BIOLOGY LIBRARY G CONTENTS. xxi The Relations of Oxygen in the Blood. PAGE § 274. The absorption of oxygen by blood is not according to ' the law of pressures ' 447 § 275. The characters of hsemoglobin , . . 450 § 276. The spectroscopic features of hsemoglobin 451 § 277. The spectroscopic features of reduced hsemoglobin .... 453 § 278. The oxygenation and reduction of hsemoglobin . . . ' . 455 § 279. The colour of venous and arterial blood 455 § 280. Carbonic-oxide-haemoglobin 457 Products of the Decomposition of Haemoglobin. § 281. Hsemoglobin splits up into hsematin and a proteid .... 458 § 282. The features of hsematin. Hsemin. Methsemoglobin ... . 460 The Relations of the Carbonic Acid in the Blood, § 283. The carbonic acid of the blood not simply absorbed . , . 461 The Relations of the Nitrogen in the Blood. § 284. The nitrogen simply absorbed , 461 SECTION XV. THE RESPIRATORY CHANGES IN THE LUNGS. § 285. The relations of the oxygen of the blood to pressure. Association of oxygen with, and dissociation from hsemoglobin. The problem stated 462 § 286. The experimental evidence 464 § 287. The relations of the oxygen in laboured breathing and asphyxia . 465 The Exit of Carbonic Acid. § 288. The exit of carbonic acid from the blood into the pulmonary alve- olus the result of ordinary diffusion 466 SECTION V. THE RESPIRATORY CHANGES IN THE TISSUES. § 289. The oxidations of the body take place mainly in the tissues and not in the circulating blood. The respiration of muscle . . . 467 § 290. The respiration of other tissues. The taking in of oxygen separate from the giving out of carbonic acid 409 § 291. A summary of respiration in its chemical aspects .... 470 SECTION VI. THE NERVOUS MECHANISM OF RESPIRATION. § 292. Respiration an involuntary act. The efferent nerves, the respiratory centre 472 ' xxii CONTENTS. £ § 293. The complex nature of the medullary respiratory centre ; the sub- sidiary spinal mechanisms ij- •>•>.; , -. v . 473 § 294. The action of the centre automatic (?. 474 § 295. The centre influenced by afferent impulses. The respiratory action of the vagus nerve. Inhibitory and augmentor effects . . 475 § 296. The double action of the centre, inspiratory and expiratory. Antag- onism between the two 479 § 297. The effects of inflation and suction. Double action of the vagus fibres. Self-regulating mechanism . . . . , . . 480 § 298. The influence on the respiratory centre of various afferent impulses 483 § 299. The respiratory centre composed of two lateral halves . . . 484 § 300. The respiratory centre influenced by the condition of the blood brought to it. Eupncea, hyperpnoea, and dyspnoea . . . 484 § 301. The direct character of these influences. Effects of heat on the respiratory centre 486 § 302. The relative shares taken by deficiency of oxygen and excess of carbonic acid in the above influences 487 § 303. Changes in the blood other than differences in the gases influence the respiratory effect. The effects of muscular exercise . . 488 § 304. The phenomena and causes of apncea 489 § 305. Secondary respiratory rhythm. The Cheyne- Stokes respiration . 490 SECTION VII. THE EFFECTS OF CHANGES IN THE COMPOSITION AND PRESSURE OF THE AlR BREATHED. 306. The phenomena of asphyxia 491 307. The effects on respiration of breathing various foreign gases . . 494 308. The effects of a diminution of pressure in the air breathed . * 494 309. The effects of an increase of atmospheric pressure .... 496 SECTION VIII. THE RELATIONS OF THE RESPIRATORY SYSTEM TO THE VASCULAR AND OTHER SYSTEMS. § 310. The respiratory movements influence the circulation. The respira- tory undulations of the blood-pressure curve .... 497 § 311. 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 499 § 312. The effects of the expansion and return of the thorax on the flow of blood through the lungs 502 § 313. The effects on the circulation of artificial respiration . . .503 § 314. An action of the cardio-inhibitory centre synchronous with that of the respiratory centre . . . . * 504 § 315. The effects of impeded respiration on the circulation in general. Traube-Hering curves. The circulation in asphyxia . . . 504 CONTENTS. xxiii PAGE The effects on respiration of changes in the circulation through the respiratory centre and through the lungs 508 § 317. The effects of exercise on respiration 509 SECTION IX. MODIFIED RESPIRATORY MOVEMENTS. § 318. Sighing, yawning, hiccough, sobbing, coughing, sneezing, laugh- ing, and crying 511 CHAPTER III. THE ELIMINATION OF WASTE PRODUCTS. § 319. The chief waste products and their channels of exit , . . . 613 SECTION I. THE COMPOSITION AND CHARACTERS OF URINE. §320. The general characters of urine .,..- . 616 § 321. The normal organic constituents of urine ,,,.>». .... 616 § 322. The inorganic salts 617 § 323. The non-nitrogenous constituents of the urine M, j0 &*(>&*•:'} • 618 § 324. The pigments of the urine . . . . . .... 519 § 325. Ferments and other bodies present in urine . . * . . 519 § 326. The relative quantities of the more important constituents of urine 520 § 327. The acidity of urine . .621 § 328. The abnormal constituents of urine . . . . ' ~ . . . 522 SECTION II. THE SECRETION OF URINE. § 329. The double nature of urinary secretion 524 § 330. The vaso-motor mechanisms of the kidney. The renal oncometer and oncograph 525 § 331. The relation of the flow of blood through the kidney to variations in blood-pressure and to vaso-motor changes in general . . 628 § 332. The vaso-constrictor nerves of the kidney 530 § 333. The vaso-dilator nerves of the kidney 531 § 334. The influence on the renal circulation of chemical substances in the blood 631 § 335. The connection between changes in the renal circulation and the secretion of urine . ... 532 xxiv CONTENTS. Secretion by the Eenal Epithelium. The evidence of the secretory activity of the epithelium. Experi- ments on amphibia. The results of injecting sulphindigotate of sodium 533 § 337. The nature of glomerular secretion ; its relation to filtration and diffusion. Albuminous urine 535 § 338. The nature of the work of the epithelium as regards the secretion of urea 538 § 339. The formation of hippuric acid - . . 539 § 340. The relations of the secretory activity of the kidney to the secretory activity of the skin 540 § 341. The relations of the secretion of urine to food and drink . . 541 § 342. Diuretics 542 § 343. Direct action of the nervous system on the kidney .... 543 SECTION III. THE DISCHARGE OF URINE. § 344. The movements of the ureter 544 Micturition. § 345. The muscles of the bladder, their action, the nerves governing them ; the sphincter vesicse . . . . . . . . 545 §346. The varying tone of the bladder . . . . . . . 546 § 347. The general nervous mechanism of micturition . : . . . 547 § 348. Involuntary and voluntary micturition . . . . ' . . 548 § 349. Changes of the urine during its stay in the bladder .... 549 SECTION IV. THE NATURE AND AMOUNT OF PERSPIRATION. § 350. Sensible and insensible perspiration. The characters and constitu- ents of sweat 550 Cutaneous Respiration. § 351. The nature and amount of cutaneous respiration. The effects of varnishing the skin . 552 § 352. Absorption by the skin 553 SECTION V. THE MECHANISM OF THE SECRETION OF SWEAT. § 353. The relation of sweating to vascular changes. The nervous mech- anism of the sweat-glands 555 § 354. The sweat-nerves, their origin and course 557 § 355. Inhibitory sweat-nerves . . . . . . . . . 558 CONTENTS. xxv CHAPTER IV. THE METABOLIC PROCESSES OF THE BODY. PAGE § 356. The general characters of the metabolism of the body . . . 659 SECTION I. THE HISTORY OF GLYCOGEN. § 357. The characters of glycogen 561 § 358. The conversion of glycogen into sugar by the liver .... 562 § 359. The influence of various foods in storing up glycogen. The storage of glycogen in the winter frog 563 § 360. The detailed characters of the hepatic cells in the frog . . . 566 § 361. The histological changes induced by food and circumstances in the hepatic cells of the frog 567 § 362. The corresponding changes in the mammal 568 § 363. The nature and meaning of these changes 568 § 364. Views as to the manner in which glycogen is stored in the hepatic cells. By simple dehydration of sugar 569 § 365. The glycogen formed by a product of the metabolism of the hepatic cells. Comparison of the two views . . v . . . 570 § 366. The uses of glycogen. The formation of fat as a store of carbon- holding material . 571 § 367. Glycogen in muscle 673 § 368. Glycogen in the placenta and in various tissues .... 574 Diabetes. § 369. Artificial diabetes 675 § 370. The nervous mechanism of the diabetic puncture . . . . 576 § 371. Temporary diabetes from the use of drugs. Natural diabetes. The 676 diminution of hepatic glycogen by arsenic and other agents . 676 SECTION II. THE SPLEEN. § 372. The movements of the spleen. The spleen curve .... 679 § 373. The spleen pulp ; the white and red corpuscles. Changes under- gone by the latter 581 § 374. The chemical constituents of the spleen 582 SECTION III. THE FORMATION OF THE CONSTITUENTS OF BILE. § 375. The formation of bilirubin from haemoglobin 584 § 376. The nature of and preparations towards this formation . . . 685 § 377. The formation of bile acids . .... 586 xxvi CONTENTS. § 378. The relations of the secretion of bilirubin to the secretion of bile acids 587 § 379. The relation of the secretion of bile to the formation of glycogen . 587 SECTION IV. ON UREA AND ON NITROGENOUS METABOLISM IN GENERAL. § 380. Urea the end-product of the metabolism of proteid matter . . 589 § 381. Urea probably the result of a series of changes . . . 590 § 382. The kreatin of muscle in its relations to urea . .... 590 § 383. Difficulties presented by the normal presence of kreatin in urine . 591 § 384. The nitrogenous metabolism of the nervous tissues .... 592 § 385. The nitrogenous metabolism of the glandular structures. The increase of urea due directly to food 593 § 386. The formation of urea in the liver 594 § 387. The synthesis of urea . 595 § 388. Uric acid ' 596 § 389. Other nitrogenous crystalline bodies, such as xanthin, &c. . . 597 § 390. Relations of urea to cyanogen compounds 598 § 391. A summary of nitrogenous metabolism 599 SECTION V. ON SOME STRUCTURES AND PROCESSES OP AN OBSCURE NATURE. § 392. The structure and functions of the thyroid body ... . . 600 §393. The pituitary body '.' " : ' '. . . 601 § 394. The structure, chemical constituents, and functions of the supra- renal bodies 601 § 395. The structure, nature, and functions of the thymus ' : "*'•'•• V .. 602 SECTION VI. THE HISTORY OF FAT. ADIPOSE TISSUE. § 396. Adipose tissue ; its changes 604 § 397. The structure of adipose tissue 604 § 398. The disappearance of fat from adipose tissue 605 § 399. The nature of fat in adipose tissue . . . . . . . 606 § 400. Fat is formed in the body 606 § 401. Formation of fat from carbohydrates and from proteids . ... 608 § 402. Limits to the construction of fat .609 SECTION VII. THE MAMMARY GLAND. § 403. The general structure of the mammary gland 610 § 404. The structure of the alveoli ; the varying appearances* of the epi- thelial cells , . 610 CONTENTS. xxvii PAGE § 405. The characters of the dormant mammary gland . . . .611 § 406. The connective-tissue of the mammary gland 612 § 407. The nature of milk ; its constituents ; their relative quantities in different animals . . . 612 § 408. Colostrum, its chemical and microscopical characters . . . 614 § 409. The mammary gland at birth 615 § 410. The nature of the act of secretion of milk 615 § 411. The secretion of milk typical of metabolism in general . . . 616 § 412. The relations of the gland to the nervous system .... 618 CHAPTER V. NUTRITION. SECTION I. THE STATISTICS OF NUTRITION. § 413. The composition of the animal body 619 § 414. The composition of the starving body and the general phenomena of starvation 620 Comparison of Income and Output of Material. § 415. The method of determining the income and output. The respira- tion chamber. The calculation of changes in the body based on a comparison of the income and output 622 § 416. Nitrogenous metabolism. ' Tissue ' proteids and ' floating ' proteids. Luxus consumption 625 § 417. The effects of fatty and carbohydrate food 627 § 418. The effects of gelatin as food • . 629 § 419. Peptone as food ... 629 § 420. The effects of salts as food 630 SECTION II. THE ENERGY OF THE BODY. The Income of Energy. § 421. The available potential energy of the several food-stuffs and of an ordinary diet 632 The Expenditure of Energy. § 422. The daily expenditure as heat and as work done. Calorimeters . 634 § 423. The energy of mechanical work does not arise exclusively from proteid metabolism ; urea and muscular exercise . . . 636 Animal Heat. § 424. The sources and distribution of heat ; the muscles the chief source 638 § 425. The temperature of the body ; cold-blooded and warm-blooded animals . . 640 xxviii CONTENTS. PAGE § 426. The regulation of the temperature of the body by variation in the loss of heat. The skin the great regulator 641 § 427. The production of heat, the circumstances determining it ; the effects of meals and of labour . .... . . 643 § 428. 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 . . 645 § 429. The portions of the central nervous system concerned in this regu- lation of heat 647 § 430. The narrow limits within which the bodily temperature is main- tained 647 § 431. Abnormally high temperatures, pyrexia 648 § 432. The effects of great heat 649 § 433. The effects of great cold 650 SECTION III. ON NUTRITION IN GENERAL. § 434. The general features of metabolism 651 § 435. The metabolism of muscle as typical of the metabolism of tissues ; the nature of the food of muscle 652 § 436. The fate of the lactic acid produced by muscle •..,.-. . . 653 § 437. A comparison of the metabolism of muscular tissue with that of other tissues 653 § 438. Proteid substance the pivot of metabolism 654 § 439. The influence of nerves on metabolism ; katabolic and anabolic nerves. The influence of the nervous system on the general nutrition of the tissues. The phenomena of disease, &c. ; trophic nerves . 654 SECTION IV. ON DIET. § 440. The normal diet, statistical and experimental 658 § 441. The necessity for all three food-stuffs, pro te ids, fats, and carbo- hydrates. The necessity and importance of salts including extractives ; alcohol, &c 660 § 442. The chemical value of articles of food to be corrected by their digestibility 662 § 443. The physiological value of a purely vegetable diet .... 664 § 444. The modifications of a normal diet needed to meet variations in size 667 § 445. The modifications of a normal diet needed to meet changes of climate 667 § 446. The modifications of a normal diet needed to promote or prevent fattening 668 § 447. The modifications of a normal diet needed to meet muscular and mental labour . . . 669 CONTENTS. xxix BOOK III. THE CENTRAL NERVOUS SYSTEM AND ITS INSTRUMENTS. CHAPTER I. THE SPINAL CORD. SECTION I. ON SOME FEATURES OF THE SPINAL NERVES. PAGE § 448. The spinal nerves 675 § 449. On efferent and afferent impulses 676 § 450. Efferent fibres run in the anterior root and afferent fibres in the posterior root 677 § 451. The " trophic " influence of the ganglion of the posterior root ; the degeneration of nerve fibres 678 SECTION II. THE STRUCTURE OF THE SPINAL CORD. § 452. The general features of the cord ; grey and white matter. The grouping of the nerve cells. The cells of the anterior and pos- terior horn, the lateral group, Clarke's column, and the lateral horn. The tracts of white matter. Median posterior column, external posterior column. The evidence of the differentiation of the white matter into tracts. Ascending and descending degeneration. Descending tracts : crossed and direct pyramidal tracts, antero-lateral descending tract. Ascending tracts : cere- bellar tract, antero-lateral ascending tract, median posterior tract 681 § 453. The special features of the several regions of the spinal cord. The conus medullaris, the lumbar, and cervical swellings. Varia- tions in the sectional area of the white matter .... 689 § 454. Variations in the sectional area of the grey matter .... 691 § 455. The relative size, form, and features of transverse sections of the cord at different levels 692 § 456. Variations in the several columns of white matter at different levels 693 SECTION III. THE REFLEX ACTIONS OF THE CORD. § 457. The difficulties attending the experimental investigation of the cen- tral nervous system ; ' shock ' and other effects of an operation 696 § 458. The differences, as regards reflex movements, between different kinds of animals. The features of a reflex act dependent on the character of the afferent impulses 698 CONTENTS. PAGE § 459. The characters of a reflex movement dependent on the strength of the stimulus 699 § 460. The characters of a reflex movement dependent on the part of the body to which the stimulus is applied 700 § 461. The complexity of many reflex movements ; their relation to intel- ligence 700 § 462. Reflex movements coordinated by afferent impulses other than the exciting impulses . . . . . . . ,- . . . 702 § 463. The characters of a reflex movement determined by the intrinsic condition of the cord 703 § 464. The reflex movements carried out by the spinal cord in man . . 704 § 465. Reflex actions resulting in changes other than movements . . 706 § 466. The inhibition of reflex actions 707 § 467. The time required for reflex actions 709 SECTION IV. THE AUTOMATIC ACTIONS OP THE SPINAL CORD. § 468. Automatic actions of the spinal cord in the frog and in the dog . 711 § 469. Automatic activity dependent on afferent impulses . . . .712 § 470. Tone of skeletal muscles . . . . . . . . .713 § 471. Tendon phenomena, knee jerk . . . .... 717 § 472. Rigidity of muscles through spinal action 717 CHAPTER IL THE BRAIN. SECTION I. ON THE PHENOMENA EXHIBITED BY AN ANIMAL DEPRIVED OF ITS CEREBRAL HEMISPHERES. § 473. The absence of distinct signs of volition and intelligence . .719 § 474. The characters of the movements of a brainless frog . . . 720 § 475. The phenomena exhibited by birds after removal of their cerebral hemispheres 723 § 476. The effects of removing the cerebral hemispheres in mammals . 725 § 477. The effects of removing the cerebral hemispheres in the dog . . 727 SECTION II. THE MACHINERY OF COORDINATED MOVEMENTS. § 478. The effects of injury to the semicircular canals. Our appreciation of the position of our body, the sense of equilibrium. Afferent impulses and sensations as factors of the coordination of move- ments 729 CONTENTS. xxxi PAGE 479. The phenomena and causation of vertigo 733 480. Forced movements 735 481. The parts of the middle brain concerned in the coordination of movements . 737 SECTION III. ON VOLUNTARY MOVEMENTS. § 482. The real distinction between voluntary and involuntary movements 739 § 483. The cortical motor areas of the dog ; the characters of the move- ments resulting from cortical stimulation 740 § 484. The cortical motor areas in the monkey 744 § 485. The cortical motor areas in the anthropoid ape .... 748 § 486. The movements of cortical origin carried out by means of the pyramidal tract ; the nature of the movements so carried out . 749 § 487. The results of the removal of a cortical area in dog and in the monkey 762 § 488. The cortical motor areas in man ; the area for speech . . . 764 § 489. The nature of the action of a motor area in carrying out a volun- tary movement ; the characters of aphasia. The same as illus- trated by the area for a limb in the dog ; the influence of sensory impulses 769 § 490. The relations of the motor area to other parts of the central nervous system ; the motor area employed in movements usually called involuntary 773 § 491. The passage of volitional impulses along the spinal cord in animals 774 § 492. Their passage in man 775 § 493. A summary of the chief facts concerning the carrying out of voluntary movements , . . 776 SECTION IV. ON THE DEVELOPMENT WITHIN THE CENTRAL NERVOUS SYSTEM OF VISUAL AND OF SOME OTHER SENSATIONS. § 494. Visual impulses and sensations ; visual fields, and binocular vision 781 § 495. The decussation of the optic nerves in the optic chiasma . . . 784 § 496. The course of the optic tract. The endings of the optic tract in the lateral corpus geniculatum, the pulvinar and the anterior corpus quadrigeminum ; the results of degeneration and atrophy experi- ments 785 § 497. The connection of the three above bodies with the cerebral cortex ; the meaning of the terms, blindness total and complete or par- tial, hemianopsia, amblyopia. The difficulties of interpretation attending experiments on the vision of animals .... 787 § 498. The nature of the movements of the eyes caused by stimulation of the occipital cortex 790 § 499. The effects on vision of removing parts of the occipital cortex in monkeys and in dogs ; the teachings of clinical histories . . 791 xxxii CONTENTS. PAGE § 500. The probable progressive development of visual sensations ; lower and higher visual centres . 793 § 501. Sensations of smell. The cortical area for smell .... 794 § 502. Sensations of taste . . 795 § 503. Sensations of hearing 796 SECTION V. ON THE DEVELOPMENT OF CUTANEOUS AND SOME OTHER SENSATIONS. § 504. Sensations of touch, heat, cold, and pain 798 § 505. Theoretical difficulties touching the cortical localisation of cutaneous sensations. The effects on cutaneous sensations of removing regions of the cortex 799 § 506. The afferent tracts from the spinal cord, their endings in the brain . 800 § 507. The effect of sections of the spinal cord on the transmission of afferent impulses influencing the vasomotor centre. Other experiments on animals as to the effects of sections of the spinal cord on the transmission of sensory impulses . '. . 802 § 508. The teachings of clinical histories ; different paths for different sensory impulses 804 § 509. General considerations on the development of sensations along the spinal cord. The cerebellar tract, the median posterior tract, the grey matter and internuncial tracts . ; • f . ' • . . 805 § 510. The terms ' sensory ' and ' motor ' not an adequate description of the processes in the central nervous system . ... 808 § 511. The transmission of sensations within the brain. The relations of the cerebellum . 810 SECTION VI. ON SOME OTHER ASPECTS OF THE FUNCTIONS OF THE BRAIN. 512. Considerations touching the cerebellum 812 513. Considerations touching the corpora quadrigemina .... 814 514. The splanchnic functions of the brain 816 SECTION VII. ON THE TIME TAKEN UP BY CEREBRAL OPERATIONS. 515. The reaction period or reaction time 819 516. Elementary analysis of psychical processes, the time taken up by each. The time required for discrimination, for the develop- ment of perception, and of the will ; the circumstances influenc- ing them 821 CONTENTS. xxxiii SECTION VIII THE LYMPHATIC ARRANGEMENTS OF THE BRAIN AND SPINAL CORD. PAGE § 517. The characters of the cerebro-spinal fluid 824 § 518. The renewal of the cerebro-spinal fluid. The purposes served by the fluid 825 SECTION IX. THE VASCULAR ARRANGEMENTS OF THE BRAIN AND SPINAL CORD. § 519. The distribution and characters of the arteries of the brain . . 827 § 520. The venous arrangements of the brain 828 § 521. The supply of blood to the brain relatively small. The methods of investigating the circulation of the brain 829 § 522. The supply of blood to the brain modified by the respiration and by changes in the general arterial pressure. The want of clear proof of special vasomotor nerves for the cerebral arteries . . 831 § 523. The flow of blood through the brain nevertheless influenced by changes taking place in the brain itself 833 CHAPTER III. SIGHT. SECTION I. ON THE GENERAL STRUCTURE OF THE EYE, AND ON THE FORMATION OF THE KETINAL IMAGE. 524. Dioptic mechanisms and visual impulses . . . . . - . 834 525. The general structure of the eye. The formation of the retinal image 835 526. A simple optic system ; its cardinal points. The refractive surfaces and media of the eye . . . ..... . .839 527. The optic constants of the eye. The diagrammatic eye . . . 841 528. The paths of the rays of light through the eye . . . . . 843 529. The retinal image in relation to the sensations excited by it . . 845 SECTION II. THE FACTS OF ACCOMMODATION. 530. The eye can accommodate for far and near objects ; far and near limits of accommodation 846 531. Schemer's experiment 847 xxxiv CONTENTS. PAGE § 532. Emmetropic, myopic, hypermetropic, and presbyopic eyes . . 849 § 533. The changes observed in the eye during accommodation . . . 850 SECTION III. THE MECHANISM OP ACCOMMODATION AND THE MOVEMENTS OP THE PUPIL. § 534. The mechanism for changing the anterior curvature of the lens . 854 § 535. The evidence that such a mechanism does effect the result . . 856 The Changes in the Pupil. § 536. Circumstances leading to constriction and to dilation of the pupil . 857 § 537. Constriction and dilation 858 § 538. The nerves supplying the pupil 859 § 539. Constriction a reflex act by means of the optic and oculo-motor nerves 860 § 540. Changes in the pupil through the action of the cervical sympathetic nerve 862 § 541. The nature of the dilating mechanism 863 § 542. Direct action of drugs and other agencies on the pupil . . . 866 § 543. The nervous mechanism of accommodation 868 § 544. The association of the movements of accommodation and the move- ments of the pupil . . 868 SECTION IV. IMPERFECTIONS IN THE DIOPTRIC APPARATUS. § 545. Imperfections of accommodation 870 § 546. Spherical aberration 871 § 547. Astigmatism 871 § 548. Chromatic aberration 873 § 549. Entoptic phenomena 874 SECTION V. ON SOME GENERAL FEATURES OP VISUAL SENSATIONS. § 550. The relation of the sensation to the intensity of the stimulus ; Weber's law 878 § 551. The relation of the sensation to the duration of the stimulus . . 881 § 552. Flickering and continuous sensations 883 § 553. Sensations produced by various changes in the retina referred to some external source of light 883 § 554. Localisation of visual sensations 885 § 655. The conditions of discrete visual sensations 886 § 556. The region of distinct vision. The limits of distinct vision . . 887 § 557. Nature of the discreteness of visual sensations ; retinal visual units 889 CONTENTS xxxv SECTION VI. ON COLOUR SENSATIONS. PAGE § 558. The existence of many kinds of colour sensations .... 891 § 559. The mixing of colour sensations 892 § 560. The several usual colour sensations result from the mixture of simpler, primary sensations 893 § 561. The conditions which determine the characters of colour sensations 895 § 562. Complementary colours 896 § 563. Any colour sensation produced by the suitable mixture of three colour sensations 897 § 564. The Young-Helmholtz theory of colour sensations .... 898 § 565. Her ing's theory of colour sensations. A comparison of the two theories 900 § 566. Variations in colour vision. Colour blindness. The different kinds of colour blindness; red blind and green blind; the Young-Helmholtz explanation of them 906 § 567. The explanation of colour blindness on Hering's theory . . . 909 §568. The probable subjective condition of the colour blind . . . 911 § 569. Blue or violet blindness ; absolute colour blindness . . . .912 § 570. Colour blindness in the periphery of the retina . . . . 913 § 571. The influence of the yellow spot 913 § 572. Colour sensations in relation to the intensity of the stimulus . . 913 SECTION VII. ON THE DEVELOPMENT or VISUAL IMPULSES. § 573. The blind spot . 916 § 574. Purkinje's figures ; their import . 917 § 575. Possible theories as to the mode of origin of visual sensations . . 920 § 576. Photochemistry of the retina ; visual purple ; the pigment epi- thelium 922 § 577. The functions of the layer of rods and cones. The ophthalmoscope 926 § 578. Possible differences of function of rods and cones .... 927 § 579. Electric currents in the retina . . . . . . . . 928 SECTION VIII. ON SOME FEATURES OF VISUAL SENSATIONS ESPECIALLY IN RELATION TO VISUAL PERCEPTIONS. 580. Simultaneous visual sensations ; the visual field .... 929 581. The psychological and physiological methods ; sensations and per- ceptions ; their want of agreement 929 582. Irradiation 932 583. Simultaneous contrast 932 584. After-images. Successive contrast . 933 xxxvi CONTENTS. PAGE § 585. The phenomena of * contrast ' in their bearing on the theories of colour vision 935 § 586. Recurrent sensations. Ocular phantoms or hallucinations . . 936 SECTION IX. BINOCULAR VISION. § 587. The movements of the eye-ball ; their limitations. Centre of rota- tion, visual axis, visual plane . . 939 § 588. The visual field and field of sight of one eye and of both eyes . . 940 § 589. Corresponding or identical points 942 § 590. The movements of the eye-ball ; the primary position and secondary positions ; the kind of movements which are possible . . 944 § 591. Listing's Law ; the experimental proof 946 § 592. The muscles of the eye-ball . . ... . . . .948 § 593. The action of the ocular muscles 949 § 594. The nervous mechanism of the movements of the eye-balls ; the coordination of the movements 952 § 595. The nervous centres for the movements of the eye-balls . . . 956 § 596. The Horopter 957 SECTION X. ON SOME FEATURES OP VISUAL PERCEPTIONS AND ON VISUAL JUDGMENTS. § 597. On the differences between the objective field of sight and the sub- jective field of vision . . . 959 § 598. The psychical processes belonging to visual perceptions ; illusions and visual judgments 961 § 599. Appreciation of apparent size 962 § 600. Judgment of distance and of actual size 964 §601. The judgment of solidity 966 § 602. The struggle of the two fields of vision 967 SECTION XI. THE NUTRITION OP THE EYE. § 603. The arrangement of the blood vessels 969 § 604. The vaso-motor changes in the eye 970 The Lymphatics of the Eye. § 605. The lymphatic vessels and lymph spaces of the eye .... 970 § 606. The aqueous humour ; the changes taking place in it ; how effected 972 § 607. The vitreous humour ; the changes taking place in it . . 974 CONTENTS. xxxvii SECTION XII THE PROTECTIVE MECHANISMS OF THE EYE. PAGE § 608. The eye-lids and their muscles 976 § 609. The conjunctiva and its glands. Tears. The secretion of tears . 977 CHAPTER IV. HEARING. SECTION I. ON THE GENERAL STRUCTURE OP THE EAR AND ON THE STRUCTURE AND FUNCTIONS OF THE SUBSIDIARY AUDITORY APPARATUS. § 610. The embryonic history of the ear. The otic vesicle . . .980 § 611. The general relations of the parts of the ear ; vestibule and cochlea, membranous and bony labyrinth, tympanum, auditory ossicles, membrana tympani and external meatus . . . 981 § 612. The general use of the several parts 986 The Conduction of Sound through the Tympanum. § 613. The chain of ossicles as a lever 988 § 614. longitudinal and transversal sonorous vibrations. The vibrations of the tympanic membrane . . . . • . • . , . 989 § 615. The conduction of vibrations through the chain of ossicles . . 991 § 616. The conduction of vibrations through the bones of the skull . . 992 § 617. The action of the tensor tympani and stapedius muscles . . 993 § 618. The Eustachian tube . 995 SECTION II. ON AUDITORY SENSATIONS. § 619. Noises and musical sounds 998 § 620. The characters of musical sounds ; loudness, pitch and quality ; fundamental and partial tones 998 § 621. The limits of auditory sensations 1000 § 622. Appreciation of differences of pitch 1001 § 623. The number of vibrations needed to excite a sensation . . . 1001 § 624. The characters of noises 1002 § 625. The effects of exhaustion . . . 1002 § 626. The fusion of auditory sensations 1003 § 627. The interference of vibrations. Beats 1004 xxxviii CONTENTS. SECTION III ON THE DEVELOPMENT OF AUDITORY IMPULSES. PAGE § 628. The transmission of impulses through the labyrinth ; the functions of the hair cells of the cochlea 1007 § 629. The analysis of complex waves of sound ; theories as to the mode of action of the organ of Corti 1013 § 630. The appreciation of the nature of sounds ultimately a psychical process 1015 § 631. Auditory functions of the vestibular labyrinth . . . . 1016 SECTION IV. ON AUDITORY PERCEPTIONS AND JUDGMENTS. § 632. Auditory phantoms 1020 § 633. The appreciation of outwardness in sounds is connected with the tympanum 1021 § 634. Hearing binaural. The judgment of the direction of sounds . . 1022 § 635. Judgment of the distance of sounds 1023 CHAPTER V. TASTE AND SMELL. SECTION I. OLFACTORY SENSATIONS. 636. The sensation due to contact of particles with the membrane . 1025 637. The chief characters of olfactory sensations 1026 638. Olfactory judgments. The olfactory nerve the nerve of smell . 1027 SECTION II. GUSTATORY SENSATIONS. 639. Sensations of taste usually or frequently accompanied by other sensations 1029 640. The different kinds of taste. Sensations of taste provoked by mechanical and electrical stimulation 1029 641. The conditions under which taste sensations are excited . . 1031 642. The distribution of the several kinds of tastes. Theories as to the mode of origin of taste sensations 1032 643. The nerves of taste ; the chorda tympani 1035 CONTENTS. xxxix CHAPTER VI. ON CUTANEOUS AND SOME OTHER SENSATIONS. SECTION I. THE GENERAL FEATURES OF CUTANEOUS SENSATIONS. PAQB § 644. Three kinds of cutaneous sensations, of pressure, of heat and cold, and of pain * ". . v . J- . . 1037 Tactile Sensations or Sensations of Pressure. § 645. The general characters of tactile sensations . „ ... 1037 § 646. The localisation of tactile sensations 1039 Sensations of Heat and Cold. § 647. Sensations of heat and cold due to sudden changes in the tem- perature of the skin ... 1041 § 648. The general characters of temperature sensations .... 1042 § 649. Tactile and temperature sensations in parts other than the external skin 1043 SECTION II. ON PAINFUL AND SOME OTHER KINDS OF SENSATION. § 650. Sensations of pain distinct from other sensations .... 1044 § 651. Sensations of pain are extreme degrees of common sensibility . 1044 § 652. Special nerve endings not necessary for sensations of pain ;• " . 1047 §653. Hunger and thirst . . -. 1048 SECTION III. ON THE MODE OF DEVELOPMENT OF CUTANEOUS SENSATIONS. § 654. The specific energy of nerves. Special terminal organs necessary for the sensations of touch and temperature as distinguished from sensations of pain 1051 § 655. The terminal organs for sensations of pressure different from those for sensations of temperature 1054 § 656. The terminal organs for sensations of heat different from those for sensations of cold . . 1055 § 657. The importance of contrast in cutaneous sensations . . . 1056 § 658. The nature of the terminal organs 1057 xl CONTENTS. SECTION IV. . THE MUSCULAR SENSE. PAGE § 659. We possess a sense of ' movement,' of ' position,' and of ' effort ' . 1059 § 660. The muscular sense distinguished from the sense of effort . . 1060 § 661. The afferent impulses forming the basis of the muscular sense are distinct from cutaneous impulses 1061 § 662. They are derived from the muscles, ligaments, and tendons . . 1063 SECTION V. ON TACTILE PERCEPTIONS AND JUDGMENTS. § 663. The ties between touch and the muscular sense .... 1066 § 664. The ties between touch and sight . . . . . . 1067 § 665. Cutaneous sensations may arise otherwise than from cutaneous events 1068 §666. Tactile Illusions 1069 CHAPTER VII. ON SOME SPECIAL MUSCULAR MECHANISMS. SECTION I. THE VOICE. § 667. The laryngoscopic view of the larynx 1070 § 668. The fundamental features of the voice ; loudness, pitch, and quality. The main conditions of the utterance of voice ; adduction and tightening of the vocal cords .... 1074 § 669. The muscles of the larynx 1076 § 670. The action of the muscles in reference to narrowing and widening the glottis and to tightening and slackening the vocal cords . 1080 § 671. The nervous mechanisms of the larynx. The respiratory move- ments of the larynx . 1081 § 672. The nervous mechanism of phonation 1084 § 673. The cortical area for movements of the larynx .... 1084 § 674. The different kinds of voice. Changes in the glottis other than those of mere adduction and general tension .... 1085 § 675. Chest-voice and head- voice. ' The registers of the voice. The com- plexity of the laryngeal movements 1087 § 676. The uses of the ventricles and other parts of the larynx . . 1091 §677. The « break ' in the voice at puberty 1091 CONTENTS. xli SECTION II. SPEECH. PAGE § 678. Speech, a mixture of musical sounds and of noises . . . 1092 § 679. Vowels and consonants 1092 § 680. The manner of formation of the several vowels . . . ^ 1093 § 681. The manner of formation of the several groups of consonants . 1096 § 682. The manner of formation of the more important individual con- sonants . . . , , 1097 SECTION III. ON SOME LOCOMOTOR MECHANISMS. § 683. The general characters of the actions of skeletal muscles ; . 1101 §684. The erect posture . : ^. . , .<• ' 1102 §685. Walking . ....... >;/ w, -;-. .... 1102 BOOK IV. THE TISSUES AND MECHANISMS OF REPRODUCTION. The general features of reproduction . . . . . . : - •. . 1109 CHAPTEE I. IMPREGNATION. SECTION I. MENSTRUATION. 687. The transference of the ovum from the ovary to the uterus. The changes in the uterine mucous membrane 1111 SECTION II. THE MALE ORGANS. 688. The movements of the spermatozoa 1114 689. The chemical constituents of semen. The vesicul£e seminales and prostate 1115 xlii CONTENTS. § 690. Erectile tissue 1115 § 691. The nature of erection 1116 § 692. The emission of semen 1117 CHAPTER II. PREGNANCY AND BIRTH. SECTION I. THE PLACENTA. § 693. The spermatozoon enters and unites with the ovum . . .1119 § 694. The formation of the decidua 1119 § 695. The decidua serotina is transformed into the placenta. The shed- ding of the placenta 1120 SECTION II. THE NUTRITION OP THE EMBRYO. $ 696. The embryo breathes by and feeds upon the maternal blood of the placenta 1123 § 697. The blood and blood-flow in the umbilical arteries and umbilical vein t-».i . 1124 § 698. The amniotic fluid, its nature and origin, its relations to the nutri- tion of the foetus 1126 § 699. The transmission of food material from the mother to the foetus . 1128 § 700. Glycogen in the foetus 1129 § 701. The movements of the foetus 1130 § 702. The digestive functions of the foetus 1130 § 703. The foetal circulation towards the close of uterine life . . .1132 § 704. The cause of the first breath 1134 § 705. The changes in the circulation taking place at birth . .. . 1134 SECTION III. PARTURITION. § 706. The period of gestation 1136 §707. The events of "labour" 1137 § 708. The reflex nature of parturition 11 40 § 709. The nerves concerned in the act . 1141 § 710. The causes determining the onset of labour . . . . .1142 J§ 711. The inhibition of parturition . . 1142 CONTENTS. xliii CHAPTER III. THE PHASES OF LIFE. PAGE §712. The composition of the babe as compared with the adult . .1144 § 713. The curve of growth from birth onwards 1145 § 714. The characters of the nutrition of the babe and infant . . r~ 1146 § 715. The nervous system of the babe 1148 § 716. Dentition 1149 § 717. Puberty. Differences of sex 1150 § 718. Old age 1151 § 719. Periodical events 1153 § 720. Sleep 1153 § 721. Other diurnal changes in the functions 1156 CHAPTER IV. DEATH. § 722. The general causation of death 1158 INDEX . 1161 LIST OF FIGUBES. FIG. PAGE 1. A muscle-nerve preparation . .56 2. Diagram of du Bois-Reymond key 58 3. Diagram illustrating apparatus arranged for experiments with muscle and nerve .. 60 4. Diagram of an induction coil ......... 62 5. The magnetic interruptor _ . . .63 6. The magnetic interruptor with Helmholtz's arrangement for equaliz- ing the make and break shocks 64 7. A muscle-curve from the gastrocnemius of a frog 66 8. The same, with the recording surface moving slowly .... 66 9. The same, with the recording surface travelling very rapidly . . 67 10. The pendulum myograph 68 11. Diagram of an arrangement of a vibrating tuning-fork with a Desprez signal 70 12. Curves illustrating the measurement of the velocity of a nervous impulse 73 13. Tracing of a double muscle-curve 76 14. Muscle-curve. Single induction-shocks repeated slowly . . . 76 15. The same, repeated more rapidly 77 16. The same, repeated still more rapidly 77 17. Tetanus produced with the ordinary magnetic interruptor ... 78 18. Non-polarizable electrodes 98 19. Diagram illustrating the electric currents of nerve and muscle . . 99 20. Diagram illustrative of the progression of electric changes . . . 103 21. Diagram of ascending and descending constant current . . . 112 22. Diagram of the electrotonic changes in irritability .... 114 23. Diagram illustrating electrotonic currents 115 24. Scheme of the nerves of a segment of the spinal cord . . . 140 25. Apparatus for investigating blood pressure 157 26. Tracing of arterial pressure in dog . ... . -. . . .158 27. Tracing of arterial pressure in rabbit . . . ... . 159 28. Lud wig's kymograph ' . . 160 29. Diagram of fall of blood pressure in arteries, capillaries and veins . 161 30. Arterial scheme . 167 31. Tracing from arterial model with little peripheral resistance .. . 168 32. The same with increased peripheral resistance . . . . 169 33. Ludwig'sstromuhr 173 34. Chauveau and Lortet's hsematachometer . . ... . - . 174 35. Diagram illustrating causes determining the velocity of the flow . . 176 36. Tracing from heart of cat 186 xliv LIST OF FIGURES. xlv FIG. PAGE 37. Marey's tambour, with cardiac sound 192 38. Tracings from right auricle and ventricle of horse (Chauveau and Marey) 193 39. Curves of endocardiac pressure by means of piston manometer . . 194 40. The membrane manometer of Hiirthle 194 41. Diagram of the same 195^ 42. Curve of ventricular pressure : membrane manometer . . . .196 43. Stolnikow's apparatus for measuring the output of the heart . ~r- 198 44. Cardiometer of Roy and Adami 199 45. • Tracing from the heart of a cat, by means of a light lever . . . 200 4(3. Cardiograms 201 47. Myocardiogram 202 48. Diagram of application of aortic and ventricular catheters . . . 203 49. Simultaneous tracings of ventricular and aortic pressure . . . 204 50. Diagram of the differential manometer of Hiirthle . . . .204 51. Simultaneous curves of aortic and ventricular pressure, and of the differential manometer ; descending systolic plateau . . . 205 52. The same, with the recording surface travelling rapidly . . . 205 53. Simultaneous curves of aortic and ventricular pressure and of the differential manometer ; ascending systolic plateau . . . 208 54. Diagram of ventricular and aortic pressure and of the cardiac impulse 209 55. Maximum and minimum manometer 210 56. Tick's spring manometer 220 57. Diagram of a sphygmograph : -. ; . . 221 58. Pulse tracing from radial artery • 223 59. Diagram of artificial pulse tracings 224 60. Diagram of progression of pulse wave . ..-'.-. . . . 225 61 . Pulse tracing with different pressures ....... 226 62. Pulse tracing from dorsalis pedis artery 227 63. Pulse tracing from carotid artery 230 64. Anacrotic pulse tracing 231 65. Dicrotic pulse tracing 231 66. A perfusion cannula 240 67. Diagram of apparatus for registering the beat of a frog's heart . . 241 68. Inhibition of heart beat in the frog 245 69. Diagram of the course of cardiac augmentor fibres in the frog . . 247 70. Cardiac inhibition in the mammal 250 71. The course of cardial inhibitory and augmentor fibres in the dog. . 254 72. Diagram of the course of vaso-constrictor fibres . . . • . . 266 73. Diagram of the nerves of the submaxillary gland 267 74. The depressor nerve 281 75. Rise of pressure due to stimulation of the sciatic nerve . . .282 76. Diagrammatic representation of the submaxillary gland of the dog with its nerves and blood vessels . 334 77. Alveoli of the pancreas of a rabbit at rest and in activity . . . 341 78. Changes in the parotid gland during secretion 343 79. Sections of the parotid gland of the rabbit at rest and after stimula- tion of the cervical sympathetic nerve 344 80. Mucous cells from the fresh submaxillary gland of the dog . . . 344 81. Alveoli of dog's submaxillary gland in loaded and in discharged phases 345 82. Gastric gland of mammal (bat) during activity 346 xlvi LIST OF FIGURES. FIG. PAGB 83. Diagram illustrating the influence of food on the secretion of the pancreatic juice 366 84. Diagram to illustrate the nerves of the alimentary canal in the dog . 384 85. Apparatus for taking tracings of the movements of the column of air in respiration 429 ' 86. Tracing of thoracic respiratory movements 432 87. Diagram of Lud wig's mercurial gas-pump 444 88. Diagram of Alvergniat's pump 446 89. The spectra of oxy-haemoglobin in different grades of concentration, of (reduced) hseinoglobin, and of carbonic-oxide-hsemoglobin . 452 90. Spectra of some derivatives of haemoglobin . . . . . . 459 91. Curve of the effect on respiration of section of one vagus . . . 476 92. Curve of the effect on respiration of section of both vagus nerves . 477 93. Curve of the quickening of respiration by gentle stimulation of the central end of the vagus trunk 477 94. Curve of respiratory increase due to stimulation of vagus nerve . 478 95. Curve of the inhibitory effects of stimulation of the superior laryngeal nerve 480 96. Curves illustrating the effects of distension and collapse of the lung . 481 97. Curve shewing the effects of repeated inflations of the lungs . . 482 98. Curve shewing the effects of repeated suctions of the lungs . . 482 99. Curves of blood-pressure and intra-thoracic pressure taken together . 498 100. Curves of blood-pressure during a suspension of breathing . . 505 101. Curve shewing Traube-Hering undulations . . ... . . 508 102. Renal oncometer 526 103. Oncograph 527 104. Tracing from renal oncometer 528 105. Section of the liver of frog 564 106. Three phases of the hepatic cells of the frog 565 107. Section of mammalian liver rich in glycogen 568 108. Section of mammalian liver containing little or no glycogen . . 568 109. Normal spleen curve from dog 580 110. A transverse dorso-ventral section of the spinal cord (human) at the level of the sixth thoracic nerve 682 111. Transverse dorso-ventral section of the spinal cord (human) at the level of the sixth cervical nerve 683 112. Transverse dorso-ventral section of the spinal cord (human) at the level of the third lumbar nerve 685 113. Diagram to illustrate the general arrangement of the several tracts of white matter in the spinal cord 686-687 114. Diagram illustrating some of the features of the1 spinal cord at differ- ent levels 688 115. Diagram shewing the united sectional areas of the spinal nerves pro- ceeding from below upwards 690 116. Diagram shewing the variations in the sectional area of the grey matter of the spinal cord, along its length 691 117. Diagram shewing the relative sectional areas of the spinal nerves as they join the spinal cord 691 118. Diagram shewing the variations in the sectional area of the lateral columns of the spinal cord, along its length 694 LIST OF FIGURES. xlvii FIG. PAGE 119. Diagram shewing the variations in the sectional area of the anterior columns of the spinal cord, along its length 694 120. Diagram shewing the variations in the sectional area of the posterior columns of the spinal cord, along its length 694 121. The areas of the cerebral convolutions of the dog .... 741 122. Outline of brain of monkey to shew the principal sulci and gyri . 744 123. Left hemisphere of the brain of monkey viewed from the left side and from above 745 124. Mesial aspect of the left half of the brain of monkey .... 747 125. Outline of horizontal section of brain, to shew the internal capsule . 750 126. Outline of a sagittal section through the hemisphere .... 751 127. Outline of a transverse dorso-ventral section of the right half of the brain 752 128. Transverse dorso-ventral section through the crus and anterior corpora quadrigemina 753 129. Transverse dorso-ventral section through the fore part of the pons . 754 130. Transverse dorso-ventral section through the pons at the exit of the fifth nerve 755 131. Transverse dorsal section through the bulb at the widest part of the fourth ventricle 756 132. Transverse dorso-ventral section through the bulb just behind the pons 757 133. Diagram to illustrate the relative size of the pyramidal tract in man, monkey and dog 761 134. Diagram of the convolutions and fissures on the lateral surface of the right cerebral hemisphere of man 767 135. The same on the mesial surface 767 136. The right lateral aspect of the cerebrum of man in outline, to illus- trate the cortical areas 76& 137. Mesial surface of the right cerebral hemisphere of man in outline, to illustrate the cortical areas 768 138. Diagram to illustrate the nervous apparatus of vision in man . . 783 139. Diagrammatic outline of a horizontal section of the eye, to illustrate the relations of the various parts ....... 836 140. Diagram of simple optical system ....... 840 141. Diagram of the schematic or diagrammatic eye .... 843 142. Diagram of the formation of a retinal image . . . . 844 143. Diagram of Scheiner's experiment 848 144. Diagram of images reflected from the eye 852 145. Diagram of the ciliary muscle as seen in a vertical radial section of the ciliary region .......... 855 146. Diagram to illustrate accommodation ...... 856 147. Diagrammatic representation of the nerves governing the pupil . 859 148. Diagram illustrating chromatic aberration 873 149. Diagram to illustrate entoptical images 876 150. Diagram of three primary colour sensations ..... 899 151. Diagram to illustrate Hering's theory of colour vision . . . 902 152. Diagram illustrating the formation of Purkinje's figures when the illumination is directed through the sclerotic . . . ' . 918 153. Diagram illustrating the formation of Purkinje's figures when the illumination is directed through the cornea 919 xlviii LIST OF FIGURES. FIG. PAGE 154. Diagram to illustrate the principles of a simple form of opthalmoscope 927 155. Figure to illustrate irradiation ........ 932 156. The visual field of the right eye 941 157. The visual fields (fields of sight) of the two eyes when the eyes converge to the same fixed point . . . . . . 942 158. Diagram illustrating corresponding points . . . . . 943 159. Figure to illustrate the insertions of the ocular muscles . . . 949 160. Diagram to illustrate the actions of the ocular muscles . . . 950 161. Diagram illustrating a simple horopter . . . . . . 957 162. Figure to illustrate the appreciation of apparent size . . . 962 163. The same 963 164. Figure to illustrate an optical effect produced by parallel slanting lines . 963 165. Figure to illustrate binocular vision ....... 967 166. Diagram to illustrate the general structure of the ear . . 982 167. The bony labyrinth 983 168. The membrana tympani 984 169. Diagram to illustrate the relations of auditory passage, tympanum and Eustachian tube 984 170. Frontal section through the tympanum ...... 985 171. Diagram of the median wall of the tympanum .... 985 172. The auditory ossicles 986 173. The ossicles in position 987 174. The ligaments of the ossicles ' . 988 175. The malleus and incus in position ....... 989 176. Diagram of the outer wall of the tympanum as seen from the mesial side 994 177. The stapes in position 995 178. The membranous labyrinth as seen from above .... 1008 179. The membranous labyrinth and the endings of the auditory nerve . 1009 180. Diagram of a transverse section of a whorl of the cochlea . . 1010 181. Diagram of the organ of Corti 1011 182. Diagram of the constituents of the organ of Corti .... 1012 183. Diagram of a laryngoscopic view of the larynx .... 1071 184. Diagram of the superior aperture of the larynx .... 1072 185. Diagram of the larynx in vertical section ...... 1072 186. Diagram of the larynx in vertical transverse section . . . 1073 187. The larynx as seen by means of the laryngoscope in different con- ditions of the glottis 1075 188. Diagram of the transverse and oblique arytenoid and of the posterior crico-arytenoid muscles ........ 1076 189. Diagram to illustrate the thyro-arytenoid muscles .... 1077 190. The internal thyro-arytenoid muscle 1078 191. The lateral crico-arytenoid muscle 1079 192. The crico-thyroid muscle 1079 193. Diagram to illustrate the contact of the feet with the ground in walking 1104 194. Diagram to illustrate running . . 1105 195. Diagram to illustrate the foetal circulation 1133 WIVBRSITY INTRODUCTION. § 1. DISSECTION, aided by microscopical examination, teaches us that the body of man is made up of certain kinds of material, so differing from each other in optical and other physical characters and so built up together as to give the body certain structural features. Chemical examination further teaches us that these kinds of material are composed of various chemical substances, a large number of which have this characteristic that they possess a considerable amount of potential energy capable of being set free, rendered actual, by oxidation or some other chemical change. Thus the body as a whole may, from a chemical point of view, be considered as a mass of various chemical substances, representing altogether a considerable capital of potential energy. § 2. This body may exist either as a living body or (for a certain time at least) as a dead body, and the living body may at any time become a dead body. At what is generally called the moment of death (but artificially so, for as we shall see the processes of death are numerous and gradual) the dead body so far as structure and chemical composition are concerned is exceed- ingly like the living body ; indeed the differences between the two are such as can be determined only by very careful examination, and are still to a large extent estimated by drawing inferences rather than actually observed. At any rate the dead body at the moment of death resembles the living body in so far as it represents a capital of potential energy. From that moment onwards however the capital is expended ; by processes which are largely those of oxidation, the energy is gradually dissipated, leaving the body chiefly in the form of heat. While these chemi- cal processes are going on the structural features disappear, and the body, with the loss of nearly all its energy, is at last resolved into " dust and ashes." ;i3;X>r :;THE /GIVING AND THE DEAD BODY. The characteristic of the dead body then is that, being a mass of substances of considerable potential energy, it is always more or less slowly losing energy never gaining energy ; the capital of energy present at the moment of death is more or less slowly diminished, is never increased or replaced. § 3. When on the other hand we study a living body we are struck with the following salient facts. 1. The living body moves of itself, either moving one part of the body on another or moving the whole body from place to place. These movements are active ; the body is not simply pulled or pushed by external forces, but the motive power is in the body •itself, the energy of each movement is supplied by the body itself. 2. These movements are determined and influenced, indeed often seem to be started, by changes in the surroundings of the body. Sudden contact between the surface of the body and some foreign object will often call forth a movement. The body is sensitive to changes in its surroundings, and this sensitiveness is manifested not only by movements but by other changes in the body. 3. It is continually generating heat and giving out heat to surrounding things, the production and loss of heat, in the case of man and certain other animals, being so adjusted that the whole body is warm, — that is, of a temperature higher than that of surrounding things. 4. From time to time it eats, — that is to say, takes into itself supplies of certain substances known as food, these substances being in the main similar to those which compose the body and being like them chemical bodies of considerable potential energy, capable through oxidation or other chemical changes of setting free a considerable quantity of energy. 5. It is continually breathing, — that is, taking in from the surrounding air supplies of oxygen. 6. It is continually, or from time to time, discharging from itself into its surroundings so-called waste matters, which waste matters may be broadly described as products of oxidation of the substances taken in as food, or of the substances composing the body. Hence the living body may be said to be distinguished from the dead body by three main features. The living body like the dead is continually losing energy (and losing it more rapidly than the dead body, the special breathing arrangements permitting a more rapid oxidation of its substance), but unlike the dead body is by means of food contin- ually restoring its substance and replenishing its store of energy. The energy set free in the dead body by the oxidation and other chemical changes of its substance leaves the body almost exclusively in the form of heat, whereas a great deal of energy leaves the living body as mechanical work, the result of various movements of the body ; and as we shall see a great deal of the INTEODUCTION. 3 energy which ultimately leaves the body as heat exists for a while within the living body in other forms than heat, though eventually transformed into heat. The changes in the surroundings affect the dead body at a slow rate and in a general way only, simply lessening or increasing the amount or rate of chemical change and the quantity of heat thereby set free, but never diverting the energy into some other form, such as that of movement ; whereas changes in the sur- roundings may in the case of the living body rapidly, profoundly, and in special ways affect not only the amount but also the kind of energy set free. The dead body left to itself slowly falls to pieces, slowly dissipates its store of energy, and slowly gives out heat. A higher or lower temperature, more or less moisture, a free or scanty supply of oxygen, the advent of many or few putrefactive organ- isms, — these may quicken or slacken the rate at which energy is being dissipated but do not divert that energy from heat into motion ; whereas in the living body so slight a change of surround- ings as the mere touch by a hair of some particular surface, may so affect the setting free of energy as to lead to such a discharge of energy in the form of movement that the previously apparently quiescent body may be suddenly thrown into the most violent convulsions. The differences therefore between living substance and dead substance though recondite are very great, and the ultimate object of Physiology is to ascertain how it is that living substance can do what dead substance cannot, — can renew its substance and replen- ish the energy which it is continually losing, and can according to the nature of its surroundings vary not only the amount but also the kind of energy which it sets free. Thus there are two great divisions of Physiology : one having to do with the renewal of substance and the replenishment of energy, the other having to do with the setting free of energy. § 4. Now, the body of man (or one of the higher animals) is a very complicated structure consisting of different kinds of mate- rial which we call tissues, such as muscular, nervous, connective, and the like, variously arranged in organs, such as heart, lungs, muscles, skin, etc., all built up to form the body according to certain morphological laws. But all this complication, though advantageous and indeed necessary for the fuller life of man, is not essential to the existence of life. The amoeba is a living being ; it renews its substance, replenishes its store of energy, and sets free energy now in one form, now in another ; and yet the amoeba may be said to have no tissues and no organs ; at all events this is true of closely allied but not so well-known simple beings. Using the more familiar amoaba as a type, and therefore leaving on one side the nucleus, and any distinction between endosarc and ectosarc, we may say that its body is homogeneous in the sense that if we divided it into small pieces, each piece would be like all 4 PEOTOPLASM. the others. In another sense it is not homogeneous; for we know that the amoeba receives into its substance material as food, and that this food or part of it remains lodged in the body until it is made use of and built up into the living substance of the body; arid each piece of the living substance of the body, must have in or near it some of the material which it is about to build up into itself. Further, we know that the amoeba gives out waste matters, such as carbonic acid and other substances ; and each piece of the amoeba must contain some of these waste matters about to be, but not yet, discharged from the piece. Each piece of the amoeba will therefore contain these three things : the actual living substance, the food about to become living substance, and the waste matters which have ceased to be living substance. Moreover, we have reasons to think that the living substance does not break down into the waste matters which leave the body at a single bound, but that there are stages in the downward progress between the one and the other. Similarly, though our knowledge on this point is less sure, we have reason to think that the food is not incorporated into the living substance at a single step, but that there are stages in the upward progress from the dead food to the living substance. Each piece of the body of the amoeba will therefore contain substances represent- ing various stages of becoming living, and of ceasing to be living, as well as the living substance itself. And we may safely make this statement though we are quite unable to draw the line where the dead food on its way up becomes living, or the living substance on its way down becomes dead. § 5. Nor is it necessary for our present purpose to be able to point out under the microscope, or to describe from a histological point of view, the parts which are living and the parts which are dead food or dead waste. The body of the amoeba is frequently spoken of as consisting of ' protoplasm.' The name was originally given to the matter forming the primordial utricle of the vegetable cell as distinguished from the cell wall on the one hand, and from the fluid contents of the cell or cell sap on the other, and also we may add from the nucleus. It has since been applied very generally to such parts of animal bodies as resemble, in their general features, the primordial utricle. Thus the body of a white blood corpuscle, or of a gland cell, or of a nerve cell, is said to consist of protoplasm. Such parts of animal bodies as do not in their general features resemble the matter of the primordial utricle are not called protoplasm, or, if they at some earlier stage did bear such resemblance, but no longer do so, are sometimes, as in the case of the substance of a muscular fibre, called ' differentiated proto- plasm.' Protoplasm in this sense sometimes appears, as in the outer part of most amoebae, as a mass of glassy-looking material, either continuous or interrupted by more or less spherical spaces or vacuoles filled with fluid, sometimes as in a gland cell as a more INTRODUCTION. 5 refractive, cloudy-looking, or finely granular material arranged in a more or less irregular network, or spongework, the interstices of which are occupied either by fluid or by some material different from itself. We shall return however to the features of this 'proto- plasm ' when we come to treat of white blood corpuscles and other ' protoplasmic ' structures. Meanwhile it is sufficient for our pres- ent purpose to note that lodged in the protoplasm, discontinuous with it, and forming no part of it, are in the first place collections of fluid, of watery solutions of various substances, occupying the more regular vacuoles or the more irregular spaces of the network, and in the second place discrete granules of one kind or another, also forming no part of the protoplasm itself, but lodged either in the bars or substance of the protoplasm or in the vacuoles or meshes. Now, there can be little doubt that the fluids and the discrete granules are dead food or dead waste, but the present state of our knowledge will not permit us to make any very definite statement about the protoplasm itself. We may probably conclude, indeed we may be almost sure, that protoplasm in the above sense is not all living substance ; that it is made up partly of the real living substance, and partly of material which is 'becoming living or has ceased to be living ; and in the case where protoplasm is described as forming a network, it is possible that some of the material occupying the meshes of the network may be, like part of the network itself, really alive. ' Protoplasm ' in fact, as in the sense in which we are now using it, and shall continue to use it, is a morphological term ; but it must be borne in mind that the same word ' protoplasm ' is also frequently used to denote what we have just now called 'the real living substance.' The word then embodies a physiological idea ; so used it may be applied to the living substance of all living structures, whatever the micro- scopical features of those structures ; in this sense it cannot at present, and possibly never will be recognised by the microscope, and our knowledge of its nature must be based on inferences. Keeping then to the phrase 'living substance' we may say that each piece of the body of the amoeba consists of living substance in which are lodged, or with which are built up in some way or other, food and waste in various stages. Now, an amoeba may divide itself into two, each half exhibiting all the phenomena of the whole ; and we can easily imagine the process to be repeated until the amoeba was divided into a multitude of exceedingly minute amoebae, each having all the properties of the original. But it is obvious, as in the like division of a mass of a chemical substance, that the division could not be repeated indefinitely. Just as in division of the chemical mass we come to the chemical molecule, further division of which changes the properties of the substance, so in the continued division of the amoeba we should come to a stage in which further division interfered with the physiological actions ; we should come 6 DIVISION OF LABOUR. to a physiological unit, corresponding to but greatly more complex than the chemical molecule. This unit to remain a physiological unit and to continue to live must contain not only a portion of the living substance but also the food for that living substance, in several at least of the stages, from the initial raw food up to the final ' living ' stages, and must similarly contain various stages of waste. §6. Now the great characteristic of the typically simple amoeba (leaving out the nucleus) is that, so far as we can ascer- tain, all the physiological units are alike ; they all do the same things. Each and every part of the body receives food more or less raw and builds it up into its own living substance; each and every part of the body may be at one time quiescent and at another in motion; each and every part is sensitive and responds by movement or otherwise to various changes in its sur- roundings. The body of man, in its first stage, while it is. as yet an ovum, if we leave aside the nucleus and neglect differences caused by the unequal distribution of food material or yolk, may also be said to be composed of like parts or like physiological units. By the act of segmentation however the ovum is divided into parts or cells which early shew differences from each other ; and these differences rapidly increase as development proceeds. Some cells put on certain characters and others other characters ; that is to say, the cells undergo Jiistological differentiation. And this takes place in such a way that a number of cells lying together in a group become eventually converted into a tissue ; and the whole body becomes a collection of such tissues arranged together according to morphological laws, each tissue having a definite structure, its cellular nature being sometimes preserved, sometimes obscured or even lost. This histological differentiation is accompanied by a physio- logical division of labour. Each tissue may be supposed to be composed of physiological units, the units of the same tissue being alike but differing from the units of other tissues ; and corre- sponding to this difference of structure, the units of different tissues behave or act differently. Instead of all the units as in the amoeba doing the same things equally well, the units of one tissue are told off as it were to do one thing especially well, or especially fully, and thus the whole labour of the body is divided among the several tissues. § 7. The several tissues may thus be classified according to the work which they have to do ; and the first great distinction is into (1) the tissues which are concerned in the setting free of energy in special ways, and (2) the tissues which are concerned in replenishing the substance and so renewing the energy of the body. Each physiological unit of the amoeba while it is engaged in INTEODUCTION. 7 setting free energy so as to move itself, and by reason of its sensitiveness so directing that energy as to produce a movement suitable to the conditions of its surroundings, has at the same time to bear the labour of taking in raw food, of selecting that part of the raw food which is useful and rejecting that which is useless, and of working up the accepted part through a variety of stages into its own living substance ; that is to say, it has at the same time that it is feeling and moving to carry on the work of digesting and assimilating. It has moreover at the same time to throw out the waste matters arising from the changes taking place in its own substance, having first brought these waste matters into a condition suitable for being thrown out. § 8. In the body of man, movements, as we shall see, are broadly speaking carried out by means of muscular tissue, and the changes in muscular tissue which lead to the setting free of energy in the form of movement are directed, governed, and adapted to the surroundings of man, by means of nervous tissue. Eays of light fall on the nervous substance of the eye called the retina, and set up in the retina changes which induce in the optic nerve other changes, which in turn are propagated to the brain as nervous impulses, both the excitation and the propagation involving an expenditure of energy. These nervous impulses reaching the brain may induce other nervous impulses which travelling down certain nerves to certain muscles may lead to changes in those muscles by which they suddenly grow short and pull upon the bones or other structures to which they are attached, in which case we say the man starts ; or the nervous impulses reaching the brain may produce some other effects. Similarly, sound falling on the ear, or contact between the skin and some foreign body, or some change in the air or other surroundings of the body, or some change within the body itself may so affect the nervous tissue of the body that nervous impulses are started and travel to this point or to that, to the brain or elsewhere, and eventually may either reach some muscular tissue and so give rise to movements, or may reach other tissues and produce some other effect. The muscular tissue then may be considered as given up to the production of movement, and the nervous tissue as given up to the generation, transformation, and propagation of nervous impulses. In each case there is an expenditure of energy, which in the case of the muscle, as we shall see, leaves the body partly as heat, and partly as work done, but in the case of nervous tissue is wholly or almost wholly transformed into heat before it leaves the body ; and this expenditure necessitates a replenishment of energy and a renewal of substance. § 9. In order that these master tissues — the nervous and muscular tissues — may carry on their important works to the best advantage, they are relieved of much of the labour which falls upon each physiological unit of the amoeba. They are not presented 8 TISSUES AND ORGANS. with raw food ; they are not required to carry out the necessary transformations of their immediate waste matters. The whole of the rest of the body is engaged (1) in so preparing the raw food, and so bringing it to the nervous and muscular tissues that these may build it up into their own substance with the least trouble ; and (2) in receiving the waste matters which arise in muscular and nervous tissues, and preparing them for rapid and easy ejection from the body. Thus to certain tissues, which we may speak of broadly as ' tissues of digestion,' is allotted the duty of acting on the food and preparing it for the use of the muscular and nervous tissues ; and to other tissues, which we may speak of as ' tissues of excretion/ is allotted the duty of clearing the body from the waste matters generated by the muscular and nervous tissues. § 10. These tissues are for the most part arranged in machines or mechanisms called organs, and the working of these organs in- volves movement. The movements of these organs are carried out, like the other movements of the body, chiefly by means of muscular tissue governed by nervous tissue. Hence we may make a dis- tinction between the muscles which are concerned in producing an effect on the world outside man's body — the muscles by which man does his work in the world — and the muscles which are con- cerned in carrying out the movements of the internal organs ; and we may similarly make a distinction between the nervous tissue concerned in carrying out the external work of the body and that concerned in regulating the movements and, as we shall see, the general conduct of the internal organs. But these two classes of muscular and nervous tissue though distinct in work and, as we shall see, often different in structure, are not separated or isolated. On the contrary, while it is the main duty of the nervous tissue as a whole (the nervous system, as we may call it) to carry out, by means of nervous impulses passing hither and thither, what may be spoken of as the work of man, and in this sense is the master tissue, it also serves as a bond of union between itself and the muscles doing external work on the one hand, and the organs of digestion or excretion on the other, so that the activity and con- duct of the latter may be adequately adapted to the needs of the former. § 11. Lastly, the food prepared and elaborated by the digestive organs is carried and presented to the muscular and nervous tissues in the form of a complex fluid known as blood, which driven by means of a complicated mechanism known as the vascular system, circulates all over the body, visiting in turn all the tissues of the body, and by a special arrangement known as the respiratory mechanism, carrying in itself to the several tissues a supply of oxygen as well as of food more properly so called. The motive power of this vascular system is supplied as in the case of the digestive system by means of muscular tissue, the INTRODUCTION. 9 activity of which is similarly governed by the nervous system, and hence the flow of blood to this part or that part is regulated according to the needs of the part. § 12. The above slight sketch will perhaps suffice to shew not only how numerous but how varied are the problems with which Physiology has to deal. In the first place there are what may be called general prob- lems, such as, How the food after its preparation and elaboration into blood is built up into the living substance of the several tissues ? How the living substance breaks down into the dead waste ? How the building up and breaking down differ in the different tissues in such a way that energy is set free in different modes, — the muscular tissue contracting, the nervous tissue thrill- ing with a nervous impulse, the secreting tissue doing chemical work, and the like ? To these general questions the answers which we can at present give can hardly be called answers at all. In the second place there are what may be called special problems, such as, What are the various steps by which the blood is kept replenished with food and oxygen, and kept free from an accumulation of waste, and how is the activity of the digestive, respiratory, and excretory organs, which effect this, regulated and adapted to the stress of circumstances ? What are the details of the working of the vascular mechanism by which each and every tissue is forever bathed with fresh blood, and how is that working delicately adapted to all the varied changes of the body ? And, compared with which all other special problems are insignifi- cant and preparatory only, How do nervous impulses so flit to and fro within the nervous system as to issue in the movements which make up what we sometimes call the life of man ? It is to these special problems that we must chiefly confine our attention, and we may fitly begin with a study of the blood. ) I o "7 ^ BOOK I. BLOOD. THE TISSUES OF MOVEMENT. THE VASCULAE MECHANISM. CHAPTER I. BLOOD. § 13. THE several tissues are traversed by minute tubes, — the capillary blood vessels, — to which blood is brought by the arteries, and from which blood is carried away by the veins. These capillaries form networks the meshes of which, differing in form and size in the different tissues, are occupied by the elements of the tissue which consequently lie outside the capillaries. The blood flowing along the capillaries consists, under normal conditions, of an almost colourless fluid, the plasma, in which are carried a number of bodies, the red and the white corpuscles. Outside the capillary walls, filling up such spaces as exist between the capillary walls and the cells or fibres of the tissue, or between the elements of the tissue themselves, is found a colourless fluid, resembling in many respects the plasma of blood and called lymph. Thus all the elements of the tissue and the outsides of all the capillaries are bathed with lymph, which, as we shall see hereafter, is continually flowing away from the tissue along special channels to pass into lymphatic vessels and thence into the blood. As the blood flows along the capillaries certain constituents of the plasma (together with, at times, white corpuscles, and under exceptional circumstances red corpuscles) pass through the capillary wall into the lymph, and certain constituents of the lymph pass through the capillary wall into the blood within the capillary. There is thus an interchange of material between the blood within the capillary and the lymph outside. A similar interchange of material is at the same time going on between the lymph and the tissue itself. Hence, by means of the lymph acting as middleman, a double interchange of material takes place between the blood within the capillary and the tissue outside the capillary. In every tissue, so long as life lasts and the blood flows through the blood vessels, a double stream, now rapid now slow, is passing from the blood to the tissue and from the tissue to the blood. The stream from the blood to the tissue carries to the tissue the material which the tissue needs for building itself up and for doing its work, including the all-important oxygen. The 14 BLOOD AN INTERNAL MEDIUM. [BOOK i. stream from the tissue to the blood carries into the blood certain of the products of the chemical changes which have been taking place in the tissue, — products which may be simple waste, to be cast out of the body as soon as possible, or which may be bodies capable of being made use of by some other tissue. A third stream, that from the lymph lying in the chinks and crannies of the tissue along the lymph channels to the larger lymph vessels, carries away from the tissue such parts of the material coming from the blood as are not taken up by the tissue itself and such parts of the material coming from the tissue as do not find their way into the blood vessel. In most tissues, as in muscle for instance, the capillary net- work is so close set and the muscular fibre lies so near to the blood vessel that the lymph between the two exists only as a very thin sheet ; but in some tissues, as in cartilage, the blood vessels lie on the outside of a large mass of tissue, the interchange be- tween the central parts of which and the nearest capillary blood vessel is carried on through a long stretch of lymph. But in each case the principle is the same ; the tissue, by the help of lymph, lives on the blood; and when in succeeding pages we speak of changes between the blood and the tissues, it will be understood, whether expressly stated so or no, that the changes are effected by means of the lymph. The blood may thus be regarded as an internal medium bearing the same relations to the constituent tissues that the external medium, the world, does to the whole individual. Just as the whole organism lives on the things around it, its air and its food, so the several tissues live on the complex fluid by which they are all bathed and which is to them their immediate air and food. All the tissues take up oxygen from the blood and give up carbonic acid to the blood, but not always at the same rate or at the same time. Moreover the several tissues take up from the blood and give up to the blood either different things or the same things at different rates or at different times. From this it follows, on the one hand, that the composition and characters of the blood must be for ever varying in different parts of the body and at different times ; and on the other hand, that the united action of all the tissues must tend to establish and maintain an average uniform composition of the whole mass of blood. The special changes which blood is known to undergo while it passes through the several tissues will best be dealt with when the individual tissues and organs come under our considera- tion. At present it will be sufficient to study the main features which are presented by blood, brought, so to. speak, into a state of equilibrium by the common action of all the tissues. Of all these main features of blood, the most striking if not the most important is the property it possesses of clotting when shed. SEC. 1. THE CLOTTING OF BLOOD. § 14, Blood, when shed from the blood vessels of a living body, is perfectly fluid. In a short time it becomes viscid : it flows less readily from vessel to vessel. The viscidity increases rapidly until the whole mass of blood under observation becomes a complete jelly. The vessel into which it has been shed can at this stage be inverted without a drop of the blood being spilt. The jelly is of the same bulk as the previously fluid blood, and if carefully shaken out will present a complete mould of the interior of the vessel. If the blood in this jelly stage be left untouched in a glass vessel, a few drops of an almost colourless fluid soon make their appearance on the surface of the jelly. Increasing in number, and running together, the drops after a while form a superficial layer of pale straw-coloured fluid. Later on, similar layers of the same fluid are seen at the sides and finally at the bottom of the jelly, which, shrunk to a smaller size and of firmer consistency, now forms a clot or crassamentum, floating in a perfectly fluid serum. The shrinking and condensation of the clot, and the corresponding increase of the serum, continue for some time. The upper surface of the clot is generally slightly concave. A portion of the clot examined under the microscope is seen to consist of a feltwork of fine granular fibrils, in the meshes of which are entangled the red and white corpuscles of the blood. In the serum nothing can be seen but a few stray corpuscles, chiefly white. The fibrils are composed of a substance called fibrin. Hence we may speak of the clot as consisting of fibrin and corpuscles ; and the act of clotting is obviously a substitution for the plasma of fibrin and serum, followed by a separation of the fibrin and corpuscles from the serum. In man, blood when shed becomes viscid in about two or three minutes, and enters the jelly stage in about five or ten minutes. After the lapse of another few minutes the first drops of serum are seen, and clotting is generally complete in from one 16 PHENOMENA OF CLOTTING. [BOOK i. to several hours. The times however will be found to vary accord- ing to circumstances. Among animals the rapidity of clotting varies exceedingly in different species. The blood of the horse clots with remarkable slowness ; so slowly indeed that many of the red and also some of the white corpuscles (both these being speci- fically heavier than the plasma) have time to sink before viscidity sets in. In consequence there appears on the surface of the blood an upper layer of colourless plasma, containing in its deeper por- tions many colourless corpuscles (which are lighter than the red). This layer clots like the other parts of the blood, forming the so- called ' buffy coat.' A similar buffy coat is sometimes seen in the blood of man, in certain abnormal conditions of the body. If a portion of horse's blood be surrounded by a cooling mixture of ice and salt, and thus kept at about 0°C., clotting may be almost indefinitely postponed. Under these circumstances a more complete descent of the corpuscles takes place, and a considerable quantity of colourless transparent plasma free from blood-corpuscles may be obtained. A portion of this plasma removed from the freezing mixture clots in the same manner as does the entire blood. It first becomes viscid and then forms a jelly, which subsequently separates into a colourless shrunken clot and serum. This shews that the corpuscles are not an essential part of the clot. If a few cubic centimetres of this colourless plasma, or of a. similar plasma which may be obtained from almost any blood by means which we will presently describe, be diluted with many times its bulk of a 0-6 p.c. solution of sodium chloride1 clotting is much retarded, and the various stages may be more easily watched. As the fluid is becoming viscid, fine fibrils of fibrin will be seen to be developed in it, especially at the sides of the containing vessel. As these fibrils multiply in number, the fluid becomes more and more of the consistence of a jelly and at the same time somewhat opaque. Stirred or pulled about with a needle, the fibrils shrink up into a small, opaque, stringy mass ; and a very considerable bulk of the jelly may by agitation be resolved into a minute fragment of shrunken fibrin floating in a quantity of what is really diluted serum. If a specimen of such diluted plasma be stirred from time to time, as soon as clotting begins, with a needle or glass rod, the fibrin may be removed piecemeal as it forms, and the jelly stage may be altogether done away with. When fresh blood which has not yet had time to clot is stirred or whipped with a bundle of rods (or anything presenting a large amount of rough surface), no jelly-like clotting takes place, but the rods become covered with a mass of shrunken fibrin. Blood thus whipped until fibrin ceases to be deposited, is found to have entirely lost its power of clotting. 1 A solution of sodium chloride of this strength will hereafter be spoken of as- 'normal saline solution.' CHAP, i.] BLOOD. 17 Putting these facts together, it is very clear that the pheno- mena of the clotting of blood are caused by the appearance in the plasma of fine fibrils of fibrin. So long as these are scanty, the blood is simply viscid. When they become sufficiently numerous, they give the blood the firmness of a jelly. Soon after their formation they begin to shrink, and while shrinking enclose in their meshes the corpuscles but squeeze out the fluid parts of the blood. Hence the appearance of the shrunken coloured clot and the colourless serum. § 15. Fibrin, whether obtained by whipping freshly-shed blood, or by washing either a normal clot, or a clot obtained from colour- less plasma, exhibits the same general characters. It belongs to that class of complex unstable nitrogenous bodies called proteids which form a large portion of all living bodies and an essential part of all living structures. ? Our knowledge of proteids is at present too imperfect, and probably none of them have yet been prepared in adequate purity, to justify us in attempting to assign to them any definite formula ; but it is important to remember their general composition. 100 parts of a proteid contain rather more than 50 parts of carbon, rather more than 15 of nitrogen, about 7 of hydrogen, and rather more than 20 of oxygen ; that is to say, they contain about half their weight of carbon, and only about ^th their weight of nitrogen ; and yet as we shall see they are eminently the nitrogenous sub- stances of the body. They usually contain a small quantity (1 or 2 p.c.) of sulphur, and many also have some phosphorus attached to them in some way or other. When burnt they leave a variable quantity of ash, consisting of inorganic salts of which the bases are chiefly sodium and potassium and the acids chiefly hydrochloric, sulphuric, phosphoric, and carbonic. They all give certain reactions, by which their presence may be recognised ; of these the most characteristic are the following : Boiled with nitric acid they give a yellow colour, which deepens into orange upon the addition of ammonia. This is called the xanthoproteic test ; the colour is due to a product of decomposi- tion. Boiled with the mixture of mercuric and mercurous nitrates known as Millon's reagent they give a pink colour. Mixed with a strong solution of sodic hydrate they give on the addition of a drop or two of a very weak solution of cupric sul- phate a violet colour which deepens on heating. These are artificial reactions, not throwing much if any light on the constitution of proteids ; but they are useful as practical tests enabling us to detect the presence of proteids. The several members of the proteid group are at present dis- tinguished from each other chiefly by their respective solubilities, especially in various saline solutions. Fibrin is one of the least soluble ; it is insoluble in water, almost insoluble in dilute neutral saline solutions, very sparingly soluble in more concentrated 2 18 PKOTEIDS OF SERUM. [BOOK i. neutral saline solutions and in dilute acids and alkalis, but is easily dissolved in strong acids and alkalis. In the process of solution it becomes changed into something which is no longer fibrin. In dilute acids it swells up and becomes transparent, but when the acid is neutralized returns to its previous condition. When suspended in water and heated to 100° C. or even to 75° C., it becomes changed ; it is still less soluble than before. It is said in this case to be coagulated by the heat ; and as we shall see. nearly all proteids have the property of being changed in nature, of undergoing coagulation and so becoming less soluble than before, by being exposed to a certain high temperature. Fibrin then is a proteid distinguished from other proteids by its smaller solubility ; it is further distinguished by its peculiar filamentous structure, the other proteids when obtained in a solid form appearing either in amorphous granules or at most in viscid masses. 16. We may now return to the serum. "his is perfectly fluid, and remains fluid until it decomposes. It is of a faint straw colour, due to the presence of a special pigment substance, differing from the red matter which gives redness to the red corpuscles. Tested by the xanthoproteic and other tests it obviously contains a large quantity of proteid matter, and upon examination we find that at least two distinct proteid substances are present in it. If crystals of magnesium sulphate be added to serum and gently stirred until they dissolve, it will be seen that the serum as it approaches saturation with the salt becomes turbid instead of remaining clear, and eventually a white amorphous granular or flocculent precipitate makes its appearance. This precipitate may be separated by decantation or filtration, washed with saturated solutions of magnesium sulphate, in which it is insoluble, until it is freed from all other constituents of the serum, and thus obtained fairly pure. It is then found to be a proteid body, distinguished by the following characters among others : — 1. It is (when freed from any adherent magnesium sulphate) insoluble in distilled water ; it is insoluble in concentrated solutions of neutral saline bodies, such as magnesium sulphate, sodium chloride, &c., but readily soluble in dilute (e.g. 1 p.c) solutions of the same neutral saline bodies. Hence from its solutions in the latter it may be precipitated either by adding more neutral saline substance or by removing by dialysis the small quantity of saline substance present. When obtained in a precipitated form, and suspended in distilled water, it readily dissolves into a clear solution upon the addition of a small quan- tity of some neutral saline body. By these various solutions and precipitations it is not really changed in nature. 2. It readily dissolves in very dilute acids (e.g. in hydro- CHAP, i.] BLOOD. 19 chloric acid even when diluted to far less than 1 p.c.), and it is similarly soluble in dilute alkalis ; but in being thus dissolved it is changed in nature, and the solutions of it in dilute acid and dilute alkalis give reactions quite different from those of the solution of the substance in dilute neutral saline solutions. By the acid it is converted into what is called acid-albumin, by the alkali into alkali-albumin, both of which bodies we shall have to study later on. 3. When it is suspended in water and heated it becomes altered in character, coagulated, and all its reactions are changed. It is no longer soluble in dilute neutral saline solutions, not even in dilute acids and alkalis ; it has become coagulated proteid, and is now even less soluble than fresh fibrin. When a solution of it in dilute neutral saline solution is similarly heated, a similar change takes place : a precipitate falls down which on examination is found to be coagulated proteid. The temperature at which this change takes place is somewhere about 75° C., though shift- ing slightly according to the quantity of saline substance present in the solution. The above three reactions are given by a number of proteid bodies forming a group called globulins, and the particular globulin present in blood-serum, is called paraglobulin. One of the proteids present in blood-serum is then para- globulin, characterised by its solubility in dilute neutral saline solutions ; its insolubility in distilled water and concentrated saline solutions ; its ready solubility, and at the same time conversion into other bodies, in dilute acids and alkalis ; and in its becoming converted into coagulated proteid, and so being precipitated from its solutions at 75° C. The amount of it present in blood-serum varies in various animals, and apparently in the same animal at different times. In 100 parts by weight of serum there are generally present about 8 or 9 parts of proteids altogether ; and of these some 3 or 4, more or less, may be taken as paraglobulin. § 17. If the serum from which the paraglobulin has been precipitated by the addition of neutral salt, and removed by fil- tration, be subjected to dialysis, the salt added may be removed, and a clear, somewhat diluted serum free from paraglobulin may be obtained. This still gives abundant proteid reactions, so that the serum still contains a proteid, or some proteids still more soluble than the globulins, since they will remain in solution, and are not precipitated, even when dialysis is continued until the serum is practically freed from both the neutral salt added to it and the diffusible salts previously present in the natural serum. When this serum is heated to 75° C. a precipitate makes its appearance; the proteids still present are coagulated at this temperature. 2—2 20 PROTELDS OF SEKUM. [BOOK i. We have some reasons for thinking that more than one proteid is present ; but they are all closely allied to each other, and we may for the present speak of them as if they were one, and call the proteid left in serum, after removal of the paraglobulin, by the name of albumin, or, to distinguish it from other albumins found elsewhere, serum-albumin. Serum-albumin is distinguished by being more soluble than the globulins, since it is soluble in dis- tilled water, even in the absence of all neutral salts. Like the globulins, though with much less ease, it is converted by dilute acids and dilute alkalis into acid- or into alkali-albumin. The percentage amount of serum-albumin in serum may be put down as 4 or 5, more or less ; but it varies, and sometimes is less abundant than paraglobulin. In some animals (snakes) it is said to disappear during starvation. The more important characters of the three proteids which we have just studied may be stated as follows : — Soluble in water and in saline solutions of all strengths . serum-albumin. Insoluble in water, readily soluble in dilute saline solutions, insoluble in concentrated saline solutions paraglobulin. Insoluble in water, hardly soluble at all in dilute saline solutions, and very little solu- ble in more concentrated saline solutions . fibrin. Besides paraglobulin and serum-albumin, serum contains a very large number of substances, generally . in small quantity, which, since they have to be extracted by special methods, are called extractives ; of these some are nitrogenous, some non- nitrogenous. Serum contains in addition important inorganic saline substances ; but to these we shall return. § 18. With the knowledge which we have gained of the pro- teids of clotted blood we may go back to the question : Clotting being due to the appearance in blood plasma of a proteid sub- stance, fibrin, which previously did not exist in it as such, what are the causes which lead to the appearance of fibrin ? We learn something by studying the most important external circumstances which affect the rapidity with which the blood of the same individual clots when shed. These are as follows : — A temperature of about 40° C., which is about or slightly above the temperature of the blood of warm-blooded animals, is perhaps the most favourable to clotting. A further rise of a few degrees is apparently also beneficial, or at least not injurious ; but upon a still further rise the effect changes, and when blood is rapidly heated to 56° C. no clotting at all may take place. At this temperature certain proteids of the blood are coagulated and precipitated before clotting can take place, and with this change the power of the blood to clot is wholly lost. If however the heating be not CHAP. i.J BLOOD. 21 very rapid, the blood may clot before this change has time to come on. When the temperature instead of being raised is lowered below 40° C. the clotting becomes delayed and prolonged ; and at the temperature of 0° or 1° C. the blood will remain fluid, and yet capable of clotting when withdrawn from the adverse circumstances, for a very long, it might almost be said for an indefinite, time. A small quantity of blood shed into a small vessel clots sooner than a large quantity shed into a larger one ; and in general the greater the amount of foreign surface with which the blood comes in contact the more rapid the clotting. When shed blood is stirred or " whipped " the fibrin makes its appearance sooner than when the blood is left to clot in the ordinary way ; so that here too the accelerating influence of contact with foreign bodies makes itself felt. Similarly, movement of shed blood hastens clotting, since it increases the amount of contact with foreign bodies. So also the addition of spongy platinum or of powdered charcoal, or of other inert powders, to tardily clotting blood, will by influence of surface, hasten clotting. Conversely, blood brought into contact with pure oil does not clot so rapidly as when in contact with glass or metal ; and blood will continue to flow for a longer time without clotting through a tube smeared inside with oil than through a tube not so smeared. The influence of the oil in such cases is a physical not a chemical one ; any pure, neutral, inert oil will do. As far as we know, these influences affect only the rapidity with which the clotting takes place ; that is, the rapidity with which the fibrin makes its appearance, not the amount of clot, not the quan- tity of fibrin formed, though when clotting is very much retarded by cold changes may ensue whereby the amount of clotting which eventually takes place is indirectly affected. Mere exposure to air exerts apparently little influence on the process of clotting. Blood collected direct from a blood-vessel over mercury so as wholly to exclude the air, clots, in a general way, as readily as blood freely exposed to the air. It is only when blood is much laden with carbonic acid, the presence of which is antagonistic to clotting, that exclusion of air, by hindering the escape of the excess of carbonic acid, delays clotting. These facts teach us that fibrin does not as was once thought make its appearance in sjied blood because the blood when shed ceases to share in the movement of the circulation, or because the blood is cooled on leaving the warm body, or because the blood is then more freely exposed to the air ; they further suggest the view that the fibrin is the result of some chemical change, the conversion into fibrin of something which is not fibrin, the change like other chemical changes being most active at an optimum temperature, and like so many other chemical changes being assisted by the influences exerted by the presence of inert bodies. And we have direct experimental evidence that plasma does contain an antecedent of fibrin which by chemical change is converted into fibrin. 22 PLASMA. [BOOK i. . §19. If blood be received direct from the blood-vessels into one-third its bulk of a saturated solution of some neutral salt such as magnesium sulphate, arid the two gently but thoroughly mixed, clotting, especially at a moderately low temperature, will be deferred for a very long time. If the mixture be allowed to stand, the corpuscles will sink, and a colourless plasma will be obtained similar to the plasma gained from horse's blood by cold, except that it contains an excess of the neutral salt. The presence of the neutral salt has acted in the same direction as cold : it has prevented the occurrence of clotting. It has not destroyed the fibrin ; for if some of the plasma be diluted with from five to ten times its bulk of water, it will clot speedily in quite a normal fashion, with the production of quite normal fibrin. The separation of the fluid plasma from the corpuscles and from other bodies heavier than the plasma is much facilitated by the use of the centrifugal machine. This consists essentially of a tireless wheel with several spokes, placed in a horizontal position and made to revolve with great velocity (1000 revolutions per minute for instance) round its axis. Tubes of metal or very strong glass are suspended at the ends of the spokes by carefully adjusted joints. As the wheel rotates with increasing velocity, each tube gradually assumes a horizontal position, bottom outwards, without spilling any of its contents. As the rapid rotation continues the corpuscles and heavier particles are driven to the bottom of the tube, and if a very rapid movement be continued for a long time will form a compact cake at the bottom of the tube. When the rotation is stopped the tubes gradually return to their upright posi- tion again without anything being spilt, and the clear plasma in each tube can then be decanted off. If some of the colourless, transparent plasma, obtained either by the action of neutral salts from any blood, or by the help of cold from horse's blood, be treated with some solid neutral salt, such as sodium chloride, to saturation, a white, flaky, somewhat sticky precipitate will make its appearance. If this precipitate be removed, the fluid no longer possesses the power of clotting (or very slightly so), even though the neutral salt present be removed by dialysis, or its influence lessened by dilution. With the re- moval of the substance precipitated, the plasma has lost its power of clotting. If the precipitate itself, after being washed with a saturated solution of the neutral salt (in which it is insoluble) so as to get rid of all serum and other constituents of the plasma, be treated with a small quantity of water, it readily dissolves,1 and the solution rapidly filtered gives a clear, colourless filtrate, which is at first perfectly fluid. Soon, however, the fluidity gives way to 1 The substance itself is not soluble in distilled water, but a quantity of the neutral salts always clings to the precipitate, and thus the addition of water virtually gives rise to a dilute saline solution, in which the substance is readily soluble. CHAP, i.] BLOOD. 23 viscidity, and this in turn to a jelly condition, and finally the jelly shrinks into a clot floating in a clear fluid ; in other words, the filtrate clots like plasma. Thus there is present in cooled plasma, and in plasma kept from clotting by the presence of neutral salts, a something, precipi table by saturation with neutral salts ; a some- thing which, since it is soluble in very dilute saline solutions, cannot be fibrin itself, but which in solution speedily gives rise to the appearance of fibrin. To this substance its discoverer, Denis, gave the name of plasmine. The substance thus precipitated is not however a single body but a mixture of at least two bodies. If sodium chloride be carefully added to plasma to an extent of about 13 per cent, a white, flaky, viscid precipitate is thrown down very much like plasmine. If after the removal of the first precipitate more sodium chloride and especially if magnesium sulphate be added, a second precipitate is thrown down, less viscid and more granular than the first. The second precipitate when examined is found to be identical with the paraglobulin, coagulating at 75° C., which we have already seen to be a constituent of serum. The first precipitate is also a proteid belonging to the globulin group, but differs from paraglobulin not only in being more readily precipitated by sodium chloride, and in being when precipitated more viscid, but also in other respects, and especially in being coagulated at a far lower temperature than paraglobulin, viz. at 56° C. Now, while isolated paraglobulin cannot by any means known to us be converted into fibrin, and its presence in the so-called plasmine does not seem to be essential to the for- mation of fibrin out of plasmine, the presence in plasmine of the body coagulating at 56° C. does seem essential to the conversion of plasmine into fibrin ; and we have reason for thinking that it is itself converted, in part at least, into fibrin. Hence it has received the name of fibrinogen. § 20. The reasons for this view are as follows. Besides blood, which clots naturally when shed, there are certain fluids in the body which do not clot naturally, either in the body or when shed, but which by certain artificial means may be made to clot, and in clotting to yield quite normal fibrin. Thus the so-called serous fluid taken some hours after death1 from the pericardial, pleural, or peritoneal cavities, the fluid found in the enlarged serous sac of the testis, known as hydrocele fluid, and other similar fluids, will in the majority of cases, when obtained free from blood or other admixtures, remain fluid almost indefinitely, shewing no disposition whatever to clot.2 Yet in most cases at 1 If it be removed immediately after death it generally clots readily and firmly, giving a colourless clot consisting of fibrin and white corpuscles. 2 In some specimens, however, a spontaneous coagulation, generally slight, but in exceptional cases massive, may be observed. 24 FIBKIN FEKMENT. [Boon i. all events, these fluids, when a little blood, or a piece of blood clot, or a little serum is added to them, will clot rapidly and firmly,1 giving rise to an unmistakeable clot of normal fibrin, differing only from the clot of blood in that, when serum is used, it is colourless, being free from red corpuscles. Now, blood (or blood clot, or serum) contains many things, to any one of which the clotting power thus seen might be attributed. But it is found that in many cases clotting may be induced in the fluids of which we are speaking by the mere addition and that even in exceedingly small quantity, of a substance which can be extracted from blood, or from serum, or from blood clot, or even from washed fibrin, or indeed from other sources, — a substance whose exact nature is uncertain, it being doubtful whether it is a proteid at all, and whose action is peculiar. If serum, or whipped blood, or a broken-up clot be mixed with a large quantity of alcohol and allowed to stand some days, the proteids present are in time so changed by the alcohol as to become insoluble in water. Hence if the copious precipitate caused by the alcohol, after long standing, be separated by filtration from the alcohol, dried at a low temperature, not exceeding 40° C., and extracted with distilled water, the aqueous extract contains very little proteid matter, — indeed very little organic matter at all. Nevertheless even a small quantity of this aqueous extract added alone to certain specimens of hydrocele fluid or other of the fluids spoken of above, will bring about a speedy clotting. The same aqueous extract has also a remarkable effect in hastening the clotting of fluids which, though they will eventually clot, do so- very slowly. Thus, plasma may, by the careful addition of a certain quantity of neutral salt and water, be reduced to such a condition that it clots very slowly indeed, taking perhaps days to complete the process. The addition of a small quantity of the aqueous extract we are describing will, however, bring about a clotting which is at once rapid and complete. The active substance, whatever it be, in this aqueous extract exists in small quantity only, and its clotting virtues are at once and for ever lost when the solution is boiled. Further, there is no reason to think that the active substance actually enters into the formation of the fibrin to which it gives rise. It appears to belong to a class of bodies playing an important part in physiological processes and called ferments, of which we shall have more to say hereafter. We may therefore speak of it as the fibrin ferment, the name given to it by its discoverer Alexander Schmidt. This fibrin ferment is present in and may be extracted from clotted or whipped blood, and from both the clot2 and the serum of clotted blood ; and since in most if not all cases where blood or 1 In a few cases no coagulation can thus be induced. 2 A powerful solution of fibrin ferment may be readily prepared by simply- extracting a washed blood clot with a 10 p.c. solution of sodium chloride. CHAP. T.] BLOOD. 25 blood clot or serum produces clotting in hydrocele or pericardial fluid, an exactly similar clotting may be induced by the mere addition of fibrin ferment, we seem justified in concluding that the clotting virtues of the former are due to the ferment which they contain. Now, when fibrin ogen is precipitated from plasma as above described by sodium chloride, re-dissolved, and reprecipitated, more than once, it may be obtained in solution, by help of a dilute neutral saline solution, in an approximately pure condition, at all events free from other proteids. Such a solution will not clot spontaneously ; it may remain fluid indefinitely ; and yet on the addition of a little fibrin ferment it will clot readily and firmly, yielding quite normal fibrin. This body fibrinogen is also present and may be separated out from the specimens of hydrocele, pericardial, and other fluids which clot on the addition of fibrin ferment ; and when the fibrinogen has been wholly removed from these fluids they refuse to clot on the addition of fibrin ferment. Paraglobulin, on the other hand, whether prepared from plasmine by separation of the fibrinogen, or from serum, or from other fluids in which it is found, cannot be converted by fibrin ferment or indeed by any other means into fibrin. And fibrinogen isolated as described above, or serous fluids which contain fibrinogen, can be made, by means of fibrin ferment, to yield quite normal fibrin in the complete absence of paraglobulin. A solution of paraglobulin obtained from serum or blood clot will, it is true, clot pericardial or hydrocele fluids containing fibrinogen, or indeed a solution of fibrinogen ; but this is apparently due to the fact that the paraglobulin has in these cases some fibrin ferment mixed with it; it is also possible that under certain conditions the presence of paraglobulin may be favourable to the action of the ferment. When the so-called plasmine is precipitated as directed in §19, fibrin ferment is carried down with the fibrinogen and para- globulin ; and when the plasmine is re-dissolved the ferment is present in the solution and ready to act on the fibrinogen. Hence the re-dissolved plasmine clots spontaneously. When fibrinogen is isolated from plasma by repeated precipitation and solution, the ferment is washed away from it, and the pure ferment-free fibrin- ogen, ultimately obtained, does not clot spontaneously. So far it seems clear that there does exist a proteid body, fibrinogen, which may by the action of fibrin ferment be directly, without the intervention of other proteids, converted into the less soluble fibrin. Our knowledge of the constitution of proteid bodies is too imperfect to enable us to make any very definite statement as to the exact nature of the change thus effected ; but we may say this much: Fibrinogen and fibrin have about the same elementary composition, fibrin containing a trifle more 26 FIBRINOGEN AND FIBRIN. [BOOK i. nitrogen. When fibrin ogen is converted into fibrin by means of fibrin ferment, the weight of the fibrin produced is always less than that of the fibrinogen which is consumed, and there is always produced at the same time a certain quantity of another proteid, belonging to the globulin family. There are reasons however why we cannot speak of the ferment as splitting up fibrinogen into fibrin and a globulin. It seems more probable that the ferment converts the fibrinogen first into a body which we might call soluble fibrin, and then turns this body into veritable fibrin ; but further inquiries on the subject are needed. The action of the fibrin ferment on fibrinogen is dependent on other conditions besides temperature ; for instance, the presence of a calcium salt seems to be necessary. If blood be shed into a dilute solution of potassium oxalate, the mixture, which need not contain more than '1 p.c. of the oxalate, remains fluid indefinitely, but clots readily on the addition of a small quantity of a calcium salt. Apparently the oxalate, by precipitating the calcium salts present in the blood, prevents the conversion of the fibrinogen into fibrin. So also a solution of fibrinogen which has been deprived of its calcium salts, by diffusion for instance, will not clot on the addition of fibrin ferment similarly deprived of its calcium salts ; but the mixture clots readily on the addition of a minute quantity of calcium sulphate. We shall have to speak later on of a somewhat analogous part played by calcium salts in the curdling of milk. It may be added that the presence of other neutral salts, such as sodium chloride, appears to influence clotting. § 21. We may conclude then that the plasma of blood when shed, or at all events soon after it has been shed, contains fibrino- gen ; and it also seems probable that the clotting comes about because the fibrinogen is converted into fibrin by the action of fibrin ferment ; but we are still far from a definite answer to the question, why blood remains fluid in the body and yet clots when shed? We have already said that blood or blood plasma, brought up to a temperature of 56° C. as soon as possible after its removal from the living blood vessels, gives a proteid precipitate and loses its power of clotting. This may be taken to shew that blood, as it circulates in the living blood vessels, contains fibrinogen as such, and that when the blood is heated to 56° C., which is the coagu- lating point of fibrinogen, the fibrinogen present is coagulated and precipitated, and consequently no fibrin can be formed. Further, while clotted blood undoubtedly contains an abundance of fibrin ferment, no ferment, or a minimal quantity only, is present in blood as it leaves the blood vessels. If blood be received directly from the blood vessels into alcohol, the aqueous extract prepared as directed above contains no ferment, or merely a trace. Appa- rently the ferment makes its appearance in the blood as the result of changes taking place in the blood after it has been shed. CHAP, i.] BLOOD. 27 We might from this be inclined to conclude that blood clots when shed but not before, because, fibrinogen being always present, the shedding brings about changes which produce fibrin ferment, not previously existing, and this acting on the fibrinogen gives rise to fibrin. But we meet with the following difficulty. A very considerable quantity of very active ferment may be injected into the blood current of a living animal without necessarily producing any clotting at all. Obviously, either blood within the blood vessels does not contain fibrinogen as such, and the fibrinogen detected by heating the blood to 56° C. is the result of changes which have already ensued before that temperature is reached ; or in the living circulation there are agencies at work which prevent any ferment which may be introduced into the circula- tion from producing its usual effects on fibrinogen ; or there are agencies at work which destroy or do away with the fibrin, little by little, as it is formed. § 22. And indeed when we reflect how complex blood is, and of what many and great changes it is susceptible, we shall not wonder that the question we are putting cannot be answered off hand. The corpuscles with which blood is crowded are living structures, and consequently are continually acting upon and being acted upon by the plasma. The red corpuscles it is true are, as we shall see, peculiar bodies, with a restricted life and a very specialized work, and possibly their influence on the plasma is not very great ; but we have reason to think that the relations between the white corpuscles and the plasma are close and important. Then again the blood is not only acting upon and being acted upon by the several tissues as it flows through the various capillaries, but along the whole of its course, through the heart, arteries, capillaries, and veins, is acting upon and being acted upon by the vascular walls, which like the rest of the body .are alive, and being alive are continually undergoing and promoting change. That relations of some kind, having a direct influence on the clotting of blood, do exist between the blood and the vascular walls is shewn by the following facts. After death, when all motion of the blood has ceased, the blood remains for a long time fluid. It is not till some time afterwards, at an epoch when post-mortem changes in the blood and in the blood vessels have had time to develope themselves, that clotting begins. Thus, some hours after death the blood in the great veins may be found still perfectly fluid. Yet such blood has not lost its power of clotting ; it still clots when removed from the body, and clots too when received over mercury without exposure to air, shewing that, though the blood, being highly venous, is rich in carbonic acid and contains little or no oxygen, its fluidity is not due to any excess of carbonic acid or absence of oxy- gen. Eventually it does clot even within the vessels, but perhaps 28 INFLUENCE OF BLOOD VESSELS. [BOOK i. never so firmly and completely as when shed. It clots first in the larger vessels, but remains fluid in the smaller vessels for a very long time, for many hours in fact, since in these the same bulk of blood is exposed to the influence of, and reciprocally exerts an influence on, a larger surface of the vascular walls, than in the larger vessels. And if it be urged that the result is here due to influences exerted by the body at large, by the tissues as well as by the vascular walls, this objection will not hold good against the following experiment. If the jugular vein of a large animal, such as an ox or horse, be carefully ligatured when full of blood, and the ligatured por- tion excised, the blood in many cases remains perfectly fluid, along the greater part of the length of the piece, for twenty-four or even forty-eight hours. The piece so ligatured may be sus- pended in a framework and opened at the top so as to imitate a living test-tube, and yet the blood will often remain long fluid, though a portion removed at any time into a glass or other vessel will clot in a few minutes. If two such living test-tubes be pre- pared, the blood may be poured from one to the other without clotting taking place. A similar relation of the fluid to its containing living wall is seen in the case of those serous fluids which clot spontane- ously. If, so soon after death as the body is cold and the fat is solidified, the pericardium be carefully removed from a sheep by an incision round the base of the heart, the pericardial fluid (which, as we have already seen, during life, and some little time after death, possesses the power of clotting) may be kept in the pericardial bag as in a living cup for many hours without clotting, and yet a small portion removed with a pipette clots at once. This relation between the blood and the vascular wall may be disturbed or overridden : clotting may take place or may be induced within the living blood vessel. When the lining mem- brane is injured, as when an artery or vein is sharply ligatured, or when it is diseased, as for instance in aneurism, a clot is apt to be formed at the injured or diseased spot ; and in certain morbid conditions of the body clots are formed in various vascular tracts. Absence of motion, which in shed blood, as we have seen, is un- favourable to clotting, is apt within the body to lead to clotting. Thus when an artery is ligatured, the blood in the tract of artery on the cardiac side of the ligature, between the ligature and the branch last given off by the artery, ceasing to share in the circula- tion, remains motionless or nearly so, and along this tract a clot forms, firmest next to the ligature and ending near where the branch is given off; this perhaps may be explained by the fact that the walls of the tract suffer in their nutrition by the stagna- tion of the blood, and that consequently the normal relation be- tween them and the contained blood is disturbed. CHAP, i.] BLOOD. 29 That the blood within the living blood vessels, though not actually clotting under normal circumstances, may easily be made to clot, that the blood is in fact so to speak always on the point of clotting, is shewn by the fact that a foreign body, such as a needle thrust into the interior of a blood vessel or a thread drawn through and left in a blood vessel, is apt to become covered with fibrin. Some influence exerted by the needle or thread, whatever may be the character of that influence, is sufficient to determine a clotting, which otherwise would not have taken place. The same instability of the blood as regards clotting is strikingly shewn, in the case of the rabbit at least, by the result of injecting into the blood vessels a small quantity of a solution of a peculiar proteid prepared from certain structures such as the thymus body. Massive clotting of the blood in almost all the blood vessels, small and large, takes place with great rapidity, leading to the sudden death of the animal. In contrast to this effect may be mentioned the result of injecting into the blood vessels of a dog a quantity of a solution of a body called albumose, of which we shall hereafter have to treat as a product of the digestion of proteid substances, to the extent of '3 grm. per kilo of body weight. So far from producing clotting, the injected albumose has such an effect on the blood that for several hours after the injection shed blood will refuse to clot of itself and remain quite fluid, though it can be made to clot by special treatment. § 23. All the foregoing facts tend to shew that the blood as it is flowing through the healthy blood vessels is, so far as clotting is concerned, in a state of unstable equilibrium, which may at any moment be upset, even within the blood vessels, and which is upset directly the blood is shed, with clotting as a result. Our present knowledge does not permit us to make an authoritative statement as to the exact nature of this equilibrium. There are reasons however for thinking that the white corpuscles play an important part in the matter. Where- ever clotting occurs naturally, white corpuscles are present ; and this is true not only of blood but also of such specimens of peri- cardial or other serous fluids as clot naturally. And many argu- ments, which we cannot enter upon here, may be adduced all pointing to the same conclusion, that the white corpuscles play an important part in the process of clotting. But it would lead us too far into controversial matters to attempt to define what that part is, or to explain the exact nature of the equilibrium of which we have spoken. What we do know is that in blood soon after it has been shed, the body which we have called fibrinogen is present as also the body which we have called fibrin ferment, that the latter acting on the former will produce fibrin, and that the appearance of fibrin is undoubtedly the cause of what is called clotting. We seem justified in concluding that the clotting of shed blood is due to the conversion by ferment of fibrinogen into 30 CLOTTING OF BLOOD. [BOOK i. fibrin. The further inference that clotting within the body is the same thing as clotting outside the body and similarly due to the transformation of fibrinogen by ferment into fibrin, though prob- able, is not proved. We do not yet know the exact nature and condition of the blood within the living blood vessels, and until we know that we cannot satisfactorily explain why blood in the living blood vessels is usually fluid but can at times clot. SEC. 2. THE CORPUSCLES OF THE BLOOD. The Red Corpuscles. § 24. The redness of blood is due exclusively to the red corpuscles. The plasma as seen in thin layers within the living blood vessels appears colourless, as does also a thin layer of serum ; but a thick layer of serum (and probably of plasma) has a faint yellowish tinge due as we have said to the presence of a small quantity of a special pigment. A single red corpuscle seen by itself under the microscope is a fairly homogeneous, imperfectly translucent biconcave disc of a very faint colour, looking yellow rather than red ; but when several corpuscles lie one upon the top of the other the mass appears distinctly red ; and though a single corpuscle is somewhat trans- lucent, a comparatively thin layer of blood is opaque ; type for instance cannot be read through even a thin layer of blood. When a quantity of whipped blood (or blood otherwise de- prived of fibrin) is frozen and thawed several times it changes colour, becoming of a darker hue, and is then found to be much more transparent, so that type can now be easily read through a moderately thin layer. It is then spoken of as laky llood. The same change may be effected by shaking the blood with ether, or by adding a small quantity of bile salts, and in other ways. Upon examination of laky blood it is found that the red corpuscles are ' broken up ' or at least altered, and that the redness which pre- viously was confined to them is now diffused through the serum. Normal blood is opaque because each corpuscle while permitting some rays of light (chiefly red) to pass through, reflects many others, and the brightness of the hue of normal blood is due to this reflection of light from the surfaces of the several corpuscles. Laky blood is transparent because there are no longer intact corpuscles to present surfaces for the reflection of light, and the darker hue of laky blood is similarly due to the absence of reflection from the several corpuscles. 32 STRUCTURE OF RED CORPUSCLE. [BOOK i. When laky blood is allowed to stand a sediment is formed (and may be separated by the centrifugal machine) which on exami- nation is found to consist of discs, or fragments of discs, of a colourless substance exhibiting under high powers an obscurely spongy or reticular structure. These colourless thin discs seen flat-wise often appear as mere rings. The substance composing them stains with various reagents and may thus be made more evident. The red corpuscle then consists obviously of a colourless frame- work, with which in normal conditions a red colouring matter is associated ; but by various means the colouring matter may be driven from the framework and dissolved in the serum. The framework is spoken of as stroma ; it is a modified or differentiated protoplasm, and upon chemical analysis yields a pro- teid substance belonging to the globulin group, and other matters, among which is the peculiar complex fat called lecithin, of which we shall have to speak in treating of nervous tissue. The red colouring matter which in normal conditions is asso- ciated with this stroma may by appropriate means be isolated, and, in the case of the blood of many animals, obtained in a crystalline form. It is called Hcemoglolin, and may by proper methods be split up into a proteid belonging to the globulin group, and into a coloured pigment, containing iron, called Hcematin. Haemoglobin is therefore a very complex body. It is found to have remarkable relations to oxygen, and indeed as we shall see the red corpuscles by virtue of their haemoglobin have a special work in respiration ; they carry oxygen from the lungs to the several tissues. We shall therefore defer the further study of hsemoglobin until we have to deal with respiration. Though the haemoglobin, as is seen in laky blood, is readily soluble in serum (and it is also soluble in plasma), in the intact normal blood it remains confined to the corpuscle ; obviously there is some special connection between the stroma and the hae- moglobin ; it is not until the stroma is altered, we may perhaps say killed (as by repeated freezing and thawing), that it loses its hold on the hsemoglobin, which thus set free passes into solution in the serum. The disc of stroma when separated from the haemo- globin has as we have just said an obscurely spongy texture ; but we do not know accurately the exact condition of the stroma in the intact corpuscle or how it holds the haemoglobin. There is certainly no definite membrane or envelope to the corpuscle, for by exposing blood to a high temperature, 60° C., the corpuscle will break up into more or less spherical pieces, each still consisting of stroma and haemoglobin. The quantity of stroma necessary to hold a quantity of haemo- globin is exceedingly small. Of the total solid matter of a corpuscle more than 90 p. c. is haemoglobin. A red corpuscle in fact is a quantity of haemoglobin held together in the form of a CHAP, i.] BLOOD. 33 disc by a minimal amount of stroma. Hence whatever effect the stroma per se may have upon the plasma, this, in the case of mammals at all events, must be insignificant : the red corpuscle is practically simply a carrier of haemoglobin. § 25. The average number of red corpuscles in human blood may be probably put down at about 5 millions in a cubic milli- meter (the range in different mammals is said to be from 3 to 18 millions), but the relation of corpuscle to plasma varies a good deal even in health, and very much in disease. Obviously the relation may be affected (1) by an increase or decrease of the plasma, (2) by an actual decrease or increase of red corpuscles. Now the former must frequently take place. The blood as we have already urged is always being acted upon by changes in the tissues and indeed is an index of those changes ; hence the plasma must be continually changing, though always striving to return to the normal condition. Thus when a large quantity of water is discharged by the kidney, the skin or the bowels, that water comes really from the blood, and the drain of water must tend to dimin- ish the bulk of the plasma, and so to increase the relative number of red corpuscles, though the effect is probably soon remedied by the passage of water from the tissues into the blood. So again when a large quantity of water is drunk, this passes into the blood and tends temporarily to dilute the plasma (and so to dimin- ish the relative number of red corpuscles), though this condition is in turn soon remedied by the passage of the superfluous fluid to the tissues and excretory organs. The greater or less number of red corpuscles then in a given bulk of blood may be simply due to less or more plasma, but we have reason to think that the actual number of the corpuscles in the blood does vary from time to time. This is especially seen in certain forms of disease, which may be spoken of under the general term of anaemia (there being several kinds of ansemia), in which the number of red corpuscles is distinctly diminished. The redness of blood may however be influenced not only by the number of red corpuscles in each cubic millimeter of blood but also by the amount of haemoglobin in each corpuscle, and to a less degree by the size of the corpuscles. If we compare, with a common standard, the redness of two specimens of blood un- equally red, and then determine the relative number of corpuscles in each, we may find that the less red specimen has as many corpuscles as the redder one, or at least the deficiency in redness is greater than can be accounted for by the paucity of red cor- puscles. Obviously in such a case the red corpuscles have too little haemoglobin. In some cases of anaemia the deficiency of haemoglobin in each corpuscle is more striking than the scantiness of red corpuscles. The number of corpuscles in a specimen of blood is determined by mixing a small but carefully measured quantity of the blood with a F. 3 34 NUMBER OF RED CORPUSCLES. [BOOK i. large quantity of some indifferent fluid, e.g. a 5 p.c. solution of sodium sulphate, and then actually counting the corpuscles in a known minimal bulk of the mixture. This perhaps may be most conveniently done by the method gener- ally known as that of Gowers (Hsemacytometer) improved by Malassez. A glass slide, in a metal frame, is ruled into minute rectangles, e.g. £mm. by £inm., so as to give a convenient area of ^th of a square mm. Three small screws in the frame permit a coverslip to be brought to a fixed distance, e.g. £mm., from the surface of the slide. The blood having been diluted, e.g. to 100 times its volume, a small quantity of the diluted (and thoroughly mixed) blood, sufficient to occupy fully the space between the coverslip and the glass slide when the former is brought to its proper position, is placed on the slide, and the coverslip brought down. The volume of diluted blood now lying over each of the rectangles will be T J5th (^x^) of a cubic mm. ; and if, when the corpuscles have subsided, the number of corpuscles lying within a rectangle be counted, the result will give the number of corpuscles previously distributed through T£ joins the primary coil pr. c., and then passes on as y111, through the •*' key " F, to the positive (zinc) plate z.p. of the battery. Over this primary coil, but quite unconnected with it, slides another coil, — the secondary coil, s.c. ; the ends of the wire forming this coil, y" and x", are continued on in the arrangement illustrated in the figure as y1 and y, and as xr and x, and terminate in electrodes. If these electrodes are in contact or con- nected with conducting material, the circuit of the secondary coil is said to be closed ; otherwise it is open. In such an arrangement it is found that at the moment when the primary circuit is closed, — i. e. when the primary current is " made," a secondary " induced " current is, for an exceedingly brief period of time, set up in the secondary coil. Thus in Fig. 2 when, by moving the '* key " F, y1" and xut (previously not in connection with' each other) are put into connection and the primary current thus made, at that instant a current appears in the wires y11 x11 &c., but almost immediately disappears. A similar almost instantaneous current is also developed when the primary current is " broken," but not till then. So long as the primary current flows with uniform intensity, no current is induced in the secondary coil. It is only when the primary current is either made or broken, or suddenly varies in intensity, that a current appears in the secondary coil. In each case the current is of very brief duration, gone in an instant almost, and may therefore be spoken of as " a shock," an induction shock, — being called a " making shock " when it is caused by the making, and a " breaking shock " when it is caused by the breaking, of the primary circuit. The direction of the current 60 INDUCTION COIL. [BOOK i. CHAP, ii.] THE CONTRACTILE TISSUES. 61 FIG. 3. DIAGRAM ILLUSTRATING APPARATUS ARRANGED FOR EXPERIMENTS WITH MUSCLE AND NERVE. A. The moist chamber containing the muscle-nerve preparation. The muscle m, supported by the clamp c/., which firmly grasps the end of the femur ft is connected by means of the S hook s and a thread with the lever /, placed below the moist chamber. The nerve nt with the portion of the spinal column n' still attached to it, is placed on tho electrode-holder el, in contact with the wires x, i/. The whole of the interior of the glass case gl. is kept saturated with moisture, and the electrode-holder is so constructed that a piece of moistened blotting-paper may be placed on it without coming into contact with the nerve. B. The revolving cylinder bearing the smoked paper on which the lever writes. (7. Du Bois-Reymond's key arranged for short-circuiting. The wires x and y of the electrode-holder are* connected through binding screws in the floor of the moist chamber with the wires x', yf, and these are secured in the key, one on either side. To the same key are attached the wires x" y" coming from the secondary coils s. c. of the induction-coil D. This secondary coil can be made to slide up and down over the primary coil pr. c., with which are connected the two wires x"' and y'". x"' is connected directly with one pole, for instance the copper pole c. p. of the battery E. y'" is carried to a binding screw a of the Morse key F, and is continued as yiv from another binding screw b of the key to the zinc pole z. p. of the battery. Supposing everything to be arranged, and the battery charged, on depressing the handle ha, of the Morse key F, a current will be made in the primary coil pr. c., passing from c. p. through x'" to pr. c., and thence through y"' to a, thence to b, and so through yiv to z. p. On removing the finger from the handle of F, a spring thrusts up the handle, and the primary circuit is in consequence immediately broken. At the instant that the primary current is either made or broken, an induced current is for the instant developed in the secondary coil s. c. If the cross bar h in the du Bois-Reymond's key be raised (as shewn in the thick line in the figure), the wires x" x' x, "the nerve between the electrodes and the wires y, y', y" form the complete secondary circuit, and the nerve consequently experiences a making or breaking induction-shock whenever the primary current is made or broken. If the cross bar of the du Bois-Reymond's key be shut down, as in the dotted line h' in the figure, the resistance of the cross bar is so slight compared with that of the nerve and of the wires going from the key to the nerve, that the whole secondary (induced) current passes from x" to y" (or from y" to x"), along the cross bar, and practically none passes into the nerve. The nerve being thus " short-circuited." is not affected by any changes in the current. The figure is intended merely to illustrate the general method of studying muscular contraction ; it is not to be supposed that the details here given are universally adopted or indeed the best for all purposes. in the making shock is opposed to that of the primary current ; thus in the figure while the primary current flows from xtfr to yrif, the induced making shock flows from y to x. The current of the breaking shock on the other hand flows in the same direction as the primary current from x to y, and is therefore in direction the reverse of the making shock. Compare Fig. 3, where arrangement is shewn in a diagrammatic manner. The current from the battery, upon its first entrance into the primary coil, as it passes along each twist of that coil, gives rise in the neighbouring twists of the same coil to a momentary induced current having a direction opposite to its own, and therefore tending to weaken itself. It is not until this 'self-induction' has passed off that the 62 INDUCTION COIL. [BOOK i. current in the primary coil is established in its full strength. Owing to this delay in the full establishment of the current in the primary coil, the induced current in the secondary coil is developed more slowly FIG. 4. DIAGRAM OF AN INDUCTION COIL. + positive pole, end of negative element; — negative pole, end of positive element of battery ; K, du Bois-Reymond's key ; pr. c. primary coil, current shewn by feathered arrow ; sc. c. secondary coil, current shewn by unfeathered arrow. than it would be were no such ' self-induction ' present. On the other hand, when the current from the battery is * broken,' or * shut off' from the primary coil, no such delay is offered to its disappearance, and consequently the induced current in the secondary coil is developed with unimpeded rapidity. We shall see later on that a rapidly de- veloped current is more effective as a stimulus than is a more slowly developed current. Hence the making shock, where rapidity of pro- duction is interfered with by the self-induction of the primary coil, is less effective as a stimulus than the breaking shock, whose development is not thus interfered with. The strength of the induced current depends, on the one hand, on the strength of the current passing through the primary coil, — that is, on the strength of the battery. It also depends on the relative position of the two coils. Thus, if a secondary coil is brought nearer and nearer to the primary coil and made to overlap it more and more, the induced current becomes stronger and stronger, though the current from the battery remains the same. With an ordinary battery, the secondary coil may be pushed to some distance away from the primary coil, and yet shocks sufficient to stimulate a muscle will be obtained. For this purpose however the two coils should be in the same line ; when the secondary coil is placed cross-wise, at right angles to the primary, no induced current is developed, and at intermediate angles the induced current has intermediate strengths. When the primary current is repeatedly and rapidly made and broken, the secondary current being developed with each make and with each break, a rapidly recurring series of alternating currents is developed in the secondary coil and passes through its electrodes. We shall frequently speak of this as the interrupted induction current, or more briefly the interrupted current ; it is sometimes spoken of as the CHAP, ii.] THE CONTKACTILE TISSUES. 63 faradaic current, and the application of it to any tissue is spoken of as faradization. Such a repeated breaking and making of the primary current may be effected in many various ways. In the instrument commonly used for the purpose, the primary current is made and broken by means of a vibrating steel slip working against a magnet ; hence the instrument is called a magnetic interrupter. See Fig. 5. FIG. 5. THE MAGNETIC INTERRUPTOR. The two wires x and y from the battery are connected with the two brass pillars a and d by means of screws. Directly contact is thus made, the current, indicated in the figure by the thick interrupted line, passes in the direction of the arrows, up the pillar a, along the steel spring b, as far as the screw c, the point of which, armed with platinum, is in contact with a small platinum plate on b. The current passes from 6 through c and a connecting wire into the primary coil p. Upon its entering into the primary coil, an induced (making) current is for the instant developed in the secondary coil (not shewn in the figure). From the primary coil p the current passes, by a connecting wire, through the double spiral ra, and, did nothing happen, would continue, to pass from m by a connecting wire to the pillar o?, and so by the wire y to the battery. The whole of this course is indicated by the thick interrupted line with its arrows. As the current however passes through the spirals m, the iron cores of these are made magnetic. They in consequence draw down the iron bar e, fixed at the end of the spring 6, the flexibility of the spring allowing this. But when e is drawn down, the platinum plate on the upper surface of 6 is also drawn away from the screw c, and thus the current is " broken " at b. (Sometimes the screw/ is so arranged that when e is drawn down a platinum plate on the under surface of b is brought into contact with the platinum-armed point of the screw/. 64 INDUCTION COIL. [BOOK i. The current then passes from b not to c but to /, and so down the pillar d, in the direction indicated by the thin interrupted line, and out to the battery by the wire y, and is thus cut off from the primary coil. But this arrangement is unnecessary.) At the instant that the cur- rent is thus broken and so cut off from the primary coil, an induced (breaking) current is for the moment developed in the secondary coil. But the current is cut off not only from the primary coil, but also from the spirals ra ; in consequence their cores cease to be magnetised, the bar e ceases to be attracted by them, and the spring £>, by virtue of its elasticity, resumes its former position in contact with the screw c. This return of the spring however re-establishes the current in' the primary coil and in the spirals, and the spring is drawn down, to be released once more in the same manner as before. Thus as long as the current is passing along x, the contact of b with c is alternately being made and broken, and the current is constantly passing into and being shut off from p, the periods of alternation being determined by the periods of vibration of the spring 6. With each passage of the current into, or withdrawal from the primary coil, an induced (making and, respectively, breaking) current is developed in a secondary coil. As thus used, each 'making shock/ as explained above, is less powerful than the corresponding ''breaking shock;' and indeed it sometimes happens that instead of each make as well as each break acting as a stimulus, giving rise to a contraction, the ' breaks ' only are effective, the several ' makes ' giving rise to no contractions. By what is known as Helmholtz's arrangement, Fig. 6, however, FIG. 6. THE MAGNETIC INTERRUPTOR WITH HELMHOLTZ ARRANGEMENT FOR EQUAL- IZING THE MAKE AND BREAK SHOCKS. the making and breaking shocks may be equalized. For this purpose the screw c is raised out of reach of the excursions of the spring 6, and CHAP, ii.] THE CONTRACTILE TISSUES. 65 a moderately thick wire w, offering a certain amount only of resistance, is interposed between the upper binding screw a1 on the pillar a, and the binding screw cf leading to the primary coil. Under these arrange- ments the current from the battery passes through a1, along the inter- posed wire to c1, through the primary coil and thus as before to m. As before, by the magnetization of m, e is drawn down and b brought in contact with /. As the result of this contact, the current from the battery can now pass by a, /, and d (shewn by the thin interrupted line) back to the battery ; but not the whole of the current, some of it can still pass along the wire w to the primary coil, the relative amount being determined by the relative resistances offered by the two courses. Hence at each successive magnetization of m, the current in the primary coil does not entirely disappear when b is brought in contact with// it is only so far diminished that m ceases to attract e, and hence by the release of b from / the whole current once more passes along w. Since at what corresponds to the ' break ' the current in the primary coil is diminished only, not absolutely done away with, self-induction makes its appearance at the ' break ' as well as at the 'make;' thus the 'breaking' and 'making' induced currents or shocks in the secondary coil are equalized. They are both reduced to the lower efficiency of the ' making ' shock in the old arrangement ; hence to produce the same strength of stimulus with this arrange- ment a stronger current must be applied or the secondary coil pushed over the primary coil to a greater extent than with the other arrange- ment. The Phenomena of a Simple Muscular Contraction. § 45. If the far end of the nerve of a muscle-nerve preparation (Figs. 1 and 3) be laid on electrodes connected with the secondary coil of an induction-machine, the passage of a single induction- shock, which may be taken as a convenient form of an almost mo- mentary stimulus, will produce no visible change in the nerve, but the muscle will give a twitch, a short, sharp contraction, — i. e., will for an instant shorten itself, becoming thicker the while, and then return to its previous condition. If one end of the muscle be attached to a lever, while the other is fixed, the lever will by its movements indicate the extent and duration of the shortening. If the point of the lever be brought to bear on some rapidly travelling surface, on which it leaves a mark (being for this purpose armed with a pen and ink if the surface be plain paper, or with a bristle or finely pointed piece of platinum foil if the surface be smoked glass or paper), so long as the muscle remains at rest the lever will describe an even line, which we may call the base line. If how- ever the muscle shortens, the lever will rise above the base line and thus describe some sort of curve above the base line. Now, 5 66 A SIMPLE MUSCULAR CONTRACTION. [BOOK i: it is found that when a; single induction-shock is sent through the nerve the twitch which the muscle gives causes the lever to de- scribe some such curve as that shewn in Fig. 7 ; the lever (after a brief interval immediately succeeding the opening or shutting the key, of which we shall speak presently) rises at first rapidly but afterwards more slowly, shewing that the muscle is correspondingly shortening, then ceases to rise, shewing that the muscle is ceasing FIG. 7. A MUSCLE-CURVE FROM THE GASTROCNEMIUS OF THE FROG. This curve, like all succeeding ones, unless otherwise indicated, is to be read from left to right, — that is to say, while the lever and tuning-fork were stationary the recording surface was travelling from right to left. a indicates the moment at which the induction-shock is sent into the nerve ; 6 the commencement, c the maximum, and d the close of the contraction. Below the muscle-curve is the curve drawn by a tuiiing-fork making 100 double vibrations a second, each complete curve representing therefore one-hundredth of a second. to grow shorter ; then descends, shewing that the muscle is length- ening again ; and finally, sooner or later, reaches and joins the base line, shewing that the muscle after the shortening has regained its previous natural length. Such a curve described by a muscle during a twitch or simple muscular contraction, caused by a single induction-shock or by any other stimulus producing the same effect, is called a curve of a simple muscular contraction or, more shortly, a " muscle-curve." It is obvious that the exact form of the curve described by identical contractions of a muscle will depend on the rapidity with which the recording surface is travelling. Thus if the surface be travelling slowly the up-stroke corresponding to the shortening will be very abrupt and the down-stroke also very steep, as in Fig. 8, which is a curve from a gastrocnemius muscle of a frog, taken with a slowly moving drum, the tuning-fork being the same as that used in Fig. 7 ; indeed with a very slow movement, the two may be hardly separable from each other. On the other hand, if the surface travel very rapidly the curve may be immensely long drawn out, as in Fig. 9, which is a curve from a gastro- FIG. 8. cnemius muscle of a frog, taken with a very rapidly moving pendulum myograph, the tuning-fork marking about 500 vibrations a second. On . examination, however, it will CHAP, ii.] THE CONTRACTILE TISSUES. be found that both these extreme curves are funda- mentally the same as the medium one, when account is taken of the different rapidities of the travelling surface in the several cases. In order to make the ' muscle-curve ' complete, it is necessary to mark on the recording surface the exact time at which the induction-shock is sent into the nerve, and also to note the speed at which the recording surface is travelling. In the pendulum ;myograph the rate of move- ment can be calculated from the length of the pendulum ; but even in this it is convenient, and in the case of the spring myograph and revolving cylinder is necessary, to measure the rate of move- ment directly by means of a vibrating tuning-fork or of some body vibrating regularly. Indeed it is best to make such a direct measurement with each curve that is taken. A tuning-fork, as is known, vibrates so many times a second according to its pitch. If a tuning- fork, armed with a light marker on one of its prongs and vibrating say ,100 a second, — i.e., executing a double vibration, moving forwards and backwards, 100 times a second, — be brought while vibrating to make a tracing on the recording surface immedi- ately below the lever belonging to the muscle, we can use the curve or rather curves described by the tuning-fork to measure the duration of any part or of the whole of the muscle-curve. It is essential that at starting the point of the marker of the tuning-fork should be exactly underneath the marker of the lever, or rather, since the point of the lever as it moves up and down describes not a straight line but an arc of a circle of which its fulcrum is the centre and itself (from the fulcrum to the tip of the marker) the radius, that the point of the marker of the tuning-fork should be exactly on the arc described by the marker of the lever, either above or below it, as may prove most convenient. If then at starting the tuning-fork marker be thus on the arc of the lever marker, and we note on the curve of the tuning-fork the place where the arc of the lever cuts it at the beginning and at the end of the muscle-curve, as at Fig. 7, we can count the number of vibrations of the tuning-fork which have taken place between the two marks, and so ascer- tain the whole time of the muscle-curve; if for instance there have been 10 double vibrations, each 67 68 PENDULUM MYOGKAPH. [BOOK i. FIG 10. THE PENDULUM MYOGRAPH. The figure is diagrammatic, the essentials only of the instrument being shewn. The smoked glass plate A swings with the pendulum B on carefully adjusted CHAP. IT. J THE CONTRACTILE TISSUES 69 bearings at C. The contrivances by which the glass plate can be removed and replaced at pleasure are not shewn. A second glass plate so arranged that the first glass plate may be moved up and down without altering the swing of the pendulum is also omitted. Before commencing an experiment the pendulum is raised up (in the figure to the right), and is kept in that position by the tooth a catching on the spring-catch 6. On depressing the catch 6 the glass plate is set free, swings into the new position indicated by the dotted lines, and is held in that position by the tooth a' catching on the catch b'. In the course of its swing the tooth a' coming into contact with the projecting steel rod c, knocks it on one side into the position indicated by the dotted line c'. The rod c is in electric continuity with the wire x of the primary coil of an induction-machine. The screw d is similarly in electric continuity with the wire y of the same primary coil. The screw d and the rod c are armed with platinum at the points in which they are in contact, and both are insulated by means of the ebonite block e. As long as c and d are in contact the circuit of the primary coil to which x and y belong is closed. When in its swing the tooth a' knocks c away from d, at that instant the circuit is broken, and a ' breaking ' shock is sent through the electrodes connected with the secondary coil of the machine, and so through the nerve. The lever /, the end only of which is shewn in the figure, is brought to bear on the glass plate, and when at rest describes a straight line, or more exactly an arc of a circle of U*rge radius. The tuning-fork f, the ends only of the two limbs of which are shewn in the figure placed immediately below the lever, serves to mark the time. occupying T^ sec., the whole curve has taken -^ sec. to make. In the same way we can measure the duration of the rise of the curve or of the fall, or of any part of it. Though the tuning-fork may, by simply striking it, be set going long enough for the purposes of an observation, it is convenient to keep it going by means of an electric current and t a magnet, very much as the spring in the ' magnetic interrupter ' (Fig. 5) is kept going. It is not necessary to use an actual tuning-fork; any rod, armed with a marker, which can be made to vibrate regularly, and whose time of vibration is known, may be used for the pur- pose ; thus a reed, made to vibrate by a blast of air, is sometimes employed. The exact moment at which the induction-shock is thrown into the nerve may be recorded on the muscle-curve by means of a « signal/ which may be applied in various ways. A light steel lever armed with a marker is arranged over a small coil by means of a light spring in such a way that when the coil by the passage of a current through it becomes a magnet it pulls the lever down to itself; on the current being broken, and the magneti- zation of the coil ceasing, the lever by help of the spring flies up. The marker of such a lever is placed immediately under (i.e., at some point on the arc described by) the marker of the muscle (or other) lever. Hence by making a current in the coil and putting the signal lever down, or by breaking an already existing current, and letting the signal lever fly up, we can make at pleasure a mark corresponding to any part we please of the muscle (or other) curve. If in order to magnetize the coil of the signal, we iise, as we may do, the primary current which generates the induction-shock, the break- ing or making of the primary current, whichever we use to produce the 70 GRAPHIC RECORD OF A CONTRACTION. [BOOK i. induction-shock, will make the signal lever fly up or come down. Hence we shall have on the recording surface, under the muscle, a mark indicating the exact moment at which the primary current was broken or made. Now, the time taken up by the generation of the induced curre.nt and its passage into the nerve between the electrodes is so infinitesimally small, that we may, without appreciable error, take the moment of the breaking or making of the primary current as the moment of the entrance of the induction-shock into the nerve. Thus we can mark below the muscle-curve, or, by describing the arc of the muscle lever, on the muscle-curve itself, the exact moment at which the induction-shock falls into the nerve between the electrodes, as is done at a in Figs. 7, 8, 9. In the pendulum myograph a separate signal is not needed. If, having placed the muscle lever in the position in which we intend to make it record, we allow the glass plate to descend until the tooth ar just touches tte rod c (so that the rod is just about to be knocked down, and so break the primary circuit) and make on the base line, which is meanwhile being described by the lever marker, a mark to indicate where the point of the marker is under these circumstances, and then bring back the plate to its proper position, the mark which we have made will mark the moment of the breaking of the primary circuit and so of the entrance of the induction-shock into the nerve. For it is just when, as the glass plate swings down, the marker of the lever comes to the mark which we have made that the rod c is knocked back and the primary current is broken. FIG. 11. DIAGRAM OP AN ARRANGEMENT or A VIBRATING TUNING-FORK WITH A DESPREZ SIGNAL. The current flows along the wire /connected with the positive (+) pole or end of the negative plate (N) of the battery, through the tuning-fork, down the pin connected with the end of the lower prong, to the mercury in the cup Hg, and so by a wire (shewn in the figure as a black line bent at right angles) to the binding screw e. From this binding screw part of the current flows through the coil d between the prongs of the tuning-fork, and thence by the wire c to the binding screw a, while another part flows through the wire g, through the coil of the Desprez signal back by the wire b, to the binding screw a. From the binding screw a the current passes back to the negative (— ) pole or end of the positive element (P) of the battery. As the current flows through the coil of the Desprez signal from g to 6, the core of coil becoming magnetized draws to it the marker of the signal. As the current flows through the coil d, the core of that coil, also becoming magnetized, draws up the lower prong of the fork. But the pin is so adjusted that the drawing up of the prong lifts the point of the pin out of the mercury. In consequence, the current, being thus broken at Hg, flows neither through d nor through the Desprez signal. In consequence, the core of the Desprez thus ceasing to be magnetized, the marker flies back, being usually assisted by a CHAP, ii.] THE CONTRACTILE TISSUES. 71 spring (not shewn in the figure). But, in consequence of the current ceasing to flow through d, the core of d ceases to lift up the prong, and the pin, in the descent of the prong, makes contact once more with the mercury. The re-establishment of the current, however, once more acting on the two coils, again pulls upon the marker of the signal, and again, by magnetizing the core of c?, pulls up the prong and once more breaks the current. Thus the current is continually made and broken, the rapidity of the interruptions being determined by the vibration periods of the tuning-fork, and the lever of the signal rising and falling synchronously with the movements of the tuning-fork. A 'signal' like the above, in an improved form known as Desprez's, may be used also to record time, and thus the awkwardness of bringing a large tuning-fork up to the recording surface obviated. For this pur- pose the signal is introduced into a circuit, the current of which is continually being made and broken by a tuning-fork (Fig. 10). The tuning-fork, once set vibrating, continues to make and break the current at each of its vibrations, and, as stated above, is kept vibrating by the current. But each make or break caused by the tuning-fork affects also the small coil of the signal, causing the lever of the signal to fall down or fly up. Thus the signal describes vibration curves synchronous with those of the tuning-fork driving it. The signal may similarly be worked by means of vibrating agents other than a tuning-fork. Various recording surfaces may be used. The form most generally useful is a cylinder covered with smoked paper, and made to revolve by clockwork or otherwise ; such a cylinder driven by clockwork is shewn in Fig. 3, B. By using a cylinder of large radius with adequate gear, a high speed, some inches for instance in a second, can be obtained. In the spring myograpk a smoked glass plate is thrust rapidly forward along a groove, by means of a spring suddenly thrown into action. In the pendulum myograph, Fig. 9, a smoked glass plate attached to the lower end of a long frame, swinging like a pendulum, is suddenly let go at a certain height, and so swings rapidly through an arc of a circle. The disadvantage of the last two methods is that the surface travels at a continually changing rate, whereas, in the revolving cylinder, careful construction and adjustment will secure a very uniform rate. § 46. Having thus obtained a time record, and an indication of the exact moment at which the induction-shock falls into the nerve, "we may for present purposes consider the muscle-curve complete. The study of such a curve, as for instance that shewn in Fig. 7, taken from the gastrocnemius of a frog, teaches us the following facts : — 1. That although the passage of the induced current from electrode to electrode is practically instantaneous, its effect, meas- ured from the entrance of the shock into the nerve to the return of the muscle to its natural length after the shortening, takes an appreciable time. In the figure, the whole curve from a to d takes up about the same time as eleven double vibrations of the tuning-fork. Since each double vibration here represents 100th of a second, the duration of the whole curve is rather more than 72 MUSCLE-CUKVE. [BOOK i. 2. In the first portion of this period, from a to b, there is no visible change, no raising of the lever, no shortening of the muscle. 3. It is not until b — .that is to say, after the lapse of about •jj^ sec. — that the shortening begins. The shortening as shewn by the curve is at first slow, but soon becomes more rapid, and then slackens again until it reaches a maximum at c ; the whole shortening occupying rather more than T|^ sec. 4. Arrived at the maximum of shortening, the muscle at once begins to relax, the lever descending at first slowly, then more rapidly, and at last more slowly again, until at d the muscle has regained its natural length ; the whole return from the maximum of contraction to the natural length occupying rather more than TO o sec- Thus a simple muscular contraction, a simple spasm or twitch, produced by a momentary stimulus, such as a single induction- shock, consists of three main phases : — 1. A phase antecedent to any visible alteration in the muscle. This phase, during which invisible preparatory changes are taking place in the nerve and muscle, is called the ' latent period.' 2. A phase of shortening, or, in the more strict meaning of the word, contraction. 3. A phase of relaxation or return to the original length. In the case we are considering, the electrodes are supposed to be applied to the nerve at some distance from the muscle. Consequently the latent period of the curve comprises not only the preparatory actions which may be going on in the muscle itself, but also the changes necessary to conduct the immediate effect of the induction-shock, from the part of the nerve between the electrodes along a considerable length of nerve down to the muscle. It is obvious that these latter changes might be elimi- nated by placing the electrodes on the muscle itself, or on the nerve close to the muscle. If this were done, the muscle and lever being exactly as before, and care were taken that the induction-shock entered into the nerve at the new spot, at the moment when the point of the lever had reached exactly the same point of the travelling surface as before, two curves would be gained having the relations shewn in Fig. 12. The two curves resemble each other in almost all points, except that in the curve taken with the shorter piece of nerve, the latent period, the distance a to b as compared with the distance a to b' is shortened : the contraction begins rather earlier. A study of the two curves teaches us the following two facts : — 1. Shifting the electrodes from a point of the nerve at some distance from the muscle to a point of the nerve close to the muscle, has only shortened the latent period a very little. Even when a very long piece of nerve is taken, the difference in the two curves is very small, and, indeed, in order that it may be clearly recognized or measured, the travelling surface must be made to CHAP, ii.] THE CONTRACTILE TISSUES. 73 travel very rapidly. It is obvious, therefore, that by far the greater part of the latent period is taken up by changes in the muscle FIG. 12. CURVES ILLUSTRATING THE MEASUREMENT OF THE VELOCITY OF A NERVOUS IMPULSE. The same muscle-nerve preparation is stimulated (1) as far as possible from the muscle, (2) as near as possible to the muscle ; both contractions are registered in exactly the same way. In (1), the stimulus enters the nerve at the time indicated by the line a, the con- traction begins at b' ; the whole latent period therefore is indicated by the distance from a to bf. In (2), the stimulus enters the nerve at exactly the same time a ; the contraction begins at 6 : the latent period therefore is indicated by the distance between a and b. The time taken up by the nervous impulse in passing along the length of nerve between 1 and 2 is therefore indicated by the distance between b and b', which may be measured by the tuning-fork curve below • each double vibration of the tuning- fork corresponds to T^ or '0083 sec. itself, changes antecedent to the shortening becoming actually visible. Of course, even when the electrodes are placed close to the muscle, the latent period includes the changes going on in the short piece of nerve still lying between the electrodes and the muscular fibres. To eliminate this with a view of determining the latent period in the muscle itself, the electrodes might be placed directly on the muscle poisoned with urari. If this were done, it would be found that the latent period remained about the same, — that is to say, that in all cases the latent period is chiefly taken up by changes in the muscular as distinguished from the nervous elements. 2. Such difference as does exist between the two curves in the figure, indicates the time taken up by the propagation, along the piece of nerve, of the changes set up at the far end of the nerve by the induction-shock. These changes we have already spoken of as constituting a nervous impulse ; and the above experiment shews that it takes a small but yet distinctly appreciable time for a nervous impulse to travel along a nerve. In the figure the difference between the two latent periods, the distance between b and &', seems almost too small to measure accurately ; but if a long piece of nerve be used for the experiment, and the recording surface be made to travel very fast, the difference between the duration of the latent period when the induction-shock is sent in at a point close to the muscle, and that when it is sent in at a point as far away as possible from the muscle, may be satisfactorily measured in fractions of a second. If the length of nerve between 74 VELOCITY OF NEKVOUS IMPULSE. [BOOK i. the two points be accurately measured, the rate at which a nervous impulse travels along the nerve to a muscle can thus be easily calculated. This has been found to be in the frog about 28, and in man about 33 metres per second, but varies considerably, especially in warm-blooded animals. Thus when a momentary stimulus, such as a single induction- shock, is sent into a nerve connected with a muscle, the following events take place : a nervous impulse is started in the nerve, and this travelling down to the muscle produces in the muscle first the invisible changes which occupy the latent period, secondly the changes which bring about the visible shortening or contraction proper, and thirdly the changes which bring about the relaxation and return to the original length. The changes taking .place in these several phases are changes of living matter : they vary with the condition of the living substance of the muscle, and only take place so long as the muscle is alive. Though the relaxation which brings back the muscle to its original length is assisted by the muscle being loaded with a weight, or otherwise stretched, this is not essential to the actual relaxation, and with the same load the return will vary according to the condition of the muscle ; the relaxation must be considered as an essential part of the whole contraction, no less than the shortening itself. § 47. Not only, as we shall see later on, does the whole con- traction vary in extent and character according to the condition of the muscle, the strength of the induction-shock, the load which the muscle is bearing, and various attendant circumstances, but the three phases may vary independently. The latent period may be longer or shorter, the shortening may take a longer or shorter time to reach the same height, and especially the relaxation may be slow or rapid, complete or imperfect. Even when the same strength of induction-shock is used, the contraction may be short and sharp, or very long drawn out, so that the curves described on a recording surface, travelling at the same rate in the two cases, appear very different ; and, under certain circumstances, as when a muscle is fatigued, the relaxation, more particularly the last part of it, may be so slow, that it may be several seconds before the muscle really regains its original length. We may add that the latent period, which in an ordinary experiment on a frog's gastro- cnemius is so conspicuous, may, under certain circumstances, be so shortened as almost, if not wholly, to disappear. Indeed, it is maintained by some that the occurrence of the latent period is not an essential feature of the whole act. Hence, if we say that the duration of a simple muscular con- traction of the gastrocnemius of a frog under ordinary circumstances is about ^Q- sec., of which T^ is taken up by the latent period, -j-J ^ by the contraction, and TJ-g by the relaxation, these must be taken as ' round numbers,' stated so as to be easily remembered. The duration of each phase as well as of the whole contraction varies in UHAP. u.] THE CONTRACTILE TISSUES. 75 different animals, in different muscles of the same animal, and in the same muscle under different conditions. The muscle-curve which we have been discussing is a curve of changes in the length only of the muscle ; but if the muscle, instead of being suspended, were laid flat on a glass plate, and a lever laid over its belly, we should find, upon sending an induction-shock into the nerve, that the lever was raised, shewing that the muscle during the contraction became thicker. And if we took a graphic record of the movements of the lever, we should obtain a curve very similar to the one just discussed ; after a latent period the lever would rise, shewing that the muscle was getting thicker, and afterwards would fall, shewing that the muscle was becoming thin again. In other words, in contraction the lessening of the muscle lengthwise is accompanied by an increase crosswise ; indeed, as we shall see later on, the muscle in contracting is not diminished in bulk at all (or only to an exceedingly small extent, about T ^ ^-Q of its total bulk), but makes up for its diminution in length by increasing in its other diameters. § 48. A single induction-shock is, as we have said, the most convenient form of stimulus for producing a simple muscular con- traction, but this may also be obtained by other stimuli, provided that these are sufficiently sudden and short in their action, as, for instance, by a prick of, or sharp blow on, the nerve or muscle. For the production of a single, simple muscular contraction, the changes in the nerve leading to the muscle must be of such a kind as to constitute what may be called a single nervous impulse, and any stimulus which will evoke a single nervous impulse only may be used to produce a simple muscular contraction. As a rule, however, most stimuli other than single induction- shocks tend to produce in a nerve several nervous impulses, and, as we shall see, the nervous impulses which issue from the central nervous system, and so pass along nerves to muscles, are, as a rule, not single and simple, but complex. Hence, as a matter of fact, a simple muscular contraction is within the living body a com- paratively rare event (at least as far as the skeletal muscles are concerned,) and cannot easily be produced outside the body other- wise than by a single induction-shock. The ordinary form of muscular contraction is not a simple muscular contraction, btit the more complex form known as a tetanic contraction, to the study of which we must now turn. Tetanic Contractions. § 49. If a single induction-shock be followed at a certain interval by a second shock of the same strength, the first simple contraction will be followed by a second simple contraction, both 76 TETANUS. [BOOK i. contractions being separate and distinct ; and, if the shocks be repeated, a series of rhythmically-recurring, separate, simple con- tractions may be obtained. If, however, the interval between two shocks be made short, — if, for instance, it be made only just long enough to allow the first contraction to have passed its maximum before the latent period of the second is over, — the curves of the two contractions will bear some such relation to each other as that shewn in Fig. 13. It will be observed that the second curve is almost in all respects like the first, except that it starts, so to speak, from the first curve instead of from the base-line. The second nervous impulse has acted on the already contracted muscle, and made it contract again just as it would have done if there had been no first impulse, and the muscle had been at rest. The two contractions are added together, and the lever is raised nearly double the height it would have been by either alone. If in the same way a third shock follows the second at a sufficiently FIG. 13. TRACING or A DOUBLE MUSCLE-CURVE. While the muscle (gastroenemius of frog) was engaged in the first contraction (whose complete course, had nothing intervened, is indicated by the dotted line), a second induction-shock was thrown in, at such a time that the second contraction began just as the first was beginning to decline. The second curve is seen to start from the first, as does the first from the base-line. short interval, a third curve is piled on the top of the second ; the same with a fourth, and so on. A more or less similar result would occur if the second contraction began at another phase of the first. The combined effect is, of course, greatest when the second contraction begins at the maximum of the first, being less both before and afterwards. Hence, the result of a repetition of shocks will depend largely on the rate of repetition. If, as in Fig. 14, the shocks follow each other so slowly that one contraction is over, or almost over, before the next begins, each contraction will be distinct, or nearly distinct, and there will be little or no combined effect. FIG. 14. MUSCLE-CURVE. SINGLE INDUCTION-SHOCK REPEATED SLOWLY. CHAP, ii.] THE CONTRACTILE TISSUES. 77 If, however, the shocks be repeated more rapidly, as in Fig. 15, each succeeding contraction will start from some part of the preceding one, and the lever will be raised to a greater height at each contraction. FIG. 15. MUSCLE-CURVE. SINGLE INDUCTION-SHOCK REPEATED MORE RAPIDLY. If the frequency of the shocks be still further increased, as in Fig. 16, the rise due to the combination of contraction will be still more rapid, and a smaller part of each contraction will be visible on the curve. FIG. 16. MUSCLE-CURVE. SINGLE INDUCTION-SHOCK REPEATED STILL MORE RAPIDLY. In each of these three curves it will be noticed that the character of the curve changes somewhat during its development. The change is the result of commencing fatigue, caused by the repetition of the contractions, the fatigue manifesting itself by an increasing prolongation of each contraction, shewn especially in a delay of relaxation, and by an increasing diminution in the height of the contraction. Thus in Fig. 14 the contractions, quite distinct at first, become fused later ; the fifth contraction, for instance, is prolonged so that the sixth begins before the lever has reached the base line ; yet the summit of the sixth is hardly higher than the summit of the fifth, since the sixth, though starting at a higher level, is a somewhat weaker contraction. So, also, in Fig. 15, the lever rises rapidly at first, but more slowly afterwards, owing to an increasing diminution in the height of the single contractions. In Fig. 16 the increment of rise of the curve due to each contraction diminishes very rapidly, and though the lever does continue to 78 TETANUS. [BOOK i. rise during the whole series, the ascent, after about the sixth contraction, is very gradual indeed, and the indications of the individual contractions are much less marked than at first. Hence, when shocks are repeated with sufficient rapidity, it results that, after a certain number of shocks, the succeeding impulses do not cause any further shortening of the muscle, any further raising of I the lever, but merely keep up the contraction already existing. | The curve thus reaches a maximum, which it maintains, subjectj, to the depressing effects of exhaustion, so long as the shocks are repeated. When these cease to be given, the muscle returns to its natural length. When the shocks succeed each other still more rapidly than in Fig. 16, the individual contractions, visible at first, may become fused together and wholly lost to view in the latter part of the curve. When the shocks succeed each other still more rapidly (the second contraction beginning in the ascending portion of the first), it becomes difficult or impossible to trace out any of the single contractions.1 The curve then described by the lever is of the kind shewn in Fig. 17, where the primary current of an FIG. 17. TETANUS PRODUCED WITH THE ORDINARY MAGNETIC INTERRUPTOR or AN INDUCTION-MACHINE. (Recording surface travelling slowly.) The interrupted current is thrown in at a. induction-machine was rapidly made and broken by the magnetic interruptor, Fig. 4. The lever, it will be observed, rises at a (the recording surface is travelling too slowly to allow the latent period to be distinguished), at first very rapidly, — in fact, in an unbroken and almost a vertical line, — and so very speedily reaches the maxi- mum, which is maintained so long as the shocks continue to be given ; when these cease to be given, the curve descends, at first very rapidly, and then more and more gradually towards the base line, which it reaches just at the end of the figure. This condition of muscle, brought about by rapidly repeated shocks, this fusion of a number .of simple twitches into an 1 The ease with which the individual contractions can be made out depends in part, it need hardly be said, on the rapidity with which the recording surface travels. CHAP, ii.] THE CONTRACTILE TISSUES. 79 apparently smooth, continuous effort, is known as tetanus, or tetanic contraction. The above facts are most clearly shewn when induction-shocks, or at least galvanic currents in some form or other, are employed. They are seen, however, what- ever be the form of stimulus employed. Thus, in the case of mechanical stimuli, while a single quick blow may cause a single twitch, a pronounced tetanus may be obtained by rapidly striking successively fresh portions of a nerve. With chemical stimulation, as when a nerve is dipped in acid, it is impossible to secure a momentary application; hence tetanus, generally irregular in character, is the normal result of this mode of stimulation. In the living body, the contractions of the skeletal muscles, brought about either by the will or otherwise, are generally tetanic in character. Even very short, sharp movements, such as a sudden jerk of a limb, or a wink of the eyelid, are, in reality, examples of tetanus of short duration. If the lever, instead of being fastened to the tendon of a muscle hung vertically, be laid across the belly of a muscle placed in a horizontal position, and the muscle be thrown into tetanus by a repetition of induction-shocks, it will be seen t>frat each shortening of the muscle is accompanied by a corresponding thickening, and that the total shortening of the tetanus is accompanied by a cor- responding total thickening. And, indeed, in tetanus we can observe more easily than in a single contraction that the muscle in contracting changes in form only, not in bulk. If a living muscle, or group of muscles, be placed in a glass jar, or chamber, the closed top of which is prolonged into a narrow glass tube, arid the chamber be so filled with water (or, preferably, with a solution of sodium chloride, '6 p. c. in strength, the "normal saline solution," which is less injurious to the tissue than simple water) that the fluid rises up into the narrow tube, it is obvious that any change in the bulk of the muscle will be easily shewn by a rising or falling of the column of fluid in the narrow tube. It is found that when the muscle is made to contract, even in the most forcible manner, the change of level in the height of the column which can be observed is practically insignificant : there appears to be a fall indicating a diminution of bulk to the extent of about one ten-thousandth of the total bulk of the muscle. So that we may fairly say that in a tetanus, and hence in a simple contraction, the lessening of the length of the muscle causes a corresponding increase in the other directions : the substance of the muscle is displaced not diminished. § 50. So far we have spoken simply of an induction-shock, or of induction-shocks, without any reference to their strength, and of a living or irritable muscle, without any reference to the degree or extent of its irritability; but induction-shocks may vary in strength, and the irritability of the muscle may vary. If we slide the secondary coil a long way from the primary 80 VARIATIONS OF IRRITABILITY. [BOOK i. coil, and thus make use of extremely feeble induction-shocks, we shall probably find that these shocks, applied even to a quite fresh muscle-nerve preparation, produce no contraction. If we then gradually slide the secondary coil nearer and nearer the primary coil, and keep on trying the effects of the shocks, we shall find that, after a while, in a certain position of the coils, a very feeble contraction makes its appearance. As the secondary coil comes still nearer to the primary coil, the contractions grow greater and greater. After a while, however, and that, indeed, in ordinary circumstances very speedily, increasing the strength of the shock no longer increases the height of the contraction ; the maximum contraction of which the muscle is capable with such shocks however strong has been reached. If we use a tetanizing or interrupted current, we shall obtain the same general results ; we may, according to the strength of the current, get no contraction at all, or contractions of various extent up to a maximum, which cannot be exceeded. Under favourable conditions the maximum contraction may be very considerable : the shortening in tetanus may amount to three-fifths of the total length of the muscle. The amount of contraction then depends on the strength of the stimulus, whatever be the stimulus; but this holds good within certain limits only ; to this point however we shall return later on. § 51. If, having ascertained in a perfectly fresh muscle-nerve preparation the amount of contraction produced by this and that strength of stimulus, we leave the preparation by itself for some time, say for a few hours, and then repeat the observations, we shall find that stronger stimuli, stronger shocks, for instance, are required to produce the same amount of contraction as before ; that is to say, the irritability of the preparation, the power to respond to stimuli, has in the meanwhile diminished. After a further interval, we should find the irritability still further diminished : even very strong shocks would be unable to evoke contractions as large as those previously caused by weak shocks. At last we should find that no shocks, no stimuli, however strong, were able to produce any visible contraction whatever. The amount of contraction, in fact, evoked by a stimulus depends not only on the strength of the stimulus but also on the degree of irritability of the muscle-nerve preparation. Immediately upon removal from the body, the preparation possesses a certain amount of irritability, not differing very materially from that which the muscle arid nerve possess while within, and forming an integral part of the body ; but after re- moval from the body the preparation loses irritability, the rate of loss being dependent on a variety of circumstances ; and this goes on until, since no stimulus which we can apply will give rise to a contraction, we say the irritability has wholly disappeared. CHAP. IT.] THE CONTRACTILE TISSUES. 81 We might take this disappearance of irritability as marking the death of the preparation, but it is followed sooner or later by a curious change in the muscle, which is called rigor mortis, and which we shall study presently ; and it is convenient to regard this rigor mortis as marking the death of the muscle. The irritable muscle, then, when stimulated either directly, the stimulus being applied to itself, or indirectly, the stimulus being applied to its nerve, responds to the stimulus by a change of form which is essentially a shortening and thickening. By the shortening (and thickening), the muscle in contracting is able to do work, to move the parts to which it is attached ; it thus sets free energy. We have now to study more in detail how this energy is set free and the laws which regulate its expenditure. SEC. 2. ON THE CHANGES WHICH TAKE PLACE IN A MUSCLE DURING A CONTRACTION. The Change in Form. § 52. An ordinary skeletal muscle consists of elementary muscle fibres, bound together in variously arranged bundles by connective . tissue which carries blood vessels, nerves and lym- phatics. The contraction of a muscle is the contraction of all or some of its elementary fibres, the connective tissue being passive ; hence while those fibres of the muscle which end directly in the tendon, in contracting pull directly on the tendon, those which do not so end pull -indirectly on the tendon by means of the connective tissue between the bundles, which connective tissue is continuous with the tendon. Each muscle is supplied by one or more branches of nerves which, running in the connective tissue, divide into smaller branches and twigs between the bundles and between the fibres, and eventually end in such a way that every muscular fibre is sup- plied with at least one nerve fibre, which joins the muscular fibre somewhere about the middle between its two ends or sometimes nearer one end, in a special nerve ending called an end-plate. It follows that when a muscular fibre is stimulated by means of a nerve fibre, the nervous impulse travelling down the nerve fibre falls into the muscular fibre not at one end but at about its mid- dle; it is the middle of the fibre which is affected first by the nervous impulse, and the changes in the muscular substance started in the middle of the muscular fibre travel thence to the two ends of the fibre. In an ordinary skeletal muscle however, the fibres and bundles of fibres begin and end at different distances from the ends of the muscle, and the nerve or nerves going to the muscle divide and spread out in the muscle in such a way that the end-plates, in which the individual fibres of the nerve end, are distributed widely over the muscle at very different CHAP, ii.] THE CONTRACTILE TISSUES. 83 distances from the ends of the muscle. Hence, if we suppose a single nervous impulse, such as that generated by a single induction-shock, or a series of such impulses to be started at the same time at some part of the trunk of the nerve in each of the fibres of the nerve going to the muscle, these impulses will reach very different parts of the muscle at about the same time and the contractions which they set going will begin, so to speak, nearly all over the whole muscle at the same time, and will not all start in any particular zone or area of the muscle. § 53. The wave of contraction. We have seen, however, that under the influence of urari the nerve fibre is unable to excite contractions in a muscular fibre, although the irritability of the muscular fibre itself is retained. Hence, in a muscle poisoned by urari the contraction begins at that part of the muscular substance which is first affected by the stimulus, and we may start a con- traction in what part of the muscle we please by properly placing the electrodes. Some muscles, such for instance as the sartorius of the frog, though of some length are composed of fibres which run parallel to each other from one end of the muscle to the other. If such a muscle be poisoned with urari so as to eliminate the action of the nerves and stimulated at one end (an induction-shock sent through a pair of electrodes placed at some little distance apart from each other at the end of the muscle may be employed, but better results are obtained if a mode of stimulation, of which we shall have to speak presently, viz. the application of the " constant cur- rent," be adopted), the contraction which ensues starts from the end stimulated, and travels thence along the muscle. If two levers be made to rest on, or be suspended from, two parts of such a muscle placed horizontally, the parts being at a known distance from each other and from the part stimulated, the progress of the contraction may be studied. The movements of the levers indicate in this case the thicken- ing of the fibres which is taking place at the parts on which the levers rest or to which they are attached; and if we take a graphic record of these movements, bringing the two levers to mark, one immediately below the other, we shall find that the lever nearer the part stimulated begins to move earlier, reaches its maximum earlier, and returns to rest earlier than does the farther lever. The contraction, started by the stimulus, in travelling along the muscle from the part stimulated reaches the nearer lever some little time before it reaches the farther lever, and has passed by the nearer lever some little time before it has passed by the farther lever ; and the farther apart the two levers are the greater will be the difference in time between their movements. In other words the contraction travels along the muscle in the form of a wave, each part of the muscle in succession from the end 84 THE WAVE OF CONTRACTION. [BOOK i. stimulated swelling out and shortening as the contraction reaches it, and then returning to its original state. And what is true of the collection of parallel fibres which we call the muscle is also true of each fibre, for the swelling at any part of the muscle is only the sum of the swelling of the individual fibres ; if we were able to take a single long fibre and stimulate it at one end, we should be able under the microscope to see a swelling or bulging accompanied by a corresponding shortening, i.e. to see a con- traction sweep along the fibre from end to end. If in the graphic record of the two levers just mentioned we count the number of vibrations of the tuning-fork which intervene between the mark on the record which indicates the beginning of the rise of the near lever (that is, the arrival of the contraction wave at this lever) and the mark which indicates the beginning of the rise of the far lever, this will give us the time which it has taken the contraction wave to travel from the near to the far lever. Let us suppose this to be '005 sec. Let us suppose the distance between the two levers to be 15 mm. The con- traction wave then has taken -005 sec. to travel 15 mm., that is to say it has travelled at the rate of 3 meters per sec. And indeed we find by this, or by other methods, that in the frog's muscles the contraction wave does travel at a rate which may be put down as from 3 to 4 meters a second, though it varies under different con- ditions. In the warm blooded mammal the rate is somewhat greater, and may probably be put down at 5 meters a second in the excised muscle, rising possibly to 10 meters in a muscle within the living body. If again in the graphic record of the two levers wre count, in the case of either lever, the number of vibrations of the tuning- fork which intervene between the mark where the lever begins to rise and the mark where it has finished its fall and returned to the base line, we can measure the time intervening between the contraction wave reaching the lever, and leaving the lever on its way onward, that is to say, we can measure the time which it has taken the contraction wave to pass over the part of the muscle on which the lever is resting. Let us suppose this time to be say •1 sec. But a wave which is travelling at the rate of 3 m. a second and takes 1 sec. to pass over any point must be 300 mm. long. And indeed we find that in the frog the length of the contraction wave may be put down as varying from 200. to 400 mm.; and in the mammal it is not very different. Now the very longest muscular fibre is stated to be at most only about 40 mm. in length ; hence, in an ordinary contraction, during the greater part of the duration of the contraction the whole length of the fibre will be occupied by the contraction wave. Just at the beginning of the contraction there will be a time when the front of the contraction wave has reached for CHAP, ii.] THE CONTRACTILE TISSUES. 85 instance only half-way down the fibre (supposing the stimulus to be applied, as in the case we have been discussing, at one end only), and just at the end of the contraction there will be a time for instance when the contraction has left the half of the fibre next to the stimulus, but has not yet cleared away from the other half. But nearly all the rest of the time every part of the fibre will be in some phase or other of contraction, though the parts nearer the stimulus will be in more advanced phases than the parts farther from the stimulus. This is true when a muscle of parallel fibres is stimulated artificially at one end of the muscles, and when therefore each fibre is stimulated at one end. It is of course all the more true when a muscle of ordinary construction is stimulated by means of its nerve. The stimulus of the nervous impulse impinges, in this case, on the muscle fibre at the end-plate which, as we have said, is placed towards the middle of the fibre, and the contraction wave travels from the end-plate in opposite directions toward each end, and has accordingly only about half the length of the fibre to run in. All the more therefore must the whole fibre be in a state of contraction at the same time. § 54. We may now turn to the question, What takes place in a muscular fibre when a contraction wave sweeps over it ? Optical Changes. Although undoubtedly the optical features of a muscular fibre change while it is contracting, it is very diffi- cult to make an authoritative statement as to what those changes are. In the first place a contraction wave, even when it is travel- ling with relative slowness, travels so rapidly that the individual features cannot be seized by the eye. We are confined to con- clusions drawn from the study of short local contractions, local thickenings and shortenings which may be obtained in the living fibre and fixed by the action of osmic acid vapour or by other means ; and it has to be assumed that these local bulgings give a true picture of a normal contraction wave by which, as we have just seen, the whole length of a fibre is occupied at the same time. In the second place the minute structure of a muscular fibre has been and still is the subject of fierce dispute. If we adopt the view that the fibre is made up of dim bands or discs of dim substance alternating with bright bands or discs of bright substance, with transverse markings in the middle of each bright band forming a line " intermediate " be- tween the two adjacent dim bands, we may, according to some observers, say that during a contraction there seems to be an interchange between the dim and bright bands so that, in ordinary light, at the height of the contraction, in the broadest part of one of the bulgings just spoken of, the previously obscure " interme- diate line " becomes a conspicuous dark band, the interval between two such changed intermediate lines becoming relatively and uni- 86 CHEMISTRY OF MUSCLE. [BOOK i. f ormly bright ; in other words there is a sort of reversal of the situation, what was bright becoming, in its middle at least, dark, and what was dim becoming relatively bright. When the fibre is examined under polarized light, by which the dim bands are shown to be largely composed of doubly refractive, anisotropic material and the bright bands chiefly of singly refractive, isotropic material, it is found that the above apparent reversal is not based on any reversal of the refractive material, the anisotropic (dim) band remains anisotropic, and the isotropic (bright) band remains isotropic. But while both bands become broader (across the fibre) and thinner (shorter along the length of the fibre), the anisotropic band does not become so much thinner as does the isotropic band, in other words the dim doubly refractive band or disc increases in bulk at the expense of the bright singly refractive band. And this accords with another feature of the fibre during contraction ; namely, that the sarcolemma, which in the fibre at rest presents a quite even line, is then indented at the middle of the bright band at about the position of the intermediate line, and bulges out opposite the dim band, that is opposite the enlarged aniso- tropic disc. It is useless, however, to dwell on these matters until the minute structure of the fibre has been more clearly and satisfactorily made out than it is at present. A contraction is obviously a transloca- tion of molecules of the muscle substance and may, very roughly, be compared to the movement by which a company, say of one hun- dred soldiers ten ranks deep, with ten men in each rank, extends out into a double line of two ranks with fifty men in each rank. The movement of translocation is obviously, in striated muscle, a very complicated one, but how the striation helps the movement we do not at present really know. All we can say is that when swift and rapid contraction is needed, the contractile tissue em- ployed puts on in nearly all cases the striated structure. The Chemistry of Muscle. § 55. We said, in the Introduction, that it was difficult to make out with certainty the exact chemical differences between dead and living substance. Muscle however in dying undergoes a remarkable chemical change, which may be studied with com- parative ease. We have already said that all muscles, within a certain time after removal from the body, or, if still remaining part of the body, within a certain time after ' general ' death of the body, lose their irritability, and that the loss of irritability, which even when rapid, is gradual, is succeeded by an event which is somewhat more sudden, viz. the entrance into the condition known as rigor mortis. The occurrence of rigor mortis, or cadaveric rigid- CHAP, ii.] THE CONTRACTILE TISSUES. 87 ity, as it is sometimes called, which may be considered as the token of the death of the muscle, is marked by the following features. The living muscle possesses a certain translucency, the rigid muscle is distinctly more opaque. The living muscle is very extensible and elastic, it stretches readily and to a considerable extent when a weight is hung upon it or when any traction is applied to it, but speedily and, under normal circumstances, completely returns to its original length when the weight or traction is removed ; as we shall see however the rapidity and completeness of the return depends on the condition of the muscle, a well-nourished, active muscle regaining its normal length much more rapidly and com- pletely than a tired and exhausted muscle. A dead, rigid muscle • is much less extensible and at the same time much less elastic ; the muscle now requires considerable force to stretch it, and when the force is removed, does not, as before, return to its former length. To the touch the rigid muscle has lost much of its former softness, and has become firmer and more resistant. The entrance into rigor mortis is moreover accompanied by a shorten- ing or contraction, which may, under certain circumstances, be considerable. The energy of this contraction is not great, so that any actual shortening is easily prevented by the presence of even a slight opposing force. Now the chemical features of the dead, rigid muscle are also strikingly different from those of the living muscle. § 56. If a dead muscle, from which all fat, tendon, fascia, and connective tissue have been as much as possible removed, and which has been freed from blood by the injection of 'normal' saline solution, be minced and repeatedly washed with water, the washings will contain certain forms of albumin and certain extractive bodies, of which we shall speak directly. When the washing has been continued until the wash-water gives no proteid reaction, a large portion of muscle will still remain undissolved. If this be treated with a 10 p. c. solution of a neutral salt, ammonium chloride being the best, a large portion of it will become dissolved ; the solution however is more or less imperfect and filters with difficulty. If the filtrate be allowed to fall drop by drop into a large quantity of distilled water, a white flocculent matter will be precipitated. This flocculent precipitate is myosin. Myosin is a proteid, giving the ordinary proteid reactions, and having the same general elementary composition as other proteids. It is soluble in dilute saline solutions, especially those of ammonium chloride, and may be classed in the globulin family, though it is not so soluble as paraglobulin, requiring a stronger solution of a neutral salt to dissolve it ; thus while soluble in a 5 or 10 p. c. solution of such a salt, it is far less soluble in a 1 p. c. solution, which as we have seen readily dissolves paraglobulin. From its solutions in neutral saline solution it is precipitated by saturation with a neutral 88 CHEMISTRY OF MUSCLE. [BOOK i. salt, preferably sodium chloride, and may be purified by being washed with a saturated solution, dissolved again in a weaker solution, and reprecipitated by saturation. Dissolved in saline solutions it readily coagulates when heated, i.e. is converted into coagulated proteid, and it is worthy of notice that it coagulates at a comparatively low temperature, viz. about 56°C. ; this it will be remembered is the temperature at which fibrinogen is coagu- lated, whereas paraglobulin, serum albumin, and many other pro- teids do not coagulate until a higher temperature, 75° C., is reached. Solutions of myosin are precipitated by alcohol, and the precipitate, as in the case of other proteids, becomes by continued action of the alcohol altered into coagulated insoluble proteid. We have seen that paraglobulin, and indeed any member of the globulin group, is very readily changed by the action of dilute acids into a body called acid albumin, characterised by not being soluble either in water or in dilute saline solutions but readily soluble in dilute acids and alkalis, from its solutions in either of which it is precipitated by neutralisation, and by the fact that the solutions in dilute acids and alkalis are not coagulated by heat. When therefore a globulin is dissolved in dilute acid, what takes place is not a mere solution but a chemical change ; the globulin cannot be got back from the solution, it has been changed into acid-albumin. Similarly when globulin is dissolved in dilute alkalis it is changed into alkali albumin ; and broadly speaking alkali, albumin precipitated by neutralisation can be changed by solution with dilute acids into acid albumin, and acid albumin by dilute alkalis into alkali albumin. Now myosin is similarly, and even more readily than is globulin, converted into acid albumin, and by treating a muscle either washed or not, directly with dilute hydrochloric acid, the myosin may be converted into acid albumin and dissolved out. Acid albumin obtained by dissolving muscle in dilute acid used to be called syntonin, and it used to be said that a muscle contained syntonin ; the muscle however contains myosin, not syntonin, but it may be useful to retain the word syntonin to denote acid albumin obtained by the action of dilute acid on myosin. By the action of dilute alkalis, myosin may similarly be converted into alkali albumin. From what has been stated above it is obvious that myosin has many analogies with fibrin, and we have yet to mention other striking analogies ; it is however much more soluble than fibrin, and speaking generally it may be said to be intermediate in its character between fibrin and globulin. On keeping, and especially on drying, its solubility is much diminished. Of the substances which are left in washed muscle, from which all the myosin has been extracted by ammonium chloride solution, little is known. If washed muscle be treated directly with dilute CHAP, ii.] THE CONTRACTILE TISSUES. 89 hydrochloric acid, a large part of the material of the muscle passes, as we have said, at once into syntonin. The quantity of syntoniri thus obtained may be taken as roughly representing the quantity of myosin previously existing in the muscle. A more prolonged action of the acid may dissolve out other proteids, besides myosin, left after the washing. The portion insoluble in dilute hydro- chloric acid consists in part of the gelatine yielding and other substances of the sarcolemma and of the connective and other tissues between the bundles, of the nuclei of these tissues and of the fibres themselves, and in part, possibly, of some portions of the muscle substance itself. We are not however at present in a position to make any very definite statement as to the relation of the myosin to the structural features of muscle. Since the dim bands are rendered very indistinct by the action of 10 p.c. sodium chloride solution, we may perhaps infer that myosin enters largely into the composition of the dim bands, and therefore of the fibrillae ; but it would be hazardous to say much more than this. § 57. Living muscle may be frozen, and yet, after certain precautions will, on being thawed, regain its irritability, or at all events will for a time be found to be still living in the sense that it has not yet passed into rigor mortis. We may therefore take living muscle which has been frozen as still living. If living contractile muscle, freed as much as possible from blood, be frozen, and while frozen, minced, and rubbed up in a mortar with four times its weight of snow containing 1 p.c. of sodium chloride, a mixture is obtained which at a temperature just below 0° C. is sufficiently fluid to be filtered, though with difficulty. The slightly opalescent filtrate, or muscle plasma as it is called, is at first quite fluid, but will when exposed to the ordinary temperature become a solid jelly, and afterwards separate into a clot and serum. It will in fact clot like blood plasma, with this difference, that the clot is not firm and fibrillar, but loose, granular, and flocculent. During the clotting the fluid, which before was neutral or slightly alkaline, becomes distinctly acid. The clot is myosin. It gives all the reactions of myosin obtained from dead muscle. The serum contains an albumin very similar to, if not identical with, serum albumin, a globulin differing somewhat from, and coagulating at a lower te'mperature than paraglobulin, and which to distinguish it from the globulin of blood has been called myo- glolulin, some other proteids which need not be described here, and various ' extractives ' of which we shall speak directly. Such muscles as are red also contain a small quantity of haemoglobin and possibly, another allied red pigment. Thus while dead muscle contains myosin, albumin, and other proteids, extractives, and certain insoluble matters, together with gelatinous and other substances not referable to the muscle 90 RIGOR MORTIS. [BOOK i. substance itself, living muscle contains no myosin, but some substance or substances which bear somewhat the same relation to myosin that the antecedents of fibrin do to fibrin, and which give rise to myosin upon the death of the muscle. There are indeed reasons for thinking that the myosin arises from the conversion of a previously existing body, which may be called myosinogen, and that the conversion takes place, or may take place, by the action of a special ferment, the conversion of myosinogen into myosin being very analogous to the conversion of tibrinogen into fibrin. We may in fact speak of rigor mortis as characterised by a clotting of the muscle plasma, comparable to the clotting of blood plasma, but differing from it inasmuch as the product is not fibrin but myosin. The rigidity, the loss of suppleness, and the dimin- ished translucency appear to be at all events largely, though probably not wholly, due to the change from the fluid plasma to the solid myosin. We might compare a living muscle to a number of fine transparent membranous tubes containing blood plasma. When this blood plasma entered into the ' jelly ' stage of clotting, the system of tubes would present many of the phenomena of rigor mortis. They would lose much of their suppleness and translucency, and acquire a certain amount of rigidity. § 58. There is however one very marked and important difference between the rigor mortis of muscle and the clotting of blood. Blood during its clotting undergoes a slight change only in its reaction ; but muscle during the onset of rigor mortis becomes distinctly acid. A living muscle at rest is in reaction neutral, or, possibly from some remains of lymph adhering to it, faintly alkaline. If on the other hand the reaction of a thoroughly rigid muscle be tested, it will be found to be most distinctly acid. This development of an acid reaction is witnessed not only in the solid untouched fibre but also in expressed muscle plasma ; it seems to be associated in some way with the appearance of the myosin. The exact causation of this acid reaction has not at present been clearly worked out. Since the coloration of the litmus pro- duced is permanent, carbonic acid, which as we shall immediately state, is set free at the same time, cannot be regarded as the active acid, for the reddening of litmus produced by carbonic acid speedily disappears on exposure. On the other hand, it is possible to ex- tract from rigid muscle a certain quantity of lactic acid, or rather of a variety of lactic acid known as sarcolactic acid l ; and we may probably regard the acid reaction of rigid muscle as due to a new formation or to an increased formation of this sarcolactic acid. There is reason however to think that the establishment of the 1 There are many varieties of lactic acid, which are isomeric, having the same composition C8H6OS, but differ in their reactions and especially in the solubility of their zinc salts. The variety present in muscle is distinguished as sarcolactic acid. CHAP, ii.] THE CONTRACTILE TISSUES. 91 acid reaction is not a perfectly simple process but a more or less complex one, other substances besides sarcolactic acid intervening. Coincident with the appearance of this acid reaction, though as we have said, not the direct cause of it, a large development of carbonic acid takes place when muscle becomes rigid. Irritable living muscular substance like all living substance is continually respiring, that is to say, is continually consuming oxygen and giving out carbonic acid. In the body, the arterial blood going to the muscle gives up some of its oxygen, and gains a quantity of carbonic acid, thus becoming venous as it passes through the muscle capillaries. Even after removal from the body, the living muscle continues to take up from the surrounding atmosphere a certain quantity of oxygen and to give out a certain quantity of carbonic acid. At the onset of rigor mortis there is a very large and sudden increase in this production of carbonic acid, in fact an outburst as it were of that gas. This is a phenomenon deserving special attention. Knowing that -the carbonic acid which is the outcome of the respiration of the whole body is the result of the oxidation of car- bon-holding substances, we might very naturally suppose that the increased production of carbonic acid attendant on the development of rigor mortis is due to the fact that during that event a certain quantity of the carbon-holding constituents of the muscle are suddenly Oxidized. But such a view is negatived by the following facts. In the first place, the increased production of carbonic acid during rigor mortis is not accompanied by a corresponding in- crease in the consumption of oxygen. In the second place, a muscle (of a frog for instance) contains in itself no free or loosely attached oxygen ; when subjected to the action of a mercurial air- pump it gives off no oxygen to a vacuum, offering in this respect a marked contrast to blood ; and yet, when placed in an atmosphere free from oxygen, it will not only continue to give off carbonic acid while it remains alive, but will also exhibit at the onset of rigor mortis the same increased production of carbonic acid that is shewn by a muscle placed in an atmosphere containing oxygen. It is obvious that in such a case the carbonic acid does not arise from the direct oxidation of the muscle substance, for there is no oxygen present at the time to carry on that oxidation. We are driven to suppose that during rigor mortis, some complex body, containing in itself ready formed carbonic acid so to speak, is split up, and thus carbonic acid is set free, the process of oxidation by which that carbonic acid was formed out of the carbon-holding con- stituents of the muscle having taken place at some anterior date. Living resting muscle, then, is alkaline or neutral in reaction, and the substance of its fibres contains a plasma capable of clotting. Dead rigid muscle on the other hand is acid in reaction, and no longer contains a plasma capable of clotting, but is laden with the 92 RIGOR MORTIS. [BOOK i. solid myosin. Further, the change from the living irritable con- dition to that of rigor mortis is accompanied by a large and sudden development of carbonic acid. It is found moreover that there is a certain amount of parallel- ism between the intensity of the rigor mortis, the degree of acid reaction and the quantity of carbonic acid given out. If we suppose, as we fairly may do, that the intensity of the rigidity is dependent on the quantity of myosin deposited in the fibres, and the acid reaction to the development if not of lactic acid, at least of some other substance, the parallelism between the three products, myosin, acid-producing substance, and carbonic acid, would suggest the idea that all three are the results of the splitting-up of the same highly complex substance. No one has at present however succeeded in isolating or in otherwise definitely proving the exist- ence of such a body, and though the idea seems tempting, it may in the end prove erroneous. § 59. As to the other proteids of muscle, such as the albumin and the globulin, we know as yet nothing definite concerning the parts which they play and the changes which they undergo in the living muscle or in rigor mortis. Besides the fat which is found, and that not unfrequently in abundance, in the connective tissue between the fibres, there is also present in the muscular substance within the sarcolemma, always some, and at times a great deal, of fat, chiefly ordinary fat, viz. stearin, palmitin, and olein in variable proportion, but with a small quantity of the more complex fat lecithin ; the latter probably is derived from the nerve fibres. As to the function of these several fats in the life of the muscle we know little or nothing. Carbohydrates, the third of the three great classes in which we may group the energy-holding substances of which the animal body and its food are alike composed, viz. proteids, fat and carbo- hydrates, are represented in muscle by a peculiar body, glycogen, which we shall have to study in detail later on. We must here merely say that glycogen is a body closely allied to starch, having a formula, which may be included under the general formula for starches n (C6H10O5), and may like it be converted by the action of acids, or by the action of particular ferments known as amylolytic ferments, into some form of sugar, dextrose (C6H1206) or some allied sugar. Many, if not all, living muscles contain a certain amount, and some, under certain circumstances, a considerable amount of glycogen. During or after rigor mortis this glycogen is very apt to be converted into dextrose, or an allied sugar. The muscles of the embryo at an early stage contain a relatively enormous quantity of glycogen, a fact which suggests that the glycogen of muscle is carbohydrate food of the muscle about to be wrought up into the living muscular substance. The bodies which we have called extractives are numerous and CHAP, ii.] THE CONTRACTILE TISSUES. 93 varied. They are especially interesting since it seems probable that they are waste products of the metabolism of the muscular substance, and the study of them may be expected to throw light on the chemical change which muscular substance undergoes during life. Since, as we shall see, muscular substance forms by far the greater part of the nitrogenous — that is, proteid — portion of the body, the nitrogenous extractives of muscle demand peculiar atten- tion. Now, the body urea, which we shall have to study in detail later on, far exceeds in importance all the other nitrogenous extrac- tives of the body as a whole, since it is practically the one form in which nitrogenous waste leaves the body ; if we include with urea, the closely allied uric acid (which for present purposes may simply be regarded as a variety of urea), we may say broadly that all the nitrogen taken in as food sooner or later leaves the body as urea ; compared with this all other nitrogenous waste thrown out from the body is insignificant. Of the urea which thus leaves the body, a considerable portion must at some time or other have existed, or, to speak more exactly, its nitrogen must have existed as the nitrogen of the proteids of muscular substance. Nevertheless, no urea at all or an absolutely minimal quantity only is, in normal conditions, present in muscular substance either living and irritable, or dead and rigid ; urea does not arise in muscular substance itself as one of the immediate waste products of muscular substance. There is, however, always present, in relatively considerable amount, on an average about *25 p.c. of wet muscle, a remarkable body, kreatin. This is in one sense a compound of urea : it may be split up into urea and sarcosin. This latter body is a methyl glycin, that is to say, a glycin in which methyl has been sub- stituted for hydrogen, and glycin itself is amido-acetic acid, a compound of amidogen, that is a representative of ammonia, and acetic acid. Hence kreatin contains urea, which has close relations with ammonia, together with another representative of ammonia, and a surplus of carbon and hydrogen arranged as a body belonging to the fatty acid series. We shall have to return to this kreatin, and to consider its relations to urea and to muscle, when we come to deal with urine. The other nitrogenous extractives, such as karnin, hypoxanthin (or sarkin), xanthin, taurin, &c., occur in small quantity, and need not be dwelt on here. Among non-nitrogenous extractives, the most important is the sarcolactic acid, of which we have already spoken ; to this may be added sugar in some form or other, either coming from glycogen or from some other source. The ash of muscle, like the ash of the blood corpuscles, and, indeed, the ash of the tissues in general, as distinguished from the blood, or plasma, or lymph on which the tissues live, is character- ised by the preponderance of potassium salts and of phosphates ; these form in fact nearly 80 p.c. of the whole ash. 94 CHEMICAL CHANGES. [BOOK i. § 60. We may now pass on to the question, What are the chemical changes which take place when a living, resting muscle enters into a contraction ? These changes are most evident after the muscle has been subjected to a prolonged tetanus ; but there can be no doubt that the chemical events of a tetanus are, like the physical events, simply the sum of the results of the consti- tuent single contractions. In the first place, the muscle becomes acid, not so acid as in rigor mortis, but still sufficiently so, after a vigorous tetanus, to turn blue litmus distinctly red. The cause of the acid reaction, like that of rigor mortis, is not quite clear, but is in all probability the same in both cases. In the second place, a considerable quantity of carbonic acid is set free ; and the production of carbonic acid in muscular contrac- tion resembles the production of carbonic acid during rigor mortis in that it is not accompanied by a corresponding increase in the consumption of oxygen. This is evident even in a muscle through which the circulation of blood is still going on ; for though the blood passing through a contracting muscle gives up more oxygen than the blood passing through a resting muscle, the increase in the amount of oxygen taken up falls below the increase in the carbonic acid given out. But it is still more markedly shewn in a muscle removed from the body ; for in such a muscle both the. contraction and the increase in the production of carbonic acid will go on in the absence of oxygen. A frog's muscle, suspended in an atmosphere of nitrogen, will remain irritable for some considerable- time, and at each vigorous tetanus an increase in the production of carbonic acid may be readily ascertained. Moreover, there seems to be a correspondence between the- energy of the contraction and the amount of carbonic acid and the degree of acid reaction produced, so that, though we are now treading on somewhat uncertain ground, we are naturally led to the view that the essential chemical process, lying at the bottom of a muscular contraction as of rigor mortis, is the splitting-up of some- highly complex substance. But here the resemblance between rigor mortis and contraction ends. We have no satisfactory evidence of the formation during a contraction of any body like myosin. And this difference in chemical results tallies with an important physical difference between rigid muscle and contracting muscle. The rigid muscle, as we have seen, becomes less extensible, less elastic, less translucent ; the contracting muscle remains no less trans- lucent, elastic, and extensible than the resting muscle, — indeed, there are reasons for thinking that the muscle in contracting becomes actually more extensible for the time being. But if, during a contraction, myosin is not formed, what changes of proteid or nitrogenous matter do take place ? We do not know. We have no evidence that kreatin, or any other nitrogenous extractive, is increased by the contraction of muscle ; we have no CHAP, ii.] THE CONTRACTILE TISSUES. 95 satisfactory evidence of any nitrogen waste at all as the result of a contraction ; and, indeed, as we shall see later on, the study of the waste products of the body as a whole leads us to believe that the energy of the work done by the muscles of the body comes from the potential energy of carbon compounds, and not of nitrogen compounds at all. But to this point we shall have to return. § 61. We may sum up the chemistry of muscle somewhat as. follows : — During life the muscular substance is continually taking up from the blood, that is from the lymph, proteid, fatty and carbo- hydrate material, saline matters and oxygen ; these it builds up into itself, how, we do not know, and so forms the peculiar complex living muscular substance. The exact nature of this living sub- stance is unknown to us. What we do know is that it is largely composed of proteid material, and that such bodies as myosinogen,, myoglobulin, and albumin, being always present in it, have probably something to do with the building of it up. During rest this muscular substance, while taking in and build- ing itself up out of, or by means of, the above-mentioned materials^ is continually giving off carbonic acid, and continually forming nitrogenous waste, such as kreatin. It also probably gives off some amount of sarcolactic acid, and possibly other non-nitrogenous waste matters. During a contraction there is a great increase in the amount of carbonic acid given off, an increased formation of lactic acid, and possibly other changes giving rise to an acid reaction, a greater consumption of oxygen, though the increase is not equal to the increase of carbonic acid, but, as far as we can learn, no increase of nitrogenous waste. During rigor mortis, there is a similar increased production of carbonic acid and of some other acid-producing substance, ac- companied by a remarkable conversion of myosinogen into myosin, by which the rigidity of the dead fibre is brought about. Thermal Changes. § 62. The chemical changes during a contraction set free a quantity of energy, but only a portion of this energy appears in the ' work done ; ' a considerable portion takes on the form of heat. .Though we shall have hereafter to treat this subject more fully, the leading facts may be given here. Whenever a muscle contracts, its temperature rises, indicating that heat is given out. When a mercury thermometer is plunged into a mass of muscles, such as those of the thigh of the dog, a rise of the mercury is observed upon the muscles being thrown into a prolonged contraction. More exact results however are obtained by means of a thermopile, by the help of which the rise of tempera- 96 THERMAL CHANGES. [BOOK i. ture caused by a few repeated single contractions, or, indeed, by a single contraction, may be observed, and the amount of heat given out approximatively measured. The thermopile may consist either of a single junction, in the form of a needle plunged into the substance of the muscle ; or of several junctions either in the shape of a flat surface carefully opposed to the surface of muscle (the pile being balanced so as to move with the contracting muscle, and thus to keep the contact exact), or in the shape of a thin wedge, the edge of which, comprising the actual junctions, is thrust into a mass of muscles and held in position by them. In all cases the fellow junction or junctions must be kept at a constant temperature. Another delicate method of determining the changes of temperature of a tissue is based upon the measurement of alterations in electric resistance which a fine wire, in contact with or plunged into the tissue, undergoes as the temperature of the tissue changes. It has been calculated that the heat given out by the muscles of the thigh of a frog in a single contraction amounts to 3'1 micro-units of heat 1 for each gramme of muscle, the result being obtained by dividing by five the total amount of heat given out in five succes- sive single contractions. It will, however, be safer to regard these figures as illustrative of the fact that the heat given out is consider- able rather than as data for elaborate calculations. Moreover, we have no satisfactory quantitative determinations of the heat given out by the muscles of warm blooded animals, though there can be no doubt that it is much greater than that given out by the muscles of the frog. There can hardly be any doubt that the heat thus set free is the product of chemical changes within the muscle, changes, which, though they cannot, for the reasons given above (§ 60), be regarded as simple and direct oxidations, yet, since they are processes dependent on the antecedent entrance of oxygen into the muscle, may be spoken of in general terms as a combustion. So that the muscle may be likened to a steam-engine, in which the combus- tion of a certain amount of material gives rise to the development of energy in two forms, as heat and as movement, there being certain quantitative relations between the amount of energy set free as heat and that giving rise to movement. We must, however, carefully guard ourselves against pressing this analogy too closely. In the steam-engine, we can distinguish clearly between the fuel which, through its combustion, is the sole source of energy, and the machinery, which is not consumed to provide energy, and only suffers wear and tear. In the muscle we cannot with certainty at present make such a distinction. It may be that the chemical changes at the bottom of a contraction do not involve the real living material of the fibre, but only some substance, manufactured by the living material and lodged in some way, we do not know 1 The micro-unit being a milligramme of water raised one degree centigrade. CHAP, ii.] THE CONTRACTILE TISSUES. 97 how, in the living material ; it may be that when a fibre contracts it is this substance within the fibre which explodes, and not the fibre itself. If we further suppose that this substance is some complex compound of carbon and hydrogen, into which no nitrogen enters, we shall have an explanation of the difficulty referred to above (§ 60), namely, that nitrogenous waste is not increased by a contraction. The special contractile, carbon-hydrogen substance may then be compared to the charge of a gun, the products of its explosion being carbonic and sarcolactic acids, while the real, living material of the fibre may be compared to the gun itself ; but to a gun which itself is continually undergoing change, far beyond mere wear and tear, among the products of which change nitrogenous bodies like kreatin are conspicuous. This view will certainly explain why kreatin is not increased during the contraction while the carbonic and lactic acids are. But it must be remembered that such a view is not yet proved ; it may be the living material of the fibre as a whole which is continually breaking down in an explosive decom- position, and as continually building itself up again out of the material supplied by the blood. In a steam-engine only a certain amount of the total potential energy of the fuel issues as work, the rest being lost as heat, the proportion varying, but the work rarely, if ever, exceeding one- tenth of the total energy, and generally being less. In the case of the muscle we are not at present in a position to draw up an exact equation between the latent energy on the one hand and the two forms of actual energy on the other. We have reason to think that the proportion between heat and work varies considerably under different circumstances, the work sometimes rising as high as one-fifth, or, according to some, as high even as one-half, some- times possibly sinking as low as one twenty-fourth of the total energy ; and observations seem to shew that the greater the re- sistance which the muscle has to overcome, the larger the proportion of the total energy expended, which goes out as work done. The muscle, in fact, seems to be so far self-regulating, that the more work it has to do, the greater, within certain limits, is the economy with which it works. Lastly, it must be remembered that the giving out of heat by the muscle is not confined to the occasions when it is actually con- tracting. When, at a later period, we treat of the heat of the body generally, evidence will be brought forward that the muscles, even when at rest, are giving rise to heat, so that the heat given out at a contraction is not s'ome wholly new phenomenon, but a temporary exaggeration of what is continually going on at a more feeble rate. Electrical Changes. § 63. Besides chemical and thermal changes a remarkable electric change takes place whenever a muscle contracts. 98 THERMAL CHANGES. [BOOK i. Muscle-currents. If a muscle be removed in an ordinary manner from the body, and two non-polarisable electrodes,1 con- nected with a delicate galvanometer of many convolutions and z.s c/t.c FIG. 18. NON-POLARISABLE ELECTRODES. a, the glass tube ; z, the amalgamated zinc slips connected with their respective wires; z. s., the zinc sulphate solution , ch. c., the plug of china clay; c', the portion of the china-clay plug projecting from the end of the tube this can be moulded into any required form. high resistance, be placed on two points of the surface of the muscle, a deflection of the galvanometer will take place, indicating the existence of a current passing through the galvanometer from the one point of the muscle to the other, the direction and amount of the deflection varying according to the position of the points. The ' muscle-currents ' thus revealed are seen to the best advantage when the muscle chosen is a cylindrical or prismatic one with parallel fibres, and when the two tendinous ends are cut off by clean incisions at right angles to the long axis of the muscle. The muscle then presents a transverse section (artificial) at each end, and a longitudinal surface. We may speak of the latter as being divided into two equal parts by an imaginary transverse line on its surface called the ' equator,' containing all the points of the surface midway between the two ends. Fig. 19 is a diagrammatic representation of such a muscle, the line ab being the equator. In such a muscle the development of the muscle-currents is found to be as follows. 1 These (Fig. 18) consist essentially of a slip of thoroughly amalgamated zinc dipping into a saturated solution of zinc sulphate, which, in turn, is brought into connection with the nerve or muscle by means of a plug or bridge of china-clay, moistened with normal sodium chloride solution , it is important that the zinc should be thoroughly amalgamated. This form of electrodes gives rise to less polarisation than do simple platinum or copper electrodes. The clay affords a connection be- tween the zinc and the tissue which neither acts on the tissue nor is acted on by the tissue. Contact of any tissue with copper or platinum is in itself sufficient to develope a current. CHAP, ir.] THE CONTRACTILE TISSUES. 99 The greatest deflection is observed when one electrode is placed at the mid-point or equator of the muscle, and the other at either cut end ; and the deflection is of such a kind as to shew that posi- tive currents are continually passing from the equator through the galvanometer to the cut end ; that is to say, the cut end is negative relatively to the equator. The currents outside the muscle may be considered as completed by currents in the muscle from the cut end to the equator. In the diagram Fig. 19, the arrows indicate the FIG. 19. DIAGRAM ILLUSTRATING THE ELECTRIC CURRENTS OF NERVE AND MUSCLE. Being purely diagrammatic, it may serve for a piece either of nerve or of muscle, except that the currents at the transverse section cannot be shewn in a nerve. The arrows shew the direction of the current through the galvanometer. ab the equator. The strongest currents are those shewn by the dark lines, as from a, at equator, to x or to y at the cut ends. The current from a to c is weaker than from a to y, though both, as shewn by the arrows, have the same direction. A current is shewn from e, which is near the equator, to/, which is farther from the equator. The current (in muscle) from a point in the circumference to a point nearer the centre of the transverse section is shewn at gh. From a to 6 or from x to y there is no current, as indicated by the dotted lines. direction of the currents. If the one electrode be placed at the equator ab, the effect is the same at whichever of the two cut ends x or y the other is placed. If, one electrode remaining at the equator, the other be shifted from the cut end to a spot c nearer to the equator, the current continues to have the same direction, but is of less intensity in proportion to the nearness of the electrodes to each other. If the two electrodes be placed at unequal distances e and /, one on either side of the equator, there will be a feeble current from the one nearer the equator to the one farther off, and the current will be the feebler, the more nearly they are equidistant from the equator. If they are quite equidistant, as, for instance, when one is placed on one cut end x, and the other on the other cut end y, there will be no current at all. If one electrode be placed at the circumference of the transverse section and the other at the centre of the transverse section, there 100 MUSCLE CURRENTS. [BOOK i. will be a current through the galvanometer from the former to the latter ; there will be a current of similar direction but of less intensity when one electrode is at the circumference g of the trans- verse section, and the other at some point h nearer the centre of the transverse section. In fact, the points which are relatively most positive and most negative to each other are points on the equator and the two centres of the transverse sections ; and the intensity of the current between any two points will depend on the respective distances of those points from the equator and from the centre of the transverse section. Similar currents may be observed when the longitudinal surface is not the natural but an artificial one ; indeed they may be wit- nessed in even a piece of muscle provided it be of cylindrical shape and composed of parallel fibres. These ' muscle-currents ' are not mere transitory currents dis- appearing as soon as the circuit is closed ; on the contrary, they last a very considerable time. They must, therefore, be maintained by some changes going on in the muscle, by continued chemical action in fact. They disappear as the irritability of the muscle vanishes, and are connected with those nutritive, so-called vital changes which maintain the irritability of the muscle. Muscle-currents, such as have just been described, may, we re- peat, be observed in any cylindrical muscle suitably prepared, and similar currents, with variations which need not be discussed here, may be seen in muscles of irregular shape with obliquely or other- wise arranged fibres. And Du Bois-Reymond, to whom chiefly we are indebted for our knowledge of these currents, has been led to regard them as essential and important properties of living muscle. He has moreover advanced the theory that muscle may be con- sidered as composed of electro-motive particles or molecules, each of which, like the muscle at large, has a positive equator and nega- tive ends, the whole muscle being made up of these molecules in somewhat the same way (to use an illustration which must not, however, be strained or considered as an exact one) as a magnet may be supposed to be made up of magnetic particles, each with its north and south pole. There are reasons, however, for thinking that these muscle- currents have no such fundamental origin, that they are in fact of surface and indeed of artificial origin. Without entering into the controversy on this question, the following important facts may be mentioned : — 1. When a muscle is examined while it still retains uninjured its natural tendinous terminations, the currents are much weaker than when artificial transverse sections have been made ; the natural tendinous end is less negative than the cut surface. But the tendinous end becomes at once negative when it is dipped in water or acid, indeed, when it is in any way injured. The less roughly, in fact, a muscle is treated the less evident are the CHAP, ii.] THE CONTRACTILE TISSUES. 101 muscle-currents ; and it is maintained that if adequate care be taken to maintain a muscle in an absolutely natural condition, no such currents as those we have been describing exist at all, that natural living muscle is isoelectric, as it is called. 2. The surface of the uninjured inactive ] ventricle of the frog's heart, which is practically a mass of muscle, is isoelectric, no current is obtained when the electrodes are placed on any two points of the surface. If, however, any part of the surface be injured, or if the ventricle be cut across so as to expose a cut surface, the injured spot or the cut surface becomes at once powerfully negative towards the uninjured surface, a strong current being developed which passes through the galvanometer from the uninjured surface to the cut surface or to the injured spot. The negativity thus developed in a cut surface passes off in the course of some hours, but may be restored by making a fresh cut and exposing a fresh surface. The temporary duration of the negativity after injury, and its renewal upon fresh injury, in the case of the ventricle, in contrast to the more permanent negativity of injured skeletal muscle, is explained by the different structure of the two kinds of muscle. The cardiac muscle, as we shall hereafter see, is composed of short fibre-cells ; when a cut is made a c.ertain number of these fibre- cells are injured, giving rise to negativity, but the injury done to them stops with them, and is not propagated to the cells with which they are in contact ; hence, upon their death the negativity and the current disappear. A fresh cut involving new cells, pro- duces fresh negativity and a new current. In the long fibres of the skeletal muscle, on the other hand, the effects of the injury are slowly propagated along the fibre from the spot injured. Now, when a muscle is cut or injured, the substance of the fibres dies at the cut or injured surface. And many physiologists, among whom the most prominent is Hermann, have been led, by the above and other facts, to the conclusion that muscle-currents do not exist naturally in untouched, uninjured muscles, that the muscular substance is naturally, when living, isoelectric, but that whenever a portion of the muscular substance dies, it becomes while dying negative to the living substance, and thus gives rise to currents. They explain the typical currents (as they might be called) manifested by a muscle with a natural longitudinal surface and artificial transverse sections, by the fact that the dying cut ends are negative relatively to the rest of the muscle. Du Bois-Reymond and those with him offer special explanations of the above facts and of other objections which have been urged against the theory of naturally existing electro-motive molecules. Into these we cannot enter here. We must rest content with the statement that in an ordinary muscle currents, such as have been described, may be witnessed, but that .strong arguments may be 1 The necessity of its being inactive will be seen subsequently. 102 MUSCLE CURRENTS. [BOOK i. adduced in favour of the view that these currents are not ' natural ' phenomena, but essentially of artificial origin. It will therefore be best to speak of them as currents of rest. § 64. Currents of action. Negative variation of the Muscle- current. The controversy whether the ' currents of rest ' observable in a muscle be of natural origin or not, does not affect the truth or the importance of the fact that an electrical change takes place, and a current is developed in a muscle whenever it enters into a contraction. When currents of rest are observable in a muscle, these are found to undergo a diminution upon the occurrence of a contraction, and this diminution is spoken of as ' the negative variation ' of the currents of rest. The negative variation may be seen when a muscle is thrown into a single contraction, but is most readily shewn when the muscle is tetanized. Thus, if a pair of electrodes be placed on a muscle, one at the equator, and the other at or near the transverse section, so that a considerable deflection of the galvanometer needle, indicating a considerable current of rest, be gained, the needle of the galvanometer will, when the muscle is tetanized by an interrupted current sent through its nerve (at a point too far from the muscle to allow of any escape of the current into the electrodes connected with the galvanometer), swing back towards zero ; it returns to its original deflection when the tetanizing current is shut off. Not only may this negative variation be shewn by the galvano- meter, but it, as well as the current of rest, may be used as a galvanic shock, and so employed to stimulate a muscle, as in the experiment known as ' the rheoscopic frog.' For this purpose the muscles and nerves need to be in thoroughly good condition, and very irritable. Two muscle-nerve preparations, A and B, having been made, and each placed on a glass plate for the sake of insula- tion, the nerve of the one, B, is allowed to fall on the muscle of the other, A, in such a way that one point of the nerve comes in contact with the equator of the muscle, and another point with one end of the muscle or with a point at some distance from the equator. At the moment the nerve is let fall and contact made, a current, viz. the ' current of rest ' of the muscle A, passes through the nerve ; this acts as a stimulus to the nerve, and so causes a contraction in the muscle connected with a nerve. Thus the muscle A acts as a battery, the completion of the circuit of which by means of the nerve of B serves as a stimulus, causing the muscle B to contract. If, while the nerve of B is still in contact with the muscle of A, the nerve of the latter is tetanized with an interrupted current, not only is the muscle of A thrown into tetanus, but also that of B ; the reason being as follows. At each spasm of which the tetanus of A is made up, there is a negative variation of the muscle current of A. Each negative variation of the muscle current of A serves as a stimulus to the nerve of B, and is hence CHAP, ii.] THE CONTRACTILE TISSUES. 103 the cause of a spasm in the muscle of B; and the stimuli following each other rapidly, as being produced by the tetanus of A, they must do, the spasms in B to which they give rise are also fused into a tetanus in B. B, in fact, contracts in harmony with A. This experiment shews that the negative variation accompanying the tetanus of a muscle, though it causes only a single swing of the galvanometer, is really made up of a series of negative variations, each single negative variation corresponding to the single spasms of which the tetanus is made up. But an electrical change may be manifested even in cases when no currents of rest exist. We have stated (§ 63) that the surface of the uninjured inactive ventricle of the frog's heart is isoelectric, no currents being observed when the electrodes of a galvanometer are placed on two points of the surface. Nevertheless, a most distinct current is developed whenever the ventricle contracts. This may be shewn either by the galvanometer or by the rheo- scopic frog. If the nerve of an irritable muscle-nerve preparation be laid over a pulsating ventricle, each beat is responded to by a twitch of the muscle of the preparation. In the case of ordinary muscles, too, instances occur in which it seems impossible to regard the electrical change manifested during the contraction as the mere diminution of a preexisting current. Accordingly those who deny the existence of ' natural ' muscle- currents speak of a muscle as developing during a contraction a ' current of action,' occasioned as they believe by the muscular sub- stance as it is entering into the state of contraction, becoming negative towards the muscular substance which is still at rest, or has returned to a state of rest. In fact, they regard the negativity of muscular substance as characteristic alike of beginning death and of a beginning contraction. So that in a muscular contraction a wave of negativity, starting from the end-plate when indirect, or from the point stimulated when direct stimulation is used, passes along the muscular substance to the ends or end of the fibre. If, for instance, we suppose two electrodes placed on two points (Fig. 20), A and B, of a fibre about to be stimulated by a single induc- tion-shock at one end. Before the stimulation the fibre is isoelectric, and the needle of the galvanometer stands at zero. At a certain time after the shock has been sent through the stimulating electrodes (#), as the wave of contraction is travelling down the fibre, the sec- tion of the fibre beneath A will become negative towards the rest of the fibre, and so negative towards FIG. 20. the portion of the fibre under B% 104 MUSCLE CURRENTS. [BOOK i. i.e. A will be negative relatively to B, and this will be shewn by a deflection of the needle. A little later, B will be entering into contraction, and will be becoming negative towards the rest of the fibre, including the part under A, whose negativity by this time is passing off; that is to say, B will now be negative towards A, and this will be shewn by a deflection of the needle in a direction opposite to that of the deflection which has just previously taken place. Hence, between two electrodes placed along a fibre, a single wave of contraction will give rise to two currents of different phases, to a diphasic change ; and this, indeed, is found to be the case. This being so, it is obvious that the electrical result of tetanizing a muscle when wave after wave follows along each fibre, is a com- plex matter ; but it is maintained that the apparent negative variation of tetanus can be explained as the net result of a series of currents of action, due to the individual contractions, the second phase of the current in each contraction being less marked than the first phase. We cannot, however, enter more fully here into a discussion of this difficult subject. When we study, as we may do with the help of appropriate apparatus, the rapidity with which the electrical change accompany- ing a muscular contraction travels, we find it to be the same as that of the contraction wave itself. The older observations seemed to shew that the electrical change fell entirely within the latent period, and might, therefore, be regarded as an outward token of invisible molecular processes, occupying the latent period, and sweeping along the muscular fibre ahead of and preparing for the visible change of form. And, indeed, since we are led to regard the change of form as the result of chemical processes taking place in the muscular substance, we must suppose that the change of form is preceded by molecular chemical changes. But, as we have said, a latent period of measurable length does not appear to be an essential feature of a muscular contraction ; we may, under certain circumstances, fail to detect a latent period. And some recent observations seem to shew that the electrical change and the change of form may begin at the same time. Indeed, some have maintained that the former is the result of the latter, and not, as suggested above, of the forerunning molecular events. The question however is one which cannot at present be regarded as settled. The Changes in a Nerve during the passage of a Nervous Impulse. § 65. The change in the form of a muscle during its contrac- tion is a thing which can be seen and felt ; but the changes in a nerve during its activity are invisible and impalpable. We stimu- late one end of a nerve going to a muscle, and we see this followed CHAP, ii.] THE CONTRACTILE TISSUES. 105 by a contraction of the muscle attached to the other end ; or we stimulate a nerve still connected with the central nervous system, and we see this followed by certain movements, or by other tokens which shew that disturbances have been set up in the central nervous system. We know therefore that some changes or other, constituting what we have called a nervous impulse, have been propagated along the nerve ; but the changes are such as we cannot see. It is possible, however, to learn something about them. § 66. The chemistry of a nerve. The medulla of a medullated nerve fibre is usually spoken of as fatty, and yet is in reality very largely composed of a substance which is not (in the strict sense of the word) a fat. When we examine chemically a quantity of nerve (or what is practically the same thing a quantity of that part of the central nervous system which is called white matter, and which is chiefly composed, like a nerve, of medullated nerves, and is to be preferred for chemical examination because it contains a relatively small quantity of connective tissue), we find that a very large proportion, according to some observers about half, of the dried matter consists of the peculiar body cholesterin. Now cholesterin is not a fat but an alcohol ; like glycerine, however, which is also an alcohol, it forms compounds with fatty acids ; and though we do not know definitely the chemical condition in which cholesterin exists during life in the medulla, it is more than probable that it exists in some combination with some of the really fatty bodies also present in the medulla, and not in- a fre^ isolated state. It is singular that besides being present in su2h large quantities in nervous tissue, and to a small extent in other tissues and in blood, cholesterin is a normal constituent of bile, and forms the greater part of gall stones when these are present ; in gall stones it is undoubtedly present in a free state. Besides cholesterin 'white' nervous matter contains a less but still considerable quantity of a complex fat, whose nature is disputed. According to some authorities rather less than half this complex fat consists of the peculiar body lecithin, which we have already seen to be present also in blood corpuscles and else- where. Lecithin contains the radicle of stearic acid (or of oleic, or of palmitic acid) associated not, as in ordinary fats, with simple glycerine, but with the more complex glycerin-phosphoric acid, and further combined with a nitrogenous body, neurin, an am- monia compound of some considerable complexity ; it is therefore of remarkable nature since, though a fat, it contains both nitrogen arid phosphorus. According to the same authorities the remainder of the complex fat consists of another fatty body, also apparently containing nitrogen but no phosphorus, called cerebrin. Other authorities regard both these bodies, lecithin and cerebrin, as products of decomposition of a still, more complex fat, called protagon. Obviously the fat of the white matter of the central 106 THE CHEMISTRY OF NERVES. [BOOK i. nervous system and of spinal nerves (of which fat by far the greater part must exist in the medulla, and form nearly the whole of the medulla) is a very complex body indeed, especially so if the cholesterin exists in combination with the lecithin, or cerebrin (or protagon). Being so complex it is naturally very unstable, and in- deed, in its instability resembles proteid matter. Hence probably the reason why the medulla changes so rapidly and so profoundly after the death of the nerve. It seems moreover that a certain though small quantity of proteid matter forms part of the medulla, and it is possible that this exists in some kind of combination with the complex fat ; but our knowledge on this point is imperfect. The presence in such large quantity of this complex fatty medulla renders the chemical examination of the other consti- tuents of a nerve very difficult, and our knowledge of the chemical nature of, and of the chemical changes going on in, the axis-cylinder, is as yet limited. Examined under the microscope the axis-cylinder gives the xanthoproteic reaction and other indications that it is largely proteid in nature. From nervous matter, and especially from the grey matter of the brain and spinal cord, there may by appropriate methods be extracted certain proteids similar to those found in leucocytes and other cells (§ 29) namely, a nucleo-albu- min and one or more globulins ; these are probably constituents both of the nerve cells and of the axis-cylinders which are pro- cesses of cells. Since kreatin and a lactic acid are present among the ' extractives ' of nervous tissue, we may infer that in a broad way the chemical changes in nerves are similar to those in muscles. Beyond this we can say very little. After the fats of the medulla (and the much smaller quantity of fat present in the axis-cylinder), the proteids of the axis-cylinder, and the other soluble substances present in one or the other, or gathered round the nuclei of the neurilemma, have by various means been dissolved out of a nerve fibre certain substances still remain. One of these in small quantity is the nuclein of the nuclei: another in larger quantity is the substance neurokeratin which forms a supporting framework for the medulla, and whose most marked characteristic is perhaps its resistance to solution. In the ash of nerves there is a preponderance of potassium salts and phosphates but not so marked as in the case of muscle. § 67. The nervous impulse. The chemical analogy between the substance of the muscle and that of the axis-cylinder would naturally lead us to suppose that the progress of a nervous im- pulse along a nerve fibre was accompanied by chemical changes similar to those taking place in a muscle fibre. Whatever changes however do or may take place are too slight to be recognized by the means at our disposal. We have no satisfactory evidence that in a nerve even repeated nervous impulses can give rise to an acid reaction or that the .death of a nerve fibre leads to such a reaction. The grey matter of the central nervous system it is true CHAP, ii.] THE CONTRACTILE TISSUES. 107 is said to be faintly alkaline during life and to become acid after death ; but in this grey matter nerve cells are relatively abundant ; the white matter, composed chiefly of nerve fibres, is and remains, during action as well as rest, and even after death, neutral or slightly alkaline. Nor have we satisfactory evidence that the progress of a nervous impulse is accompanied by any setting free of energy in the form of heat. In fact, beyond the terminal results, such as a muscular con- traction in the case of a nerve going to a muscle, or some affection of the central nervous system in the case of a nerve still in con- nection with its nervous centre, there is one event and one event only which we are able to recognize as the objective token of a nervous impulse, and that is an electric change. For a piece of nerve removed from the body exhibits nearly the same electric phenomena as a piece of muscle. It has an equator which is electrically positive relatively to the two cut ends. In fact the dia- gram Fig. 19, and the description which was given in § 63 of the electric changes in muscle may be applied almost as well to a nerve, except that the currents are in all cases much more feeble in the case of nerves than of muscles, and the special currents from the circumference to the centre of the transverse sections cannot well be shewn in a slender nerve ; indeed it is doubtful if they exist at all. During the passage of a nervous impulse the ' natural nerve current' undergoes a negative variation, just as the 'natural muscle current' undergoes a negative variation during a con- traction. There are moreover reasons in the case of the nerve, as in the case of the muscle, which lead us to doubt the pre-exist- ence of any such ' natural ' currents. A nerve in an absolutely natural condition appears to be, like a muscle, isoelectric ; hence we may say that in a nerve during the passage of a nervous impulse, as in a muscle during a muscular contraction, a ' current of action ' is developed. This ' current of action ' or ' negative variation' may be shewn either by the galvanometer or by the rheoscopic frog. If the nerve of the ' muscle nerve preparation ' B (see § 64 ) be placed in an appropriate manner on a thoroughly irritable nerve A (to which of course no muscle need be attached), touching for instance the equator and one end of the nerve, then single induc- tion-shocks sent into the far end of A will cause single spasms in the muscle of B, while tetanization of A, i. e. rapidly repeated shocks sent into A, will cause tetanus of the muscle of B. That this current, whether it be regarded as an independent ' current of action ' or as a negative variation of a ' pre-existing ' current, is an essential feature of a nervous impulse is shewn by the fact that the degree or intensity of the one varies with that of the other. They both travel too at the same rate. In describ- 108 ELECTRIC CURRENTS IN NERVES. [BOOK i. ing the muscle-curve, and the method of measuring the muscular latent period, we have incidentally shewn (§ 46) how at the same time the velocity of the nervous impulse may be measured, and stated that the rate in the nerves of a frog is about 28 meters a second. By means of a special and somewhat complicated apparatus it is ascertained that the current of action travels along an isolated piece of nerve at the same rate. It also, like the contraction, travels in the form of a wave, rising rapidly to a maximum at each point of the nerve and then more gradually declining again. The length of the wave may by special means be measured, and is found to be about 18 mm. When an isolated piece of nerve is stimulated in the middle, the current of action is propagated equally well in both direc- tions, and that whether the nerve be a chiefly sensory or a chiefly motor nerve, or indeed if it be a nerve-root composed exclusively of motor or of sensory fibres. Taking the current of action as the token of a nervous impulse, we infer from this that when a nerve fibre is stimulated artificially at any part of its course, the nervous impulse set going travels in both directions. We used just now the phrase ' tetanization of a nerve/ mean- ing the application to a nerve of rapidly repeated shocks such as would produce tetanus in the muscle to which the nerve was attached, and we shall have frequent occasion to employ the phrase. It must however be understood that there is in the nerve, in an ordinary way, no summation of nervous impulses com- parable to the summation of muscular contractions. Putting aside certain cases which we cannot discuss here we may say that the series of shocks sent in at the far end of the nerve start a series of impulses ; these travel down the nerve and reach the muscle as a series of distinct impulses ; and the first changes in the muscle, the molecular changes which, sweeping along the fibre, initiate the change of form, and which we may perhaps speak of as constituting a muscle impulse, also probably form a series the members of which are distinct. It is not until these molecular changes become transformed into visible changes of form that any fusion or summation takes place. § 68. Putting together the facts contained in this and the pre- ceding sections, the following may be taken as a brief approximate history of what takes place in a muscle and nerve when the latter is subjected to a single induction-shock. At the instant that the induced current passes into the nerve, changes occur, of whose nature we know nothing certain except that they cause a ' current of action ' or ' negative variation ' of the ' natural ' nerve current. These changes propagate themselves along the nerve in both directions as a nervous impulse in the form of a wave, having a wave-length of about 18 mm., and a velocity (in frog's nerve) of about 28 m. per sec. Passing down the nerve fibres to the muscle, flowing along the branching and narrowing tracts, the wave at last CHAP, ii.] THE CONTRACTILE TISSUES. 109 breaks on the end-plates of the fibres of the muscle. Here it is transmuted into what we have called a muscle impulse, which with a greatly diminished velocity (about 3 m. per sec.), travels from each end-plate in both directions to the end of the fibre, where it appears to be lost, at all events we do not know what becomes of it. As this impulse wave sweeps along the fibre it initiates an explosive decomposition of material, leading to a discharge of carbonic acid, to the appearance of some substance or substances with an acid reaction, and probably of other unknown things, with a considerable development of heat. This explosive decomposition gives rise to the visible contraction wave ; the fibre, as the wave passes over it, swells and shortens and thus brings its two ends nearer together. When repeated shocks are given, wave follows wave of nervous impulse, muscle impulse, and visible contraction ; but the last do not keep distinct, they are fused into the continued shortening which we call tetanus. SEC. 3. THE NATURE OF THE CHANGES THROUGH WHICH AN ELECTRIC CURRENT IS ABLE TO GENE- RATE A NERVOUS IMPULSE. Action of the Constant Current. § 69. In the preceding account, the stimulus applied in order to give rise to a nervous impulse has always been supposed to be an induction-shock, single or repeated. This choice of stimulus has been made on account of the almost momentary duration of the induced current. Had we used a current lasting for some consider- able time, the problems before us would have become more com- plex, in consequence of our having to distinguish between the events taking place while the current was passing through the nerve, from those which occurred at the moment when the current was thrown into the nerve, or at the moment when it was shut off from the nerve. These complications do arise when, instead of employing the induced current as a stimulus, we use a constant current, i.e. when we pass through the nerve (or muscle) a current direct from the battery, without the intervention of any induc- tion-coil. Before making the actual experiment, we might, perhaps, naturally suppose that the constant current would act as a stimu- lus throughout the whole time during which it was applied ; that, so long as the current passed along the nerve, nervous impulses would be generated, and that these would throw the muscle into some- thing at all events like tetanus. And under certain conditions this does take place ; occasionally it does happen that at the moment the current is thrown into the nerve the muscle of the muscle- nerve preparation falls into a tetanus, which is continued until the current is shut off ; but such a result is exceptional. In the vast majority of cases what happens is as follows. At the moment that the circuit is made, the moment that the current is thrown into the nerve, a single twitch, a simple contraction, the so-called making contraction, is witnessed ; but after this has passed away CHAP, ii.] THE CONTRACTILE TISSUES. Ill the muscle remains absolutely quiescent in spite of the current continuing to pass through the nerve, and this quiescence is maintained until the circuit is broken, until the current is shut off from the nerve, when another simple contraction, the so- called breaking contraction, is observed. The mere passage of a constant current of uniform intensity through a nerve does not, under ordinary circumstances, act as a stimulus generating a nervous impulse; such an impulse is only set up when the current either falls into or is shut off from the nerve. It is the entrance or the exit of the current, and not the continuance of the current, which is the stimulus. The quiescence of the nerve and muscle during the passage of the current is, however, dependent on the current remaining uniform in intensity or at least not being suddenly increased or diminished. Any sufficiently sudden and large increase or diminution of the intensity of the current will act like the entrance or exit of a current, and, by generating a nervous impulse, give rise to a contraction. If the intensity of the current, however, be very slowly and gradually increased or di- minished, a very wide range of intensity may be passed through without any contraction being seen. It is the sudden change from one condition to another, and not the condition itself, which causes the nervous impulse. In many cases, both a ' making ' and a ' breaking ' contraction, each a simple twitch, are observed, and this is perhaps the commonest event ; but when the current is very weak, and again when the current is very strong, either the breaking or the making contraction may be absent, i.e. there may be a contraction only when the current is thrown into the nerve, or only when it is shut off from the nerve. Under ordinary circumstances the contractions witnessed with the constant current, either at the make or at the break, are of the nature of a ' simple ' contraction, but, as has already been said, the application of the current may give rise to a very pronounced tetanus. Such a tetanus is seen sometimes when the current is made, lasting during the application of the current, sometimes when the current is broken, lasting some time after the current has been wholly removed from the nerve. The former is spoken of as a ' making,' the latter as a ' breaking ' tetanus. But these excep- tional results of the application of the constant current need not detain us now. The great interest attached to the action of the constant current lies in the fact that during the passage of the current, in spite of the absence of all nervous impulses, and, therefore, of all muscular contractions, the nerve is for the time both between and on each side of the electrodes profoundly modified in a most peculiar manner. This modification, important both for the light it throws on the generation of nervous impulses and for its practical applications, is known under the name of electrotonus. 112 ELECTROTONUS. [BOOK i. § 70. Electrotonus. The marked feature of the electrotonic condition is that the nerve, though apparently quiescent, is changed in respect to its irritability ; and that in a different way in the neighbourhood of the two electrodes respectively. Suppose that on the nerve of a muscle-nerve preparation are placed two (non-polarizable) electrodes (Fig. 21, a, k), connected with a battery and arranged with a key so that a constant current can at pleasure be thrown into or shut off from the nerve. This constant current, whose effects we are about to study, may be called the ' polarizing current.' Let a be the positive electrode or anode, and k the negative electrode or kathode, both placed at some distance from the muscle, and also with a certain interval between each other. At the point x let there be applied a pair of electrodes connected with an induction-coil. Let the muscle further be connected with a lever, so that its contractions can be recorded, and their amount measured. Before the polarizing current is thrown into the nerve, let a single induction-shock of known intensity (a weak one being chosen, or at least not one which would cause in the muscle a maximum contraction) be thrown in at x. A contraction of a certain amount will follow. II * x II < _ ^ * FIG. 21. MUSCLE-NERVE PREPARATIONS, with the nerve exposed in A to a descending and in B to an ascending constant current. In each a is the anode, k the kathode of the constant current, x represents the spot where the induction-shocks used to test the irritability of the nerve are sent in. That contraction may be taken as a measure of the irritability of the nerve at the point x. Now, let the polarizing current be thrown in, and let the kathode or negative pole be nearest the muscle, as in Fig. 21 A, so that the current passes along the nerve in a direction from the central nervous system towards the muscle ; such a current is spoken of as a descending one. The entrance of the polarizing current into the nerve will produce CHAP, ii.] THE CONTKACTILE TISSUES. 113 a ' making ' contraction ; this we may neglect. If while the current is passing, the same induction-shock as before be sent through x, the contraction which results will be found to be greater than on the former occasion. If the polarizing current be now shut off, a ' breaking ' contraction will probably be produced ; this also we may neglect. If now the point x, after a short interval, be again tested with the same induction-shock as before, the contraction will be no longer greater, but of the same amount, or perhaps not so great, as at first. During the passage of the polarizing current, therefore, the irritability of the nerve at the point x has been temporarily increased, since the same shock applied to it causes a greater contraction during the presence than in the absence of the current. But this is only true so long as the polarizing current is a descending one, so long as the point x lies on the side of the kathode. On the other hand, if the polarizing current had been an ascending one, with the anode or positive pole nearest the muscle, as in Fig. 21 B, the irritability of the nerve at x would have been found to be diminished instead of increased by the polarizing current ; the contraction obtained during the passage of the constant current would be less than before the passage of the current, or might be absent altogether, and the contraction after the current had been shut off would be as great or perhaps greater than before. That is to say, when a constant current is applied to a nerve, the irritability of the nerve between the polar- izing electrodes and the muscle is, during the passage of the current, increased when the kathode is nearest the muscle (and the polarizing current descending), and diminished when the anode is nearest the muscle (and the polarizing current ascending). The same result, mutatis mutandis, and with some qualifications which we need not discuss, would be gained if x were placed not between the muscle and the polarizing current, but on the far side of the latter. Hence,jt may be stated generally that during the passage I of a constant current through a nerve, the irritability of the nerve I is increased in the region of the kathode, and diminished in the region of the anode. The changes in the nerve which give risejjo this increase of irritability in the region of the kathode are spoken of as Jcatelectroionu8t and the nerve is said to be in a katelectfotonic condition. Similarly the changes in the region of the anode are spoken of as anelectrotonus, and the nerve is said to be in an anelectrotonic condition. It is also often usual to speak of the katelectrotonic increase, and anelectrotonic decrease of irritability. This law remains true whatever be the mode adopted for determining the irritability. The result holds good not only with a single induction-shock, but also with a tetanizing inter- rupted current, with chemical and with mechanical stimuli. It further appears to hold good not only in a dissected nerve-muscle preparation, but also in the intact nerves of the living body. The 8 114 ELECTKOTONUS. [BOOK i. increase and decrease of irritability are most marked in the immediate neighbourhood of the electrodes, but spread for a considerable distance in each direction in the extrapolar regions. The same modification is not confined to the extrapolar region, but exists also in the intrapolar region. In the intrapolar region there must be of course a neutral or indifferent point, where the katelectrotonic increase merges into the anelectrotonic decrease, and where, therefore, the irritability is unchanged. When the polarizing current is a weak one, this indifferent point is nearer the anode than the kathode, but as the polarizing current increases in intensity, draws nearer and nearer the kathode (see Fig. 22). \ The amount of increase and decrease is dependent : (1) On the \ strength of the current, the stronger current up to a certain limit \producing the greater effect. (2) On the irritability of the nerve, the more irritable, better conditioned nerve being the more affected by a current of the same intensity. In the experiments just described the increase or decrease of irritability is taken to mean that the same stimulus starts in the one case a larger or more powerful, and in the other case a smaller or less energetic impulse ; but we have reason to think that the mere propagation or conduction of impulses started elsewhere is also affected by the electrotonic condition. At all events anelectrotonus appears to offer an obstacle to the passage of a nervous impulse. A + fr FIG. 22. DIAGRAM ILLUSTRATING THE VARIATIONS OF IRRITABILITY DURING ELECTRO- TONUS, WITH POLARIZING CURRENTS OF INCREASING INTENSITY (from Pfliiger). The anode is supposed to be placed at A, the kathode at B ; AB is consequently the intrapolar district. In each of the three curves, the portion of the curve below the base line represents diminished irritability, that above, increased irritability. yl represents the effect of a weak current ; the indifferent point xl is near the anode A. In ?/2, a stronger current, the indifferent point x% is nearer the kathode B, the diminution of irritability in anelectrotonus and the increase in katelactro- tonus being greater than in y± ; the effect also spreads for a greater distance along the extrapolar regions in both directions. In yz the same events are seen to be still more marked. § 71. Electrotonic Currents. During the passage of a constant current through a nerve, variations in the electric currents belonging to the nerve itself may be observed ; and these variations have certain relations to the variations of the irritability of the nerve. Thus, if a constant current, supplied by the battery P (Fig. 23), be applied CHAP, ii.] THE CONTRACTILE TISSUES. 115 to a piece of nerve by means of two non-polarizable electrodes p, pf, the " currents of rest " obtainable from various points of the nerve will be different during the passage of the polarizing current from those which were manifest before or after the current was applied ; and, moreover, the changes in the nerve-currents produced by the polarizing current will not be the same in the neighbourhood of the anode (p) as those in the neighbourhood of the kathode (pf). Thus let G and H be two galvanometers so connected with the two ends of the nerve as to afford good and clear evidence of the "currents of rest." Before the polarizing current is thrown into the nerve, the needle of U will occupy a position indicating the passage of a current of a certain intensity from h to h1 through the galvanometer (from the positive longitudinal surface to the negative cut end of the nerve), the circuit being completed by a current in the nerve from h' to h, i.e. the current K FIG. 23. DIAGRAM ILLUSTRATING ELECTROTONIC CURRENTS. P the polarizing battery, with k a key,/> the anode, and p' the kathode At the left end of the piece of nerve the natural current flows through the galvanometer G from g to g', in the direction of the arrows ; its direction, therefore, is the same as that of the polarizing current ; consequently it appears increased, as indicated by the sign -J-. The current at the other end of the piece of nerve, from h to /t', through the galvanometer H, flows in a contrary direction to the polarizing current ; it consequently appears to be diminished, as indicated by the sign — . N. B. For simplicity's sake, the polarizing current is here supposed to be thrown in at the middle of a piece of nerve, and the galvanometer placed at the two ends. Of course it will be understood that the former may be thrown in anywhere, and the latter connected with any two pairs of points which will give currents. 116 ELECTKOTONUS. [BOOK i. will flow in the direction of the arrow. Similarly the needle of G will by its deflection indicate the existence of a current flowing from g to g' through the galvanometer, and from g1 to g through the nerve, in the direction of the arrow. At the instant that the polarizing current is thrown into the nerve &tppr, the currents at gg', hh1 will undergo a " negative variation ; " that is, the nerve at each point will exhibit a " current of action " correspond- ing to the nervous impulse, which, at the making of the polarizing current, passes in both directions along the nerve, and may cause a contraction in the attached muscle. The current of action is, as we have seen, of extremely short duration : it is over and gone in a small fraction of a second. It therefore must not be confounded with a permanent effect, which, in the case we are dealing with, is observed in both galvanometers. This effect, which is dependent on the direction of the polarizing current, is as follows : Supposing that the polarizing current is flowing in the direction of the arrow in the figure, that is, passes in the nerve from the positive electrode or anode p to the negative electrode or kathode pf, it is found that the current through the galvanometer G is increased, while that through If is diminished. The polarizing current has caused the appearance in the nerve outside the electrodes of a current, having the same direction as itself, called the ' electrotonic ' current ; and this electrotonic current adds to, or takes away from, the natural nerve-current or " current of rest," according as it is flowing in the same direction as that, or in an opposite direction. The strength of the electrotonic current is dependent on the strength of the polarizing current, and on the length of the intrapolar region, which is exposed to the polarizing current. "When a strong polarizing current is used, the electromotive force of the electrotonic current may be much greater than that of the natural nerve-current. The strength of the electrotonic current varies with the irritability, or vital condition of the nerve, being greater with the more irritable nerve ; and a dead nerve will not manifest electrotonic currents. More- over, the propagation of the current is stopped by a ligature, or by crushing the nerve. We may speak of the conditions which give rise to this electrotonic current as a physical electrotonus analogous to that physiological electro- tonus, which is made known by variations in irritability. The physical electrotonic current is probably due to the escape of the polarizing current along the nerve under the peculiar conditions of the living nerve ; but we must not attempt to enter here into this difficult subject, or into the allied question as to the exact connection between the physical and the physiological electrotonus, though there can be little doubt that the latter is dependent on the former. § 72. These variations of irritability at the kathode and anode respectively, thus brought about by the action of the constant current, are interesting theoretically, because we may trace a con- nection between them and tbe nervous impulse which is the result of the making or breaking of a constant current. For we have evidence that a nervous impulse is generated when a portion of the nerve passes suddenly from a normal CHAP, ii.] THE CONTKACTILE TISSUES. 117 condition to a state of katelectrotonus, or from a state of anelec- trotonus back to a normal condition ; but that the passage from a normal condition to anelectrotonus or from katelectrotonus back to a normal condition is unable to generate an impulse. Hence, when a constant current is * made/ the impulse is gen- erated only at the kathode where the nerve passes suddenly into katelectrotonus ; when the current, on the other hand, is ' broken,' the impulse is generated only at the anode where the nerve passes suddenly back from anelectrotonus into a normal condition. We have an indirect proof of this in the facts to which we drew attention a little while back, viz. that a contraction sometimes occurs at the ' breaking ' only, sometimes at the ' making ' only of the constant current, sometimes at both. For it is found that this depends partly on the strength of the current in relation to the irritability of the nerve, partly on the direction of the current, whether ascending or descending ; and the results obtained with strong, medium and weak descending and ascending currents have been stated in the form of a ' law of contraction.' We need not enter into the details of this ' law,' but will merely say that the results which it formulates are best explained by the hypothesis just stated. We may add that when the constant current is applied to certain structures composed of plain muscular fibres, whose rate of contraction we have seen to be slow, the making contraction may be actually seen to begin at the kathode and travel towards the anode, and the breaking contraction to begin at the anode and travel thence towards the kathode. Since in katelectrotonus the irritability is increased, and in anelectrotonus decreased, both the entrance from the normal condition into katelectrotonus, and the return from anelectrotonus to the normal condition, are instances of a passage from a lower stage of irritability to a higher stage of irritability. Hence, the phenomena of electrotonus would lead us to the conception that a stimulus in provoking a nervous impulse produces its effect by, in some way or other, suddenly raising the irritability to a higher pitch. But what we are exactly to understand by raising the irritability, what molecular change is the cause of the rise, and how either electric or other stimuli can produce this change, are matters which we cannot discuss here. Besides their theoretical importance, the phenomena of electro- tonus have also a practical interest. When an ascending current is passed along a nerve going to a muscle or group of muscles, the region between the electrodes and the muscle is thrown into anelectrotonus, and its irritability is diminished. If the current be of adequate strength, the irritability may be so much lessened that nervous impulses cannot be generated in that part of the nerve, or cannot pass along it. Hence, by this means the irregular contractions of muscles known as ' cramp ' may be abolished. Similarly, by bringing into a condition of anelectrotonus a portion 118 EFFECTS OF CONSTANT CURRENT. [BOOK i. of a sensory nerve in which violent impulses are being generated, giving rise in the central nervous system to sensations of pain, the impulses are toned down or wholly abolished, and the pain ceases. So on the other hand we may at pleasure heighten the irritability of a part by throwing it into katelectrotonus. In this way the constant current, properly applied, becomes a powerful remedial means. Lastly, though we are dealing now with nerves going to muscles, that is to say, with motor nerves only, we may add that what we have said about electro tonus and the development of nervous impulses by it appears to apply equally well to sensory nerves. § 73. In a general way muscular fibres behave towards an electric current very much as do nerve fibres ; but there are certain important differences. In the first place, muscular fibres, devoid of nerve fibres, are much more readily thrown into contractions by the breaking and making of a constant current than by the more transient induction-shock ; the muscular substance seems to be more sluggish than the nervous substance and requires to be acted upon for a longer time. This fact may be made use of, and indeed is in medical practice made use of, to determine the condition of the nerves supplying a muscle. If the intramuscular nerves be still in good condition, the muscle as a whole responds readily to single induction-shocks because these can act upon the intramuscular nerves. If these nerves on the other hand have lost their irrita- bility, the muscle does not respond readily to single induction- shocks, or to the interrupted current, but can still easily be thrown into contractions by the constant current. In the second place, while in a nerve no impulses are as a rule generated during the passage of a constant current, between the break and the make, provided that it is not too strong, and that it remains uniform in strength, in an urarized muscle on the other hand, even with moderate and perfectly uniform currents, a kind of tetanus or apparently a series of rhythmically repeated contractions is very frequently witnessed during the passage of the current. The exact nature and cause of these phenomena in muscle, we must not however discuss here. SEC. 4 THE MUSCLE-NERVE PREPARATION AS A MACHINE. § 74. The facts described in the foregoing sections shew that a muscle with its nerve may be justly regarded as a machine which, when stimulated, will do a certain amount of work. But the actual amount of work which a muscle-nerve preparation will do is found to depend on a large number of circumstances, and conse- quently to vary within very wide limits. These variations will be largely determined by the condition of the muscle and nerve in repect to their .nutrition ; in other words, by the degree of irrita- bility manifested by the muscle or by the nerve or by both. But quite apart from the general influences affecting its nutrition and thus its irritability, a muscle-nerve preparation is affected, as regards the amount of its work, by a variety of other circumstances, which we may briefly consider here, reserving to a succeeding section the study of variations in irritability. We may here remark that a muscle may be thrown into contraction under two different conditions. In the one case it may be free to shorten : by the lifting of the weight or otherwise, the one end of the muscle may approach the other; and this is the kind of contraction which we have taken, and may take as the ordinary one. But the muscle may be placed under such circum- stances that, when it contracts, the one end is not brought nearer to the other, the muscle remains of the same length, and the effect of the contraction is manifested only as an increased strain. In this latter case, the contraction is spoken of as an "isometric," in the former case as an " isotonic " contraction. The influence of the nature and mode of application of the stimulus. When we apply a weak stimulus, a weak induction- shock, to a nerve, we get a small contraction, a slight shortening of the muscle ; when we apply a stronger stimulus, a stronger in- duction-shock, we get a larger contraction, a greater shortening of the muscle. We take, other things being equal, the amount of contraction of the muscle as a measure of the nervous impulse, and say that in the former case a weak or slight, in the latter case a stronger or larger nervous impulse has been generated. Now the muscle of the muscle-nerve preparation consists of many muscular fibres and the nerve of many nerve fibres ; and we may 120 CHARACTERS OF STIMULI. [BOOK i. fairly suppose that in two experiments we may in the one experi- ment bring the induction-shock or other stimulus to bear on a few nerve fibres only, and in the other experiment on many or even all the fibres of the nerve. In the former case only those muscular fibres in which the few nerve fibres stimulated end will be thrown into contraction, the others remaining quiet, and the shortening of the muscle as a whole, since only a few fibres take part in it, will necessarily be less than when all the fibres of the nerve are stimulated and all the fibres of the muscle contract. That is to say, the amount of contraction will depend on the number of fibres stimulated. For simplicity's sake however we will in what follows, except when otherwise indicated, suppose that when a nerve is stimulated, all the fibres are stimulated and all the muscular fibres contract. This bsing premised, we may say that, other things being equal, the magnitude of a nervous impulse, and so the magnitude of the ensuing contraction, is directly dependent on what we may call the strength of the stimulus. Thus taking a single induction- shock as the most manageable stimulus, we find that if, before we begin, we place the secondary coil (Fig. 4, sc.) a long way off the primary coil pr. c., no visible effect at all follows upon the discharge of the induction-shock. The passage of the momentary weak current is either unable to produce any nervous impulse at all, or the weak nervous impulse to which it gives rise is unable to stir the sluggish muscular substance to a visible contraction. As we slide the secondary coil towards the primary, sending in an induction-shock at each new position, we find that at a certain distance between the secondary and primary coils, the muscle responds to each induction-shock l with a contraction which makes itself visible by the slightest possible rise of the attached lever. This position of the coils, the battery remaining the same and other things being equal, marks the minimal stimulus giving rise to the minimal contraction. As the secondary coil is brought nearer to the primary, the contractions increase in height corre- sponding to the increase in the intensity of the stimulus. Very soon however an increase in the stimulus caused by further sliding the secondary coil over the primary fails to cause any increase in the contraction. This indicates that the maximal stimulus giving rise to the maximal contraction has been reached ; though the shocks increase in intensity as the secondary coil is pushed further and further over the primary, the contractions remain of the same height, until fatigue lowers them. With single induction-shocks then the muscular contraction, and by inference the nervous impulse, increases with an increase in the intensity of the stimulus, between the limits of the minimal 1 In these experiments either the breaking or making shock must be used, not sometimes one and sometimes the other, for, as we have stated, the two kinds of shock differ in efficiency, the breaking being the most potent. CHAP, ii.] THE CONTRACTILE TISSUES. 121 and maximal stimuli ; and this dependence of the nervous impulse, and so of the contraction, on the strength of the stimulus may be observed not only in electric but in all kinds of stimuli. It may here be remarked that in order for a stimulus to be effective, a certain abruptness in its action is necessary. Thus as we have seen the constant current when it is passing through a nerve with uniform intensity does not give rise to a nervous impulse, and indeed it may be increased or diminished to almost any extent without generating nervous impulses, provided that the change be made gradually enough ; it is only when there is a sudden change that the current becomes effective as a stimulus. And the reason why the breaking induction-shock is more potent as a stimulus than the making shock is because as we have seen (§ 44) the current which is induced in the secondary coil of an induction-machine at the breaking of the primary circuit, is more rapidly developed, and has a sharper rise than the current which appears when the primary circuit is made. Similarly a sharp tap on a nerve will pro'duce a contraction, when a gradually increasing pressure will fail to do so; and in general the efficiency of a stimulus of any kind will depend in part on the suddenness or abruptness of its action. A stimulus, in order that it may be effective, must have an action of a certain duration, the time necessary to produce an effect varying according to the strength of the stimulus and being differ- ent in the case of a nerve from what it is in the case of a muscle. It would appear that an electric current applied to a nerve must have a duration of at least about -0015 sec. to cause any contrac- tion at all, and needs a longer time than this to produce its full effect. A muscle fibre apart from its nerve fibre requires a still longer duration of the stimulus, and hence, as we have already stated, a muscle poisoned by urari, or which has otherwise lost the action of its nerves, will not respond as readily to induction- shocks as to the more slowly acting, breaking and making of a constant current. In the case of electric stimuli, the same current will produce a stronger contraction when it is sent along the nerve than when it is sent across the nerve ; indeed it is maintained that a current which passes through a nerve in an absolutely transverse direction is powerless to generate impulses. § 75. We have seen that when single stimuli are repeated with sufficient frequency, the individual contractions are fused into tetanus ; as the frequency of the repetition is increased, the individual contractions are less obvious on the curve, until at last we get a curve on which they seem to be entirely lost and which we may speak of as a complete tetanus. By such a tetanus a much greater contraction, a much greater shortening of the muscle is of course obtained than by single contractions. The exact frequency of repetition required to produce com- 122 REPETITION OF CONTRACTIONS IN TETANUS. [BOOK i. plete tetanus will depend chiefly on the length of the individual contractions, and this varies in different animals, in different muscles of the same animal, and in the same muscle under differ- ent conditions. In a cold blooded animal a single contraction is as a rule more prolonged than in a warm blooded animal, and tetanus is consequently produced in the former by a less frequent repetition of the stimulus. A tired muscle has a longer contrac- tion than a fresh muscle, and hence in many tetanus curves the individual contractions, easily recognised at first, disappear later on, owing to the individual contractions being lengthened out by the exhaustion caused by the tetanus itself. In many animals, e. g. the rabbit, some muscles (such as the adductor magnus femoris) are pale, while others (such as the semitendinosus) are red. The red muscles are not only more richly supplied with blood vessels, but the muscle substance of the fibres contains more haemoglobin than the pale, and there are other structural differences. Now the single contraction of one of these red muscles is more prolonged than the single contraction of one of the pale muscles produced by the same stimulus. Hence the red muscles are thrown into complete tetanus with a repetition of much less frequency than that required for the pale muscles. Thus, ten stimuli in a second are quite sufficient to throw the red muscles of the rabbit into complete tetanus, while the pale muscles require at least twenty stimuli in a second. So long as signs of the individual contractions are visible on the curve of tetanus it is easy to recognise that each stimulation produces one of the constituent single contractions, and that the number so to spaak of the vibrations of the muscle making up the tetanus corresponds to the number of stimulations; but the question whether, when we increase the number of stimulations beyond that necessary to produce a complete tetanus, we still increase the number of constituent single contractions is one not so easy to answer. And connected with this question is another difficult one. What is the rate of repetition of single contrac- tions making up those tetanic contractions which as we have said are the kind of contractions by which the voluntary, and indeed other natural, movements of the body are carried out ? What is the evidence that these are really tetanic in character ? When a muscle is thrown into tetanus, a more or less musical sound is produced. This may be heard by applying a stethoscope directly over a contracting muscle, and a similar sound but of a more mixed origin and less trustworthy may be heard when the masseter muscles are forcibly contracted or when a finger is placed in the ear, and the muscles of the same arm are contracted. When the stethoscope is placed over a muscle, the nerve of which is stimulated by induction-shocks repeated with varying frequency, the note heard will vary with the frequency of the shocks, being of higher pitch with the more frequent shocks. CHAP, ii.] THE CONTRACTILE TISSUES. 123 Now it has been thought that the vibrations of the muscle giving rise to the " muscle sound " are identical with the single con- tractions making up the tetanus of the muscle. And since, in the human body, when a muscle is thrown into contraction in a voluntary effort, or indeed in any of the ordinary natural move- ments of the body, the fundamental tone of the sound corresponds to about 19 or 20 vibrations a second, it has been 'concluded that the contraction taking place in such cases is a tetanus of which the individual contractions follow each other about 19 or 20 times a second. But investigations seem to shew that the vibrations giving rise to the muscle sound do not really correspond to the shortenings and relaxations of the individual contractions, and that the pitch of the note cannot therefore be taken as an indica- tion of the number of single contractions making up the tetanus ; indeed, as we shall s'ee in speaking of the sounds of the heart, a single muscular contraction may produce a sound which though differing from the sound given out during tetanus has to a certain extent musical characters. Nevertheless the special characters of the muscle sound given out by muscles in the natural move- ments of the body may be taken as shewing at least that the contractions of the muscle in these movements are tetanic in nature, and the similarity of the note in all the voluntary efforts of the body and indeed in all movements carried out by the central nervous system is at least consonant with the view that the repetition of single contractions is of about the same frequency in all these movements. What that frequency is, and whether it is exactly identical in all these movements, has not at present been clearly determined ; though certain markings on the myro- graphic tracings of these movements and other facts seem to indicate that it is about 12 a second. § 76. The Influence of the Load. It might be imagined that a muscle, which, when loaded with a given weight, and stimulated by a current of a given intensity, had contracted to a certain extent, would only contract to half that extent when loaded with twice the weight and stimulated with the same stimulus. Such however is not necessarily the case ; the height to which the weight is raised may be in the second instance as great, or even greater, than in the first. That is to say, the resistance offered to the contraction actually augments the contraction, the ten- sion of the muscular fibre increases the facility with which the explosive changes resulting in a contraction take place. And we have other evidence that anything which tends to stretch the muscular fibres, that any tension of the muscular fibres, whether during rest or during contraction, increases the metabolism of the muscle. There is, of course, a limit to this favourable action of the resistance. As the load continues to be increased, the height of the contraction is diminished, and at last a point is reached at which the muscle is unable (even when the stimulus chosen, is the strongest possible) to lift the load at all. 124 THE WORK DONE. [BOOK i. In a muscle viewed as a machine we have to deal not merely with the height of the contraction, that is with the amount of shortening, but with the work done. And this is measured by multiplying the number of units of height to which the load is raised into the number of units of weight of the load. Hence it is obvious from the foregoing observations that the work done must be largely dependent on the weight itself. Thus there is a certain weight of load with which in any given muscle, stimu- lated by a given stimulus, the most work will be done ; as may be seen from the following example : Load, in grammes 0 50 100 150 200 250 Height of contractions in millimeters 149 7 5 2 0 Work done, in gram-millimeters ... 0 450 700 750 400 0 § 77. The Influence of the Size and Form of the Muscle. Since all known muscular fibres are much shorter than the wave-length of a contraction, it is obvious that the longer the fibre, the greater will be the shortening caused by the same contraction wave, the greater will be the height of the contraction with the same stimulus. Hence in a muscle of parallel fibres, the height to which the load is raised as the result of a given stimulus applied to its nerve, will depend on the length of the fibres, while the maximum weight of load capable of being lifted will depend on the number of the fibres, since the load is distributed among them. Of two muscles therefore of equal length (and of the same quality) the most work will be done by that which has the larger number of fibres, that is to say, the fibres being of equal width, which has the greater sectional area ; and of two muscles with equal sectional areas, the most work will be done by that which is the longer. If the two muscles are unequal both in bngth and sectional area, the work done will be the greater in the one which has the larger bulk, which contains the greater number of cubic units. In speaking therefore of the work which can be done by a muscle, we may use as a standard a cubic unit of bulk, or, the specific gravity of the muscle being the same, a unit of weight. We learn then from the foregoing paragraphs that the work done, by a muscle-nerve preparation, will depend, not only on the activity of the nerve and muscle as determined by their own irritability, but also on the character and mode of application of the stimulus, on the kind of contraction (whether a single spasm, or a slowly repeated tetanus or a rapidly repeated tetanus) on the load itself, and on the size and form of the muscle. Taking the most favourable circumstances, viz. a well-nourished, lively preparation, a maximum stimulus causing a rapid tetanus and an appropriate load, we may determine the maximum work done by a given weight of muscle, say one gramme. This in the case of the muscles of the frog has been estimated at about four gram- meters for one gramme of muscle. SEC. 5. THE CIRCUMSTANCES WHICH DETERMINE THE DEGREE OF IRRITABILITY OF MUSCLES AND NERVES. § 78. A muscle-nerve preparation, at the time that it is re- moved from the body, possesses a certain degree of irritability, it responds by a contraction of a certain amount to a stimulus of a certain strength, applied to the nerve or to the muscle. After a while, the exact period depending on a variety of circumstances, the same stimulus produces a smaller contraction, i.e. the irritability of the preparation has diminished. In other words, the muscle, or nerve, or both, have become partially ' exhausted ; ' and the exhaustion subsequently increases, the same stimulus producing smaller contractions, until at last all irritability is lost, no stimulus however strong producing any contraction, whether applied to the nerve or directly to the muscle ; and eventually the muscle, as we have seen, becomes rigid. The progress of this exhaustion is more rapid in the nerves than in the muscles ; for some time after the nerve trunk has ceased to respond to even the strongest stimulus, contractions may be obtained by applying the stimulus directly to the muscle. It is much more rapid in the warm blooded than in the cold blooded animals. The muscles and nerves of the former lose their irritability, when removed from the body, after a period varying according to circumstances from a few minutes to two or three hours ; those of cold blooded animals (or at least of an amphibian or a reptile) may, under favourable conditions, remain irritable for two, three, or even more days. The duration of irritability in warm blooded animals may, however, be considerably prolonged by reducing the temperature of the body before death. If with some thin body a sharp blow be struck across a muscle which has entered into the later stages of exhaustion, a wheal lasting for several seconds is developed. This wheal appears to be a contraction wave limited to the part struck, and disappearing very slowly, without extending to the neighbouring muscular substance. It has been called 126 DEGENERATION OF NERVES. [BOOK j. an ' idio-muscular ' contraction, because it may be brought out even when ordinary stimuli have ceased to produce any effect. It may how- ever be accompanied at its beginning by an ordinary contraction. It is readily produced in the living body on the pectoral and other muscles of persons suffering from phthisis and other exhausting diseases. This natural exhaustion and diminution of irritability in muscles and nerves removed from the body may be modified both in the case of the muscle and of the nerve, by a variety of circum- stances. Similarly, while the nerve and muscle still remain in the body, the irritability of the one or of the other may be modified either in the way of increase or of decrease by certain general influences, of which the most important are, severance from the central nervous system, and variations in temperature, in blood supply, and in functional activity. The Effects of Severance from the Central Nervous System. When a nerve, such for instance as the sciatic, is divided in situ, in the living body, there is first of all observed a slight increase of irritability, noticeable especially near the cut end ; but after a while the irritability diminishes, and gradually disappears. Both the slight initial increase and the subsequent decrease begin at the cut end and advance centrifugally towards the peripheral terminations. This centrifugal feature of the loss of irritability is often spoken of as the Ritter-Valli law. In a mammal it may be two or three days, in a frog, as many, or even more weeks, before irritability has disappeared from the nerve trunk. It is maintained in the small (and especially in the intramuscular) branches for still longer periods. This centrifugal loss of irritability is the forerunner in the peripheral portion of the divided nerve of structural changes which proceed in a similar centrifugal manner. In the central portion of the divided nerve these structural changes may be traced as far only as the next node of Ranvier. Beyond this the nerve usually remains in a normal condition. Such a degen- eration may be observed to extend down to the very endings of the nerve in the muscle, including the end-plates, but does not at first affect the muscular substance itself. The muscle, though it has lost all its nervous elements, still remains irritable towards stimuli applied directly to itself : an additional proof of the existence of an independent muscular irritability. If the muscle thus deprived of its nervous elements be left to itself its irritability, however tested, sooner or later diminishes ; but if the muscle be periodically thrown into contractions by artificial stimulation with the constant current, the decline of irritability and attendant loss of nutritive power may be postponed for some considerable time. But so far as our experience goes at present the artificial stimulation cannot fully replace the natural one, and sooner or later the muscle like the nerve suffers degeneration, loses CHAP, ii.] THE CONTRACTILE TISSUES. 127 all irritability and ultimately its place is taken by connective tissue. For some time the irritability of the muscle, as well towards stimuli applied directly to itself as towards those applied through the impaired nerve, seems to be diminished ; but after a while a peculiar condition (to which we have already alluded, § 73) sets in, in which the muscle is found to be not easily stimulated by single induction-shocks but to respond readily to the make or break of a constant current. In fact it is said to become even more sensitive to the latter mode of stimulation than it was when its nerve was intact and functionally active. At the same time it also becomes more irritable towards direct mechanical stimuli, and very frequently fibrillar contractions, more or less rhythmic and apparently of spontaneous origin, though their causation is obscure, make their appearance. This phase of heightened sensitiveness of a muscle, especially to the constant current, appears to reach its maximum, in man at about the seventh week after nervous impulses have ceased, owing to injury to the nerves or nervous centre, to reach the muscle. § 79. The influence of temperature. We have already seen that sudden heat (and the same might be said of cold when sufficiently intense), applied to a limited part of a nerve or muscle, as when the nerve or muscle is touched with a hot wire, will act as a stimulus. It is however much more difficult to gene- rate nervous or muscular impulses by exposing a whole motor nerve l or muscle to a gradual rise of temperature. A muscle may be gradually cooled to 0° C. or below without any contraction being caused ; but when it is heated to a limit, which in the case of frog's muscles is about 45 °, of mammalian muscles»about 50°, a sudden change takes place : the muscle falls, at the limiting temperature, into a rigor mortis, which is initiated by a forcible contraction or at least shortening. Moderate warmth, e. g. in the frog an increase of temperature up to somewhat below 45° C., favours both muscular and nervous irritability. All the molecular processes are hastened and facili- tated : the contraction is for a given stimulus greater and more rapid, i. e. of shorter duration, and nervous impulses are generated more readily by slight stimuli. Owing to the quickening of the chemical changes, the supply of new material may prove insuffi- cient ; hence muscles and nerves removed from the body lose their irritability more rapidly at a high than at a low temperature. The gradual application of cold to a nerve produces effects which differ according to the kind of stimulus employed in testing the condition of the nerve ; but it may be stated in general that a low temperature, especially one near to 0°, slackens all the mole- cular processes, so that the wave of nervous impulse is lessened and prolonged, the velocity of its passage being much diminished, 1 The action of cold and heat on sensory nerves will be considered in the later portion of the work. 128 INFLUENCE OF ACTIVITY. [BOOK i. e. g. from 28 metres to I metre per sec. At about 0°, the irrita- bility of the nerve disappears altogether. When a muscle is exposed to similar cold, e. g. to a tempera- ture very little above zero, the contractions are remarkably pro- longed ; they are diminished in height at the same time, but not in proportion to the increase of their duration. Exposed to a temperature of zero or below, muscles soon lose their irritability, without however undergoing rigor mortis. § 80. The influence of blood supply. When a muscle still within the body is deprived by any means of its proper blood supply, as when the blood vessels going to it are ligatured, the same gradual loss of irritability and final appearance of rigor mortis are observed as in muscles removed from the body. Thus if the abdominal aorta be ligatured, the muscles of the lower limbs lose their irritability and finally become rigid. So also in systemic death, when the blood supply to the muscles is cut off by the cessation of the circulation, loss of irritability ensues, and rigor mortis eventually follows. In a human corpse the muscles of the body enter into rigor mortis in a fixed order : first those of the jaw and neck, then those of the trunk, next those of the arms, and lastly those of the legs. The rapidity with which rigor mortis comes on after death varies considerably, being determined both by external circumstances and by the internal conditions of the body. Thus external warmth hastens and cold retards the onset. After great muscular exertion, as in hunted animals, and when death closes wasting diseases, rigor mortis in most cases comes on rapidly. As a general rule it may be said that the later it is in making its appearance, the more pronounced it is, and the longer it lasts ; but there are many exceptions, and when the state is recognised as being fundamentally due to a clotting of the muscle substance, it is easy to understand that the amount of rigidity, i. e. the amount of the clot, and the rapidity of the onset, i. e. the quickness with which clotting takes place, may vary independently. When rigor mortis has once become thoroughly established in a muscle through deprivation of blood, it cannot be removed by any sub- sequent supply of blood. Mere loss of irritability, even though complete, if stopping short of the actual clotting of the muscle substance, may be with care removed. The influence of blood supply cannot be so satisfactorily studied in the case of nerves as in the case of muscles ; there can however be little doubt that the effects are analogous. § 81. The influence of functional activity. This too is more easily studied in the case of muscles than of nerves. When a muscle within the body is unused, it wastes ; when used, it (within certain limits) grows. Both these facts shew that the nutrition of a muscle is favourably affected by its functional activity. Part of this may be an indirect effect of the increased blood supply which occurs when a muscle contracts. When a CHAP, ii.] THE CONTRACTILE TISSUES. 129 nerve going to a muscle is stimulated, the blood vessels of the muscle dilate. Hence at the time of the contraction more blood flows through the muscle, and this increased flow continues for some little while after the contraction of the muscle has ceased. But, apart from the blood supply, it is probable that the ex- haustion caused by a contraction is immediately followed by a reaction favourable to the nutrition of the muscle ; and this is a reason, possibly the chief reason, why a muscle is increased by use, that is to say, the loss of substance and energy caused by the con- traction is subsequently more than made up for by increased met- abolism during the following period of rest. A muscle, even within the body, after prolonged action is fatigued, i. e. a stronger stimulus is required to produce the same contraction ; in other words, its irritability may be lessened by functional activity. Whether functional activity therefore is in- jurious or beneficial depends on its amount in relation to the condition of the muscle. It is worthy of notice that a motor nerve is far less susceptible of being fatigued by artificial stimulation than is a muscle ; in fact it seems extremely difficult to tire a nerve by mere stimula- tion. In an animal poisoned by urari the sciatic nerve may be stimulated continuously with powerful currents for even several hours and yet remain irritable. So long as the urari is produc- ing its usual effect, the muscles sheltered by it are not thrown into contraction by the stimulation of the nerve and so are not fatigued ; as the effect of the urari passes off, contractions make their appearance in response to the stimulation of the sciatic nerve, shewing that this, in spite of its having been stimulated for so long a time, has not been exhausted. And other experi- ments point to a similar conclusion. It would seem that the molecular processes constituting a nervous impulse unlike those constituting a muscular contraction, are of such a nature or take place in such a way, that after the development of one impulse the substance of the nerve fibre is at once ready for the develop- ment of a second impulse. The sense of fatigue of which, after prolonged or unusual exer- tion, we are conscious in our own bodies, is probably of complex origin, and its nature, like that of the normal muscular sense of which we shall have to speak hereafter, is at present not thoroughly understood. It seems to be in the first place the result of changes in the muscles themselves, but is possibly also caused by changes in the nervous apparatus concerned in muscular action, and especially in those parts of the central nervous system which are concerned in the production of voluntary impulses. In any case it cannot be taken as an adequate measure of the actual fatigue of the muscles ; for a man who says he is absolutely exhausted may under excite- ment perform a very large amount of work with his already weary muscles. The will in fact rarely if ever calls forth the greatest contractions of which the muscles are capable. 130 CAUSES OF EXHAUSTION. [BOOK n. Absolute (temporary) exhaustion of the muscles, so that the strongest stimuli produce no contraction, may be produced even within the body by artificial stimulation : recovery takes place on rest. Out of the body absolute exhaustion takes place readily. Here also recovery may take place. Whether in any given case it does occur or not, is determined by the amount of contraction causing the exhaustion, and by the previous condition of the muscle. In all cases recovery is hastened by renewal (natural or artificial) of the blood stream. The more rapidly the contractions follow each other, the less the interval between any two contractions, the more rapid the exhaustion. A certain number of single induction-shocks repeated rapidly, say every second or oftener, bring about exhaustive loss of irritability more rapidly than the same number of shocks repeated less rapidly, for instance every 5 or 10 seconds. Hence tetanus is a ready means of producing exhaustion. In exhausted muscles the elasticity is much diminished ; the tired muscle returns less readily to its natural length than does the fresh one. The exhaustion due to contraction may be the result : — Either of the consumption of the store of really contractile material present in the muscle. Or of the accumulation in the tissue of the products of the act of contraction. Or of both of these causes. The restorative influence of rest, in the case of a muscle removed from the circulation, may be explained by supposing that during the repose, either the internal changes of the tissue manufacture new explosive material out of the comparatively raw material already present in the fibres, or the directly hurtful pro- ducts of the act of contraction undergo changes by which they are converted into comparatively inert bodies. A stream of fresh blood may exert its restorative influence not only by quickening the above two events, but also by carrying off the immediate waste products while at the same time it brings new raw material. It is not known to what extent each of these parts is played. That the products of contraction are exhausting in their effects, is shewn by the facts that the injection of a solution of the muscle-extractives into the vessels of a muscle produces exhaustion, and that exhausted muscles are recovered by the simple injection of inert saline solu- tions into their blood vessels. But the matter has not yet been fully worked out. One important element brought by fresh blood is oxygen. This, as we have seen, is not necessary for the carrying out of the actual contraction, and yet is essential to the maintenance of irritability. The oxygen absorbed by the muscle apparently enters in some peculiar way into the formation of that complex explosive material the decomposition of which in the act of contraction, though it gives rise to carbonic acid and other products of oxidation, is not in itself a process of direct oxidation. SEC. 6. ON SOME OTHER FORMS OF CONTRACTILE TISSUE. Plain, Smooth or Unstriated Muscular Tissue. § 82. This, in vertebrates at all events, rarely occurs in isolated masses or muscles, as does striated muscular tissue, but is usually found taking part in the structure of complex organs, such for instance as the intestines ; hence the investigation of its properties is beset with many difficulties. § 83. So far as we know plain muscular tissue in its chemical features resembles striated muscular tissue. It contains albumin, some forms of globulin, and antecedents of myosin which upon the death of the fibres become myosin; for plain muscular tissue after death becomes rigid, losing its extensibility and probably becoming acid, though the acidity is not so marked as in striated muscle. Kreatin has also been found, as well as glycogen, and indeed it seems probable that the whole metabolism of plain muscular tissue is fundamentally the same as that of the striated muscles. § 84. In their general physical features plain muscular fibres also resemble striated fibres, and like them they are irritable and contractile ; when stimulated they contract. The fibres vary in natural length in different situations, those of the blood vessels for instance being shorter and stouter than those of the intestine ; but in the same situation the fibres may also be found in one of two different conditions. In the one case the fibres are long and thin, in the other case they are reduced in length, it may be to one half or even to one third, and are correspondingly thicker, broader and less pointed at the ends, their total bulk remaining unaltered. In the former case they are relaxed or elongated, in the latter case they are contracted. The facts of the contraction of plain muscular tissue may be studied in the intestine, the muscular coat of which consists of an outer thin sheet composed of fibres and bundles of fibres disposed longitudinally and of an inner much thicker sheet of fibres disposed circularly ; in the ureter a similar arrangement of two coats obtains. If a mechanical or electrical (or indeed any other) stimulus be 132 CONTRACTION OF PLAIN MUSCLES. [BOOK i. brought to bear on a part of a fresh living still warm intestine (the small intestine is the best to work with) a circular contraction is seen to take place at the spot stimulated; the intestine seems nipped in ringwise, as if tied round with an invisible cord ; and the part so constricted, previously vascular and red, becomes pale and bloodless. The individual fibres of the circular coat in the region stimulated have each become shorter, and the total effect of the shortening of the multitude of fibres all having the same circular disposition is to constrict or narrow the lumen or tube of the in- testine. The longitudinally disposed fibres of the outer longitudinal coat in a similar manner contract or shorten in a longitudinal direction, but this coat being relatively much thinner than the circular coat, the longitudinal contraction is altogether over- shadowed by the circular contraction. A similar mode of contrac- tion is also seen when the ureter is similarly stimulated. The contraction thus induced is preceded by a very long latent period and lasts a very considerable time, in fact several seconds, after which relaxation slowly takes place. We may say then that over the circularly dispersed fibres of the intestine (or ureter) at the spot in question there has passed a contraction-wave remarkable for its long latent period and for the slowness of its development, the wave being propagated from fibre to fibre. From the spot so directly stimulated, the contraction may pass also as a wave (with a length of 1 cm. and a velocity of from 20 to 30 millimetres a second in the ureter), along the circular coat both upwards and downwards. The longitudinal fibres at the spot stimulated are as we have said also thrown into contractions of altogether similar character, and a wave of contraction may thus also travel longitudi- nally along the longitudinal coat both upwards and downwards. It is evident however that the wave of contraction of which we are now speaking is in one respect different from the wave of contrac- tion treated of in dealing with striated muscle. In the latter case the contraction-wave is a simple wave propagated along the in- dividual fibre and starting from the end-plate or, in the case of direct stimulation, from the part of the fibre first affected by the stimulus ; we have no evidence that the contraction of one fibre can communicate contraction to neighbouring fibres or indeed in any way influence neighbouring fibres. In the case of the intestine or ureter, the wave is complex, being the sum of the contraction- waves of several fibres engaged in different phases and is propagated from fibre to fibre, both in the direction of the fibres, as when the whole circumference of the intestine is engaged in the contraction, or when the wave travels longitudinally along the longitudinal coat, and also in a direction at right angles to the axes of the fibres, as when the contraction-wave travels lengthways along the circular coat of the intestine, or when it passes across a breadth of the longitudinal coat ; that is to say, the changes leading to contraction are communicated not only in a direct manner across the cement CHAP, ii.] THE CONTRACTILE TISSUES. 133 substance uniting the fibres of a bundle but also in an indirect manner, probably by means of nerve fibres, from bundle to bundle across the connective tissue between them. Moreover, it is obvious that even the contraction-wave which passes along a single un- striated fibre differs from that passing along a striated fibre, in the very great length both of its latent period and of the duration of its contraction. Hence, much more even than in the case of a striated muscle, the whole of each fibre must be occupied by the contraction-wave, and indeed be in nearly the same phase of the contraction at the same time. Waves of contraction thus passing along the circular and longi- tudinal coats of the intestine constitute what is called peristaltic action. Like the contractions of striated muscle the contractions of plain muscles may be started by stimulation of nerves going to the part, the nerves supplying plain muscular tissue, running for the most part as we have said in the so-called sympathetic system, but being as we shall see ultimately connected with the spinal cord or brain. Here however we come upon an im- portant distinction between the striated skeletal muscles, arid the plain muscles of the viscera. . As a general rule the skeletal muscles are thrown into contraction only by nervous impulses reaching them along their nerves; spontaneous movements of the skeletal muscles, that is contractions arising out of changes in the muscles themselves are extremely rare, and when they occur are abnormal ; so-called ' cramps ' for instance, which are prolonged tetanic contractions of skeletal muscles independent of the will, though their occurrence is largely due to the condition of the muscle itself, generally the result of overwork, are probably actually started by nervous impulses reaching them from without. On the other hand the plain muscles of the viscera, of the intestine, uterus and ureter, for instance, and of the blood vessels very fre- quently fall into contractions and so carry out movements of the organs to which they belong quite independently of the central nervous system. These organs exhibit ' spontaneous ' movements quite apart from the will, quite apart from the central nervous system, and under favourable circumstances continue to do this for some time after they have been entirely isolated and removed from the body. So slight indeed is the connection between the move- ments of organs and parts supplied with plain muscular fibres, and the will, that these muscular fibres have sometimes been called involuntary muscles ; but this name is undesirable since some muscles consisting entirely of plain muscular fibres (e. g. the ciliary muscles by which the eye is accommodated for viewing objects at different distances) are directly under the influence of the will, and some muscles composed of striated fibres (e. g. those of the heart) are wholly removed from the influence of the will. We shall best study however the facts relating to the move- 134 CILIARY MOVEMENT. [BOOK i. merits of parts provided with plain muscular fibres when we come to consider the parts themselves. Like the skeletal muscles, whose nervous elements have been rendered functionally incapable (§ 73), plain muscles are much more sensitive to the making and breaking of a constant current than to induction shocks ; a current, when very brief, like that of an induction-shock, produces little or no effect. The contraction of plain muscular fibres is as we said very slow in its development and very long in its duration, even when started by a momentary stimulus, such as a single induction-shock. The contraction after a stimulation often lasts so long as to raise the question, whether what has been produced is not a single contrac- tion but a tetanus. Tetanus, however, that is the fusion of a series of contractions, seems to be of rare occurrence, though probably it may be induced, in plain muscular tissue ; but some of the ends of tetanus are gained by a kind of contraction which, not prom- inent in skeletal muscle, becomes of great importance in plain muscular tissue, by a kind of contraction called a tonic contraction. The subject is one not without difficulties, but it would appear that a plain muscular fibre may remain for a very considerable time in a state of contraction, the amount of shortening thus maintained being either small or great: it is then said to be in a state of tonic contraction. This is especially seen in the case of the plain muscular tissue of the arteries, and we shall have to return to this matter in dealing with the circulation. The muscular tissue which enters into the construction of the heart is of a peculiar nature, being on the one hand striated, and on the other in some respects similar to plain muscular tissue, but this we shall consider in dealing with the heart itself. Ciliary Movement. § 85. Nearly all the movements of the body which are not due to physical causes, such as gravity, the diffusion of liquids &c., are carried out by muscles, either striated or plain ; but some small and yet important effects in the way of movement are produced by the action of cilia, and by those changes of form which are called amoeboid. Cilia are generally appendages of epithelial cells. § 86. Ciliary action, in the form in which it is most common in mammals and indeed vertebrates, consists in the cilium (i. e. the tapering filament spoken of above) being at one moment straight or vertical, at the next moment being bent down suddenly into a hook or sickle form, and then more slowly returning to the straight erect position. When the cilia are vigorous, this double move- ment is repeated with very great rapidity, so rapidly that the individual movements cannot be seen ; it is only when, by reason CHAP, ii.] THE CONTRACTILE TISSUES. 135 of fatigue, the action becomes slow that the movement itself can be seen; what is seen otherwise is simply the effect of the movement. The movements when slow have been counted at about eight (double movements) in a second; probably when vigorous they are repeated from twelve to twenty times a second. The flexion takes place in one direction only, and all the cilia of each cell, and indeed of all the cells of the same epithelium move in the same direction. Moreover the same direction is maintained during the whole life of the epithelium ; thus the cilia of the epithelium of the trachea and bronchial passages move during the whole of life in such a way as to drive the fluid lying upon them upwards towards the mouth ; so far as we know in vertebrates, or at least in mammals, the direction is not and cannot by any means be reversed. The flexion is very rapid but the return to the erect position is much slower ; hence the total effect of the blow, supposing the cilium and the cell to be fixed, is to drive the thin layer of fluid in which the cilium is working, and which always exists over the epithelium, and any particles which may be floating in that fluid, in the same direction as that in which the blow is given. If the cell be not attached but floating free the effect of the blow may be to drive the cell itself backward ; and when perfectly fresh ciliated epithelium is teased out and examined in an inert fluid such as normal saline solution, isolated cells or small groups of cells may be seen rowing themselves about as it were by the action of their cilia. All the cilia of a cell move, as we have just said, in the same direction, but not quite at the same time. If we call the side of the cell towards which the cilia bend the front of the cell and the opposite side the back, the cilia at the back move a trifle before those at the front so that the movement runs over the cell in the direction of the movement itself. Similarly, taking any one cell, the cilia of the cells behind it move slightly before, and the cilia of the cells in front of it slightly after, its own cilia move. Hence in this way along a whole stretch of epithelium the movement or bending of the cilia sweeps over the surface in ripples or waves, very much as, when the wind blows, similar waves of bending sweep over a field of corn or tall grass. By this arrangement the efficacy of the movement is secured, and a steady stream of fluid carrying particles is driven over the surface in a uniform continued direction ; if the cilia of separate cells, and still more if the separate cilia of each cell, moved independently of the others, all that would be produced would be a series of minute ' wobbles,' of as little use for driving the fluid definitely onwards as the efforts of a boat's crew all rowing out of time are for propelling the boat. Swift bending and slower straightening is the form of ciliary movement generally met with in the ciliated epithelium of mam- mals and indeed of vertebrates ; but among the invertebrates we 136 CILIARY MOVEMENT. [BOOK i. find other kinds of movement, such as a to and fro movement, equally rapid in both directions, a cork-screw movement, a simple undulatory movement, and many others. In each case the kind of movement seems adapted to secure a special end. Thus even in the mammal while the one-sided blow of the cilia of the epithelial cells secures a flow of fluid over the epithelium, the tail of the spermatozoon, which is practically a single cilium, by moving to and fro in an undulatory fashion drives the head of the sperma- tozoon onwards in a straight line, like a boat driven by a single oar worked at the stern. Why and exactly how the cilium of the epithelial cells bends swiftly and straightens slowly, always acting in the same direction, is a problem difficult at present to answer fully. Some have thought that the body of the cell is contractile, or contains contractile mechanisms pulling upon the cilia, which are thus simple passive puppets in the hands of the cells. But there is no satisfactory evidence for such a view. On the whole the evidence is in favour of the view that the action is carried out by the cilium itself, that the bending is a contraction of the cilium, and that the straight- ening corresponds to the relaxation of a muscular fibre. But even then the exact manner in which the contraction bends and the relaxation straightens the filament is not fully explained. We have no positive evidence that a longitudinal half, the inside we might say, of the filament is contractile, and the other half, the outside, elastic, a supposition which has been made to explain the bending and straightening. In fact no adequate explanation of the matter has as yet been given, and it is really only on general grounds we conclude that the action is an effect of contractility. In the vertebrate animal, cilia are, so far as we know, wholly independent of the nervous system, and their movement is prob- ably ceaseless. In such animals however as Infusoria, Hydrozoa, &c. the movements in a ciliary tract may often be seen to stop and to go on again, to be now fast now slow, according to the needs of the economy, and, as it almost seems, according to the will of the creature ; indeed in some of these animals the ciliary move- ments are clearly under the influence of the nervous system. Observations with galvanic currents, constant and interrupted, have not led to any satisfactory results, and, so far as we know at present, ciliary action is most affected by changes of temperature and chemical media. Moderate heat quickens the movements, but a rise of temperature beyond a certain limit (about 40°C. in the case of the pharyngeal membrane of the frog) becomes injurious ; cold retards. Very dilute alkalis are favourable, acids are injurious. An excess of carbonic acid or an absence of oxygen diminishes or arrests the movements, either temporarily or permanently, accord- ing to the length of the exposure. Chloroform or ether in slight doses diminishes or suspends the action temporarily, in excess kills and disorganises the cells. CHAP. ii. J THE CONTRACTILE TISSUES. 137 Amoeboid Movements. § 87. The white blood corpuscles, as we have said (§ 28), are able of themselves to change their form and by repeated changes of form to move from place to place. Such movements of the substance of the corpuscles are called amoeboid, since they closely resemble and appear to be identical in nature with the movements executed by the amoeba and similar organisms. The movement of the endoplasm of the vegetable cell seems also to be of the same kind. The amoeba changes its form (and shifts its place) by throw- ing out projections of its substance, called pseudopodia, which may be blunt and short, broad bulgings as it were, or may be so long and thin as to be mere filaments, or may be of an intermedi- ate character. As we watch the outline of the hyaline ectosarc we may see a pseudopodium beginning by a slight bulging of the outline; the bulging increases by the neighbouring portions of the ectosarc moving into it, the movement under the microscope reminding one of the flowing of melted glass. As the pseudo- podium grows larger and engages the whole thickness of the ectosarc at the spot, the granules of the endosarc may be seen streaming into it forming a core of endosarc in the middle of the bulging of ectosarc. The pseudopodium may continue' to grow larger and larger at the expense of the rest of the body, and eventually the whole of the amoeba including the nucleus may as it were have passed into the pseudopodium ; the body of the amoeba will now occupy the place of the pseudopodium instead of its old place ; in other words it will in changing its form have also changed its place. During all these movements, and during all similar amoeboid movements, the bulk of the organism will, so far as can be ascertained, have remained unchanged ; the throwing out a pseu- dopodium in one direction is accompanied by a corresponding retraction of the body in other directions ; if as sometimes happens the organism throws out pseudopodia in various directions at the same time, the main body from which the pseudopodia project is reduced in thickness ; from being a spherical lump for instance it becomes a branched film. The movement is brought about not by increase or decrease of substance but by mere translocation of particles ; a particle which at one moment was in one position moves into a new position, several particles thus moving towards the same point cause a bulging at that point, and several particles moving away from the same point cause a retraction at that point ; but no two particles get nearer to each other so as to occupy together less space and thus lead to condensation of sub- stance, or get farther from each other so as to occupy more space and thus lead to increase of bulk. 138 AMCEBOID MOVEMENTS. [BOOK I. In this respect, in that there is no change of bulk, but only a shifting of particles in their relative position to each other, the amoeboid movement resembles a muscular contraction ; but in other respects the two kinds of movement seem different, and the question arises, have we the right to speak of the substance which can only execute amoeboid movements as being contractile ? We may, if we admit that contractility is at bottom simply the power of shifting the relative position of particles, and that muscular contraction is a specialized form of contraction, the shifting of particles is specialized in the sense that it has always .a definite relation to the long axis of the fibre. The protoplasm of the amoeba or of a white corpuscle is, as we have said, of a consistency which we for want of better terms call semi-solid or semi-fluid. Consequently when no internal changes are prompting its particles to move in this or that direction, the influences of the surroundings will tend to give the body, as they will other fluid or semi-fluid drops, a spherical form. Hence the natural form of the white corpuscle is more or less spherical. If under the influence of some stimulus internal or external, some of the particles are stirred to shift their place, amoeboid move- ments follow, and the spherical form is lost. If however all the particles were stirred to move with equal energy, they would neutralize each other's action, no protrusion or retraction would take place at any point of the surface and the body would remain a sphere. Hence in extreme stimulation, in what in the muscle corresponds to complete tetanus, the form of the body is the same as in rest; and the tetanized sphere would not be appreciably smaller than the sphere at rest, for that would imply change of bulk, but this as we have seen does not take place. This result shews strikingly the difference between the general contractility of the amoeba, and the special contractility of the muscle. CHAPTER III. ON THE MOKE GENEKAL FEATURES OF NEKVOUS TISSUES. § 88. IN the preceding chapter we have dealt with the pro- perties of nerves going to muscles, the nerves which we called motor, and have incidentally spoken of other nerves which we called sensory. Both these kinds of nerves are connected with the brain and spinal cord and form part of the General Nervous System. We shall have to study hereafter in detail the brain and spinal cord ; but the nervous system intervenes so repeatedly in the processes carried out by other tissues that it will be desirable, before pro- ceeding further, to discuss some of its more general features. The Nervous System consists (1) of the Brain and Spinal Cord forming together the cerebrospinal axis, or central nervous system ; (2) of the nerves passing from that axis to nearly all parts of the body, those which are connected with the spinal cord being called spinal, and those which are connected with the brain, within the cranium, being called cranial ; and (3) of ganglia distributed along the nerves in various parts of the body. The spinal cord obviously consists of a number of segments or metameres, following in succession along its axis, each metamere giving off on each side a pair of spinal nerves ; and a similar division into metameres may be traced in the brain, though less distinctly, since the cranial nerves are arranged in manner some- what different from that of the spinal nerves. We may take a single spinal metamere, represented diagrammatically in Fig. 24, as illustrating the general features of the nervous system ; and since the half on one side of the median line resembles the half on the other side, we may deal with one lateral half only. Each spinal nerve arises by two roots. The metamere of the central nervous system C consists, as we shall hereafter see, of grey 140 A NEURAL METAMERE. [BOOK i. TIG. 24. SCHEME OF THE NERVES OF A SEGMENT OF THE SPINAL CORD. Gr grey, W white matter of spinal cord. A anterior, P posterior root. G ganglion on the posterior root. N whole nerve, N' spinal nerve proper, ending in M skeletal or somatic muscle, S somatic sensory cell or surface, X in other ways. V visceral nerve (white ramus communicans) passing to a ganglion of the sympathetic chain 2, and passing on as V to supply the more distant ganglion tr, then as V" to the peripheral ganglion af and ending in m splanchnic muscle, s splanchnic sensory cell or surface, .r other possible splanchnic endings. From 2 is given off the revehent nerve r. v (grey ramus communicans), which partly passes backward towards the spinal cord, and partly runs as v. m, in connection CHAP, in.] FEATUKES OF NERVOUS TISSUES. 141 with the spinal nerve, to supply vasomotor (constrictor) fibres to the muscles (mf) of blood vessels in certain parts, for example, in the limbs. Sy, the sympathetic chain uniting the ganglia of the series 2. The terminations of the other nerves arising from 2, auricles are similarly synchronous in action. It has been maintained, however, that the synchronism may at times not be perfect. Before we attempt to study in detail the several parts of this complicated series of events, it will be convenient to take a rapid survey of what is taking place within the heart during such a cycle. § 109. The cardiac cycle. We may take as the end of the cycle the moment at which the ventricles having emptied their contents have relaxed and returned to the diastolic or resting position and form. At this moment the blood is flowing freely with a fair rapidity, but, as we have seen, at a very low pressure, through the venae cavae into the right auricle (we may confine ourselves at first to the right side), and since there is now nothing to keep the tricuspid valve shut, some of this blood probably finds its way into the ventricle also. This goes on for some little time, and then comes the sharp, short systole of the auricle, which, since it begins, as we have seen, as a wave of contraction running forwards along the ends of the venae cavse, drives the blood not back- wards into the veins, but forwards into the ventricle ; this result is further secured by the fact that the systole has behind it on the venous side the pressure of the blood in the veins, increasing as we have seen backwards towards the capillaries, and before it the relatively empty cavity of the ventricle in which the pressure is at first very low. By the complete contraction of the auricular walls the complete or nearly complete emptying of the cavity is ensured. No valves are present in the mouth of the superior vena cava, for they are not needed ; and the imperfect Eustachian valve at the mouth of the inferior vena cava cannot be of any great use in the adult, though in its more developed state in the foetus it had an important function in directing the blood of the inferior vena cava through the foramen ovale into the left CHAP. iv. J THE VASCULAR MECHANISM. 183 auricle. The valves in the coronary vein are, however, probably of some use in preventing a reflux into that vessel. As the blood is being driven by the auricular systole into the ventricle, a reflex current is probably set up, by which the blood, passing along the sides of the ventricle, gets between them and the flaps of the tricuspid valve and so tends to float these up. It is further probable that the same reflux current, continuing somewhat later than the flow into the ventricle, is sufficient to bring the flaps into apposition, without any regurgitation into the auricle, at the close of the auricular systole, before the ventri- cular systole has begun. The auricular systole is, as we have said, immediately followed by that of the ventricle. Whether the contraction of the ven- tricular walls (which as we shall see is a simple though prolonged contraction and not a tetanus) begins at one point, and swiftly travels over the rest of the fibres, or begins all over the ventricle at once, is a question not at present definitely settled ; but in any case the walls exert on the contents a pressure which is soon brought to bear on the whole contents and very rapidly rises to a maximum. The effect of this increasing intra-ventricular pressure upon the valve is undoubtedly to render the valve more firmly and securely closed ; but the exact behaviour of the valve in thus firmly closing is a matter on which observers are not agreed. From the disposition of the flaps of the valve, and their relations to the papillary muscles, the chordae tendinese of a papillary muscle being attached to the edges of and spreading over the surfaces of two adjacent flaps, we may infer that when the papillary muscles contract, taking their share in the whole ventri- cular systole, they on the one hand bring at least the edges, if not part of the surfaces of adjacent flaps, into opposition, and, on the other hand, tend to pull down the whole of the valve, more or less in the form of a narrow funnel, into the cavity of the ventricle. If we assume, as some observers do, that the papillary muscles begin their contraction at the same time as the rest of the ventricular wall, we may conclude that the valve is in this manner firmly closed by their action at the very beginning of the systole. Other observers find that a tracing, obtained by attaching a hook to the apex of one of the flaps of the valve, and connecting it with a thread passing through the auriculo- ventricular orifice, and the auricle to a lever, indicates that the apex of the flap does not begin to move downwards until some appreciable time after the beginning of the systole. This they interpret as meaning that the papillary muscles do not begin to contract until some time after the ventricular wall has begun its contraction ; (and the tracing in question similarly indicates that the papillary muscle ceases its contraction before the ventricular wall does). If we assume this interpretation of the tracing to be correct, we must conclude that, at the first, the pressure exerted by the commencing systole would 184 THE CARDIAC CYCLE. [BOOK i. tend, while bringing the edges of the flaps together, to bulge the whole valve upwards towards the auricle, but that, later, when the papillary muscles contract, these pull the valve in a funnel shape down into the ventricle with the edges of the flaps in complete apposition. On the one view, the papillary muscles serve merely to secure the adequate closure of the valve ; on the other view, they add to the pressure exerted by the ventricular wall, by pulling the already closed valve down on the ventricular contents, or, according to an old opinion, obviate, by their shortening, the slackening of the chordae which might result from the shortening of ventricle during the systole. Whichever view be taken, it may be worth while to remark that the borders of the valves are excessively thin, so that when the valve is closed, these thin portions are pressed flat together back to back ; hence, while the tougher central parts of the valves bear the force of the ventricular systole, the opposed thin, membranous edges, pressed together by the blood, more completely secure the closure of the orifice. At the commencement of the ventricular systole, the semilunar valves of the pulmonary artery are closed, and are kept closed by the high pressure of the blood in the artery. As, however, the ventricle continues to press with greater and greater force on its contents, making the ventricle hard and tense to the touch, the pressure within the ventricle becomes at length greater than that in the pulmonary artery, and this greater pressure forces open the semilunar valves, and allows the escape of the contents into the artery. The ventricular systole may be seen and felt in the exposed heart to be of some duration ; it is strong enough and long enough to empty the ventricle more or less completely, — indeed, in some cases, it may last longer than the discharge of blood, so that there is then a brief period during which the ventricle is empty but yet contracted. During the ventricular systole the semilunar valves are pressed outwards towards but not close to the arterial walls, reflux currents probably keeping them in an intermediate position, so that their orifice forms an equilateral triangle with curved sides ; they offer little obstacle to the escape of blood from the cavity of the ventricle. The exact mode and time of closure of the semilunar valves is a matter which has been and, indeed, is still disputed, and which we shall have to discuss in some detail later on. Meanwhile it will be sufficient to say, after the blood has ceased to flow from the ventricle into the aorta, whether this be due to the cessation of the ventricular systole, or to the whole of the ventricular contents having been already discharged, a reflux of blood in the aorta towards the ventricle at once completely fills and renders tense the pockets, causing their free margins to come into close and firm contact, and thus entirely blocks the way. The corpora Arantii meet in the centre, and the thin, membranous festoons or lunulae are brought into exact apposition. As in the CHAP, iv.] THE VASCULAR MECHANISM. 185 tricuspid valves, so here, while the pressure of the blood is borne by the tougher bodies of the several valves, each two thin, adjacent lunulae, pressed together by the blood acting on both sides of them, are kept in complete contact, without any strain being put upon them ; in this way the orifice is closed in a most efficient manner. As the ventricular systole passes off, the muscular walls relax- ing, the ventricle returns to its previous form and position, and the cycle is once more ended. What thus takes place in the right side takes place in the left side also. There is the same sudden, sharp, auricular systole beginning at the roots of the pulmonary veins, the same systole of the ventricle, but, as we shall see, one much more powerful and exerting much more force ; the mitral valve with its two flaps acts in the main like the tricuspid valve, and the action of the semilunar valves of the aorta simply repeats that of the valves of the pulmonary artery. We may now proceed to study some of the cardiac events in detail. § 110. The change of form. The exact determination of the changes in form and position of the heart, especially of the ven- tricles, during a cardiac cycle is attended with difficulties. The ventricles, for instance, are continually changing their form; they change while their cavities are being filled from the auricles, they change while the contraction of their walls is getting up the pressure on their contents, they change while under the influence of that pressure their contents are being discharged into the arteries, and they change when, their cavities having been emptied, their muscular walls relax. With regard to changes in external form, there seems no doubt that the side-to-side diameter is much lessened during the systole. There is also evidence that the front-to-back diameter is greater during the systole than during the diastole, the increase taking place during the first part of the systole. If a light lever be placed so as to press very gently on the surface of the heart of a mammal, the chest having been opened and artificial respiration being kept up, some such curve as that represented in Fig. 36 may be obtained. The rise of the lever in describing such a curve is due to the elevation of the part of the front surface of the heart on which the lever is resting Such an elevation might be caused, especially if the lever were placed near the apex, by the heart being " tilted " upwards during the systole, but only a small portion at most of the rise can be attributed to this cause ; the rise is perhaps best seen when the lever is placed in the middle portion of the ventricle, and must be chiefly due to an increase in the front-to-back diameter of the ventricle during the beat. We shall discuss this curve later on in connection with other curves, and may here simply say that the part of the curve from b' to d 186 THE CHANGE OF FORM. [BOOK i. probably corresponds to the actual systole of the ventricle, that is, to the time during which the fibres of the ventricle are under- going contraction, the sudden fall from d onwards representing the relaxation which forms the first part of the diastole. If this a\ 6\6*> c\ c\ d \ W////^!/WIWI^^ FIG. 36. TRACING FROM HEAP.T OF CAT, OBTAINED BY PLACING A LIGHT LEVER ON THE VENTRICLE, THE CHEST HAVING BEEN OPENED.1 THE TUNING-FORK CURVE MARKS 50 VIBRATIONS PER SEC. interpretation of the curve be correct, it is obvious that the front-to-back diameter is greater during the whole of the systole than it is during diastole, since the lever is raised up all this time. It may, however, be argued that the heart thus exposed is subject to abnormal conditions arid is, in diastole, somewhat flattened by the weight of its contents, that this flattening is increased by even slight pressure, arid that therefore the above conclusion is not 1 The vertical or rather curved lines (segments of circles) introduced into this and many other curves are of use for the purpose of measuring parts of the curve. A complete curve should exhibit an 'abscissa' line. This may be drawn by- allowing the lever, arranged for the experiment but remaining at rest, to mark with its point on the recording surface set in motion ; a straight line, the abscissa line, is thus described, and may be drawn before or after the curve itself is made, and may be placed above or, preferably, below the curve. When a tuning-fork or other time marker is used, the line of the time marker or a line drawn through the curves of the tuning-fork will serve as an abscissa line. After a tracing has been made, the recording surface should be brought back to such a position that the point of the lever coincides with some point of the curve which it is desired to mark ; if the lever be then gently moved up and down, the point of the lever will describe a segment of a circle (the centre of which lies at the axis of the lever), which segment should be made lung enough to cut both the curve and the abscissa line (the tuning-fork curves or other time-marking line) where this is drawn. By moving the recording surface backwards and forwards, similar seg- ments of circles may be drawn through other points of the curve. The lines a, b, c in Fig. 36 were thus drawn. The distance between any two of these points may thus be measured on the tuning-fork curve or other time curve, or on the abscissa line. Similar lines may be drawn on the tracing after its removal from the recording instrument in the following way. Take a pair of compasses, the two points of which are fixed just as far apart as the length of the lever used in the experiment, measured from its axis to its writing point. By means of the compasses find the position on the tracing of the centre of the circle of which any one of the previously drawn curved lines forms a segment. Through this centre draw a line parallel to the abscissa. By keeping one point of the compass on this line but moving it along the line backwards or forwards, a segment of a circle may be drawn so as to cut any point of the curve that may he desired, and also the abscissa line or the time line. Such a segment of a circle may he used for the same purposes as the original one and any number of such segments may be drawn CHAP, iv.] THE VASCULAR MECHANISM. 187 valid. And, indeed, it is maintained by 'some that the front-to- back diameter does actually diminish during systole. But it is at least clear that the front-to-back diameter, even if it does not increase, diminishes far less than does the side-to-side diameter ; and hence during the systole there is a change in the form of the section of the base of the ventricles. During the diastole this has somewhat the form of an ellipse with the long axis from side to side, but with the front part of the ellipse much more convex than the back, since the back surface of the ventricles is somewhat flattened. During the systole this ellipse is converted into a figure much more nearly resembling a circle. It is urged, moreover, that the whole of the base is constricted, and that the greater efficiency of the auriculo-ventricular valves is thereby secured. As to the behaviour of the long diameter from base to apex, observers are not agreed ; some maintain that it is shortened, and others that it is practically unchanged. And, in any case, a change in this diameter plays little or no part in the expulsion of the contents of the ventricle ; this expulsion is effected by the contrac- tion of the more transversely disposed fibres, whereby the cavity is reduced to an elongated slit. Moreover, if any shortening does take place it must be compensated by the elongation of the great vessels, which, as stated above, may be seen in an inspection of the beating heart. For there is evidence that the apex, though, as we have seen, it is somewhat twisted round during the systole, and at the same time brought closer to the chest-wall, does not change its position up or down, i.e. in the long axis of the body. If in a rabbit or dog a needle be thrust through the chest-wall so that its point plunges into the apex of the heart, though the needle quivers, its head moves neither up nor down, as it would do if its point in the apex moved down or up. During systole, broadly speaking, the ventricles undergo a diminution of total volume, equal to the volume of contents discharged into the great vessels (for the walls themselves like all muscular structures retain their volume during contraction save for changes which may take place in the quantity of blood contained in their blood vessels, or of lymph in the intermuscular spaces), while they undergo a change of form which may be described as that from a roughly hemispherical figure with an irregularly elliptical section to a more regular cone with a more nearly circular base. § 111. Cardiac Impulse. If the hand be placed on the chest, a shock or impulse will be felt at each beat, and on examination this impulse, ' cardiac impulse,' will be found to be synchronous with the systole of the ventricle. In man, the cardiac impulse may be most distinctly felt in the fifth costal interspace, about an inch below and a little to the median side of the left nipple. In an animal the same impulse may also be felt in another way, viz. 188 THE CARDIAC IMPULSE. [BOOK i. by making an incision 'through the diaphragm from the abdo- men, and placing the finger between the chest-wall and the apex. It then can be distinctly recognized as the result of the hardening of the ventricle during the systole. And the impulse which is felt on the outside of the chest is chiefly the effect of the same hardening of the stationary portion of the ventricle in contact with the chest-wall, transmitted through the chest- wall to the finger. In its flaccid state, during diastole, the apex is (in a standing position at least) at this point in contact with the chest-wall, lying, somewhat flattened, between it and the tolerably resistant diaphragm. During the systole, while being brought even closer to the chest- wall, by the tilting of the ventricle and by the movement to the front and to the right of which we have already spoken, it suddenly grows tense and hard, and becomes rounder. The ventricles, in executing their systole, have to contract against resistance. They have to produce within their cavities, pressures greater than those in the aorta and pulmonary arteries, respectively. This is, in fact, the object of the systole. Hence, during the swift systole, the ventricular portion of the heart becomes suddenly tense, somewhat in the same way as a bladder full of fluid would become tense and hard when forcibly squeezed. The sudden pressure exerted by the ventricle thus rendered sud- denly tense and hard, aided by the closer contact of the apex with the chest-wall (which, however, by itself, without the hardening of contraction, would be insufficient to produce the effect), gives an impulse or shock both to the chest-wall and to the diaphragm. If the modification of the sphygmograph (an instrument of which we shall speak later on, in dealing with the pulse), called the cardio- graph, be placed on the spot where the impulse is felt most strongly, the lever is seen to be raised during the systole of the ventricles, and to fall again as the systole passes away, very much as if it were placed on the heart directly, A tracing may thus be obtained, see Fig. 46, of which we shall have to speak more fully later on, see § 115. If the button of the lever be placed, not on the exact spot of the impulse, but at a little distance from it, the lever will be depressed during the systole. While at the spot of impulse itself the contact of the ventricle is increased during systole, away from the spot the ventricle (owing to its change of form and subsequently to its diminution in volume) retires from the chest- wall, and hence, by the mediastinal attachments of the pericardium, draws the chest-wall after it. § 112. The Sounds of the Heart. When the ear is applied to the chest, either directly or by means of a stethoscope, two sounds are heard, — the first a comparatively long, dull, booming sound, the second a short, sharp, sudden one. Between the first and second sounds the interval of time is very short, too short to be easily measured, but between the second and the succeeding first sound there is a distinct pause. The sounds have been likened CHAP, iv.] THE VASCULAR MECHANISM. 189 to the pronunciation of the syllables lubb dup, so that the cardiac cycle, as far as the sounds are concerned, might be represented by : — lubb, dup, pause. The second sound, which is short and sharp, presents no diffi- culties. It is coincident in point of time with the closure of the semilunar valves, and is heard to the best advantage over the second right costal cartilage, close to its junction with the sternum, i. e. at the point where the aortic arch comes nearest to the surface, and to which sounds generated at the aortic orifice would be best conducted. Its characters are such as would belong to a sound generated by membranes like the semilunar valves being suddenly made tense, and so thrown into vibrations. It is obscured and altered, or replaced by ' a murmur/ when the semilunar valves are affected by disease, and may be artificially obliterated, a murmur taking its place, by passing a wire down the arteries, and hooking up the aortic valves. There can be no doubt, in fact, that the second sound is due to the semilunar valves being thrown into vibrations at their sudden closure. The sound heard at the second right costal cartilage is chiefly that generated by the aortic valves, and murmurs or other alterations in the sound caused by changes in the aortic valves are heard most clearly at this spot. But even here the sound is not exclusively of aortic origin, for in certain cases, in which the semilunar valves on the two sides of the heart are not wholly synchronous in action, the sound heard here is double (" reduplicated second sound " ), one being due to the aorta, and one to the pulmonary artery. When the sound is listened to on the left side of the sternum at the same level, the pulmonary artery is supposed to have the chief share in producing what is heard, and changes in the sound heard more clearly here than on the right side are taken as indications of mischief in the pulmonary valves. The first sound, longer, duller, and of a more ' booming ' character than the second, heard with greatest distinctness at the spot where the cardiac impulse is felt, presents many difficulties in the way of a complete explanation. It is heard distinctly when the chest-walls are removed. The cardiac impulse, therefore, can have little or nothing to do with it In point of time, it is coincident with the systole of the ventricles, and may be heard to the greatest advantage at the spot of the cardiac impulse ; that is to say, at the place where the ventricles come nearest to the surface, and to which sounds generated in the ventricles would be best conducted. It is more closely coincident with the closure and consequent vibrations of the auriculo-ventricular valves than with the entire systole; for on the one hand it dies away before the second sound begins, whereas, as we shall see, the actual systole lasts at least up to the closure of the semilunar valves, and on the other hand the auriculo-ventricular valves cease to be tense 190 THE SOUNDS OF THE HEART. [BOOK r. and to vibrate so soon as the contents of the ventricle are driven out. This suggests that the sound is caused by the sudden tension of the auriculo-ventricular valves, and this view is sup- ported by the facts that the sound is obscured, altered or replaced by murmurs when the tricuspid or mitral valves are diseased, and that the sound is also altered or, according to some observers, wholly done away with when blood is prevented from entering the ventricles by ligature of the venae cavse. On the other hand, the sound has not that sharp character which one would expect in a sound generated by the vibration of membranes such as the valves in question, but in its booming qualities rather suggests a muscular sound. Further, according to some observers, the sound, though somewhat modified, may still be heard when the large veins are clamped so that no blood enters the ventricle, and, indeed, may be recognized in the few beats given by a mammalian ventricle rapidly cut out of the living body by an incision carried below the auriculo-ventricular ring. Hence the view has been adopted that this first sound is a muscular sound. In discussing the muscular sound of skeletal muscle (see § 75), we saw reasons to distrust the view that this sound is generated by the repeated, individual, simple contrac- tions which make up the tetanus, and hence corresponds in tone to the number of those simple contractions repeated in a second, and to adopt the view that the sound is really due to a repetition of unequal tensions occurring in a muscle during the contraction. Now, the ventricular systole is undoubtedly a simple contraction, a prolonged simple contraction, not a tetanus, and, therefore, under the old view of the nature of a muscular sound, could not produce such a sound ; but accepting the other view, and reflecting how complex must be the course of the systolic wave of contraction over the twisted fibres of the ventricle, we shall not find great difficulty in supposing that that wave is capable in its progress of producing such repetitions of unequal tensions as might give rise to a ' muscular sound,' and, consequently, in regarding the first sound as mainly so caused. Accepting such a view of the origin of the sound we should expect to find the tension of the muscular fibres, and so the nature of sound, dependent on the quantity of fluid present in the ventricular cavities and hence modified by liga- ture of the great veins, and still more by the total removal of the auricles with the auriculo-ventricular valves. We may add that we should expect to find it modified by the escape of blood from the ventricles into the arteries during the systole itself, and might regard this as explaining why it dies away before the ventricle has ceased to contract. Moreover, seeing that the auriculo-ventricular valves must be thrown into sudden tension at the onset of the ventricular systole, which, as we have* seen, is developed with considerable rapidity, not far removed at all events from the rapidity with which the CHAP. iv.J THE VASCULAR MECHANISM, 191 semihmar valves are closed, a rapidity, therefore, capable of giving rise to vibrations of the valves adequate to produce a sound, it is difficult to escape the conclusion that the closure of these valves must also generate a sound, which in a normally beating heart is mingled with the sound of muscular origin. If we accept this view that the sound is of double origin, partly 'muscular,' partly 'valvular/ both -causes being dependent on the tension of the ventricular cavities, we can perhaps more easily understand how it is that the normal first sound is at times so largely, indeed, we may say so completely altered and obscured in diseases of the auriculo-ventricular valves, and how it may also be modified in character by changes, such as hypertrophy, of the muscular walls. Since the left ventricle forms the entire left apex of the heart, the murmurs or other changes of the first sound heard most distinctly at the spot of cardiac impulse belong to the mitral valve of the left ventricle. Murmurs generated in the tricuspid valve of the right ventricle are heard more distinctly in the median line below the end of the sternum. § 113. Endocardiac Pressure. Since it is the pressure exerted upon the contents of the ventricle by the contraction of the ventricular walls which drives the blood from the heart into the aorta, and so maintains the circulation, the study of this pressure, endocardiac pressure, is of great importance. The mercurial manometer, so useful in a general way in the study of arterial pressure, is unsuited for the study of endocardiac pressure, since the great inertia of the mercury prevents the instrument respond- ing properly to the exceedingly rapid changes of pressure which take place in the heart. We are obliged to have recourse to other instruments. One method, having been used by Chauveau and Marey in researches which have become ' classic,' deserves to be noticed, though it is not now employed. It consists in introducing, in a large animal, such as a horse, through a blood vessel into a cavity of the heart, a tube ending in an elastic bag, Fig. 37 A, both tube and bag being filled with air, and the tube being connected with a recording * tambour.' of appropriate curvature, A. b. Fig. 37, is furnished at its an elastic bag or < ampulla ' a. Such an instrument is A tube end with an spoken of as a * cardiac sound.' When it is desired to explore simul- taneously both auricle and ventricle, the sound is furnished with two ampullae, one at the extreme end and the other at such a distance that when the former is within- the cavity of the ventricle the latter is within the cavity of the auricle. Each ' ampulla ; communicates by a separate air-tight tube with an air-tight tambour (Fig. 37 B) on which a lever rests, so that any pressure on the ampulla is communicated to the cavity of its respective tambour, the lever of 192 ENDOCARDIAC PRESSURE. [BOOK i. which is raised in proportion. When two ampullae are used, the writing points of both levers are brought to bear on the same re- cording surface exactly underneath each other. The tube is carefully introduced through the right jugular vein into the right side of the heart until the lower (ventricular) ampulla is fairly in the cavity of the right ventricle, and, consequently, the upper (auricular) ampulla in the cavity of the right auricle. Changes of pressure on either ampulla, then, cause movements of the corresponding lever. When the pressure, for instance, on the ampulla in the auricle is increased, the auricular lever is raised and describes on the recording surface an FIG. 37. MAREY'S TAMBOUR, WITH CARDIAC SOUND. A. A simple cardiac sound such as may be used for exploration of the left ventricle. The portion a of the ampulla at the end is of thin india rubber, stretched over an open framework with metallic supports above and below. The long tube 6 serves to introduce it into the cavity which it is desired to explore. B. The Tambour. The metal chamber m is covered in an air-tight manner with the india rubber c, bearing a thin, metal plate m', to which is attached the lever /, moving on the hinge h. The whole tambour can be placed by means of the clamp d at any height on the upright *'. The india rubber tube t serves to connect the interior of the tambour either with the cavity of the ampulla of A or with any other cavity. Supposing that the tube t were connected with b, any pressure exerted on a would cause the roof of the tambour to rise and the point of the lever would be proportionately raised. ascending curve ; when the pressure is taken off, the curve descends, — and so also with the ventricle. The 'sound' may in a similar manner be introduced through the carotid artery into the left ventricle, being slipped past the aortic valves, and thus the changes taking place in that chamber also may be explored. CHAP. iv.J THE VASCULAR MECHANISM. 193 When this instrument is applied to the right auricle and ventricle some such record is obtained as that shewn in Fig. 38, where the upper curve is a tracing taken from the right auricle, and the lower curve from the right ventricle of the horse, both curves being taken simultaneously on the same recording surface. In these curves the rise of the lever indicates pressure exerted upon the corresponding ampulla, and the upper curve, from the right auricle, shews the sudden, brief pressure b exerted by the sudden and brief auricular systole. The lower curve, from the right ventricle, shews that the pressure exerted by the ventric- ular systole begins almost immediately after the auricular systole, increases very rapidly indeed, so that the lever rises in almost a straight line up to cf, is continued for some considerable time, and then falls very rapidly to reach the base line. The figure, it must be understood, does not, by itself, give any information as to the relative amounts of pressure exerted by the auricle and ventricle respectively ; indeed, the movements of the auricular lever are much too great compared with those of the ventricular lever. The figure is chiefly useful for giving a graphic general view of the series of events within the cardiac cavi- ties during a cardiac cycle, the short auricular pressure, the long-continued vpntrirnlflr nrp^nrp la^Hncr nparlv half FlG' 38t SIMULTANEOUS TRACINGS ventricular pressure, lasting nearly nair the whole period, and the subsequent pause when both parts are at rest or in diastole. Among the more trustworthy methods of recording the changes of endocardiac pressure, we may first mention that of Roy and Rolleston. By means of a short cannula introduced through a large vessel, or directly, as a trocar, through the walls of the ventricle (or auricle), the blood in the cavity is brought to bear on an easily moving piston. The movements of the piston are recorded by a lever, and the evils of inertia are met by making the piston and lever work against the torsion of a steel ribbon, the length of which, and consequently the resistance offered by which, and hence the excursions of the piston, can be varied at pleasure. r Ji 3 J. L- — — *" - / V ^~- 'X -\. _— - 0 A /< r> 7J ' t - i — • l' FROM THE RIGHT AURICLE, VENTRICLE, OF THE HORSE. (AFTEK CHAUVEAU AND MAKEY.) We give as examples of curves obtained by this method two curves from the left ventricle, one (Fig. 39 A) of a rapidly beating, and the other (Fig. 39 B) of a slowly beating heart. 13 194 EISTDOCARDIAC PRESSURE. [BOOK i. 8 FIG. 39. CURVES OF ENDOCARDIAC PRESSURE. FROM LEFT VENTRICLE OF DOG. (Roy and Rolleston.) A. a quickly beating, B. a more slowly beating heart. An instrument which has been much used of late, and the use of which has given very valuable results is the " membrane-mano- meter" of Hurthle. FIG. 40. THE MEMBRANE-MANOMETER OF HuRTHLE.1 1 For this figure I am indebted to Mr. Albrecht, the University Instrument- maker at Tubingen. CHAP, iv.] THE VASCULAR MECHANISM. 195 This consists essentially of a very small metal drum or tambour (Fig. 41 a) somewhat like that of Mare}^ but hemispherical and not more than 15 mm. in diameter, ending below in a tube b. In Fig. 40 the instrument, with its holder, is seen from above. The second lever, which is motionless, is for the purpose of describing the base line. The screw-tap on the tube leading, in the figure, up to the tambour, is for the purpose of diminish- ing the calibre of the tube and so of 'damping ' the instrument. On the right of the tambour in the figure are seen the arrangements for adjust- ing the levers. In Fig. 41 the tube b by which the catheter is connected with the tambour, is, for convenience of illustration, shewn as FlG-41- directed parallel to the lever, instead of, as in the instrument itself, at right angles to it. THLE'S MEMBRANE MA- The roof of the tambour is supplied by a care- NOMETER. fully chosen delicate elastic membrane c which bears at its centre a thin metal disc d, connected by a short upright e with a lever I. A catheter, opened at the end or with a lateral 'eye ' and filled with a solution of magnesium sulphate or with some fluid tending to check the clotting of blood, is introduced into the cavity of the heart which it is desired to explore. It may be introduced by the jugular vein into the right auricle, and past the auricle into the right ventricle, or through the carotid artery into the aorta, and so, between the semilunar valves, or piercing one of the flaps (the perforation seems to introduce no error) into the cavity of the left ventricle ; or the end of the catheter may be left in the aorta above the semilunar valves when it is desired to Investigate the pressure at the root of the aorta. The cavity of the tambour also is filled, not witli air, as in Marey's tambour, but with the same fluid as is the catheter, or with water j and the tube of the tambour is connected with the catheter. Variations of pressure within the cavity of the heart are transmitted through the fluid of the catheter to the fluid in the tambour, and thus put into movement the elastic roof of the tambour ; the movements of the elastic roof are, in turn, transmitted to the lever, which records, in the usual manner, on some recording surface. For measuring the amount of the changes of pressure, the instrument must be graduated expert mentally. There are many details in the instrument which need not be described here ; but we may state that the instrument may be ' damped,' rendered less sensitive, and thus the features of the curves due to inertia lessened, by narrowing, through a screw-tap, the communication between the catheter and the cavity of the tambour. The membrane of the tambour may, by means of an ivory button, be brought to bear on one end of a slip of steel, placed horizontally and fastened at the other end, so as to act as a spring. The instrument then becomes a " spring-manometer." The small movements of the spring caused by the movements of the membrane of the tambour are magnified by a recording lever. 196 ENDOCARDIAC PRESSURE. [BOOK i. Fig. 42 gives a curve of endocardiac pressure of the left ventricle of the dog obtained by this method. The recording surface is travelling quickly, and the movements of the lever are not great. 12 345 The manometer of Gad differs FIG. 42. CURVE OF PRESSURE from that of Hiirthle in the membrane IN THE LEFT VENTRICLE OF being replaced by a thin, elastic disc THE DOG, HURTHLE'S MEM- e mafol BRANE-MANOMETER. 16lal' In the instrument of Frey and Krehl, which is a modification of one by Fick, the transmission is effected partly by fluid and partly by an air tambour, the button of which presses against a horizontal steel spring. A catheter, filled with fluid to prevent clotting and introduced into a cavity of the heart, is connected with a glass cylinder, maintained carefully in a vertical position, the lower half of which is tilled with the same fluid as is the catheter. The upper half of the cylinder, con- taining air only, is connected by a very narrow, in fact a capillary tube, with a small tambour. The changes of pressure within the heart are transmitted through the fluid of the catheter to the air in the cylinder, and so to the air in the tambour, the membrane of which moves accordingly in and out. A button on the membrane presses on a hori- zontal steel spring, and the small movements of the membrane thus transmitted to the spring are recorded by means of a magnifying lever. Other instruments have been employed by other observers. When we examine the curves which we have given (Figs. 38, 39, 42), obtained by three several methods, we find that they agree in the following main features. The curve of pressure in the ventricle, whether right or left, rises at the very beginning of the systole with very great rapidity, very soon reaches its maximum or nearly its maximum, maintains nearly the same height for some time, and then very rapidly descends to the base line (which in these figures indicates the pressure of the atmosphere) or even falls, for a brief space, slightly below it, and remains at or near the base line, until, at the next beat, it repeats the same changes. This means that the contraction of the ventricular walls in the systole acts in such a manner as very suddenly to raise up to a certain height the pressure within, the ventricle, which during the diastole was at, or not far removed from that of the atmosphere, that the pressure is maintained without any very great change for a considerable time, and that it then falls back to its original level with great suddenness, almost, if not quite, as suddenly as it was raised. These are the important features of the pressure within the ventricle ; in these features all the three curves agree. We may add that the same features are shewn also in curves of pres- CHAP. iv.J THE VASCULAR MECHANISM. 197 sure taken by other methods ; and, indeed, as shewn in Fig. 36 and in others which we shall give, corresponding features occur in curves of other changes in the heart. All these curves shew a flattening maintained, with smaller variations, during the con- tinuance of the systole ; this is so characteristic that it has been called the ' systolic plateau.' It is true that curves of ventri- cular pressure taken by certain methods, that of Frey and KrehPs for instance, do not shew this ' plateau,' the curve in such cases rising gradually to a maximum and immediately beginning to fall, so that the summit is a simple peak. And it is argued that such a curve is the true curve of ventricular pressure always obtained so long as the blood in the ventricle has free access to the interior of the catheter, and that the plateau is only seen when the end of the catheter is too near the apex, and its opening closed, at the height of the systole, by the ventricular walls coming together ; the top of the true curve is thus, as it were, cut off. But the evidence is, on the whole, opposed to this view, and we shall accept the plateau as being a true representation. Though the curves given above agree in these main features, they differ in many minor features, and other features also of minor value appear in curves of endocardiac pressure according to the various circumstances in which the heart finds itself. Some of these minor features we shall presently find useful in discussing the mechanism of the beat. § 114. The output. Since the use of the pressure exerted by the ventricle is to drive a quantity of blood out of the ventricle into the aorta (or pulmonary artery) it is important to study the ' output ' or quantity of blood so oSriven out ; and since, under normal circumstances, the quantity ejected by the right ventricle is the same as that ejected by the left ventricle, we may confine our attention to the latter. The normal or average output has been calculated in various ways, by help of certain assumptions ; but these we may put on one side since the matter has now been made the subject of direct experimental determination. j • Methods. Method of Stolnikow. This consists in allowing the blood to flow from the carotid into a vessel until a certain measured quantity has escaped, and then returning this blood to the right auricle while the blood from the carotid is flowing into a second similar vessel to be similarly returned, and in repeating this manoeuvre a certain number of times. One carotid is tied (the animal being a dog), and the arch, of the aorta plugged beyond (Fig. 43 p}. The circulation is thus confined to the lungs and the coronary system. Into the other carotid is tied a tube connected by a forked branching la and 2a with two vessels I. and II., which also communicate by a similar forked branching Iv and 2v with the right auricle. The blood is allowed to flow through la into I. until a certain quantity has escaped. Then la is closed, while 2a and Iv are opened. The blood 198 THE OUTPUT OF THE HEART. [BOOK i. from I. flows back by \v to the right auricle, while the blood from the carotid flows into II. by 2a. When a certain quantity has escaped into II., the action is reversed, and I. is once more filled ; and so on. FIG. 43. DIAGRAM OF STOLNIKOW'S APPARATUS. In this way the quantity of blood which the heart delivers, its ' output ' during a given time can be measured ; the quantity discharged at a single beat can similarly be determined. By means of recording floats in I. and II., a graphic record of the output may also be obtained. The other methods are plethysmographic (§ 104) in nature. The volume of the heart changes only with the volume of its contents, for we may neglect, in the first instance at least, as insignificant the changes of volume due to changes in the amount of blood held by the coronary system, and we may wholly neglect the changes of volume due to changes in the quantity of lymph present in the cardiac tissues. An increase in the volume of the heart means that more blood is flowing into it than is leaving it, a decrease that more is leaving it than is flowing into it. Hence, if we measure the diminution of volume which takes place during the systole, this gives us the volume of blood dis- charged by the two ventricles during that systole, the effect of changes in the auricles being neglected ; and since the two ventricles discharge equal quantities, half this will give us the quantity of blood discharged by the left ventricle during the systole. In the method of Tigerstedt and others the pericardial cavity is CHAP, iv.] THE VASCULAR MECHANISM. 199 employed as the plethysmographic chamber, the changes of volume in it being transmitted by air to the recording apparatus. A cannula is introduced into the pericardium, a little air entering at the same time, and is connected by an air tube with a delicate piston, the movements of which are recorded in the usual way. FIG. 44. CARDIOMETER OF ROY AND ADAMI. In the method of Roy and Adami the heart is placed in a rigid metal box, Fig. 44 5, the cavity of which, filled with warmed oil, is connected with a light piston c and so with a recording lever. The pericardium being laid open, the two halves of the box are placed round the heart, are securely fixed by means of an india rubber ring a, to the parietal pericardium round the roots of the great vessels, and are brought together. The cavity is then filled with oil, and the piston, also filled with oil, is brought into connection with the box, the levor 200 THE OUTPUT OF THE HEART. [BOOK i. and rod of the piston being placed by means of the india rubber spring d, in such a position that the pressure within the box is some few mm. Hg below that of the atmosphere. By these methods it has been determined that the diminution of the volume of the heart at a systole, the " contraction volume" as it has inconveniently been called, that is to say, the quantity of blood discharged at a systole, the output of a systole, or the " pulse-volume " as we may call it, for it is this which causes the pulse, varies very much under various circumstances. We shall have to discuss later on some of^the influences bearing on its amount. Meanwhile we merely call attention to the fact that it does vary largely, and that any numerical statement as to a normal pulse-volume has relatively little value. Another fact of considerable importance brought to light by these methods is that under certain circumstances, at all events, the output by the left ventricle during a number of beats may be less than the intake through the right auricle. This means that under these circumstances the ventricle does not at the systole discharge the whole of its contents ; some of the blood remains behind in the cavity of the ventricle at the close of the systole. Hence the assumption that the ventricle, in its systole, always discharges the whole of its contents, so as to be quite empty at the onset of diastole, is not true ; the ventricle may completely empty itself but it by no means always does so. The Mechanism of the Beat. § 115. We may now attempt to consider in rather more detail what we may call the mechanism of the beat, that is to say, the exact manner in which the heart receives and ejects the blood. For this purpose we shall need certain data in addition to those on which we have already dwelt. In addition to the curve obtained by placing a light lever on the exposed heart (Fig. 45), a method which though useful is open vwmwvwww/w^^ Fig. 45. (Repeated from Fig. 36.) CHAP, iv.] THE VASCULAR MECHANISM. 201 to objection, we may obtain what is very nearly the same thing, viz. a cardiographic tracing (Fig. 46) or cardiogram, that is to say, a tracing of the cardiac impulse, a curve of the changes in the pressure exerted by the apex of the heart on the chest-wall. Various forms of cardiograph have been used to record the cardiac impulse. In some the pressure of the impulse is transmitted directly to a lever which writes upon a travelling surface. In others the impulse is, by means of an ivory button, brought to bear on an air- chamber, connected by a tube with a tambour like that in Fig. 37 ; the pressure of the cardiac impulse compresses the air in the air-chamber, and through this the air. in the chamber of the tambour, whereupon the lever is raised. In others the impulse, being received by a small, elastic bag rilled with fluid and introduced through an opening made in the chest-wall, the pleura being left intact, is transmitted through fluid along a tube to a membrane-manometer. Or, to avoid opening the chest-wall, the tube may be made to begin in a small, trumpet- shaped opening or " receiver " covered with an elastic membrane, bearing a central button of cork or other material ; the button being lightly pressed on the spot where the impulse is felt, the impulse is transmitted along the fluid of the tube from the elastic membrane of the receiver to that of the manometer. In Fig. 46 we give two such cardiograms obtained by different methods, in Fig. 54 a more diagrammatic curve. FIG. 46. CARDIOGRAMS. The left-hand figure is from Roy and Adami. Since it is the contraction of the ventricular fibres which is the actual propelling force, an exact record of this contraction, after the manner of a muscle-curve, would serve, could it be obtained, as the basis of discussion. Owing to the intricate arrangement of the cardiac muscular fibres, such a simple record cannot be obtained ; the nearest approach to it is the record of the changes in the distance between two points on the surface of the heart brought about during a beat. 202 THE MECHANISM OF THE BEAT. [BOOK i. In the instrument of Roy and Adaini, by an ingenious arrangement into the details pf which we need not go, a delicate rod placed horizon- tally in connection with two points of the surface of the heart, of the ventricles, for instance, as it glides to and fro, according as the two points approach or recede from each other, records its movements by means of a light lever. We give in Fig. 47 such a myocardiographic tracing, as it is called ; the rise of the lever indicates an approach, the fall a receding of two points taken transversely across the ventricle of a dog. What conclusions can we draw from the features of the various curves which we have given ? We have reproduced in some cases more than one curve representing the same event, for the important reason that certain FIG. 47. MYOCARDIO- of the features of almost every curve are due> to some extent at least' to the instru- ment itself, and must not be taken as exact records of what is actually taking place in the heart ; the inertia of one or other part of this or that instrument used plays a more or less important part in determining the form of the curve. It will therefore be readily understood that the interpretation of various heart curves is attended with great difficulties, and has led to much discussion. We must content ourselves here with confining our attention to the more important points, leaving many details, however interesting, on one side. Let us begin with the beginning of the ventricular systole. All the curves, curve of endocardiac pressure, cardiogram, myocar- diogram, and others, shew the important fact that the systole begins suddenly and increases swiftly until it reaches the beginning of what we have called the " systolic plateau," c in Figs. 38, 39, 45, 3 in Fig. 46, d in Fig. 47. In some curves, as in Figs. 38, 39 B, 42, the rise is unbroken ; in others, as in Figs. 39 A, 45, the rise is marked with a shoulder. In Fig. 47, this shoulder b has been interpreted, by those who maintain that papillary muscles begin their contraction later than the main ventricular wall, as indicating that event. We will not discuss the question here. In some of the pressure curves, as in Fig. 38, the rise of pressure in the ventricle due to the actual systole is preceded by & slight temporary rise. This has been interpreted as indicating a slight rise of pressure in the ventricle due to the auricular systole just preceding the ventricular systole ; but this interpretation has been debated, and indeed the slight rise in question is not always seen. Similarly, some curves shew a gradual but very slight increase of pressure in the ventricle during the preceding diastole ; this has been interpreted as indicating a rise of pressure due to the gradual CHAP, iv.] THE VASCULAR MECHANISM. 203 inflow of blood from the auricle and veins , but it, too, is not always present. Both the steady though slight rise of the lever throughout the diastole, with a sudden increase at the end, coin- cident with the auricular systole, are often seen in cardiograms ; see the diagrammatic curve in Fig. 54. The ventricle as a whole enlarges under the venous inflow, and is more suddenly enlarged by the auricular systole. The feature on which we wish to insist is the rapid rise of the intra- ventricular pressure, and the sudden change at the commencement of the systolic plateau. What does this sudden change mean ? To answer this question we must ascertain what is taking place at the same time in the aorta. § 116. If two catheters be in- troduced at the same time into the left side of the heart of a dog, being so arranged that while the end of one catheter lies in the left ventricle, Fig. 48, V, that of the other lies in the aorta A° above the semilunar valves, and if each catheter be con- nected with a membrane-manometer, the two manometers recording on the same surface, one below the other, we obtain some such result as that shewn in Fig. 49. An examination of the two curves thus obtained shews us the following. At 0, the beginning of the ventricular systole, or rather the time when the contraction of the ventricular fibres is beginning to raise the pressure within the ventricle, no effect is being produced in the aorta ; the blood in the aorta is completely sheltered by the closed aortic valves. A little later, however, at 1, the pressure in the aorta begins to rise. This means that the semilunar valves are now opened, so that the force of the ventricular systole can make itself felt in the aorta. Up to 1, the pressure in the ventricle, though increasing, is still less than that remaining in the aorta after the last beat, but at 1 the pressure in the ventricle becomes equal to or rather slightly greater than that in the aorta, and the valves are thrown open. This is also shewn by comparing, as may be done by means FIG. 48. DIAGRAM ILLUSTRATING THE METHOD OF RECORDING SI- MULTANEOUSLY THE PRESSURE IN THE LEFT VENTRICLE AND AT THE ROOT OF THE AORTA. HURTHLE. 204 THE MECHANISM OF THE BEAT. [BOOK i. of the " differential manometer," the changes of pressure in the ventricle and in the aorta at the same time. o 1 2 vwwwvwwv t X. 34 5 in A_n. 012 345 FIG. 49. SIMULTANEOUS TRACINGS or VENTRICULAR AND AORTIC PRESSURE. HiJRTHLE. On the left side the recording surface is travelling slowly, on the right more swiftly, the tuning-fork vibrations, t, being 100 a second. AQ. aortic. V. ventricular curve, x — x base line to each. The vertical lines 1, 2, 3, 4, 5, cut each curve at exactly the same time. In the differential manometer, Fig. 50, the two tambours of two membrane manometers T and Tj (the mouths of the tubes opening into each are seen in section) are arranged so that the central discs of both, T, FIG. 50. DIAGRAM OF THE DIFFERENTIAL MANOMETER OF HURTHLE. d and dv work on a balance above them. When the pressure in the two tambours is equal, the balance is horizontal ; any difference of pressure between the two leads to an upward or downward movement of one or other arm, and this working against the light steel spring s, by means of e and e1 moves the lever I. In Figs. 51, 52 we give simultaneous tracings of the pressure in the left ventricle V, and in the aorta AQ, and of the movements of the lever of the balance indicating differences of pressure D between the ventricle and the aorta. At the base line x — x of D the two pressures are equal. The course of the curve below this base line indicates that the pressure in the ventricle is below that of the aorta ; as the curve approaches towards the base line the pressure in the ventricle becomes more and more nearly equal to that in the aorta ; and such part of the curve as lies above the base line indicates (except in so far as it may be due to the inertia of the CHAP, iv.] THE VASCULAR MECHANISM. 205 instrument) that the pressure in the ventricle is for the time being above that in the aorta. \J\J \- FIG. 51. SIMULTANEOUS CURVES OF AORTIC AND VENTRICULAR PRESSURE AND OF THE DIFFERENTIAL MANOMETER. HURTHLE. /I0, aorta. F. ventricle. D. differential manometer, x — x, the base line in each respectively. The recording surface is travelling slowly, the time marker t, t mark- ing seconds. 0 1 2 1 2 3 4 0 1 FIG. 52. THE SAME. 3 4 The recording surface Is travelling quickly ; the vibrations of the tuning-fork t, t, are 100 (double vibrations) a second. An examination of the figures shews that the pressures in the ventricle and the aorta become equal at the mark (1). Before this though the pressure in the ventricle is rising rapidly that in the aorta is not rising, indeed is continuing to sink ; the closed 206 THE MECHANISM OF THE BEAT. [BOOK i. semilunar valves shelter the blood in the aorta from the ventricu- lar pressure. But immediately after (1) the pressure in the aorta also begins to rise ; this shews that the semilunar valves are now open, the blood in the ventricle and that in the aorta now forming a continuous column, and allowing the pressure of the ventricle to be felt in the aorta. A very slight excess of pressure on the ventricular side of the valves is sufficient to push aside the flaps of the valve ; so that we may fairly say that the valves open immediately after (1), which marks the point at which the curve of difference of pressure between the ventricle and the aorta has reached the base line x — x ; that is to say, at which the difference between the two has become nil. It will be observed, however, that the mark (1) cuts the ventri- cular curve not at the summit of its rise but short of this ; the pressure in the ventricle continues to rise after the valves are open, the curve continues after this to ascend rapidly up to (2), which marks the beginning of the systolic plateau. During the interval between (1) and (2) the pressure is rising in the aorta also. During this interval the pressure in the ventricle, continuing to rise, becomes greater than that in the aorta, the curve of difference rises above the base line ; but the excess of pressure in the ventricle does not become very great, the curve of difference does not rise to any great height, because that very excess of pressure is used up in driving the contents of the ventricle into the aorta through the open semilunar valves. During this interval the pressure in the aorta continues to rise because, until the height of pressure at (2) is reached, the pressure is not yet sufficient to drive the blood on along the arterial system with adequate rapidity. With the point (2) the systolic plateau begins. During this plateau the exact course taken by the curve of ventricular pressure differs in different cases. We will take first the perhaps more ordinary case in which the curve with intermediate variations which we may at present pass over gradually declines until the point (3) is reached, when the plateau comes to an end by reason of the sudden fall of the ventricular pressure. There can be no doubt that the sudden fall after (3) is due to the sudden cessation of the contraction of the ventricular walls, to their sudden relaxation. But what is taking place during the systolic plateau before this point is reached ? It used to be argued, taking count of the distension only of the aorta as indicated by the sphygmograph, an instrument of which we shall speak later on, that the ventricular contents escape into the aorta during the period of the distension of the aorta and during this only, having ceased to flow by the time that this distension passes away giving place to a sequent shrinking of the aorta. Now when this period of distension is carefully measured it is found to be much shorter than the systole of the CHAP. iv. J THE VASCULAR MECHANISM. 207 ventricle, as measured by the length of the systolic plateau. Hence, it being further assumed that the whole of the contents of the ventricle were ejected at each systole, it was inferred that the ventricle remained empty and yet contracted for an appreciable period after the discharge of its contents. And this led, in turn, to a great divergence of opinion as to the exact time at which the semilunar valves were closed. But when we carefully explore the pressure in the aorta and in the ventricle at the same time, making use .of the differential manometer, we come upon facts which seem to disprove this view. Examining Fig. 52 we find that, while during the systolic plateau the pressure is falling in both aorta and ventricle, the curve of difference of pressure D remains above the base line, though not far above it and continually approaching it, up to the mark (3) at the very end of the plateau. At this point, however, at the end of the plateau, at the beginning of relaxation, a very great difference of pressure is established ; while the ventricular pressure falls suddenly and soon reaches or even passes the base line (becoming in the latter case negative, i.e. below that of the atmosphere), the pressure in the aorta undergoes relatively little change, — indeed, immediately afterwards receives an increase of which we shall have to speak later on as the dicrotic crest of the pulse wave ; and the curve of difference D falls with very great abruptness. The interpretation of this seems to be as follows. During the whole of the systolic plateau up to the mark (3) the semi- lunar valves are open, the cavity of the ventricle and the root of the aorta form a common cavity which is occupied by a continuous column of blood. Hence the curves of ventricular and aortic pressure, of the pressure at the one end and at the other end of this column, follow the same general course, and, indeed, shew the same secondary variations ; this general course is, in the case which we are studying, a -descending one by reason, as we have said, of the relatively free escape of blood from the arterial system through the peripheral resistance. But the column of blood in question is a column in motion, the ventricular pressure is driving the blood from the ventricle into the aorta ; to effect this the pressure in the ventricle must continue to be higher than that which it is itself generating in the aorta, the curve of difference must remain above the base line. And, since the curve of difference does remain above the base line right up to the mark (3), we may infer that up to this point blood does pass from the ventricle into the aorta. At (3), however, there is a sudden change. The systole suddenly ceases, and with that the curve of difference suddenly sinks below the base line ; the flow from ventricle ceases not because there is no more blood to come, but because the pressure in the ventricle now becomes lower than that in the aorta ; arid, indeed, the blood would flow back from the aorta to the region of lower pressure, to the ventricle, were it not that the very first effect 208 THE MECHANISM OF THE BEAT. [BOOK i. of the reflux is to close the semilunar valves. So soon as these are closed, the pressures in the ventricle and the aorta, which were previously following similar courses, now take separate courses; the latter falls suddenly, the former decreases gradually, and continues to decrease until the next systole once more opens the semilunar valves. We may add that this view is consistent with the conclu- sion mentioned in § 114, that not only the pulse-volume may vary, but also, at times at least, the whole contents are not driven out at the systole, some blood remaining behind. Moreover, the pressure does not always gradually decline during the systolic plateau ; sometimes it gradually rises during the whole of the period of the plateau, reaching its highest point just before the final sudden fall. This is shewn in Fig. 53. WWW^^ o 1 FIG. 53. CURVE OF AORTIC AND VENTRICULAR PRESSURE, WITH AN ASCENDING SYSTOLIC PLATEAU. HiJRTHLE. In this figure the general features are the same as in Fig. 52, save that the curve of ventricular pressure rises during the whole of the systolic plateau. But the curve of aortic pressure also rises in a corresponding manner, and the curve of difference, if shewn, would be the same as in Fig. 52. The explanation of the difference between the two cases is that in Fig. 52 the peripheral resistance in the arterial flow (§ 99) is not very great, and the ventricular systole soon overcomes it to such an extent as to lead at once to some fall of pressure in the aorta (and in the ventricle). In Fig. 53 the peripheral resistance is very great ; it is not overcome at first, the ventricle does its best working against it, and produces the most effect, raising the pressure to the highest point, just before its systole comes to an end. We may add that a similar course of the curve may be seen even when the pressure in the aorta is not very high, provided that the pulse-volume, the quantity discharged at the systole is very great; the form of the curve depends on the relative amounts which are entering the arterial system from the heart, and leaving it by the peripheral vessels. It is possible that under some circumstances the whole of the CHAP, iv.] THE VASCULAR MECHANISM. 209 contents may be discharged before the actual systole ends ; but the observations and arguments which we have just related, shew that such an event must be regarded as of exceptional, and not, as has been contended, of normal occurrence. Of the smaller secondary variations visible on the systolic plateau, conspicuous in some curves (4, 5, 6, 7 in Fig. 46), various explanations have been given. Into the discussion of these we cannot enter here ; we may however say that in many observations, which we may probably regard as correct, these secondary markings are identical in the curves of ventricular pressure, of aortic pressure and of the cardiac impulse, or of the change in the outward form of the heart ; the events which cause them tell in the same way on all three. ^ 0,1 0,2 0,3 0,4 0,5 0,6 0,7 08 Systole Diastole FIG 54. DIAGRAM OP VENTRICULAR AND AORTIC PRESSURE AND OF THE CARDIAC IMPULSE. HURTHLE. We give in Fig. 54 a diagram of the cardiac events according to the exposition which we have just made. The curves previously given were copies of actual curves obtained by experiment ; this is a constructed diagram. The upper curve is the curve of the cardiac impulse. The middle curve is the curve of pressure in the 210 NEGATIVE PKESSUKE. [BOOK i. left ventricle ; the unbroken line represents the course of the curve when, the peripheral resistance being small, the pressure needed to drive onward the blood is not very high, in the figure less than 150 mm. Hg. The dotted line represents the course of the curve when, the peripheral resistance being great, the pressure is high, in the figure nearly 200 mm. Hg. The lower curve is the curve of pressure at the root of the aorta, the unbroken and the dotted lines having the same significance as in the ventricular curve. The line 0 marks the commencement of the ventricular systole, the line 1 the opening of the semilunar valves, and 3 the end of the systole. The line 4 marks the beginning of what in dealing with the pulse, we shall speak of as the dicrotic wave. The semi- lunar valves are closed between 3 and 4 ; the closure is the result at 3 of the cessation of the systole and as we shall see the cause at 4 of the dicrotic wave of the pulse. The time is given in tenths of a second. § 117. In many curves, as in some of those given above, the pressure in the ventricle at the beginning of diastole falls not only to the base line, which is the line of atmospheric pressure, but even below it ; that is to say, becomes negative. Such a negative pressure may be shewn by means of a minimum manometer, that is, a mano- meter arranged so as to shew the lowest pressure which has been reached in a series of events. The mercury manometer, which as we FIG. 55. THE MAXIMUM MANOMETER or GOLTZ AND GAULE. At e a connection is made with the tube leading to the heart. When the screw clamp k is closed, the valve v conies into action, and the instrument, in the position of the valve shewn in the figure, is a maximum manometer. By reversing the direction of v it is converted into a minimum manometer. When Ic is opened, the variations of pressure are conveyed along a, and the instrument then acts like an ordinary manometer. CHAP, iv.] THE YASCULAK MECHANISM. 211 have said, is unsuitable for following the rapid changes constituting a single beat, may be used as a maximum or minimum instrument for determining the highest or lowest pressure reached in one or other of the heart's cavities during a series of beats. The principle of one form of maximum manometer, Fig. 55, consists in the introduction into the tube leading from the heart to the mercury column, of a (modified cup-and-ball) valve, opening, like the aortic semilunar valves, easily from the heart, but closing firmly when fluid attempts to return to the heart. The highest pressure is that which drives the longest column of fluid past the valve, raising the mercury column to a corresponding height. Since this column, once past the valve, cannot return, the mercury remains at the height to which it was raised by it, and thus records the maximum pressure. By reversing the direction of the valve, the manometer is converted from a maximum into a minimum instrument. A simpler form of maximum and minimum manometer is that of Hiirthle, which consists of a small chamber connected with two mano- meters, the opening of each manometer into the chamber being armed with a valve of thin membrane, so arranged that it permits in the case of one manometer, the maximum one, the entrance only of the mercury, in the case of the other, the minimum one, the exit only. By means of the maximum manometer the pressure in the left ventricle in the dog has been observed to reach a maximum of about 140 mm. (mercury), in the right ventricle of about 60 mm. and in the right auricle of about 20 mm. These figures, however, are given as examples, and not as averages. Simi- larly negative pressures of from — 50 mm. to — 20 in the left ventricle of the dog, of about — 15 mm. in the right ventricle, and of from — 12 mm. to — 7 mm. in the right auricle, have been observed by the minimum manometer. Part of this diminution of pressure in the cardiac cavities is due, as will be explained in a later part of this work, to the aspiration of the thorax in the respiratory movements. But even when the thorax is opened, and artificial respiration kept up, under which circumstances no such aspiration takes place, a negative pressure may be still observed, the pressure in the left ventricle sinking according to some obser- vations as low as — 24 mm. Now, what the instrument actually shews is that at some time or other during the number of beats which took place while the instrument was applied (and these may have been very few), the pressure in the ventricle sank so many mm. below that of the atmosphere. Since, however, the negative pressure may be observed when the heart is beating quite regularly, each beat being exactly like the others, we may infer that the negative pressure is repeated at some period or other of each cardiac cycle. The instrument itself gives us no information as to the exact phase of the beat in which the negative pressure occurs ; but it is clear from what we have already seen that when it occurs, it must take place at the end of the systole, at the beginning of the 212 DURATION OF CAEDIAC PHASES. [BOOK i. diastole. It is obvious, moreover, from what has gone before, that the semilunar valves are closed before it occurs, and we may dismiss the view which has been put forward that it is of the same nature as the negative pressure which makes its appearance behind a column of fluid moving rapidly and suddenly ceasing, as when a rapid flow of water through a tube is suddenly stopped by turning a tap. We may probably attribute it to the relaxation of the ventricular walls. This, as all the curves shew, is a rapid process, something quite distinct from the mere filling of the ventricular cavities with blood by the venous inflow; and, though some have objected to the view, it may be urged that this return of the ventricle from its contracted condition to its normal form would develop a negative pressure. This return we may probably regard as simply the total result of the return of each fibre to its natural condition, though some have urged that the extra quantity of blood thrown into the coronary arteries at the systole helps to unfold the ventricles somewhat in the way that fluid driven between the two walls of a double-walled collapsed ball or cup will unfold it. We may further conclude that such a negative pressure, when it occurs, will assist the circulation (and it may be remarked that the return of the thick-walled left ventricle naturally exerts a greater negative pressure than the thin-walled right ventricle) by sucking the blood which has meanwhile been accumulated in the auricle from that cavity into the ventricle, the auriculo-ventricular valves easily giving way. At the same time this very flow from the auricle will at once put an end to the negative pressure, which obviously can be of brief duration only. It should, however, be added that many observers find the development of a negative pressure to be by no means of such constant occurrence, and not to reach such marked limits as might be inferred from the numbers given above, at least in the unopened chest. If so it cannot be an important factor in the work of the circulation. § 118. The duration of the several phases. We may first of all distinguish certain main phases : (1) The systole of the auricles. (2) The systole, proper, of the ventricles, during which their fibres are in a state of contraction. (3) The diastole of the ventricles, that is to say, the time intervening between their fibres ceasing to contract, and commencing to contract again. To these we may add; (4) The pause or rest of the whole heart, comprising the period from the end of the relaxation of the ventricles to the beginning of the systole of the auricles ; during this time the walls are undergoing no active changes, neither contracting nor relaxing, their cavities being simply passively filled by the influx of blood. The mere inspection of almost any series of cardiac curves however taken, those, for instance, which we have just discussed, will shew, apart from any accurate measurements, that the systole CHAP, iv.] THE VASCULAR MECHANISM. 213 of the auricles is always very brief, that the systole of the ven- tricles is always very prolonged, always occupying a consider- able portion of the whole cycle, and that the diastole of the whole heart, reckoned from the end either of the systole, or of the relaxation of the ventricle, is very various, being in quickly beating hearts very short and in slowly beating hearts decidedly longer. When we desire to arrive at more complete measurements, we are obliged to make use of calculations based on various data ; and the value of some of these has been debated. Naturally the most interest is attached to the duration of events in the human heart. A datum which has been very largely used is the interval between the beginning of the first and the occurrence of the second sound. This may be determined with approximative correctness, and is found to vary from -301 to '327 sec., occupying from 40 to 46 p.c. of the whole period, and being fairly constant for different rates of heart beat. That is to say in a rapidly beating heart it is the pauses which are shortened and not the duration of the actual beats. The observer, listening to the sounds of the heart, makes a signal at each event on a recording surface, the difference in time between the marks being measured by means of the vibrations of a tuning-fork recorded on the same surface. By practice it is found possible to reduce the errors of observation within very small limits. Now whatever be the exact causation of the first sound, it is undoubt3dly coincident with the systole of the ventricles, though possibly the actual commencement of its becoming audible may be slightly behind the actual beginning of the muscular con- tractions. Similarly the occurrence of the second sound, which, as we have seen, is certainly due to the closure of the semilunar valves, may in accordance with the view expounded a little while back, be taken to mark the close of the ventricular systole. And on this view the interval between the beginning of the first and the occurrence of the second sound may be regarded as indicating approximatively the duration of the ventricular systole, i.e. the period during which the ventricular fibres are contracting. By an ingenious arrangement a microphone attached to a stethoscope may be made to record the heart sounds through the stimulation of a muscle-nerve preparation ; and the record so obtained may be compared with the various cardiac curves. When this is done, the first sound is found to begin somewhere on the systolic ascent of the ventricular curve, the exact point varying, and the second sound to occur just as the ventricular curve begins its diastolic descent. There has been however as we stated above great divergence of 214 DURATION OF CARDIAC PHASES. [BOOK i. opinion and much discussion as to the exact time of the closure of the semilunar valves ; the view given in the text above, though it seems to be supported by adequate arguments, is not the only one which is held. Accepting the view given in the text, we may make the following statement. In a heart beating 72 times a minute, which may be taken as the normal rate, each entire cardiac cycle would last about 0*8 sec., and taking 0'3 sec. as the duration of the ventricular systole, the deduction of this would leave O5 sec. for the whole diastole of the ventricle including its relaxation, the latter occupying less than -1 sec. At the end of the diastole of the ventricle there occurs the systole of the auricle, the exact duration of which it is difficult to determine, it being hard to say when it really begins, but which, if the contraction of the great veins be included, may perhaps be taken as lasting on an average 0*1 sec. The 'passive interval,' therefore, during which neither auricle nor ventricle is undergoing contraction, lasts about 4 sec., and the absolute pause or rest, during which neither auricle nor ventricle is contracting or relaxing, about '3 sec. The systole of the ventricle follows so immediately upon that of the auricle, that practically no interval exists between the two events. In the systole of the ventricle we may distinguish the phase during which pressure is being got up before the semilunar valves are opened ; this is exceedingly short, probably from "02 to '03 sec. During the rest of the -3 sec. of the systole, the contents of the ventricle are being pressed into the aorta. The duration of the several phases may for convenience sake be arranged in a tabular form as follows : sees. sees. Systole of ventricle before the open- ing of the semilunar valves, while ^ pressure is still getting up '03 Continued contraction of the ventricle, and Escape of blood into aorta •$ Total systole of the ventricle Diastole of both auricle and ventricle, neither contracting, or " passive in- terval " Systole of auricle (about or less than) Diastole of ventricle, including relaxa- tion and filling, up to the beginning of the ventricular systole *5 Total Cardiac Cycle -8 CHAP, iv.] THE VASCULAK MECHANISM. 215 Summary. § 119. We may now briefly recapitulate the main facts con- nected with the passage of blood through the heart. The right auricle during its diastole, by the relaxation of its muscular fibres, and by the fact that all backward pressure from the ventricle is prevented by the closing of the tricuspid valves, offers but little resistance to the ingress of blood from the veins. On the other hand, the blood in the trunks of both the superior and inferior vena cava is under a pressure, which, though diminishing towards the heart, remains higher than the pressure obtaining in the interior of the auricle ; the blood in consequence flows into the empty auricle, its progress in the case of the superior vena cava being assisted by gravity. At each inspiration this flow (as we shall see in speaking of respiration) is favoured by the diminution of pressure in the heart and great vessels caused by the respiratory movements. Before this flow has gone on very long, the diastole of the ventricle begins, its cavity dilates, the flaps of the tricuspid valve fall back, and blood for some little time flows in an un- broken stream from the venae cavaa into the ventricle. How far the entrance of blood from the auricle into the ventricle is, under ordinary circumstances, aided by the negative pressure in the ventricle following the close of the systole, must, as we have said, be left for the present uncertain. In a short time, probably before very much blood has had time to enter the ventricle, the auricle is full ; and forthwith its sharp, sudden systole takes place. Partly by reason of the backward pressure in the veins, which increases rapidly from the heart towards the capillaries, and which at some distance from the heart is assisted by the presence of valves in the venous trunks, but still more from the fact that the systole begins at the great veins themselves, and spreads thence over the auricle, the force of the auricular contraction is spent in driving the blood, not back into the veins, but into the ventricle, where the pressure is still exceedingly low. Whether there is any backward flow at all into the great veins, or whether by the progressive character of the systole, the flow of blood continues, so to speak, to follow up the systole without break, so that the stream from the veins into the auricle is really continuous, is at present doubtful ; though a slight positive wave of pressure synchronous with the auricular. systole, travelling backward along the great veins, has been observed at least in cases where the heart is beating vigorously. The ventricle thus being filled by the auricular systole, the play of the tricuspid valves described above comes into action, the auricular systole is followed by that of the ventricle, and the pressure within the ventricle, cut off from the auricle by the tricuspid valves, is brought to bear on the pulmonary semilunar valves, and the column of blood on the other side of those valves. 216 SUMMAEY OF HEAET BEAT. [BOOK i. As soon as by the rapidly increasing shortening of the ventricular fibres the pressure within the ventricle becomes greater than that in the pulmonary artery, the semilunar valves open, and the still continuing systole discharges the contents of the ventricle into that vessel. During the whole of this time the left side has with still greater energy been executing the same manoeuvre. At the same time that the venae cavae are tilling the right auricle, the pulmonary veins are tilling the left auricle. At the same time that the right auricle is contracting, the left auricle is contracting too. The systole of the left ventricle is synchronous with that of the right ventricle, but executed with greater force ; arid the flow of blood is guided on the left side by the mitral and aortic valves in the same way that it is on the right by the tricuspid valves and the valves of the pulmonary artery. As the ventricles become filled with blood, and so increased in volume, the apex begins to press steadily on the chest-wall, as may be often seen in the cardiogram, the curve of the cardiac impulse. The fuller distension due to the auricular systole is more obvious in the same curve ; but both these changes are insignificant compared to the effect of the change of form, and of the position of the apex during the ventricular systole, by which the lever of the cardiograph is rapidly and forcibly moved. With this systole of the ventricles the first sound is heard. We may more conveniently follow the remaining events in the left ventricle. The effect of the discharge of the contents of the left ventricle is to raise the pressure at the root of the aorta to nearly the same height as that in the ventricle itself. The ventricular pressure continues for some time, giving rise to the " systolic plateau " of the various cardiac curves. In some cases this pressure soon reaches a maximum, after which it gradually declines, the curve of pressure sloping,, with some secondary undulations, gently down- wards. In other cases where there is great resistance to the outflow along the arterial system, the pressure may continue to rise during the whole of the ventricular systole. In both cases the curves of the ventricular pressure and of the aortic pressure are similar. Then comes the sudden cessation of contraction, the sudden relaxation of the ventricular fibres. The pressure in the ventricle becomes less than that which it itself has generated in the aorta, and the semilunar valves suddenly close as the blood flows back from the region of high pressure, the aorta, towards the region of low pressure, the ventricle. At this moment the second sound is heard. Owing to the semilunar valves being closed, the pressures in the ventricle and in the aorta, which before were following the CHAP, iv.] THE VASCULAR MECHANISM. 217 same course, now become different. While the pressure sinks rapidly in the ventricle, falling it may be below that of the atmos- sphere, and thus becoming a negative pressure, which in some cases may possibly be considerable, that in the aorta does not sink to a corresponding degree ; in fact, as we shall see, it is reinforced to a certain extent in a secondary rise, the so-called dicrotic rise. We have reason to believe not only that the quantity of blood ejected at the systole may vary from time to time, but also that at times at all events if not normally, the whole of the blood present in the ventricle at the systole may fail to leave the ventricle during the systole, more or less remaining behind at the close ; the ventricle in such cases does not completely empty itself. On the other hand, we may perhaps admit that, at least under cer- tain circumstances, when, for instance, the contents of the ventricle are small, and the ventricle vigorous or the systole prolonged, the whole of the contents may be discharged in the earlier part of the systole, the ventricle remaining contracted for some little time after it has emptied itself. The Work done. § 120. We have already (§ 114) spoken of that most important factor in the determination of the work of the heart, the pulse- volume, or the quantity ejected from the ventricle into the aorta at each systole, and of the various methods by which it may be estimated. We have seen that it probably varies within very considerable limits. We may here repeat the remark that exactly the same quantity must issue at a beat from each ventricle ; for if the right ventricle at each beat gave out rather less than the left, after a certain number of beats the whole of the blood would be gathered in the systemic circulation. Similarly, if the left ventricle gave out less than the right, all the blood would soon be crowded into the lungs. The fact that the pressure in the right ventricle is so much less than that in the left (probably 30 or 40 mm. as compared with 200 mm. of mercury), is due, not to differences in the quantity of blood in the cavities, but to the fact that the peripheral resistance which has to be overcome in the lungs is so much less than that in the rest of the body. Not only does the amount ejected vary, but the pressure under which it is ejected also varies within very considerable limits. Moreover, the number of times the systole is repeated within a given period may also vary considerably. The work done, therefore, varies very much. But it may be interesting and instructive to note the results of calculating out a very high estimate. Thus if we take 180 grms. as the quantity, in man, ejected at each stroke at a pressure of 250 mm. of mercury, which is 218 THE WORK DONE. [BOOK i. equivalent to 3*21 meters of blood, this means that the left ventricle is capable at its systole of lifting 180 grins. 3*21 m. high, i. e. it does 578 gram-meters of work at each beat. Supposing the heart to beat 72 times a minute, this would give for the day's work of the left ventricle nearly 60;000 kilogram-meters. Calcu- lating the work of the right ventricle at one-fourth that of the left, the work of the whole heart during the day would amount to 75,000 kilogram-meters, which is just about the amount of work done in the ascent of Snowdon by a tolerably heavy man. SEC. 4. THE PULSE. § 121. We have seen that the arteries, though always dis- tended, undergo, each time that the systole of the ventricle drives the contents of the ventricle into the aorta, a temporary additional expansion so that when the finger is placed on an artery, such as the radial, an intermittent pressure on the finger, coming and going with the beat of the heart, is felt, and when a light lever is placed on the artery, the lever is raised at each beat, falling between. This intermittent expansion, which we call the pulse, cor- responding to the jerking outflow of blood from a severed artery, is present in the arteries only, being, except under particular circumstances, absent from the veins and capillaries. The expan- sion is frequently visible to the eye, and in some cases, as where an artery has a bend, may cause a certain amount of locomotion of the vessel. We may, by applying various instruments to the interior of an artery, study the temporary increase of pressure which is the cause of the temporary increase of expansion. This makes itself felt, as we have seen, in the curve of arterial pressure taken by the mercury manometer ; but the inertia of the mercury prevents the special characters of each increase becoming visible. In order to obtain an adequate record of these special characters we must have recourse to other instruments. The membrane-manometer, of which we have already spoken (§ 113), and on the results gained by which when applied to the root of the aorta by means of a catheter we have dwelt (§ 116), may also be applied to other arteries, the tube leading to the tambour of the manometer being connected with the artery by means of a cannula in the ordinary way. In Fick's spring-manometer, in its original form, Fig. 56, the artery is connected by means of a cannula and a rigid tube containing fluid with the interior of a curved spring ; an increase of pressure unfolds the curve of the spring, the movements of the end of which may be recorded by means of a lever. In Fick's improved form the membrane of a small air-tambour works against a horizontal slip of steel which acts as a spring; this instrument, like Frey and Erehl's manometer 220 METHODS OF KECOKDING PULSE. [BOOK i. which is only a modification of it (see § 113), can be applied to an artery by a cannula in the ordinary way. The " sphygmoscope " consists of a small elastic bag, the end of an india rubber finger, for instance, fitted on to a conical cork, through which passes a tube opening . into the bag, and connected by a cannula with the artery ; both bag and tube are, before being connected with the artery, filled with fluid of a nature to hinder clotting. The bag, by means of the conical cork, is firmly fitted into the end of a small glass tube, the cavity of which filled with air is connected with a recording air tambour. The changes of pressure within the artery are transmitted to the elastic bag, and through this to the air of the glass tube and so to the recording tambour. , The tambour-sphygmoscope of Hurthle is a combination of the membrane-manometer with a tambour. The membrane of the manometer works not directly on a lever, but on a recording air tambour, the move- ments of which are recorded in the usual way. In the sphygmotonometer of Roy, the artery is, by means of a cannula, and rigid tube filled with fluid, connected with a cylinder in which a light piston works by means of a delicate membrane. FIG. 56. FICK'S SPRING MANOMETER. The flattened tube in the form of a hoop is firmly fixed at one end, while the other free end is attached to a lever. The interior of the tube, filled with spirit, is brought, by means of a tube containing sodium carbonate solution, into connection with an artery, in much the same way as in the case of the mercury manometer. The increase of pressure in the artery being transmitted to the hollow hoop, tends to straighten it, and correspondingly moves the attached lever. CHAP, iv.] THE VASCULAB MECHANISM. 221 And there are still other instruments which may be used in a similar way. It is not necessary, however, to open the artery ; we may study indirectly the changes of pressure by recording the expansions and retractions of the artery, the changes in its diameter, which are produced by the changes of pressure. The most common method of registering the expansion of an artery and at the same time one of the simplest, is that of bringing a light lever to bear on the outside of the artery. A lever specially adapted to record a pulse tracing is called a sphygniograph, the instrument generally comprising a small travelling recording surface on which the lever writes. There are many different forms of sphygmograph, but the general plan of structure is the same. Fig. 57 represents in a diagrammatic form the essential parts of the sphygmograph known as Dudgeon's, which we have chosen for repre- sentation, not because it is best, but because it is one very largely employed in medical practice. The instrument is generally applied to the radial artery because the arm affords a convenient support to the fulcrum of the lever, and because the position of the artery, near to the FIG. 57. DIAGRAM OP A SPHYGMOGRAPH (Dudgeon's). Certain supporting parts are omitted so that the multiplying levers may be displayed. a is a small metal plate which is kept pressed on the artery by the spring b. The vertical movements of a cause to-and-fro movements of the lever c about the fixed point d. These are communicated to and magnified by the lever e, which moves round the fixed point f. The free end of this lever carries a light steel marker which rests on a strip of smoked paper g. The paper is placed beneath two small wheels, and rests on a roller which can be rotated by means of clock-work contained in the box h. The paper is thus caused to travel at a uniform rate. The screw graduated in ounces Troy is brought to bear on the spring b by means of a camm, and by this the pressure put on the artery can be regulated. The levers magnify the pulse movements fifty times. 222 METHODS OF KECORDING PULSE. [BOOK i. surface and with the support of the radius below so that adequate pressure can be brought to bear by the lever on the artery, is favour- able for making observations. It can, of course, be applied to other arteries. The membrane-manometer of Hiirthle may also be applied directly to an unopened artery. The cannula is replaced by a small funnel, the mouth of which is covered by membrane bearing at its centre a small block of cork. If the cork be pressed lightly on an artery, the expansions of the artery move the membrane of the funnel, and the movements of this are transmitted along the fluid of a rigid tube to the recording tambour. A pulse tracing may also be indirectly obtained by the plethysmo- graphic method. If the arm be introduced into a plethysmograph (§ 104), a tracing may be obtained of the rhythmic expansions of the arm, that is, of the rhythmic expansions of the arteries of the arm, due to the heart beats. If the plethysmograph chamber be filled with air instead of fluid, the changes of pressure in the chamber may be brought to bear on a sensitive flame, the changes of which in turn may be photographed. If the artery be laid bare, other methods may be adopted. In some cases, in that of the aorta, for instance, it is sufficient to attach a light hook into the outer coat of the artery, and to connect the hook by means of a thread with a carefully balanced lever. The movements of the coat of the artery are then recorded by the lever. The sphygmotonometer of Roy may also be used without opening the artery. For this purpose a length of the artery is enclosed in a tube with rigid walls, filled with fluid, which acts as a plethysmograph, the movements of the fluid around the artery being recorded by means of a piston working a lever. If the artery be ligatured and divided, one end may be drawn into the tube for the distance required. The tube may also be made of two halves, one of which is slipped under the artery simply laid bare, the other placed above it, and the two halves are brought together round the artery, the two ends of the tube bein# closed with membrane. And still other methods may be employed. The several tracings obtained by these several methods differ of course in minor features, but they agree in general features ; and from a comparative study of the results obtained by di fie rent methods we are able, in many cases at all events, to form conclu- sions as to which of the minor features of a curve are due to the in- strument itself, and which represent events actually taking place in the artery. On the whole, the curve obtained by directly record- ing the pressure within the artery is concordant with that obtained by recording the expansions of the artery ; the curve obtained by the manometer or by the sphygmoscope very closely resembles that obtained by the sphygmograph, and the more completely the incidental errors of each instrument are avoided, the more closely do the two curves agree. We may accordingly in treating of the pulse confine ourselves largely to the results obtained by the sphyg- mograph. Any of the various instruments applied to the radial CHAP, iv.] THE VASCULAR MECHANISM. 223 artery would give some such tracing as that shewn in Fig. 58 which is obtained by means of the sphygrnograph. At each heart beat the FIG. 58. PULSE TRACING FROM THE RADIAL ARTERY OF MAN. The vertical curved line, L, gives the tracing which the recording lever made when the blackened paper was motionless. The curved interrupted lines shew the distance from one another in time of the chief phases of the pulse-wave, viz. x = commencement, and A end of expansion of artery, p, predicrotic notch, d, di- crotic notch. C, dicrotic crest. D, post-dicrotic crest, ft the post-dicrotic notch. These terms are explained in the text later on. curve rises rapidly, and then falls more gradually in a line which is more or less uneven. § 122. We have now to study the nature and characters of the pulse in greater detail. We may say at once, and, indeed, have already incidentally seen, that the pulse is essentially due to physical causes ; it is the physical result of the sudden injection of the contents of the ventricle into the elastic tubes called arteries. Its features depend on the one hand on the systole of the ventricle, on the quantity of blood which is thereby discharged into the aorta, and on the manner in which it is discharged, and on the other hand on the elasticity of the arterial walls. The more important of these features may be explained on physical principles, and may be illustrated by means of an artificial model, so far at least as we can imitate the action of the heart. We may confine ourselves, in the first instance, to the simple expansion of the arterial tube and its return to its previous condition, neglecting for the present all secondary events. If two levers be placed on the arterial tubes of an artificial model Fig. 30, S. a., S'. a., one near to the pump, and the other near to the peripheral resistance, with a considerable length of tubing between them, and both levers be made to write on a recording surface, one immediately below the other, so that their curves can be more easily compared, the following facts may be observed, when the pump is set to work regularly. They are 224 ARTIFICIAL PULSE. [BOOK i. perhaps still better seen if a number of levers be similarly arranged at different distances from the pump as in Fig. 59. 6ov\/V\AAAAAAAAAAAAA/ FIG. 59. Pulse-curves described by a series of sphygmographic levers placed at intervals of 20 cm. from each other along an elastic tube, into which fluid is forced by the sudden stroke of a pump. The pulse-wave is travelling from left to right, as indicated by the arrows over the primary (a) and secondary (b, c) pulse-waves. The dotted vertical lines drawn from the summit of the several primary waves to the tuning-fork curve below, each complete vibration of which occupies -^ sec., allow the time to be measured which is taken up by the wave in passing along 20 cm. of the tubing. The waves a' are waves reflected from the closed distal end of the tubing ; this is indicated by the direction of the arrows. It will be observed that in the more distant lever VI. the reflected wave, having but a slight distance to travel, becomes fused with the primary wave. (From Marey.) At each stroke of the pump, each lever rises until it reaches a maximum (Fig. 59, la, 2a, &c.), and then falls again, thus describing a curve. The rise is due to the expansion of the part of the tube under the lever, and the fall is due to that part of the CHAP, iv.] THE VASCULAR MECHANISM. 225 tube returning after the expansion to its previous calibre. The curve is therefore the curve of the expansion (and return) of the tube at the point on which the lever rests. We may call it the pulse-curve. It is obvious that the expansion passes by the lever in the form of a wave. At one moment the lever is at rest: the tube beneath it is simply distended to the normal amount indicative of the mean pressure which at the time obtains in the arterial tubes of the model ; at the next moment the pulse expan- sion reaches the lever, and the lever begins to rise ; it continues to rise until the top of the wave reaches it, after which it falls again until finally it comes to rest, the wave having completely passed by. It may perhaps be as well at once to warn the reader that the figure which we call the pulse-curve is not a representation of the pulse-wave itself ; it is simply a representation of the movements, up and down, of the piece of the wall of the tubing at the spot on which the lever rests during the time that the wave is passing over that spot. We may roughly represent the wave by the diagram Fig. 60, in which the wave shewn by the dotted line is FlG. 60. A ROUGH DIAGRAMMATIC REPRESENTATION OF A PULSE-WAVE PASSING OVER AN ARTERY. passing over the tubs (shewn in a condition of rest by the thick double line) in the direction from H to 0. It must, however, be remembered that the wave thus figured is a much shorter wave than is the pulse-wave in reality (that being, as we shall see, about 6 meters long), i.e. occupies a smaller length of the arterial system from the heart H towards the capillaries C. Moreover, the actual pulse-wave has secondary features, which we are neglecting for the present, and which, therefore, we do not attempt to shew in the figure. The curves below, X, Y, Z, represent, in a similarly diagram- matic fashion, the curves described, during the passage of the wave, 15 226 ARTIFICIAL PULSE. [BOOK i. by levers placed on the points x, y, z. At Z the greater part of the wave has already passed under the lever, which, during its passage, has already described the greater part of its curve, shewn by the thick line, and has only now to describe the small part, shewn by the dotted line, corresponding to the remainder of the wave from Z to H. At Kthe lever is at the summit of the wave. At X the lever has only described a small part of the beginning of the wave, viz. from C to x, the rest of the curve, as shewn by the dotted line, having yet to be described. But to return to the consideration of Fig. 59. § 123. The rise of each lever is somewhat sudden, but the fall is more gradual, and is generally marked with some irregularities which we shall study presently. The rise is sudden because the sharp stroke of the pump suddenly drives a quantity of fluid into the tubing, and so suddenly expands the tube ; the fall is more gradual because the elastic reaction of the walls of the tube, which, after the expanding power of the pump has ceased, brings about the return of the tube to its former calibre driving the fluid onwards to the periphery, is more gradual in its action. These features, the suddenness of the rise or up-stroke, and the more gradual slope of the fall or down-stroke, are seen also in natural pulse-curves taken from living arteries (Figs. 58, 61 &c.). We shall see, however, that under certain circumstances this contrast between the up-stroke and the down-stroke is not so marked. It may here be noted that the actual size of the curve, that is the amount of excursion of the lever, depends in part (as does also to a great extent the form of the curve) on the amount of pressure exerted by the lever on the tube. If the lever only just touches the tube in its expanded state, the rise will be insignificant. If, on the other hand, the lever be pressed down too firmly, the tube beneath will not be able to expand as it otherwise would, and the rise of the lever will be proportionately dimin- ished. There is a certain pressure which must be exerted by the lever on the tube, the exact amount depending on the expansive power of the tubing, and on the pressure exerted by the fluid in the tube, order that the tracing may be A9 P P ABC FIG. 61. PULSE TRACINGS FROM THE SAME RADIAL ARTERY UNDEK DIF- FERENT PRESSURES OF THE LEVER. in The letters are explained in a later part of the text. Takeii with Dudgeon's sphygmograph. best marked. This is shewn in Fig. 61, in which are given three tracings taken from the same CHAP, iv.] THE VASCULAR MECHANISM. 227 radial artery with the same instrument ; in the lower curve the pressure of the lever is too great, in the upper curve too small, to bring out the proper characters of the pulse ; these are seen more distinctly in the middle curve with a medium pressure. § 124. It will be observed that in Fig. 59, curve I., which is nearer the pump, rises more rapidly and rises higher than curve II., which is farther away from the pump ; that is to say, at the lever farther away from the pump the expansion is less and takes place more slowly than at the lever nearer the pump. Similarly in curve IV. the rise is still less, and takes place still less rapidly than in II., and the same change is seen still more marked in V. as compared with IV. In fact if a number of levers were placed at equal distances along the arterial tubing of the model, and the model were working properly, with an adequate peripheral resist- ance, we might trace out step by step how the expansion, as it travelled along the tube, got less and less in amount, and at the same time became more gradual in its development, the curve becoming lower and more flattened out, until, in the neighbourhood of the artificial capillaries, there was hardly any trace of it left. In other words, we might trace out step by step the gradual disappearance of the pulse. The same changes, the same gradual lowering and flattening of the curve, may be seen in natural pulse tracings ; compare, for instance, Fig. 62, which is a trac- ing from the dorsalis pedis artery, with the tracing from the radial artery Fig. 61, taken from the same individual with the same instrument on the same occasion. This feature is, of course, not ob- F«>- 62. PULSE TRACING FROM DOR- vinnci in all rml«p riirvpsj takpn SALIS PEDIS TAKEN FROM THE SAME yious in ail pulse-curves taKen 1NDIVIDUAL AS FlG. 6i. from different individuals with different instruments and under varied circumstances ; but if a series of curves from different arteries were carefully taken under the same conditions, it would be found that the aortic tracing is higher and more sudden than the carotid tracing, which again is higher and more sudden than the radial tracing, the tibial tracing being in turn still lower and more flattened. The pulse-curve dies out by becoming lower and lower, and more and more flattened out. And a little consideration will shew us that this must be so. The systole of the ventricle drives a quantity of blood into the already full aorta. The sudden injection of this quantity of blood expands the portion of the aorta next to the heart, the part immediately adjacent to the semilunar valves beginning to expand first, and the expansion travelling thence on to the end of this portion. In the same way the expansion travels on from this portion through all the succeeding portions of the arterial system. 228 DISAPPEARANCE OF PULSE. [BOOK i. For the total expansion required to make room foi the new quantity of blood is not provided by that portion alone of the aorta into which the blood is actually received ; it is supplied by the whole arterial system : the old quantity of blood which is replaced by the new in this first portion has to find room for itself ill the rest of the arterial space. As the expansion travels onward, however, the increase of pressure, which each portion transmits to the succeeding portion, will be less than that which it received from the preceding portion. For the whole increase of pressure due to the systole of the ventricle has to be distributed over the whole of the arterial system ; the general mean arterial pressure is, as we have seen, maintained by repeated systoles, and any one systole has to make its contribution to that mean pressure ; the increase of pressure which starts from the ventricle must there- fore leave behind at each stage of its progress a fraction of itself ; that is to say, the expansion is continually growing less, as the pulse travels from the heart to the capillaries. Moreover, while the expansion of the aorta next to the heart is, so to speak, the direct effect of the systole of the ventricle, the expansion of the more distant artery is the effect of the systole transmitted by the help of the elastic reaction of the arterial tract between the heart and the distant artery ; and since this elastic reaction is slower in development than the actual systole, the expansion of the more distant artery is slower than that of the aorta, the up-stroke of the pulse-curve is less sudden, and the whole pulse-curve is more flattened. The object of the systole is to supply a contribution to the mean pressure, and the pulse is an oscillation above and below that mean pressure, an oscillation which diminishes from the heart onwards, being damped by the elastic walls of the arteries, and so, little by little, converted into mean pressure until in the capillaries the mean pressure alone remains, the oscillations having dis- appeared. § 125. If in the model the points of the two levers at different distances from the pump be placed exactly one under the other on the recording surface, it is obvious that, the levers being alike except for their position on the tube, any difference in time between the movements of the two levers will be shewn by an interval between the beginnings of the curves they describe, the recording surface being made to travel sufficiently rapidly. If the movements of the two levers be thus compared, it will be seen that the far lever (Fig. 59, II.) commences later than the near one (Fig. 59, I.) ; the farther apart the two levers are, the greater is the interval in time between their curves. Compare the series I. to VI. (Fig. 59). In the same way it would be found that the rise of the near lever began some fraction of a second after the stroke of the pump. This means that the wave of expansion, the pulse-wave, takes some time to travel along the tube. CHAP, iv.] THE VASCULAR MECHANISM. 229 The velocity with which the pulse-wave travels depends chiefly on the amount of rigidity possessed by the tubing. The more extensible (with corresponding elastic reaction) the tube, the slower is the wave ; the more rigid the tube becomes, the faster the wave travels ; in a perfectly rigid tube, what in the elastic tube would be the pulse, becomes a mere shock travelling with very great rapidity. The width of the tube is of much less influence, though according to some observers the wave travels more slowly in the wider tubes. The rate at which the normal pulse-wave travels in the human body has been variously estimated at from 10 to 5 meters per second. In all probability we may take 6 meters as an average rate ; but it must be remembered that the rate may vary very considerably under different conditions. According to all observers the velocity of the wave in passing from the groin to the foot is greater than that in passing from the axilla to the wrist (6 m. against 5 m.). This is probably due to the fact that the femoral artery with its branches is more rigid than the axillary and its branches. So, also, the wave travels more slowly in the arteries of children than in the more rigid arteries of the adult. The velocity is also increased by circumstances which heighten, and decreased by those which lower the mean arterial pressure, since with increasing pressure the arterial walls become more, and with diminishing pressure less rigid. Probably also the velocity of the pulse-wave depends on conditions of the arterial walls, which we cannot adequately describe as mere differences in rigidity. In experimenting with artificial tubes it is found that different qualities of india rubber give rise to very different results. Care must be taken not to confound the progress of the pulse- wave, i.e. of the expansion of the arterial walls, with the actual onward movement of the blood itself. The pulse-wave travels over the moving blood somewhat as a rapidly moving natural wave travels along a sluggishly flowing river. Thus while the velocity of the pulse-wave is 6 or possibly even 10 meters per sec., that of the current of blood is not more than half a meter per sec., even in the large arteries, and is still less in the smaller ones. § 126. Referring again to the caution given above, not to regard the pulse-curve as a picture of the pulse-wave, we may now add that the pulse- wave is of very considerable length. If we know how long it takes for the pulse-wave to pass over any point in the arteries and how fast it is travelling, we can easily calculate the length of the wave. In an ordinary pulse-curve the artery, owing to the slow return, is seen not to regain the calibre which it had before the expansion, until just as the next expansion begins, that is to say, the pulse-wave takes the whole time of a cardiac cycle, viz. •^ths sec., to pass by the lever. Taking the velocity of the pulse- wave as 6 meters per sec., the length of the wave will be -j^ths of 6 m., that is, nearly 5 meters, And even if we took a smaller 230 VELOCITY OF PULSE WAVE. [BOOK i. estimate, by supposing that the real expansion and return of the artery at any point took much less time, say yftth sec., the length of the pulse-wave would still be more than 2 meters. But even in the tallest man the capillaries farthest from the heart, those in the tips of the toes, are not 2 m. distant from the heart. In other words, the length of the pulse-wave is much greater than the whole length of the arterial system, so that the beginning of each wave has become lost in the small arteries and capillaries some time before the end of it has finally passed away from the beginning of the aorta. We must now return to the consideration of certain special features in the pulse, which, from the indications they give or suggest of the condition of the vascular system, are often of great interest. § 127. Secondary waves. In nearly all pulse tracings, the curve of the expansion and recoil of the artery is broken by two, three, or several smaller elevations and depressions : secondary waves are jmposed upon the fundamental or primary wave. In the sphygmographic tracing from the carotid, Fig. 63, and in many of the other tracings given, these secondary elevations are marked FIG. 63. PULSE TRACING FROM CAROTID ARTERY OF HEALTHY MAN (Moens). x, commencement of expansion of the artery. A, summit of the first rise. C, dicrotic secondary wave. B, predicrotic secondary wave ; p, notch preceding this. D, succeeding secondary wave. The curve above is that of a tuning-fork with ten double vibrations in a second. as B, C, D. When one such secondary elevation only is conspic- uous, so that the pulse-curve presents two notable crests only, the primary crest and a secondary one, the pulse is said to be " dicrotic " ; when two secondary crests are prominent, the pulse is often called " tricrotic " ; when several, " poly erotic." As a general rule, the secondary elevations appear only on the descending limb of the primary wave as in most of the curves given, and the curve is then spoken of as " katacrotic." Sometimes, however, the first elevation or crest is not the highest, but appears on the ascending portion of the main curve : such a curve is spoken of as " anacrotic " Fig. 64. As we have already seen (§ 116) the curve of pressure at the root of the aorta, and, indeed, that of endocardiac pressure may be in like manner " anacrotic " (Figs. 53, 54). CHAP, iv.] THE VASCULAK MECHANISM. 231 Of these secondary elevations, the most frequent, conspicuous, and important is the one which appears some way down on the descending limb, and is marked C on Fig. 63 and on most of the curves here given. It is more or less distinctly visible on all sphygmograms, and may be seen in those of the aorta as well as of other arteries. Sometimes it is so slight as to be hardly discernible ; at other times it may be so marked as to give rise to a really double pulse (Fig. 65), i.e. a pulse which can be felt as double by the finger : hence it has been called the dicrotic elevation or the dicrotic wave, the notch preceding the elevation being spoken of as the " dicrotic notch." \J FIG. 64. ANACROTIC SPHYG- MOGRAPH TRACING FROM THE ASCENDING AORTA (Aneurism). FlG. 65. TWO GRADES OP MARKED DICROTISM IN RADIAL PULSE OF MAN. (Typhoid Fever.) Neither it nor any other secondary elevations can be recognized in the tracings of blood pressure taken with a mercury manometer. This may be explained, as we have said § 121, by the fact that the movements of the mercury column are too sluggish to repro- duce these finer variations. Moreover, when the normal pulse is felt by the finger, most persons find themselves unable to detect any dicrotism. But that it does really exist in the normal pulse is shewn by the fact that it appears, sometimes to a marked extent, sometimes to a less extent, not only in sphygmograms and in curves of arterial pressure taken by adequate instruments, but also and in a most unmistakeable manner in the tracing obtained by allowing the blood to spirt directly from an opened small artery, such as the dorsalis pedis, upon a recording surface. Less constant and conspicuous than the dicrotic wave, but yet appearing in most sphygmograms, is an elevation which appears higher up on the descending limb of the main wave ; it is marked B in Fig. 63, and on several of the other curves, and is frequently called the predicrotic wave ; it may become very prominent. Some- times other secondary waves, often called ' post-dicrotic,' are seen following the dicrotic wave, as at D in Fig. 63, and some other curves ; but these are not often present, and usually even when present inconspicuous. When tracings are taken from several arteries, or from the same artery under different conditions of the body, these secondary waves are found to vary very considerably, giving rise to many 232 THE DICROTIC WAVE. [BOOK i. characteristic forms of pulse-curve. Were we able with certainty to trace back the several features of the curves to their respective causes, an adequate examination of sphygmographic tracings would undoubtedly disclose much valuable information concerning the condition of the body presenting them. The problems, how- ever, of the origin of these secondary waves and of their variations are complex and difficult ; so much so that the detailed interpre- tation of a sphygmographic tracing is still in many cases and in many respects very uncertain. § 128. The Dicrotic Wave. The chief interest attaches to the nature and meaning of the dicrotic wave. In general the main conditions favouring the dicrotic wave are (1) a highly extensible and elastic arterial wall ; (2) a comparatively low mean pressure, leaving the extensible and elastic reaction of the arterial wall free scope to act; and (3) a vigorous and rapid stroke of the ventricle, discharging into the aorta a considerable quantity of blood. The origin of this dicrotic wave has been and indeed still is much disputed. In the first place, observers are not agreed as to the part of the arterial system in which it first makes its appearance. In such a system as that of the arteries we have to deal with two kinds of waves. There are the waves which are generated at the pump, the heart, and travel thence onwards towards the periphery ; the primary pulse-wave due to the discharge of the contents of the ventricle is of this kind. But there may be other waves which, started somewhere in the periphery, travel backwards towards the central pump ; such are what are called ' reflected ' waves. For instance, when the tube of the artificial model, bear- ing two levers, is blocked just beyond the far lever, the primary wave is seen to be accompanied by a second wave, which at the far lever is seen close to, and often fused into, the primary wave (Fig. 59, VI. a'), but at the near lever is at some distance from it (Fig. 59, I. ft'), being the farther from it the longer the interval between the lever and the block in the tube. The second wave is evidently the primary wave reflected at the block and travelling backwards towards the pump. It thus, of course, passes the far lever before the near one. And it has been argued that the dicrotic wave of the pulse is really such a reflected wave, started either at the minute arteries and capillaries, or at the several points of bifurcation of the arteries, and travelling backwards to the aorta. But if this were the case the distance between the primary crest and the dicrotic crest ought to be less in arteries more distant from, than in those nearer to the heart, just as in the artificial scheme the reflected wave is fused with a primary wave near the block (Fig. 59, VI. 6 a. a'), but becomes more and more separated from it the farther back towards the pump we trace it (Fig. 59, I. 1. a. a'). Now this is not the case with the dicrotic CHAP, iv.] THE VASCULAR MECHANISM. 233 wave ; careful measurements shew that the distance between the primary and dicrotic crests is either the same or certainly not less in the smaller or more distant arteries than in the larger or nearer ones. This feature indeed proves that the dicrotic wave cannot be due to reflection at the periphery or indeed in any way a retrograde wave. Besides the multitudinous peripheral division would probably render one large peripherically reflected wave im- possible. Again, the more rapidly the primary wave is oblite- rated or at least diminished on its way to the periphery the less conspicuous should be the dicrotic wave. Hence increased ex- tensibility and increased elastic reaction of the arterial walls which tend to use up rapidly the primary wave, should also lessen the dicrotic wave. But as a matter of fact these conditions, as we have said, are favourable to the prominence of the dicrotic wave. We may conclude then that the dicrotic wave like the primary wave begins at the heart, and travels thence towards the periphery. But even if this be admitted observers are not agreed as to the mechanism of its production. The following view is the one which seems the most satisfactory, though it is not accepted by all inquirers. The simultaneous curves of endocardiac and aortic pressure (Fig. 54 and others) shew us that the dicrotic notch as it is called, the depression immediately preceding the dicrotic wave is, in a normal beat, coincident with the end of the systole. The curve of the differential manometer further shews us that this is the point at which the pressure in the ventricle begins to become less than in the aorta. We may therefore reason in the following way. The flow from the ventricle into the aorta ceases because the systole ceases ; the cessation takes place while the two cavi- ties are still open to each other, and probably, in most cases at least, while there is still more or less blood in the ventricle. The pressure in the ventricle tends to become less than that in the aorta, and the blood in the aorta tends to flow back into the ventricle. But the first effect of this is to close firmly the semilunar valves. The expansion of the aorta, (which in many cases had been lessen- ing even during the systole owing to the flow through the periphery of the arterial system being more rapid than the flow from the ventricle, but in some cases, in the anacrotic instances, had not,) lessens with the cessation of the flow ; the aorta shrinks, press- ing upon its contents. But part of this pressure is spent on the closed semilunar valves, and the resistance offered by these starts a new wave of expansion, the dicrotic wave, which travels thence onwards towards the periphery in the wake of the primary wave. If we admit that the blood is flowing from the ventricle during the whole of the systole, we must also admit that the semilunar valves do not close until the end of the systole, and this being, as shewn by the curves, just antecedent to the dicrotic wave, we may attribute this wave to the rebound from the closed valves. It is 234 THE DICROTIC WAVE. [BOOK i. not necessary that the valves should act perfectly, and the dicrotic wave may occur in cases where the valves are more or less in- competent ; all that is required for its production is an adequate obstacle to the return of blood from the aorta to the ventricle, and without such an obstacle the circulation could not be carried on. § 129. Moreover it must be remembered that though we may thus regard the closed valves as so to speak the determining cause of the dicrotic wave, the wave itself is an oscillation of the arterial walls, and the remarks made a little while back concerning the inertia of the walls hold good for this explanation also. Hence the conditions which determine the prominence or otherwise of the dicrotic wave are conditions relating to the elasticity of the arterial walls, and to the circumstances which call that elasticity into play. For instance, the dicrotic wave is less marked in rigid arteries (such as those of old people) than in healthy elastic ones ; the rigid wall neither expands so readily nor shrinks so readily, and hence does not so readily give rise to secondary waves. Again, the dicrotic wave is, other things being equal, more marked when the mean arterial pressure is low than when it is high ; indeed it may be induced when absent, or increased when slightly marked, by diminishing, in one way or another, the mean pressure. Now when the pressure is high, the arteries are kept continually much expanded, and are therefore the less capable of further expansion, that is to say, are, so far, more rigid. Hence the additional expansion due to the systole is not very great ; there is a less tendency for the arterial walls to swing backwards and forwards, so to speak, and hence a less tendency to the development of secondary waves. When the mean pressure is low, the opposite state of things exists ; supposing of course that the ventricular stroke is adequately vigorous (the low pressure being due, not to a diminished cardiac stroke but to diminished peripheral resistance) the relatively empty but highly distensible artery is rapidly expanded, and falling rapidly back enters upon a secondary (dicrotic) expansion, and may even exhibit a third. Moreover the same principles may be applied to explain why sometimes dicrotism will appear marked in a particular artery while it remains little marked in the rest of the system. In experimenting with an artificial tubing such as the arterial model, the physical characters of which remain the same throughout, both the primary and the secondary waves retain the same characters as they travel along the tubing save only that both gradually diminish towards the periphery; and in the natural circulation, when the vascular conditions are fairly uniform throughout, the pulse-curve, as a rule, possesses the same general characters throughout, save that it is gradually * damped off.' But suppose we were to substitute for the first section of the tubing a piece of perfectly rigid tubing , this at the stroke of the CHAP, iv.] THE VASCULAR MECHANISM. 235 pump on account of its being rigid would shew neither primary nor secondary expansion, but the expanding force of the pump's stroke would be transmitted through it to the second, elastic section, and here the primary and secondary waves would at once become evident. This is an extreme case, but the same thing- would be seen to a less degree in passing from a more rigid, that is less extensible and elastic section, to a less rigid, more exten- sible and elastic section ; the primary and secondary expansions, in spite of the general damping effect, would suddenly increase. Similarly in the living body a pulse-curve which so long as it is travelling along arteries in which the mean pressure is high, and which are therefore practically somewhat rigid, is not markedly dicrotic, may become very markedly dicrotic when it comes to a particular artery, in which the mean pressure is low (we shall see presently that such a case may occur), and the walls of which are therefore for the time being relatively more distensible than the rest. Lastly we may recall the observation made above § 123 that the curve of expansion of an elastic tube is modified by the pres- sure exerted by the lever employed to record it, and that hence, in the same artery, and with the same instrument, the size, form, and even the special features of the curve vary according to the amount of pressure with which the lever is pressed upon the artery. Accordingly the amount of dicrotism apparent in a pulse may be modified by the pressure exerted by the lever. In Fig. 61 for instance the dicrotic wave is more evident in the middle than in the upper tracing. § 130. Concerning the other secondary waves on the pulse-curve such as that which has been called the * predicrotic ' wave (B on Fig. 63 and on some of the other pulse-curves) it will not be desirable to say much here. They have been the occasion of much discus- sion, especially when considered under the view that the ventricle rapidly emptied itself at the earlier part of the systole. We will content ourselves with the following remark. The predicrotic and the other secondary waves in question are, like the dicrotic wave, propagated from the heart towards the periphery, they are seen in sphygmograms taken from the root of the aorta as well as from more peripheral arteries, and some are also seen in the curves of ventricular pressure. Some of the features of these secondary waves may be due to imperfections in the instruments used, to inertia and the like, but the main features undoubtedly represent events taking place in the vascular system itself. When we com- pare the curve of pressure in the aorta with that in the ventricle, we observe that up to the dicrotic notch, (in what may be called the systolic part of the pulse-curve, the part which corresponds to the systole of the ventricle, in contrast to the diastolic part which follows and which includes the dicrotic wave) , the variations seen in the aortic curve, the secondary waves of which we are speaking, 236 THE VENOUS PULSE. [BOOK I. are exactly reproduced in the ventricular curve. And it has, with considerable reason, been urged that both in the aorta (and so in the other arteries) and in the ventricle they are due to events taking place in the ventricle, the systole for instance not being equally sustained. We may further call once to mind the fact to which we have already called attention that, while sometimes the curve of ven- tricular pressure reaches its maximum at the very beginning of the systole, declining more or less slowly afterwards, at other times the maximum is reached at the end of the systole, the curve of pressure being anacrotic ; we may add that the maximum may also occur at any intermediate point. Further, and this is the matter to which we wish to call attention, the curve of aortic pressure follows that of the ventricular pressure, both being kata- crotic or anacrotic as the case may be. As we have urged, the anacrotic curve is seen when the peripheral resistance is such that, for some time during the systole, the flow from the aorta towards the periphery is slower than the flow from the ventricle into the aorta. Such a condition is apt to be met with when the arteries are more rigid than normal, and under these circumstances the anacrotic characters of the pulse may become prominent. § 131. Venous Pulse. Under certain circumstances the pulse may be carried on from the arteries through the capillaries into the veins. Thus, as we shall see later on, when the salivary gland is actively secreting, the blood may issue from the gland through the veins in a rapid pulsating stream. The nervous events which give rise to the secretion of saliva, lead at the same time, by the agency of vaso-motor nerves, of which we shall presently speak, to a widen- ing of the small arteries of the gland. When the gland is at rest, the minute arteries are, as we shall see, somewhat constricted and narrowed, and thus contribute largely to the peripheral resistance in the part ; this peripheral resistance throws into action the elastic properties of the small arteries leading to the gland, and the remnant of the pulse reaching these arteries is, as we before explained, finally destroyed. When the minute arteries are dilated, their widened channels allow the blood to flow more easily through them and with less friction ; the peripheral resistance which they normally offer is thus lessened. In consequence of this the elasti- city of the walls of the small arteries is brought into play to a less extent than before, and these small arteries cease to do their share in destroying the pulse which comes down to them from the larger arteries. As in the case of the artificial model, where the * peripheral ' tubing is kept open, not enough elasticity is brought into play to convert the intermittent arterial flow into a con- tinuous one, and the pulse which reaches the arteries of the gland passes on through them and through the capillaries, and is con- tinued on into the veins. A similar venous pulse is also some- times seen in other organs. CHAP, iv.] THE VASCULAR MECHANISM. 237 Careful tracings of the great veins in the neighbourhood of the heart shew elevations and depressions, which appear due to the variations of endocardiac pressure, and which may perhaps be spoken of as constituting a ' venous pulse,' though they have a quite different origin from the venous pulse just described in the salivary gland. In such a pulse it is the depression of the wave, not the elevation, which corresponds to the systole of the ventricle, the pulse-wave is the negative of the arterial pulse-wave ; the matter however needs further study. In cases again of insufficiency of the tricuspid valves, the systole of the ventricle makes itself distinctly felt in the great veins ; and an expansion travelling backwards from the heart becomes very visible in the veins of the neck. This, in which the elevation of the wave like that of the arterial pulse-wave corresponds to the ventricular systole, is also spoken of as a venous pulse. Variations of pressure in the great veins due to the respiratory movements are also sometimes spoken of as a venous pulse ; the nature of these variations will be explained in treating of respi- ration. SEC. 5. THE REGULATION AND ADAPTATION OF THE VASCULAR MECHANISM. The Regulation of the Seat of the Heart. § 132. So far the facts with which we have had to deal, with the exception of the heart's beat itself, have been simply physical facts. All the essential phenomena which we have studied may be reproduced on a dead model. Such an unvary- ing mechanical vascular system would however be useless to a living body whose actions were at all complicated. The promi- nent feature of a living mechanism is the power of adapting itself to changes in its internal and external circumstances. And the vascular mechanism in all animals in which it is present is capable of local and general modifications, adapting it to local and general changes of circumstance. These modifications fall into two great classes : 1. Changes in the heart's beat. These, being central, have of course a general effect ; they influence or may influence the whole body. 2. Changes in the peripheral resistance, due to variations in the calibre of the minute arteries, brought about by the agency of their contractile muscular coats. These changes may be either local, affecting a particular vascular area only, or general, affecting all or nearly all the blood vessels of the body. These two classes of events are chiefly governed by the nervous system. It is by means of the nervous system that the heart's beat and the calibre of the minute arteries are brought into relation with each other, and with almost every part of the body. It is by means of the nervous system acting either on the heart, or on the small arteries, or on both, that a change of CHAP, iv.] THE VASCULAR MECHANISM. 239 circumstances affecting either the whole or a part of the body is met by compensating or regulative changes in the flow of blood. The study of these changes becomes therefore to a large extent a study of nervous actions. The circulation may also be modified by events not belonging to either of the above two classes. Thus, in this or that peripheral area, changes in the capillary walls and the walls of the minute arteries and veins may lead to an increase of the tendency of the blood corpuscles to adhere to the vascular walls, and so, quite apart from any change in the calibre of the blood vessels, may lead to increase of the peripheral resistance. This is seen in an extreme case in inflammation, but may possibly intervene to a less extent in the ordinary condition of the circulation, and may also be under the influence of the nervous system. Further, any decided change in the quantity of blood actually in circulation must also influence the working of the vascular mechanism. But both these changes are unimportant compared with the other two kinds of changes. Hence, the two most important problems for us to study are, 1, how the nervous system regulates the beat of the heart, and 2, how the nervous system regulates the calibre of the blood vessels. We will first consider the former problem. The Development of the Normal Beat. § 133. The heart of a mammal or of a warm blooded animal generally ceases to beat within a few minutes after being removed from the body in the ordinary way, the hearts of newly-born animals continuing however to beat for a longer time than those of adults. Hence, though by special precautions and by means of an artificial circulation of blood, an isolated mammalian heart may be preserved in a pulsating condition for a much longer time, our knowledge of the exact nature and of the causes of the cardiac beat is as yet very largely based on the study of the hearts of cold blooded animals, which will continue to beat for hours, or under favourable circumstances even for days, after they have been removed from the body with only ordinary care. We have reason to think that the mechanism by which the beat is carried on varies in some of its secondary features in different kinds of animals : that the hearts, for instance, of the eel, the snake, the tortoise and the frog, differ in some minor details of behaviour, both from each other and from those of the bird and of the mammal ; but we may, at first at all events, take the heart of the frog as illustrating the main and important truths concerning the causes and mechanism of the beat. 240 GRAPHIC RECORD OF HEART BEAT. [BOOK i. In studying closely the phenomena of the beat of the heart it becomes necessary to obtain a graphic record of the various movements. 1. In the frog, or other cold blooded animal, a light lever may be placed directly on the ventricle (or on an auricle, &c.), and changes of form, due either to distension by the influx of blood, or to the systole, will cause movements of the lever, which may be recorded on a travel- ling surface. The same method as we have seen may be applied to the mammalian heart. 2. Or, as in Gaskell's method, the heart may be fixed by a clamp carefully adjusted round the auriculo-ventricular groove, while the apex of the ventricle and some portion of one auricle are attached by threads to horizontal levers, placed respectively above and below the heart. The auricle and the ventricle each in its systole pulls at the lever attached to it ; and the times and extent of the contractions may thus be recorded. Or the thread may be attached to the apex of the ven- tricle only, the heart being fixed by the aorta or left in position in the body. 3. A record of endo-cardiac pressure may be taken in the frog or tortoise, as in the mammal, by means of an appropriate manometer. And in these animals, at all events, it is easy to keep up an artificial circulation. A cannula is introduced into the sinus venosus, and another into the ventricle through the aorta. Serum or dilute blood (or any other fluid which it may be desired to employ) is driven by moderate pressure through the former ; to the latter is attached a tube connected by means of a side piece with a small mercury or other manometer. So long as the exit-tube is open at the end, fluid flows freely through the heart and apparatus. Upon closing the exit-tube at its far end, the force of the ventricular systole is brought to bear on the manometer, the index of which registers in the usual way. Newell Martin has succeeded in applying a modification of this method to the mammalian heart. 4. The movements of the ventricle may be regis- tered by introducing into it, through the auriculo- ventricular orifice, a so-called ' perfusion ' cannula, Figs. 66 and 67 I., with a double tube, one inside the other, and tying the ventricle on to the cannula at the auriculo-ventricular groove, or at any level below that which may be desired. The blood or other fluid is driven at an adequate pressure through the tube a, enters the ventricle, and returns by the tube b. If b be connected with a manometer, as in method 3, the movements of the ventricle may be registered. j?1G 6g ^ pER. FUSION CANNULA. 5. In the apparatus of Roy, Fig. 67 II., the exit- tube is free, but the ventricle (the same method may be adopted for the whole heart) is placed in an air-tight chamber, filled with oil, or partly with normal saline solution and partly with oil. By means of the tube b the interior of the chamber a is continuous with that of a small cylinder c, in which a piston d, secured by thin, flexible, animal membrane, works CHAP, iv.] THE VASCULAR MECHANISM. 241 up and down. The piston again bears on a lever e by means of which its movements may be registered. When the ventricle contracts, and by contracting diminishes in volume, there is a lessening of pressure in FIG. 67. PURELY DIAGRAMMATIC FIGURES OF I. PerfusioD canimla tied into frog's ventricle, a, entrance, b, exit-tube ; a, wall of ventricle ; ft, ligature. II. Hoy's apparatus modified by Gaskell. a, chamber filled with saline solution and oil, containing the ventricle a tied on to the profusion cannulay; b, tube leading to cylinder c, in which moves piston d, working the lever e. the interior of the chamber ; this is transmitted to the cylinder, and the piston correspondingly rises, carrying with it the lever. As the ventricle subsequently becomes distended, the pressure in the chamber is increased, and the piston and lever sink. In this way variations in the volume of the ventricle may be recorded, without any great inter- ference with the flow of blood or fluid through it. The heart of the frog, as we have just said, will continue to beat for hours after removal from the body, even though the cavi- ties have been cleared of blood, and, indeed, when they are almost empty of all fluid. The beats thus carried out are in all import- ant respects identical with the beats executed by the heart in its normal condition within the living body. Hence we may infer that the beat of the heart is an automatic action : the muscular contractions which constitute the beat are due to causes which arise spontaneously in the heart itself. In the frog's heart, as in that of the mammal, § 108, there is a distinct sequence of events which is the same whether the heart be removed from, or be still in its normal condition within the body. First comes the beat of the sinus venosus, preceded by a more or less peristaltic contraction of the large veins leading into it ; next follows the sharp beat of the two auricles together ; then comes the longer beat of the ventricle ; and lastly the cycle is completed by the 16 242 GRAPHIC RECORD OF HEART BEAT. [BOOK i. beat of the bulbus arteriosus, which does not, like the mammalian aorta, simply recoil by elastic reaction after distension by the ventricular stroke but carries out a distinct muscular contraction passing in a wave from the ventricle outwards. When the heart in dying ceases to beat, the several move- ments cease, as a rule, in an order the inverse of the above. Omitting the bulbus arteriosus, which sometimes exhibits great rhythmical power, we may say that first the ventricle fails, then the auricles fail, and lastly the sinus venosus fails. The heart after it has ceased to beat spontaneously remains for some time irritable, that is capable of executing a beat, or a short series of beats, when stimulated either mechanically as by touching it with a blunt needle or electrically by an induction shock or in other ways. The artificial beat so called forth may be in its main features identical with the natural beat, all the divisions of the heart taking part in the beat, and the sequence of events being the same as in the natural beat. Thus when the sinus is pricked the beat of the sinus may be followed by a beat of the auricles and of the ventricle ; and even when the ventricle is stimulated, the directly following beat of the ventricle may be succeeded by a complete beat of the whole heart. Under certain circumstances however the division directly stimulated is the only one to beat ; when the ventricle is pricked for instance it alone may beat, or when the sinus is pricked it alone may beat. The results of stimulation moreover may differ according to the condition of the heart and according to the particular spot to which the stimulus is applied. With an increasing loss of irritability, the response to stimu- lation ceases in the several divisions in the same order as that of the failure of the natural beat ; the ventricle ceases to respond first, then the auricles, and lastly the sinus venosus, which fre- quently responds to stimulation long after the other divisions have ceased to make any sign. It would appear as if the sinus venosus, auricles, and ventricle formed a descending series in respect to their irritability and to the power they possess of carrying on spontaneous rhythmic beats, the sinus being the most potent. This is also seen in the following experiments. In order that the frog's heart may beat after removal from the body with the nearest approach in rapidity, regularity, and en- durance to the normal condition, the removal must be carried out so that the excised heart still retains the sinus venosus intact. When the incision is carried through the auricles so as to leave the sinus venosus behind in the body, the sinus venosus beats forcibly and regularly, having suffered hardly any inter- ruption from the operation ; but the auricles and ventricle remain motionless, often for a considerable time, and when they do re- sume spontaneous beats these have a rhythm different from that of the sinus, and are less vigorous and lasting than those of the CHAP, iv.] THE VASCULAR MECHANISM. 243 entire heart. If the incision be carried between the auricles and ventricle, the former with the sinus beat regularly and forcibly while the latter often exhibits no spontaneous beats at all, or if these do appear they last for a short time only. Lastly if the ventricle be cut across leaving the upper third attached to the auricles, this beats regularly with the sinus and auricles, but the detached lower two-thirds do not beat spontaneously at all. Now, while ganglia are abundant over the sinus, are numer- ous over the auricles, and, as Bidder's ganglia, are present at the auriculo-ventricular junction, no nerve cells are present in the lower part of the ventricle. Hence the view has suggested itself that the rhythmic spontaneous beating is due to impulses pro- ceeding rhythmically from the nerve cells of the ganglia. But serious objections may be urged against this view. Even in the case of the frog, the lower part of the ventricle, the mere tip almost, may under specially favourable circumstances beat in an apparently spontaneous manner ; this occurs when it is tied round the end of a perfusion cannula (Fig. 66), and fed with blood or serum at a somewhat high pressure. And in the case of the tortoise a mere strip of muscle, quite free from nerve cells, cut out of the ventricle may be made to beat, in an apparently spon- taneous manner, with great regularity for a considerable time. Without entering into any lengthy discussion concerning a matter which is and has been much debated, we may say that the cardiac muscular fibre differs in properties, as it does in struc- ture, from the skeletal muscular fibre, that it is not to the same extent as that, a mere instrument, so to speak, in the hands of a motor nerve fibre, but has, itself, largely to do with originating its own contraction. The muscular contraction, we may here observe, of which the beat is a development, is not a tetanus, but a somewhat long continued simple contraction. This may be readily shewn to be the case on the slip of the tortoise ven- tricle just referred to. Such a slip, when attached to a lever, and stimulated with a single induction shock, gives what is obviously a simple contraction, and a beat of the slip occurring naturally has exactly the same features. And the electric change shewn at any part of the heart during a beat natural or induced by stimulation is that characteristic of a simple contraction. The intact ventricle at rest is as we have already said (§ 63) isoelec- tric, but each part just as it is entering into a state of contraction becomes negative towards the rest. Hence when the electrodes of a galvanometer are placed on two points A, B of the surface of the ventricle a diphasic variation of the galvanometer needle is seen when a beat, natural or excited, occurs. Supposing that the wave of contraction reaches A first, this will become negative towards the rest of the ventricle, including B, but when the wave sometime afterwards reaches B, B will become negative towards the rest of the ventricle, including A. Compare § 64. But the contraction of cardiac muscle differs from that of a 244 FEATURES OF CARDIAC CONTRACTION. [BOOK i. skeletal muscle in the following important feature. When we stimulate a skeletal muscle with a strong stimulus we get a large contraction, when we apply a weak stimulus we get a small contraction; within certain limits (see § 74) the contraction is proportional to the stimulus. This is not the case with the qui- escent ventricle or heart. When we apply a strong induction- shock we get a beat of a certain strength ; if we now apply a weak shock we get either no beat at all or quite as strong a beat as with a stronger stimulus. That is to say the magnitude of the beat depends on the condition of the ventricle (or heart) and not on the magnitude of the stimulus. If the stimulus can stir the ventricle up to beat at all, the beat is the best which the ventricle can at the time accomplish ; the stimulus produces either its maximum effect or none at all. It would seem as if the stimulus does not produce a contraction in the same way that it does when it is brought to bear on a skeletal muscle, but rather stirs up the heart in such a way as to enable it to execute a spontaneous beat which, without the extra stimulus, it could not bring about. And we have reason to think that the normal beat of the heart within the body is the maximum beat of which it is capable at the moment. These and other special features of the contraction of cardiac muscle lead to the conclusion that the rhythmic power does not reside wholly in the ganglia ; but we must not here discuss the question further, nor enter upon the difficult problem of how the remarkable sequence in contraction of the several parts is developed and as a rule maintained. § 134. In the above we have dealt chiefly with the heart of the cold blooded animal, but so far as we know the same general conclusions hold good for the mammalian heart also. There is, it is true, in the mammal, no prepotent sinus venosus, but as in the frog the auricles are dominant, and their beat determines the beat of the ventricles. Even more clearly than in the frog however, the ventricles, though they normally follow the auricles in their beat, being initiated as it were by them, possess an independent rhythmic power of their own. By a mechanical contrivance all conduction of nervous or muscular impulses between the auricles and ventricles may be abolished, though the blood may continue to flow from the cavities of the former to those of the latter. When this is done the ventricles go on beating rhythmically, but at a rate which is quite independent of that of the auricular beats. We may now turn to the nervous mechanisms by which the beat of the heart, thus arising spontaneously within the tissues of the heart itself, is modified and regulated to meet the require- ments of the rest of the body. The Government of the Heart Beat "by the Nervous System. § 135. It will be convenient to begin with the heart of the frog. This is connected with the central nervous system through, CHAP. iv. J THE VASCULAR MECHANISM. 245 and therefore governed by, the two vagus nerves, each of which though apparently a single nerve contains, as we shall see, fibres of different origin and nature. If while the beats of the heart of a frog are being carefully registered an interrupted current of moderate strength be sent through the vagus nerve, the heart is seen to stop beating. It remains for a time in diastole, perfectly motionless and flaccid ; all the muscular fibres of the several chambers are for the time being in a state of relaxation. The heart has been inhibited by the impulses descending the vagus from the part of the nerve stimulated. If the duration of the stimulation be short and the strength of the current great, the standstill may continue after the current has been shut off ; the beats, when they reappear, are generally at first feeble and infrequent, but soon reach or even go beyond their previous vigour and frequency. If the duration of the stimulation be very long, the heart may recommence beating while the stimula- tion is still going on, but the beats are feeble and infrequent though gradually increasing in strength and frequency. The effect of the stimulation is at its maximum at or soon after the com- mencement of the application of the stimulus, gradually declining afterwards ; but even at the end of a very prolonged stimulation the beats may still be less in force or in frequency, or in both, than they were before the nerve was stimulated, and on the removal of the current may shew signs of recovery by an increase in force and frequency. The effect is not produced instantaneously ; if on the curve the point be exactly marked when the current is thrown in, as at on Fig. 68, it will frequently be found that one beat at FIG. 68. INHIBITION OF FROG'S HEART BY STIMULATION OF VAGUS NERVE. I on marks the time at which the interrupted current was thrown into the vagus, o/f when it was shut off. The time marker below marks seconds. The beats were registered by suspending the ventricle from a clamp attached to the aorta and attaching a light lever to the tip of the ventricle. least occurs after the current has passed into the nerve; the development of that beat has taken place before the impulses descending the vagus have had time to affect the heart. 246 AUGMENTATION OF THE BEAT. [BOOK i. The stimulus need not necessarily be the interrupted current ; mechanical, chemical or thermal stimulation of the vagus will also produce inhibition ; but in order to get a marked effect it is desirable to make use of not a single nervous impulse but a series of nervous impulses ; thus it is difficult to obtain any recognisable result by employing a single induction shock of moderate intensity only. As we shall see later on ' natural ' nervous impulses descend- ing the vagus from the central nervous system, and started there, by afferent impulses or otherwise, as parts of a reflex act, may produce inhibition. The stimulus may be applied to any part of the course of the vagus from high up in the neck right down to the sinus ; indeed, very marked results are obtained by applying the electrodes directly to the sinus where as we have seen the two nerves plunge into the substance of the heart. The stimulus may also be applied to either vagus, though in the frog, and some other animals, one vagus is sometimes more powerful than the other. Thus it not unfrequently happens that even strong stimulation of the vagus on one side produces no change of the rhythm, while even moderate stimulation of the nerve on the other side of the neck brings the heart to a standstill at once. If during the inhibition the ventricle or other part of the heart be stimulated directly, for instance mechanically by the prick of a needle, a beat may follow; that is to say, the impulses descending the vagus, while inhibiting the spontaneous beats, have not wholly abolished the actual irritability of the cardiac tissues. With a current of even moderate intensity, such a current for instance as would produce a marked tetanus of a muscle-nerve preparation, the standstill is complete, that is to say, a certain number of beats are entirely dropped ; but with a weak current the inhibition is partial only, the heart does not stand absolutely still but the beats are slowed, the intervals between them being prolonged, or weakened only without much slowing, or both slowed and weakened. Sometimes the slowing and sometimes the weakening is the more conspicuous result. § 136. It sometimes happens that, when in the frog the vagus is stimulated in the neck, the effect is very different from that just described ; for the beats are increased in frequency, thougli they may be at first diminished in force. And, occasionally, the beats are increased both in force and in frequency : the result is augmentationj|not inhibition. But this is due to the fact that in the frog the vagus along the greater part of its course is a mixed nerve and contains fibres other than those of the vagus proper. If we examine the vagus nerve closely, tracing it up to the brain, we find that just as the nerve has pierced the cranium, just where it passes through the ganglion (G- V, Fig. 69), certain fibres pass into it from the sympathetic nerve of the neck, Sy, of the further connections of which we shall speak presently. CHAP, iv.] THE VASCULAR MECHANISM. 247 This being the case, we may expect that we should £ results according as we stimulated (1) the vagus in tl V.r. [et different te cranium, FIG. 69. DIAGRAMMATIC REPRESENTATION OF THE COURSE AUGMENTOR FlBRES IN THE FfiOG. OF CARDIAC Vr. roots of vagus (and ixth) nerve. GV. ganglion of same. Cr. line of cranial wall. Vg. vagus trunk, ix. ninth, glosso-pharyngeal nerve. S'.V.C. superior vena cava. Sy. sympathetic nerve in neck. G.C. junction of sympathetic ganglion with vagus ganglion, sending i.e. intracranial fibres passing to Gasserian ganglion. The rest of the fibres pass along the vagus trunk. G1 sympathetic ganglion connected with the first spinal nerve. Gn sympathetic ganglion of the second spinal nerve. An.V. annulus of Vieussens. A.sb. subclavian artery. Gm sympathetic ganglion of the third spinal nerve. ///. third spinal nerve, r.c. ramus communicans. The course of the augmentor fibres is shewn by the thick black line. They may be traced from the spinal cord by the anterior root of the third spinal nerve, through the ramus communicans to the corresponding sympathetic ganglion Gm and thence by the second ganglion G", the annulus of Vieussens, and the first ganglion G1 to the cervical sympathetic Su, and so by the vagus trunk to the superior vena cava S.Y.C. before it was joined by the sympathetic, (2) the sympathetic fibres before they join the vagus, and (3) the vagus trunk, containing both the real vagus and the sympathetic fibres. What we have pre- viously described are the ordinary results of stimulating the mixed 248 AUGMENTATION OF THE BEAT. [BOOK i, trunk, and tnese, as we have said, are not wholly constant, though, usually and in the main, most distinct inhibitory results follow. If we stimulate the sympathetic in the neck as at Sy, Fig. 69, cutting the nerve below so as to block all impulses from passing downwards, and only allow impulses to pass up to the vagus and thence down the mixed vagus trunk to the heart, we get very remarkable results. The beat of the heart instead of being inhib- ited is augmented, the beats are increased either in frequency or in force, or most generally both in frequency and in force. The effect is perhaps best seen when the heart before stimulation is beating slowly and feebly ; upon stimulation of the cervical sympathetic the beats at once improve in vigour and frequency ; indeed, a heart which for one reason or another has almost ceased to beat may, by proper stimulation of the sympathetic, be called back into vigorous activity. If, on the other hand, we stimulate the vagus before it has been joined by the sympathetic fibres (and to ensure the result not being marred by any escape of the stimulating current on to the sympathetic fibres it is necessary to stimulate the vagus within the cranium) we get pure and constant inhibitory results, the beats are for a time wholly abolished, or are slowed, or are weakened, or are both slowed and weakened. Obviously, then, the heart of the frog is supplied through the vagus by two sets of fibres coming from the central nervous system, the one by the vagus proper and the other by the cervical sym- pathetic nerve, and these two sets have opposite and antagonistic effects upon the heart. The one set, those belonging to the vagus proper, are inhibitory; they weaken the systole and prolong the diastole, the effect with a strong stimulation being complete, so that the heart is for a time brought to a standstill. Sometimes the slowing, sometimes the weakening is the more prominent. When the nerve and the heart are in good condition, it needs only a slight stimulus, a weak current, to produce a marked effect, and it may be mentioned that the more vigorous the heart, the more rapidly it is beating, the easier is it to bring about inhibition. Although, as we have said, the effect is at its maximum soon after the beginning of stimula- tion, a very prolonged inhibition may be produced by prolonged stimulation ; indeed, by rhythmical stimulation of the vagus the heart may be kept perfectly quiescent for a very long time and yet beat vigorously upon the cessation of the stimulus. In other words, the instruments of inhibition, that is, the fibres of the vagus and the part or substance of the heart upon which these act to produce inhibition, whatever that part or substance may be, are not readily exhausted. Further, the inhibition when it ceases is, frequently at all events, followed by a period of reaction, during which the heart for a while beats more vigorously and rapidly than before. Indeed the total effect of stimulating the vagus CHAP, iv.] THE VASCULAR MECHANISM. 249 fibres is not to exhaust the heart, but rather to strengthen it ; and by repeated inhibitions carefully administered, a feebly beating heart may be nursed into vigorous activity. The other set, those joining the vagus from the sympathetic, are ' augmentor ' or ' accelerating ' fibres ; the latter name is the more common but the former is more accurate, since the effect of stimulating these fibres is to increase not only the rapidity but the force of the beat ; not only is the diastole shortened but the systole is strengthened, sometimes the one result and sometimes the other being the more prominent. These augmentor fibres need a somewhat strong stimulation to produce an effect, the time required for the maximum effect to be produced is long, and the effect, when produced, may last for some time. A slowly or weakly beating heart is more easily augmented than is a strong one. Further, the augmentation is followed by a period of reac- tion in which the beats are feebler, by a stage of exhaustion; and indeed by repeated stimulation of these sympathetic fibres a fairly vigorous heart, especially a bloodless one, may be reduced to a very feeble condition. By watching the effects of stimulating the sympathetic nerve at various points of its course we may trace these augmentor fibres from their junction with the vagus down the short sympa- thetic of the neck through the sympathetic ganglion connected with the first spinal nerve, G1, Fig. 69, through one or both the loops of the annulus of Vieussens, An. V, through the second ganglion, connected with the second spinal nerve, 6r7/, to the third ganglion connected with the third spinal nerve, G111, and thence through the ramus communicans or visceral branch of that ganglion, r.c., to the third spinal nerve, ///, by the anterior root of which they reach the spinal cord. § 137. Both sets of fibres, then, may be traced to the central nervous system ; and we find accordingly that the heart may be inhibited or augmented by nervous impulses which are started in the nervous system either by afferent impulses as part of a reflex act or otherwise, and which pass to the heart by the inhibitory or by the augmenting tract. Thus if the spinal bulb or a particular part of the spinal bulb which is specially connected with the vagus nerve be stimulated, the heart is inhibited ; if, for instance, a needle be thrust into this part the heart stands still. This nervous area may be stirred to action, in a 'reflex' manner, by afferent impulses reaching it from various parts of the body. Thus if the abdomen of a frog be laid bare, and the intestine be struck sharply with the handle of a scalpel, the heart will stand still in diastole with all the phenomena of vagus inhibition. If the nervi mesenterici or the connections of these.iierves with the spinal cord be stimulated with the interrupted current, cardiac inhibition is similarly pro- duced. If in these two experiments both vagi are divided, or the 250 INHIBITION IN THE MAMMAL. [BOOK i. spinal bulb is destroyed, inhibition is not produced, however much either the intestine or the mesenteric nerves be stimulated. This shews that the phenomena are caused by impulses ascending along the mesenteric nerves to the spinal bulb, and so affecting a portion of that organ as to give rise by reflex action to impulses which descend the vagus nerve or nerves as inhibitory impulses. The portion of the spinal bulb thus mediating between the afferent and efferent impulses may be spoken of as the cardio-inhiMtory centre. This centre may be thrown into activity, and so inhibition produced, by afferent impulses reaching it along various nerves; by means of it reflex inhibition through one vagus may be brought about by stimulation of the central end of the other. And we have reason to think that in a similar manner augmentor impulses are developed in the central nervous system either as part of a reflex chain or otherwise. § 138. So far we have been dealing with the heart of the frog, but the main facts which we have stated regarding inhi- bition and augmentation of the heart beat apply also to other vertebrate animals including mammals, and, indeed, we meet similar phenomena in the hearts of invertebrate animals. If in a mammal the heart be exposed to view by opening the thorax, and the vagus nerve be stimulated in the neck, the heart may be seen to stand still in diastole, with all the parts flaccid and at rest. If the current employed be too weak, the result, as in the frog, is not an actual arrest but a slowing or weakening of the beats. By placing a light lever on the heart or by other methods, a graphic record of the standstill, or of the slowing, of the complete or incomplete inhibition may be obtained. The result of stimulating the vagus is also well shewn on the blood FIG. 70. TRACING, SHEWING THE INFLUENCE OF CARDIAC INHIBITION ON BLOOD PRESSURE. FROM A RABBIT. x the marks on the signal line when the current is thrown into, and y shut off from the vagus. The time marker below marks seconds, the heart, as is frequently the case in the rabbit, beating very rapidly. CHAP, iv.] THE VASCULAR MECHANISM. 251 pressure curve, the effect of complete cardiac inhibition on blood pressure being most striking. If, while a tracing of arterial pressure is being taken, the beat of the heart be suddenly arrested by vagus stimulation, some such curve as that represented in Fig. 70 will be obtained. It will be observed that two beats follow the application of the current marked by the point a, which corresponds to the signal x on the line below. Then for a space of time no beats at all are seen, the next beat & taking place almost immediately after the shutting off the current at y. Immediately after the last beat following a, there is a sudden fall of the blood pressure. At the pulse due to the last systole, the arterial system is at its maximum of distention; forthwith the elastic reaction of the arterial walls propels the blood forward into the veins, and, there being no fresh fluid injected from the heart, the fall of the mercury is unbroken, being rapid at first, but slower afterwards, as the elastic force of the arterial walls is more and more used up. With the returning beats the pressure correspondingly rises in successive leaps until the normal mean pressure is regained. The size of these returning leaps of the mercury may seem disproportionately large, but it must be re- membered that by far the greater part of the force of the first few strokes of the heart is expended in distending the arterial system, a small portion only of the blood which is ejected into the arteries passing on into the veins. As the arterial pressure rises, more and more blood passes at each beat through the capillaries, and the rise of the pressure at each beat becomes less and less, until at last the whole contents of the ventricle pass at each stroke into the veins, and the mean arterial pressure is established. To this it may be added, that, as we have seen, the force of the individual beats may be somewhat greater after than before inhi- bition. Besides/when the mercury manometer is used, the inertia of the mercury tends to magnify the effects of the initial beats. The above is an example of complete inhibition, of a total stand- still for a while of the whole heart, such as may be obtained by powerful stimulation of the vagus ; both auricles and ventricles remain for a period free from all contractions ; and as the previously existing arterial pressure drives the blood onward from the arteries through the capillaries and veins towards the heart, the cavities of the heart become distended with blood, especially on the right side. A weaker stimulation of the vagus produces an incomplete inhibition, the heart continues to beat but with a different rhythm and stroke, and by careful observation many interesting features may be observed. If a record be obtained, by one or other of the methods mentioned in § 113 or elsewhere, of the behaviour of the auricles and ventricles respectively, it will be observed that the inhibition tells much more on the auricles than on the ventricles. The extent of the auricular contractions is 252 INHIBITION IN THE MAMMAL. [BOOK i. especially affected, more so than that of the ventricles, and it may sometimes be observed that the auricles are brought to complete quiescence while the ventricles still continue to beat ; the latter now exhibit that independent rhythm of which we spoke in § 134. In a somewhat similar manner the stimulation of the vagus, by affecting the rhythm of the auricles more than that of the ventricles, may lead to a want of coordination between the two, the especially slowed auricles beating at one rate, the ventricles at another. It is indeed maintained by some that the vagus acts directly on the auricles only, the changes in the ventricles being of a secondary nature, caused by the changes in the auricles. When the output from the ventricles during vagus stimulation is measured, by the cardiometer or otherwise, it is found, as might be expected, that this is lessened. The diminution during a given period may be due to the mere slowing of the beat; but the individual pulse volume is in some cases, at least, also lessened. It may by the same method be observed that the quantity remain- ing in the ventricle at the end of the systole is increased ; the ventricle appears to expand more during diastole. Of the effects thus produced on the circulation we shall speak later on. We may now turn to some further details concerning the course of these inhibitory fibres. They run in the trunk of the vagus ; this is clear not only in the case of an animal like the rabbit, in which the vagus runs separate from the cervical sym- pathetic but also in the case of the dog, in which the two nerves are more or less bound up together. Leaving the vagus by the cardiac branches, they reach the cardiac tissues by the cardiac plexuses. When we trace the fibres in the other direction to- wards the central nervous system, we have to bear in mind that the fibres which compose the trunk of the vagus have, as we shall see in studying the central nervous system, two distinct central origins. On the one hand, there are the fibres which are the proper vagus fibres which, leaving the spinal bulb, pass through both the jugular ganglion and trunk ganglion (Fig. 71 r. GJ. G. Tr. Vg.). On the other hand, there are fibres which, belonging to the spinal accessory nerve (Sp. Ac.) and to what we shall learn to speak of as the bulbar division of that nerve, pass after leaving the spinal bulb to the trunk ganglion of the vagus, and thence form part of the vagus trunk. Now, it is these fibres of the spinal accessory nerve and not the proper vagus fibres which supply the inhibitory fibres to the heart. Thus, if the bulbar roots of the spinal accessory be divided, those of the vagus proper being left intact, the spinal accessory fibres in the vagus trunk degenerate, and when this has taken place stimulation of the vagus fails to produce the ordinary inhibitory effect. Within the spinal bulb these inhibitory fibres are connected, in the mammal as in the frog, with a cardio-inhibitory centre ; and in the mammal as in the frog inhibition may be brought about CHAP, iv.] THE VASCULAR MECHANISM. 253 not only by artificial stimulation of the vagus, but by stimulation in a reflex manner or otherwise of the cardio-inhibitory centre. Thus the fainting which often follows upon a blow on the stomach is a repetition of the result mentioned a little while ago as obtained on the frog by striking the stomach or stimulating the nervi mesenterici. So also the fainting, complete or partial, which accompanies severe pain or mental emotion, is an illustration of cardiac inhibition by the vagus. These are familiar examples of more or less complete inhibition ; but simple slowing or weakening of the beat through the inhibitory mechanism is probably an event of much more common occurrence. For instance, a rise of general blood pressure, or, and perhaps more especially, a rise in the blood pressure of the vessels of the brain, sets going inhibitory impulses by which the work of the heart is lessened, and the high blood pressure lowered, the dangers of a too high pressure being thus averted. Again, the inhibition may be brought about in a reflex manner by impulses started in the heart itself and ascending to the central nervous system along afferent fibres which run in the vagus trunk from the heart to the spinal bulb. In this way the heart regulates its own action according to its condition and its needs. There is also some reason for thinking that, in some animals at least, the central nervous system by means of the cardiac inhibitory fibres keeps, as it were, a continual rein on the heart, for, in the dog for example, section of both vagi causes a quickening of the heart's beat. But we shall have to speak of these matters more than once later on. Meanwhile we may turn to the augmentor fibres. So much of our knowledge of the nervous work of the heart and especially of the action of the augmentor fibres has been gained by experiments on dogs that it may be desirable to give a few details con- cerning the nerves of the heart in this animal. In the dog the vagus soon after it issues from its trunk ganglion (G. Tr. Vg., Fig. 71) is joined by the sympathetic nerve proceeding from the superior cervical ganglion, the two forming the vago-sym pathetic trunk. As this trunk enters the thorax, the sympathetic portion bears a ganglion (G. C.) usually called the lower cervical ganglion. To this ganglion there pass from the stellate ganglion (G.St.) of the thoracic sympathetic chain, two nerves, one running ventral to, the other dorsal to the subclavian artery, and thus forming with the two ganglia, the .i., D.\i.y D.iu., D.rv., D.\., first, second, third, fourth and fifth thoracic spinal nerves, r. c. ramus communicans. n. c. nerves (cardiac) passing to the heart from the cervical ganglion and from the annulus of Vieussens. The inhibitory fibres, shewn by black lines, run in the upper (bulbar) roots of the spinal accessor)', by the internal branch of the spinal accessory, past the ganglion trunci vagi, along the trunk of the vagus, and so by branches to the heart. The augmentor fibres, also shewn by black lines, pass from the spinal cord by the anterior roots of the second and third thoracic nerves (possibly also from the first, fourth and fifth as indicated by broken black lines), pass the stellate ganglion by the annulus of Vieussens to the lower cervical ganglion, from whence, as also from the annulus itself, they pass along the cardiac nerves to the heart. An occasional tract from the stellate ganglion itself is not shewn in the figure. slender nerve from the superior cervical ganglion passing independently to the heart. The arrangement is not exactly the same on the two sides of the body, and the minor details differ in different individuals. As in other animals the various cardiac nerves mingle in the cardiac plexuses. In the dog it has been ascertained by separate stimulation of these several cardiac nerves, that augmentor fibres are contained in some or other of the nerves passing from the lower cervical ganglion and the adjoining vagus trunk, from the annulus of Vieussens,. especially the lower, ventral, limb, and sometimes from the stellate ganglion itself. The results differ a good deal in different in- dividuals, and there are reasons for thinking that the nerves in question may contain efferent fibres other than augmentor fibres, by reason of which stimulation of them may give rise to other than pure augmentor effects. Speaking broadly, however, we may say that we may trace, the augmentor fibres back from the cardiac plexuses through the lower cervical ganglion and the annulus of Vieussens to the stellate ganglion. This ganglion is in reality several sympathetic ganglia fused together. It undoubtedly, in the dog, represents the first, second and third thoracic sympathetic ganglia, receiving, as it does, branches, rami communicantes, from the first, second and third thoracic spinal nerves. Since it also receives branches from the eighth and seventh cervical nerves, it has been argued that it represents not only the three thoracic sympathetic ganglia, but also what in man and other animals is called the lower cervical ganglion ; if so, what has been called above the lower cervical ganglion should be regarded as the middle cervical ganglion. From the stellate ganglion the sympathetic cord passes to the ganglion, which is connected by a ramus communicans with the 256 AUGMENTOR FIBRES IN MAMMAL. [BOOK i. fourth thoracic spinal nerve, and which is therefore, in reality, the fourth thoracic ganglion, and so on to the rest of the thoracic chain. Now, when the several rami communicantes, or the anterior roots, of the lower cervical and upper thoracic nerves are separately stimulated, it is found that augmentor effects make their appear- ance with considerable constancy when the second and third thoracic nerves are stimulated ; the effects are, less constant with the first and fourth thoracic nerves ; sometimes some effect may appear with the fifth thoracic nerve, but not with any other thoracic nerves, or with any of the cervical nerves. We may therefore say that, in the dog, augmentor impulses leave the spinal cord by the anterior roots of the second and third, to some extent the first and fourth, and possibly the fifth thoracic nerves, travel by the several rami communicantes to the stellate ganglion, and pass thence to the cardiac plexuses, and so to the heart, by nerves from the stellate ganglion itself, or from the annulus of Vieussens, or from the so-called lower cervical ganglion. In the cat the path of the augmentor impulses is very similar, and we may regard the statement just made as representing, in a broad way, the path of these impulses in the mammal generally. They leave the spinal cord by the upper thoracic nerves, and pass to the heart through the lower cervical and upper thoracic sympathetic ganglia. The effect of stimulating these augmentor fibres is, in some cases, to increase the rapidity of the rhythm. When the heart is beating very slowly this acceleration may be very conspicuous, but when the heart is beating quickly, or even at what may be called a normal rate, the acceleration observed may be very slight. A more constant and striking effect is the increase in the force of the beat. When tracings are taken of the movements of the auricles and ventricles separately, it is observed that in the case both of the auricles and of the ventricles, the extent of the systole is increased ; moreover, it would seem also that both cavities undergo a larger expansion : they are filled with a larger quantity of blood during the diastole. This means that the output of the heart is increased by the action of the augmentor nerves, and that such is the effect may be directly shewn by the cardiometer. Moreover, this increase of the output may take place in spite of a concomitant rise of arterial pressure, so that the effect of the action of the augmentor nerves is distinctly to increase the work of the heart ; and this may take place even though no marked acceleration occurs. In the mammal as in the case of the frog, when the augmentor fibres are stimulated, some time elapses before the maximum effect is witnessed and the influence of the stimulation may last some considerable time after the stimulation has ceased. When records are taken of the behaviour of the heart during the stimulation of afferent nerves, such as the sciatic or the splanchnic, the records shew that the heart may behave very much CHAP, iv.] THE VASCULAR MECHANISM. 257 in the same way as when the augmentor fibres are directly stimu- lated ; there is a marked increase in the force of the auricular and of the ventricular systole, and at times an obvious acceleration of the rhythm. We may infer that in such a case the augmentor fibres are thrown into activity through the afferent impulses as part of a reflex act. At the same time it must be remembered, that afferent impulses may increase the beat of the heart not by exciting the augmentor mechanism, but by depressing, that is by inhibiting a previously existing activity of the cardio-inhibitory centre ; to this point we shall again have to refer. We may however conclude that both the inhibitory and the augmentor mechanisms of the heart can be brought into action by means of the central nervous system. Speaking broadly the effect of the former is to diminish the work of the heart, and so to lower the blood pressure, and that of the latter to increase the work of the heart, and so to heighten the blood pressure. § 139. If, either in a frog or a mammal, or other animal, after the vagus fibres have been proved, by trial, to produce, upon stimu- lation, the usual inhibitory effects, a small quantity of atropin be introduced into the circulation (when the experiment is con- ducted on a living animal, or be applied in a weak solution to the heart itself when the experiment is conducted, in the frog for instance, on an excised heart or after the circulation has ceased), it will after a short time be found, not only that the stimu- lation, the application of a current for instance, which previously when applied to the vagus produced marked inhibition, now produces no inhibition, but even that the strongest stimulus, the strongest current applied to the vagus, will wholly fail to affect the heart, provided that there be no escape of current on to the cardiac tissues themselves ; under the influence of even a small dose of atropin, the strongest stimulation of the vagus will not produce standstill or appreciable slowing or weakening of the beat. Further, this special action of atropin on the heart is so to speak complemented by the action of muscarin, the active principle of many poisonous mushrooms. If a small quantity of muscarin be introduced into the circulation, or applied directly to the heart, the beats become slow and feeble, and if the dose be adequate the heart is brought to a complete standstill. The effect is in some respects like that of powerful stimulation of the vagus. Now if, in a frog, the heart be brought to a standstill by a dose of muscarin, the application of an adequate quantity of atropin will bring back the beats to quite their normal strength and rhythm. The one drug is so far as the heart is concerned (and indeed in many other respects) the antidote of the other. These and other results have been taken to indicate that there exists in the heart a special inhibitory mechanism, and that it is through this special mechanism that the inhibitory fibres of the vagus produce inhibi- tion, while atropin produces the effect just mentioned by paralys- 258 INHIBITION AND AUGMENTATION. [BOOK i. ing, by rendering incapable of activity, and muscarin its effect by exciting, stimulating into activity, this same inhibitory mechan- ism. It has further been suggested that some of the ganglia in the heart furnish the mechanism in question, And it has been sup- posed that there is a corresponding augmenting mechanism. But objections may be urged against this view, and it is safer to leave as an open question the exact manner in which inhibition and augmentation are brought about. One point is perhaps worthy of mention. We have seen that inhibition may be followed by a phase of increased activity, and that on- the whole the heart is strengthened rather than weakened by the process, while on the other hand augmentation is followed by depression and the process is distinctly an exhausting one. Hence whatever be the exact mechanism of inhibition and of augmentation, whatever be the particular elements of the cardiac structures which are concerned in the one or the other, augmenta- tion means increased expenditure, inhibition means a lessened ex- penditure, of. energy on the part of the muscular tissue of the heart. Whatever the manner in which the respective fibres act, the effect of the activity of the augmentor fibres is to hurry on the downward, catabolic changes of the cardiac tissue, while that of the inhibitory fibres is an opposite one, and we may probably say that the latter assists the constructive, anabolic, changes. Other Influences regulating or modifying the Beat of the Heart. § 140. Important as is the regulation of the heart by the nervous system, it must be borne in mind that other influences are or may be at work. The beat of the heart may for instance be modified by influences bearing directly on the nutrition of the heart. The tissues of the heart, like all other tissues, need an adequate supply of blood of a proper quality ; if the blood vary in quality or quantity the beat of the heart is correspondingly affected. The excised frog's heart, as we have seen, continues to beat for some considerable time, though apparently empty of blood. After a while however the beats diminish and eventually disappear ; and their disappearance is greatly hastened by washing out the heart with normal saline solution, which when allowed to flow through the cavities of the heart readily permeates the tissues on account of the peculiar construction of the ventricular walls. If such a * washed out ' quiescent heart be fed by means of a perfu- sion cannula, in the manner described (§ 133), with diluted blood (of the rabbit, sheep, &c.), it may be restored to functional activity. A similar but less complete restoration may be witnessed if serum be used instead of blood ; and a heart fed regularly with fresh supplies of blood or even of serum may be kept beating for a very great length of time. CHAP, iv.] THE VASCULAR MECHANISM. 259 Now, serum is as we have seen a very complex fluid containing several proteids, many ' extractives ' and various inorganic salts. As regards proteids experiments have shewn that peptone and albuinose so far from being beneficial are directly poisonous to the heart, that paraglobulin is without effect, but that serum-albumin will maintain the beats for a long time and will restore the beats of a ' washed-out ' heart. We might infer from this that serum- albumin is directly concerned in the nutrition of the cardiac tissue ; but we are met with the striking fact that a frog's heart may be maintained in vigorous pulsation for many hours, and that a ' washed-out ' frog's heart may be restored to vigorous pulsation by being fed with normal saline fluid to which a calcium salt with a trace of a potassium salt has been added.1 On the other hand, serum from which the calcium salts have been removed by precipitation with sodium oxalate is powerless to maintain or to restore cardiac pulsations. Obviously in the changes, whatever they may be, through which such fluids as serum, milk and the like (for milk and other fluids have been found efficient in this respect) maintain the beat of the heart, calcium salts play an important part ; and it is tempting to connect this with the relation of calcium salts to the clotting of blood (§ 20). We are not however justified in inferring because serum is ineffective in the absence of calcium salts, that the serum albumin is useless ; and, indeed the beneficial effects of the calcic saline fluid are not so complete as those of serum or of blood ; moreover the possible influences of the various extrac- tives, such as sugar for instance, present in the serum have to be con- sidered. We may in addition call to mind, what we said in treating of the skeletal muscles (§ 81), that fatigue or exhaustion may have a double nature, the using up of contractile material on the one hand and on the other hand the accumulation of waste products ; and the nutritive or restorative influence over the heart of any material may bear on the one or the other of these. Thus the beneficial effect of alkalies is probably in part due to their antagonizing the acids which as we have seen are being constantly produced during muscular contraction. In the various experiments which have been made in thus feeding hearts with nutritive and other fluids two facts worthy of notice have been brought to light. One is that various substances have an effect on the mus- cular walls, apart from the direct modification of the contractions. The muscular fibres of the heart over and above their rhythmic contractions are capable of varying in length, so that at one time they are longer, and the chambers when pressure is applied to them internally are dilated beyond the normal, while at another time they are shorter, and the chambers, with the same internal 1 By Ringer's Heart-Fluid, for instance, which is made by saturating in the cold normal saline solution (-65 p. c. sodium chloride) with calcium phosphate, and adding to 100 c.c. of the mixture, 2 c.c. of a 1 p. c. solution of potassium chloride. 260 REGULATION BY NUTRITION. [BOOK i. pressure, are contracted beyond the normal. In other words, the heart possesses what we shall speak of in reference to arteries as tonicity or tonic contraction, and the amount of this tonic contrac- tion, and in consequence the capacity of the chambers, varies accord- ing to circumstances. The presence of some substances appears to increase, of others to diminish this tonicity and thus to diminish or increase the capacity of the chambers during diastole. This of course would have an effect, other things being equal, on the output from the heart and so on its work ; and indeed there is some evidence that the augmentor and inhibitory impulses may also affect this tonicity, but observers are not agreed as to the manner in which and extent to which they may thus act. Another fact worthy of notice is when the heart is thus artifi- cially fed with serum, or other fluids or even with blood, the beats, whether spontaneous or provoked by stimulation, are apt to become intermittent and to arrange themselves into groups. This intermit- tence is possibly due to the fluid employed being unable to carry on nutrition in a completely normal manner, and to the consequent production of abnormal chemical substances ; and it is probable that cardiac intdhnittences seen during life are in certain cases thus brought about by some direct interference with the nutrition of the cardiac tissue and not through extrinsic nervous impulses descend- ing to the heart from the central nervous system. Various chemical substances in the blood, arising within the body or introduced as drugs, may thus affect the heart's beat by acting on its muscular fibres, or its nervous elements, or both, and that probably in various ways, modifying in different directions the rhythm, or the individual contractions, or both. Concerning the effect on the heart of blood which has not been adequately changed in the lungs we shall speak when we come to treat of respiration. The physical or mechanical circumstances of the heart also affect its beat ; of these perhaps the most important is the amount of the distention of its cavities. The contractions of cardiac muscle, like those of ordinary muscle (see § 76), are increased up to a certain limit by the resistance which they have to overcome ; a full ventricle will, other things being equal, contract more vigorously than one less full ; though, as in ordinary muscle, the limit at which resistance is beneficial may be passed, and an over- full ventricle will fail to beat at all. Hence an increase in the quantity of blood in the ventricle will augment the work done in two ways ; the quantity thrown out will, unless antagonistic influences intervene, be greater, and the increased quantity will be ejected with greater force. Further, since the distention of the ventricle at the commencement of the systole at all events is dependent on the auricular systole, the work of the ventricle (and so of the heart as a whole) is in a measure governed by the auricle. CHAP, iv.] THE VASCULAR MECHANISM. 261 An interesting combination of direct mechanical effects and indirect nervous effects is seen in the relation of the heart's beat to blood pressure. When the blood pressure is high, not only is the resistance to the ventricular systole increased, but, other things being equal, more blood flows (in the mammalian heart) through the coronary arteries. Both these events would increase the activity of the heart, and we might expect that the increase would be manifest in the rate of the rhythm as well as in the force of the individual beats. As a matter of fact, however, we do not find this. On the contrary, the relation of heart beat to pressure may be put almost in the form of a law, that " the rate of the beat is in inverse ratio to the arterial pressure ; " a rise of pressure being accompanied by a diminution, and fall of pressure by an increase of the rate of the rhythm. This however only holds good if the vagus nerves be intact. If these be previously divided, then in whatever way the blood pressure be raised — whether by injecting blood or clamping the aorta, or increasing the peripheral resistance, through an action of the vaso-motor nerves which we shall have to describe directly — or in whatever way it be lowered, no such clear and decided inverse relation between blood pressure and pulse-rate is observed. It is inferred therefore that increased blood pressure causes a slowing of the beat, when the vagus nerves are intact, because the cardio-inhibitory centre in the medulla is stimulated by the high pressure, either directly by the pressure obtaining in the blood vessels of the medulla, or in some indirect manner, and the heart in consequence more or less inhibited. SEC. 6. CHANGES IN THE CALIBRE OF THE MINUTE ARTERIES. VASO-MOTOR ACTIONS. § 141. All arteries contain plain muscular fibres, for the most part circularly disposed, and most abundant in, or sometimes al- most entirely confined to, the middle coat. Further as the arteries become smaller, the muscular element as a rule becomes more and more prominent as compared with the other elements, until, in the minute arteries, the middle coat consists almost entirely of a series of plain muscular fibres wrapped round the internal coat. Nerve fibres, of whose nature and course we shall presently speak, are distributed largely to the arteries, and appear to end chiefly in fine plexuses round the muscular fibres, but their exact terminations have not as yet been clearly made out. By mechanical, electrical, or other stimulation, this muscular coat may, in the living artery, be made to contract. During this contraction, which has the slow character belonging to the contractions of all plain muscle, the calibre of the vessel is diminished. The veins also as we have seen possess muscular elements, but these vary in amount and distribution very much more in the veins than in the arteries. Most veins however are contractile, and may vary in calibre according to the condition of their muscular elements. Veins are also supplied with nerves. It will be of advantage however to consider separately the little we know concerning the changes in the veins and to confine ourselves at present to the changes in the arteries. If any individual small artery in the web of a frog's foot be watched under the microscope, it will be found to vary considerably in calibre from time to time, being sometimes narrowed and sometimes dilated; and .these changes may take place without any obvious changes either in the heart beat or in the general circulation ; they are clearly changes of the artery itself. During the narrowing, which is obviously due to a contraction of the muscular coat of the artery, the capillaries fed by the artery and the veins into which these lead become less filled with blood, and CHAP, iv.] THE VASCULAR MECHANISM. 263 therefore paler. During the widening, which corresponds to the relaxation of the muscular coat, the same parts are fuller of blood, and redder. It is obvious that, the pressure at the entrance into any given artery remaining the same, more blood will enter the artery when relaxation takes place, and consequently the resistance offered by the artery is diminished, and less when contraction occurs, and the resistance is consequently increased; the blood flows in the direction of least resistance. The extent and intensity of the narrowing or widening, of the constriction or dilation which may thus be observed in the frog's web, vary very largely. Variations of slight extent, either more or less regular and rhythmic or irregular, occur even when the animal is apparently subjected to no disturbing causes, and may be sjpoken of as spontaneous^Alarger changes may follow events occurring in various parts/of the body ; while as the result of experimental interference (the arteries may become either constricted, in some cases almost Vto obliteration, or dilated until they acquire double or more than 'double their normal diameter. This constriction or dilation may "be brought about \not only by treatment applied directly to "the ;web, but also by \changes affecting the nerves of the leg or other .'parts of the body. /Thus section of the nerves of the leg is generally followed by a widening which may be slight or which may be very marked, and which is sometimes preceded by a passing constriction ; while stimulation of the peripheral stump of a divided nerve by an interrupted current of moderate in- tensity gives rise to constriction, often so great as almost to obliterate some of the minute arteries. Obviously, then, the contractile muscular elements of the minute arteries of the web of the frog's foot are capable by contraction or relaxation of causing decrease or increase of the calibre of the arteries; and this condition of constriction or dilation may be brought about through the agency of nerves. Indeed, not only in the frog, but also, and still more so, in warm blooded animals, have we evidence that in the case of a very large number of, if not all, the arteries of the body, the condition of the muscular coat, and so the calibre of the artery, is governed by means of nerves ; these nerves have received the general name of vaso-motor nerves. § 142. If the ear of a rabbit, preferably a light coloured one, be held up before the light, a fairly conspicuous artery will be seen running up the middle line of the ear, accompanied by its broader and more obvious veins. If this artery be carefully watched it will be found, in most instances, to be undergoing rhythmic changes of calibre, constriction alternating with dilation. At one moment the artery appears as a delicate, hardly visible pale streak, the whole ear being at the same time pallid. After a while the artery slowly widens out, becomes broad and red, the whole ear blushing, and many small vessels previously invisible coming into view. Again the artery narrows and the blush fades away ; and this may be 264 CHANGES IN CALIBRE OF ARTERIES. [BOOK i. repeated at somewhat irregular intervals of a minute, more or less. The extent and regularity of the rhythm are usually markedly increased if the rabbit be held up by the ears for a short time previous to the observation. Similar rhythmic variations in the calibre of the arteries have been observed in several regions of the body, ex. gr. in the vessels of the mesentery and elsewhere ; probably they are widely spread. Sometimes no such variations are seen, the artery remains constant in a condition intermediate between the more extreme widening and extreme narrowing just described. In fact, we may speak of an artery as being at any given time in one of three phases. It may be very constricted, in which case its muscular fibres are very much contracted ; or it may be very dilated, in which case its muscular fibres are relaxed ; or it may be mode- rately constricted, the muscular fibres being contracted to a certain extent, and remaining in such a condition that they may on the one hand pass into stronger contraction, leading to marked con- striction, or, on the other hand, into distinct relaxation, leading to dilation. We have reason to think, as we shall see, that many arteries of the body are kept habitually, or at least for long periods together, in this intermediate condition, which is fre- quently spoken of as tonic contraction or tonus, or arterial tone. § 143. If, now, in a vigorous rabbit, in which the heart is beating with adequate strength, and the whole circulation is in a satisfactory condition, the cervical sympathetic nerve be divided on one side of the neck, remarkable changes may be observed in the blood vessels of the ear of the same side. The arteries and veins widen, they, together with the small veins and the capillaries, become full of blood, many vessels previously invisible come into view, the whole ear blushes, and if the rhythmic changes described above were previously going on, these now cease ; in conse- quence of the extra supply of warm blood the whole ear becomes distinctly warmer. Now, these changes take place, or may take place, without any alteration in the heart beat or in the general circulation. Obviously the arteries of the ear have, in conse- quence of the section of the nerve, lost the tonic contraction which previously existed ; their muscular coats previously some- what contracted have become quite relaxed, and whatever rhythmic contractions were previously going on have ceased. The more marked the previous tonic contraction, and the more vigorous the heart beats, so that there is an adequate supply of blood to fill the widened channels, the more striking the result. Sometimes, as when the heart is feeble, or the pre-existing tonic contraction is slight, the section of the nerve produces no very obvious change. If now the upper segment of the divided cervical sympathetic nerve, that is the portion of the nerve passing upwards to the head and ear, be laid upon the electrodes of an induction machine, and a gentle interrupted current be sent through the nerve, fresh changes CHAP, iv.] THE VASCULAR MECHANISM. 265 take place in the blood vessels of the ear. A short time after the application of the current, for in this effect there is a latent period of very appreciable duration, the ear grows paler and cooler, many small vessels, previously conspicuous, become again invisible, the main artery shrinks to the thinnest thread, and the main veins become correspondingly small. When the current is shut off' from the nerve, these effects still last some time, but eventually pass off; the ear reddens, blushes once more, and, indeed, may become even redder and hotter, with the vessels more filled with blood than before. Obviously the current has generated in the cervical, sympathetic, nerve impulses which, passing upward to the ear and finding their way to the muscular coats of the arteries of the ear, have thrown the muscles of those coats into forcible contractions, and have thus brought about a forcible narrowing of the calibre of the arteries, a forcible constriction. Through the narrowed con- stricted arteries less blood finds its way, and hence the paleness and coldness of the ear. If the impulses thus generated be very strong, the constriction of the arteries may be so great that the smallest quantity only of blood can make its way through them, and the ear may become almost bloodless. If the impulses be weak the constriction induced may be slight only ; and, indeed, by careful manipulation the nerve may be induced to send up to the ear impulses only just sufficiently strong to restore the moderate tonic constriction which existed before the nerve was divided. We infer from these experiments that among the various nerve fibres making up the cervical sympathetic, there are certain fibres which, passing upwards to the head, become connected with the arteries of the ear, and that these fibres are of such a kind that impulses, generated in them and passing upwards to the ear, lead to marked contraction of the muscular fibres of the arteries, and thus produce constriction. These fibres are vaso-motor fibres for the blood vessels of the ear. From the loss of tone, so frequently following section of the cervical sympathetic, we may further infer, that, normally during life, impulses of a gentle kind are continually passing along these fibres, upwards through the cervical sympathe- tic, which impulses, reaching the arteries of the ear, maintain the normal tone of those arteries. But, as we said, the existence of this tone is not constant, and the effects of these tonic impulses are not so conspicuous as those of the artificial .constrictor im- pulses generated by stimulation of the nerve. § 144. The above results are obtained whatever be the region of the cervical sympathetic which we divide or stimulate between the upper and the lower cervical ganglion. We may therefore describe these vaso-motor impulses as passing upwards from the lower cer- vical ganglion along the cervical sympathetic, to the upper cervical ganglion, from which they issue by branches which ultimately find their way to the ear. But these impulses do not start from the lower cervical ganglion ; on the contrary, by repeating the experi- 266 VASO-MOTOB, FIBRES OF THE EAR. [BOOK i. [Aur. VM.C G.C.S An.Y.~ G.St.- ments of division and stimulation in a series of animals, we may trace the path of these impulses from the lower cervical ganglion, Fig. 72, through the annulus of Vieussens to the ganglion stellatum and upper part of the thoracic sympathetic chain, and thence along the rami communicantes of some or other of the upper thoracic spinal nerves to the anterior roots of those nerves, and so to the spinal cord. In the cat and the dog, and probably in other higher mammals, the chief path of the impulses lies in the second and third thoracic nerves, though some pass by the fourth, and a variable small number by the fifth and the first; in the rabbit the path is more widespread, and reaches lower down, for while the impulses pass chiefly by the fourth and fifth thoracic nerves, some pass by the second and third, and others by the sixth, seventh, and even eighth nerves. The exact path also differs in different indi- viduals of the same species. It will be observed that from the spinal cord up to the annulus of Vieussens, and the lower cervical ganglion, these vaso-motor impulses for the ear, and the augmentor impulses for the heart, (cf. Fig. 71) follow much the same path ; but there they part company. We Fig. 72. DIAGRAM ILLUSTRATING THE PATHS OF VASO-CONSTRICTOR FIBRES ALONG THE CERVICAL SYMPATHETIC AND (PART OF) THE ABDOMINAL SPLANCHNIC. Aur. artery of ear. G.C.S. superior cervical ganglion. Abd. Spl. upper roots of and part of abdominal splanchnic nerve. V.M.C. vaso-motor centre in spinal bulb. The other references are the same as in Fig. 71, § 138. The paths of the constrictor fibres are shewn by the arrows. The dotted line along the middle of the spinal cord, Sp. C., is to indicate the passage of constrictor impulses down the cord from the vaso-motor centre in the spinal bulb. can thus trace these vaso-motor impulses backwards along the cer- vical sympathetic to the anterior roots of certain thoracic nerves, and through these to the thoracic region of the spinal cord, where we will for the present leave them. We may, accordingly, speak of vaso-motor fibres for the ear as passing from the thoracic spinal cord to the ear along the track just marked out ; stimulation of these fibres at their origin from the spinal cord, or at any part of their course (along the anterior roots of the second, third or other upper thoracic nerves, visceral branches [rami communicantes] of those nerves, ganglion stellatum or upper part of thoracic sympathetic chain, annulus of Vieussens, &c. &c.), leads to constriction in the blood vessels of the ear of that side ; and section of these fibres at any part of the same course tends to abolish any previously CHAP, iv.] THE VASCULAR MECHANISM. 267 existing tonic constriction of the blood vessels of the ear, though the effect of section is not so constant or striking as that of stimulation. § 145. We must now turn to another case. In dealing with digestion we shall have to study the submaxillary salivary gland. We may for the present simply say that this is a glandular mass well supplied with blood vessels, and possessing a double nervous supply. On the one hand it receives fibres from the cervical sympathetic, Fig. 73 v. sym. (in the dog, in which the effects which we are about to describe are best seen, the vagus and cervical cTi.t' FIG. 73. DIAGRAMMATIC REPRESENTATION OF THE SUBMAXILLARY GLAND OP THE DOG WITH ITS NERVE AND BLOOD VESSELS. (The dissection has 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 submaxillary gland, into the duct (sm. d.) of which a cannula has been tied The sublingual gland and duct are not shewn, n. I., n. I'. The lingual branch of the fifth nerve, the part n. I. 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. I. is not shewn, sm. gl. The submaxillary 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, q. cer. s. The upper cervical ganglion, two branches of which forming a plexus (a. f.) 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. 268 CONSTRICTOR AND DILATOR FIBRES. [BOOK i. sympathetic are enclosed in a common sheath so as to form what appears to be a single trunk), which reach the gland in company with the arteries supplying the gland (n, sym. sm.). On the other hand it receives fibres from a small nerve called the chorda tympani (ch. t.), which, springing from the 7th cranial (facial) nerve, crosses the tympanum of the ear (hence the name), and, joining the lingual branch of the 5th nerve, runs for some distance in company with that nerve, and then ends partly in the tongue, and partly in a small nerve which, leaving the lingual nerve before reaching the tongue, runs along the duct of the submaxillary gland, and is lost in the substance of the gland ; a small branch is also given off to the sublingual gland. Now, when the chorda tympani is simply divided, no very remarkable changes take place in the blood vessels of the gland, but if the peripheral segment of the divided nerve, that still in connection with the gland, be stimulated, very marked results follow. The small arteries of the gland become very much dilated, and the whole gland becomes flushed. (As we shall see later on the gland at the same time secretes saliva copiously, but this does not concern us just now.) Changes in the calibre of the blood vessels are, of course, not so readily seen in a compact gland as in a thin extended ear ; but if a fine tube be placed in one of the small veins by which the blood returns from the gland, the effects on the blood flow of stimulating the chorda tympani become very obvious. Before stimulation the blood trickles out in a thin, slow stream of a dark venous colour ; during stimulation the blood rushes out in a rapid full stream, often with a distinct pulsation, and frequently of a colour which is still scarlet and arterial in spite of the blood having traversed the capillaries of the gland ; the blood rushes so rapidly through the widened blood vessels that it has not time to undergo completely that change from arterial to venous which normally occurs while the blood is traversing the capillaries of the gland. This state of things may continue for some time after the stimulation has ceased, but before long the flow from the veins slackens, the issuing blood becomes darker and venous, and eventually the circulation becomes normal. We shall have occasion later on to speak of the nervi erigentes, the stimulation of which gives rise to the erection of the penis. The erection of the penis is partly due to a widening of the arteries supplying the peculiar erectile tissue of that organ, whereby that tissue becomes distended with blood, and the widening is brought about by impulses passing along the nerves in question. Obviously the chorda tympani and the nervi erigentes contain fibres which we may speak of as ' vaso-motor ' since stimulation of them produces a change in, brings about a movement in the blood vessels ; but the change produced is of a character the very opposite to that produced in the blood vessels of the ear by stimulation of the cervical sympathetic. There stimulation of the CHAP, iv.] THE VASCULAR MECHANISM. 269 nerve caused contraction of the muscular fibres, constriction of the small arteries ; here stimulation of the nerve causes a widen- ing of the arteries, which widening is undoubtedly due to relaxa- tion of the muscular fibres. Hence we must distinguish between two kinds of vaso-motor fibres, fibres the stimulation of which produces constriction, vaso-constrictor fibres, and fibres the stimu- lation of which causes the arteries to dilate, vaso-dilator fibres, the one kind being the antagonist of the other. § 146. In the chorda tympani, the vaso-motor fibres are exclusively vaso-dilator fibres, and this is true both of the part of the nerve ending in the submaxillary and sublingual glands, and the rest of the ending of the nerve in the tongue. Stimula- tion of the chorda tympani (so far as the vaso-motor functions of the nerve are concerned, for it has, as we shall see, other func- tions), at any part of its course from its leaving the facial nerve to its endings in the gland or tongue, produces only vaso-dilator effects, never vaso-constrictor effects. The cervical sympathetic on the other hand is not exclusively vaso-constrictor. It con- tains as we have seen vaso-constrictor fibres for the ear. It also contains vaso-constrictor fibres for other regions of the head and face. For instance the branches of the cervical sympathetic going to the submaxillary gland of which we just spoke (Fig. 73 n. sym. sm.), contain vaso-constrictor fibres for the vessels of the gland ; stimulation of these fibres produces, on the vessels of the gland, an effect exactly the opposite of that produced by stimula- tion of the chorda tympani; to this point we shall have to return when we deal with the gland in connection with digestion. And we might give other instances ; in fact the dominant effect on the blood vessels of stimulating the cervical sympathetic is a vaso-constrictor effect. There are however certain cases in which the opposite effect, a vaso-dilator effect, in certain regions has been observed as the result of stimulating the cervical sympa- thetic. And we may now turn to other nerves in which such a double effect, now a vaso-constrictor, now a vaso-dilator effect, may be more readily obtained. In the frog as we have seen, division of the nerves of the leg leads to a widening of the arteries of the web of the foot of the same side, and stimulation of the peripheral end of the nerve causes a constriction of the vessels, which, if the stimulation be strong, may be so great that the web appears for the time being to be devoid of blood. Also in a mammal division of the sciatic nerve causes a similar widening of the small arteries of the skin of the leg. Where the condition of the circulation can be readily examined, as for instance in the hairless balls of the toes, espe- cially when these are not pigmented, the vessels are seen to be dilated and injected ; and a thermometer placed between the toes shews a rise of temperature amounting, it may be, to several degrees. If moreover the peripheral end of the divided nerve be 270 VASO-MOTOR NERVES OF THE LIMBS. [Boon i. stimulated, the vessels of the skin become constricted, the skin grows pale, and the temperature of the foot falls. And very similar results are obtained in the forelimb by division and subsequent stimulation of the nerves of the brachial plexus. The quantity of blood present in the blood vessels of a part of the body or of an organ of the mammal may sometimes be observed directly by means of the plethysmo graph, of which we have already spoken (§ 104), but has frequently to be determined indirectly. The temperature of a passive structure subject to cooling influences, such as the skin, is largely dependent on the supply of blood: the more abundant the supply, the warmer the part. Hence in these parts variations in the quantity of blood may be inferred from variations of temperature; but in dealing with more active structures such as muscles there are obviously sources of error in the possibility of the treatment adopted, such as the stimulation of a nerve, giving rise to an increase of temperature due to increased metabolism, independent of variations in blood supply. So far the results are quite like those obtained by division and stimulation of the cervical sympathetic, and we might infer that the sciatic nerve and brachial plexus contain vaso-constrictor fibres only for the vessels of the skin of the hind limb and fore limb, vaso-dilator fibres being absent. But sometimes a different result is obtained ; on stimulating the divided sciatic nerve the vessels of the foot are not constricted but dilated, perhaps widely dilated. And this vaso-dilator action is almost sure to be mani- fested when the nerve is divided, and the peripheral stump stimu- lated some time, two to four days, after division, by which time commencing degeneration has begun to modify the irritability of the nerve. For example, if the sciatic be divided, and some days afterwards, by which time the flushing and increased tempera- ture of the foot, following upon the section, has wholly or largely passed away, the peripheral stump be stimulated with an inter- rupted current a renewed flushing and rise of temperature is the result. We are led to conclude that the s"ciatic nerve (and the same holds good for the brachial plexus) contains both vaso-con- strictor and vaso-dilator fibres, and to interpret the varying result as due to variations in the relative irritability of the two sets of fibres. The constrictor fibres appear to predominate in these nerves, and hence constriction is the more common result of stimulation ; the constrictor fibres also appear to be more readily affected by a tetanizing current than do the dilator fibres. When the nerve after division commences to degenerate the constrictor fibres lose their irritability earlier than the dilator fibres, so that at a certain stage a stimulus, such as the interrupted current, while it fails to affect the constrictor fibres, readily throws into action the dilator fibres. The latter, indeed, appear to retain their irritability after section of the nerve for a much longer time than CHAP, iv.] THE VASCULAR MECHANISM. 271 do ordinary motor nerves (§ 78). The result is perhaps even still more striking if a mechanical stimulus, such as that of " crimp- ing " the nerve by repeated snips with the scissors, be employed. Exposure to a low temperature again seems to depress the con- strictors more than the dilators ; hence when the leg is placed in ice-cold water stimulation of the sciatic, even when7 the nerve has been but recently divided, throws the dilator only into action and produces flushing of the skin with blood. Slow rhythmical stimu- lation moreover of even a freshly divided nerve may produce dila- tion. And there are other facts which support the same view that the sciatic nerve (and brachial plexus) contains both vaso- constrictor and vaso-dilator fibres which are differently affected by different circumstances. In the splanchnic nerves which supply fibres to the blood ves- sels of so large a part of the abdominal viscera, there .is abundant evidence of the presence of vaso-constrictor fibres. Division of this nerve leads to a widening of the blood vessels of the abdo- minal viscera, stimulation of the nerve to a constriction ; and as we shall see, since the amount of blood vessels thus governed by this nerve is very large indeed, interference either in the one direction or the other with its vaso-motor functions produces very marked results, not only on the circulation in the abdomen but on the whole vascular system. There is some evidence that the splanchnic nerves also contain vaso-dilator fibres, but this evi- dence is of a more or less indirect character, and in any case, the number of such fibres must be small. So far as we know, the vaso-motor fibres contained in the sciatic and the like spinal nerves are distributed chiefly at least to the blood vessels of the skin. Though so large a part of the fibres of these nerves end in the muscles, the evidence of vaso- motor fibres passing to the blood vessels of the muscles is by no means clear and undisputed. The blood vessels of a muscle un- doubtedly may change in calibre. For instance, when a muscle contracts there is always an increased flow of blood through the muscle ; this may be in part a mere mechanical result of the change of form, the shortening and thickening of the fibres open- ing out the minute blood vessels, but is also, if not chiefly, due to the widening of the arteries by relaxation of their muscular walls. Such a widening may be seen when a thin muscle of a frog is made, in the living body, to contract under the microscope. But this widening has not been proved beyond dispute to be due to the action of vaso-dilator fibres. Indeed it has been argued that when a muscle contracts, some of the chemical products of the metabolism of the muscle may, by direct, local action on the minute blood vessels, lead to a widening of those blood vessels. And in some other organs, the brain and the kidney for instance, we find functional activity accompanied by a widening of the blood vessels under circumstances which seem to preclude the 272 THE COURSE OF VASO-MOTOR FIBRES, [BOOK i. possibility of the widening 'being d>ue to vaso-dilator impulses reaching the organ from without ; in such instances it is sug- gested that the widening is due to a local effect of the products of the activity of the organ. To this point we shall return. With regard to vaso-constrictor fibres also the evidence that they are supplied to muscles is, in like manner, not beyond dispute. Section or stimulation of the nerves induces it is true changes in the temperature of the muscles as it does in that of the skin. But, as we urged just now, to argue from this that changes in the blood supply have taken place is not wholly safe ; moreover the changes in temperature observed are slight. Again, the fact that when the nerve of a muscle is divided the blood vessels of the muscle widen, somewhat like the blood vessels of the ear after division of the cervical sympathetic, has been brought forward as indicating the presence of vaso-constrictor fibres carrying the kind of influence which we called tonic, leading to an habitual moder- ate constriction. Neither arguments can be regarded as abso- lutely conclusive. The knowledge we possess at present leaves us in fact in doubt whether the blood-flow through the muscles, though these form so large a part of the body, is really governed by the central nervous system. The two parts of the body undoubtedly and pre-eminently sup- plied by vaso-constrictor fibres proceeding from and governed by the central nervous system are on the one hand the skin and on the other hand the abdominal viscera. As we shall see, the vari- ations in the blood supply to the skin are more strikingly of use to the body at large, in regulating the temperature of the body for instance, than they are to the skin itself. The variations in the blood supply to the abdominal viscera also serve important general purposes ; they play their part in the regulation of the temperature of the body, and through them the viscera serve as a reservoir to which blood may without harm be shunted when occasion demands. It would appear as if the vaso-constrictor mechanism were chiefly used for the general purposes of the economy. Accepting the view that the presence of vaso-dilator fibres in the nerves going to muscles is not definitely proved and disregard- ing the scanty and more or less obscure vaso-dilators of the sciatic and other spinal nerves, we find that in special cases only, in cases where it would seem that special means are needed to secure an ample flow of blood through a particular part, unmis- takably vaso-dilator fibres are present. The Course of Vaso-motor Fibres. § 147. Both the vaso-constrictor and the vaso-dilator fibres have their origin in the central nervous system, the spinal cord CHAP, iv.] THE VASCULAR MECHANISM. 273 or the brain, but it will be desirable to speak of the course of the two sets separately. Vaso-constrictor Fibres. In the mammal, so far as we know at present, all the vaso-constrictor fibres for the whole body take their origin in the middle region of the spinal cord, or rather, leave the spinal cord by the nerves belonging to this middle region. Thus in the dog the vaso-constrictor fibres, not only for the trunk but for the limbs, head, face and tail, leave the spinal cord by the anterior roots of the spinal nerves reaching from about the second thoracic to the fourth lumbar nerve, both inclu- sive, though some few may pass by the first thoracic and by the fifth lumbar. Those for the head and neck leave the spinal cord as we have seen, § 144, chiefly by the second and third thoracic nerves, though some leave by the fourth and a variable small number by the fifth and by the first ; those for the fore limbs leave by a number of thoracic nerves reaching from the fourth to the ninth or even the tenth, those by the seventh being the most numerous. Those for the hind limbs leave by the nerves reaching from the eleventh thoracic to the third lumbar, some passing by the tenth thoracic and the fourth lumbar. Those for the tail leave by the first, second and third lumbar. And those for the trunk leave by the successive spinal nerves supplying the trunk. This ar- rangement may be taken as indicating generally how these fibres leave the spinal cord, bearing in mind that the fourth lumbar nerve of the dog corresponds to about the second lumbar of man, and that the details differ in different kinds of animals and indeed in different individuals. Running in the case of each nerve root to the mixed nerve trunk these vaso-constrictor fibres pass along the visceral branch, white ramus communicans, to the thoracic and abdominal sympa- thetic ganglia (Fig. 72). From thence they reach their destina- tion in various ways. Thus, those going to the head and neck pass upward through the annulus of Vieussens to the lower cervical ganglion and thence, as we have seen, up the cervical sympa- thetic ; many of the fibres for the neck however pass directly from the stellate ganglion. Those for the abdominal viscera pass off in a similar way by the splanchnic nerves, Fig. 72, abd. spl. and by smaller nerves joining the inferior mesenteric ganglion. Those destined for the arm, making their way backwards by grey rami communicantes (Fig. 23 r. v.), join the nerves of the brachial plexus ; while those for the hind leg pass in a similar way through some portion of the abdominal sympathetic before they join the nerves of the sciatic plexus. These as we have seen are dis- tributed chiefly to the skin, and the constrictor fibres of the skin of the trunk probably reach the spinal nerves in which they ultimately run in a similar manner. All the vaso-constrictor fibres, whatever their destination, leave the spinal cord by the 18 274 COURSE OF VASO-CONSTRICTOR FIBRES. [BOOK i. anterior roots of spinal nerves, and then passing through the appropriate visceral branches, join the thoracic or abdominal sympathetic ganglia. In their course the fibres undergo a re- markable change. Along the anterior root and along the visceral branch they are medullated fibres, but before they reach the blood vessels for which they are destined they become non-medullated fibres ; they appear to lose their medulla in some or other of the ganglia. We are in many cases able to determine experimentally by the following method, the ganglion or ganglia in which particular fibres end, that is to say in which they become connected with nerve cells. It is found that the drug nicotin abolishes or sus- pends the action of vaso-motor fibres and of other fibres running in the sympathetic system. Thus in a rabbit, after a certain dose of nicotin has been given, stimulation of the cervical sympathetic nerve in the neck no longer causes constriction of the vessels of the ear. But it is found in such cases that though stimulation of the trunk of the nerve in the neck is without effect, stimulation of the appropriate nerve branches passing off from the superior cervical ganglion on their way to the ear, does produce constric- tion of the vessels of the ear. Obviously the nicotin does not affect the peripheral fibres and endings of the nerve, but some part of the nerve more central than the branches proceeding from the superior cervical ganglion. Further, if the ganglion itself be cautiously painted with a weak (1 p.c.) solution of nicotin, care being taken to avoid excess, stimulation of the nerve in the neck has no effect on the vessels of the ear, whereas if the nicotin be applied to a corresponding extent to the trunk of the nerve in the neck, none being allowed to have access to the ganglion, stimu- lation of the trunk in the neck, even if applied to the very spot on which the nicotin has been placed, produces the usual con- striction of the vessels of the ear. Obviously the nicotin produces its paralysing effects by acting on the nerve cells, or on the fibres just as they are becoming connected with nerve cells. If the solution of nicotin be applied not to the upper, but to the middle or to the lower cervical ganglion, stimulation of the nerve between the ganglion and the spinal cord produces the usual constrictor effects. This shews that the constrictor fibres pass through the lower and the middle ganglion as fibres, not connected with cells, otherwise they would be here affected by nicotin ; they are affected by nicotin in the upper ganglion, and we therefore infer that they end in, that is, are connected with cells in that ganglion. In the same way it may be found that the vaso-constrictor fibres of the abdominal splanchnic are connected with cells in the solar plexus. Indeed by this method we may determine in what ganglia the vaso-constrictor and other fibres of the sympathetic system end ; and a remarkable distribution, determined by morphological causes among others, has in this way been made out, some fibres CHAP, iv.] THE VASCULAR MECHANISM. 275 very speedily becoming connected with nerve cells, others run- ning a very long course before they so end. § 148. Vaso-dilator Fibres. Some of these appear to run much the same course as the vaso-constrictors. Such are the vaso-dilator fibres running in spinal nerves like the sciatic and brachial, those which seem to be present in the splanchnic, and certain fibres of the cervical sympathetic which in some animals at least act as vaso-dilators towards certain parts of the mouth and face. With regard to these, the evidence of .whose existence, as we have seen, is at least in most cases, difficult, special or indirect, we have at present no proof that their general course is essentially different from that of the constrictors. The more distinct and notable vaso-dilators however do run a different course. These are found in the nerves coming from the cranial and sacral regions of the central nervous system whence, as we have seen, no vaso-constrictor fibres are known to issue. Thus the vaso-dilator fibres for the sub-maxillary gland running in the chorda tympani may be traced as we have seen back to the facial or seventh nerve ; and the continuation of the chorda tympani along the lingual nerve to the tongue contains vaso-dila- tor fibres for that organ ; when the lingual is stimulated, the blood vessels of the tongue dilate owing to the stimulation of the conjoined chorda tympani fibres. The ramus tympanicus of the glossopharyngeal nerve contains vaso-dilator fibres for the parotid gland, and it appears probable that the trigeminal nerve contains vaso-dilator fibres for the eye and nose and possibly for other parts. The vaso-dilator fibres which pass into the nervi erigentes, leave the sacral region of the cord by the anterior roots of the sacral nerves, the particular nerves differing in different animals ; thus in the dog and cat they pass by the first, second and third, in the rabbit by the second, third and fourth, in man by the third, fourth and fifth sacral nerves. In these instances the vaso-dilator fibres, as they leave the central nervous system, are, like the vaso-constrictor fibres, fine medullated fibres, but unlike the majority at least of the vaso- constrictors they retain their medulla for the greater part of their course and only lose it near their termination in the tissue whose blood vessels they supply. The Effects of Vaso-motor Actions. § 149. A very little consideration will shew that vaso-motor action is a most important factor in the circulation. In the first place the whole flow of blood in the body is adapted to and governed by what we may call the general tone of the arteries of the body at large. In a normal condition of the body, the muscular fibres of a very large number of the minute arteries 276 EFFECTS OF VASO-MOTOR ACTIONS. [BOOK i. of the body are in a state of tonic, i. e. of moderate, contraction, and it is the narrowing due to this contraction which forms a large item of that peripheral resistance which we have seen to be one of the great factors of blood pressure. The nor- mal general blood pressure, and therefore the normal flow of blood, is in fact dependent on the ' general tone ' of the minute arteries. In the second place local vaso-motor changes in the condi- tion of the minute arteries, changes, that is to say, of any par- ticular vascular area, have very decided effects on the circulation. These changes, though local themselves, may have effects which are both local and general, as the following considerations will shew. Let us suppose that the artery A is in a condition of normal tone, is midway between extreme constriction and dilation. The flow through A is determined by the resistance in A and in the vascular tract which it supplies, in relation to the mean arterial pressure, which again is dependent on the way in which the heart is beating and on the peripheral resistance of all the small arteries and capillaries, A included. If, while the heart and the rest of the arteries remain unchanged, A be constricted, the peripheral resistance in A will increase, and this increase of resistance will lead to an increase of the general arterial pressure. Since, as we have seen, § 101, it is arterial pressure which is the immediate cause of the flow from the arteries to the veins, this increase of arterial pressure will tend to drive more blood from the arteries into the veins. The constriction of A however, by increasing the resistance, opposes any increase of the flow through A itself, in fact will make the flow through A less than before. The whole increase of discharge from the arterial into the venous system will take place through the arteries in which the resistance remains un- changed, that is, through channels other than A. Thus, as the result of the constriction of any artery there occur, (1) diminished flow through the artery itself, (2) increased general arterial pressure, leading to (3) increased flow through the other arteries. If, on the other hand, A be dilated, while the heart and other arteries remain unchanged, the peripheral resistance in A is diminished. This leads to a lowering of the general arterial pressure, which in turn tends to drive less blood from the arteries into the veins. The dilation of A however, by diminishing the resistance, permits, even with the lowered pressure, more blood to pass through A itself than before. Hence the diminished flow tells all the more on the rest of the arteries in which the resistance remains unchanged. Thus, as the result of the dilation of any artery, there occur (1) increased flow of blood through the artery itself, (2) diminished general pressure, and (3) diminished flow through the other arteries. Where the artery thus constricted or dilated is small, the local effect, the diminution or increase of flow CHAP, iv.] THE VASCULAR MECHANISM. 277 through itself, is much more marked than the general effects, the change in blood pressure and the flow through other arteries. When, however, the area the arteries of which are affected is large, the general effects are very striking. Thus if while a tracing of the blood pressure is being taken by means of a manometer connected with the carotid artery, the abdominal splanchnic nerves be divided, a conspicuous but steady fall of pressure is observed, very similar to but more marked than that which is shewn in Fig. 74. The section of the abdominal splanchnic nerves causes the arteries of the abdominal viscera to dilate, and these being very numerous, a large amount of peripheral resistance is taken away, and the blood pressure falls accordingly ; a large increase of flow into the portal veins takes place, and the supply of blood to the face, arms, and legs is proportionally diminished. It will be observed that the dilation of the arteries is not instantaneous but somewhat gradual, as shewn by the pressure sinking not abruptly but with a gentle curve. The general effects on blood pressure by vaso-motor changes are so marked that the manometer may be used to detect vaso- motor actions. Thus, if the stimulation of a particular nerve or any other operation leads to a marked rise of the mean blood pressure, unaccompanied by any notable changes in the heart beat, we may infer that constriction has taken place in the arteries of some considerable vascular area; and similarly, if the effect be a fall of blood pressure, we may infer that constriction has given way to dilation. Vaso-motor .Functions of the Central Nervous System. § 150. The central nervous system, to which we have traced the vaso-motor nerves, makes use of these nerves to regulate the flow of blood through the various organs and parts of the body ; by the local effects thus produced it assists or otherwise influences the functional activity of this or that organ or tissue ; by the general effects it secures the well being of the body. When the vaso-dilators are brought into play the chief effect is a local one ; when a general effect has to be produced the vaso-con- strictors are employed, though these of course also bring about local effects. And we may consider the two separately. The vaso-dilator nerves, .the use of which is more simple than that of the vaso-constrictors in so far as it appears not to be complicated by the presence of habitual tonic influences, occur as parts of distinct mechanisms used chiefly at least as reflex mechanisms, with centres placed in different regions of the central nervous system. Thus, when food is placed in the mouth afferent impulses, generated in the nerves of taste, give rise in the central nervous system to efferent impulses, which descend 278 USE OF VASO-DILATOR FIBRES. [BOOK i. the chorda tympani and other nerves to the salivary glands and, by dilating the blood vessels, secuia a copious flow of blood through the glands while, as we shall see later on, they excite the glands to secrete. The centre of this reflex action appears to lie in the spinal bulb and may be thrown into activity not only by impulses reaching it along the specific nerves- of taste, but also by impulses passing along other channels ; thus, emotions started in the brain by the sight of food or otherwise may give rise to impulses passing down along the central nervous system itself to the spinal bulb, or events in the stomach may send impulses up the vagus nerve, or stimulation of one kind or another may send impulses up almost any sentient nerve, and these various impulses reaching the spinal bulb may, by reflex action, throw into activity the vaso-dilator fibres of the chorda tympani and other analogous nerves, and bring about a flushing of the salivary glands, while at the same time they cause the glands to secrete. The vaso-dilator fibres of the nervi erigentes may be thrown into activity in a similar reflex way, the centre, which is also easily thrown into activity by impulses descending down the spinal cord from the brain, being placed in the sacral and perhaps also in the upper lumbar or lower thoracic region of the spinal cord. That such a centre does exist is shewn by the fact that, when in a dog the spinal cord is completely divided in the thoracic region, erection of the penis may readily be brought about by stimulation of appropriate sentient surfaces. And other instances might be quoted in which vaso-dilator fibres appear as part of a reflex mechanism the centre of which is placed in the central nervous system not far from the origin of the nerves in which the vaso-dilator fibres run. § 151. Turning now to the vaso-constrictor fibres we find that these form a more coherent system ; and this is in accordance with the feature of the vaso-constrictor mechanisms, that they are largely employed to produce general effects Moreover their utility is increased, though at the same time their use becomes somewhat more complicated, by reason of the existence of tonic influences ; since the same fibres may, on the one hand, by an increase in the impulses passing along them, be the means of constriction, and on the other hand, by the removal or diminution of the tonic influences passing along them, be the means of dilation. We have already traced all the vaso-constrictor fibres from the middle region of the spinal cord to the sympathetic system in the thorax and abdomen ; from thence they pass (1) by the splanchnic, hypogastric, and other nerves to the viscera of the abdomen and pelvis, (concerning the vaso-motor nerves of the thoracic viscera we know at present very little), (2) by the cervical sympathetic to the skin of the head and neck, the salivary glands and mouth, the eyes and other parts, and possibly the brain including its CHAP, iv.] THE VASCULAR MECHANISM. 279 membranes, though the presence of vaso-motor fibres in the brain itself is much disputed, (3) by the brachial and sciatic plexuses to the skin of the fore- and hind-limbs, and by various other nerves to the skin of the trunk. The chief parts of the body supplied by vaso-constrictor fibres appear to be the skin with its appendages, and the alimentary canal with its appendages, glandular and other ; the great mass of skeletal muscles appears, as we have seen, to receive a relatively small supply of vaso-con- strictor fibres. If in an animal the spinal cord be divided in the lower thoracic region, the skin of the legs becomes flushed, their temperature frequently rises, and there is a certain amount of fall in the general blood pressure as measured, for instance, in the carotid ; and this state of things may last for some considerable time. Obviously the section of the spinal cord has cut off the usual tonic influences descending to the lower limbs ; in consequence the blood vessels have become dilated, in consequence the general peripheral resistance has become proportionately diminished, and in consequence the general blood pressure has fallen. The tonic vaso-constrictor impulses for the lower limbs, therefore, have their origin in the central nervous system higher up than the lower thoracic region of the spinal cord. If the spinal cord be divided higher up, say above the roots of the fifth or sixth thoracic nerves, the cutaneous blood vessels of the lower limbs dilate, as in the former case, and on examination it will be found that the blood vessels of the abdomen are also largely dilated ; at the same time the blood pressure undergoes a very marked fall, it may indeed be reduced to a very few milli- meters of mercury. Obviously the tonic vaso-constrictor impulses passing to the abdomen and to the lower limbs take origin in the central nervous system higher up than the level of the fifth thoracic nerve. If the section of the spinal cord be made above the level of the second thoracic nerve, in addition to the abovementioned results the vessels of the head and face also become dilated ; but in consequence of the fall of general blood pressure just mentioned, these vessels never become so full of blood, the loss of tone is not so obvious in them as after simple division of the cervical sym- pathetic, since the latter operation produces little or no effect on the general blood pressure. Obviously then the tonic vaso-constrictor impulses, which passing to the skin and viscera of the body maintain that tonic narrowing of so many small arteries by which the general peri- pheral resistance, and so the general blood pressure, is maintained, proceed from some part of the central nervous system higher up than the upper thoracic region of the spinal cord. And, since exactly the same results follow upon section of the spinal cord in the cervical region right up to the lower limit of the spinal 280 VASO-MOTOR CENTRE. [BOOK i. bulb, we infer that these tonic impulses proceed from the spinal bulb. On the other hand we may remove the whole of the brain right down to the upper limits of the spinal bulb, and yet produce no flushing, or only a slight transient flushing, of any part of the body and no fall at all, or only a slight transient fall, of the general blood pressure. We therefore seem justified in assuming the existence in the spinal bulb of a nervous centre, which we may speak of as a vaso-motor centre, or the lulbar vaso-motor centre, from which proceed tonic vaso-constrictor impulses, or which regulates the emission and distribution of such tonic vaso- constrictor impulses or influences over various parts of the body. § 152. The existence of this vaso-motor centre may, moreover, be shewn in another way. The extent or amount of the tonic constrictor impulses proceeding from it may be increased or diminished, the activity of the centre may be augmented or inhibited, by impulses reaching it along various afferent nerves ; and provided no marked changes in the heart beat take place at the same time, a rise or fall of general blood pressure may be taken as a token of an increase or decrease of the activity of the centre. In the rabbit there is found in the neck, lying side by side with the cervical sympathetic nerve and running for some distance in company with it, a slender nerve which may be ultimately traced down to the heart, and which, if traced upwards, is found to come off somewhat high up from the vagus, by two or more roots, one of which is generally a branch of the superior laryngeal nerve. This nerve (the fibres constituting which are in the dog bound up with the vagus, and do not form an independent nerve) appears to be exclusively an afferent nerve ; when after division of the nerve the peripheral end, the end still in connection with the heart, is stimulated no marked results follow. The beginnings of the nerve in the heart are therefore quite different from the endings of the inhibitory fibres of the vagus, or of the augmentor fibres of the sympathetic system ; the nerve has nothing to do with the nervous regulation of the heart treated of in Sec. 5. If now, while the pressure in an artery such as the carotid is being registered, the central end of the nerve (i.e. the one connected with the brain) be stimulated with the interrupted current, a gradual but marked fall of pressure (Fig. 74) in the carotid is observed, lasting, when the period of stimulation is short, some time after the removal of the stimulus. Since the beat of the heart is not markedly changed, the fall of pressure must be due to the diminution of peripheral resistance occasioned by the dilation of some arteries. And it is probable that the arteries thus dilated are chiefly if not exclusively those arteries of the ab- dominal viscera which are governed by the splanchnic nerves; for if these nerves are divided on both sides previous to the experi- CHAP, iv.] THE VASCULAR MECHANISM. 281 ment, the fall of pressure when the nerve is stimulated is very small, in fact almost insignificant. The inference we draw is as follows. The afferent impulses passing upwards along the nerve FIG. 74. TRACING, SHEWING THE EFFECT ON BLOOD PRESSURE OF STIMULATING THE CENTRAL END OF THE DEPRESSOR NERVE IN THE RABBIT. On the time marker below the intervals correspond to seconds. At x an interrupted current was thrown into the nerve. in question have so affected some part of the central nervous system that the influences which, in a normal condition of things, passing along the splanchnic nerves keep the minute arteries of the abdominal viscera in a state of moderate tonic constriction, fail altogether, and those arteries in consequence dilate just as they do when the splanchnic nerves are divided, the effect being possibly increased by the similar dilation of other vascular areas. Since stimulation of the nerve of which we are speaking always produces a fall, never a rise of blood pressure, the amount of fall of course being dependent on circumstances, such as the condition of the nervous system, state of blood pressure and the like, the rierve is known by the name of the depressor nerve. As we shall point put later on, by means of this afferent nerve from the heart the peripheral resistance is, in the living body, lowered to suit the weakened powers of a labouring heart. This gradual lowering of blood pressure by diminution of peripheral resistance affords a marked contrast to the sudden lowering of blood pressure by cardiac inhibition ; compare Fig. 74 with Fig. 70. § 153. But the general blood pressure may be modified by afferent impulses passing along other nerves than the depressor, the modification taking on, according to circumstances, the form either of decrease or of increase. Thus, if in an animal placed under the influence of urari (some anesthetic other than chloral &c. being used), the central stump of the divided sciatic nerve be stimulated, an increase of blood pressure (Fig. 75) almost exactly the reverse of the 282 DEPRESSOR NERVE. [BOOK i. decrease brought about by stimulating the depressor, is observed. The curve of the blood pressure, after a latent period during which no changes are visible, rises steadily, reaches a maximum and FIG. 75. EFFECT ON BLOOD PRESSURE CURVE OF STIMULATING SCIATIC NERVE UNDER URARI (Cat). x marks the moment in which the current was thrown into the nerve. Artificial respiration was carried on, and the usual respiratory undulations are absent. soon slowly falls again, the fall sometimes beginning to appear before the stimulus has been removed. This rise of pressure, since it may be observed in the absence of any increase in the heart beat, such at least as could give rise to it, must be due to the constriction of certain arteries ; the arteries in question being those of the splanchnic area certainly, and possibly those of other vascular areas as well. The effect is not confined to the sciatic ; stimulation of any nerve containing afferent fibres may produce the same rise of pressure, and so constant is the result that the experiment has been made use of as a method for determining the existence of afferent fibres in any given nerve and even tfye paths of centripetal impulses through the spinal cord. If, on the other hand, the animal be under the influence not of urari but of a large dose of chloral, instead of a rise of blood pressure a fall, very similar to that caused by stimulating the depressor, is observed when an afferent nerve is stimulated. The condition of the central nervous system seems to determine whether the effect of afferent impulses on the central nervous system is one leading to an augmentation of vaso-constrictor impulses, and so to a rise, or one leading to a diminution of vaso- constrictor impulses and so to a fall of blood pressure. § 154. We have used the words ' central nervous system ' in speaking of the above ; we have evidence, however, that the part of the central nervous system acted on by the afferent impulses is the vaso-motor centre in the spinal bulb, and that the effects in the way of diminution (depressor) or of augmentation (pressor) are the results of afferent impulses inhibiting or augmenting the tonic activity of this centre or of a part of this centre especially connected with the splanchnic nerves. The whole brain may be removed right down to the bulb, and yet the effects of stimulation in the direction either of diminution or of augmentation may still be brought about. If the bulb be removed, these effects are no CHAP, iv.] THE VASCULAR MECHANISM. 283 longer seen, though all the rest of the nervous system be left intact. Nay, more, by partially interfering with the bulb, we may partially diminish these effects and mark out, so to speak, the limits of the centre in question within the bulb itself. Thus, in an intact animal under urari, stimulation of the sciatic nerve with a stimulus of a certain strength will produce a rise of blood pressure up to a certain extent. After removal of the whole brain right down to the bulb, the same stimulation will produce the same rise as before ; the vaso-motor centre has not been interfered with. Pro- ceeding downwards, however, and removing the bulb piecemeal by successive transverse sections a level is soon met with, beyond which removal of the nervous substance causes an obvious dim- inution in the effect produced by the stimulation of the sciatic ; this marks the upper limit of the centre. Proceeding still further downwards with successive slices, stimulation of the sciatic pro- duces less and less rise of blood pressure, until at last a level is reached, at which even strong stimulation of the sciatic or any other afferent nerve produces no effect at all on blood pressure ; this marks the lower limit of the centre. In this way the lower limit of the bulbar vaso-motor centre has been determined in the rabbit at a horizontal line drawn about 4 or 5 mm. above the point of the calamus scriptorius, and the upper limit at about 4 mm. higher up, i.e. about 1 or 2 mm. below the corpora quadri- gemina. We may add that the centre appears to be bilateral, the halves being placed not in the middle line but more sideways and rather nearer the anterior than the posterior surface. But we will reserve what we have to say as to the structural features of this centre until we come to study the spinal bulb in detail. § 155. The above experiments appear to afford adequate evi- dence that, in a normal state of the body, the integrity of the bulbar vaso-motor centre is essential to the production and dis- tribution of those continued constrictor impulses by which the general arterial tone of the body is maintained, and that an increase or decrease of vaso-con stricter action in particular arteries, or in the arteries generally, is brought about by means of the same bulbar vaso-motor centre. But we must not therefore conclude that this small portion of the spinal bulb is the only part of the central nervous system which can act as a centre for vaso-con- strictor fibres ; and, so we have seen, there is no evidence at present that the vaso-dilator fibres are connected with either this or any other one centre. In the frog reflex vaso-motor effects may be obtained by stimulating various afferent nerves after the whole spinal bulb has been removed, and, indeed, even when only a com- paratively small portion of the spinal cord has been left intact, and connected, on the one hand, with the afferent nerve which is being stimulated, and, on the other, with the efferent nerves in which run the vaso-motor fibres, whose action is being studied. In the mammal such effects do not so readily appear, but may with care 284 SUMMARY OF VASO-MOTOR ACTIONS. [BOOK i. and under special conditions be obtained. Thus in the dog, when the spinal cord is divided in the thoracic region, the arteries of the hind limbs and hinder part of the body, as we have already said, § 150, become dilated. This one would naturally expect as the result of their severance from the. bulbar vaso-motor centre. But if the animal be kept in good condition for some time, a normal or nearly normal arterial tone is after a while re-estab- lished; and the tone thus regained may, by afferent impulses reaching the cord below the section, be modified in the direction certainly of diminution, i. e. dilation, and possibly, but this is not so certain, of increase, i. e. constriction ; dilation of various cutane- ous vessels of the limbs may be readily produced by stimulation of the central stump of one or another nerve. These and other results lead to the conclusion that the bulbar vaso-motor centre is not to be regarded as the sole vaso-motor centre, whence alone can issue tonic constrictor impulses or whither afferent impulses from this or that part of the body must always travel before they can affect the vaso-constrictor impulses passing along this or that nerve. We are rather to suppose that the spinal cord along its whole length contains, interlaced with the reflex and other mechanisms by which the skeletal muscles are governed, vaso-motor centres and mechanisms of varied com- plexity, the details of whose functions and topography have yet largely to be worked out. As in the absence of the sinus venosus the auricles and ventricle of the frog's heart may still continue to beat, so in the absence of the spinal bulb these spinal vaso-motor centres provide for the vascular emergencies which arise. § 156. We may sum up the history of vaso-motor actions somewhat as follows. In the case of at least a very large number of the arteries of the body we have direct experimental evidence that these arteries are connected with the central nervous system by nerve fibres, called vaso-motor fibres, the action of which varies the amount of contraction of the muscular coats of the arteries and so leads to changes in calibre. The action of these vaso-motor fibres is more manifest, and probably more important in the case of small and minute arteries than in the case of large ones. These vaso-motor fibres are of two kinds. The one kind, vaso- constrictor fibres, are of such a nature or have such connections at their peripheral endings that stimulation of them produces narrowing, constriction of the arteries. During life these fibres appear to be the means by which the central nervous system exerts a continued tonic influence on the arteries and maintains an arterial ' tone ; ' and this arterial tone may be modified by the action of the central nervous system, so as to give place on the one hand to constriction and on the other to widening. The other kind, vaso-dilator fibres, are of such a kind, or have such connec- tions, that stimulation of them produces widening, dilation of the CHAP, iv.] THE VASCULAR MECHANISM. 285 arteries. There is no adequate evidence that these vaso-dilator fibres serve as channels for tonic dilating impulses or influences. The vaso-constrictor fibres leave the spinal cord by the anterior roots of the nerves coining from the middle region only of the spinal cord. In the dog, this region extends from about the first or second thoracic to the fourth or fifth lumbar nerve ; and in other animals is probably of corresponding extent. Leaving the spinal nerves by the respective visceral branches, rami communi- cantes, the fibres pass into the sympathetic system, the majority joining the main sympathetic chain of ganglia in the thorax and abdomen, but some, for instance those going to certain parts of the intestine and some other viscera, leaving that chain on one side and passing directly to more peripheral ganglia, such as the solar plexus and the inferior mesenteric ganglia. From the sym- pathetic chain the fibres run to their destination in such nerves as the cervical sympathetic and splanchnic, those allotted to the skin of the limbs and trunk running back again to join the respec- tive spinal nerves. In the ganglia of the sympathetic chain or in other more peripheral ganglia the fibres lose their medulla, and continue their course as non-medullated fibres. In the intact organism the emission and distribution along these vaso-constrictor fibres of tonic constrictor impulses, by which general and local arterial tone is maintained and regulated, is governed by a limited portion of the spinal bulb known as the bulbar vaso-motor centre ; and when some change of conditions or other natural stimulus brings about a change in the activity of the vaso-constrictor fibres of one or more vascular areas, or of all the arteries supplied with vaso-constrictor fibres, this same bulbar vaso-motor centre appears in such cases to play the part of a centre of reflex action. Nevertheless, in cases where the nervous connections of this bulbar vaso-motor centre with a vascular area are cut off by an operation, as by section of the cord, other parts of the spinal cord may act as centres for the vaso-constrictor fibres of the area, and possibly these subordinate centres may be to a certain extent in action in the intact organism. The vaso-dilator fibres of whose existence we have clear and undisputed experimental evidence, are very limited in distribution. In the cases best known, the fibres leave certain regions of the central nervous system and proceed to their destination along certain cerebro-spinal nerves ; they do not lose their medulla until they approach their termination. But as we have seen there is evidence of vaso-dilator fibres also running in nerves of the sympathetic system. The vaso-dilator fibres are generally thrown into action as part of a reflex act, and the centre, in the reflex act, appears in each case to lie in the central nervous system not far from the origin of the ordinary motor fibres which the dilator fibres accompany. The effects of the activity of the vaso-dilator fibres appear to be 286 EXAMPLES OF VASO-MOTOR ACTIONS. [BOOK i. essentially local in nature. When any set of the fibres come into action the vascular area which these govern is dilated ; and the vascular areas so governed are relatively so small that changes in them produce little or no effect on the vascular system in general ; the fibres are called into play to produce special effects in special organs. The effects of changes in the activity of the vaso-constrictor fibres are both local and general. They are also double in nature ; by an inhibition of tonic constrictor impulses a certain amount of dilation may be effected ; by an augmentation of constrictor im- pulses, constriction, it may be of considerable extent, may be brought about. When the vascular area so affected is small the effects are local, more or less blood is distributed through the area ; when the vascular area affected is large, the inhibition of constric- tion may lead to a marked fall, and an augmentation of constric- tion to a marked rise of general blood pressure. Broadly speaking, we may say that whenever a vascular change is needed for the general well-being of the economy, it is this vaso-constrictor system which is called into play. The distribution of clearly proved vaso-dilator fibres is as we have said very limited, and even the vaso-constrictor fibres are most abundant in the nerves going to the skin and to the viscera. In respect to the arteries supplying the numerous skeletal mus- cles, there is much dispute as to whether they are supplied by vaso-dilator fibres ; and the supply of vaso-constrictor fibres to them is at least not large. We may perhaps infer that the vascu- lar changes in the muscles are intended chiefly for the benefit of the muscles themselves, and are not to any great extent, like those of the skin and viscera, utilized for the more general purposes of the economy. § 157. We shall have occasion later on again and again to point out instances of the effects of vaso-motor action both local and general, but we may here quote one or two characteristic examples. " Blushing " is one. Nervous impulses started in some parts of the brain by an emotion produce a powerful inhibi- tion of that part of the bulbar vaso-motor centre which governs the vascular areas of the head supplied by the cervical sympa- thetic, and hence has an effect on the vaso-motor fibres of the cervical sympathetic almost exactly the same as that produced by section of the nerve. In consequence the muscular walls of the arteries of the head and face relax, the arteries dilate and the whole region becomes suffused. Sometimes an emotion gives rise not to blushing, but to the opposite effect, viz. to pallor of the face. In a great number of cases this has quite a different cause, being due to a sudden diminution or even temporary arrest of the heart's beats ; but in some cases it may occur without any change in the beat of the heart, and is then due to a condition the very converse of that of blushing, that is, to an increased arterial constriction ; CEIAP. iv.] THE VASCULAR MECHANISM. 287 and this increased constriction, like the dilation of blushing, is effected through the agency of the central nervous system and the cervical sympathetic. Blushing and its opposite pallor are most marked in the face ; but other parts of the body may blush (or grow pale) the change being brought about by appropriate nerves. The vascular condition of the skin at large affords another instance. When the temperature of the air is low the vessels of the skin are constricted, and the skin is pale ; when the temperature of the air is high the vessels of the skin are dilated, and the skin is red and flushed. In both these cases the effect is mainly a reflex one, it being the central nervous system which brings about augmen- tation of constriction in the one case and inhibition in the other ; though possibly some slight effect is produced by the direct local action of the cold or heat on the vessels of the skin. Moreover the vascular changes in the skin are accompanied by corresponding vascular changes in the viscera (chiefly abdominal) of a reverse kind. When the vessels of the skin are dilated those of the viscera are constricted, and vice versa; so that a considerable portion of the whole blood ebbs and flows, so to speak, according to circumstances from skin to viscera and from viscera to skin. By these changes, as we shall see later on, the maintenance of the normal temperature of the body is in large measure secured. We shall see later on that the secretion of urine is in a peculiar way dependent on the flow of blood through the kidney. A very favourable condition for this flow is a dilated condition of the renal arteries coincident with a high general blood pressure, and this condition as we shall see leads to a copious secretion of urine. The high general blood pressure in this case is largely caused by very general arterial constriction, leading to great increase of peripheral resistance, while the dilated state of the renal arteries appears to be due to a lack of the usual tonic constrictor impulses ; though these constrictor impulses are increased in respect to other arteries, they are diminished in respect to the renal arteries themselves. When food is placed in the mouth the blood vessels of the salivary glands as we have seen are flushed with blood as an idjuvant to the secretion of digestive fluid ; and as the food passes along the alimentary canal each section in turn, with the glandular appendages belonging to it, welcomes its advent by flushing with blood. As we have already said, we have, at present, no satisfactory evidence, except in the case of the salivary glands, that this flushing is carried out by special vaso-dilator nerves. Along the rest of the alimentary canal the widening of the arteries and thus the increased flow seems to be brought about by diminution of vaso-constrictor impulses, so far at least as it is ensured by the intervention of the central nervous system. We say ' so far ' because as we shall see we have evidence that the vessels of the kidney may change in calibre independently of any influences 288 VASO-MOTOR NERVES OF THE VEINS. [BOOK i. proceeding from the central nervous system, after for instance all the nerves going to the kidney have been divided ; in such cases the changes in the calibre of the renal vessels seem to be due to some direct local action ; and it is possible that the flushing of the alimentary canal when food enters it is similarly, in part or at times, the result of some local action on the blood vessels. § 158. Vaso-motor nerves of the Veins. Although the veins are provided with muscular fibres and are distinctly contractile, and although rhythmic variations of calibre due to contractions may be seen in the great veins opening into the heart, in the veins of the bat's wing, and elsewhere, our knowledge as to any nervous arrangements governing the veins is at present very limited. The portal vein, the walls of which are conspicuously muscular, the muscular fibres being arranged both as a circular and as a longi- tudinal coat, is like the veins just mentioned subject to rhythmic variations of calibre ; these might be due to active rhythmic contractions of the portal vein itself or might be of a passive nature, due to a rhythmic rise and fall in the quantity of blood discharged into it from the vessels of the viscera. The former view is supported by the observation that after the aorta has been obstructed, so that no blood can pass into the portal vein from the mesenteric and other arteries, contractions of the portal vein may be obtained by stimulating the splanchnic nerves. The great distention of the venous system with blood which occurs in the frog when the brain and spinal cord are destroyed, and which renders the heart almost bloodless, the greater part of the blood being lodged in the veins, has also been supposed to point to some normal tone of the veins dependent on the central nervous system. SEC. 7. THE CAPILLARY CIRCULATION. § 159. We have already, sonie time back (§ 99), mentioned some of the salient features of the circulation through the capil- laries, viz. the difficult passage of the corpuscles (generally in single file, though sometimes in the larger channels two or more abreast) and plasma through the narrow channels, in a stream which though more or less irregular is steady and even, not broken by pulsations, and slower than that in either the arteries or the veins. We have further seen (§ 94) that the capillaries^ vary very much in width from time to time ; and there can be no doubt that the changes in their calibre are chiefly of a passive nature. They are expanded when a large supply of blood reaches them through the supplying arteries, and, by virtue of their elasticity, shrink again when the supply is lessened or withdrawn ; they may also become expanded by an obstacle to the venous outflow. On the other hand, there is a certain amount of evidence that, in young animals at all events, the calibre of a capillary canal may vary, quite independently of the arterial supply or the venous outflow, in consequence of changes in the form of the epithelioid cells, allied to the changes which in a muscle-fibre or muscle-cell constitute a contraction ; and though the matter re- quires further investigation, it is possible that these active changes play an important part in determining the quantity of blood pass- ing through a capillary area ; but there is as yet no satisfactory evidence that they, like the corresponding changes in the arteries, are governed by the nervous system. Over and above these changes of form, the capillaries and minute vessels are subject to still other changes and so exert influences by virtue of which they play an important part in the work of the circulation. Their condition determines the amount of resistance offered by their channels to the flow of blood through those channels, and determines the amount and character of that interchange between the blood and the tissues which is the main fact of the circulation. 19 290 INFLAMMATION. [BOOK i. If the web of the frog's foot, or, better still, if some transparent tissue of a mammal be watched under the microscope, it will be ob- served that, while in the small capillaries the corpuscles are pressed through the channel in single file, one after the other, each corpuscle as it passes occupying the whole bore of the capillary, in the larger capillaries (of the mammal), and especially in the small arteries and veins which permit the passage of more than one corpuscle abreast, the red corpuscles run in the middle of the channel, forming a coloured core, between which and the sides of the vessels all round is a colourless layer, containing no red corpuscles, called the ' plasmatic layer ' or ' peripheral zone.' This division into a peripheral zone and an axial stream is due to the fact that in any stream passing through a closed channel the friction is greatest at the sides, and diminishes towards the axis. The corpuscles pass where the friction is least, in the axis. A quite similar axial core is seen when any fine particles are driven with a sufficient velocity in a stream of fluid through a narrow tube. As the velocity is diminished the axial core becomes less marked and disappears. In the peripheral zone, especially in that of the veins, are frequently seen white corpuscles, sometimes clinging to the sides of the vessel, sometimes rolling slowly along, and in general moving irregularly, stopping for a while and then suddenly moving on. The greater the velocity of the flow of blood, the fewer the white corpuscles in the peripheral zone, and with a very rapid flow they, as well as the red corpuscles, maybe all confined to the axial stream. The presence of the white corpuscles in the peripheral zone has been attributed to their being specifically lighter than the "red corpuscles, since when fine particles of two kinds, one lighter than the other, are driven through a narrow tube, the heavier particles flow in the axis and the lighter in the more peripheral portions of the stream. But, besides this, the white corpuscles have a greater tendency to adhere to surfaces than have the red, as is seen by the manner in which the former become fixed to the glass slide and cover-slip when a drop of blood is mounted for microscopical examination. They probably thus adhere by virtue of the amoeboid movements of their protoplasm, so that the adhesion is to be considered not so much a mere physical as a physiological process, and hence may be expected to vary with the varying nutritive conditions of the corpuscles and of the blood vessels. Thus while the appearance of the white corpuscles in the peripheral zone may be due to their lightness, their temporary attachment to the sides of the vessels and characteristic progression is the result of their power to adhere ; and as we shall presently see their amoeboid movements may carry them on beyond mere adhesion. § 160. These are the phenomena of the normal circulation, and may be regarded as indicating a state of equilibrium between CHAP, iv.] THE VASCULAR MECHANISM. 291 the blood on the one hand and the blood vessels with the tissues on the other ; but a different state of things sets in when that equilibrium is overthrown by causes leading to what is called inflammation or to allied conditions. If an irritant, such as a drop of chloroform or a little diluted oil of mustard, be applied to a small portion of a frog's web, tongue, mesentery, or some other transparent tissue, the following changes may be observed under the microscope ; they may be still better seen in the mesentery or other transparent tissue of a mammal. The first effect that is noticed is a dilation of the arteries, accompanied by a quickening of the stream. The irritant, probably by a direct action on the muscular fibres of the arteries, has led to a re- laxation of the muscular coat, and hence to a widening ; and we have already, § 105, explained how such a widening in a small artery may lead to a temporary quickening of the stream. In consequence of the greater How through the arteries, the capillaries become filled with corpuscles, and many passages, previously invisible or nearly so on account of their containing no corpuscles, now come into view. The veins at the same time appear enlarged and full. If the stimulus be very slight, this may all pass away, the arteries gaining their normal constriction, and the capillaries and veins returning to their normal condition ; in other words, the effect of the stimulus in such a case is simply a temporary blush. Unless, however, the chloroform or mustard be applied with especial care, the effects are much more profound, and a series of remarkable changes set in. In the normal circulation, as we have just said, white corpuscles may be seen in the peripheral, plasmatic zone, but they are scanty in number, and each one, after staying for a little time in one spot, suddenly gets free, sometimes almost by a jerk as it were, and then rolls on for a greater or less distance. In the area now under consideration a large number of white corpuscles soon gather in the peripheral zones, especially of the veins and venous capillaries (that is of the larger capillaries which are joining to form veins), but also, of the other capillaries, and, to a less extent, of the arteries ; and this takes place although the vessels still remain dilated and the stream still continues rapid, though not so rapid as at first. Each white corpuscle appears to exhibit a greater tendency to stick to the sides of the vessels, arid though driven away from the arteries by the stronger arterial stream, becomes lodged so to speak in the veins. Since new white corpuscles are continually being brought by the blood stream on to the scene, the number of them in the peripheral zones of the veins increases more and more, and this may go on until the inner surface of the veins and venous capillaries appears to be lined with a layer of white corpuscles. The small capillaries too contain more white corpuscles than usual, and even in the arteries these are abundant, though not forming the distinct layer seen in the veins. The white cor- 292 MIGRATION OF WHITE CORPUSCLES. [BOOK i. puscles, however, are not the only bodies present in the peri- pheral zone. Though in the normal circulation blood-platelets (see § 33) cannot be seen in the peripheral zone, and hence (on the view, which has the greater support, that these bodies are really present in quite normal blood) must be confined to the axial stream, they make their appearance in that zone during the changes which we are now describing. Indeed, in many cases they are far more abundant than the white corpuscles, the latter appear- ing imbedded at intervals in masses of the former. Soon after their appearance the individual platelets lose their outline, and run together into formless masses. § 161. This much, the appearance of numerous white cor- puscles and platelets in the peripheral zones, may take place while the stream, though less rapid than at the very first, still remains rapid ; so rapid at all events that, owing to the increased width of the passages, in spite of the obstruction offered by the adherent white corpuscles, the total quantity of blood flowing in a given time through the inflamed area is greater than normal. But soon, though the vessels still remain dilated, the stream is observed most distinctly to slacken, and then a remarkable phenomenon makes its appearance. The white corpuscles lying in contact with the walls of the veins or of the capillaries are seen to thrust processes through the walls ; and, the process of a corpuscle increasing at the expense of the rest of the body of the corpuscle, the whole cor- puscle, by what appears to be an example of amoeboid movement, makes its way through the wall of the vessel into the lymph space outside ; the perforation appears to take place in the cement substance joining the epithelioid plates together. This is the migration of the white corpuscles to which we alluded in § 32, and takes place chiefly in the veins and capillaries, not at all or to a very slight extent in the arteries. Through this migration the lymph spaces around the vessels in the inflamed area become crowded with white corpuscles. At the same time fluid passes from the interior of the blood vessels through the altered walls into the lymph spaces more rapidly than it escapes from the lymph spaces along the lymphatic channels ; these lymph spaces become distended with lymph, which also changes somewhat in its chemical characters ; it tends to clot more readily and more firmly, and is sometimes spoken of as ' exudation fluid,' or by the older writers as 'coagulable lymph.' This turgescence of the lymph spaces, together with the dilated crowded condition of the blood vessels, gives rise to the swelling which is one of the features of inflammation. If the inflammation now passes off the white corpuscles cease to emigrate, cease to stick for any length of time to the sides of the vessels, the stream of blood through the vessels quickens again, and the vessels themselves, though they may remain for a long time dilated, eventually regain their calibre, and a normal circulation is CHAP, iv.] THE VASCULAR MECHANISM. 293 re-established. The migrated corpuscles move away from the region along the labyrinth of lymph spaces, and the surplus lymph also passes away along the lymph spaces and lymphatic vessels. A more powerful action of the irritant may lead to still other events. More and more white corpuscles, arrested in their passage, crowd the channels and block the way, so that though the vessels remain dilated, the stream becomes slower and slower, until at last it stops altogether, arid ' stagnation ' or ' stasis ' sets in. The red corpuscles are driven in, often in masses, among the white cor- puscles and platelets, the distinction between axial stream and peripheral zone becoming lost ; and arteries, veins and capillaries, all distended, sometimes enormously so, are filled with a mass of mingled red and white corpuscles and platelets. The red corpuscles run together so that their outlines are no longer distinguishable ; they appear to become fused into a homogeneous red mass. And it may now be observed that, not only white corpuscles but also red corpuscles, make their way through the distended and altered walls of the capillaries, chiefly, at all events, at the junctions of the epithelioid plates, into the lymph spaces beyond. This is spoken of as the diapedesis of the red corpuscles. This condition of 'stasis' may be the prelude to further mischief, and, indeed, to the death of the tissue, but it, too, like the earlier stage of inflammation, may pass away. As it passes away the outlines of the corpuscles become once more distinct, those on the venous side of the block gradually drop away into the neigh- bouring currents, little by little the whole obstruction is removed, and the current through the area is re-established. § 162. The slowing or the arrest of the blood current described above is not due to any lessening of the heart's beat ; the arterial pulsations, or at least the arterial flow, may be seen to be continued in full force down to the affected area, and there to cease very suddenly. It is not due to the peripheral resistance being increased by any constriction of the small arteries, for these continue dilated, sometimes exceedingly so. It must, therefore, be due to some new and unusual resistance occurring in the area itself, and this we are by many reasons led to attribute to an increased tendency of the corpuscles, especially of the white corpuscles, to stick to the sides of the vessels. The increase of adhesiveness is not caused by any change confined to the corpuscles themselves ; for if after a temporary delay one set of corpuscles has managed to pass away from the affected area, the next set of corpuscles brought to the area in the blood stream is subjected to the same delay. The cause of the increased adhesiveness must therefore lie in the walls of the blood vessels, or in the tissue of which these form a part. That the increased adhesion is due to the vascular walls and not primarily to the corpuscles themselves is further shewn by the fact that if, in the frog, an artificial blood of normal saline solution, to which milk has been added, be substituted for normal blood, a 294 INFLAMMATION. [BOOK i. stasis may by irritants be induced in which oil-globules play the part of corpuscles, and by their aggregation bring about an arrest of the flow. We are led to conclude that there exist in health certain relations between the blood on the one hand, and the walls of the vessels on the other, by which the tendency of the corpuscles to adhere to the blood vessels is kept within certain limits ; these relations consequently determine the normal flow, with its axial stream and peripheral zone, and the normal amount of peripheral resistance; in inflammation, these relations, in a manner we cannot as yet fully explain, are disturbed so that the tendency of the corpuscles to adhere to the sides of the vessels is largely and progressively increased. Hence the tarrying of the corpuscles in spite of the widening of their path, and finally their agglomera- tion and fusion in the distended channels. The changes occurring in the vascular walls at the same time also modify the passage from the blood to the tissue of the fluid parts of the blood, the lymph of inflamed areas being more abundant and richer in proteids than normal lymph. There is a greater outflow from the interior of the blood vessel into the lymph spaces outside, and, indeed, it has been urged that this, carrying the blood corpuscles with it, mechanically promotes the gathering of the white corpuscles at the sides of the vessel and their subsequent passage through the walls. We must not, however, pursue this subject of inflammation any further. We have said enough to shew that the peripheral re- sistance (and consequently all that depends on that peripheral resistance) is not wholly determined by the varying width of the minute passages, but is also dependent on the vital condition of the tissue of which the walls of the passages form a part. When the tissue is in health, a certain resistance is offered to the passage of blood through the capillaries and other minute vessels, and the whole vascular mechanism is adapted to overcome this resistance to such an extent that a normal circulation can take place. When the tissue becomes affected, the disturbance of the relations between the tissue and the blood may so augment the re- sistance that the passage of the blood becomes, as in inflammation, difficult, or, as in stasis, impossible. And it is quite open to us to suppose that under certain circumstances the reverse of the above may occur in this or that area, that conditions may arise in which the resistance is lowered below the normal, and the circulation in the area quickened. Thus the vital condition of the tissue becomes a factor in the maintenance of the circulation ; and it is possible, though not yet proved, that these vital conditions are directly under the dominion of the nervous system. § 163. Changes in the peripheral resistance may also be brought about by changes in the character of the blood, especially by changes in the relative amount of gases present. When a CHAP, iv.] THE VASCULAR MECHANISM. 295 stream of defibrinated blood is artificially driven through a perfectly fresh excised organ, such as the kidney, it is found that the resistance to the flow of blood through the organ, measured, for instance, by the amount of outflow in relation to the pressure exerted, varies considerably owing to changes taking place in the organ, and may be increased by increasing the venous character, and diminished by increasing the arterial character of the blood. Remarkable changes in the resistance are also brought about by the addition of small quantities of certain drugs such as chloral, atropin &c. to the blood. These changes have been attributed to the altered blood acting on the walls of the vessels, inducing, for instance, constriction or widening of the small arteries, or, it may be, affecting the capil- laries, for it has been asserted that the epithelioid plates of the capillaries vary in form according to the relative quantities of carbonic acid and oxygen present in the blood. But this is not the whole explanation of the matter, since similar variations in resistance are met with when blood is driven through fine capil- lary tubes of inert matter. In such experiments it is found that the resistance to the flow increases with a diminution of the oxygen carried by the red corpuscles, and is modified by the addition to the blood of even small quantities of certain drugs. It is obvious, then, that in the living body the peripheral resistance, being the outcome of complex conditions, may be modified in many ways. Experiment teaches us that, even in dealing with non-living inert matter, the flow of fluid through capillary tubes may be modified on the one hand by changes in the substance of which the tubes are composed, and on the other hand by changes in the chemical nature (even independent of the specific gravity) of the fluid which is used. In the living body both the fluid and the tubes, both the blood and the walls of the minute vessels, are subject to incessant change ; the vessels are continually changing because they are living structures, and the blood is continually changing not only because it too is in part at least alive, but also because all the tissues of the body are working upon it. The changes in the one, moreover, are capable of reacting upon and inducing changes in the other ; and, lastly, the changes both of the one and of the other may be primarily set going by events taking place in some part of the body far away from the region in which these changes are modifying the resistance to the flow. SEC. 8. CHANGES IN THE QUANTITY OF BLOOD. § 164. In an artificial scheme, changes in the total quantity of fluid in circulation will have an immediate and direct effect on the arterial pressure, increase of the quantity heightening and decrease diminishing it. This effect will be produced partly hy the pump being more or less filled at each stroke, and partly by the peri- pheral resistance being increased or diminished by the greater or less fulness of the small peripheral channels. The pressure along the whole system and hence the venous pressure will under all circumstances be raised with the increase of fluid, but an increase of the arterial pressure beyond that of the venous pressure will be observed only so long as the elasticity of the arterial tubes can be brought into play. In the natural circulation, the direct results of change of quan- tity are modified by compensatory arrangements. Thus experi- ment shews the following when an animal with normal blood pressure is bled from one carotid. The pressure in the other carotid sinks so long as the bleeding is going on ; this is chiefly because the free opening in the vessel, from which the bleeding is going on, cuts off a great deal of the peripheral resistance, and so leads to a general lowering of the blood pressure. It remains depressed for a brief period after the bleeding has ceased, but in a short time regains or nearly regains the normal height. This recovery of blood pressure, after haemorrhage, is witnessed so long as the loss of blood does not amount to more than about 3 per cent, of the body-weight. Beyond that, a large and frequently a sudden dangerous permanent depression is observed. The restoration of the pressure after the cessation of the bleeding is too rapid to permit us to suppose that the quantity of fluid in the blood vessels is replaced by the withdrawal of lymph from the extra- vascular elements of the tissues, In all probability the result is gained by an increased action of the vaso-constrictor nerves increasing the peripheral resistance, the vaso-motor centre being thrown into increased action by the diminution of its blood supply ; when the blood by ligature of the arteries in the CHAP, iv.] THE VASCULAR MECHANISM. 297 neck is suddenly cut off from the brain and so from the spinal bulb, a rise of blood pressure is observed. When the loss of blood has gone beyond a certain limit, this vaso-constrictor action is insufficient to compensate the diminished quantity (possibly the vaso-niotor centre in part becomes exhausted), and a considerable depression takes place ; but at this epoch the loss of blood frequently causes ansernic convulsions. Similarly, when an additional quantity of blood is injected into the vessels, no marked increase of blood pressure is observed so long as the vaso-motor centre in the spinal bulb is intact. If, however, the cervical spinal cord be divided previous to the in- jection, the pressure, which, on account of the removal of the bulbar vaso-motor centre, is very low, is permanently raised by the injection of blood. At each injection the pressure rises ; it falls somewhat afterwards, but eventually remains at a higher level than before. This rise is stated to continue until the amount of blood in the vessels above the normal quantity reaches from 2 to 3 per cent, of the body-weight, beyond which point it is said no further rise of pressure occurs. The absence of any marked rise of blood pressure, so long as the bulbar vaso-motor centre is intact, shews that the addition of the extra quantity of blood stimulates that centre to increased activity. But while a diminution of blood supply seems to affect the centre directly, an increase of blood supply probably acts in an indirect manner. When the arteries in the neck are ligatured, the rise of blood pressure is much more marked if the depressor nerves be divided ; so long as these nerves are intact impulses passing along them from the heart withstand the stimulating effects on the vaso-motor centre of the loss of blood. And we may perhaps infer that when an extra quantity of blood is injected, the greater fulness stimulates the endings of the depressor nerves in the heart, and so by developing depressor impulses lessens the activity of the vaso- motor centre. The facts stated seem, then, to shew, in the first place, that when the volume of the blood is increased, compensation is effected by a lessening of the peripheral resistance by means of a diminished action of the vaso-motor centre, so that the normal blood pressure remains constant. They further shew that a much greater quantity of blood can be lodged in the blood vessels than is normally present in them. That the additional quantity injected does remain in the vessels is proved by the absence of extravasations, and of any considerable increase of the extra-vascular lymphatic fluids. It has already been insisted that, in health, the veins and capillaries must be regarded as being far from filled ; for were they to receive all the blood which they can, even at a low pressure, hold, the whole quantity of blood in the body would be lodged in them alone. In these cases of large addition of blood, the extra quantity appears to be lodged in the small veins and capillaries (especially 298 CHANGES IK QUANTITY OF BLOOD. [BOOK i. of the internal organs), which are abnormally distended to contain the surplus. We learn, also, from these facts the two practical lessons : first, that blood pressure cannot be lowered directly in a mechanical manner by bleeding, unless the quantity removed be dangerously large ; and secondly, that there is no necessary connection between a high blood pressure and fulness of blood or plethora, since an enormous quantity of blood may be driven into the vessels without any marked rise of pressure. When a quantity of blood or, indeed, of fluid is injected into the veins, the output from the heart is increased and observations seem to shew that the increase in the output is out of proportion to the quantity of fluid injected, indicating that the result is of complex origin. In spite of this increased output, the blood pressure is not raised ; the effect is compensated by vascular dilation somewhere. Conversely when blood is withdrawn, the output is diminished, but here again the effect on the blood pressure is soon compensated, this time by vascular constriction. SEC. 9. A REVIEW OF SOME OF THE FEATURES OF THE CIRCULATION. § 165. The facts dwelt on in the foregoing sections have shewn us that the factors of the vascular mechanism may be regarded as of two kinds: one constant, or approximately constant; the other variable. The constant factors are supplied by the length, natural bore, and distribution of the blood vessels, by the extensibility and elastic reaction of their walls, and by such mechanical contrivances as the valves. By the natural bore of the various blood vessels is meant the diameter which each would assume if the muscular fibres were wholly at rest, and the pressure of fluid within the vessel were equal to the pressure outside. It is obvious, however, that even these factors are only approximately constant for the life of an individual. The length and distribution of the vessels change with the growth of the whole body or parts of the body, and the physical qualities of the walls, especially of the arterial walls, their extensibility and elastic reaction change continually with the age of the individual. As the body grows older, the once supple and elastic arteries become more and more stiff and rigid, and often in middle life, or it may be earlier, a lessening of arterial resilience which proportionately impairs the value of the vascular mechanism as an agent of nutrition, marks a step towards the grave. The chief variable factors are on the one hand the beat of the heart, and on the other the peripheral resistance, the variations in the latter being chiefly brought about by muscular contraction or relaxation in the minute arteries, but also, though to what extent has not yet been accurately determined, by the condition of the minute vessels according to which the blood can pass through them with less or with greater ease, as well as by the character of the circulating blood. These two chief variables, the beat of the heart and the width of the minute arteries, are known to be governed and regulated by the central nervous system, which adapts each to the circumstances 00 INTRINSIC REGULATION OF HEART BEAT. [BOOK i. of the moment, and at the same time brings the two into mutual dependence ; but the central nervous system is not the only means of government : there are other modes of regulation, and so other safeguards. § 166. Let us first consider the heart. The object, if we may use the expression, of the systole of the ventricle is to secure the needed arterial pressure ; it is this, as we have seen, which drives the blood through the capillaries back to the heart. To do this the ventricle must deliver at the stroke a certain quantity of blood, exerting the pressure required to lodge the blood in the arteries, and repeating the stroke at appropriate intervals. Hence the work done will, in part, depend on the quantity of blood collected in the ventricle during the diastole, that is, on the inflow from the venous system. If the quantity brought be too small, then though the whole contents of the ventricle be ejected with adequate force at each stroke, and the stroke repeated regularly, the ventricle will fail in its object ; speaking generally we may say that a lessened venous inflow will tend to lessen, and an increased venous inflow will tend to increase the work of the heart. This venous inflow is dependent on various causes, and may be variously modified by various events. The blood in filling the ventricle distends its walls, and this distension, especially the fuller distension resulting from the auricular systole, also influences the ventricular stroke ; for the contraction of the cardiac fibre, like that of the skeletal muscular fibre, is increased up to a certain limit by the fibre being put on the stretch (§ 140). This influence, however, is more distinctly seen on the arterial side. The greater the arterial pressure against which the ventricle has to deliver its contents, the greater the tension of the ventricular wralls ; and hence, a high arterial pressure tends of itself to enforce the ventricular systole. As in the skeletal muscle, however, this beneficial influence soon reaches its limit. § 167. The spontaneous beat of the heart is the outcome of the nutrition of the cardiac tissues. In the absence of all inter- ference by inhibitory or augmentor fibres, the heart will continue beating with a certain rhythm and force, determined by the metabolism going on in its muscular and nervous elements. The beat therefore will be influenced by anything which affects that metabolism. And the obvious and direct cause of changes in the nutrition and so in the behaviour of the heart lies in changes in the quantity and quality of the blood supplied to the cardiac tis- sues. In the mammal this means the quantity and quality of the blood flowing through the coronary arteries. If in a mammal the coronary arteries be tied or otherwise occluded the heart in a few seconds comes to a standstill ; this, which always results if both arteries be tied, sometimes if one only be tied, is preceded by an irregularity or by changes in the CHAP. iv.] THE VASCULAR MECHANISM. 301 beat and is followed by fibrillar contractions of parts of the ven- tricles. This is an extreme case, but it illustrates in a striking manner how closely the rhythmic contraction of the cardiac fibres is dependent on the blood supply. The quantity of blood flowing through the coronary arteries is dependent on the pressure in the aorta, or rather on the difference between that pressure and the pressure in the right auricle into which the coronary veins open, and on the resistance offered by the coronary vessels. Hence with a high aortic pressure, more blood passes to the cardiac tissue. This is at least favourable to the development of the beat, and may be the direct cause of a stronger stroke ; indeed observations seem to shew this. Thus a high aortic pressure itself helps the heart to the effort necessary to overcome that high pressure. Conversely a low aortic pressure would similarly tend to spare the heart an unnecessary exertion. As to how the heart may be influenced by changes in the width of the coronary arteries brought about by vaso-motor action, we have at present but little definite knowledge. More important still than the quantity is the quality of the blood flowing through the coronary vessels. We shall have occasion in treating of respiration to speak of the manner in which blood deficient in oxygen or overladen with carbonic acid affects the beat of the heart ; and we may here be content to point out that every change in the constitution of the blood, whether arising from the presence of substances such as drugs and poisons, introduced from without, or of substances manufactured in this or that tissue of the body or resulting from the absence or paucity or from excess of one or more of the normal constituents, may unfavourably or, it may be, favourably affect the heart beat, by directly influencing the cardiac tissues through the coronary arteries. These changes in the blood may of course also work upon the heart through the central nervous system, and this indirect effect may possibly be different from the direct effect. Thus, when the breathing is interfered with, the too highly venous blood, while it acts directly on the cardiac tissues and that unfavourably, also stimulates the cardio-inhibitory centre, whereby the heart is slowed and its expenditure of energy lessened. § 168. As is well known, the beat of the heart may become temporarily or permanently irregular. That many hearts go on beating day after day, year after year, without any such irregu- larity is a striking proof of the complete balance which usually obtains between the several factors of which we are speaking. Sometimes such cardiac irregularities, those of a transient nature and brief duration, are the results of extrinsic nervous influences. Some events taking place in the stomach, for instance, give rise to afferent impulses which ascending from the mucous membrane of the stomach along certain afferent fibres of the vagus to the spinal bulb, so augment the action of the cardio-inhibitory centre 302 IRREGULAR HEART BEAT. [BOOK i. as to stop the heart for a beat or two, the stoppage being fre- quently followed by a temporary increase in the rapidity and force of the beat Such a passing failure of the heart beat, in its sudden onset, in its brief duration, and in the reaction which fol- lows, very closely resembles the complete but temporary inhibition brought about by artificial stimulation of the vagus. And as we have seen the inhibitory action of the vagus is especially prone to be set going by afferent impulses passing up to the central ner- vous system from the viscera. The effects however which we produce by our rough means of direct stimulation of the trunk of the vagus do not afford a true picture of the action of the cardie-inhibitory mechanism in the living body; we come nearer to this when we obtain inhibition in a reflex manner. From the knowledge gained in this way we may infer that the fainting which comes from pain, emotions and the like, is due to the action of the inhibitory mechanism. Several forms of irregular heart beat are probably brought about by the same mechanism ; we may in this relation call to mind that one effect of the action of the inhibitory fibres is to produce not merely slowing or weakening but distinct irregularity of the heart beat. Many observations shew that the cardio-inhibitory mechanism may be affected by afferent impulses or otherwise in two different ways. On the one hand the cardio-inhibitory centre may be thrown into action, or when already in action may have its action increased ; on the other hand if already in action, that action may be lessened ; the inhibition may itself be inhibited. The division of both vagus nerves in the dog affords an instance of the effect on the heart of arresting previously existing inhibitory impulses. Hence it becomes difficult in the complex living body to distin- guish between an augmentation due to activity of the augmentor mechanism and one due to suspension of the previously active inhibitory mechanism. The two may probably be distinguished by studying the details of the behaviour of the heart in the two cases. Failing this it is difficult to say whether a case of that irregularity of the heart which wTe call 'palpitation' has been brought about positively by the one mechanism or negatively by the other. We must remember, moreover, that irregularity in the heart beat in at least a large number of cases is the result not of ner- vous influences from without, but of intrinsic events. For in- stance, in many cases the irregularity of the heart beat is wholly unaffected by atropin, and therefore cannot be due to vagus action. It is very often the result of what we may call a dis- ordered nutrition of the cardiac substance, though we cannot state the exact nature of the disorder. § 169. We may repeat that the effect of inhibitory action is to lessen the expenditure of energy and so to assist the heart for CHAP, iv.] THE VASCULAR MECHANISM. 303 future efforts ; it saves the heart at the expense of the rest of the economy. The heart, so far as we know, cannot in the working of the living economy be brought to a final arrest by the simple action of the vagus. The effect of the augmentor action on the other hand is to increase the expenditure of energy ; it saves the rest of the economy at the expense of the heart. And probably in some cases augmentor action may bring about the cessation of the heart beat. Disordered cardiac nutrition shews itself fre- quently in a dilated condition of the ventricles ; the systole is inadequate to secure an adequate discharge into the arteries, the residual blood in the ventricles is increased. If the augmentor mechanism be brought to bear on such a weakened and dilated ventricle, it may induce a fruitless expenditure of energy ; the beat though increased is still inadequate to secure the needed discharge of the contents, while the fibre is exhausted by the increased metabolism. And the final result of such an effort may be the cessation of the beat. § 170. Turning now to the minute arteries and the peripheral resistance which they regulate, we may call to mind the existence of the two kinds of mechanism, the vaso-con stricter mechanism, which, owing to the maintenance by the central nervous system of a tonic influence, can be worked both in a positive constrictor, and in a negative dilator direction, and the vaso-dilator mechanism, which, so far as we know, exerts its influence in one direction only, viz. to dilate the blood vessels. The latter, dilator mechan- ism seems, as we have seen, to ba used in special instances only, as seen in the cases of the chorda tympani and nervi erigentes ; the use of the former, constrictor mechanism appears to be more general. Thus the relaxation of the cutaneous arteries of the head and neck, which is the essential feature in blushing, seems due to mere loss of tone, to the removal of constrictor influences previ- ously exerted through the vaso-constrictor fibres of the cervical sympathetic. Though probably dilator fibres pass directly along the roots of the cervical and of certain cranial nerves to the nerves of the head and neck, we have no evidence that these come into play in blushing ; as we have seen, blushing may be imitated by mere section of the cervical sympathetic. So also the ' glow ' and redness of the skin of the whole body, i. e. general dilation of the cutaneous arteries, which is produced by external warmth, is probably another instance of diminished activity of tonic con- strictor influences ; though the result, that the dilation produced by warming an animal in an oven is greater than that produced by section of nerves, seems to point to the dilator fibres for the cutaneous vessels which, as we have seen, probably exist in the sciatic and brachial plexuses and possibly in all the spinal nerves, also taking part in the action. A similar loss of constrictor action in the cutaneous vessels may be the result of certain emotions, whether going so far as actual blushing of the body, or merely 304 THE EFFECTS OF BODILY EXERCISE. [BOOK i. producing a 'glow/ The warm and flushed condition of the skin, which follows the drinking of alcoholic fluids, is probably, in a similar manner the result of an inhibition of that part of the vaso- motor centre which governs the cutaneous arteries. The effect of cold on the other hand, and of certain emotions, or of emotions under certain conditions, is to increase the constrictor action on the cutaneous vessels, and the skin grows pale. It may be worth while to point out, that in both the above cases, while both the cold and the warmth produce their effects, chiefly at all events through the central nervous system, and very slightly, if at all, by direct action on the skin, their action on the central nervous system is not simply a general augmentation or inhibition of the whole vaso-motor centre. On the contrary, the cold, while it constricts the cutaneous vessels, so acts on the vaso-motor centre as to inhibit that portion of the vaso-motor centre which governs the abdominal splanchnic area ; while less blood is carried to the colder skin, by the opening up of the splanchnic area more blood is turned on to the warmer regions of the body, and the rise of blood pressure which the constriction of the cutaneous vessels tended to produce, and which might be undesirable, is hereby prevented. Conversely, when warmth dilates the cutaneous ves- sels, it at the same time constricts the abdominal splanchnic area, and prevents an undesirable fall of pressure. § 171. The influence on the body of exercise illustrates both the manner in which the two vascular factors, the heart beat and the peripheral resistance, are modified by circumstances, and the mutual action of these on each other. This influence is exceed- ingly complex, and we cannot treat it properly until we have studied several physiological matters to which we shall come later on. We can here only touch in a general way on some salient points. We know from superficial observation that during active exertion the breathing is increased, the heart beats more quickly and apparently with greater vigour, and the skin, flushed with blood, perspires freely. The repeated strong contractions of the skeletal muscles to which we turn as the ultimate cause of these events affect the body in two main ways, the one chemical, the other physical. When the muscles contract they take from the blood a larger amount of oxygen, they give up to the blood a larger amount of carbonic acid, and they discharge into the blocd, either directly into the capillaries of the muscles or indirectly through the lymph stream, a quantity of substances, probably of several kinds, such as sarcolactic acid and the like, which arise from the metabolism of the muscular substance. The blood leaving a muscle at work is chemically different from the blood leaving a muscle at rest. There is also a' physical change. During the contraction of a muscle the blood vessels are dilated ; this when many muscles CHAP, iv.] THE VASCULAR MECHANISM. 305 are at work would lead unless compensated to a lessening of peri- pheral resistance, and so to a fall of arterial pressure, for the minute vessels of the muscles form a large part of the whole system of minute vessels of the body ; at the same time it would increase the venous inflow into the heart. Now we shall later on point out that the increased breathing which follows upon exertion is due to the chemical changes thus produced in the blood, and not only to the diminution of oxygen and increase of carbonic acid, but also and perhaps especially to the presence of the other products of metabolism referred to above. Indeed we have reason to think that the increase in breathing is sufficient to maintain the blood in a normal condition so far .as oxygen and carbonic acid are concerned; the blood is not more venous during exertion than during rest, it is possibly less venous. The increased breathing however, though it clears the blood of the excess of carbonic acid, leaves behind in the blood the other muscular products, ready to produce their effects on the body before they are got rid of by organs other than the lungs. This increased breathing promotes mechanically, as we shall point out later on, the flow of blood to the heart and through the lungs. And this together with the increased venous flow from the contracting muscles favours the beat of the heart, supplying the means for a greater output and probably also tending to increase the force of the systole. But there are other influences at work on the heart. The changes in the blood and probably the presence of the above mentioned metabolic products, no less than the excess of carbonic acid, so affect the vaso-motor centre as to lead to a great widening of the cutaneous vessels ; at the same time as we shall see these so affect other parts of the central nervous system as to lead to a great activity of the sweat glands, by means of which the products in question are got rid of or rendered inert. But the widening of the vessels of the skin and of many muscles at the same time must unless compensated lead to a fall of arterial pressure. We have evidence however that the arterial pressure does not fall, in fact may be higher than normal ; a very marked compensation must therefore take place. This is probably of a double nature. On the one hand, the altered blood increases the work of the heart, enabling it by a quicker rhythm or a stronger stroke or by both combined, to avail itself of the advantages of the greater venous inflow and to increase its output, whereby the arterial pressure increases. We cannot suppose that this increased work is due to the direct effect of the altered blood on the cardiac muscles, for the altered blood, is distinctly injurious to muscular tissue. The increase of the heart's work is gained in spite of this influence of the altered blood, and is due to the intervention of the central nervous system. There are several facts which seem to support the view that the altered blood throws into activity the 20 306 THE EFFECTS OF FOOD. [BOOK x. augmentor system, and thus by increasing the work of the heart raises or maintains the arterial pressure. On the other hand, we have reason to think that while that part of the vaso-motor centre which governs the cutaneous vas- cular area is being inhibited, that part which governs the abdominal splanchnic area is on the contrary being augmented. In this way a double end is gained. On the one hand, the mean blood pressure is maintained or increased in a more economical manner than by increasing the heart beats, and on the other hand, the blood during the exercise is turned away from the digestive organs which at the time are or ought to be at rest and therefore requiring comparatively little blood. These organs certainly at all events ought not during exercise to be engaged in the task pf digesting and absorbing food, and the old saying, " after dinner sit awhile," may serve as an illustration of the working of the vascular mechanism with which we are dealing. The duty which some of the digestive organs have during exercise to carry out in the way of excretion of metabolic waste products is as we have already said probably taken on by the flushed and perspiring skin. It is true that at the beginning of a period of exercise, before the skin so to speak has settled down to its work, an increased flow of urine, dependent on or accompanied by an increased flow of blood through the kidney, may make its appearance ; but in this case, as we shall see later on in dealing with the kidney, the flow of blood through the kidney may be increased in spite of constriction of the rest of the splanchnic area, and, besides, such an initial increase of urine speedily gives way to a decrease. § 172. The effect of food on the vascular mechanism affords a marked contrast to the effect of bodily labour. The most prominent result is a widening of the whole abdominal vascular area, accom- panied by so much constriction of the cutaneous vascular area and so much increase of the heart's beat as are sufficient to neutra- lize the tendency of the widening of the abdominal vascular area to lower the mean pressure, or perhaps even sufficient to raise slightly the mean pressure. The widening of the abdominal vascular area, as we have seen (§ 157), is probably an inhibition of tonic vaso-constrictor impulses as a reflex act, assisted possibly by some local action due to the presence of the food and similar to that supposed to take place in the skeletal muscles during contraction. We have at present no clear evidence that the absorbed products of digestion play any important part in this splanchnic dilation by acting on the central nervous system ; but the concomitant increase of the heart beat is probably due to this cause. We have no exact knowledge of how the absorbed products bring this about, and possibly the mode of action differs with the different constituents of food. With regard to alcohol, which is so often part of a meal, we may perhaps say that the character of its CHAP, iv.] THE VASCULAR MECHANISM. 307 effects, the quickening and strengthening of the beats, seems to point to its setting in action the augmentor mechanism, but it also probably acts directly on the cardiac tissues. In any case the effects depend largely on the dose, and if this is large the direct effects become prominent, and the ultimate result is a deleterious weakening. Any large widening of the cutaneous area, especially if accom- panied by muscular labour and the incident widening of the arteries of the muscles, would tend so to lower the general blood pressure (unless met by a wasteful use of cardiac energy) as injuriously to lessen the flow through the active digesting viscera. A moderate constriction of the cutaneous vessels on the other hand, by throwing more blood on the abdominal splanchnic area without tasking the heart, is favourable to digestion, and is probably the physiological explanation of the old saying, " If you eat till you 're cold, you '11 live to be old." In fact during life there seems to be a continual give-and-take between the blood vessels of the somatic and those of the splanchnic divisions of the body : to fill the one the other is proportionately emptied, and vice versa. § 173. In the following sections of this work we shall see re- peated instances, similar to or even more striking than the above, of the management of the vascular mechanism by means of the nervous system, and we therefore need dwell no longer on the sub- ject. We may simply repeat that at the centre lies the cardiac muscular fibre, and at the periphery the plain muscular fibre of the minuts artery. On these two elements the central nervous system, directed by this or that impulse reaching it along afferent nerve fibres, or affected directly by this or that influence, is during life continually playing, now augmenting, now inhibiting, now the one, now the other, and so, by help of the elasticity of the arteries and the mechanism of the valves, directing the blood flow according to the needs of the body. BOOK II. THE TISSUES OF CHEMICAL ACTION WITH THEIR EESPECTIVE MECHANISMS. NUTRITION. CHAPTER I. THE TISSUES AND MECHANISMS OF DIGESTION. § 174. 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 more 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 food, 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. 312 FOOD-STUFFS. [BOOK n. 2. Fats, frequently but erroneously called Hydrocarbons. These vary very widely in chemical composition, ranging from such a comparatively simple fat as butyrin to the highly complex lecithin (§ 66) ; 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 inasmuch 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 apart, 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, § 175. 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 corpuscles. Its reaction in a healthy subject is alkaline, espe- cially 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 T002 to 1-006. Of these solids, rather less than half, about •2 p.c., are salts (including at times a minute quantity of potas- sium 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 con- stituent, 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 carefully with a glass rod, shrinks, becoming opaque, clings to the glass rod and may be thus removed from the fluid. If the quan- tity of mucin be small and the saliva be violently shaken or stirred while the acid is being added, the mucin is apt to be pre- cipitated 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 an€ other salts ; thus after the addition of sodium chloride acetic acid even in con- siderable excess will not cause a precipitate of mucin. 314 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 (O'l p.c.) solutions of potassium hydrate, more slowly in solutions of alka- line 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. 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. § 176. 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 specific 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 hemoglobin, 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 inter- stices, 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 tur- bid, 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 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 with iodine. The formula is C6H1005 or more correctly (CcH]006)n CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 315 since the molecule of starch is some multiple (n being not less than 5) of the simpler formula. A kind of starch, known as soluble 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, achroodextrin, 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 (C6H1005)rtf. 3. Dextrose, also called glucose or grape-sugar, giving no coloration with iodine, but characterised by the power of reducing 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 cane- sugar, give this reaction ; whether the dextrins do is doubtful. The formula for dextrose is CtJHl206 ; it is more simple than that of starch or dextrin and contains an additional H2O for every 0,.. 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 Cl2H2iOu. 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 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 316 ACTION OF SALIVA. [BOOK n. 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 charac- ters 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 presence of dextrin (erythrodextrin) ; the violet colour is due to the red being mixed with the blue of still unchanged 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 staich, the relative proportions varying according to circumstances. 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 com- paratively 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. Eaw 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 granulose, 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. Hence the saliva can only get at the granulose by traversing the coats of cellulose, and the conversion of the former is thereby much hindered and delayed. § 177. The conversion of starch into sugar, and this we may speak of as the amylolytic action of saliva, will go on at the ordinary CHAP. i.J TISSUES AND MECHANISMS OF DIGESTION. 317 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 soor^ 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 contain other bodies besides the really active constituent. What- ever 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. 318 THE AMYLOLYTIC FERMENT. [BOOK n. 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 want 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 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 affected 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;1 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. § 178. 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 saKva 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 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, 1 Ferments may, for the present at least, be divided into two classes, commonly called organised and unorganised. Of the former, yeast may be taken as a well- known example The fermentative activity of veast 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. 319 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, and removed the remainder by evaporation at a low tempera- ture, 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. 320 GASTRIC JUICE. [BOOK n. Gastric Juice. § 179. 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 fiuid with a sour taste and odour. In the operation for gastric fistula, 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 natural fistula in man, its specific gravity has been found to differ little from that of water, varying from 1-001 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. 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 CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 321 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. § 180. 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 hydrochloriQ 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 hydrochloric 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 dis- solving 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 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 21 v • 322 DIGESTION OF PROTEIDS. [BOOK n. 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 Ir^drochloric 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, &c.), arising from the digestion of the mucous membrane itself.1 3. The mucous membrane, similarly prepared and minced, is thrown into a comparatively large quantity of concentrated glycerine, and allowed to stand. The membrane may be previously dehydrated by being allowed to stand under alcohol, but this is not necessary, and a too prolonged action of the alcohol injures or even destroys the activity of the product. The decanted clear glycerine, in which a comparatively small quantity of the ordinary proteids of the mucous membrane are dissolved, if added to h3Tdrochloric acid of -2 p.c. (about 1 c.c. of the glycerine to 100 c.c. of the dilute acid is sufficient), makes an artificial juice tolerably free from ordinary proteids and peptone, and of remarkable potency, the presence of the glycerine not interfer- ing with the results. Before proceeding to study the action of gastric juice on pro- teids it will be useful to review very briefly the chief characters of the more important members of the group. The more important proteids which we have thus far studied are : 1. Fibrin, insoluble in water and not really soluble (i.e. without change) in saline solutions. 2. Myosin, insoluble in water but soluble in saline solutions, provided these are not too dilute or too concentrated. 3. Globulin (including paraglobulin, fibrinogen &c.), insoluble in water, but readily soluble in even very dilute saline solutions. 4. Albumin, serum- albumin, soluble in water in the absence of all salts. 5. Acid-albumin, into which globulins and myosin are rapidly converted by the action of dilute acids, the particular acid-albumin into which the myosin of muscle is changed being sometimes called syntonin. If the reagent used be not dilute acid but dilute alkali, the product is called alkali- albumin. The two bodies, acid-albumin and alkali-albumin, are very parallel in their characters, and may readily be converted the one into the other by the use of dilute alkali or dilute acid respectively. Their most important common characters are in- solubility in water and in saline solutions and ready solubility in dilute acids and alkalis. 6. Coagulated proteids. As we have seen, when fibrin suspended in water, serum-albumin in solution, 1 These however may he removed by concentration at 40° C. and subsequent dialysis. CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 323 acid-albumin or alkali-albumin suspended in water, or paraglo- bulin suspended in water or dissolved in a dilute saline solution, are heated to a temperature, which for the whole group may be put down at about 75° — 80° C., each of them becomes coagulated, and after the change is insoluble in water, saline solutions, dilute acids &c., in fact in everything but very strong acids. Myosin and fibrinogen undergo a similar change at a lower temperature, viz. about 56° C. We may, for present purposes, speak of all these proteids thus changed under the one term of coagulated proteids. To the above list we may now add two other proteids, viz. : 7. A kind of albumin which forms the great bulk of the proteid matter present in raw ' white of egg/ and which, since it differs in minor characters from the albumin of blood and of the tissues, is called egg-albumin. 8. The peculiar proteid casein, an impor- tant constituent of milk. This may perhaps be regarded as a naturally occurring alkali-albumin since it has many resemblances to the artificial alkali-albumin ; but for several reasons it is desir- able to consider it as an independent body. Egg-albumin like serum-albumin becomes coagulated at a temperature of about 75° — 80° C., and though casein as it natu- rally exists in milk is not coagulated on boiling, when separated out in a special way, and suspended in water in which it is in- soluble, it becomes coagulated at about 75^ — 80° C. It will be observed that all these proteids form, as regards their solubilities, a descending series, in the following order. Coagulated Proteids. Fibrin. Acid-albumin with Alkali-albu- min, and Casein. Myosin, Globulins. Serum-albumin with Egg- albumin. We must now return to the action of gastric juice. If a few shreds of fibrin, obtained by whipping blood, after being thoroughly washed and boiled and thus by the boiling coagulated, be thrown into a quantity of gastric juice, and the mixture be exposed to a temperature of from 35° to 40° C., the fibrin will speedily, in some cases in a few minutes, be dissolved. The shreds first swell up and become transparent, then gradually dissolve, and finally disappear with the exception of some granular debris, the amount of which, though generally small, varies accord- ing to circumstances. If raw, that is unboiled, uncoagulated fibrin be employed the same changes may be observed, but they take place much more rapidly. If small morsels of coagulated albumin, such as white of egg, be treated in the same way, the same solution is observed. The pieces become transparent at their surfaces ; this is especially seen at the edges, which gradually become rounded down ; and solution steadily progresses from the outside of the piece inwards. If any other form of coagulated albumin (e.g. precipitated acid- or alkali-albumin,, suspended in water and boiled) be treated 324 DIGESTION OF PROTEIDS. [BOOK n. in the same way, a similar solution takes place. The readiness with which the solution is effected, will depend, cceteris paribus, on the smallness of the pieces, or rather on the amount of surface as compared with bulk, which is presented to the action of the juice. Gastric juice then readily dissolves coagulated proteids, which otherwise are insoluble, or soluble only, and that with difficulty, in very strong acids. When proteids, which are soluble in water or in dilute acid, are treated with gastric juice, no visible change takes place ; but nevertheless, it is found on examination that the solutions have undergone a remarkable change, the nature of which is easily seen by contrasting it with the change effected by dilute acid alone. If raw white of egg, largely diluted with water and strained, be treated with a sufficient quantity of dilute hydrochloric acid, the opalescence or turbidity which appeared in the white of egg on dilution (and which is due to the precipitation of various forms of globulin accompanying the egg-albumin in the raw white) dis- appears, and a clear mixture results. If a portion of the mixture be at once boiled, a large deposit of coagulated albumin occurs. If, however, the mixture be exposed to 50° or 55° C. for some time, the amount of coagulation which is produced by boiling a specimen becomes less, and, finally, boiling produces no coagula- tion whatever. By neutralisation, however, the whole of the albumin (with such restrictions as the presence of certain neutral salts may cause) may be obtained in the form of acid-albumin, the nitrate after neutralisation containing no proteids at all (or a very small quantity). Thus the whole of the albumin present in the white of egg may be, in time, converted, by the simple action of dilute hydrochloric acid, into acid-albumin. Serum-albumin similarly treated undergoes, in course of time, a similar conversion into acid-albumin, and we have already seen (§ 56) that solutions of myosin or of any of the globulins are with remarkable rapidity converted into acid-albumin. Thus simple dilute hydrochloric of the same degree of acidity as gastric juice, merely converts these proteids into acid-albumin, the rapidity of the change differing with the different proteids, being in some cases very slow, and requiring a relatively high temperature. If the same white of egg or serum-albumin be treated with gastric juice instead of simple dilute hydrochloric acid, the events for some time seem the same. Thus after a while boiling causes no coagulation, while neutralisation gives a considerable precipitate of a proteid body, which, being insoluble in water and in sodium chloride solutions, and soluble in dilute alkali and acids, at least closely resembles acid-albumin. But it is found that only a portion of the proteid originally present in the white of egg or serum-albumin can thus be regained by precipitation. Though the neutralisation be carried out with the greatest care it will bo CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 325 found, on filtering off the neutralisation precipitate, that the fil- trate, as shewn on employing the various tests for proteid (see § 15) or on adding an adequate quantity of strong alcohol, still contains a very considerable quantity of proteid matter ; and, on the whole, the longer the digestion is carried on, the greater is the proportion borne by the proteid remaining in solution to the precipitate thrown down on neutralisation ; indeed, in some cases at all events, all the proteid matter originally present remains in solution, and there is no neutralisation precipitation at all, or at finost a wholly insignificant one. § 181. The proteid matter, thus remaining in solution after neutralisation, differs from all the proteids which we have hitherto studied in as much as, though existing in a neutral solution, it is not coagulated by heat, like the egg-albumin or serum-albumin from which it has been produced ; the solution, after the neutrali- sation precipitate has been filtered off, remains quite clear when boiled. The only other solutions of proteids which do not coagu- late on boiling are solutions of acid or alkali-albumin ; but these solutions must be acid or alkali respectively ; the acid-albumin or alkali-albumin is insoluble in a neutral solution, and when simply suspended in water is readily coagulated at a temperature of 75°. This new proteid matter of which we are speaking is soluble in neutral solutions, indeed in distilled water, and can under no circumstances be coagulated by heat. Upon examination we find that the new proteid matter thus left in solution consists of at least two distinct proteid bodies. If to the solution neutral ammonium sulphate be added to saturation, part of the proteid matter is precipitated while part is still left in solution. The proteid body thus thrown down is called dlbumose. The body which is not thrown down by ammo- nium sulphate is called peptone. Now peptone is characterised by being diffusible ; it will pass through membranes. The diffu- sion is not nearly so rapid as that of salts, sugar, and other simi- lar substances ; indeed solutions of peptones may be freed from salts by dialysis. But it is very marked as compared with that of other proteids ; these pass through membranes with the great- est difficulty, if at all. Peptone is insoluble in alcohol, and may be precipitated from its solutions by the addition of an adequate quantity of this reagent ; but for this purpose a very large excess of alcohol is needed, otherwise much of the peptone remains in solution. It may be kept under alcohol for a long time without undergoing change, whereas other proteids are more or less slowly coagulated by alcohol. A useful test for peptone is furnished by the fact that a solution of peptone, mixed with a strong solution of caustic potash, gives on addition of a mere trace of cupric sul- phate in the cold a pink colour, whereas other proteids give a violet colour. In applying this test, known as the ' biuret ' test, however, care must be taken not to add too much cupric sulphate 326 DIGESTION OF PROTEIDS. [BOOK n. since in that case a violet colour, deepening on boiling, that is the ordinary proteid reaction, is obtained. There are reasons for thinking that there are several kinds or at least more than one kind of peptone ; but we may for the present speak of the sub- stance as one. Albuniose differs from peptone, not only in being precipitated by ammonium sulphate but also in being much less diffusible, and in other minor characters. Albumose like peptone gives the biuret reaction. We are able to distinguish several kinds of albumose, but into the details of these we need not enter. The amount of albumose appearing in a digestion experiment, rela- tive to the amount of true peptone, depends on the activity of the juice, and other circumstances. We may regard albumose as a less complete product of digestion than peptone. For a long time albumose was confounded with peptone, and many of the commercial forms of "peptone" consist largely of albumose. When fibrin, either raw or boiled, or any form of coagulated proteid is dissolved and seems to disappear under the influence of gastric juice, the same products, albumose and peptone, make their appearance. The same bodies result when myosin or any one of the globulins or acid-albumin or alkali-albumin is subjected to the action of the juice. Besides albumose other bodies, which may also be regarded as less complete products of digestion, make their appearance, to a variable extent under different circumstances when proteid is digested with gastric juice. On these bodies however, known as parapeptone and by other names, we need not dwell. It is obvious that the effect of the action of the gastric juice is to change the less soluble proteid into a more soluble form, the change being either completed up to the stage of peptone, the most soluble of all proteids, or being left in part incomplete. This will be seen from the following tabular arrangement of proteids according to their solubilities. Soluble in distilled water. Aqueous solutions not coagulated on boiling. Diffusible Peptone. Much less diffusible Albumose. Aqueous solutions coagulated on boiling . Albumin. Insoluble in distilled water. Eeadily soluble in dilute saline solutions (NaCl 1 per cent.) Globulins. Soluble only in stronger saline solutions (NaCl 5 to 10 p. c.) Myosin. CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 327 Insoluble in dilute saline solutions. 111 • j-i j -J /Trm 1 \ ( Acid-albumin. Eeadily soluble in dilute acid (HC1 1 p.c.) \ Alkali_albumin> in the cold (Casein. Soluble with difficulty in dilute acid, that is at high temperature (60° C.) and after prolonged treatment only . . . Fibrin. Insoluble in dilute acids, soluble only in strong acids Coagulated Proteid. Milk when treated with gastric juice is first of all "curdled." This is the result partly of the action of the free acid but chiefly of the special action of a particular constituent of gastric juice, of which we shall speak hereafter. The curd consists of a particular proteid matter mixed with fat ; and this proteid matter is sub- sequently dissolved with the same appearance of peptone, albu- mose and other bodies as in the case of other proteids. In fact, the digestion by gastric juice of all the varieties of proteids con- sists in the conversion of the proteid into peptone, with the con- comitant appearance of a certain variable amount of albumose and other bodies. § 182. Circumstances affecting gastric digestion. The solvent action of gastric juice on proteids is modified by a variety of cir- cumstances. The nature of the proteid itself makes a difference, though this is determined as well by physical as by chemical characters. Hence in making a series of comparative trials the same proteid should be used, and the form of proteid most con- venient for the purpose is fibrin. If it be desired simply to ascertain whether any given specimen has any digestive powers at all, it is best to use boiled fibrin, since raw fibrin is eventually dissolved by dilute hydrochloric acid alone, probably on account of some pepsin previously present in the blood becoming entangled with the fibrin during clotting. But in estimating quantitatively the peptic power of two specimens of gastric juice under different conditions, raw fibrin prepared by Griitzner's method is the most convenient. Portions of well washed fibrin are stained with carmine and again washed to remove the superfluous colouring matter. A fragment of this coloured fibrin thrown into an active juice on becoming dissolved, gives up its colour to the fluid. Hence if the same stock of coloured fibrin be used in a series of experiments, and the same bulks of fibrin and of fluid be used in each case, the amount of fibrin dissolved may be fairly estimated by the depth of tint given to the fluid. Fibrin thus coloured with carmine may be preserved in ether. Since, if sufficient time be allowed, even a small quantity of gastric juice will dissolve at least a very large if not an indefinite 328 GASTRIC DIGESTION. [BOOK n. quantity of fibrin, we are led to take, as a measure of the activity of a specimen of gastric juice, not the quantity of fibrin which it will ultimately dissolve, but the rapidity with which it dissolves a given quantity. The greater the surface presented to the action of the juice, the more rapid the solution ; hence minute division and constant move- ment favour digestion. And this is probably, in part at least, the reason why a fragment of spongy filamentous fibrin is more readily dissolved than a solid clump of boiled white of egg of the same size. Neutralisation of the juice wholly arrests digestion • fibrin may be submitted for an almost indefinite time to the action of neutralised gastric juice without being digested. If the neutialised juice be properly acidified, it may again become active ; when gastric juice however has been made alkaline, and kept for some time at a temperature of 35°, its solvent powers are not only suspended but actually destroyed. Digestion is most rapid with dilute hydro- chloric 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. maybe substituted for hydrochloric; but they are not so effec- tual, and the degree of acidity most useful varies with the dif- ferent acids. The presence of neutral salts, such as sodium chloride, in excess is injurious. The action of mammalian gastric juice is most rapid at 35° — 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- drochloric acid (*2 p.c.), or if the mixture 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. § 183. Nature of the action. All these facts go to shew that the digestive action of gastric juice on proteids, like that of saliva on starch, is a ferment-action ; in other words, that the solvent action of gastric juice is essentially due to the presence in it of a CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 329 ferment-body. To this ferment-body, which as yet has been only approximately isolated, the name of pepsin 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. Concerning its exact nature we cannot make any definite statement ; we have no absolute proof that it is a proteid, probable as this may seem. We are as yet unable to define it by any chemical characters. 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 perfectly neutral medium, and there seems to be no special con- nection between the ferment and any alkali or acid. In gastric juice, however, there is a strong tie between the acid and the fer- ment, 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 fairly 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 water in a Papin's digester, that is to say by means of agents which, in other cases, produce their effects by bringing about hydrolytic changes. § 184. All proteids, so far as we know, are converted by pep- sin into peptone. Concerning the action of gastric juice on other nitrogenous substances more or less allied to proteids but not truly proteid in nature 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 dis- solved 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 gela- tinisation is entirely lost. Chondrin and the elastic tissues undergo a similar change. § 185. Action of gastric juice on milk. It has long been 330 DIGESTION OF MILK. [BOOK n. 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 temperature 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 neutralised 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 is destroyed by previous boiling of the juice or rennet. These facts suggest that a ferment is at the bottom of the matter ; and indeed, all the features of the action support this view. More- over, as a matter of fact, a curdling ferment may be extracted by glycerine and by the other methods used for preparing ferments. The ferment, however, is not pepsin, but some other body ; and the two may be separated from each other. It might be thought that the rennet-ferment, rennin we may call it, acted by inducing a fermentation in the sugar of milk, giving rise to lactic acid which precipitated the casein by virtue of its being an acid. But this view is disproved by the following facts which shew that the ferment produces its curdling effect by acting directly on the natural casein itself. Casein may be pre- cipitated unchanged, that is, capable of redissolving in water (the presence of calcic phosphate being assumed) by saturating milk with neutral saline bodies (such as sodium chloride or magnesium sulphate) ; and by being precipitated and redissolved more than once may be obtained largely free from fat and wholly free from milk-sugar. Such solutions of isolated casein freed from milk- sugar may be made to curdle like natural milk by the addi- tion of rennin, shewing that the milk-sugar has nothing to do with the matter. Moreover the precipitate thrown down from milk by dilute acids, lactic acid included, is itself unaltered or very slightly altered casein not curd, and with care may be so prepared as to be redissolved into solutions which curdle CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 331 with rennin, like solutions of casein prepared by means of neutral salts. When isolated casein is curdled by means of rennin two pro- teids, it is stated, make their appearance, one of which is soluble and allied to albumin, and another, which is insoluble and forms the curd. Curdling, therefore, according to this result appears to be the splitting up by a ferment of a more complex body ; and it is interesting to observe, as perhaps throwing light on the some- what analogous formation of fibrin, that this curdling action will not take place if calcic phosphate be wholly absent from the mix- ture. The calcic phosphate appears to play a peculiar part in determining the insolubility of the curd, for there is evidence that in the absence of calcic phosphate the ferment has power to attack the casein and split it up, but that both products remain in solution ; if calcic phosphate be present, the one, viz. the curd, becomes insoluble. Eennin is abundant in the gastric 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 speak of as the antecedent of the ferment or zymogen, is 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. SEC. 2. THE ACT OF SECRETION OF SALIVA AND GASTRIC JUICE AND THE NERVOUS MECHANISMS WHICH REGULATE IT. § 186. The saliva and gastric juice whose properties we have studied, though so different from each other, are both drawn ulti- mately from one common source, the blood, and they are poured into the alimentary canal, not in a continuous now, 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 dis- tance 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 mechan- ism 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 cal- culated 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 sub- maxillary gland. CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 333 § 187. The submaxillary gland is supplied with two sets of nerves. These are represented in Fig. 76, which is a very dia- grammatic rendering of the appearances presented when the sub- maxillary 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 tympani nerve (ch.tff). This is a small nerve, which branches off from the facial or seventh cranial nerve in the Fallo- pian 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 ultimately 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.tf) with the lingual or gustatory 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 (sm.d) 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 abundant 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 end- ing has not yet been definitely made out. Along its whole course 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 § 144. § 188. If a tube be placed in the duct, it is seen that when sapid substances are placed on the tongue, or the tongue is stimu- lated in any other way, or the lingual nerve is laid bare and stimu- lated 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 pro- duces 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 334 NERVES OF THE SUBMAXILLARY GLAND. [BOOK n. it, as at n.l', Fig. 76, stimulation of the (front part of) tongue pro- duces, under ordinary circumstances, no flow. This shews that the centre of the reflex action is higher up than the point of sec- tion ; it lies in fact in the brain. FIG. 76. DIAGRAMMATIC REPRESENTATION OF THE SUBMAXILLARY GLAND OP THE DOG WITH ITS NERVES AND BLOOD VESSELS. (The dissection has 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 submaxillary gland, into the duct (sm.d) of which a cannula has been tied. The sublingual gland and duct are not shewn. n.I, nl'. The lingual branch of the fifth nerve, the part nJ. 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.l'. and afterwards diverging passes as cht.t. to the gland along the duct ; the continuation of the nerve in company with the lingual n.l. is not shewn, sm.yl. The submaxillary ganglion with its several roots. n.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, r.s.in. The anterior and posterior veins from the gland, falling into v.j. the jugular vein, v.sym. The conjoined vagus and sympathetic trunks, gl.cer.s. The upper cervical ganglion, two branches of which forming a plexus (a.f.) 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 diagrammatically in Fig. 76 sm.gL). 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 CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 335 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 gas- tric 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 oblongata, apparently not far removed from the vaso-motor centre. When the brain is removed down to the medulla oblongata, 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. When 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 may therefore state that, practically, the chorda tympani is the sole efferent nerve. 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 lin- gual, 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. § 189. In life, then, the flow of saliva is brought about by the 336 SECRETION AND BLOOD SUPPLY. [BOOK n. 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 flow ? If in a dog a tube be introduced into Wharton's duct, and the chorda be divided, the 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, § 145) 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 O ± J 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 § 102) 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 CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 337 only to the accumulation in the cell of the constituents of the 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 walls, tend to check that transit. Again, if the head of an animal be rapidly cut off, and the chorda immedi- ately stimulated, a flow 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 fibres, one which we may call se :retory 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 secreting cells, and calling them 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. Since the chorda acts thus directly on the secreting cells, we should expect to find an anatomical connection between the cells and the nerve ; but concerning this our knowledge is as yet im- perfect. §190. When the cervical sympathetic is stimulated, the vascular effects, as we have already said, § 146, are the exact 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 22 338 SECRETION OF GASTRIC JUICE. [BOOK n. gland is almost arrested. The sympathetic therefore acts as a vaso-constrictor 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. 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 vas- cular phenomena may assist, but are not the direct cause of, the flow. § 191. 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 of the fifth nerve but originating possibly in the glossopharyngeal, 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 ; stimulation of the cervical sympathetic gives rise in the rabbit to a secretion 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. § 192. 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 CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 339 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 secre- tion of saliva. § 193. 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 some direct local action ; and this view is sup- ported 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. The stomach is supplied with nerve-fibres from the two vagi nerves and from the solar plexas of the splanchnic system. Our knowledge however of the action of the nervous system upon the stomach by means of these two sets of fibres is very imperfect. There are many facts which shew that the central nervous system may affect the secretion of gastric juice. On the other hand 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 so far as possible severed. § 194. 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 the 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 which we shall speak later on, succeeded in isolating a portion of the fundus from the rest of the stomach ; that is to say, he cut out a portion of the fundus, 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 340 SECRETION OF GASTRIC JUICE. [BOOK n. orifice. When 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 fundus 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. § 195. 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, wiiile the animal is not only alive but under such conditions that the gland- remains in a nearly 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, the outlines of the individual cells lining the alveolus are very in- distinct, the lurnen 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 mem- brane, or it may be hardly any such zone at all. Fig 77 A. The gland is said to be ' loaded ' or at rest. 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. 77 B} have become smaller and much more distinct in 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 CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 341 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 FIG. 77. 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. 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 striae 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 th°, 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 342 CHANGES IN PANCREATIC CELLS. [Boon n. therefore the gland has been for some time actively secreting, the granules are far less numerous, and the clear outer zone accord- ingly 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, haematoxylin &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 consumed in forming the granules. During the act of secretion the granules are discharged to form part of the secretion, other matters including water, as we shall see, making up the 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 con- siderable distinctness and ease in the pancreas, is seen with more or less distinctness in other glands. § 196. When we study an ' albuminous,' or ' serous ' salivary 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 pancreas. During rest (Fig. 78 A), the cells are large, their outlines very indistinct, in fact almost invisible, and the cell-substance is studded with granules. Dur- ing activity (Fig. 78 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. 78 (7, the cells are still smaller with 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 CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 343 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 pan- creas. For, the demarcation of an inner and outer zone is not a necessary feature of a secreting cell at rest. What is essential FIG. 78. CHANGES IN THE PAROTID DURING SECRETION. (Langley.) The figure, which is somewhat diagrammatic, represents the microscopic changes which may be observed in the living 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. 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 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 speci- mens have disappeared. In consequence, in sections of hardened and prepared albuminous glands the differences between resting or loaded and active or discharged cells are not so conspicuous as in the pancreas. The difference however even in hardened speci- mens between the parotid of the rabbit at rest, and that excited by stimulation of the sympathetic is well marked. During rest, the cells (Fig. 79 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 cell-substance becomes turbid (Fig. 79 B\ and stains much more readily, while the nuclei are no longer irregular in outline but round and large, with conspicuous nucleoli, the whole cell at the 344 CHANGES IN ALBUMINOUS CELLS. [BOOK n. same tim?, at least after prolonged stimulation, becoming distinctly smaller. § 197. In a mucous salivary gland the changes which take place are of a like kind, though apparently somewhat more com- plicated, owing probably to the peculiar characters of the mucin which is so conspicuous a constituent of the secretion. FIG. 79. SECTIONS OF THE PAROTID OP THE BABBIT. A at rest, B after stimu- lation of the cervical sympathetic. Both sections are from hardened gland. (After Heidenhain.) If a piece of resting, loaded submaxillary gland be teased out, while fresh and warm from the body, in normal saline solution, the cell-substance of the mucous cells (Fig. 80 a) is seen to be crowded FIG. 80. Mucous CELLS FROM A FRESH SUBMAXILLARY GLAND OF DOG. (Langley.) a and 6 isolated in 2 p.c. salt solution ; a, from loaded gland, b from discharged gland (the nuclei are usually more obscured by granules than is here represented). (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. with granules or spherules which may fairly be compared with the granules of the pancreas, though perhaps less dense and solid than these. CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 345 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. 80 b) the granules are far less numerous and largely confined 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 call. 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 dis- charged cell) be irrigated with water or with dilute acids or dilute alkalis the granules swell up (Fig. 80 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 ap- pearance very similar to that shewn in sections of mucous glands hardened and stained in the ordinary way. In the loaded mucous cell in such hardened and stained pre- parations (Fig. 81 a) there is seen a small quantity of protoplasmic a FIG. 81. ALVEOLI OF DOG'S SUBMAXILLARY GLAND HARDENED IN ALCOHOL AND STAINED WITH CARMINE. (Langley.) (The network is diagrammatic.) a, from a loaded gland. b, from a discharged gland ; the chorda tympani having been stimulated at short intervals during five hours. 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 346 CHANGES IN GASTRIC CELLS. [BOOK n. 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 simi- lar preparations (Fig. 81 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 protoplas- mic 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 FIG. 82. GASTRIC GLAND OF MAMMAL (Bat) DURING ACTIVITY. (Langley.) c, the mouth of the gland with its cylindrical cells. n, 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. certain material in the form of granules. During secretion these granules disappear and presumably form part of the secretion. § 198. The ' central ' or ' chief ' cells of the gastric glands also exhibit similar changes. In such an animal as the newt CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 347 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. 82. 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 granu- lar ; 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 up. In the loaded cell 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 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 alco- hol, 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 basement membrane, but no characteristic disappearance of gran- ules 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. § 199. 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 348 TRYPSIN AND TRYPSINOGEN. [BOOK n. cases. In each case the * protoplasmic ' cell-substance manufac- tures and lodges in itself material destined to form part of the juice secreted. In the fresh cell this material may generally be recognized under the microscope by its optical characters as gran- ules ; 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 differ- entiate 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 neces- sary 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 gran- ules, and that the formative activity should cease when the secre- tory 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 actu- ally take place, so that no distinction in granules can be observed between resting and active cells. § 200. 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 transparent material lodged in the spaces of the cell- substance, which material even if not exactly identical with at least closely resembles the mucin found in the secretion ; and ap- parently, 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 appear- ing in the secretion but an antecedent of that substance. CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 349 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 converting them into peptone and other substances. Though in many respects alike, pepsin and trypsin are quite distinct bodies, and differ markedly in this, that while an acid medium is necessary for the action of pepsin, an alkaline medium is necessary for the action of trypsin ; and accordingly the pancreatic juice is alkaline in contrast to the acid- ity of gastric juice. Trypsin, can, like pepsin (§ 183), be extracted with glycerine from substances in which it occurs ; glycerine ex- tracts of trypsin however need for. the manifestation of their powers the presence 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 which 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 pancreas of an animal, even of one in full digestion, be treated, while still warm from tlie body, with glycerine, the glyce- rine 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 instead 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 solu- tion, 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 present in it a body which, by some kinds of decomposition, gives birth to the ferment. We may remark incidentally that though the presence of an alkali is essential to the proteolytic action of the actual ferment, the formation of the ferment out of its fore- runner 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 350 NATURE OF THE ACT OF SECRETION. [BOOK n. 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 undeniably proteid body, the name of zymogen has been applied. But it is better to reserve the term zymogen as a gene- ric 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 particu- lar 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. § 201. 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 filters as it were from the common store of the blood the several constituents of the juice, is unten- able. 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 know that certain important constituents of each juice, the pepsin of gastric juice, the mucin of saliva and the like are formed in the cell, 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 way 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 CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 351 promoting the discharge of water, while stimulation of the sym- pathetic has a marked effect in promoting the discharge of uiucin. 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 now 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 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. The whole act of secretion is a very complicated one, probably too complicated to be described as consisting merely of the two processes mentioned above. § 202. Throughout the above we have spoken as if the secre- tion were furnished exclusively by the cells of the alveoli or se- creting 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 352 THE ACT OF SECRETION. [BOOK n. 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. § 203. 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 ; 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 certain can at present be stated as to the mechanism of that decomposition. In the frog, while pepsin free from acid is secreted by the glands in the lower portion of the oesophagus, an acid juice is afforded by glands in the stomach itself, which have accordingly been called oxyntic {b^vveiv 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. § 204. Seeing the great solvent power of both gastric and pancreatic juice, the question is naturally suggested, Why does not the stomach digest itself ? After death, the stomach is CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 353 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. We cannot answer this question at all at present, any more than the similar one, why the delicate proto- plasm of the amoeba 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 bullse and the breaking up of the protoplasm. SEC. 3. THE PROPERTIES AND CHARACTERS OF BILE, PANCREATIC JUICE AND SUCCUS ENTERICUS. § 205. 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 juice 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 con- venient 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, sometimes a greenish yellow: of CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 355 herbivorous animals, a yellowish green, or a bright green, or a dirty green, according to circumstances, 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 914 Fats, &c 9-2 Cholesterin 2*6 Mucus and Pigment 29'8 Inorganic Salts 7*8 140-8 The entire absence of proteids is a marked feature of bile ; pan- creatic 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 and which deserve chief attention, are the pigments and the bile-salts; of these we shall speak im- mediately. 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 anct 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 pig- ment of bile, itself free from iron, is derived from iron-holding haemoglobin ; some, at least, of the iron set free during the con- version of haemoglobin 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 manganese 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 com- plex body lecithin. The peculiar body cholesterin, which though fatty looking (hence the name ' bile fat ' ) is really an alcohol with the composi- tion CseH^O, is conspicuous by its quantity and constancy. It forms the greater part of most gall-stones, though some are com- posed chiefly of pigment. Insoluble in water and cold alcohol, 356 BILE-SALTS. [Boon H. though soluble in hot alcohol and readily soluble in ether, chloro- form &c., it is dissolved by the bile-salts in aqueous solution and hence is present in solution in bile. Its physiological functions are obscure. 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. § 206. 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 pow- der, or of well-formed rhombic tablets and prisms. Insoluble in water, and but little soluble in ether and alcohol, it is readily soluble in chloroform, and in alkaline fluids. Its composition is C16H18N203. 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 bili- rubin is the basis of the so-called Gmelin's test for bile-pigments. Each of these stages represents a distinct pigmentary substance. As alkaline solution of bilirubin, exposed in a shallow vessel to the action of the air, turns green, becoming converted into BiU- verdin (C16H18N O4), the green pigment of herbivorous bile. Bili- verdin 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 oxidiiing agents biliverdin runs through the same series of colours as bilirubin, with the exception of the initial golden red. § 207. The Bile-salts. These consist, in man and many ani- mals, of sodium glycocliolate 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 dry ness and extracted with alcohol. If not colourless, the alcoholic CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 357 filtrate must be further decolourized with animal charcoal, and the alcohol distilled off. The dry residue is treated with absolute alcohol, and to the alcoholic filtrate anhydrous ether is added as long as any precipitate is formed. On standing the cloudy precipitate becomes 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 glycin C26H43N06 + H20 = C24H40O5 + CH2 . NH2 (CO . OH) taurocholic acid cholalic acid taurin CasH^NSOT + 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 decomposition 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 compounds 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 characteristic spectrum. A similar colour may however often be produced by the action of the same bodies on albumin, amyl alcohol, and some other organic bodies. § 208. Action of Bile on Ftfod. 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 358 PANCREATIC JUICE. [BOOK n. of the pancreatic juice. To peptic action it is distinctly antago- nistic ; 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 di- gestion, a precipitate takes place, consisting of parapeptone (when present), peptone, pepsin and bile salts. The precipitate is redis- solved in an excess of bile or solution of bile-salts ; but the pepsin though redissolved 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. Bile 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 circumstances at all events facilitated by the pres- ence 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. 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 filter-paper kept wet with a solution of bile-salts, whereas 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. § 209. 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; but CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 359 with permanent fistulse the secretion is apt to become altered in nature, and to lose many of its characteristic properties. Some, however, have succeeded in obtaining permanent fistulse without any impairment of the secretion. 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. The 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. § 210. 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^ase of pancreatic juice, except that the activity of the latter IB 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 takeh 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 jui©$ 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. The 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 360 TRYPTIC DIGESTION. [BOOK n. 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 former case the fibrin does 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 peptic 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 alka- line digestion ; the action is most energetic when some alkali is present ; and the activity of an alkaline juice is hindered or de- layed 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 mix- ture be supplied with sodium carbonate to the extent of 1 p.c., digestion proceeds rapidly, just as does a peptic mixture when acidulated with hydrochloric acid to the extent of -2 p.c. Sodium carbonate of 1 p.c. seems in fact to play in tryptic digestion a part altogether comparable to that of hydrochloric acid of -2 p.c. in gastric digestion. And just as pepsin is rapidly destroyed by being heated to about 40° with a 1 p.c. solution of sodium carbo- nate, so trypsin is rapidly destroyed by being similarly heated with dilute hydrochloric acid of *2 p.c. Alkaline bile, which arrests peptic digestion, seems, if anything, favourable to tryptic digestion. Pancreatic digestion and gastric digestion agree in that by both proteids are converted into peptones. Naturally in the alka- line pancreatic digestion no bye products allied to acid-albumin, such as parapeptone, make their appearance ; there are however various bye products on which we need not dwell. Albumoees are not conspicuous in pancreatic digestion, they are very rapidly carried on to the further stage of peptone. In one respect there is an essential difference between gastric and pancreatic digestion. In gastric digestion the products are not carried beyond the proteid stage ; in pancreatic digestion part of the proteid is changed into something which is no longer proteid. During the pancreatic digestion of proteids, two remarkable nitrogenous crystalline bodies, leucin and tyrosin make their appear- ance. 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 ; and the longer the digestive action, the greater up to a certain point is this apparent loss. If a pancreatic digestion mixture be freed from the bye products by neutralisation and filtration, the filtrate yields, when concentrated by evaporation, a crop of crystals of CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 361 tyrosin. If these be removed the peptone may be precipitated from the concentrated nitrate by the addition of a large excess of alcohol and separated by nitration. The second nitrate 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 leucia, tyrosin, and probably several other bodies, such as fatty acids and volatile substances. We said that in gastric digestion more than one kind of peptone was probably formed, and the same may be said of pancreatic digestion. We may now add that in both gastric and pancreatic digestion two kinds of peptone are probably formed, one of which resists the action of trypsin, and undergoes no further change, but the other of which, whether arising from gastric or pancreatic digestion undergoes further change by the action of trypsin and it is this which is the source of the leucin and other bodies of which we are speaking. 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 C,;HI3NO2 or C5H10.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, C9HnNO3, 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. We 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 362 TRYPTIC DIGESTION. [BOOK n. 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. On the gelatiniferous elements of the tissues in the condition in which they actually exist in the tissue previous to any treat- ment pancreatic juice appears to have no solvent action. The fibrillse and bundles of fibrillse 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 treated with acid or boiled so as to become con- verted into actual gelatine, trypsin is able to dissolve them, appar- ently 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 place 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 pancre- atic 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 pancreatic juice splits up neutral fats into their respective acids and glycerine. Thus palmitin (or tripalmitin) (Ci5H31 . CO . 0)3 . C5HS is with the assumption of 3H2O 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 capat.c CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 363 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- 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, § 200, is active in proportion as the trypsinogen has been converted into trypsin. Succus Entericus. § 211. 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 fistulae 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 invert cane- sugar rapidly, and by a fermentative action to convert cane-sugar 364 SUCCUS ENTERICUS. [BOOK n. 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. But even at the best, its actions are slow and feeble. Moreover many observers have obtained negative results, so that the various state- ments 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 caecum and large intestine, we shall speak when we come to consider the changes in the alimentary canal. § 212. 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 discoloured 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 combi- nation 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. Gall- stones consisting almost entirely of inorganic salts, calcic carbon- ates and phosphates, are also occasionally met with. In the lower animals, in oxen for instance, bilirubin gallstones are not uncom- mon, but cholesterin 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. 4. THE SECRETION OF PANCREATIC JUICE AND OF BILE. § 213. 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 continu- ous, 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. 83 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 maxi- mum 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 § 194 ; and a similar absorp- 366 SECRETION OF PANCREATIC JUICE. [BOOK n. tion may contribute to the first rise also, but it is more probable that so marked and sudden a rise as this is carried out by some 2 |3|4|5|6|7|8|9|lO|ll|l2|l3il*ll5il6| \ I 2 1 3 |4| 5 I 61 7J-8 iQJID FIG. 83. DIAGRAM ILLUSTRATING THE INFLUENCE OF FOOD ON THE SECRETION OF PANCREATIC JUICE. (N. O. Bernstein.) The abscissae represent hours after taking food ; the ordinates 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 0, 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. nervous mechanism. The details of this mechanism have how- ever not as yet been satisfactorily worked out. Stimulation of the medulla oblongata, or of the spinal cord, will call forth secretion in a quiescent pancreas, or increase a secretion already going on. On the other hand 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 is probably brought about in this way. This effect however is not confined to the vagus, it occurs also after stimulation of other afferent nerves, such as the sciatic. § 214. 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 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 fluids so applied have little or no effect. When no such CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 367 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 fistuhe, 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 clogs, in from four to eight hours. There seems to bs 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. § 215. 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 portse ; it moreover, as we shall see, is distributed in capillaries among the small inter- 368 BLOOD-SUPPLY OF LIVER. [BOOK n. lobular branches of the vena portae 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 portse ; and this supply is not, like an arterial supply, a fairly uniform one, modified chiefly by the vase-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 portre 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 § 172), a relatively large quantity of blood rushes into the vena porUe 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 § 103), 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 the central nervous system by a single nervous tie, the tide of blood through the liver would ebb and flow according to the absence or presence of food in the alimentary canal. An increase of blood-supply does not of course necessarily mean an increase of secretory activity. As we have seen, § 189, in the presence of atropine, the secretion of saliva may stand still in spite of dilated blood vessels 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 work, 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. CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 369 And as a matter of fact we do find vaso-motor action domi- nant 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 ma- terially 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, chiefly 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 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, espe- cially 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 now 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-supply, 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 matter. § 216. It is interesting to observe that the pressure under which the bile is secreted is relatively low, 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 (§189) the pressure is greater than the blood-pressure in the carotid artery. But, in the case of bile, since the blood which flows 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 24 370 BLOOD-SUPPLY OF LIVER. [BOOK n. 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. mer- cury, 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 mesen- teric 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 pres- sure 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. § 217. 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 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 constitu- ents 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. 5. THE MUSCULAR MECHANISMS OF DIGESTION. § 218. 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 mastication, or its more complete mixture with the digestive juices, or its forward progress through the alimentary canal. Peristaltic Movements. The dominant movement in the ali- mentary canal is of the kind called peristaltic, carried out by means of the circular and longitudinal muscular coats. This is seen in its simplest form in the small intestine, is somewhat modi- fied in other parts as in the stomach, and at the beginning and end of the canal is replaced or assisted by complicated movements carried out by various muscles. The main part of a peristaltic movement, as seen in the small intestine, is a wave of contraction progressing longitudinally over the circular coat (§ 84). A contraction of the circular coat takes place at some level or other, narrowing the intestine at this level. From thence, the circularly disposed bundles contracting in sequence, the contraction travels as a wave downwards or up- wards or both downwards and upwards. As a rule the wave, when started naturally, travels downwards from a part nearer the mouth to a part nearer the rectum. Thus a narrowing or con- striction of the tube travels onwards as a wave driving the contents of the tube before it ; when a butcher empties the contents of the intestine of a slaughtered animal by squeezing it high up with his . hand or his thumb or forefinger, and then 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. This action of the circular coat is further aided by a corre- sponding contraction of the longitudinal coat When a length of the longitudinal coat is thrown into contraction, that length of the tube is shortened and widened ; the effect is the antagonist of that produced by the contraction of the circular coat. Hence 372 DEGLUTITION. [BOOK n. the two coats must contract at different times, otherwise they would neutralise each other's action. Most probably a section of the longitudinal coat contracts in front of the section of the cir- cular coat which is about to contract, thus affording room for the contents which are about to be driven on, or even itself drawing them forward ; but a contraction of the longitudinal coat, even if it followed after that of the circular coat, might still be useful in helping to bring back the tube to its normal width. 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 on- ward 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. We may con- sider the several special movements of the different parts of the canal. 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 arid fore-and-aft movement. The lower jaw is raised by means 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 condyles, 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 tempo- ral 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 con- tact 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. § 219. Deglutition. The food when sufficiently masticated is, CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 373 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 the styloglossus — the bolus is thrust back between the tongue and the palate through the anterior pillars of the fauces or isth- mus faucium. Immediately before it arrives there, the soft palate is raised by the levator palati, and so brought to touch the poste- rior 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 in- troducing 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 tilled 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 glottidis, while the epiglottis itself is depressed over the larynx. The 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 contrac- tions, that is to say, by 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 move- 374 DEGLUTITION. [BOOK n. nient 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 shoot it in fact, along the lax oesophagus before the muscles of that organ have time to contract. In such a mode of swallowing the 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. Deglu- tition in this fashion still remains possible after these constrictors have become paralysed by section of their motor nerves. When a second act of deglutition succeeds a first with sufficient rapidity, the nervous changes which start the pharyngeal move- ments of the second act appear to inhibit the oesophageal move- ments 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 differ- ent regions, a sound is heard during deglutition ; sometimes two sounds are heard. The first and most constant is coincident with the passage of the bolus, and is due to this and to the muscular sound of the contracting muscles. The later and less constant sound appears 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 peris- taltic 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 as rapid as possible. The third stage is the descent through the grasp of the constrictors. Here the food has passed the respira- tory orifice, and in consequence its passage again becomes compar- atively 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 oesophageal 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 exer- CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 375 else 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 voluntary and involuntary kingdoms, must be 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 differ- ent 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. § 220. 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. 376 MOVEMENTS OF (ESOPHAGUS. [BOOK n. It will be remembered that the muscular bundles of the oeso- phagus 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 movements 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 im- pulses started in the pharynx and passing to the medulla oblongata, give rise to reflex efferent impulses which descend along 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 con- traction, 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, viz. 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 oesophageal movements can easily be excited by centripetal stimulation of the superior laryngeal. The centre lies in the medulla oblongata, being a part of the general 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 oesophageal plexuses of the vagus (Fig. 84). Section of the trunk of the vagus ' renders difficult the passage of food along the oeso- phagus, and stimulation of the peripheral stump causes oesophageal 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 CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 377 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 pre- vent 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. § 221. Movements of the Stomach. While the object of the oesophageal 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 the constituents of the contents that may be necess.ary, 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 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 th'e 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. 378 VOMITING. [BOOK n. 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 circu- lar 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 con- tents; 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 a thick fluid condition somewhat resembling pea soup and often called chyme, to strain oft this more fluid part into the duodenum, and to submit the remaining still solid pieces to the further action of the gastric juice. As digestion proceeds, more and more material leaves the stomach, which is thus gradually emptied, the last portions which are carried through being those parts of the food which are least digestible, and any wholly indigestible foreign bodies which happen to have been swallowed ; the latter may perhaps never leave the stomach at all. The presence of food leads to the development of the movements; but evidently it is not the mere mechanical repletion of the organ which is the cause of the movements, since the stomach is fullest at the beginning when the movements are slight, and becomes emptier as they grow more forcible. The one thing which does increase pari passu with the movements is the acidity, which is at a minimum when the (generally alka- line) food has been swallowed, and increases steadily onwards. It has not however been definitely shewn that the increasing acidity is the efficient stimulus, giving rise to the movements. The movements of even a full stomach are said to cease during sleep. The nervous mechanism of the gastric movements had better be considered in connection with that of the intestinal movements. § 222. Vomiting. In a conscious individual this act is preceded by feelings of nausea, during which a copious flow of saliva into the mouth takes place. This being swallowed carries down with it a certain quantity of air, the presence of which in the stomach, by assisting in the opening of the cardiac sphincter, subsequently facilitates the discharge of the gastric contents. The nausea is CHAP, i.l TISSUES AND MECHANISMS OF DIGESTION. 379 generally succeeded at first by ineffectual retching in which a deep mspiratory effort is made, so that the diaphragm is thrust down as low as possible against the stomach, the lower ribs being at the same time forcibly drawn in ; since during this inspiratory effort the glottis is kept closed, no air can enter into the lungs ; but some is drawn into the pharynx, and thence probably descends by a swallowing action into the stomach. When retching passes on to actual vomiting this inspiratory effort is succeeded by a sudden violent expiratory contraction of the abdominal walls, the glottis still being closed, so that the whole force of the effort is spent, as we shall see it is in defeecation, in pressure on the abdominal contents. The stomach is therefore forcibly compressed from without. At the same time, or rather immediately before the expiratory effort, by a contraction of its longitudinal fibres the oesophagus is shortened and the cardiac orifice of the stomach brought close under the diaphragm, while apparently by an inhibition of the circular sphincter, aided perhaps by a contraction of the fibres which radiate from the end of the oesophagus over the stomach, the cardiac orifice, which is normally closed, is somewhat suddenly dilated. This dilation opens a way for the contents of the stomach, which, pressed upon by the contraction of the abdomen, and to a certain but probably only to a slight extent by the contraction of the gastric walls, are driven forcibly up the oesophagus. The mouth being widely open, and the neck stretched to afford as straight a course as possible, the vomit is ejected from the body. At this moment there is an additional expiratory effort which serves to prevent the vomit passing into the larynx. In most cases too the posterior pillars of the fauces are approximated, in order to close the nasal passage against the ascending stream. This however in severe vomiting is frequently ineffectual. Thus in vomiting there are two distinct acts : the dilation of the cardiac orifice and the extrinsic pressure of the abdominal walls in an expiratory effort. Without the former the latter, even when distressingly vigorous, is ineffectual. Without the latter, as in urari poisoning, the intrinsic movements of the stomach itself are rarely sufficient to do more than eject gas, and, it may be, a very small quantity of food or fluid. Pyrosis or waterbrash is however probably brought about by this intrinsic action of the stomach, During vomiting the pylorus is generally closed, so that but little material escapes into the duodenum. When the gall-bladder is full, a copious flow of bile into the duodenum accompanies the act of vomiting. Part of this may find its way into the stomach, as in bilious vomiting, the pylorus then having evidently been opened. The nervous mechanism of vomiting is complicated and in many aspects obscure. The efferent impulses which cause the 380 MOVEMENTS OF THE SMALL INTESTINE. [BOOK n. expiratory effort must come from the respiratory centre in the medulla ; with these we shall deal in speaking of respiration. The dilation of the cardiac orifice is caused, in part at least, by impulses descending the vagi, since when these are cut real vomiting with discharge of the gastric contents, if it takes place at all, becomes difficult through want of readiness in the dilation. Such intrinsic movements of the stomach as do take place, and the movements of the oesophagus appear to be carried out by the usual nerves. The efferent impulses which cause the flow of saliva in the introductory nausea also descend along the usual nerves such as the chorda tympani. These various impulses may best be considered as start- ing from a vomiting centre in the medulla, having close relations with the respiratory centre. This centre may be excited, may be thrown into action, in a reflex manner, by stimuli applied to periph- eral nerves, as when vomiting is induced by tickling the fauces, or by irritation of the gastric membrane, or by obstruction of the intestine due to ligature, hernia, etc. That the vomiting in the last instance is due to nervous action, and not to any regurgita- tion of the intestinal contents, is shewn by the fact that it will take place when the intestine is perfectly empty and may be pre- vented by section of the mesenteric nerves. The vomiting attend- ing renal and biliary calculi is apparently also reflex in origin. Vomiting in fact as a rule is a reflex action, the afferent impulses passing along one or other nerves, but most frequently along those connected with the alimentary canal, that is along afferent fibres running in the vagus or in the splanchnic nerves. The centre however may be affected directly, as probably in the cases of some poisons, and in some instances of vomiting from disease of the medulla oblongata. Lastly, it may be thrown into action by im- pulses reaching it from parts of the brain 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. Many emetics, such as tartar emetic, appear to act directly on the centre, since, introduced into the blood, they will produce vom- iting after a bladder has been substituted for the whole stomach. Others again, such as mustard and water, act in a reflex manner by irritation of the gastric mucous membrane. With others, again, which cause vomiting by developing a nauseous taste, the action involves parts of the brain higher than the centre itself. § 223. Movements of the Small Intestine. 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 fibres. 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 CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 381 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 up- wards ; 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 movements also varies very considerably. § 224. 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 the move- ment may perhaps be described as almost intermittent from sacculus to sacculus, the contents of one sacculus being driven 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-caecal valve are placed transversely across the caecum, not only does distention 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 faeces, are supported by the bladder and the sacrum, so that they do not press on the sphincter ani. § 225. Defoecation. 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 shel- tered 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 382 DEFECATION. [BOOK n. 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 defecation 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 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 defsecation 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 aftbrds a more or less fixed support pull the rectum and its contents down ; the latter, by means of contractions travelling from above downwards but taking place somewhat later, narrow the rectum and so squeeze the contents onwards and outwards. Defsecation then appears to take place in the following man- ner. 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 fseces 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 con- traction 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. CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 383 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 defaecation, 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 thoracic cord. In such cases the whole act must be purely reflex, excited by the presence of fasces in the rectum. § 226. The 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 plain muscular fibres. The alimentary canal therefore, like the heart, though to a less degree, possesses within itself such mechan- isms 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 oesoph- agus 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 pro- duces 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 simi- lar to that already described in reference to the oasophagus. 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. 84, R. V. L. V., and reach the intestines by the portion of the right or posterior vagus, Fig, 84, R'. V ., which passes into the solar plexus and thence by the mesenteric nerves. The afferent impulses 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 somewhat 384 NERVES OF AILMENTARY CANAL. [BOOK n. as follows. The alimentary canal possesses a power of spontane- ous 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 RY Ret. FIG. 84. 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 the anatomical relations. Oe to Ret. — The alimentary canal, ossophagus, stomach, small intestine, large intes- tine, rectum. LV. Left vagus nerve, ending on front of stomach, r.l. recurrent laryngeal nerve supplying upper part of oesophagus. R. 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 mesenteric ganglion (or plexus) m.gl. — a. branches from the solar plexus to stomach and small intestine, and from the meseuteric ganglion to the large intestine. Spl. maj. Large splanchnic nerve arising from the thoracic ganglia and rami com- municantes r.c. belonging to dorsal nerves from the 6th to the 9th (or 10th). Spl. 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), proceeding by the hypogastric plexus to the longitudinal muscles of the rectum. €HAP. i.] TISSUES AND MECHANISMS OF DIGESTION. 385 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 bentral 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 movements of a piece of intes- tine isolated from the rest of the alimentary canal but retaining its connections with the central nervous system. Under this view the peristaltic movements produced by centrifugal stimu- lation of the vagus in the neck are comparable not so much with the contraction of a skeletal muscle when its motor nerve is stimu- lated as with the beats which may be called forth in an inhib- ited or otherwise quiescent heart by stimulation of the cardiac augmentor fibres. Indeed we may perhaps call the vagus fibres which pass to the stomach and intestines augmentor 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 stimu- lated the bowels are brought to rest, often in a very abrupt and marked manner. Inhibitory fibres therefore run in the splanch- nic nerves, Fig. 84, Spl. mag. and min., passing along them from the spinal cord to the abdominal plexuses, and thence to the alimentary canal. This view however that the movements of the alimentary canal are of a spontaneous nature, simply augmented on the one hand and inhibited on the other by tne central nervous sys- tem, can only be applied to the middle regions, to the stomach -and intestines in which peristaltic action is seen in its simple form. At the beginning of the alimentary canal, at the mouth and phar- ynx and also at the oesophagus, the central nervous system inter- venes in a decided manner : the movements of these parts, as we have seen, are carried out directly by the central nervous sys- tem. Something similar is also seen at the end of the canal, at the rectum and sigmoid flexure. These parts are governed on the one hand by fibres reaching them from the lower regions of the cord by the sympathetic system, by the hypogastric nerves and hypogastric plexus, and on the other hand \>y fibres reaching them along certain cerebro-spinal, namely sacral, nerves (in the dog the second and third sacral nerves) by the branches of these nerves, called nervi erigentes (Fig. 84). And the government by these nerves is one in which the movements are directly carried out by means of the central nervous system. Hence this is the part of intestinal movement which fails in diseases of the central nervous system ; the failure leading to 25 386 MOVEMENTS OF ALIMENTARY CANAL. [BOOK ir, obstinate constipation if not to actual difficulty of defaecation. The presence of faeces in the sigmoid flexure no longer stirs up the reflex mechanism for their discharge ; meanwhile the more independent movements of the higher parts of the canal con- tinue to drive the contents onward ; and hence the faeces accu- mulate 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 obstruc- tion is frequently thrown into violent peristaltic movements. § 227. 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 respiration is seriously interfered with, peristaltic movements become very pronounced. Thus, in death by asphyxia or suf- focation, an involuntary discharge of faeces, which is in part at least the result of increased peristaltic action, is not an unfre- quent 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 sug- gested, 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 oxy- gen ; 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, provoke 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 in- creased by the too venous blood stimulating the central nervous system and thus sending augment or 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 nicotine 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. 6. THE CHANGES WHICH THE FOOD UNDER- GOES IN THE ALIMENTARY CANAL. § 228. Having studied the properties of the digestive juices as exhibited outside the body, and the various 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 fseces. The events which lead to this conversion are two- fold. On the one hand the digestive juices do bring about, inside the alimentary 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 company with water, is going on along the whole length of the canal, and especially in the small and large intestines. It will be convenient 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 conve- nient 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 387 388 CHANGES IN THE STOMACH. [BOOK 11. mouth of the horse is insufficient to produce any marked con- version of the starch it may contain. During the rapid transit through the oesophagus no appreciable change takes place. The amount of absorption of digested material, or even of simple water from the mouth or ossophagus, must always be insignificant. The Changes in the Stomach. § 229. 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 prob- ably 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 mat- ters, 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 containing 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 CHAP, i.] TISSUES AND MECHANISMS OF DIGESTION. 389 is dissolved in the stomach, 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 microscope 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 filtration the clear filtrate contains besides salts, pepsin and free hydrochloric acid (the constituents of the gastric juice), a small amount of sugar, of some of the bye products of proteid digestion, and of albumose and peptone. The sugar is often absent, 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-digested 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, becom- ing 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. Water taken by itself appears to be passed on at once into the small intestine. 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 filled 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 pep- tone 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 so soon as it is formed. There is also evidence that fat may to a certain extent undergo in the stom- 390 CHANGES IN THE SMALL INTESTINE. [BOOK n. ach 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 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 duo- denal 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 dif- ferent 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 con- verted 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 eruc- tation 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 sim- ilarly 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 pos- sible 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. § 230. The semi-digested acid food, or chyme, as it passes over the biliary orifice, causes as we have seen (§ 215) gushes of bile, and at the same time the pancreatic juice flows into the