neighbouring lymphatic vessels. This lymph space or lymph-sinus as it is called thus forms a hollow jacket filled with lymph round the spherical mass of adenoid tissue, but is not complete, being broken by the entering and issuing blood vessels, or by imperfect partitions passing from the tissue without to the adenoid tissue within. The blood vessels and bridles in question are covered by a layer of epithelioid plates continuous with that lining the outer wall of the jacket, as also with the one which more or less completely invests the inner mass of adenoid tissue. The leucocytes which occupy the meshes are of different sizes. Some are as large or almost as large as white blood-corpuscles, from which indeed they chiefly differ in the fact that their nuclei exhibit a nuclear network which as we have seen (§ 28) is apparently not present in the white corpuscle of the blood. The majority however are much smaller than white blood corpuscles, their smallness being chiefly due to the small amount of cell- substance surrounding the nucleus ; in some only a mere film of cell-substance can be detected so that the nucleus appears almost as a so-called ' free ' nucleus. Many of the leucocytes may be seen to be undergoing karyomitosis, indicating that they are multi- plying by division ; and indeed there are many reasons for thinking that in the adenoid tissue of these follicles and other similar structures a very considerable multiplication of leucocytes takes place. Many of the leucocytes of these follicles exhibit under favourable circumstances amoeboid movements, and the smaller leucocytes, indeed even the smallest, seem at times as active as the larger ones. A solitary follicle then may be considered as consisting in the first place of a rounded capillary network fed and drained by small arteries and veins, all supported by a minimal amount of ordinary connective tissue. In the second place the interstices of this vascular network are filled up with adenoid tissue the fine meshes of which are crowded with leucocytes of variable but on the whole small size. Lastly the rounded mass thus constituted is surrounded by a lymph sinus, the fluid of which on the one hand CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 491 bathes the mass and on the other hand is free to pass away into the neighbouring lymphatic canals. As the blood streams through the capillary network part of the plasma passing through the capillary walls becomes lymph in the meshes of the adenoid tissue. Hence, after probably acting on and being acted on by the leucocytes, it passes into the lymph sinus and so away into the general lymphatic stream. In all probability the lymph sinus is chiefly filled from the fluid thus coming from the adenoid tissue, so that a main current flows from the lymph sinus into neighbour- ing lymphatics in all directions; but it may be that the lymph sinus is partly supplied by the lymphatics around, so that some of the lymph from adjoining structures, while flowing in the sinus around the adenoid tissue, is subjected to the action of that tissue. In all probability too the transit of material from the blood to the adenoid tissue is accompanied by a reverse current from the adenoid tissue to the blood, so that the blood in passing through the follicles not only gives but also takes. Since multiplication of leucocytes appears to be continually going on in the adenoid tissue and since the follicles do not increase indefinitely in size some of the leucocytes must disappear. There is every reason to think that they pass away into the lymph sinus and so joining the general lymph stream become the corpuscles of the lymph of which we shall presently speak. If the central adenoid mass is, as some think, invested with a continuous coat of sinuous epithelioid plates, the leucocytes which leave the follicle must pass through the coat in the same manner that the white corpuscles of the blood migrate through the walls of the blood vessels ; but it is more probable that, as others think, the coating is discontinuous, the spaces of the adenoid tissue opening freely at intervals into the lymph sinus, and thus affording an easy path not only for the leucocytes but also for the fluid. The lenticular glands of the stomach appear to be only less condensed, less completely arranged masses of adenoid tissue ; and as we shall see hereafter small masses of adenoid tissue more or less condensed, more or less transformed into definite follicles are met with in various parts of the body. § 291. A Peyers Patch is, as the phrase " agminated gland " indicates, merely an aggregation of solitary follicles. A well formed Peyer's patch consists of a variable number, in man fifty or even a hundred or fewer, of solitary follicles arranged in a single layer close under the epithelium, but stretching down into the submucous tissue, the distinction of which from the mucous membrane proper is to a great extent lost by the breaking up of the muscularis mucosa?. Between the constituent follicles glands of Lieberkiihn are found encircling the follicles, and villi project from the surface, while between and below the glands blood vessels and lymphatics are abundant. Over each follicle both glands and villi are absent so that the upper surface of the 492 PEYER'S PATCHES. [BOOK n. follicle is in contact with the epithelium of the intestine, which is here shorter and more cubical than elsewhere. Each follicle consists of a somewhat spherical vascular mass of adenoid tissue surrounded more or less completely by a lymph sinus ; in fact the structure of each of these aggregated follicles repeats so completely that of a solitary follicle that the same description and discussion will serve for both. § 292. Lymphatic glands. If the structure of a follicle just described be borne in mind, that of a lymphatic gland is made more easy; for, as a Peyer's patch is a mere aggregation of otherwise unchanged follicles, so a lymphatic gland is a collection of similar follicles differentiated into a compact and somewhat complex organ. A typical lymphatic gland has, though the form varies a good deal, the shape of a kidney, in so far at all events that a more or less convex side can be distinguished from a concave side in which is placed the hilus where the blood vessels enter and issue ; from the hilus also issue lymphatic vessels, which since they carry lymph away from the gland are called efferent lymphatics. The afferent vessels carrying lymph to the gland pass into the gland in a scattered fashion on the convex side. The gland is invested by a capsule of connective tissue, containing in the case of many animals a very considerable number of plain muscular fibres. Two layers may at times be distinguished in the capsule : an outer layer of coarser and an inner layer of finer connective tissue, a rich plexus of lymphatic vessels being placed between the two. From the capsule a number of partitions or trabeculcB, starting from various points of the surface and consisting, like the capsule, of closely interwoven bundles of connective-tissue mixed up with a variable number of plain muscular fibres, pass into the gland in a direction converging towards the hilus. In the outer or circumferential part of the gland these trabecula1 are large, run in a straight direction, are but little branched, and are so arranged that they cut up the outer part of the gland into a number of chambers, having more or less the form of truncated pyramids, converging to or radiating from the inner portion of the gland near the hilus. These chambers have been called alveoli, and constitute together the cortex of the gland, the inner portion being called the medulla. On reaching the medulla the trabeculae, the course of which as we have just said is in the cortex on the whole straight and unbranched, rapidly divide becoming thinner and more slender and, running and joining together in all directions, form an irregular open network giving rise to a labyrinth of passages into which the alveoli of the cortex open. The trabeculse in fact starting from the capsule divide the gland into a number of spaces which in the cortex are arranged in a regular manner and have the form of converging chambers or CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 493 alveoli, communicating laterally with each other to a small extent only, but which in the medulla rapidly diminish in size and, opening freely into each other on all sides, form a labyrinth. At the hilus the medulla comes to the surface of the gland, but elsewhere is separated from the surface by the cortex. The number of and regularity of division among the alveoli, and the sharpness of distinction between the cortex and the medulla differ in the glands of different animals. Each alveolus of the cortex consists in its central part, constituting about two-thirds or more of the whole chamber, of a mass of adenoid tissue crowded with leucocytes ; this mass which follows the form of the chamber, is wholly like, in fact repeats almost exactly the structure of the mass of adenoid tissue of a solitary follicle of the intestine ; it is spoken of as the follicular or glandular substance or more briefly the follicle, of the alveolus. This follicle is separated on all sides from the capsule and trabecuke which form the walls of the alveolus (or from the trabeculse alone where as in some cases the alveolus is a small one lying between the larger superficial alveoli and the true medulla) by a space which is occupied as a rule not by true adenoid tissue but by a coarser more open reticular tissue, the meshes of which are larger and less regular and the bars of which are more membranous, having more the characters of being branches of nucleated branched-cells than, as we have seen, is the case with true adenoid tissue. The meshes of this reticulum like those of adenoid tissue are occupied by leucocytes ; but these are not so numerous, and moreover more readily escape from this situation than from the follicles, so that when a section of a fresh gland is brushed with a camel's hair pencil or shaken up in normal saline solution, the spaces of which we are speaking are to a large extent cleared of the leucocytes previously present, while the follicular substance still remains crowded with them. After treatment with silver nitrate it is seen that the surface of the trabeculse (and capsule) bordering this space in each alveolus is lined with sinuous epithelioid plates, and a coating of similar plates may sometimes be made out on the surface of the follicular substance. In other words this space between the trabeculae and the follicular substance is a lymph-space corresponding to the lymph sinus of the solitary follicle of the intestine, and indeed is spoken of as the lymph sinus or lymph channel ; the lymph sinus of an alveolus of a , lymphatic gland differs from the lymph sinus of a solitary follicle of the intestine in its space being much broken up by reticular tissue. The irregular passages of the medulla are similarly occupied by a central mass of follicular substance surrounded by a lymph sinus; but, whereas in the alveoli the masses of follicular substance take on the form of more or less pyramidal blocks, in the medulla the follicular substance is arranged in the form of branching and 494 LYMPHATIC GLANDS. [Booic 11. anastomosing cords, the medullary cords, surrounded by a tubular branching and anastomosing jacket of lymph sinus. At the junction of the cortex and medulla the follicles of the alveoli of the former branch off into and become the medullary cords of the latter, and the lymph sinuses of the former are similarly continuous with the labyrinth of lymph sinuses of the latter. The gland in fact may be considered as consisting of three parts : — the skeleton supplied by the capsule and trabeculae and dividing the interior of the gland into the regular alveoli of the cortex and the labyrinth of the medulla; the follicular substance occupying the centre both of the alveoli and of the labyrinth and continuous throughout both, as if it had originally filled up the whole of the spaces of the skeleton and had subsequently shrunk away on all sides ; and lastly the lymph channel occupying all the spaces left between the follicular substance and the skeleton, and thus forming a labyrinth of its own throughout the gland. Obviously a lymphatic gland is a consolidated and differentiated collection of lymphatic follicles or Peyer's patch. In a Peyer's patch each follicle is distinct and independent; in a lymphatic gland the follicles are fused together, partially so in the cortex but completely so in the nu-dulla. The afferent lymphatic vessels, which are small or medium sized vessels with the structure described in § 286, after forming a plexus between the two layers of the capsule open out into the lymph sinuses of the alveoli beneath the cortex ; these lymph sinuses are practically lymph-capillaries into which the regular afferent lymphatic vessels break up. The efferent lymphatic vessels are similarly connected with the lymph sinuses of the medulla at the hilus; here the lymph-capillaries of the me- dulla open into and form the regular lymphatic vessels which issue from the gland at this point. In the afferent vessels the lymph is flowing as we shall see, at a certain rate and under a certain pressure ; it continues to flow through the labyrinth of the lymph sinuses of the gland, bathing as it flows the follicular substance, its course being retarded by the reticulum of the lymph sinuses ; it finally issues by the efferent vessels. The small arteries entering the gland at the hilus run along the skeleton of trabeculae, dividing as they go ; at intervals they send off small branches which, leaving the trabecular support, traverse the lymph sinus and plunging into the follicular substance break up into capillaries. By far the greater part of the blood sent to the gland thus runs in capillary networks in the follicular substance of the alveoli and medulla. From these capillaries the blood finds its way back by veins through the lymph sinus to the trabecula?, and so issues from the gland at the hilus. § 293. Obviously here, as in the lymphatic follicle of the in- testine, the adenoid tissue, or follicular substance, is the seat of an interaction between the blood and the lymph ; here the blood gives CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 495 something to and takes something from the lymph, or at least is in some way changed; here the lymph takes from and gives up to tin' blood. We maybe confident that these changes take place, though our knowledge as to the exact nature of these changes is at present very limited. One event taking place in the gland seems tolerably certain. The leucocytes which occupy the meshes of the follicular substance, and the characters of which are similar to those of the leucocytes of a follicle of the intestine, multiply in the follicular substance. Cell-division appears to be particularly active in, but not exclusively confined to, certain areas in the follicles spoken of as lymph-knots. In nuclear-stained sections, that is in preparations so treated that while the nuclei are stained deeply the cell bodies are very lightly stained or not at all, there may be frequently seen in a follicle an area (or more than one area) consisting of a very light centre surrounded by a deeply stained ring. In the light centre the cell bodies of the leucocytes are, relatively to the nuclei, larger than in the surrounding zone ; and since the cell bodies are not stained the central portion appears lighter. It is in the clearer central area that nuclei undergoing mitosis, and indicating cell division, are especi- ally abundant. The surplus cell population thus arising appears to pass, chiefly at all events, into the lymph sinus, and to leave the gland by the efferent lymphatic vessels ; on examination it is found that lymph which has passed through a number of glands is richer in lymph corpuscles than the lymph which is coming to the glands. Many lymphatic glands contain a quantity of black pigment which is chiefly deposited in the branched cells of the reticulum of the lymph sinuses. This is probably, in many cases at all events, pigment brought to the gland in the lymph vessels, and arrested in its course through the lymph sinus ; and in the bronchial lymphatic glands the pigment simply consists of minute particles of carbon introduced into the bronchial passages by the inspired air, and carried from the bronchial passages to the glands. In some cases, however, pigment is also found in the bodies of the leucocytes of the follicular substance, and this pigment has probably a different origin ; its history and purpose are not however as yet known. SEC. 10. THE NATURE AND MOVEMENTS OF LYMPH (INCLUDING CHYLE). § 294. From what has been said in the preceding section we are led to regard the multitudinous spaces, both small and great, of connective tissue all over the body, including among these the " serous cavities," as forming the beginning or roots of the lymphatic system. Into these- spares certain parts. of the plasma of the blood transude and so become lymph ; (whether the epithe- lioid lining of the large serous cavities plays any distinct part in regulating the transudation of serous fluid, i.e. of lymph into those cavities we do not know) ; from these spaces the lymph is con- tinually flowing through the lymph-capillaries into the lymphatic vessels, and so by the thoracic duct and right lymphatic trunk back into the blood system. The amount of lymph occupying the lymph spaces, lymph capillaries, and minute lymphatic vessels of any region varies from time to time according to circumstances. A hand for instance which has been kept hanging down for some time becomes swollen and the skin tense ; if it be raised the swelling lessens and the skin becomes loose ; and a similar temporary swelling of the skin of the limbs, and of the skin generally, is frequently the result of active exercise. Such a swelling is partly due to the blood vessels being dilated, or to the return flow along the veins being retarded so that the blood capillaries become distended with blood, but is much more largely owing to the lymph-spaces and lymphatic vessels of the skin and underlying structures being unusually filled with lymph. On the other, hand the skin may become shrivelled and dry from a deficiency of lymph in the lymph-spaces and vessels. Under even normal circumstances the quantity of lymph in the tissues may vary considerably, and under abnormal circum- stances a very large amount of lymph may greatly distend the spaces of the connective tissue of the skin and other structures, giving rise to oedema or dropsy. Obviously there are agencies at work in the body by which the appearance of lymph in the spaces or its removal thence along the lymph-channels, or both, may be either increased or diminished. CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 49' The Characters of Lymph. § 295. As it slowly Hows from its origin in the tissues to the mouth of the thoracic duct (we may for simplicity's sake omit the right lymphatic trunk) the lymph is subjected to the influence of the lymphatic glands, and is possibly affected by the walls of the lymph-vessels. Moreover the lymph coming from one tissue differs more or less in certain characters from the lymph arising in another tissue, just as the venous blood of one organ differs from the venous blood of another organ ; and these differences may be exaggerated by the activity of the one or other tissue. Of these differences by far the most striking is that between the lymph coming from the alimentary canal during active digestion and known as chyle, and the lymph coming from other parts of the body. When digestion is not going on, and when consequently no considerable absorption of material from the alimentary canal into the lacteals is taking place, the fluid flowing along the lacteals is lymph, not differing from the lymph of other regions to any marked degree. The fluid accordingly which flows along the thoracic duct in an animal which has not been fed for some considerable time may be taken as illustrating the general characters of lymph. The contents of the thoracic duct may be obtained by laying bare the junction of the subclavian and jugular (in the dog the junction of the axillary and jugular) veins, and introducing a cannula into the duct as it enters into the venous system at that point. The operation is not unattended with difficulties. Lymph, so obtained, is a clear transparent or slightly opalescent fluid, which left to itself soon clots. The clotting is not so pronounced as that of blood, but clotting is caused as in blood by the appearance of fibrin. The fibrin which is formed though scanty, '05 p.c., is identical apparently with that of blood, and as far as we know, all that has been said previously, §§ 14 — 23, concerning the nature of clotting in blood applies equally well to lymph. Examined with the microscope Lymph contains a number of corpuscles, lymph-corpuscles, which in all their characters as far as is at present known are identical with white blood corpuscles ; they vary in size from 5 p to 15 //,, and the smaller corpuscles are much more abundant in lymph than in blood. Like the white blood corpuscles of blood they exhibit amoeboid move- ments. Their number varies in different animals, and, apparently, in the same animal, according to circumstances ; on the whole perhaps it may be said that lymph corpuscles are about as numerous in lymph as white corpuscles in blood. Even when every care is taken to avoid admixture with blood, lymph, and especially chyle, not unfrequently contains a certain number of red blood corpuscles ; sometimes these are sufficient to give the F. 32 498 CHARACTERS OF LYMPH. [BOOK n. lymph (or chyle) a reddish tinge. They have been observed within the living lymphatic vessels, even within small ones, and have probably in some manner or other made their way from the blood into the lymph channels. § 296. The chemical composition of lymph, even when taken in each case from the thoracic duct, varies a good deal. The total solids are much less than in blood, amounting in general to not \ more than 5 or G p.c. Hence the venous blood of a vascular area contains rather more solids than the arterial blood of the same area, since the blood in giving rise to the lymph during its passage through the capillaries from the arteries to the veins has parted with relatively more water than solid matter. The proteids amount on the average to about 3 or 4 p.c., that is to say, to about half as much as in blood, the particular proteids present being the same as in blood, viz. albumin, paraglobulin and antecedents of fibrin. In lymph, as distinguished from chyle, the quantity of fat is small, and consists of the usual neutral fats and the soaps of their fatty acids, together with lecithin ; cholesterin may also be present. A certain amount of sugar (dextrose) appears to be always present, and several observers have found an appreci- able quantity of urea, The ash of lymph like that of blood serum contains a considerable quantity of sodium chloride, while phos- phates and potash are scanty ; it also contains iron , apparently in too great a quantity to be accounted for by the few red corpuscles which may be present. From lymph a certain amount of gas can be extracted, consisting chiefly or almost exclusively of carbonic acid, with a small quantity of nitrogen, the amount of oxygen present being exceedingly small. The importance of this we shall see when we come to study respiration. Broadly speaking we may say that all the substances present in blood-plasma are present also in lymph, but are accompanied by a larger quantity of water. § 297. Lymph may also be obtained from separate regions of the body, as from the lower or upper limbs, for instance, by intro- ducing a fine cannula into a lymphatic vessel. In its general features the lymph so obtained resembles that taken from the thoracic duct. Analyses of the lymph distending the subcuta- neous connective tissue in cases of dropsy shew that this contains much less solid matter than normal lymph taken from the thoracic duct or larger lymphatic vessels. From this it has been inferred that the lymph normally existing in the lymph-spaces, lymph- capillaries and minute vessels contains an excess of water ; and indeed it has been asserted that the per-centage of solids increases in passing from the smaller to the larger vessels ; but this cannot be regarded as distinctly proved. The number of cor- puscles however, as we have already said, appears to be increased in passing through the lymphatic glands. It has also been stated that the lymph in the finer lymph-vessels clots even less firmly than CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 499 that in the thoracic duct. From this we may infer that some of the leucocytes in the adenoid tissue of the follicles of a lymphatic gland find their way into the lymph-sinus, and so into the efferent lymphatics, and that some of the fibrin factors are added to the lymph, or at least that some changes favourable to clotting are brought about. § 298. We shewed in § 289 that the large serous cavities of the peritoneum, pericardium &c. were to be considered as parts of the lymphatic system, and that the ' serous fluid ' in these cavities was continually joining the lymph stream ; indeed pericardial or other serous fluid has all the general characters of lymph. We have already said, § 20, that these fluids when taken fresh from the body, clot (this is, at least, the case in most animals) ; the clot when examined microscopically is found to consist of colourless corpuscles like those of lymph or of blood entangled in the meshes of fibrin. Both in their proteid and other chemical constituents these serous fluids resemble lymph. Analyses of the accumulations of fluid occasionally occurring in these cavities shew that they contain sometimes less and sometimes more solid matter than ordinary lymph. The aqueous humour of the eye contains very little solid matter ; and the cerebro-spinal fluid is so peculiar that it had better be considered by itself in connection with the nervous system. § 299. Chyle. In fasting animals the fluid flowing along the lacteals, as may be seen by inspection of the mesentery, is clear and transparent ; it is lymph, differing as we have said, in no essential respects from the lymph flowing along other lymphatic vessels. Shortly after a meal containing fat (and every meal does contain some fat), the lymph becomes white and opaque like milk, the more so the richer the meal is in fat ; it is then called chyle. Owing to the relatively large quantity of this milky fluid which for some time after a meal continues to be poured into the thoracic duct, the contents of that duct also become milky, and are also called chyle. In the thoracic duct the chyle of the lacteals is more or less mixed with lymph from other lymphatic vessels, but the former is so preponderating that the contents of the duct may be taken as illustrating the nature of chyle. Chyle differs from lymph in one important respect, and one I only : whereas lymph ordinarily contains a small quantity only of ' fat, chyle contains a very large amount. The actual amount of fat present in the chyle of the thoracic duct varies, as may be expected, very considerably, according to the nature of the meal, the stage of digestion, and various circumstances. Five per cent, is a very common amount ; in the dog it has been found to vary from 2 to 15 per cent. The increase in fat is chiefly if not ex- clusively due to an increase in the neutral fats ; though whether the small quantity of soaps and of lecithin present is greater than in lymph has not been distinctly ascertained. Cholestcriu 32—2 500 CHYLE. [BOOK n. is probably present in greater amount than in lymph, since it probably comes from the bile poured into the intestine during digestion ; but this is not certain. How far the nature of the fat, that is, the proportion of the various kinds of fat, of stearin, ^c., varies with the fats present in the meal has not been definitely ascertained. The condition of the fat in chyle is peculiar. Some of it exists, like the fat in milk, in the form of fat globules of various sizes, but all small. A very considerable quantity however is present in the form of exceedingly minute spherules or granules, far smaller than any globules to be seen in milk ; these exhibit active ' Brow man movements.' The fat present in this form is spoken of as the 'molecular basis' of chyle, and is very distinctive of chyle. In the emulsified contents of the intestine, often called chyle, the fat is finely divided, and to a large extent into small globules, but there is nothing corresponding to this molecular basis; the fat does not assume this condition until it has passed out of the intestine into the lacteals. Lymph examined \vith the microscope shews besides the white em jiuveles only very few oil-globules, and nothing of this molecular basis. Just as in fact lymph is. broadly speaking, blood minus its red corpuscles, so chyle is lymph plus a very large quantity of minutely divided neutral fat. The total amount of lymph or of chyle which enters the blood system through the thoracic duct, though it probably varies con- siderably, is probably also always very large. It has been calculated that in a well-fed animal a quantity equal at least to that of the whole blood may pass through the thoracic duct in 24 hours, and of this it is supposed that about half comes through the lacteals from the alimentary canal, and therefore to a large extent from food, and the remainder from the body at large. These calculations are based on uncertain data, and cannot therefore be taken as of exact value, but we may use them for the sake of an illustration. Thus in a man of average weight, that is, about 154 kilos., the quantity of blood (§ 38) being j1^ of the body weight is about 12 kilos. The quantity of lymph or chyle therefore discharged into the blood in an hour would be according to this calculation half a kilo, or something less than half a litre ; and since the flow must vary considerably in the 24 hours, would be sometimes less and therefore sometimes even more than this. The Movements of Lymph. § 300. Making every allowance for the uncertainty of the calculation detailed in the preceding paragraph, it is obvious that the lymph must flow with a not inconsiderable rapidity (if we take about half the above estimate, the rate will be about 5 c.c. per minute) through the thoracic duct, and therefore must also be CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 501 continually streaming into that duct, along the various lymphatic channels from the manifold lymph-spaces of the body. This onward progress of the lymph is determined by a variety of circumstances. In the first place, the remarkably wide-spread - presence of valves (§ 286) in the lymphatic vessels causes every pressure exerted on the tissues in which they lie to assist in the propulsion forward of the lymph. Hence all muscular movements increase the flow. If a camiula be inserted in one of the larger lymphatic trunks of the limb of a dog, the discharge of lymph from the cannula will be more distinctly increased by movements, even passive movements, of the limb than by anything else. When we come to speak of the entrance of chyle into the lacteal radicles of the villi we shall see that, at all events according to one view, the muscular fibres of the villus act as a kind of muscular pump, driving the chyle past the valved end of the lacteal radicle into the lymphatic canals below. In addition to the presence of valves along the course of the vessels, the opening of the thoracic duct into the venous system is guarded by a valve, so that every escape of lymph or chyle from the duct into the veins becomes itself a help to the flow. In the second place, we have already seen that the blood-pressure in the capillaries and minute vessels is considerably greater than that in the large veins, such as the jugular ; in fact this difference of pressure is the cause of the flow of blood from the capillaries to the heart. Now the lymph in the lymphatic spaces outside the capillaries and minute vessels undoubtedly stands at a lower pressure than the blood inside the capillaries ; otherwise the transudation from the blood into the tissues would be checked ; but the difference is probably much less than the difference between the pressure in the capillaries and that in the large venous trunks. So that the lymph in the lymph-spaces of the tissues may be considered a^ standing at a higher pressure than the blood in the venous trunks, for instance in the jugular vein. That is to say, the lymphatic vessels as a whole form a system of channels leading from a region of higher pressure, viz. the lymph-spaces of the tissues, to a region of lower pressure, viz. the interior of the jugular and subclavian veins. This difference of pressure will, as in the case of the blood vessels, cause the lymph to flow onward in a con- tinuous stream. Further, this flow, caused by the lowness of the mean venous pressure at the subclavian vein, will be assisted at every respiratory movement, since at every inspiration the pressure in the venous trunks becomes, as we shall see in dealing with respiration, negative, and thus lymph will be sucked in from the thoracic duct, while the increase of pressure in the great veins during expiration is warded off from the duct by the valve at its opening. In the third place, the flow may be increased by rhythmical contractions of the walls of the lymphatics themselves, which, as we have seen, are remarkably muscular ; and the 502 .MOVEMENT OF LYMPH. [BOOK n. peculiar interlacing of the muscular fibres above eaeh valve suggests that the walls here act after the fashion of a tiny heart and by a rhythmical systole drive on the fluid, which by the action of the valve below eolleets at the spot. We have however no experimental proof of this; for, though rhythmic variations ha\r been observed in the lacteals of the mesentery, it is maintained that these are simply passive, i.e. caused by the rhythmic peristaltic action of the intestine, each contraction of the intestine filling the lymph-channels more fully, and are not due to contractions of the walls of the lacteal vessels themselves. In some of the lower animals, for instance in the frog, the muscular walls of the vessels are developed at places into distinctly contractile propulsive-organs, spoken of as lymph-hearts, of which we shall have something to say presently. Lastly, it is at least open for us, on the strength of the analogy that osmosis may give rise to increased pressure on one side of a diffusion septum, to suppose that the very processes which give rise to the- appearance of lymph in the lymph-spaces of the tissues, tend themselves to promote the flow of lymph. We have at least, under all circumstances, one or other of these causes at work, promoting a continual flow from the lymphatic roots to the great veins. They are together sufficient to drive, in man, the lymph from the lower limbs and trunk, against the effects of gravity, into the veins of the neck. In the upper limb, the influences of gravity owing to the varied movements of the limb, are as often favourable to, as opposed to, the natural flow of the lymph; but as we have already said, a long-continued unfavourable action of gravity, especially in the absence of the aid of movements in the skeletal muscles, as when the arm hangs down motionless for some time, leads to accumulation of lymph at its origin in the lymph - spaces. The strength of the causes combining to drive on the lymph is strikingly shewn in animals when the thoracic duct is ligatured ; in such cases a very great distension of the lymphatic vessels below the ligature is observed. § 301. Although the phenomena of disease and, perhaps, general considerations render it probable, that the nervous system governs in some way the stream of lymph, regulating it may be not only the flow along the definite lymph-canals but also the transit of plasma into the lymph-spaces and the escape of lymph thence into the definite canals, our knowledge on these points is very imperfect. We have no proof that the muscular fibres in the wralls of the lymphatic vessels are governed by nerves, or that the lymph spaces are influenced directly by nervous action ; and most of the attempts to demonstrate any direct action of the nervous system on the lymphatics have hitherto failed. It is very difficult to dissociate any such direct action from an indirect influence through vaso-motor changes; for the condition of the vascular system largely affects the formation and hence the flow of lymph. Thus if, in a dog, cannulse having been placed CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 503 in the lymphatic trunks leading from each of the hind feet, the sciatic nerve on one side is divided, the How of lymph from the foot on that side is greater than on the intact side, but is diminished on stimulation of the peripheral end of the nerve, the diminution being followed by a subsequent increase. The section of the nerve however leads to arterial dilation, the stimulation of the nerve to arterial constriction ; and until other reasons be shewn, we may attribute the increased or diminished flow of lymph to an increased or diminished transudation from the fuller or emptier blood vessels. And this interpretation is supported by the fact that when stimulation of the nerve is so conducted as to lead to arterial dilation (§ 168) the result is not a diminished but an increased flow of lymph. Again if the cervical sympathetic in a rabbit be divided on one side and a solution of the blue pigment, sulphindigotate of soda, be injected into the venous system, the ear on that side becomes blue before the other, because the pigment passes more rapidly from the blood vessels into the lymph- spaces of the connective tissue and the blueness also passes away sooner because it is sooner washed away by the subsequent uncoloured lymph. But here too the increased transudation may be regarded as simply the result of the greater fulness of the blood vessels. § 302. The passage of material, namely, of water containing certain substances in solution, from the interior of the blood vessel where they form part of the plasma into the lymph-capillary where they are called lymph consists of two steps : the passage from the blood vessel into the lymph space, and the passage from the lymph space into the lymph-capillary ; for, as we have seen, it is only in particular places that the lymph-capillary immediately surrounds the blood vessel. Once arrived in the lymph-capillary the lymph finds an open path along the rest of the lymphatic system, but the connection between the lymph-space and the lymph-capillary is, as we have seen, peculiar and at least not a free and open one. The passage of material from the blood vessel into the lymph- space we speak of as transudation. What can we say as to the nature of this process ? There are two known physical processes with which we may compare it : diffusion through a membranous or other porous partition, and filtration through a similar partition. Diffusion, though influenced by fluid pressure, is not the direct result of fluid pressure but may on the contrary be the cause of differences of pressure on the two sides of the partition, and may work against fluid pressure. When a strong solution and a weak solution of salt are separated by a diffusion septum, diffusion takes place whether the columns of fluid be at the same level on the two sides of the septum or at different levels ; and if the columns be at the same level to start with, that of the stronger solution soon comes to exceed the other in height, on account of the osmotic 504 TRANSUDATION. [Boon n. How of water from the weaker into the stronger solution. Filtra- tion on the other hand is the direct result of pressure ; without difference of pressure filtration does not take place ; and, the filter remaining of the same nature and in the same condition, the amount of filtrate is dependent on the amount of pressure. May we speak of the process of transudation as a simple process of diffusion or a simple process of filtration, that is to say, can all the phenomena of transudation be explained as simply the results of one or other of these physical processes ? Diffusion by itself will —not account for the results ; for the proteids of the blood-plasma are indiffnsible or very nearly so and yet the lymph contains a considerable quantity of these proteids. We have no satisfactory knowledge of the exact composition of lymph as it exists in the lymph-spaces. In the lymph of the larger lymph-trunks the diffusible saline substances are present in about the same pro- portion, and the indiffusible proteids to about or less than half as much as in blood-serum ; and we may perhaps assume that the lymph in the lymph-spaces contains relatively less proteids but has otherwise the same composition as blood-plasma. Mere diffusion would not give rise to a fluid of such a nature. Can we speak of fcransudation then as a filtration? The blood is undoubtedly flowing through the capillaries and other small vessels under a certain pressure; we have seen (§ 116) that the pressure is roughly speaking about 30 mm. Hg. ; aud it would be possible to select such a filter or porous partition as would at about this pressure permit the passage of a certain quantity of the inorganic and crystalline constituents of blood-plasma to pass through in company with a relatively smaller quantity of the proteids and a large quantity of the water, the red and white corpuscles being excluded. Such a filtrate would be more or less of the nature of lymph ; and so far we might be justified in speaking of the transudation of lymph as a process of filtration. But the transit through the living wall of the blood vessel is affected bv circumstances in a manner so different from the i/ manner in which the same circumstances affect the transit through an ordinary lifeless filter, that we gain but little, and may be led into error by speaking of the process as a filtration. Sub- stances in solution or otherwise, pass through a filter when the pressure is sufficient to drive them through the passages furnished by the interstices existing in the substance of the filter. In the case of an ordinary filter the substance of the filter is within limits permanent, and the passages correspondingly constant. The living wall of a capillary however is not a constant unchanging thing. The epithelioid plates and other elements which constitute it are alive, and being alive are continually undergoing change and are especially subject to change ; moreover, as we have seen, (§§ 22, 23) the vascular walls appear to be continually acting upon and being acted upon by the blood. Hence a change in the blood CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 505 tends to cause changes in them ; and those changes may materially affect in one direction or another their action as filters. In an ordinary hlter increase of pressure necessarily entails increase of filtration ; in a living filter it may or may not, and the same increase of pressure may according to circumstances produce very different results as regards the transudation of lymph. Thus it seems reasonable to suppose as we have suggested (§ 227) that, other things being the same, an increase of blood- pressure should necessarily increase the transudation of lymph. Hence when a small artery dilates, since the pressure in the still smaller branches and capillaries of that artery is, as we have more than once pointed out, increased, more lymph appears in the lymph-spaces; indeed it is one of the main purposes of the widening of small arteries to supply the elements of the tissue with more lymph, that is, with more food. But it does not therefore follow that under all circumstances widening of the artery should increase the passage of lymph ; something may occur to counteract the natural effect of the increased pressure in the blood vessels. An instance of this seems to be afforded by the case of the submaxillary gland, when the chorda nerve is stimulated while the gland is under the influence of atropin. As we have seen, though the arteries dilate, no secretion takes place; and we cannot explain the absence of a flow into the alveoli by supposing that the extra amount of lymph which would in normal circumstances form part of the secretion, and in the case of a fairly copious secretion would be considerable, now passes away by the lymphatics without reaching the cells of the alveoli, for in such cases no extra flow in the lymphatics leading from the gland has been observed, and there is no accumulation of lymph in the con- nective tissue of the gland. Apparently, for some reason or other, in spite of the increased pressure in the blood vessels more lymph than usual does not pass into the lymph-spaces. Then again, as we shall presently have occasion to point out, an increase of pressure in the blood vessels produced by obstruction to the venous outflow is much more efficient in promoting an increase of transudation, at all events an abnormal increase, than is an increase of arterial pressure ; and the difference between the two cases appears to be too great to be accounted for on the ground that an obstruction to the venous outflow raises the pressure within the capillaries and small vessels more readily and to a higher degree than does the widening of the arteries. Moreover that obstruction to venous outflow does not produce its effects in the way of transudation simply and merely by raising the capillary pressure is shewn by the fact that the same amount of obstruction may or may not give rise to excessive transudation according to the condition of the blood or other circumstances. For instance, though the obstruction produced by ligaturing a vein frequently causes excessive transudation, it does not always 506 TRANSUDATION. [BOOK n. cause it, and the femoral vein of a dog may be ligatured without any excessive transudatiou taking place ; yet if, after the ligature, certain changes be induced in the blood excessive transudation occurs in the leg, the vein of which has been ligatured but not elsewhere. Pointing towards the same conclusion is the fact that excessive transudation more readily occurs when a vein is plugged by a thrombus arising from abnormal conditions of the vascular system than when a vein is simply ligatured. And in general we may say, and this is a point to which we shall return, that two things chiefly determine the amount of transudation : the pressure of the blood in the blood vessels, and the condition of the vascular walls in relation to the blood, the latter being at least as important as the former. Another aspect of the matter moreover deserves attention. In filtration the movement takes place through the filter in one direction only, whereas in the living body, the passage of material through the capillary wall takes place in two opposite directions. In all the tissues, though more perhaps in certain tissues than in others, the passage from the blood vessel into the lymph-space is accompanied by a passage from the lymph-space into the blood ; while food for the tissue passes in one direction, waste products pass in the other. In a secreting gland the greater part of the lymph corning from the blood vessels, the water and other matters, pass away into the lumen of the alveolus after undergoing changes in the cell ; but even in such a case there is some return from the cells into the blood vessels, carbonic acid for instance if nothing else is given up by the cells to the blood ; and in such organs as a muscle or the liver, the backward stream of material from the tissue to the blood is extensive and important. Moreover this back- ward stream works against pressure ; indeed, as may be seen in a muscle, it is when the blood vessels are dilated and the pressure in the capillaries and small vessels highest, as during and after the contraction of the muscle, that the passage from the tissue into the blood is most energetic. Many of the waste products of the tissue are it is true diffusible, and we might be tempted to say that while the lymph which feeds the tissue traverses the vascular wall by filtration in the direction of pressure the waste products return to the blood against pressure by diffusion ; but such a view cannot at present be regarded as proved ; and if it be true as is maintained by some, that lymph, including the proteids, may at times be re-absorbed from the tissue into the blood vessels, it is distinctly contradicted. We shall have to return to this question when we come to deal with the secretion of urine ; but meanwhile we may adopt the conclusion, which is especially supported by the phe- nomena of disease, that while diffusion and filtration play their respective parts, diffusible substances passing in and out of the blood more readily than indiffusible substances and an increase of pressure tending to promote transudation, the condition of the CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. f>07 vascular wall so profoundly influences the transit of material as to render the process very complex. We may probably regard it as too complex to be compared even with filtration through a filter capable of widely changing in texture from time to time, and as more nearly resembling the process of secretion. Concerning the passage of the lymph from the confined lymph- spaces into the open gangways of the lymph-capillaries we know very little. If, as some think, the cavity of the lymph-capillary is shut off on all sides and completely by a continuous lining of sinuous epithelioid plates, then the passage from the lymph-space into it must be regarded as a sort of repetition of the passage from the blood-capillary into the lymph- space, as a second transudation. But if as others think, and as on the whole seems more probable, the lymph-spaces open, at places, directly into the lymph-capillaries the passage is a simply mechanical affair determined by the freedom of these openings. In either case the flow from the lymph-spaces will be facilitated by all events which promote, and checked by those which hinder the flow of lymph along the lymph-capillaries and the other lymphatic channels. We may here remark as influencing the quantity of lymph in the lymph-spaces and vessels, that the quantity of lymph taken up from the lymph-spaces by the actual elements of the tissue may vary considerably. We remarked in § 30 on the peculiar relations of living tissue to water, and there are reasons for thinking that the very substance of a cell or a fibre (a muscular fibre for instance) may hold in itself a larger quantity of water at one time than at another. The water thus taken up or given out, and the substances which may be carried in solution by that water, come from and go to the lymph. The condition of the tissue determines by itself the amount of lymph in the lymph - spaces. § 303. Under the influence of all these several actions the lymph in the various lymph-spaces of the body varies in amount from time to time, but under normal circumstances never exceeds certain limits. Under pathological conditions those limits may be-f exceeded, and the result is known as oedema or dropsy. Similar excessive accumulations of lymph may occur not in the ordinary lymph-spaces, but in those larger lymph-spaces, the serous cavities, any large excess of fluid in the peritoneal cavity being known as ascites. The possible causes of oedema are on the one hand an obstruc- tion to the flow of lymph from the lymph-spaces, and on the other hand an excessive transudation, the lymph gathering in the lymph- spaces faster than it can be carried away by a normal flow ; with the former the lymphatic system itself, with the latter chiefly the vascular system is concerned. As a matter of fact however oedema is almost always, if not always, due to abnormal conditions f)08 OEDEMA. [BOOK n. of the vascular system, and is the result not of hindered outflow but of excessive transudation. Owing to the numerous anastomoses of the lymph-vessels and the consequent establishment of collateral streams, obstruction in the lymph -passages themselves rarely if ever gives rise to oedema ; and it may be here remarked that owing to the same free collateral communication between the lymph-vessels the laby- rinthine passages of the lymphatic-glands do not offer the serious obstacle to the onward flow of the general lymph-stream as might at first sight be supposed. Nor have we at present any knowledge which would lead us to suppose that any physiological changes in the walls of the lymphatic-vessels or of the lymph-capillaries, or in the lymph-spaces, by giving rise in some way to obstacles to the flow of lymph, ever lead to an accumulation of lymph in the latter. One kind of ojdcma we have already touched upon in speaking of the capillary circulation (§183), viz. the "inflammatory" oedema. In this kind of oedema owing to changes in the vascular walls a larger amount of transudation parses into the lymph-spaces, and that transudation is richer in proteid matters, and contains a larger amount of the fibrin factors or at all events is much more distinctly coagulable than ordinary lymph, as well as crowded with migrating corpuscles. Allied to this inflammatory o-dema. is the increase of lymph, also apparently changed somewhat in character, which appears as "effusion" in the serous cavities when these are inflamed, as in pleurisy and peritonitis. One of the most common forms of oedema is an oedema of primarily, though not wholly, mechanical origin, oedema arising from obstruction to the venous flow: under these circumstances more lymph passes into the lymph-spaces than the lymph-vessels are able to carry away. If the femoral vein be tied the leg may become oedematous, and, as we have said, oedema is a common result of the plugging or obstruction of veins through disease; the oedema which is so common an accompaniment of heart- disease involving obstruction to the return of venous blood to the right side of the heart, and the ascites which follows upon hindrance to the portal flow are instances of oedema of this kind. We have already remarked on the relation of transudation to blood-pressure ; and in venous obstruction the rise of pressure within the small blood vessels is distinguished from that due to arterial dilation by being accompanied with a want of adequate renewal of the blood ; this probably affects the epithelioid lining of the blood vessels in such a way as to increase the transu- dation. And indeed, as is seen in cases of heart disease with prolonged or repeated venous obstruction, the oedema as time goes on and the tissues become impaired is more easily excited and with greater difficulty removed, though the actual amount of obstruction, the actual increase of pressure in the small vessels, remains the same, or at least is not proportionally increased. CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 50!» Still another kind of oedema is one due to changes taking ^ place in the blood, quite apart from variations of blood-pressure. This kind of oedema is seen in some diseases of the kidney, in "Blight's disease" for instance. In such cases the blood contains less proteids, and indeed less solids, is more watery and of lower specific gravity than is normal. But the oedema is not in these cases to be explained on the view that the more watery blood passes more readily through the capillary walls, for it may be shewn experimentally that the mere thinning of the blood, as by the injection of normal saline solution into the blood vessels, will not at once lead to oedema, at least in the limbs and trunk, and it is these which in Blight's disease especially become cedematous. In all probability the oedema of Bright's disease if it be really due to the abnormal character of the blood, is produced by the abnormal blood so acting on the blood vessels that these allow a transu- dation greater than the normal. But these are pathological questions into which we must not enter here. We have touched upon them because they illustrate the important processes taking place in the lymph-spaces, and as we have more than once insisted the lymph in the lymph-spaces is the middleman of all the tissues, and hence facts illustrating the laws which govern the flow of lymph into and out of the lymph- spaces are of fundamental physiological importance. § 304. Lymph-hearts. In the frog and other amphibia and in reptiles the flow of lymph into the venous system is assisted by rhythmically pulsating muscular lymph-hearts, which present many curious analogies with the blood-heart. The frog possesses four lymph-hearts. Of these two, belonging to the hind limbs, are placed one on each side of the coccyx, near its end, and, being covered only by aponeurosis and the skin, may, without dissection, be seen beating. Two anterior ones are placed on the transverse pro- cesses of the third vertebra?, and are covered from view by the shoulder girdle. Each lymph-heart is a more or less oval sac- lying in one of those lymph sacs or cavities lined with sinuous epithelioid plates, which as we have said are present in the frog. It is continued at one end, by an orifice guarded with valves, into a small vein which opens, in the case of the posterior heart, into a crural vein, and in the case of the anterior hearts, into a jugular vein. The wall consists of muscular fibres arranged in a plexiform manner, and supported by a considerable amount of connective tissue. These fibres are striated and branched, and are intermediate in character between cardiac and skeletal mus- cular fibres. Nerve fibres terminate in these muscular fibres, and the muscular wall, unlike that of the blood-heart, is supplied with capillary blood vessels. The interior is lined with epithelioid plates of sinuous outline, and this lymphatic lining is continued along a number of openings or pores, by which the cavity of the heart opens into the surrounding lymph-space. When the 510 LYMPH-HEARTS. [BOOK n. heart contracts the contents are driven into the vein, the lym- phatic pores being closed by the approximation of the contracting muscular fibres ; when the heart dilates, the fluid in the vein is prevented from returning by the valves at its mouth, while the lymph enters readily from the surrounding space through the now open pores. In the frog regular lymphatic vessels are scanty ; hence these lymph-hearts become of considerable importance in promoting the flow of lymph. The lymph-hearts of reptilia are similar in structure and function. In the frog, in which they have been chiefly studied, the action of the lymph-hearts is in a measure dependent on the spinal cord. The posterior lymph-hearts belonging to the hind limbs are connected by means of the delicate tenth pair of spinal nerves with a region of the cord opposite the sixth or seventh vertebra, in such a way that section of the nerve or destruction of the particular region of the cord suspends or destroys their activity. The anterior pair are similarly connected with a region of the spinal cord opposite the third vertebra. Each pair therefore seems to have a ' centre ' in the spinal cord ; but it is probable, though observers are not wholly agreed, that the hearts, after destruction of their spinal centre, ultimately resume their rhythmic beats, so that the dependence of their activity on the spinal centre is not an absolute one. Like the heart of the blood-system, the lymph-hearts may be inhibited, and that in a reflex manner, the inhibition centre being moreover in the medulla oblongata If a frog be carefully observed, the activity of the lymph-hearts will be found to vary largely, and these variations appear to be in part due to nervous influences ; so that in this way the movement of lymph, and hence the pro- cesses of absorption, are in this animal directly dependent on the nervous system. SEC. 11. ABSORPTION FROM THE ALIMENTARY CANAL. § 305. We may now return to consider the absorption of the products of digestion, that is to say, the passage of these bodies from the interior of the alimentary canal, where they are really outside the body proper, into the body itself. For simplicity's sake we may consider digestion in a broad way as the conversion of practically non-diffusible proteids and starch into more diffusible peptone and highly diffusible sugar, and as the emulsifying, or division into minute particles, of fats. We have seen reason to believe that some of the sugar may be changed into lactic acid or even into butyric or other acids, that some of the proteids are carried beyond the peptone condition into leucin and other bodies, and that some of the fat may be saponified ; and it may be that some of the proteid material of the food passes into the body as albumose or even as parapeptone, or in some other little changed condition. But we may probably with safety, for present purposes, assume that the greater part of the proteid is absorbed as peptone, that carbohydrates are mainly absorbed as sugar, and that the greater part of the fat passes into the body as emulsified but otherwise unchanged neutral fat ; and we may neglect the other conditions of digested food as subsidiary, and as far as absorption is concerned, unimportant. We have seen that two paths are open for these products of digestion, one by the capillaries of the portal system, the other by the lacteals. It cannot be a matter of indifference which course is taken. For if the products pass by the lacteals they fall into the general blood-current after having undergone only such changes as they may experience in the lymphatic system ; while if they pass into the portal vein they are subjected to certain powerful influences of the liver (which we shall study in a future chapter) before they find their way to the right side of the heart. We may therefore consider first which of the two paths is, as a matter of fact, taken by the several products, and subsequently study the mechanism of absorption in the two cases. 512 ABSORPTION OF FAT. [B°OK «• The Course taken by the Several Products of Digestion. § 306. From what has already been said we have been led to regard the villi as the most active organs of absorption, and the structure of a villus leads us further to conclude that the dif- fusible peptones and sugar pass, together with the water in which they are dissolved, into the superficially placed capillary network of the villus and so into the portal system, while the merely emulsified fat, unable to traverse the wall of the capillary, passes on to the deep-seated lacteal radicle, and so finds its way into the lymphatic system. And the results of observation and experi- ment, as far as they go, support this view. Fats. After a meal containing fat the lymph of the lacteals contains fat, and is now called chyle; and the richer the meal in fat the more conspicuous is the fat in the lymph-vessels. We cannot however prove that all the fat of a meal absorbed from the alimentary is poured by the thoracic duct into the venous system. If a meal containing a known quantity of fat be given to a dog and the small quantity of fat present in the faeces corresponding to the meal be subtracted from that amount, we can determine the amount of fat absorbed, for we have no evidence whatever that any appreciable amount of fat undergoes a destructive decomposition in the alimentary canal. Collecting by means of a cannula inserted into the thoracic duct the whole of the chyle during and after the meal so long as it remains milky, shewing that fat is being absorbed, we can ascertain the quantity of absorbed fat, which would, but for the operation, have passed into the venous system. When this has been done, a very remarkable deficit, amounting it may be to 40 or 50 p.c. has been observed ; that is to say, of every 100 parts of fat which disappear from the alimentary canal only about 60 parts find their way through the thoracic duct into the venous system. Are we then to conclude that the missing quantity finds its way into the portal system ? Now the portal blood does, during digestion, contain a certain quantity of fat ; indeed the serum is said at times to appear milky from the presence of fat. But the whole circulating blood during the digestion of a fatty meal contains, for a while, the fat poured into it by the thoracic duct ; and it has been ascertained in the dog that the blood of the portal vein during digestion contains not more but less fat than the blood of the carotid artery, so that the fat which appears in the portal blood during digestion is, for the most part at least, not fat absorbed by the capillaries of the alimentary canal but fat absorbed by the lacteals. Moreover, when the chyle of the thoracic duct is diverted through a cannula, and not allowed to flow into the blood, the quantity of fat in the portal blood as in the blood at large is very small indeed. Lastly, when a villus of an intestine in full CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 513 digestion of fat is treated with osmic acid, fat cannot be recognized by the microscope within the capillaries or other blood vessels, though it abounds outside them in the substance of the villus and in the lacteal radicle. We may probably therefore infer with safety that all or at least very nearly all the fat absorbed from the intestine takes the path of the lacteals. As to the deficit mentioned above, that is as yet without explanation. It may be that in some way, on its course, in the lymphatic glands, for instance, the fat is taken away from the chyle, hidden so to speak somewhere away from both chyle and blood ; but on this point we have no exact infor- mation. § 307. Water and Salts. If, in an animal, the rate of flow of lymph or chyle through a cannula placed in the thoracic duct be watched, and water or, to avoid the injurious effect of simple water on the mucous membrane, normal saline solution be then injected in not too great quantity into the intestine, no marked increase in the flow of chyle through the cannula is observed. From this we may infer that the water of the intestinal contents is absorbed not into the lacteals but into the portal system. If however a very large quantity of the normal saline solution be injected so as to distend the intestine, then the flow of chyle is increased to some extent. It would appear therefore that while under normal conditions the water passes from the intestine mainly into the portal blood, some of it may under circumstances pass into the lacteals. With regard to the course taken by ordinary saline matters we possess no detailed information. When special salts such as potas- sium iodide and others, easily recognized by appropriate tests, are introduced into the intestine, they may be speedily detected both in the blood and in the contents of the thoracic duct; but whether, in such cases, these salts find their way into the thoracic duct by the lacteal radicle of the villi, or pass into the lymph stream at some later part of its course, we do not know. Nor can we with regard to such a salt as sodium chloride, state absolutely that it passes mainly with the water into the portal blood, though we may fairly suppose this to be the case. § 308. Sugar. Both blood and chyle contain, normally, a certain small amount of sugar; and careful inquiries shew that the percentage of sugar in chyle and in general blood is fairly constant, neither being to any marked extent increased by even amylaceous meals ; on the other hand, a meal containing sugar or - starch does temporarily increase the quantity of sugar in the portal blood. From this we may infer that such portions of the sugar of the intestinal contents as are absorbed as sugar pass exclusively by the portal vein. We may however here call attention to the difficulties attending an argument of this kind. In the first place the quantitative determination of a small amount F. 33 514 PATH TAKEN BY SUGAR. [BOOK n. of sugar in so complex a fluid as blood is attended with great difficulties and uncertainties. In the second place a very large quantity of blood is at any one moment streaming through the capillaries of the alimentary canal ; and we may perhaps speak of the quantity which passes through them during the whole period of digest iun as being enormous. Hence though each 100 cc. in passing through the capillaries might take up a quantity of sugar so small as to fall almost within the limits of errors of observation, yet the win >lc quantity absorbed during the hours of digestion might be considerable ; or to put it in another way, an error of observation, unavoidable with our present means of analysis, on a sample of blood taken from the portal vessels might lead to a wholly unwarranted conclusion that sugar was or was not being absorbed. Making every allowance however for these difficulties, the increase of sugar which has been observed in the portal blood during digestion seems too great to permit of any other conclusion than that sugar is really absorbed from the alimentary canal by the blood vessels. When however a large quantity of sugar dissolved in a large quantity of water is present in the intestine, the sugar in the chyle is said to lie increased. In such a case the excess of water, as stated above, passes into the lacteals, and in so doing appears to carry some of the sugar with it. § 309. Proteids. The difficulties attending the experimental determination of the path taken by proteids are greater even than in the case of sugar; for the exact quantitative estimation of peptone in blood (and we are assuming that proteids are mainly absorbed as peptone) is a task of the greatest difficulty, one compared with which that of estimating sugar appears almost easy. Bearing this in mind we may state that all observers are agreed that peptone is absent from chyle or at least that its presence cannot be satisfactorily proved. On the other hand, while some observers have succeeded in finding peptone in the portal blood after food, but not during fasting, many have failed to demonstrate the presence of peptone in the blood either of the portal vein or of the vessels at large even after a meal containing large quantities of proteids. Of course, as we argued in speaking of the absorption of sugar, the quantity of peptone passing into the portal blood at any moment might be small, and yet a considerable quantity might so pass during the hours of digestion. We may suppose moreover that that which does pass is imme- diately converted, possibly by some ferment action, into one or other of the natural proteids of the blood, or otherwise disposed of; and indeed peptone injected carefully and slowly into a vein disappears from the blood, though little or even none passes out by the kidney. And the view that peptone is so changed, possibly in the very act of absorption, is supported not only by the state- ment that peptone may be found in the practically bloodless wall, CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 515 that is, mucous membrane, of the intestine removed from a dead animal even when it appears to be absent from the blood, but also and especially by the following observation. If an artificial circu-^ lation of blood be kept up in the mesenteric arteries supplying a loop of intestine removed from the body, the loop may be kept alive for some considerable time. During this survival a con- siderable quantity of peptone placed in the cavity of the loop will disappear, i.e. will be absorbed, but cannot be recovered from the blood which is being used for the artificial circulation, and which escapes from the veins after traversing the intestinal capillaries. The disappearance is not due to any action of the blood itself, for peptone introduced into the blood before it is driven through the mesenteric arteries in the experiment may be recovered from the blood as it escapes from the mesenteric veins. It would seem as if the peptone were changed before it actually gets from the interior of the intestine into the interior of the capillaries. But the argument that the absence of peptone from the blood is no proof that peptone is not absorbed into the blood may also be applied to the chyle, and thus leaves us unable to draw a conclusion as to the path of the proteids. The following indirect proof that peptone does not pass into the chyle has been offered, but it too is open to objection. We shall see hereafter that the absorption of proteid material leads to an increase in the elimi- nation of urea by the kidneys. So marked is this increase, that unless there be clearly some other causes at work leading to an increase of urea, such as fever for instance, an increase of urea in the urine following upon the administration of proteid food may be taken as a proof that the proteid food has been digested and absorbed. Now if in a dog the thoracic duct be successfully ligatured so that the chyle cannot pass as usual into the blood, and the dog be fed on proteid food, as free as possible from fat, so as not unnecessarily to load the obstructed lacteals, an increase in the urea of the urine is observed as usual. Obviously in such - a case the proteid food is absorbed, and obviously also does not pass into the blood through the thoracic duct (the success of the ligature having been proved by post mortem examination). But the experiment, though as far as it goes supporting, does not rigorously prove the view that the proteids are absorbed by the capillaries of the alimentary canal ; for the thoracic duct and lymphatics below the ligature were found largely distended, and lymph and chyle appear to have escaped from the vessels ; hence it is possible that some at least of the proteids were absorbed by the lacteals of the intestine, but finding their usual path blocked made their way into the blood stream. We may therefore say that the results of experiment while they do not definitely prove, give some support to, and at least do not contradict, the view which we a little while ago put forward as probable, namely that the proteids, transformed into 33—2 516 MECHANISM OF ABSORPTION. [Boon n. diffusible peptones, pass into the blood vessels and not into the lacteals. But, if this view be provisionally accepted, it must be on the understanding that it is probable only ; and it may be that proteids do not take the same paths and are not absorbed in the same condition in all animals. The experiments just related were performed on dogs, that is to say on carnivorous animals whose (natural) food contains a considerable quantity of fat, and whose lacteals might therefore be considered as preoccupied in the ^absorption of fat. The food of herbivora on the other hand contains a relatively small amount of fat ; and if in these animals all the proteids and carbohydrates are absorbed by the blood vessels, there is comparatively little left for the lacteals to do. Yet in these animals the lacteals and the lymphatics are well developed. In the villus of a herbivorous guinea-pig or rabbit, though the reticular tissue is very scanty as compared with that present in the villus of a dog, the lacteal chamber is, relatively to the diameter of the villus, not merely as large as but much larger than in the dog. It is difficult to suppose that this wide chamber is intended solely for the absorption of the relatively small amount of fat present in vegetable food. The question which we are discussing is clearly at present to be regarded as by no means settled. The Mechanism of Absorption. § 310. The Absorption of Fats. We have now to consider the manner in which these several substances pass into either the lacteal radicle or the capillary blood vessel. It will be con- venient to begin with the absorption of the fats. We have seen reason § 280 to think that the fats, remaining chiefly as neutral fats, are emulsified in the intestine, by means of the bile and pancreatic juice, the small quantity of soap which is formed probably serving simply the purpose of facilitating the euiulsincation. The neutral fats so emulsified pass in the first instance into the bodies of the columnar cells of the villi. It has, it is true, been maintained by some that they pass between the cells and not into them ; but the evidence is distinctly against this view. The cells may again and again be seen crowded with fat, and the cases in which the fat has been seen between the cells and not in them are due to the extrusion of the fat, during the shrink- ing of the villus in the course of preparation, from the cells into spaces between the cells. In the frog, in which there are no villi, and in which the folds of mucous membrane serving the purposes of villi do not so readily shrink, the presence of fat globules in the cells after a fatty meal can always be easily demonstrated by osmic acid preparations. Since no such collections of fat globules CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 517 are B66D in the cubical cells of tin- glands of Lieberkiihn we infer that those have nothing to do with the absorption of fat. How the fat enters into the substance of the cell we do not know. We may presume that the striated border plays some part, but what part we do not know. Though, as we have seen, the rods making up the border appear able to move, to change their form, we have no evidence that the fat is introduced into the cells by means of any movements of these rods. We may imagine that the globules pass into the cell substance by help in some way of these rods, through amoeboid movements comparable with the ingestive movements of the body of an amoeba; but we have no positive evidence to support this view. We said (§ 247) that bile promotes the passage of fat through membranes, possibly by in some way promoting a closer contact between the particles of fat and the substance of the membrane ; but even if bile has this effect on the surface of the cells, its action in this respect can be subsidiary only. Within the columnar cell the fat may be seen, both in osmic acid preparations, and in fresh living cells, to be disposed in globules of various sizes, some large and some small, each globule placed in a space of the protoplasmic cell substance. It does not follow that the fat actually entered the cell exactly in the form of these globules ; it may be that the fat passes the striated border in very minute spherules which, reaching the body of the cell, run together into larger globules ; but whether this is so or not we do not know. From the columnar cell the fat passes into the spaces of the reticular tissue of the villus. It has, it is true, been contended that it passes along the substance of the bars of the reticulum ; but in carefully prepared osmic acid specimens of a villus in active digestion of fatty food, the fat may be distinctly recognized as largely filling up, still in the form of globules of various sizes, the spaces in the meshes of the reticulum which are not occupied by the leucocytes or allied wandering cells. We have seen (§ 260) that the bases of the columnar cells, through the gaps in the basement membrane, directly abut upon the labyrinth of spaces ; and the fat once out of the base of the cell is free in the spaces of this labyrinth. How it issues from the cell we do not! exactly know : possibly by a process analogous to the excretion of solid matters by an amoeba. From the labyrinth of spaces of the reticulum of the villus the fat passes into the cavity of the lacteal radicle ; and it is worthy ' of note that in the passage it undergoes a change. In the interior of the intestine, in the substance of the columnar cell, and ap- parently in the labyrinth of the reticulum it is simply emulsified fat consisting of globules small and large ; within the lacteal radicle it consists partly of the same easily recognized globules but partly of the extremely divided ' molecular basis ' (§ 299) ; it is now no longer emulsified fat but chyle. How and by what means this 518 ABSORPTION OF FAT. [BOOK n. extremely minute division of the globular fat into the 'molecular basis' takes place we do not know; nor do we know the exact manner in which the fat passes from the spaces of the reticulum into the interior of the radicle. If the sheet of sinuous epithelioid plates which forms the sole wall of the chamber is discontinuous, presenting heiv ;ind there gaps between the plates, the passage presents no difficulty in itself, but does raise the difficulty why there is so great a difference between the chyle inside the chamber and the fat outside. On the other hand, if as observations seem to shew the lining in question is actually continuous, the fat must pa— into the lacteal radicle either through the substance of the plates or through the junction lines i.f cement. Such a passage present- difficulties; but at the same time \\e can conceive that in the struggles of such a pas-age .sumo of the fat might be converted into the molecular basis. We may here perhaps remark that the contents of the lacteal radicle consist nut exclusively <>t' tat, but of fat accompanied by the proteid and other substances which go to make up the chyle. Proteid and other sub-tances beside- fat are also present in the lymph which occupies in part the labyrinth of the body of the villus, and are derived, like the lymph elseuhere, from the blond of adjacent capillaries: at least, they are in part so derived, though it may be not wholly, for as we have ju-t seen the passage of proteid material from the intestine into the substance of the villus past the capillaries though not proved, must still be con- sidered as possible. \Ve ha\e seen (§ 202) that the spaces of the reticulum of the villus are more or less occupied by wandering cells of which we spoke under the general term of leucocytes. These do not all present the same appearances and most probably are not all of the same kind. A number of them may be distinguished by the fact that the cell body is loaded with discrete granules which stain readily and deeply with certain anilin dyes, and which though not of a fatty nature turn black with osmic acid. Some of these leucocytes wander not only through the labyrinth of the reticulum but pass into the epithelium between the cells, and may project processes into, or even make their way eventually into the interior of the intestine ; or following the reverse course may wander from between the epithelium cells into the body of the villus ; some of them moreover undoubtedly contain fat. ' Hence the view has been suggested that these leucocytes are important agents, indeed the chief agents in the absorption of fat. It has been supposed that they, receiving the globules of fat into their cell substance, in fact eating the fat exactly after the manner of an amoeba, either while projecting between the columnar cells, in which case they carry their burden of fat through the epithelium into the villus, or while wandering in the labyrinth of the villus, bear it away bodily into the lymphatic system. But the number of CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 519 leucocytes really containing any appreciable quantity of fat is too small to account for the amount of fat absorbed ; since as we just pointed out in a certain kind of these cells, and this kind is often very abundant, the granules in the cell substance which stain with osmic acid are not fat. Nor is the abundance of leucocytes in the mucous membrane during the period of digestion a sure proof that they are concerned in absorption, but rather an indication only that active changes of some kind are going on, since after the administration of a saline such as magnesium sulphate, which produces effects the very reverse of absorption, these leucocytes are present in unusual numbers. Moreover under some circumstances, as in the villi of a new-born puppy after a meal of milk, they are absent even when digestion of fat is rapidly going on and the lacteals are filling with fat. In fact, what we stated above concerning the presence of fat in the bodies of the columnar cells shews that leucocytes can have little to do in transferring fat from the interior of the intestine into the body of villus ; and there are no adequate reasons for attributing to them any real share in the transference of fat from the body of the villus into the lacteal chamber. § 311. The lacteal chamber opens at the base of the villus into the valved lymphatic vessels lying below, and in these the flow of lymph (chyle) is being promoted by the various causes detailed in § 300. The pressure for instance exerted by the peristaltic contractions of the intestine helps to empty the lym- phatic vessel into which a lacteal chamber opens and so promotes the emptying of the latter. In addition to this the plain muscular fibres of the villus supply a special muscular pump for the empty- ing and filling of the lacteal chamber. These fibres and small bundles of fibres though running in various directions (§ 262) and varying in number and arrangement in different animals, take on the whole a longitudinal direction parallel to the long axis of the . villus. It has been supposed that in contracting and shortening the villus they compress the lacteal and thus empty it, and that when they relax and the villus elongates again, the emptied chamber fills once more. But a different interpretation of their action has been offered somewhat as follows. When the muscular fibres , contract they shorten the villus. In thus becoming shorter the body of the villus becomes proportionately broader, since probably no great change of bulk in the reticulum takes place ; in this broadening the part to give way will be the lacteal chamber, which thus becomes broader and larger. When the muscular fibres relax, the reticulum, the bars of which have been put on the stretch in a lateral direction, by elastic reaction brings back the villus to its former length, and the lacteal chamber elongates and narrows. On this view the muscular contraction expands and so fills, while the relaxation narrows and so empties the lacteal chamber. Which- ever view we adopt, we may at least conclude that contractions 520 ABSORPTION OF DIFFUSIBLE SUBSTANCES. [BOOK n. and relaxations of the muscular fibres in some way or other alternately fill and empty the lacteal chamber, and in all probabi- lity, at all events during digestion, rhythmical contractions of these fibres are continually going on. When the villus is shortened by the contraction of the muscular fibres, the columnar cells are compressed, becoming longer and narrower; when the muscular fibres relax and the villus elongates, the columnar cells return to their previous form. The alternating changes of form to which the columnar cells are thus subjected, and the alternating changes of pressure taking place in the reticulum, may also serve to promote the passage of material through the one and through the other. § 312. The A bsorption of Diffusible Substances and of Water. On the provisional assumption which we have made that the proteids are converted into peptone, we may consider, for the present at all events, peptone, sugar and soluble salts as together forming a class distinguished from fats by their being diffusible, some more so than others. And we have made the further provisional assumption that these pass into the blood vessels and not into the lacteals. The network of capillary blood vessels is spread as we have seen (§ 262) immediately beneath the basement membrane, and all the material which enters the lacteal chamber has to run the gauntlet of the meshes of this network. During digestion the capillaries of the intestine are filled and distended, so that at a time when absorption is taking place these meshes between the capillaries are unusually narrow. From the interior of these capillaries, here as elsewhere, transudation is taking place ; these r.-ipillarirs supply the lymph which helps to fill up the labyrinth of the reticulum and the lacteal chamber. But to a much greater extent than elsewhere (cf. § 302) this current of transudation from within the capillary to without is accompanied by a reverse current from without to within. The diffusible substances in question pass from the intestine through the layer of epithelium cells, through the attenuated reticular lymph-space between the base- ment membrane and the capillary Avail, and through the capillary wall into the blood current. Their passage consists of two stages ; that through the epithelium cells from the intestine to the lymph- space, and that from the lymph-space into the blood vessels. These two stages may be expected to differ, seeing that the structures concerned are different ; but we may at first consider them as one, and speak of the passage from the intestine into the blood as a single event. In speaking of these substances as diffusible we are using the term in reference to the well-known passage of such substances through thin membranes or porous partitions. When a strong solution of sugar or of common salt is separated by a thin mem- brane (vegetable parchment, dead urinary bladder, dead intestine, &c.) from a weak solution of sugar or of salt, the sugar or salt CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 521 passes with a certain rapidity from the stronger to the weaker solution, and water passes from the weaker solution to the stronger ; if, to begin with, simple water be substituted for the weaker solution the effect is at first still more striking. Peptone passes in thr same manner but as we have seen much mure slowly. The process is spoken of as a physical one since it is not accom- panied, necessarily, by any chemical change in the diffusing substance, nor is there any necessary change in the membrane or partition. The rate at which a substance diffuses, and the total amount of diffusion which can take place, are determined by certain qualities of the substance (which we may call physical though they depend on the chemical nature of the substance) in relation to certain qualities of the membrane ; thus two salts may diffuse through the same membrane at different rates, with different rates in the associated current of water, the osmotic current as it is called, from the weaker to the stronger solution ; and the same substance may pass at different rates through different membranes. By a number of observations, in which various substances in solution and several known membranes or partitions have been employed, a certain number of " laws of diffusion " have been established. Now if by the statement that diffusible substances pass by diffusion into the blood-capillaries of the intestine we are led to expect that the passage takes place exactly according to the laws established by observations on ordinary membranes we should be led into error ; for the disappearance of these substances from > the interior of the intestine does not take place according to the laws which regulate their disappearance from one side of an ordinary diffusion septum. This can be ascertained by introducing solutions of the substances, of various strength, into a loop of intestine, isolated in the living animal by the method described in § 250, and watching their disappearance by analysis of the contents of the loop. No very large number of experiments have been made in this way, but such as have been made all shew the difference on which we are dwelling. For instance, sodium sulphate passes through an ordinary diffusion septum with a rapidity rather greater than that of dextrose, whereas dextrose disappears from the intestine distinctly more rapidly than sodium sulphate ; peptone which diffuses very slowly indeed through an ordinary diffusion septum disappears rapidly (though not so rapidly as dextrose) from the intestine ; and when the details of the disap- pearance from the intestine of weak solutions of two salts which diffuse through an ordinary membrane at different rates, which have as it is said different osmotic equivalents, are studied, these details are quite different from those of ordinary diffusion. The more the matter is studied the more decidedly apparent becomes the difference between ordinary diffusion and the absorption of diffusible substances from the intestine. 522 ABSORPTION OF DIFFUSIBLE SUBSTANCES. [BOOK n. Moreover, in such experiments on an isolated loop of intestine, the disappearance of material from the intestine is accompanied by the appearance of material in the intestine, namely proteid and other substances ; these are derived from the blood. And the question arises, If AVC allow ourselves to regard the passage of material from the interior of the intestine into the blood as carried out by ordinary diffusion, why we should not regard tin- passage of material from the blood into the interior of the intestine as being also carried out by means of diffusion ? But such a passage we speak of elsewhere as a "secretion"; and everything which we ha\e hitherto learnt has led us to the conclusion that secretion is a different and much more complex thing from mere diffusion. Even admitting that the succus entericus is of subor- dinate importance in carrying out digestive changes, we cannot doubt that the glands of Lieberkulm secrete, and may with some reason suppose that the columnar cells of the villi do so also. Hence even if we assume the existence of an ordinary diffusion current from the blood into the intestine, accompanying and complementary to an ordinary diffusion current from the intestine into the blood, we are compelled to admit that with this there coexists, at times at all events, and in varying intensity, a current of a different and more complex nature, a current which is the result of Decretory activity. And results which at first sight seem explicable by the former, may, after all, be due to the latter. Thus the How of water into the intestine with the subsequent production of a watery stool, which follows upon the introduction into the alimentary canal of a concentrated solution of magnesium or sodium sulphate, may at first sight seem to be simply the osmotic current passing from the weaker solution of the salt, namely the blood, to the stronger solution of the salt, namely the intestinal contents. But the difference between these effects of a dose of magnesium sulphate and those of a corresponding dose of sodium chloride are much greater than can be accounted for by the diffusion phenomena, by the differing osmotic equivalents of the two substances ; and the more the matter is studied the more reason have we to believe that the flow of water produced by the former is to a large extent the result of suddenly increased secretory activity. So also the fact that the contents of the small intestine throughout its length retain the same amount of water relatively to the solids, that is to say maintain the same or nearly the same fluidity, whereas in the large intestine the water relatively diminishes until at last the faeces become firm and even dry, cannot be wrholly explained without calling into our aid variations in active secretion as distinguished from mere physical diffusion. And in the case of a purgative such as croton oil producing a watery stool, when only a minimal, we might almost say an infinitesimal amount of its own substance can at any one time be present in the intestinal walls, the result is obviously due to active secretion. CHAP, i.] TISSUES AND MECHANISMS 0V DIGESTION. 52:5 If, however, we arc thus driven to the conclusion that, the passage from the blood into the intestine is a manifestation of secretory activity in which epithelium cells play a part, gradually becoming little by little, more intelligible to us, why should we not admit that the passage from the intestine to the blood, which as we have seen does not accord in its phenomena with known processes of ordinary diffusion, is also brought about by the activity of cells, is in fact a kind of inverted secretion, and hence like ordinary secretion presents problems which cannot be solved by any off-hand references to known physical processes ? Indeed this is the conclusion towards which observation and experiment seem to be steadily leading us. Were the alveolus of a salivary gland habitually filled with a fluid of mixed and varied nature like the contents of the alimentary canal, we should probably in our study of the gland find ourselves compelled to speak of a double current as existing in the gland, of a current from the cells to the lumen of the alveolus, and of a current from the lumen to the cells. And all along the intestine both the columnar and cubical cells, which everywhere bear the marks of being " active " cells, may perhaps be regarded as engaged in a like double function. Over the villi the receptive function, in the -f glands of Lieberkiihn the ejective function is predominant ; but as we have suggested, § 265, in the glands reception probably is not wholly absent, and we may imagine that in the villi some amount of ejection (quite apart from the action of the goblet cells) may take place. If this view be accepted, if we admit that the entrance of digested food does not take place by ordinary diffusion, the question may be asked why are the digestive changes directed towards increased diffusibility, why are proteids converted into diffusible peptones, and why is starch converted into sugar ? Because though i the cell is not an apparatus for diffusion, diffusion is an instrument' of which the cell makes use. When we say that peptone does not enter the blood by ordinary diffusion we do not mean that diffusion has nothing to do with the matter. The activity of a living cell is an activity, built up upon and making use of various chemical and physical processes ; in it the processes of ordinary diffusion play their part as do the processes of ordinary chemical decomposition ; but the cell uses and modifies them for its own ends. If as we have every reason to believe the cell of a villus passes the sugar unchanged from the intestine into the blood capillary, it makes use of diffusion to effect that passage ; and if it does change the proteid into something else before it passes it on, it receives it into itself in the first instance by help of diffusion. When we say that substances - do not enter the blood by ordinary diffusion we mean that the dif- fusion which takes place in a living cell is something so different in the results from ordinary diffusion through a dead membrane that it is undesirable to speak of it by the same name. In ordinary 52-i ABSORPTION OF DIFFUSIBLE SUBSTANCES. [BOOK 11. diffusion the results depend on the relation of the molecules of the diffusing substance to the minute pores or canals or spaces in the diffusion septum. These canals or spaces are constant in an ordinary septum ; but a film of a living cell may be conceived of as a diffusion septum the pores of which are continually varying, and moreover as closing up or opening out at the touch of this or that substance ; hence the passage of material through the pores of a living cell takes place according to laws quite different from those of ordinary diffusion. § 313. The whole act of the absorption of substances with which we are dealing consists, as we have said, of two parts : the passage from the interior of the intestine through the epithelium cell into the lymph-spaces or reticulum of the villus, and the passage thence through the capillary wall into the blood- stream. In the experiments referred to above it has not been possible to distinguish between these two stages of the whole process; in each case \\e have had to make use of the terms 'from the interior of the intestine into the blood ' and ' from the blood into the interior of the intestine.' Nevertheless the remarks which have just been made may be taken as referring more especially to the first stage. They lead us to the conclusion that both fats and diffusible subtances, though in different ways, are carried into the interior of the villus by the activity of the epithelium cells. In respect to the second stage of the absorption of diffusible substances, it might be expected that part of one or other of these substances, part of the sugar for instance, arrived inside the basement membrane should slip by the capillary blood vessel and passing through the meshes of the capillary network make its way into the lacteal. And indeed, as we have seen, § 308, under certain circumstances some amount of sugar appears to take this course. But, as we have also seen, under ordinary circumstances the current, whatever be its exact nature, from the narrow lymph-spaces lying between the epithelium and the capillary into the blood-stream is strong enough to carry all or nearly all the sugar into the blood. In the establishment of this current, in this second stage of absorption diffusion always plays a part, and probably a still more conspicuous and decided part than in the first stage, seeing that the epithelioid plate of the capillary wall is a far less active structure than the columnar cell of a villus. Indeed it might be open for us to contend that this second stage was merely a matter of diffusion, whatever might be the nature of the first stage. But remembering what was said above, § 302, in discussing the transudation of lymph, it seems more in accordance with what we already know, to conclude that in this second stage also diffusion is the servant and not the master of the living capillary wall. A word may be added concerning the special case of the CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 525 peptones. As we have said, the peptones in being absorbed appear to undergo a change somewhere in the mucous membrane. We do not know exactly where or how the change takes place. It seems probable that so marked and difficult a change should require the intervention of some active living tissue, and we may therefore suppose that it is effected by the epithelium cells; but we have no exact knowledge on this point. If the change be thus carried out by means of the epithelium cells, then the latter stage of the absorption of proteids, namely the passage from the epithelium into the interior of the capillary is not a passage of diffusible peptone, but of some other non-diffusible kind of proteid. It may be however that the change takes place during the very passage of the material through the capillary wall. The view that leucocytes are the agents of the absorption of fat, by bodily taking up the fat into their cell-substance, has by some been extended to proteids ; it has been urged that these take up proteids either as peptones or in some other form and so carry them into the lymphatic system. But the evidence for this view is even less convincing than in the case of fat. CHAPTER II. RESPIRATION. SEC. 1. THE STRUCTURE OF THE LUNGS AND BRONCHIAL PASSAGES. § 314. ONE particular item of the body's income, viz. oxygen, U peculiarly associated with one particular item of the body's waste, viz. carbonic acid, in as much as the means which art- applied for the introduction of the former are also used for the getting rid of the latter. Both are gases, and the ingress of the one as well as the egress of the other is far more dependent on the simple physical process of diffusion than on any active vital processes carried on by means of tissues. Oxygen passes from the air into the blood mainly by diffusion, and mainly by diffusion also from the blood into the tissues; in the same way carbonic acid passes mainly by diffusion from the tissues into the blood, and from the blood into the air. Whereas, as we have seen, in the secretion of the digestive juices the epithelium-cell plays an all-important part, in respiration the entrance of oxygen from the lungs into the blood, and from the blood into the tissue, and the passage of carbonic acid in the contrary direction, are affected, if at all, in a wholly subordinate manner, by the behaviour of the pulmonary, or of the capillary epithelium. What we have to deal with in respiration then is not so much the vital activities of any particular tissue, as the various mechanisms by which a rapid interchange between the air and the blood is effected, the means by which the blood is enabled to carry oxygen and carbonic acid to and from the tissues, and the manner in which the several tissues take oxygen from and give carbonic acid up to the blood. We have reasons for thinking that oxygen can be taken into the blood, not only from the lungs, but also to a certain small extent CHAP, ii.] RESPIRATION. 527 from the skin, and, as we have seen, from the alimentary canal also; ;inue, crowded with a close-set capillary network, and covered on each side with an epithelium. The connective tissue is richly pro- vided with fine elastic fibres, but t he ordinary gelatiniferous fibnllse are imperfectly developed, the blood vessels being to a large extent imbedded as it were in a homogeneous matrix. The septum, especially towards its summit, is often so thin that the capillary is exposed to the air on both sides. The cells of the epithelium, which is much better shewn in the lung of a young animal, and indeed is in the adult very difficult to see, are for the most part transformed into small flat transparent plates from which the nuclei have disappeared; their outlines may be distinctly shewn by silver nitrate treatment but otherwise are often very indistinct. Between these clear Hat plates there occur small groups of cells distinguished by possessing nuclei, and by their cell-substance being granular and staining with the ordinary reagents. These granular cells, which are thicker than the clear plates, are placed in groups in the meshes of the capillary networks, so that the capillaries themselves are covered only by the thin nucleus-less plates. The wall of the iiifundibulum which forms the bases of the several alveoli has a similar structure, and is lined with an epithelium of similar character, the chief difference between the sides and the base of an alveolus being that while the blood in the capillaries of the latter is exposed to the air of the alveolus on one side only, that of the former is often exposed on both sides of even the same capillary. § 319. In describing the bronchial passages wTe had perhaps better begin with the trachea. CHAP. u. | RESPIRATION. :>:il The trachea consists of a ciliated nnicons membrane, resting on ;i coat of connective tissue, strengthened with hoops or imperfect rings of cartilage and provided with a certain amount of plain muscular tissue. A vertical section of the mucous membrane shews an epithelium consisting of three or more layers of cells, those in the uppermost layer being columnar ciliated cells (§ 93), and those in the lower layers small rounded cells, the cell- substance being scanty in proportion to the nucleus; it is supposed that some of these small cells may at times develope into ciliated cells in order to replace loss. Among ciliated cells are seen a certain number of goblet cells (§ 261). Beneath the epithelium runs a fairly distinct basement membrane, and below this in turn is seen some tine reticular tissue, like that in the small intestine (§ 259), containing in its meshes a certain number of leucocytes. Mixed u]) with the reticular tissue, which in different animals varies much in the amount present, are seen a certain but variable number of fine elastic fibres. These structures constitute together the mucous membrane, below which is a somewhat conspicuous layer of elastic fibres, arranged more or less in a network, but running distinctly longitudinally and forming a longitudinal elastic layer separating the mucous membrane above from the loose submucous connective tissue below. In this submucous tissue are placed a number of small mucous or albuminous glands, like those of the oesophagus, the ducts of which passing through the elastic layer, reticular tissue and epithelium,, open into the canal of the trachea. The outer part of this submucous tissue forms a somewhat denser coat of connective tissue, in which are lodged hoops of hyaline cartilage, that is to say, rings which are imperfect behind. Stretching trans- versely between the ends of each hoop of cartilage are several bundles of plain muscular fibres, completing the ring as it were by a muscular band ; a few longitudinally disposed muscular bundles may also be seen outside the transverse bundles. These t w< > sets of muscular fibres may be taken as being the remains of the original complete double muscular coat of the alimentary canal, almost obliterated by the introduction of the cartilaginous hoops. The main purpose served by these several structures is to provide a wide flexible elastic tube, the bore of which remains large and open and the lining smooth during the bending of the tube. The mucous fluid secreted by the goblet cells and small glands helps to arrest solid particles carried in by the inspired air, while the cilia are continually driving that mucus, with the particles entangled in it, upwards to the larynx and so into the mouth. The elastic layer adapts the mucous membrane to the variations in the length of the tube during its bending, and so keeps it smooth. The transverse muscles by contracting can some- what narrow the bore, when required; but their effect in this direction can be slight only. 34—2 532 STRUCTURE OF BRONCHIA. [BOOK n. § 320. In passing from the trachea to the bronchi and larger bronchia, the chief changes to be observed are that the cartilage- are in> longer in the form of regular hoops, but are plates placed irregularly, becoming smaller and more irregular in disposition tin- smaller the tube, and that the transverse muscular fibres become more and more prominent, forming a distinct circular coat of some thickness. The cartilages, supported by a fibrous coat of con- nective tissiK-. lie entirely outside the muscular coat, and the small glamls have their ducts lengthened so that the bodies of the glands instead of lying in the submucous tissue, lie outside the muscular layer which is pierce* 1 by their ducts. The tube becomes m>\\ distinctly a muscular tube, though the patency of its bore and ;>. certain amount of rigidity combined \\ith flexibility is still secured by the scattered plates and Hakes of car! ilage. After death, o\\in- to the contraction of the circular muscular fibres, the nmc»u^ membrane, like the internal coat of an artery in the same circum- stances, is thrown into longitudinal folds. In the smaller bronchia the cartilages disappear altogether, and the tube then consists of an outer coat of connective tissue with abundant elastic fibres and a considerable number of circularly disposed muscular fibres, and an inner coat of mucous membrane with its o\\n elastic layer: the supply of small glands still continues. As one of these bronchia plunging into a lobule divides into bronchioles, the columnar cells of the mucous membrane lose their cilia, become shorter so as to be cubical, and are disposed in a single layer or at nn>si in \ \vo layers only. At the same time the muscular fibres become more scanty, and an- disposed not as a continuous coat but in scattered rings, the connective tissue coat becomes thinner, and the glands disappear. In the bronchioles themselves as they prepare to open into infundibula, the epithelium cells become flat though still retaining granular cell-bodies. Among these however may now be seen patches in which the cells are flat transparent plates, many of which do not possess a nucleus; and towards the infundibulum these patches increase in number until the epithelium assumes the character which we previously described as characteristic of the alveoli. The muscular fibres disappear or spread out longitudi- nally, and the previously compact layer of elastic fibres now becomes scattered and spread out over the alveoli of the infundibulum and bronchiole. In this way the structure of the bronchiole gradually merges into that of an alveolus. § 321. In an infundibulum and in each of its constituent alveoli what we may consider as the original wall of a pulmonary passage, namely, a mucous membrane separated by submucous connective tissue from a muscular coat, is reduced to a thin sheet of connective tissue in which bundles of fibrillae are scanty or even absent, and which is rather to be considered as a membrane CHAP. 11.] RESPIRATION. r>:;:', of homogeneous nature containing imbedded in itself a largo i lumber of elastic fibres and fibrils with a few connective tissue corpuscles, and a network of capillaries so close set that the membrane seems to be merely elastic material filling up the meshes of the network. On the outside, this capillary membrane, if we may so call it, is continuous with the looser ordinary connective tissue, still however containing abundant elastic elements, which carries the small arteries and veins going to and coming from the capillary network, and which unites the infun- dibula and bronchioles into lobules. On the inside lies the attenuated epithelium, all the cells of which are flat and some of which are mere nucleus-less plates. The muscular fibres have either wholly disappeared or, according to some observers, persist as a few straggling fibres spreading over the infundibulum. The terminal portion of the pulmonary passage is a sac, whose walls are reduced to almost the greatest possible thinness consistent with their retaining very great elastic power. The bronchial passages of medium size are essentially elastic muscular tubes, capable like the arteries of varying their calibre, but unless their muscular fibres are thrown into unusually power- ful contractions, remaining always fairly open ; the smaller ones however, those which are devoid of cartilage, may perhaps close by collapse. These passages are lined by mucous membrane, the cells of which are well formed and active, some secreting mucus, and others by their cilia driving that mucus onwards towards the trachea. The air which passes into the lungs is frequently laden with impurities, these are entangled in the mucus of the passages, especially the smaller ones, and so are either carried upwards in the mucus, or as we shall see otherwise disposed of. The larger passages are open flexible tubes becoming more rigidly open, and less susceptible to change in calibre by muscular contraction the larger they are. § 322. The lungs are well provided with lymphatics. The reticular tissue underlying the epithelium of the mucous membrane is here and there developed into masses of true adenoid tissue crowded with leucocytes, that is to say, into more or less completely differentiated lymphatic follicles, and similar follicles are met with in deeper parts. Among the flat polygonal epithelioid plates which form the surface of the pleura! membrane investing the lung are numerous stomata (§290); and during the rhythmic movements of the lungs in breathing the lymph or serous fluid of the pleural cavity is continually being pumped into the lymphatic vessels of the lungs. These lymphatic vessels, arising from lymph-spaces in all parts of the lungs including the connective tissue around the alveoli, and running in the connective tissue binding together infundibula, bronchial tubes and blood vessels into lobules, and the lobules into lobes, find their way at last, after traversing several lymphatic (bronchial) glands to the roots of the lungs, whence 534 LYMPHATICS OF LUNG. [BOOK n. they pass from the left lung to the thoracic duct, and from the right lung to the right lymphatic trunk. The impurities in the inspired air spoken of above as arrested in the mucus lining the bronchial passages often make their way through the epithelium into the lymphatics below and, earned away in the lymph stream, are often retained in the bronchial lymphatic glands. At times these glands become in this way loaded with particles of carbon. The blood vessels of the lungs do not call for any special comment save perhaps that the pulmonary veins are destitute of valves ; and that special arteries, the bronchial arteries, starting from the aorta, are distributed to the walls of the bronchial passages, to the blood vessels, to the lymphatic glands and to the sub-pleural tissue, the blood returning from them along the bronchial veins into the right vena azygos on the right side, and into the superior intercostal vein on the left side. § 323. The nerves to the lungs come chiefly from the vagus. As, on each side, the \.-igus nerve winds round the root of the 1'iiig, it gives off in front branches to form the anterior pulmonary plexus, and then, behind, stouter branches to form the posterior pulmonary plexus. Both these, but especially the latter, are joined by filaments from the sympathetic- system, more especially from the second, third, and fourth thoracic ganglia; and it is maintained by some that fibres pass direct from the spinal (intercostal) nerves into these pulmonary plexuses. The upper part of the trachea is supplied by twigs from the recurrent laryngeal nerve on each side, and the lower part by twigs, (trachea! branches) coming direct from the vagus trunks. Some of the nerve fibres thus reaching the lung along the vagus nerve are efferent fibres for the muscular fibres of the bronchial passages and trachea. But, as we shall see, the chief and most important fibres are afferent fibres concerned in the regulation of respiration. The functions of the fibres coming from the sympathetic system have not yet been clearly ascertained ; but there is evidence that some of the fibres coming from the thoracic ganglia are vaso-motor (constrictor) fibres for the pulmo- nary vessels. SEC. 2. THE MECHANICS OF PULMONARY RESPIRATION. § 324. The lungs are placed, in a state which is always one of distension, sometimes greater, sometimes less, in the air-tight thorax, the cavity of which they, together with the heart, great blood vessels and other organs, completely fill. By the contraction of certain muscles the cavity of the thorax is enlarged. The lungs must follow this enlargement and be themselves enlarged ; other- wise the pleural cavities would be enlarged, but this is impossible so long as the walls are intact. The enlargement of the lung consists chiefly in an enlargement or expansion of the pulmonary alveoli, the air in which becomes by the expansion rarified. That is to say the pressure of the air within the lungs becomes less than that of the air outside the body ; and this difference of pressure causes a rush of air through the trachea into the lungs until an equilibrium of pressure is established between the air inside the lungs and that outside. This constitutes inspiration. Upon the relaxation of the inspiratory muscles (the muscles whose contrac- tions have brought about the thoracic expansion), the elasticity of the lungs and chest-walls, aided perhaps to some extent by the con- traction of certain muscles, causes the chest to return to its original size ; in consequence of this the pressure within the lungs now becomes greater than that outside, and thus air rushes out of the trachea until equilibrium is once more established. This consti- tutes expiration ; the inspiratory and expiratory act together form- ing a respiration. The fresh air introduced into the upper part of the pulmonary passages by the inspiratory movement contains more nxygen and less carbonic acid than the old air previously present in the lungs. By diffusion the new or tidal air, as it is frequently called, gives up its oxygen to, and takes carbonic acid from, the old or stationary air, as it has been called, and thus when it leaves the chest in expiration has been the means of both introducing oxygen into the chest and of removing carbonic acid from it. In this way, by the ebb and flow of the tidal air, and by diffusion between it and the stationary air, the whole air in the lungs is being 536 PUNCTURE OF PLEURA. [BOOK n. constantly renewed through the alternate expansion and run- traction of the chest. § 325. In ordinary respiration, the expansion of the chest never reaches its maximum ; by more forcible muscular contrac- tions, by what is called laboured inspiration, an additional thoracic expansion can be brought about, leading to tin- inrush of a certain additional quantity of air before equilibrium is established. Thi- additional quantity is often spoken of as complemental air. In the same way, in ordinan respiration, the contraction of the chest never reaches its maximum. By calling into use additional muscles, by a laboured expiration, an additional quantity of air, the so-called reserve or supplemental air, may be driven out. But even after the most toivible expiration, a considerable quantity of air, the residual air, still remains in the lungs. The natural condition of the lungs in the chest is in fact one of partial distension. The elastic pulmonary tissue is always to a certain extent on the stretch ; it is always, so to speak, striving to pull asunder the pulmonary from the parietal pleura ; but this it cannot do, because the air can have no access to the pleural cavity. \Vhen, however, the chest ceases to be air-tight. \\heii by a puncture of the cht st-wall or diaphragm, air is freely introduced into the pleural chamber, the elasticity of the lung- pulls the pulmonary away from the parietal pleura, and the lungs collapse, driving out by the windpipe a considerable quantity of the residual air. Even then, ho\\c\rr, the lungs are not completely emptied, some air still remaining in them; this is probably air imprisoned in the infundibula by collapse of the bronchioles, which as we have seen ha\e flaccid and not rigid walls. If in a living animal the pressure of the atmosphere continue to have access to the outside of a lung the air thus imprisoned is gradually absorbed and the lung becomes solid. The same result may occur from the pressure of fluid accumulated in the pleural cavity. It need hardly be added that when the pleura is punctured, and air can gain free admittance from the exterior into the pleural chamber, since the resistance to the entrance of the air into the pleural chamber is far less than the resistance to the entrance into the lungs, the effect of the respiratory move- ments is simply to drive air in and out of that chamber, instead of in and out of the lung. There is in consequence no renewal of the air within the lungs under those circumstances. If there be a sufficient obstacle to the entrance of air into the pleural chamber, such as a fold of tissue blocking up the opening, the expansion of the chest may still lead to a distension of the lungs ; and in this way in some cases puncture of the chest walls has not seriously interfered with respiration. The parietal and pulmonary pleura are, in normal circumstances, separated by a very thin layer only of fluid, so that we may perhaps speak of them as being in a state of ' adhesion,' such as obtains between two wet membranes superimposed. And it has been suggested CHAP, ii.] RESPIRATION. 537 that this adhesion, having to be overcome before the two surfaces can separate, assists in preventing the entrance of air into the pleural cavity after puncture of the thorax; but it has not been dearly shown that this is really of importance in the matter. ^ 326. Before birth the lungs contain no air; they are in the condition called atelectatic. The walls of the alveoli, the epithelial lining of which is at that time well developed, consisting of distinctly nucleated cells with granular cell-substance, are in contact, the cavity of the alveolus not having as yet come into existence ; the walls of the bronchioles are similarly in a collapsed condition, with their walls touching ; the more rigid bronchia, like the trachea, possess some amount of lumen which, however, is occupied by fluid. When the chest expands with the first breath taken, the pressure of the inspired air has to overcome the " ad- hesion," obtaining between the walls of the alveoli thus in contact with each other and also those of the bronchioles. The force spent in thus opening out and unfolding, so to speak, the alveoli and bronchioles is considerable, and in the expiration succeeding the first inspiration most of the air thus introduced remains, the force exerted by the chest in returning to its previous dimensions after the breathing in, and the elastic action of the alveoli being in- sufficient to bring the walls of the alveoli again into contact. Succeeding breaths unfold the lungs more and more until all the alveoli and bronchioles are opened up, and then the whole force of the expiratory act is directed to driving out the previously in- spired air. It is not, however, until sometime after birth that the lungs pass into that further distended state of which we spoke above. In a newly-born animal there is no negative pressure obtaining in the pleural cavities, the lungs when at rest are not on the stretch, and opening the thorax does not lead to collapse of the lungs. The state of things obtaining later on is established, not at once but gradually, and is apparently brought about by the thorax growing more rapidly, and so becoming relatively more capacious than the lungs. The distension of the lungs in the adult may be familiarly described as being due to the chest being too large for the lungs. § 327. In man the pressure exerted by the elasticity of the lungs alone amounts to about 5 or 7 mm. of mercury. This is ~k estimated by tying a manometer into the windpipe of a dead subject and observing the rise of mercury which takes place when the chest- walls are punctured. If we took 7'(i mm. as the pressure, this would be just 1/100 of the pressure of the atmosphere. If the chest be forcibly distended beforehand, a much larger rise of the mercury is observed, amounting, in the case of a distension corresponding to a very forcible inspiration, to 30 mm. In tin- living body this mechanical elastic force of the lungs may be assisted by the contraction of the plain muscular fibres of the 538 BREATHING CAPACITY. [BOOK n. bronchi ; the pressure, however, which can be exerted by these probably does not exceed 1 or 2 mm. When a manometer is introduced into a lateral opening of the windpipe of an animal, the mercury will fall, indicating a negative pressure as it is called, during inspiration, and rise, indicating a positive pressure, during expiration, both fall and rise being slight and varying according to the freedom with which the air passes in and out of the chest. When a manometer is fitted with air-tight closure into the mouth, or better, in order to avoid the suction- action of the mouth, into one nostril, the other nostril and the mouth being closed, and efforts of inspiration and expiration are made, the mercury falls or undergoes negative pressure with inspiration, and rises, or undergoes positive pressure during expiration. It has been found in this way that the negative pressure of a strong inspiratory effort may vary from 30 to 74 mm., and the positive pressure of a strong expiration from G2 to 100 mm. The total amount uf air which can be given out by the most forcible expiration following upon a most forcible inspiration, that is, the sum of the complements!, tidal and reserve airs, has been called 'the vital capacity;' 'extreme differential capacity 'is abetter phrase. It may be measured by a modification of a gas-meter called a spirnnieter ; and though it varies largely, the average may be put down at 3—4000 c.c. (200 to 250 cubic inches). Of the whole measure of vital capacity, about 500 c.c. (30 c. inch) may be put down as the average amount of tidal air, the remainder being nearly equally divided between the complemental and reserve airs. The quantity left in the lungs after the deepest expiration amounts to about 1400 or 2000 c.c. Since the respiratory movements are so easily afl'ectecl by various circumstances, the simple fact of attention being directed to the breath- ing being sufficient to cause modifications both of the rate and depth of the respiration, it becomes very difficult to fix the volume of an average breath. Thus various authors have given figures varying from 53 c.c. to 792 c.c. The statement made above is the mean of observations varying from 177 to 699 c.c. § 328. Graphic Records of Respiratory Movements. These may be obtained in many various ways. The simplest, readiest and perhaps the most generally useful method is that of recording the movements of the column of air. This may be effected by introducing a T piece into the trachea, one cross piece being left open, and the other connected with a Marey's tambour or with a receiver which in turn is connected with a tambour, see Fig. 37, and Fig. 71. The movements of the column of air in the trachea are transmitted to the tambour, the consequent expansions and contractions of which are transmitted to the recording drum by means of a lever resting on it. CHAP, ii.] INSPIRATION. 539 LD 540 GRAPHIC RECORDS OF RESPIRATION. [BOOK n. FIG. 71. AITAIUTUS FOR TAKING TRACINGS OF THE MOVEMENTS OF THK COLUMN OF AIR IN RESPIKATION. The recording apparatus shewn is the ordinary cylinder recording apparatus. The cylinder A covered with smoked paper is by means of the friction-plate B put into revolution by the spring clock-work in C regulated by Foucault's regulator D. By means of the screw E, the cylinder can be raised or lowered, and by means of the screw F its speed may be increased or diminished. The tracheotomy tube t fixed in the trachea of an animal is connected by india- rubber tubing a with a glass T piece inserted into the large jar G. From the other end of the T piece proceeds a second piece of tubing b, the end of which can be either closed or partially obstructed at pleasure by means of the screw clamp c. From the jar proceeds a third piece of tubing d, connected with a Marey's tambour m (see Fig. 37), the lever of which / writes on the recording surface. When the tube b is open the animal breathes freely through this, and the movements in the air of G and consequently in the tambour are slight. On closing the clamp c, the animal breathes only the air contained in the jar, and the movements of the lever of the tambour become consequently much more marked, Below the lever is seen a small time-marker n connected with an electro-magnet, the current through which coming from a battery by the wires x and y is made and broken by a clock-work or metronome. If, a receiver being used, the open end of the |— be closed, the animal breathes into and out of the receiver, and the movements of the tambour are greatly increased. This has the disadvantage that the air in the receiver soon becomes unfit for further respiration. A similar increase of the movements of the lever of the tambour may be obtained by connecting a piece of india-rubber tubing to the open end of the |— . By increasing the length of this tube, or slightly constricting it, the movements of the lever may be increased without very seriously interfering \\itli the breathing of the animal. In another method the movements of the chest are recorded. When a small animal such as a rabbit is used, the whole animal may be placed in an air-tight box, breathing being carried on by means of a tube inserted into the trachea and carried through an air-tight orifice in the wall of the box. By another orifice and tube the air in the box is brought into connection with a tambour, which accordingly registers the changes of pressure in the air of the box produced by the move- ments of the chest (and body) and thus indirectly the movements of the chest. In man and larger animals the changes in the girth of the chest may be conveniently recorded by means of Marey's pneumograph. This consists of a hollow elastic cylinder, or a cylinder with elastic ends, the interior of which is connected with a tambour. By means of a strap attached to each end of the cylinder the instrument can be buckled round the chest like a girdle. When the chest expands, the ends of the cylinder are pulled out, and the air within the chamber rarefied ; in consequence the lever of the tambour connected with its interior is depressed ; conversely, when the chest contracts, the lever is elevated. The pneumatograph of Fick is somewhat similar. Or changes in one or other diameter of the chest may be recorded by what may be called the 'callipers' method, as in the recording stethometer of Burden-Sanderson. This consists of a rectangular framework con- structed of two rigid parallel bars joined at right angles to a cross piece. The free ends of the bars, the distance between which can be regulated at pleasure, are armed, the one with a tambour, the other simply with an ivory button. The tambour bears on the metal plate CHAP, ii.] UKS1MKATION. :> 11 of its membrane (///' Fig. .°>7) a small ivory button in place of the lever. "When it is desired to record the changes occurring in any diameter of the chest, >•.sels, and arranged so that while one end of the slip is securely fixed to the chest wall as a tixed point, the other end can by a thread be brought to bear on a lever. The slip, even when thus arranged, appears to contract rhythmically in complete unison with the con- tractions of the whole rest of the diaphragm ; it serves so to speak as a sample of the diaphragm ; and hence its contractions like those of the whole diaphragm may be taken as a record of respiratory movement^ The record has to be corrected for variations in the position of the tixed point. §329. In these various ways curves are obtained, which, while differing in detail, exhibit the same general features, and more or less i-r^mble the curve' shewn in Fig. 72. FIG. I'l. TRACING OF THORACIC RESPIRATORY MOVEMENTS OBTAINED BY MEANS OF MAREY'S PNEI-.MO<;RAPH. A whole respiratory phase is comprised between a and «: inspiration, during which the lever , and expiration from b to a. Tho undulations at c are caused by the heart's beat. As the figure shews, inspiration begins somewhat suddenly and advances rapidly, being followed immediately by expiration, which is carried out at first rapidly, but afterwards more and more slowly. Such pauses as are seen usually occur between the end of expiration and the beginning of inspiration. In normal breathing, hardly any such pause exists, but in cases where the respiration becomes infrequent, pauses of considerable length may be observed. As we shall see in detail hereafter, the several parts of the whole act vary much, under various circumstances, in relation to each other. Sometimes expiration, sometimes inspiration is prolonged ; and either inspiration or expiration may be slow or rapid in its development. At times the chest may remain for a while at the height of inspiration, thus making a pause between inspiration and expiration. In what may be considered as normal breathing, the respiratory act is repeated about 17 times a minute, the duration of the inspiration as compared with that of the expiration (and such pause as may exist) being about as ten to twelve ; but the rate varies very largely ; and in this as in the volume of each breath it CHAP, ii.] RKSPIKATION. 543 i- M TV difficult. to lix a satisfactory average, the figures given varying from '20 to 13 a minute. It varies accord ing to age and sex. It is influenced by the position of the bod)', being quicker in standing than in lying, :md in lying than in sitting. Muscular d* */ <_? ' \J C3 CJ exertion and emotional conditions affect it deeply. In fact, almost every event which occurs in the body may influence it. We shall have to consider in de-tail hereafter the manner in which these influences are brought to bear. When the ordinary respiratory movements prove insufficient to effect the necessary changes in the blood, their rhythm and character become changed. Normal respiration gives place to laboured respiration, and this in turn to dyspnoea, which, unless some restorative event occurs, terminates in asphyxia. These abnormal conditions we shall study more fully hereafter. The Respiratory Movements. § 330. When the movements of the chest during normal breathing are watched, or when a graphic record is taken by one or other of the methods just described, it is seen that during inspira- tion an enlargement takes place in the antero-posterior diameter, the sternum being thrown forwards, and at the same time moving upward. The lateral width of the chest is also increased. The vertical increase of the cavity is not so obvious from the outside, though when the movements of the diaphragm are watched by means of an inserted needle or otherwise, it is clear that the upper surface of that organ descends at each inspiration, the anterior walls of the abdomen bulging out at the same time. In the female hitman subject, the movement of the upper part of the chest is very conspicuous, the breast rising and falling with every respiration ; in the male, however, the movements are almost entirely confined to the lower part of the chest. In laboured respiration all parts of the chest are alternately expanded and contracted, the breast rising and falling as well in the male as in the female. We have now to consider these several movements in greater detail, an< 1 t o study the means by which they are carried out. § 331. Inspiration. There are two chief means by which the chest is enlarged in normal inspiration, viz. the descent of the diaphragm and the elevation of the ribs. The former causes that movement in the lower part of the chest and abdomen so characteristic of male breathing, which is hence called diaphragm- atic ; the latter causes the movement of the upper chest character- istic of female breathing, which is called costal. These two main factors are assisted by less important and subsidiary events. Even in the female human subject, the share taken in respira- tion by the diaphragm is an important one, in the male the diaphragm must be regarded as the chief respiratory agent, and in some animals its use, for this purpose, is so prominent that the 544 MOVEMENTS OF INSPIRATION. LBoOK "• movements of the ribs may in normal breathing be almost neglected. In the rabbit for instance, in normal breathing, almost all the respiratory \vork is done by the contractions of the dia- phragm. Tin- descent of the diaphragm is effected by means of the contraction of its muscular fibres. When at rest the diaphragm presents a convex surface to the thorax; \vhen contracted it becomes much Halter, and in consequence the level of the chest- tloor is lowered, the vertical diameter of the chest being pro- portionately enlarged. In descending, the diaphragm presses OE the abdominal viscera, and 80 causes a projection of the flaccid ab- dominal walls. From it s attachments to the sternum and the false ribs, the diaphragm, while contracting, naturally tends to pull the sternum and the upper false ribs downwards and inwards, and the lower false ribs upwards and inwards, towards the lumbar spine. In normal breathing, this tendency produces little effect, being counteracted by the accompanying general costal elevation, and by certain special muscles to be mentioned presently. In forced inspiration, however, and especially where there is any obstruction to the entrance of air into the lungs, the lower ribs may be so much drawn in by the contraction of the diaphragm, that the girth of the trunk at this point i- obviously diminished. §332. The elevation of the rib*« is a much more complex matter than the descent of the diaphragm. If we examine anyone rib, such as the fifth, we find that while it moves freely on its vertebral articulation, it inclines \\hen in the position of rest in an oblique direction from the spine to the sternum; hence it is obvious that when the rib is raised, its sternal attachment must not only be carried upward, but also thrown forward. The rib may in tact be regarded as a radius, moving on the vertebral articulation as a centre, and causing the sternal attachment to describe an arc of a circle in the vertical plane of the body; as the rib is carried upwards from an oblique to a more horizontal position, the sternal attachment must of necessity be carried farther awa\ in front of the spine. Since all the ribs have a downward slanting direction, they must all tend, when raised towards the horizontal position, to thrust the sternum forward, some more than others according to their slope and length. The elasticity of the sternum and costal cartilages, assisted by the articulation of the sternum to the clavicle above, permits the front surface of the chest to be thus thrust forwards as well as upwards, when the ribs are raised. By this action, the antero-posterior diameter of the chest is enlarged. Since the ribs form arches which increase in their sweep as one proceeds from the first down wards as far at least as the seventh, it is evident that when a lower rib such as the fifth is elevated so as to occupy or to approach towards the position of the one above it, the chest at that level will become wider from side to CHAP, ii.] RESPIRATION. :,\:> in proportion as the (it'lh ,-uvli is wider than the fourth. Thus the elevation of the rib increases not only the antero-posterior but also the transverse diameter of the chest. Further, on account of the resistance of the sternum, the angles between the ribs and their cartilages are, in the elevation of the ribs, somewhat opened out, and thus also the transverse as well as the antero-posterior diameter, somewhat increased. In more than one way, then, the elevation of the ribs enlarges the dimensions of the chest. § 333. The ribs are raised by the contraction of certain muscles. Of these the external intercostals are perhaps the most important. Even in the case where two ribs, such as the fifth and sixth, are isolated from the rest of the thoracic cage, by section of the structures occupying the intercostal spaces above and below, the contraction of the external intercostal muscle of the inter- vening space raises the two ribs, thus bringing them towards the position in which the fibres of the muscle have the shortest length, viz. the horizontal one. — This elevating action is, in the entire chest, further favoured by the fact that the first rib is less moveable than the second, and so affords a comparatively fixed base for the action of the muscles between the two, the second in turn supporting the third, and so on, while the scaleni muscles in addition .serve to render fixed, or to raise, the first two ribs. ^>So| that in normal respiration, the act may probably be described as beginning by a contraction of the scaleni. The first two ribs being thus raised or at least fixed, the contraction of the series of external intercostal muscles acts at a great advantage. While the elevating, i.e. inspiratory action of the external intercostals is admitted by nearly all authors, the function of the internal intercostals has been much disputed. Some regard their action as wholly inspiratory ; others maintain, what is perhaps the more commonly adopted view, that while those parts of them which lie between the sternal cartilages act like the external intercostals as elevators, i.e. as inspiratory in function, those parts which lie between the osseous ribs act as depressors, i.e. as ex- piratory in function. In the well-known model consisting of two rigid bars, repre- senting the ribs, moving vertically by means of their articulations with an upright representing the spine, and connected at their free ends by a piece representing the sternum, it is undoubtedly true that stretched elastic bands attached to the bars in such a way as to represent respectively the external and internal intercostals, viz. sloping in the one case downwards and forwards and in the other downwards and backwards, do, on being left free to contract, in the former case elevate and in the latter depress the ribs. Such a. model however does not fairly represent the natural conditions of the ribs, which are not straight, and rigid, but peculiarly curved and of varying elasticity, capable moreover of rotation on their own axes, and having their movements determined by the characters of F. 35 546 MOVEMENTS OF THE RIBS. [BOOK n. their vertebral articulations. The mechanical conditions in fact of these muscles are so complex, that a deduction of their actions from simple mechanical principles, or from the direction of the fibres, must be exceedingly difficult and dangerous. Actual experi- ments on the cat and dog tend to shew that in these animals the contraction of the internal intercostals, along their whole length, takes place, in point of time, alternately with that of the diaphragm, and thus afford an argument in favour of these muscles being expiratory in function. Next in importance to the external intercostals come the levatores costarum, which, though small muscles, are able, from the nearness of their costal insertions to the fulcrum, to produce considerable movement of the sternal ends of the ribs. The external intercostals and the levatores costarum with the scaleni may fairly be said to be the elevators of the ribs, i.e. the chief muscles of costal inspiration in normal breathing. It must be added however that some observers deny that either set of intercostal muscles take' any important part in raising the ribs. They hold thai the chief if not the only use of these muscles is by their contraction t<> render the intercostal spaces firm and the whole thoracic cage rigid, so that the thorax is moved as a whole by the other muscles mentioned, and the intercostal spaces do not give way during the respiratory movements. Additional space in the transverse diameter is afforded probably by the rotation of the ribs on an antero-posterior axis; but this movement is quite subsidiary and unimportant. When the chest is at rest, the ribs are somewhat inclined with their lower borders directed inwards as well as downwards. When they are drawn up by the action of the intercostal muscles, their lower borders are everted. Thus their flat sides are presented to the thoracic cavity, which is thereby slightly increased in width. $ 334. Lulniirt'd Inspiration. When respiration becomes laboured, other muscles are brought into play. The scaleni are strongly contracted, BO as distinctly to raise or at least give a very fixed support to the first and second ribs. In the same way the serratus posticus superior, which descends from the fixed spine in the lower cervical and upper dorsal regions to the second, third, fourth, and fifth ribs, by its contractions raises those ribs. In laboured breathing a function of the lower false ribs, not very noticeable in easy breathing, comes into play. They are depressed, retracted, and fixed, thereby giving increased support to the diaphragm, and directing the whole energies of that muscle to the vertical enlargement of the chest. In this way the serratus posticus inferior, which passes upward from the lumbar aponeurosis to the last four ribs, by depressing and fixing those ribs becomes an adjuvant inspiratory muscle. The quadratus lumborum and lower portions of the sacro-lumbalis may have a similar function. All these muscles may come into action even in breathing CHAI>. ii.] RESPIRATION. 547 which, though deeper than usual, can hardly perhaps be called laboured. When, however, the need for greater inspiratory efforts becomes urgent, all the muscles which can, from any fixed point, act in enlarging the chest, come into play. Thus the arms and shoulder being fixed, the serratus inagnus passing from the scapula to the middle of the first eight or nine ribs, the pectoralis minor passing from the coracoid to the front parts of the third, fourth, and fifth ribs, the pectoralis major passing from the humerus to the costal cartilages, from the second to the sixth, and that portion of the latissimus dorsi which passes from the humerus to the last three ribs, all serve to elevate the ribs and thus to enlarge the chest. The sterno-mastoid and other muscles passing from the neck to the sternum, are also called into action. In fact, every muscle which by its contraction can either elevate the ribs or contribute to the fixed support of muscles which do elevate the ribs, such as the trapezius, levator anguli scapulae and rhomboidei by fixing the scapula, may, in the inspiratory efforts which accompany dyspnoea, be brought into play. § 335. Expiration. In normal easy breathing, expiration is in the main a simple effect of elastic reaction. By the inspiratory effort the elastic tissue of the lungs is put on the stretch ; so long as the inspiratory muscles continue contracting, the tissue remains stretched, but directly those muscles relax, the elasticity of the lungs comes into play and drives out a portion of the air contained in them. Similarly the elastic sternum and costal cartilages are by the elevation of the ribs put on the stretch : they are driven into a position which is unnatural to them. When the intercostal and other elevator muscles cease to contract, the elasticity of the ster- num and costal cartilages causes them to return to their previous position, thus depressing the ribs, and diminishing the dimensions of the chest. When the diaphragm descends, in pushing down the abdominal viscera, it puts the abdominal walls on the stretch : and hence, when at the end of inspiration the diaphragm relaxes, the abdominal walls return to their place, and by pressing on the ab- dominal viscera, push the diaphragm up again into its position of rest. ^-"Expiration then during easy breathing is, in the main?— simple elastic reaction; but there is probably some, though possibly in most cases, a very slight, expenditure of muscular energy to bring the chest more rapidly to its former condition. This is, as we have seen, supposed by many to be afforded by the internal intercostals acting as depressors of the ribs. If these do not act in this way, we may suppose that the elastic return of the abdominal walls is accompanied and assisted by a contraction of the abdominal muscles. The triangularis sterni, the effect of whose contraction is to pull down the costal cartilages, may also be regarded as an expiratory muscle. When expiration becomes laboured, the abdominal muscles become important expiratory agents. By pressing on the contents 35—2 548 MUSCLES OF EXPIRATION. [BOOK n. of the abdomen, they thrust them and therefore the diaphragm also up towards the chest, the vertical diameter of which is thereby lessened, while by pulling down the sternum and the middle and lower ribs they lessen also the cavity of the chest in its antero-posterior and transverse diameters. They are, in fact, the chief expiratory muscles, though they are doubtless assisted by the serratus posticus inferior and portions of the sacro-lumbalis, since when the diaphragm is not contracting, the depression of the lower ribs which the contraction of these muscles causes, serves only to narrow the chest. As expiration becomes more and more forced, every muscle in the body which can either by contracting depress the ribs, or press on the abdominal viscera, or afford fixed support to muscles having those actions, is called into play. >j 336. Facial and Laryngeal Respiration. The thoracic respiratory movements are accompanied by associated respiratory movements of other parts of the body, more particularly of the face and of the glottis. In normal healthy respiration the current of air which passes in and out of the lungs, travels, not through the mouth but through the nose, chiefly through the lower nasal meatus. The ingoing air, by exposure to the vascular mucous membrane of the narrow and winding nasal passages, is more efficiently warmed than it would be if it passed through the mouth ; and at the same time the mouth is thereby protected from the desiccating effect of the continual inroad of comparatively dry air. During each inspiratory effort the nostrils are expanded, pro- bably by the action of the dilatores naris, and thus the entrance of air facilitated. The return to their previous condition during expi- ration is effected by the elasticity of the nasal cartilages, assisted perhaps by the compressores naris. This movement of the nostrils, perceptible in many people even during tranquil breathing, becomes very obvious in laboured respiration. When the mouth is closed, the soft palate which is held some- what tense, is swayed by the respiratory current, but entirely in a passive manner, and it is not until the larynx is reached by the in- going air that any active movements are met with. When the larynx (the details of which we shall have to deal with at a later part of this work) is examined with the laryngoscope, it is frequently seen that, while during inspiration the glottis is widely open, with each expiration the arytenoid cartilages approach each other so as to narrow the glottis, the cartilages of Santorini projecting inwards at the same time. Thus, synchronous with the respiratory expan- sion and contraction of the chest, and the respiratory elevation and depression of the alas nasi, there is a rhythmic widening and narrowing of the glottis. Like the movements of the nostril, this respiratory action of the glottis is much more evident in laboured than in tranquil breathing. Indeed in the latter case it is frequently absent. The manner in which this rhythmic opening CHAP, ii.] INSPIRATION. :,|0 and aarrowing is effected will !><• described when we come to study the- production of the voice. Whether there exists a rhythmic contraction and expansion of the trachea and bronchial passages, especially the smaller and more exclusively muscular ones, effected by means of the plain muscular tissue of those organs and synchronous with the respiratory movements of the chest, is uncertain. SEC. 3. CHANGES OF THE AIR IN RESPIRATION. § 337. During its stay in the lungs, or rather during its stay in the bronchial passages, the tidal air (by means of diffusion chiefly) effects exchanges with the stationary air ; in consequence the expired air differs from inspired air in several important particulars. The temperature of expired air is variable, but under ordinary circumstances is higher than that of the inspired air. At an average temperature of the atmosphere, for instance at about 20° C., the temperature of expired air is, in the mouth 33'9°, in the nose 35 '3°. When the external temperature is low, that of the ex- pired air sinks somewhat, but not to any great extent, thus at -6'3°C. it is 29-8° C. When the external temperature is high, the expired air may become cooler than the inspired, thus at 41 '9° it has been found to be 3S'1°. The expired air takes its temperature from that of the body, that is, of the blood, and this as we shall see later on while generally higher may, at times, be lower than that of the atmosphere. The exact temperature of the expired air in fact depends on the relative temperatures of the blood and inspired air, and on the depth and rate of breathing. The change in temperature takes place not in the lungs but in the upper passages, and chiefly in the nose and pharynx. § 338. The expired air is loaded with aqueous vapour. The point of saturation of any gas, that is, the utmost quantity of water which any given volume of gas can take up as aqueous vapour, varies with its temperature, being higher with the higher temperature. For its own temperature expired air is, according to most observers, saturated with aqueous vapour. The moisture, like the warmth, is imparted not in the depths of the lung but in the upper passages. The inspired air as it passes into the bronchia is already saturated with moisture. § 339. The expired air contains about 4 or 5 p.c. less oxygen, and about 4 p.c. more carbonic acid than the inspired air, the quantity of nitrogen suffering but little change. Thus oxygen. nitrogen. carbonic acid. Inspired air contains 20'81 7915 '04 Expired „ „ 16'033 79 "587 4'38 CHAP, ii.] RESPIRATION. The quantity of nit rogm in the expired air is sometimes found to be >lightly greater than, as in the table above, but sometimes equal to. and son iet inies less t han, that of the inspired ;tir. In a single breath the air is rieher in carbonic acid (and poorer in oxygen) at the end than at the beginning of the breath. Hence the longer the breath is held, the greater the (artificial) pause between inspiration and expiration, the higher the per- centage of carbonic acid in the expired air. Thus by increasing (lie interval between two expirations to 100 seconds, the per- centage may be raised to 7 '5. When the rate of breathing remains the same, by increasing the depth of the breathing the percentage of carbonic acid in each breath is lowered, but the total quantity of carbonic acid expired in a given time is increased. Similarly, when the depth of breath remains the same, by quickening the rate the percentage of carbonic acid in each breath is lowered, but the quantity expired in a given time is increased. Taking, as we have done, the amount of tidal air passing in and out of the chest of an average man at 500 c.c., such a person will expire about 22 c.c. of carbonic acid at each breath ; this, reckoning the rate of breathing at 17 a minute, would give over 500 litres of carbonic acid for the day's production. Actual de- terminations however give a rather smaller total than this ; thus in a series of experiments of which we shall have to speak hereafter, the total daily excretion of carbonic acid in an average man was found to be 800 grms., i.e. rather more than 400 litres (400), containing 218-1 grms. carbon, and 581'9 grms. oxygen, the oxygen which actually disappeared from the inspired air at the same time being about 700 grms. This amount it should be said represents, owing to the manner in which the experiment was conducted, the gases given out and taken in, not by the lungs only, but by the whole body ; but the amount of carbonic acid given out by other channels than the lungs is, as we shall see, very slight (10 grms. or even less), so that 800 grms. may be taken as the average production of carbonic acid by an average man. The quantity however, both of oxygen consumed and of carbonic acid given out, is subject to very wide variations ; thus in the observations of which we are speaking the daily quantity of car- bonic acid varied from 686 to 1285 grms., and that of the oxygen I'm m 594 to 1072 grms. These variations and their causes will be discussed when we come to deal with the problems of nutrition. ^ 340. When the total quantity of tidal air given out at any expiration is compared with that taken in at the corresponding inspiration, it is found that, both being dried and measured at the -ame temperature and pressure, the expired air is less in volume than the inspired air, the difference amounting to about ^th or '(ih of the volume of the latter. Hence, when an animal is made •to breathe in a con lined space, the air is absolutely diminished in volume. The approximate equivalence in volume between inspired 552 NATURE OF EXPIRED AIR. [BOOK n. ami expired air arises from the fact that the volume of any given quantity of carbonic acid is equal to the volume of the oxygen consumed to produce it ; the slight falling short of the expired air is due to the circumstance that all the oxygen inspired does not reappear in the carbonic acid expired, some having formed within the body other combinations. § 341. Besides carbonic acid, expired air contains various substances which may be spoken of as impurities, many of an unknown nature, and all in small amounts. Traces of ammonia have been detected in expired air. even in that taken directly from the trachea, in which case its presence could not be due to decomposing food lingering in the mouth. When the expired air is condensed by bein- conveyed into a cooled receiver, the aqueous product is found to contain organic matter, which, from the presence of micro-organisms, introduced in the inspired air, is very apt rapidly to putrefy. The organic substances thus shewn to be present in the expired air are the cause in part of the odour of breath. Jt is probable that some of them are of a poisonous nature, cither poisonous in themselves as coming direct from and produced in some way or other in the pulmonary apparatus, or poisonous as being the products of putrefactive decomposition; for various animal substances and fluids give rise by decomposition to distinct poisonous products, known as ptomaines, and it is possible that some of the constituents of expired air are of an allied nature. In any case the substances present have a deleterious action, for an atmosphere containing simply 1 p.c. of carbonic acid (with a corresponding diminution of oxygen) has very little effect on the animal economy, vJieivas an atmosphere in which the carbonic acid has been raised to 1 p.c. by \ breathing, is highly injurious. In fact, air rendered so far impure I by breathing that the carbonic acid amounts to '08 p.c. is dis- tinctly unwholesome, not so much on account of the carbonic acid, ' as of the accompanying impurities. Since these impurities are of unknown nature and cannot be estimated, the easily determined carbonic acid is usually taken as an indirect measure of their presence. We have seen that the average man loads, at each breath, 500 c.c. of air with carbonic acid to the extent of 4 p.c. He will accordingly at each breath load 2 litres to the extent of 1 p.c.; and in one hour, if he breathe 17 times a minute, will load rather more than 2000 litres to the same extent. At the very least then a man ought to be supplied with this quantity of air hourly ; and if the air is to be kept fairly wholesome, that is with the carbonic acid reduced considerably below '1 p.c., he should have even more than ten times as much. SEC. 4. THE RESPIRATORY CHANGES IN THE BLOOD. § 342. While the air in passing in and out of the lungs is thus robbed of a portion of its oxygen, and loaded with a certain quantity of carbonic acid, the blood as it streams along the pulmonary capillaries undergoes important correlative changes. As it leaves the right ventricle it is venous blood of a dark purple or maroon colour ; when it falls into the left auricle it is arterial blood of a bright scarlet hue. In passing through the capillaries of the body from the left to the right side of the heart, it is again changed from the arterial to the venous condition. We have to inquire, What are the essential differences between arterial and venous blood, by what means is the venous blood changed into arterial in the lungs, and the arterial into venous in the rest of the body, and what relations do these changes in the blood bear to the changes in the air which we have already studied ? The facts, that venous blood at once becomes arterial in appearance on being exposed to or shaken up with air or oxygen, and that arterial blood becomes venous in appearance when kept for some little time in a closed vessel, or when submitted to a current of some indifferent gas such as nitrogen or hydrogen, prepare us for the statement that the fundamental difference between venous and arterial blood is in the relative proportion of the oxygen and carbonic acid gases contained in each. From both, a certain quantity of gas can be extracted by means which do not otherwise materially alter the constitution of the blood ; and this gas when obtained from arterial blood is found to contain more oxygen and less carbonic acid than that obtained from venous blood. This is the real differential character of the two bloods ; all other differences are either, as we shall see to be the case with the colour, dependent on this, or are unimportant and fluctuating. If the quantity of gas which can be extracted by the mercurial air-pump from 100 vols. of blood be measured at 0° C., and a pressure of 760 mm., it is found to amount, in round numbers, to CO vols. 554 MERCURIAL GAS-PUMP. [BOOK n. a FIG. 73. DIAGRAMMATIC ILLUSTRATION OF LUDWIG'S MERCURIAL GAS-PUMP. A and B are two glass globes, connected by strong india-rubber tubes, a and b, with two similar glass globes A' and B'. A is further connected by means of the stopcock c with the receiver C containing the blood (or other fluid) to be analysed, and B by means of the stopcock d and the tube e with the receiver D for receiving the gases. A and B are also connected with each other by means of the stopcocks / and g, the latter being so arranged that B also communicates with B' by the passage g'. A' and B' being full of mercury and the cocks k, /, g, and d being open but c and g' closed, on raising A' by means of the pulley p the mercury of A' fills A, driving out the air contained in it, into B, and so out through e. When the mercury has risen above g, / is closed, and g' being opened, B' is in turn raised till B is completely filled with mercury, all the air previously in it being driven out through e. Upon closing d, and lowering B', the whole of the mercury in B falls in B', and a vacuum consequently is established in B. On closing g', but opening g, f, and k and lowering A', a vacuum is similarly established in A and in the junction between A and B. If the cock c be now opened the gases of the blood in C escape into the vacuum of A and B. By raising A', after the closure of c, and opening of d, the gases so set free are driven from A into B, and by the raising of B' from B, through c into the receiver D, standing over mercury. CHAP, ii.] RESPIRATION. 555 The vacuum produced by the ordinary mechanical air-pump is in- sufficient to extract all the gas from blood. Hence it becomes necessary to use a mercury pump capable of producing a large Torricellian v.-iruuin. In the form of mercurial pump which bears Ludwig's naim- (Fig. 73) two large globes of glass, one fixed and the other moveable, are connected by a flexible tube ; the fixed globe is made to com- municate by means of air-tight stopcocks alternately with a receiver containing the blood, and with a receiver to collect the gas. When the moveable globe tilled with mercury is raised above the fixed one, the mercury from the former runs into and completely fills the latter, the air previously present being driven out. After adjusting the cocks, the moveable globe is then depressed thirty inches below the fixed one, in which the consequent fall of the mercury produces an almost complete vacuum. By turning the proper cock this vacuum is put into connection with the receiver containing the blood, which thereupon be- comes proportionately exhausted. By again adjusting the cocks and once more elevating the moveable globe, the gas thus extracted is driven out of the fixed globe into a receiver. The vacuum is then once more established and the operation repeated as long as gas con- tinues to be given off from the blood. A modified form of pump working on the same principles as that of Ludwig, but involving the use of only one globe to be made vacuous and one moveable reservoir for mercury, has been constructed by Pfliiger. It presents several advantages over the one just described, the chief being that (i) non-defibrinated blood may be used for the extraction of its gases, (ii) the vacuum into which the gases are evolved is large, (iii) this vacuum is kept dry by being connected laterally with a vacuous chamber containing sulphuric acid. The details of its construction are however complicated, and the greatest care is required in its use to avoid breakage. Of later years a simplified form of pump has been introduced for laboratory work. It was first used by Grehant and Paul Bert, and is now frequently called an Alvergniat's pump, from the name of its present maker. Fig. 74 gives a diagrammatic representation .of its construction. A is a glass bulb some five inches in diameter, blown on to a glass tube a below and on to a vertical tube b above. The lower end of a is connected by a thick-walled india-rubber tube with a reservoir for mercury £, which can be raised and lowered by means of a string passing over a pulley c. The vertical tube b is thickened at one place, and into this thickened portion a three-way tap d is ground. The upper end of b is prolonged (above the three-way tap) into a fine point. This point passes by a tight joint through the bottom of a vessel e, which can be partly filled with mercury, and over which a receiver f, filled with mercury for the collection of the gases, can be inverted. A tube y fused on laterally to one opening of the three-way tap d places the latter in connection with a thick-walled Woulflf's bottle C con- taining a layer of strong sulphuric acid. The second tubulure of this bottle is .similarly connected by an elastic tube with the vessel Z>, into which blood or other fluid may be introduced by means of the tap Ji. All the moveable joints of the apparatus are protected by india-rubber tubes into which water can be poured, and a metal casing round the tap d, which may also be filled with water, similarly prevents the possibility of any leakage here. 556 MERCURIAL GAS-PUMP. [BOOK ii. The pump is used as follows. By placing the tap d in the position shewn in the figure and raising B, the bulb A may be tilled with mercury FIG. 74. DIAGRAM OF ALVERGXIAT'S PUMP. up to the top, the contained air 1 icing expelled through the upper end of b. By a slight turn of the tap all connection between A and either the tube g or the upper part of b may be cut off, and on lowering B a vacuum is established in the bulb A and part of the tube a. A may now be connected by the tap d with the tube g, and hence with C and D, and, h being closed, a partial vacuum is established in C and D. By means of the tap c/ the air in A may be cut oft' from g, and on raising B and placing the plug of d as shewn in the figure this air may be expelled through the upper end of b. By slightly turning d and lowering B a vacuum is again established in A, and as before a further portion of air in C and D may be allowed to pass over into A and the vacuum in D and C increased. In this way all the air in D can be extracted, the final stages being facilitated by the admission of a little water into D, the last traces of air being driven over into A by the rush of vapour from the water. A known volume of blood having been collected over mercury in a small tube is now allowed to enter 1) through the tap h and yields up its gases to the vacuum. A repetition CHAP. IL] RESPIRATION. 557 of the processes by which the air in I) \va.s originally extracted will now remove the gases which have been given off from the known volume of blood, the only difference being that now the tube y filled with mercury is inverted in the trough e over the, upper end of the tube It. In this way the gases originally in D are not allowed to escape into the air, as uas the case when the apparatus was being originally made vacuous, but are collected in f for subsequent analysis. During the extraction of the gases from the blood the bulb D is immersed in a vessel of warm water, to facilitate the exit of the gases and, by causing the formation of large quantities of aqueous vapour, to sweep the gases rapidly over into A. The sulphuric acid chamber C dries the vacuum before the admission of the blood into _£>, and hence makes it more perfect and causes the most complete and rapid evolution of gases from the blood. The average composition of the gas thus obtained from each of the two kinds of blood (the arterial blood being taken from a large artery, and the venous blood from the right side of the heart) is, stated in round numbers, as follows : From 100 vols. may be obtained Of oxygen, of carbonic acid, of nitrogen. Of Arterial Blood, 20 vols. 40 vols. 1 to 2 vols. Of Venous Blood, 8 to 12 vols. 46 vols. 1 to 2 vols. all measured at 760 mm. and 0° C. That is to say, venous blood, as compared with arterial blood, contains 8 to 12 p.c. less oxygen and 6 p.c. more carbonic acid. It must be remembered, however, that while arterial blood from whatever artery taken has always nearly the same proportion of gases, or at all events the same amount of oxygen, the amount of oxygen in venous blood, even when taken from the same vein, may vary a good deal, still more so when it is taken from different veins. The reason of this we shall see hereafter. It will be convenient to consider the relations of each of these gases separately. The relations of Oxygen in the Blood. § 343. When a liquid such as water is exposed to an atmosphere containing a gas such as oxygen, some of the oxygen will be dissolved in the water, that is to say, will be absorbed from the atmosphere. The quantity which is so absorbed will depend on the pressure of the oxygen in the atmosphere above ; the greater the pressure of the oxygen, the larger the amount which will be absorbed. If the pressure of the whole atmosphere remain the same, at 760 mm. of mercury for instance (the ordinary at- mospheric pressure), the pressure of the oxygen may be increased or diminished by increasing or diminishing the proportion of oxygen in the atmosphere. So that with an atmosphere remain- 558 RELATIONS OF OXYGEN IN BLOOD. [BOOK n. ing at any given pressure the quantity of oxygen absorbed will depend on the quantity present in that atmosphere. If on the other hand water, already containing a good deal of oxygen dis- solved in it, be exposed to an atmosphere containing little or no oxygen, the oxygen will escape from the water into the atmosphere. The oxygen, in fact, which is dissolved in the water, like the oxygen in the atmosphere above, stands at a certain pressure, the amount of pressure depending on the quantity dissolved ; and when water containing oxygen dissolved in it is exposed to any atmosphere, the result, that is, whether the oxygen escapes from the water into the atmosphere, or passes from the atmosphere into the water, depends on whether the pressure of the oxygen in the water is greater or less than the pressure of the oxygen in the atmosphere.>^Hence when water is exposed to oxygen, the oxygen either escapes or is absorbed until equilibrium is established between the pressure of the oxygen in the atmosphere above and the' pressure of the oxygen in the wrater below. This result is, as far as mere absorption and escape are concerned, quite inde- pendent of what other gases are present in the water or in the atmosphere. Suppose a half-litre of water was lying at the bottom of a two-litre flask, and that the atmosphere in the flask above the water was one-third oxygen: it would make no dif- ference, as far as the absorption of oxygen by the water was concerned, whether the remaining two-thirds of the atmosphere was carbonic acid, or nitrogen, or hydrogen, or whether the space above the water was a vacuum tilled to one-third with pure oxygen. Hence it is said that the absorption of any gas depends on the partial j injure of that gas in the atmosphere to which the liquid is exposed. This is true not only of oxygen and water, but of all gases and liquids which do not enter into chemical combination with each other. Different liquids will of course absorb different gases with differing readiness ; but, with the same gas and the same liquid, the amount absorbed will depend directly on the partial pressure of the gas in the overlying space. It should be added that the process is much influenced by temperature. Hence, to state the matter generally, the ab- sorption of any gas by any liquid will depend on the nature of the gas, the nature of the liquid, the pressure of the gas, and the temperature at which both stand. Now it might be supposed, and indeed was once supposed, that the oxygen in the blood was simply dissolved by the blood. If this were so, then the amount of oxygen present in any given quantity of blood exposed to any given atmosphere, ought to rise and fall steadily and regularly as the partial pressure of oxygen in that atmosphere is increased or diminished ; the absorption (or escape) of oxygen ought to follow what is known as the Henry-Dalton law of pressures. But this is found not to be the case. If we expose blood containing little or CHAP, ii.] RESPIRATION. :,;,'.» in) oxygen lo a succession of atmospheres containing increasing quantities of oxygen, we find that at first there is a very rapid absorption of the available oxygen, and then this somewhat suddenly ceases or becomes very small; and if on the other hand \ve submit arterial blood to successively diminishing pressures, we find that fora long time very little oxygen is given off, and then suddenly the escape becomes very rapid. XDio absorption of oxygen by blood does not follow the general law of absorption according to pressure. The phenomena on the other hand suggest the idea that the oxygen in the blood is in some particular combination with a substance or some substances present in the blood, the combination being of such a kind that it holds good during a lowering of pressure down to a certain limit, and that then dissociation readily occurs ; we may add that this limit is very closely dependent on temperature. It is, however, not to be supposed that as the pressure is lowered, no oxygen whatever is given off from the substance until a certain point is reached, and t hat at that point the whole store is in an instant dissociated, no more remaining to be given off. The case is rather that while pressure is being lowered down to a certain point, no appreciable dissociation takes place, and that then having begun it increases rapidly with each further lowering of pressure until the whole of the oxygen is given off. During this narrow range, between the first beginning to give off oxygen and the completion of the giving off, the compound of the oxygen with the substance or substances may be spoken of as partly, that is more or less, dissociated. What is the substance or what are the substances with which the oxygen is thus peculiarly combined ? If serum, free from red corpuscles, be used in such absorption experiments, it is found that, as compared with the entire blood, very little oxygen is absorbed, about as much as would be absorbed by the same quantity of water ; and such as is absorbed does follow the law of pressures. In natural arterial blood the quantity of oxygen which can be obtained from serum is exceed- ingly small ; it does not amount to half a volume in one hundred volumes of the entire blood to which the serum belonged.-V- It is evident that the oxygen which is present in blood is in some way or other peculiarly connected with the red corpuscles. Now the distinguishing feature of the red corpuscles is the presence of haemoglobin. We have already seen (§ 24) that this constitutes 90 per cent, of the dried red corpuscles. There can be d priori little doubt that this must be the substance with which the oxygen is associated; and to the properties of this body we must there fore direct our attention. § 344. Hcemoylobin. When separated from the other con- stituents of the serum, haemoglobin appears as a substance, either amorphous or crystalline, readily soluble in water (especially in warm water) and in serum. 560 HEMOGLOBIN. [BOOK n. Since haemoglobin is soluble in serum, and since the identity of the crystals observed occasionally within the corpuscles with those obtained in other ways shews that the haemoglobin as it exists in the corpuscle is the same thing as that which is artificially prepared from blood, it is evident that some peculiar relationship between the stroma and the haemoglobin must, in natural blood, keep the latter from being dissolved by the serum. Hence in preparing haemoglobin it is necessary first of all to break up this connection and to set the hemoglobin free from the corpuscles. This may be done by the addition of water, of ether, of chloroform or of bile salts, or by repeatedly freezing and thawing ; blood so treated becomes 'laky,' cf. >$ :M. ft is also of advantage previously to remove the alkaline serum as much as possible so as to operate only on the red corpuscles. The stroma and hemoglobin being thus separated, a solution of haemoglobin is the result. The alkalinity of the solution, \\hen present, being reduced by the cautious addition of dilute acetic acid, and the solvent power of the aqueous medium being diminished by the addition of one-fourth its bulk of alcohol, the mixture, set aside in a temperature of 0° C. in order still further to reduce the solubility of the hemoglobin, readily crystallizes, when the blood used is that of the dog, cat, horse, rat, guinea-pig, &c. In the case of the dog indeed it is simply sufficient to add ether carefully to the blood until it just becomes 'laky/ and then to let it stand in a cool place; the mixture soon becomes a mass of crystals. The crystals may be separated by filtration, redissolvecl in water and re- crystallized. Haemoglobin from the blood of the rat, guinea-pig, squirrel, hedgehog, horse, cat, dog, goose, and some other animals, crystal- lizes readily, the cry>tals being generally slender four-sided prisms, belonging to the rhombic system, and often appearing quite acicular. The crystals from the blood of the guinea-pig are octahedral, but also belong to the rhombic system ; those of the squirrel are six-sided plates. The blood of the ox, sheep, rabbit, pig, and man, crystallizes with difficulty. Why these differences exist is not known ; but the composition and the amount of water of crystallization vary somewhat in the crystals obtained from different animals. In the dog, the percentage composition of the crystals has been determined as C. 53'85, H. 7'32, N. 1617, 0. 21-84, S. 0-39, Fe. -4:3, with 3 to 4 per cent, of water of crystal- lization. It will thus be seen that haemoglobin contains, in addition to the other elements usually present in proteid sub- stances, a certain amount of iron ; that is to say, the element iron is a distinct part of the haemoglobin molecule : a fact which of itself renders haemoglobin remarkable among the chemical sub- stances present in the animal body. § 345. The crystals, when seen in a sufficiently thick layer under the microscope, have the same bright scarlet colour as arterial blood has to the naked eye ; when seen in a mass they naturally appear darker. An aqueous solution of hsemoglobin, obtained by dissolving purified crystals in distilled water, has also CHAP, ii.] RESPIRATION. 561 i In- same bright arterial colour. A tolerably dilute solution placed be ton1 the spectroscope is found to absorb certain rays of light in a peculiar and characteristic manner. A portion of the red end of the spectrum is absorbed, as is also a much larger portion of the blue end ; but what is most striking is the presence of two strongly marked absorption bands, lying between the solar lines D and E. (See Fig. 75.) Of these the one towards the red side, M'liietimes spoken of as the band a, is the thinnest, but the most intense, and in extremely dilute solutions (Fig. 75, 1) is the only one visible ; its middle lies at some little distance to the blue side of D. Its position may be more exactly defined by expressing it in wave-lengths. As is well known the rays of light which make up the spectrum differ in the length of their waves, diminish- ing from the red end, where the waves are longest, to the blue end, where they are shortest. Thus Frauenhofer's line D corresponds to rays having a wave-length of 589'4 millionths of a millimeter. Using the same unit, the centre of this absorption band a of haemo- globin corresponds to the wave-length 578 ; as may be seen in Fig. 75, where however the numbers of the divisions of the scale indicate only 100,000 of a millimeter. The other, sometimes called £?, much broader, lies a little to the red side of E, its blue ward edge, even in moderately dilute solutions (Fig. 75, 2) coming close up to that line ; its centre corresponds to about wave-length 539. Each baud is thickest in the middle, and gradually thins away at the edges. These two absorption bands are extremely character- istic of a solution of hemoglobin. Even in very dilute solutions both bands are visible (they may be seen in a thickness of 1 c.m. in a solution containing 1 grm. of haemoglobin in 10 litres of water), and that when scarcely any of the extreme red end, and very little of the blue end, is cut off. They then appear not only faint but narrow. As the strength of the solution is increased, the bauds broaden, and become more intense ; at the same time both the red end, and still more the blue end, of the whole spectrum, are encroached upon (Fig. 75, 3). This may go on until the two absorption bands become fused together into one broad band (Fig. 75, 4). The only rays of light which then pass through the hemoglobin solution are those in the green between the blueward edge of the united bands and the general absorption which is now rapidly advancing from the blue end, and those in the red between the united bands and the general absorption at the red end. If the solution be still further increased in strength, the interval on the blue side of the united bands becomes absorbed also, so that the only rays which pass through are the red rays lying to the red side of D ; these are the last to disappear, and hence the natural red colour of the solution as seen by transmitted light. Exactly the same appearances are seen when crystals of hemoglobin are examined with a microspectroscope. They are also seen when arterial blood itself (diluted with saline solutions so that the F. 36 562 HEMOGLOBIN. [BOOK ii. FIG. 75. (After Preyer and Gamgee.) THE SPECTRA OF OXY-HJEMOGLOBIN ix DIFFERENT GRADES OF CONCENTRATION, OF (REDUCED) HEMOGLOBIN AND OF CAEBONIC-OxiDE-H^MOGLOBIN. 1 to 4. Solution of Oxy-Haarnoglobin containiog (1) less than '01 p.c., (2) -09 p.c., (3) -37 p.c., (4) -8 p.c. 5. ,, ,, (reduced) Haemoglobin containing about -2 p.c. 6. ,, ,, carbonic oxide Hemoglobin. In each of the six cases the layer brought before the spectroscope was 1 c.m. in thickness. The letters (A, a &c.) indicate Frauenhofei's lines, and the figures wave- lengths expressed in 100,000th of a millimetre. CHAP, ii.] RESPIRATION. 563 corpuscles remain in as natural a condition as possible) is examined with the spectroscope, as well as when a drop of blood, which from the necessary exposure to air is always arterial, is examined with the micro-spectroscope. In fact, the spectrum of haemoglobin is the spectrum of normal arterial blood. § 346. When crystals of haemoglobin, prepared in the way described above, are subjected to the vacuum of the mercurial air- pump, they give off a certain quantity of oxygen, and at the same time they change in colour. The quantity of oxygen given off is definite, 1 grin, of the crystals giving off T59 c.cm. of oxygen measured at 760 mm. Hg and 0° C. In other words, the crystals JL- of hemoglobin, over and above the oxygen which enters intimately into the composition of the molecule (and which alone is given in the elementary composition previously stated), contain another quantity of oxygen, which is in loose combination only, and which may be dissociated from them by subjecting them to a sufficiently low pres- sure. The change of colour which ensues when this loosely combined oxygen is removed, is characteristic ; the crystals become darker and more of a purple hue, and at the same time dichroic, so that while the thicker ridges are purple, the thin edges appear greenish. An ordinary solution of haemoglobin, like the crystals from which it is formed, contains a definite quantity of oxygen in a similarly peculiar loose combination ; this oxygen it also gives up when subjected in the air-pump to a sufficiently low pressure, becoming at the same time of a purplish hue. This loosely combined oxygen may also be removed by passing a stream of hydrogen or other indifferent gas through the solution; the stream of hydrogen acts like an oxygen-vacuum to the hemo- globin and thus dissociation is effected. Carbonic acid gas is unsuitable for this purpose, since, as we shall see, being an acid it acts in another way on the haemoglobin. The oxygen may also be removed from the hemoglobin not only by physical but also by chemical means, as by the use of reducing agents. Thus if a few drops of ammonium sulphide or of an alkaline solution of ferrous sulphate, kept from precipitation by the presence of tarfcaric acid, be added to a solution of hemoglobin, or even to an unpurified solution of blood corpuscles such as is afforded by the washings from a blood clot, the oxygen in loose combination with the hemoglobin is immediately seized upon by the reducing agent. This may be recognised at once, by the characteristic change of colour ; from a bright scarlet the solution becomes of a purplish claret colour, when seen in any thickness, but greenish when sufficiently thin : the colour of the reduced solution is exactly like that of the crystals from which the loose oxygen has been removed by the air-pump. Examined by the spectroscope, this reduced solution, or solution of reduced Jicemoylobin, as we may now call it, offers a spectrum (Fig. 75, 5) very different from that of the unreduced solution. 36—2 564 HEMOGLOBIN. [BOOK n. The two absorption bands have disappeared, and in their place there is seen a single, much broader, but at the same time much fainter band, whose middle occupies a position about midway between the two absorption bands of the unreduced solution, though the redward edge of the band shades away rather farther towards the red than does the other edge towards the blue ; its centre corresponds to about wave length 555. At the same time the general absorption of the spectrum is different from that of the unreduced solution ; less of the blue end is absorbed. Even when the solutions become tolerably concentrated, many of the bluish-green rays to the blue side of the single band still pass through. Hence the difference in colour between haemoglobin which retains the loosely combined oxygen1, and haemoglobin which has lost its oxygen and become reduced. In tolerably concentrated solutions, or tolerably thick layers, the former lets through the red and the orange-yellow rays, the latter the red and the bluish-green rays. Accordingly, the one appears scarlet, the other purple. In dilute solutions, or in a thin layer, the reduced haemoglobin lets through so much of the green rays that they preponderate over the red, and the resulting impression is one of green. In the unreduced haemoglobin or oxyhsemoglobin, the potent yellow which is blocked out in the reduced haemoglobin makes itself felt, so that a very thin layer of oxy haemoglobin, as in a single corpuscle seen under the microscope, appears yellow rather than red. It must be remembered that when we speak of reduced haemoglobin (or more briefly haemoglobin), with a purple colour and a characteristic onebauded spectrum, we mean haemoglobin which has lost all its loosely associated oxygen. If a quantity of »»xy haemoglobin be exposed to an insufficiently low pressure, or to the action of an insufficient quantity of the reducing action, it gives up a part only of its oxygen ; it is only partly reduced. Such a partly reduced solution still shews the two bands of oxyhaemoglobin. § 347. When the haemoglobin solution (or crystal) which has lost its oxygen by the action either of the air-pump or of a reducing agent or by the passage of an indifferent gas, is exposed to air containing oxygen, an absorption of oxygen at once takes place. If sufficient oxygen be present, the haemoglobin seizes upon sufficient oxygen to obtain its full complementjc^Bach gramme taking up in combination 1*59 c.cm. of oxygen; if there be an insufficient quantity of oxygen the haemoglobin still remains partly reduced ; or perhaps we may say that a part only of the haemo- globin gets its allowance while the remainder continues reduced. If the amount of oxygen be sufficient, the solution (or crystal), as 1 For brevity's sake we may call the haarnoglobin containing oxygen in loose combination, oxyhcemof/lobin, and the haemoglobin from which this loosely combined oxygen has been removed, reduced haemoglobin or simply hasmoglobin. CHAP, n.] RESPIRATION. 565 it takes up the oxygen, regains its bright scarlet colour and its characteristic absorption spectrum, the single band being replaced by the two. Thus if a solution of oxyhaemoglobin in a test- tube, after being reduced by the action of a drop or two of ammonium sulphide solution and thus shewing the purple colour and the single band, be shaken up with air, the bright scarlet colour at once returns, and when the fluid is placed before the spectroscope, it is seen that the single faint broad band of the reduced hasmoglobin has wholly disappeared, and that in its place are the two sharp thinner bands of the oxyhaemoglobin. If left to stand in the test-tube the quantity of reducing agent still present is generally sufficient again to rob the haemoglobin of the oxygen thus newly acquired, and soon the scarlet hue fades back again into the purple, the two bands giving place to the one. Another shake and exposure to air will however again bring back the scarlet hue and the two bands ; and once more these may dis- appear. In fact, a few drops of the reducing fluid will allow this game of haemoglobin taking oxygen from the air and giving it up to the reducer to be played over and over again ; at each turn of the game the colour shifts from scarlet to purple, and from purple to scarlet, while the two bands exchange for the one, and the one for the two. § 348. Colour of Venous and Arterial Blood. Evidently we have in these properties of hemoglobin an explanation of at least one-half of the great respiratory process, and they teach us the meaning of the change of colour which takes place when venous blood becomes arterial or arterial venous. In venous blood, as it issues from the right ventricle, the oxygen present is insufficient to satisfy wholly the haemoglobin of the red corpuscles ; the haemoglobin is, to a large extent, reduced, hence the purple colour of venous blood. When ordinary venous blood, diluted without access of oxygen, is brought before the spectroscope, the two bands of oxyhsemoglobin are seen. This is explained by the fact that in partly reduced haemoglobin, which we may conveniently regard as a mixture of oxyhaemoglobin and (reduced) haemoglobin, the two sharp bands of the former are always much more readily seen than the much fainter band of the latter. Now in ordinary venous blood there is always some loose oxygen, removable by diminished pressure or otherwise; the haemo- globin is only partly reduced, there is always some, indeed a considerable quantity, of oxyhannoglobin as well as (reduced) haemoglobin. It is only under special circumstances, as for instance after death by what we shall presently speak of as asphyxia, that all the loose oxygen of the blood disappears ; and then the two bands of the oxyhtemoglobin vanish too.l If even only a small quantity of oxygen be present so distinct'are the two bands that a solution of completely reduced haemoglobin may be used as a test for the presence of oxygen ; if oxygen be present in any fluid 566 COLOUR OF BLOOD. LBoOK «• to which the reduced haemoglobin is added, the single band immediately gives way to the two bands of oxyhaemoglobin. As the venous blood passes through the capillaries of the lungs, this reduced haemoglobin takes from the pulmonary air its comple- ment of oxygen, all or nearly all the haemoglobin of the red corpuscles becomes oxyhaemoglobiu, and the purple colour forthwith shifts into scarlet. For careful observations shew that the rutmo- globiu of arterial blood is saturated or nearly saturated with oxygen ; it probably falls short of complete saturation by about 1 vol. of oxygen in 100 vols. of blood. By increasing the pressure of the oxygen, an additional quantity may be driven into the blood, but this, after the haemoglobin has become completely saturated, is effected by simple absorption. The quantity so added is extremely small compared with the total quantity combined with the haemoglobin. Passing from the left ventricle to the capillaries of the tissues the oxyhsemoglobin gives up some of its oxygen to the tissues, becoming, in part, reduced haemoglobin, and the blood in conse- quence becomes once more venous, with a purple hue. Thus the red corpuscles by virtue of their hemoglobin are emphatically oxygen-carriers. Undergoing no intrinsic change in itself, the haemoglobin combines in the lungs with oxygen, which it carries to the tissues ; these, more greedy of oxygen than itself, rob it of its charge, and the reduced haemoglobin hurries back to the lungs in the venous blood for another portion. The change from venous to arterial blood is then in part (for as we shall see there are other events as well) a peculiar combination of hemoglobin with oxygen, while the change from arterial to venous is, in part also, a reduc- tion of oxyhaemoglobin ; and the difference of colour between venous and arterial blood depends almost entirely on the fact that the reduced hemoglobin of the former is of purple colour, while the oxyhaemoglobin of the latter is of a scarlet colour. There may be other causes of the change of colour, but these are wholly subsidiary and unimportant. When a corpuscle swells, its refractive power is diminished, and in consequence the number of rays which pass into and are absorbed by it are increased at the expense of those reflected from its surface ; anything therefore which swells the corpuscles, such as the addition of water, tends to darken blood, and anything, such as a concentrated saline solution, which causes the corpuscles to shrink, tends to brighten blood. ' Carbonic acid has apparently some influence in swelling the corpuscles, and therefore may aid in darkening the venous blood. § 349. We have spoken of the combination of haemoglobin with oxygen as being a peculiar one. The peculiarity consists in the facts that the oxygen may be associated and dissociated, with- out any general disturbance of the molecule of haemoglobin, and that dissociation may be brought about very readily. Haemoglobin combines in a wholly similar manner with other gases. If carbonic CHAP, ii.] RESPIRATION. 567 oxide (monoxide) be passed through a solution of haemoglobin, a change of colour takes place, a peculiar bluish tinge making its ap- pearance. At the same time the spectrum is altered ; two bands are still visible, but on accurate measurement it is seen that they are placed more towards the blue end than are the otherwise similar bands of oxyha?moglobin (see Fig. 75, G) ; their centres corre- sponding respectively to about wave-lengths 572 and 533, while those of oxy haemoglobin as we have seen correspond to 578 and 539. When a known quantity of carbonic oxide gas is sent through a haemoglobin solution, it will be found on examination that a certain amount of the gas has been retained, an equal volume of oxygen appearing in its place in the gas which issues from the solution. If the solution so treated be crystallized, the crystals will have the same characteristic colour, and give the same absorption spectrum as the solution ; when subjected to the action of the mercurial pump, they will give off a definite quantity of carbonic oxide, 1 grm. of the crystals yielding T59 c.cm. of the gas. In fact, haemoglobin combines loosely with carbonic oxide just as it does with oxygen ; but its affinity with the former is greater than with the latter. While carbonic oxide readily turns out oxygen, oxygen cannot so readily turn out carbonic oxide. Indeed, carbonic oxide has been used as a means of driving out and measuring the quantity of oxygen present in any given blood. This property of carbonic oxide explains its poisonous nature. When the gas is breathed, the reduced and the unreduced haemo- globin of the venous blood unite with the carbonic oxide, and hence the peculiar bright cherry-red colour observable in the blood and tissues in cases of poisoning by this gas. The carbonic oxide ha?moglobin, however, is of no use in respiration; it is not an oxygen-carrier, nay more, it will not readily, though it does so slowly and eventually, give up its carbonic oxide for oxygen, when the- poisonous gas ceases to enter the chest and is replaced by pure air. The organism is killed by suffocation, by want of oxygen, in spite of the blood not assuming any dark venous colour ; to adopt a phrase which has been used, the corpuscles are paralysed. Haemoglobin similarly forms a compound, having a character-* istic spectrum, with nitric oxide, more stable even than that with carbonic oxide. It has been supposed by some that the oxygen thus associated with haemoglobin is in the condition known as ozone ; but the arguments urged in support of this view are inconclusive. Products of the decomposition of Htvmoglobin. § 350. Although a crystalline body, haemoglobin diffuses with great difficulty. This arises from the fact that it is in part a proteid body; it consists of a colourless proteid, associated with a coloured substance, which may be separated out from the hasmo- 568 H^EMATIN. [BOOK n. globin, though not in the exact condition in which it naturally exists in the compound ; this substance when separated out appears as a brownish-red body known as hcematin. All the iron belonging to the ha?moglobin is in reality attached to the hpematin. A solution of haemoglobin, when heated, coagulates, the exact degree at which the coagulation takes place depending on the amount of dilution ; at the same time it turns brown from the setting free of the hsematin. If a strong solution of ha?moglobin be treated with acetic (or other) acid, the same brown colour, from the appearance of hamatin, is observed. The proteid constituent however is not coagulated, but by the action of the acid passes into the state of acid-albumin. On adding ether to the mixture, and shaking, the hn -matin is dissolved in the supernatant acid ether, which it colours a dark red, and which, examined with the spectroscope, is found to possess a well-marked spectrum, the spectrum of the so-called acid ha-matin of Stokes (Fig. 76, 6). The proteid in the water below the ether appears in a coagulated form owing to the action of the ether. In a somewhat similar manner alkalis split up haemoglobin into a proteid constituent and hsematin. The exact nature of the proteid constituent of haemoglobin has not as yet been clearly determined. It was supposed to be globulin (hence the name ha-matoglobulin, contracted into haemoglobin), but though belonging to the globulin family, has characters of its own ; it is possibly a mixture of two or more distinct proteids. It has been provisionally named globiji and is said to be free from ash. § 351. H;t -matin when separated from its proteid fellow, and purified, appears as a dark-brown amorphous powder, or as a scaly mass with a metallic lustre, having the probable composition of C32, H34, N4, Fe, 05. It is fairly soluble in dilute acid or alkaline solutions, and then gives characteristic spectra (Fig. 76, 1, 2, 5). An interesting feature in ha-matin is that its alkaline solution is capable of being reduced by reducing agents, the spectrum changing at the same time (Fig. 76, 3), and that the reduced solution will, like the haemoglobin, take up oxygen again on being brought into contact with air or oxygen. This would seem to indicate that the oxygen-holding power of haemoglobin is connected exclusively with its hrematin constituent. By the action of strong sulphuric acid ha-matin may be robbed of all its iron. It still retains the feature of possessing colour, the solution of iron-free hamatin being a dark rich brownish red ; but is no longer capable of combining loosely with oxygen. This indicates that the iron is in some way associated with the peculiar respiratory functions of haemoglobin ; though it is obviously an error to suppose, as was once supposed, that the change from venous to arterial blood consists essentially in a change from a ferrous to a ferric salt. CHAP, ii.] RESPIRATION. 569 a i -S3 cO -N .£P A 1 I o o h) o o a EH o 02 w PH 3 « w Q Ed a O tc K H cc o> Oj 6C a 03 570 METH^MOGLOBIN. [BOOK n. Though not crystallizable itself, huiematin forms with hydro- chloric acid a compound, occurring in minute rhombic crystals, known as hcemin crystals. When blood is left until it decomposes, the haemoglobin is very apt to become changed into a peculiar body known as nwthfBnw- fjlobin, in the spectrum of which a very conspicuous band is seen in the red between C and D (see Fig. 76, 4). The same change may be brought about by the action of weak acids, such as carbonic acid, by ozone, and by other agents such as nitrites and potassium permanganate. When a stream of carbonic acid is driven through blood or through a solution of haemoglobin the band in the red characteristic of methaemoglobin soon makes its appearance. Metha-moglobin differs but little it' at all in elementary composition from haemoglobin ; it is maintained that it contains the same quantity of oxygen as oxy-ha^moglobrn but in a more stable condition, more intimately associated with the molecule. In conclusion, the condition of oxygen in the blood is as follows. Of the whole quantity of oxygen in the blood, only a minute fraction is simply absorbed (.r dissolved according to the law of pressures (the Henry- Dalton law). The great mass is in a stare of combination with the luemoglobin, the connection being of such a kind that while the haemoglobin readily combines with the "\ygeii of the air to which it is exposed, dissociation readily occurs at low pressures, or in the presence of indifferent ^ases, or by the action of substances having a greater affinity for oxygen than has haemoglobin itself. The difference between venous and arterial blood, as far as oxygen is concerned, is that while in arterial blood the haemoglobin holds nearly its full complement of oxygen and may be spoken of a- nearly wholly oxyruemoglobin, in venous blood the haemoglobin is to a large but variable extent, reduced ; and the characteristic colours of venous and arterial blood are in the main due to the fact that the colour of reduced haemoglobin is purple, while that of oxyhgemoglobin is scarlet. The relations of the Carbonic Acid in the Blood. § 352. The presence of carbonic acid in the blood appears to be determined by conditions more complex in their nature and at present not so well understood as those which determine the presence of oxygen. The carbonic acid is not simply dissolved in the blood ; its absorption by blood does not follow the law of pressures. 7 It exists in association with some substance or sub- stances in the blood, and its escape from the blood is a process of dissociation. 'We cannot however speak of it as being associated, to the same extent as is the oxygen, with the haemoglobin of the red corpuscles. So far from the red corpuscles containing the great mass of the carbonic acid, the quantity of this gas which is CHAP, ii.] RESPIRATION. 571 present ill a volume of serum is according to some observers actually greater than that which is present in an equal volume of blood, i.e. an equal volume of mixed corpuscles and serum ; that is to say, the carbonic acid is much more largely associated with the serum (or, in the living blood, with the plasma) than with the red corpuscles. When serum is subjected to the action of the mercurial pump, by far the greater part of the carbonic acid is given off; but a small additional quantity (2 to 5 vols. per cent.) may be extracted by the subsequent addition of an acid. This latter portion may be spoken of as ' fixed ' carbonic acid in distinction to the larger ' loose ' portion which is given off to the vacuum. When however the whole blood is subjected to the vacuum until the carbonic acid ceases to be given off, the subsequent addition of acid is said not to set free any further quantity ; so that when serum is mixed with corpuscles all the carbonic acid may be spoken of as ' loose ' ; and it is stated that the excess of carbonic acid in a quantity of serum over that present in the same bulk of entire blood, corresponds to the fixed portion in serum which has to be driven off by an acid. Moreover, even those who maintain that the quantity of carbonic acid in entire blood is less than that in an equal volume of serum, admit that the carbonic acid exists in some way or other at a higher pressure in, and is more readily given off from entire blood than from serum. If these statements be accepted it seems probable that the ) carbonic acid exists associated with some substance or substances/ in the serum, or rather plasma, but that the conditions of its, association (and therefore of its dissociation) are determined by the action of some substance or substances present in the cor- puscles. It has been suggested that the association of the carbonic acid in the plasma is with one or other of the proteids of the plasma ; but it has also been suggested that the association is one with sodium as sodium bicarbonate, and further that the ha?moglobin of the corpuscles plays a part in promoting the dissociation of the sodium bicarbonate or even the carbonate, and thus keeping up the carbonic acid of the entire blood. Other observers however maintain that the plasma does not hold this exclusive possession of the carbonic acid, but that a considerable quantity of this gas is in some way associated with the red corpuscles. Indeed further investigations are necessary before the matter can be said to have been placed on a satisfactory footing. The relations of the Nitrogen in the Blood. § 353. The small quantity of this gas which is present in both arterial and venous blood seems to exist in a state of simple solu- tion. SEC. 5. THE RESPIRATORY CHANGES IN THE LUNGS. The Entrance of Oxygen. § 354. We have already seen that the blood in passing through the lungs takes up a certain variable quantity (from 8 to 12 vols. p.c.) of oxygen. We have further seen that the quantity so taken up, putting aside the insignificant fraction simply absorbed, enters into direct but loose combination with the haemoglobin. In drawing a distinction between the oxygen simply absorbed and that entering into combination with the haemoglobin, it must not be understood that the latter is wholly independent of pressure. On the contrary, all chemical compounds are in various degrees subject to dissociation at certain pressures and temperatures ; and the existence of the somewhat loose compound of oxygen and haemoglobin is dependent on the partial pressure of oxygen in the atmosphere to which the haemoglobin is exposed. Not only will a solution of haemoglobin or a quantity of blood either absorb oxygen and thus undergo association or undergo dissociation and give off oxygen according as the partial pressure of oxygen in the atmosphere to which it is exposed is high or low, but also the amount taken up or given off will depend on the degree of the partial pressure ; the haemoglobin as Ave have seen may be partially as well as wholly reduced. The law however according to which absorption or escape thus takes place is quite different from that observed in the simple absorption of oxygen by liquids. The association or dissociation is further especially depen- dent on temperature, a high temperature favouring dissociation, so that at a high temperature less oxygen is taken up than would be taken up (or, as the case may be, more given oft' than would be given off) at a lower temperature, the partial pressure of the oxygen in the atmosphere remaining the same. Moreover in the blood we have to deal not with haemoglobin in simple solution, in which the molecules are dispersed uniformly through the solvent, but with the ha?moglobin segregated into CHAP, ii.] RESPrRATION. 573 minute isolated masses, bottled up as it. were in the individual corpuscles. The ha'inoglobiii of each corpuscle is separated I'roin its fellows by a layer, thin it may l>e but still a distinct layer, of colourless, hsemoglobinless plasma. As the corpuscle makes its wav through tin- narrow capillary paths of a pulmonary alveolus, it is separated from the air of the alveolus by a thin layer of 1 «/ «/ plasma as well as by the film of the conjoined capillary and alveolar walls; and a like layer of plasma separates it from its fellows as it journeys in company with them through the wider passages of the arteries ami veins. Through this layer of plasma, which containing no haemoglobin can hold oxygen in simple solution only, the oxygen has to pass on its way to and from the corpuscle ; and every corpuscle may be considered as governing, as far as oxygen is concerned, a zone of plasma immediately surround- ing itself. The corpuscle takes its oxygen directly from this zone and gives up its oxygen directly to this zone ; and the pressure at which at any moment the oxygen exists in this zone will depend on the pressure of oxygen outside the zone, in the air of the pulmonary alveolus for instance, and on the smaller or greater amount of oxygen associated with the haemoglobin of the cor- puscle. The film of the conjoined capillary and alveolar wall is a thin membrane soaked with lymph and wet ; we cannot speak of it as actually secreting a liquid secretion into the alveolus, for the cavity of the alveolus is filled with air which, though saturated with moisture, is air, not a liquid ; still enough passes through the film to keep it continually moist. Through this film the oxygen has to make its way in order to gain access to the plasma and so to the corpuscle ; it makes its way dissolved in the fluid, that is the lymph, which keeps the film moist. This film more- over is composed of living matter, and the considerations which a little while back (§ 312) we urged concerning the diffusion through a living membrane of solid substances in solution, hold good also for the diffusion of gases in solution. We have now to consider the question, Are the conditions in which haemoglobin and oxygen exist in ordinary venous blood as it flows to the lungs, of such a kind that the venous blood in passing through the pulmonary capillaries will find the partial pressure of the oxygen in the pulmonary alveoli sufficient to bring about the association of the additional quantity of oxygen wrhereby the venous is converted into arterial blood ? We may say at once that we have, at present at all events, no satisfactory evidence that the film spoken of above exerts any influence, as a living film, on the entrance of oxygen from the alveolus into the blood. Nor have we any evidence that as a mere membrane or septum it exerts any such influence ; the oxygen appears to pass into the blood in the same way that it would, if the blood were freely exposed without any intervening 574 THE ENTRANCE OF OXYGEN. [BOOK n. partition to the alveolar air. Further, the evidence, so far as it goes, seems to shew that blood absorbs oxygen in the same way as an aqueous solution of haemoglobin of the same concentration ; the zone of plasma spoken of above as surrounding each corpuscle behaves as far as regards the passage of oxygen to and from the corpuscles in no essentially different respect from the way the molecules of water, belonging to a molecule of dissolved haemo- globin, behave in regard to the absorption or the giving-off of oxygen by an aqueous solution of haemoglobin. § 355. In man, as we have seen, expired air contains about 16 p.c. of oxygen. The air in the pulmonary alveoli must contain less than this, since the expired air consists of tidal air mixed by diffusion with the stationary air. How much less it contains we do not exactly know, but probably the difference is not very great. At the ordinary atmospheric pressure of 760 mm. 16 p.c. is equivalent to a partial pressure of 122 mm. The question therefore stands thus, Will venous blood, exposed at the tempe- rature of the body to a partial pressure of less than 122 mm. (less than 16 p.c.) of oxygen take up sufficient oxygen (from 8 to 12 vols. p.c.) to convert it into arterial blood? Numerous experiments have been made (chiefly but not exclusively on the dog) to determine on the one hand the oxygen-pressure of both arterial and venous blood (i.e. the partial pressure of oxygen in an atmosphere exposed to which the arterial blood neither gives up nor takes in oxygen, and the same for venous blood), and on the other hand the behaviour at the temperature of the body or at ordinary temperatures of blood or of solutions of haemoglobin (for the two as we have just said behave in this respect very much alike) towards an atmosphere in which the partial pressure of oxygen is made to vary./ Without going into detail, we may state that these experiments shew that the partial pressure of oxygen in the lungs is amply sufficient to bring about, at the temperature of the body, the association of that additional amount of oxygen by which venous blood becomes arterial. When a solution of haemoglobin or when blood is successively exposed to increasing oxygen pressures, as the partial pressure of oxygen is gradually increased, the curve of absorption rises at first very rapidly but afterwards more slowly ; that is to say, the later additions of oxygen at the higher pressures are proportionately less than the earlier ones at the lower pressures. And this is consonant with what appears to be the fact that the hemoglobin of arterial blood though nearly saturated with oxygen, i.e. associated with almost its full complement of oxygen, is not quite saturated. When arterial blood is thoroughly exposed to air it takes up rather more than 1 vol. p.c. of oxygen ; and that appears to represent the difference between exposing blood to pure air, such as enters or ought to enter the mouth in inspiration, and exposing blood to the air as it exists in the pulmonary alveoli. The greater relative CHAP, ii.] RESPIRATION. 575 absorption at the lower pressures has a beneficial effect in as much as it still permits a considerable quantity of oxygen to be absorbed even when the partial pressure of oxygen in the air in the lungs is largely reduced, as in ascending to great heights. Observations made both with dog's blood and ox's blood seem to shew that arterial blood ceases to take up oxygen and begins to give off oxygen, in other words, that dissociation begins to take place, when the partial pressure of the oxygen in the atmosphere to which it is exposed sinks to about 60 mm. of mercury, that is to say, when the whole atmospheric pressure is reduced from 700 mm. to about 300 mm. or when the percentage of oxygen in the atmosphere is reduced by decidedly more than half. And this accords with the observation that, in man, when the oxygen of inspired air is gradually diminished, without any other change in the air, symptoms of dyspnoea do not make their appearance until the oxygen sinks to 10 p.c. in the inspired air and must therefore be less than this in the pulmonary alveoli. We may remark that at ordinary altitudes, even taking into account the diminution the oxygen undergoes before it reaches the pulmonary alveoli, the partial pressure of the oxygen in the atmosphere leaves a wide margin of safety. But at an altitude of 5500 metres (17000 feet) at which the pressure of the whole atmo- sphere stands at about the limit given above of 300 mm., the partial pressure of the oxygen will be such that the venous blood cannot take up the quantity of oxygen proper to convert it into arterial blood, since at this limit arterial blood begins to give off oxygen. We may add that it is at this altitude that breathing becomes especially difficult, but to this we shall return. § 356. The statements made so far refer to ordinary breathing, but the question may be asked, What happens when the renewal of the air in the pulmonary alveoli ceases, as when the trachea is obstructed ? In such a case the oxygen in the alveoli is found to diminish rapidly, so that the partial pressure of oxygen in them soon falls below the oxygen-pressure of ordinary venous blood. But in such a case the blood is no longer ordinary venous blood ; instead of being moderately, it is largely and increasingly reduced ; instead of containing a comparatively small amount, it contains a large and gradually increasing amount, of reduced haemoglobin. And as the reduction continues to increase, the oxygen-pressure of the venous blood also continues to decrease ; it thus keeps below that of the air in the lungs. Hence apparently even the last traces of oxygen in the lungs may be taken up by the blood, and carried away to the tissues. The Exit of Carbonic Acid. § 357. It seems natural to suppose that the carbonic acid would escape by diffusion from the blood of the alveolar capillaries 576 THE EXIT OF CARBONIC ACID. [BOOK n. } into the air of the alveoli. But in order that diffusion should thus take place, the carbonic acid pressure of the air in the pulmonary alveoli must always be less than that of the venous blood of the pulmonary artery, and ought not to exceed that of the blood of the pulmonary vein. There are however many practical difficulties in the way of an exact determination of the carbonic acid pressure of the pulmonary alveoli (for though it must be greater than that of the expired air, it is difficult to say how much greater), and of the carbonic acid pressure of the blood at the same time, so as to be in a position to compare the one with the other. In the case of oxygen, there is always present in the lungs a surplus of the gas, a portion only being absorbed at each breath ; in the case of carbonic acid, the whole quantity comes direct from the blood, and any modifications in breathing seriously affect the amount given out. Thus when the breath is held for some time the percentage of carbonic acid in the expired air reaches 7 or 8 p.c., but we cannot take this as a measure of the normal percentage of carbonic acid in the pulmonary alveoli, since by the mere holding of the breath the carbonic acid in the blood and hence in the pulmonary alveoli is increased beyond the normal. The difficulties of the problem seem however to have been overcome by an ingenious experiment in which there is introduced into the bronchus of the lung of a dog a catheter, round which is arranged a small bag ; by the inflation of this bag the bronchus, whenever desired, can be completely blocked up. Thus, without any marked disturbance of the general breathing, and therefore without any marked change in the normal proportions of the gases of the blood, the experimenter is able to stop the ingress of fresh air into a limited portion of the lung. At the same time he is enabled by means of the catheter to withdraw a sample of the air of the same limited portion, and by analysis to determine the amount of carbonic acid which it contains, or in other words, the partial pressure of the carbonic acid. The blood passing through the alveolar capillaries of this limited portion of the lung naturally possesses the same carbonic acid pressure as the rest of the venous blood flowing through the pulmonary artery, a pressure which, though varying slightly from moment to moment, will maintain a normal average. On the supposition that carbonic acid passes simply by diffusion from the pulmonary blood into the air of the alveoli, because the carbonic acid pressure of the latter is normally lower than that of the former, one would expect to find that the air in the occluded portion of the lung would continue to take up carbonic acid until an equilibrium was established between it and the carbonic acid pressure of the venous blood. Consequently, if after an occlusion, say of some minutes (by which time the equilibrium might fairly be assumed to have been established), the carbonic acid pressure of the air of the occluded portion were determined, it Cii.viMi.l I JKSIM RATION. 577 ought tn be found to In- ec|Ual to, and not more than e