-', #<?!, 
 
 CORNELL UNIVERSITY. 
 
 THE 
 THE GIFT OF 
 
 ROSWELL P. FLOWER 
 
 FOR THE USE OF 
 
 THE N. Y. STATE VETERINARY COLLBQE. 
 
 1897 
 
PI Cornell University 
 f) Library 
 
 The original of tliis book is in 
 tine Cornell University Library. 
 
 There are no known copyright restrictions in 
 the United States on the use of the text. 
 
 http://www.archive.org/details/cu31924104225291 
 

 AN INVESTIGATIO]^ ^ T ^/ 
 
 MICROSCOPIC ANATOMY '^•'J^ 
 
 INTERSTITIAL NEPHRITIS; 
 
 a 0olli IKclral 3i:i)ests 
 
 FOR THE DEGREE OP M.D. IN THE UNIVERSITY 
 OF EDINBURGH, 
 
 BEYAN CHAELES WALLEE, M.D, F.E.C.S. (Ed.) 
 
 LECTURER ON PATHOLOGY IN THE SCHOOL OF MEDICINE, EDINBURGH, 
 
 AiXlvov aiXivov eliri to S' ev viKarOi. 
 
 jEsch.: Agam., 121, 159. 
 
 EDINBUEGH : E. & S. LIVINGSTONE 
 57 SOUTH BEIDGE and 15 TEVIOT PLACE 
 

 I I Printed by Porteous and Denholm, 
 
 s4d jea<M!!^ ^" ^^ ^' LIVINGSTONE, EDINBURGH 
 
 T,,xTT>nxT S SIMPKIN, MAKSHAWj, AND CO., BAILLIEBE, 
 
 LONDON t , , , \ ■ 
 
 ( TINDALL, AND COX, AND DAVID BOGUE 
 
 DUBLIN .... FANNIN AND CO. 
 
PEEFACE. 
 
 The following monograph comprises the suhstance of a Thesis 
 presented to the Medical Faculty of the University of Edin- 
 burgh for the degree of M.D., which was fortunate enough 
 to he deemed worthy of the award of a Gold Medal. It is 
 therefore with the greater confidence that the Author now 
 suhmits it to a more extended audience of his professional 
 brethren. 
 
 The original Thesis was illustrated hy a large number of 
 water-colour drawings, and by more than two hundred and 
 fifty microscopical preparations, derived from twenty-five 
 distinct cases of interstitial nephritis. The Author has 
 since examined specimens from fifteen additional cases, which 
 have further served to confirm the results he had previously 
 arrived at. It wiU thus be seen that the views now advocated 
 are based on the evidence aflbrded by about forty specimens 
 of interstitial nephritis, comprising every stage of the lesion, 
 from the most incipient to the most advanced. Specimens 
 from three cases of glomerulo-nephritis were submitted with 
 the Thesis, and two more have been examined subsequently ; 
 these cases being found not only interesting in themselves, 
 but valuable also from the important side-light which they 
 cast on the histogeny of the ordinary varieties of interstitial 
 nephritis. 
 
 The Author's thanks are due to his friend Mr James 
 Eodger, M.B., Pathologist to the Aberdeen Infirmary, for 
 
VI PREFACE 
 
 many fine specimens, and much welcome courtesy ; to Mr A. 
 B. Stirling, Sub-Curator of the Anatomical Museum of 
 the University of EcUnhurgh, for one or two valuable hints 
 on histological technique, and for a reference on the subject of 
 the anatomical structure of the glomeruli; to Mr D. J. 
 Hamilton, for several good specimens of granulation tissue, 
 and for a receipt for logwood staining fluid ; to Mr Charles 
 A. Doyle for the transference of two drawings to the wood ; 
 to his late class assistant, Mr James Eyan, for two drawings ; 
 and to Miss E. P. Burton of Morton House, for care and 
 pains in the faithful execution of the engravings. 
 
 In concluding his Preface, the Author would venture to 
 recall to the minds of friendly critics a certain saying of old 
 Dan Chaucer's, applicable alike to the works of the disciples 
 of the Apollo latros, as to those of the votaries of his more 
 brilliant alter ego, the Musagetes : — 
 
 " For every word men may not chide or pleine, 
 For in this world certain ne wight there is 
 That he ne doth or sayth sometime amis." 
 
TO THE MEMOEY 
 
 OP 
 
 THOMAS LOVELL BEDDOES, M.D. 
 
 POET AND PHYSIOLOGIST, 
 
 PROFESSOE-ELECT OF THE UNIVBESITY OF ZURICH 
 
 AND 
 
 ATJTHOE, OF "THE BEIDE's TEAGEDY," 
 
 THIS WOEK 
 
 IS AFFECTIONATELY AND REGRETFULLY DEDICATED 
 
 BY 
 
 HIS YOUNGER BEOTHER IN MEDICINE AND SONG 
 
 THE AUTHOE. 
 
 "Apx^Te SiKeXiKoi tu irivdeos, iipx^Te Moiirai. 
 dS. at Tol fmXdxai liiv iirlai Kark Kawov SKai/Tai, 
 ij Toi x^'^P^ aiXiva, t6 t' eidaXh oS\ov Hvijdoi' 
 vffTepov ad i^djovTi, Kal els ^os &\\o 0i5oj'Ti' 
 &IJ,ftes S'oi /icydXoi Kal Kaprepol i) <ro(pol avSpes, 
 oiriroTe Trpwra fldcw/tcs, dvdKoot V x^o"^ Koi\(/. 
 efiSoyUes eO pAXa pjaKpiv drippxiva viiypeTov iimov, 
 
 MoscHUS : Elegy ore Bion. 
 
INTERSTITIAL NEPHRITIS 
 
 .CHAPTEE I. 
 
 INTRODUCTORY. 
 
 Many and various have been tte views which, from the 
 days of Dr Bright down to our own time, have been broached 
 respecting the morbid anatomy of the small red granular, or 
 contracted kidney. Theories "near the mark, or farther 
 from the mark, or even altogether far away from any mark," 
 of these, as Carlyle says, "there have been enough." The 
 literature of the subject is extensive, and includes papers of 
 aU degrees of merit, some of them chiefly noticeable on 
 account of the daring and poetic imagination evinced by their 
 authors, who with the eye of faith behold appearances other- 
 wise invisible to mortal ken ; some, on the other hand, rich 
 in observation and research, and bearing that unmistakeable 
 - imprint which long and careful study never faUs to bestow. 
 Other writers, again, probably with a view to the conserva- 
 tion of energy, have adopted at second hand one or another 
 of the plentiful stock of ready-made theories, dressing and 
 bedizening the changeHng in accordance with their several 
 tastes, without troubling themselves in the least with super- 
 fluous inquiries into the legitimacy of its parentage. These, 
 in too many cases, are blind men led by the blind ; and it 
 is to be feared that the ditch is but too often their ultimate, 
 and perhaps not uncongenial, resting-place. Thus it is not to 
 be wondered at, if a large percentage of the dissertations on 
 the nature of the contracted kidney are worth precisely the 
 paper they are printed on, and are valuable chiefly to the 
 butterman as envelopes for his unctuous wares. Well would 
 it be, if being worthless, they were also harmless ; but such is 
 not the case, for the bewildered learner or busy practitioner 
 
2 INTERSTITIAL NEPHRITIS. 
 
 with no opportunities for actual observation, is swept away 
 by contending currents of opinion into a whirlpool of con- 
 flicting authorities, and there abandoned, like a ship without 
 a rudder, tossed about by every wind of doctrine. For the 
 student, too, there is yet another danger — there are the 
 sunken rocks of examinations; and as examiners are but 
 men, and for the most part each one strives, pUot-Uke, to steer 
 the medical aspirant into their own pet harbour of theory, 
 'tis oftentimes more by good luck than good guidance if the 
 victim's ribs and keel are not grazed in the process by some 
 theoretical reef, capable of working very practical damage. 
 Fully aware, therefore, of the harm done to the cause of 
 science by those who add to its literature without just cause, 
 due thought, and assiduous labour; who build upon its 
 foundations a superstructure of wood, hay, and stubble, when 
 gold, silver, and precious stones lie ready to their hands, it 
 has been the author's earnest endeavour, throughout the pre- 
 sent investigation, to form no crude opinions, to promulgate 
 no groundless theories, and to rush into no hasty and ill- 
 digested, generalisations. How fat he has succeeded must 
 now be determined by the arbitrament of others, to whose 
 judgment the author, hopefully, yet somewhat diifidently, com- 
 mits the results of the constant labour of about two years. 
 One thing, however, he can confidently aver — that, whatever 
 be the value of his conclusions, they have, at least, been 
 arrived at independently; for, though not overweerdngly 
 confident in the light of his own lantern, he has, at any rate, 
 the satisfaction of knowing, that in following its guidance, 
 he has been pursuing no will-o'-the-wisp. Throughout the 
 whole research he has striven to think for himself, and to 
 divest his mind of any previously acquired predilections in 
 favour of one theory or another; and though necessarily 
 obliged to cultivate an acquaintance with the works of others, 
 he has never, consciously, adopted their views, save when 
 in accordance with the testimony of his own experience and 
 the evidence of his own eyesight. It has been his object to 
 take nothing upon trust, and to adopt as his own the motto 
 of erudite and cultivated Horace, who preferred to manufac- 
 ture his ideas at home, and to be " NuUius addictus jurare 
 ad verba magistri," rather than save himself the trouble of 
 independent reflection, by accepting those so assiduously, yet 
 so fruitlessly, instilled into him by the worthy "plagosus 
 Orbilius." 
 
INTEODUCTOKY. 3 
 
 The chief microspopical powers employed in the course of 
 this investigation have heen Hartnack's objectives, 3 and 
 7, and his oculars, 3 and i; Eaker's 1-inch, §-inch, and 
 •^inch objectives, with oculars A and B; and for very 
 high magnifying powers, Hartnack's objectives 8 and 9, and 
 Eoss's ^inch. Two stands have been used — a fuU-sized one 
 of Eoss's pattern, and a small and extremely convenient one 
 by Bryson of Edinburgh, after a design by Swift. A word 
 or two seems advisable on the subject of the accompanying 
 drawings., Accuracy rather than artistic merit has been the 
 author's aim, and this, he believes, he has attained. Great 
 pains have been taken to ensure their being as nearly as 
 possible facsimiles of the objects as seen through the micro- 
 scope.* Most of the microscopic sections which furnished the ' 
 materials for this Thesis were cut with the freezing microtome, 
 and are, in some instances, of a size which may weU be termed 
 enormous, often including the whole of the kidney substance, 
 from capsule to papUla. The continuity thus obtainable 
 wUl be easUy seen to be of immense advantage to the histo- 
 logist, in that it enables him to direct his attention to a large 
 connected area, and thus more accurately to appreciate the 
 distribution of the pathological changes over different por- 
 tions of the organ under examination. In addition to this, 
 sections so cut, though of such a size as to look like tracts of 
 country under a high power, are surprisingly uniform in 
 thickness, thus affording a flat field instead of one fuU of hUls 
 and hoUows, as is the case with even the best sections cut by 
 other means. The introduction of the freezing microtome has 
 created a revolution in histology ; and the present author is 
 more fortunate than many of his predecessors in having been 
 able to avail himself of its aid. How in any other way could 
 sections be cut measuring an inch and a-half across, and of 
 mathematically regulated thickness — sections, in fact, abso- 
 lutely perfect for the purposes for which they are designed ? 
 And yet the author has quite recently seen a book or paper — 
 he forgets which-^in which the freezer was condemned as 
 iiseless ! May one be pardoned the thought, that the fault 
 
 * This Thesis was originally illustrated by about sixty coloured 
 drawings; but owing to the great expense of engraving, the Author 
 has only been able to reproduce a small selection from them. It is 
 hoped however, that enough are included to render the text of the 
 Thesis' intelligible. The whole of the original drawings have been 
 deposited in the Library of the University of Edinburgh. 
 
4 INTERSTITIAL NEPHKITIS. 
 
 lay, perhaps, not so much with the tool as with the workman 1 
 Like most other things worth doing, section-cutting cannot 
 he learned by the light of nature; hut a little practice will 
 soon render any one not intolerably clumsy an adept iu 
 the art. 
 
 CHAPTEE II. 
 
 ON THE METHODS OF PRESERVATION, PREPARATION, STAINING, 
 AND MOUNTING OF SPECIMENS. ^ 
 
 As certain methods of preparation, and the use of various 
 reagents have been sometimes not unreasonably credited with 
 the production of pseudo-pathological appearances, the author 
 proposes in the present chapter to give a short account of the 
 different processes to which his preparations were subjected, 
 in order to eliminate as far as possible aU chance of error in 
 this direction. 
 
 In most cases the fresh specimen was cut into pieces, 
 and hardened, first for a fortnight or so in MiOler's fluid, 
 and next transferred to a :| per cent, solution of chromic acid, 
 where it has been suffered to remain until properly hardened. 
 Better results are thus obtained than by placing the specimen 
 directly in chromic acid, which does not penetrate so well as 
 the bichromate, and is apt, especially if the pieces are large, 
 to cause hardening at the circumference, while the centre 
 remains nearly unaffected. This untoward result is obviated 
 by the previous use of MuUer's fluid, which saturates the 
 tissues completely, and acts as a pioneer for the chromic acid. 
 On the other hand, it is not advisable to trust to MtiUer's 
 fluid alone, as kidney so prepared is scarcely ever sufficiently 
 hardened, and almost always cuts badly, the epithelium being 
 disturbed in the tubules, and the microscopic appearances 
 thus rendered untrustworthy. 
 
 Chromic acid specimens often evince a great tendency to 
 resist the effects of carmine staining. Though left for an 
 hour or upwards in strong carmine solution, it will generally 
 be found that almost all the dye comes off on washing. This, 
 were there no means of obviating it, would be of itself an 
 
ON THE PKESERYATION, ETC., OF SPECIMENS. 5 
 
 almost fatal objection to the employment of chromic acid as 
 a hardening agent ; for experience has convinced the author 
 that preparations containing carmine are the most suitahle 
 pigments for staiaing kidney substance. Tortunately, the 
 remedy is easy and effectual. The water in which the 
 sections are washed after staining, should be slightly 
 acidulated with a few drops of 1 to 8 solution of acetic 
 acid. This admixture prevents the washing off of too much 
 carmine, and at the same time brightens the colour, and 
 renders it more agreeable to the eye. But whUe avoiding the 
 Scylla of washing off too much of the dye, we must be careful 
 not to fall into the Charybdis of acidulating the water too 
 strongly, as ia that case the sections wiU be far too deeply 
 and coarsely coloured to admit of examination under high 
 powers. Diffuse colouring is to be avoided : the carmine 
 should stain only the nuclear tissues (protoplasts), leaving the 
 general stroma comparatively untinged. Under low powers 
 delicately stained sections do not look, perhaps, so distinctive as 
 those which have retained more of the colouring matter ; but 
 with a power of 300 diameters or upwards (such as Hart. oc. 3, 
 obj. 7), these specimens come out beautifully, whereas the 
 heavily coloured ones are weU-nigh entirely useless. 
 
 The principal staiuiug reagents employed during this re- 
 search were carmine, picro-carmine, logwood solution, and 
 one-haK per cent, osmic acid solution. We shall say a word 
 or two on each of these. 
 
 Osmic acid, besides blackening fat, is also a general 
 staining reagent of great delicacy. It tinges the outlines of 
 cells, and defines the boundaries between different structures. 
 When he first began to work on the kidney, the author was 
 accustomed to use it alone ; but afterwards, seeing how admir- 
 ably sections thus stained bore further colouring with 
 carmine, he has latterly had recourse largely to this method 
 of double staining. The sections are left for an hour in one- 
 half per cent osmic acid solution, then taken out and washed, 
 floated upon a slide, and . covered with strong carmine 
 solution, in which they are likewise allowed to remain an 
 hour. They are then washed in acidulated water, again 
 placed on a sMe, and mounted. If more acid is mixed with 
 the water, they will stain sufficiently with carmine in from 
 fifteen to twenty minutes. 
 
 It has been said that osmic acid will only stain fresh 
 specimens ; but this is a mistake, for it acts with great beauty 
 
INTERSTITIAL NEPHRITIS. 
 
 and certainty even on specimens hardened in cliroinic acid. 
 The staining, slight at first, deepens and improves on mount- 
 ing and exposure to light. 
 
 Strong carmine and logwood solutions have been used 
 
 throughout this investigation. The author has had some 
 
 experience of weaker fluids, hut has not been compensated 
 
 by any appreciably more satisfactory results for the extra 
 
 expenditure of time and labour entailed by their employment. 
 
 The following is the formula of the carmine solution : — 
 
 Carmine, purest . . . , 5i. 
 
 Strong ammonia . . . . 3i. 
 
 Water ...... 5iv. 
 
 Make the ammonia and the carmine into a paste in a mortar, 
 and then add the water. 
 
 This fluid stains most tissues in from five to twenty 
 minutes, but chromic acid preparations often require longer. 
 If the pigment tends to precipitate, the fluid should be 
 filtered. 
 
 Logwood staining is especially useful for low powers, but 
 is usually inferior in delicacy to carmine ; though sometimes 
 from some unknown cause, the colouring is very delicate 
 and beautiful, and shows well under a power of 300 diameters 
 or upwards. 
 
 The chief difficulty with logwood is to procure a good 
 solution. Martindale of London manufactures a satisfactory 
 one; but the following receipt, for which the author is 
 indebted to Mr D. J. Hamilton, Pathologist to the Eoyal 
 Infirmary, Edinburgh, is perhaps the best he has ever 
 worked with. Much, ' however, depends on the quality of 
 the extract used in its preparation : — 
 
 Formula. — ^Finest Extr. Hcematox. (in cake) 3ii. 
 
 Alum Sulphate . . . grs. xx. 
 
 Dissolve in 20 oz. of water, letting the mixture stand 
 
 for a week, and shaking every day. Then filter, 
 
 add 10 oz, of glycerine, and evaporate away one 
 
 fourth of the liquid : if the colour precipitates, 
 
 add a few grains more alum. WhUe hot, add 5i. 
 
 of pure refined carbolic acid. 
 
 This solution stains in from three to seven minutes ; but 
 
 a better result is obtained by allowing the tissue to remain in 
 
 the fluid for fifteen minutes or so, and then removing the 
 
 excess of colouring matter with glacial acetic acid, which 
 
 washes out diffuse staining, leaving only protoplasts affected 
 
ON THE PRESERVATION", ETC., OF SPECIMENS. ■ 7 ' 
 
 hj the colouring matter. After being dyed, the section 
 should be washed in water, floated out quite flat on a slide, 
 and covered with glacial acetic acid by means of a glass rod. 
 When its deep purple colour changes to a sort of dirty 
 brown, it should again be thoroughly washed, and then 
 mounted. If the logwood fluid be weak, or of inferior 
 quality, dilute acetic acid (1 to 8) should be used instead 
 of glacial, as the strong acid may in that case remove the 
 colour entirely. 
 
 Picro-carmine, when well prepared, after Eanvier's receipt, 
 is a very valuable reagent. It may be used either alone or 
 with osmic acid. Picro-carmine is especially useful in deter- 
 mining the qusestio vexata as to' which coat ^f the renal 
 arteries is hypertrophied in interstitial nephritis. 
 
 Most of the preparations were mounted in thick Farrant's 
 solution, though Eimmington's glycerine jeUy was used in a 
 few instances. Dammar was sometimes employed for mount- 
 ing injected preparations ; but it is not suitable for the general 
 demonstration of kidney, as it renders the tubules too trans- 
 parent. But one section was mounted in pure glycerine, and 
 this only with a view of showing how misleading are the 
 effects produced by this preservative. Indeed, the author 
 believes, as will be stated in an ensuing chapter, that had Sir 
 "William Gull and Dr Sutton used Parrant's solution instead 
 of glycerine and camphor water in the mounting of those 
 preparations which gave rise to the formation of their well- 
 known " Arterio-CapUlary Pibrotic " theory, a serious modi- 
 fication, not to say radical change, might have been effected 
 in their views. 
 
 Every specimen was stained and mounted with the 
 author's own hands,* the utmost care being taken not to tear 
 or otherwise alter the appearance of the section by rough 
 and careless usage. 
 
 A few sections of injected cat's kidney, illustrative of 
 certain points in the normal anatomy, were made by hand 
 with a long sharp thin-bladed knife. The kidney from 
 which they were cut had been kept for a long time in spirit, 
 and was so brittle as to cut badly in the freezer, though the 
 author has since been able to freeze and cut kidneys so over- 
 
 * Some few of the preparations were hardened when they came into 
 the Author's possession, and several were actually ready cut ; but the 
 Author is able to state that the method of hardening was in every case 
 identical with that detailed above. 
 
8 INTEESTITIAL NEPHEITIS. 
 
 hardened, with extreme ease, hy soaking them for several days 
 in strong gum water. The best pattern of hand section knife 
 much resemhles the so-called " Brain Knife " iu an ordinary 
 post-mortem case. Such an instrument is far preferable to 
 the clumsy razor still in general use, the blade of which is 
 too short and unwieldy for such delicate work. The blade of 
 the section knife should be weU wetted with alcohol, and the 
 tissues to be cut embedded in some suitable substance, such 
 as waxy liver. If, however, this not omnipresent substance 
 is not forthcoming, a mixture of paraffin and oil of cloves, or, 
 in default, a piece of common carrot, will yield an available 
 substitute. The carrot should not be stringy, or the knife 
 will suffer. Hand section knives should be made of special 
 temper, very thin in the edge, and flat on both sides of the 
 blade, which should be of sufficient length, perfectly straight, 
 and rather more than haK-an-inch broad. Special care 
 should be bestowed on their setting, as, if blunt, they not 
 only waste the tissue to be cut, but seriously damage the 
 good temper of the operator. They are favourites with 
 surgical instrument makers, for they cost a smaU fortune to 
 keep in order. What is sharpness in any other knife, is 
 bluntness in them ; they are necessary evils, as the Dean of 
 St Patrick's said of servants. But necessary they are, and 
 wiU be, for aU the more delicate and friable tissues, until 
 Time, Chance, or Ingenuity, discover some new and improved 
 method of hardening. 
 
 CHAPTEE III. 
 
 ON CERTAIN POINTS BBLATING TO THE HISTOLOGY OP THE NOEMAL 
 KIDNEY. 
 
 It would serve no nseful purpose to devote much space in 
 the present dissertation to the consideration of the histology 
 of the normal kidney, as the subject has been already amply 
 and ably treated by many competent authorities, whose 
 writings are easily acessible. Among these the author may 
 mention the following works, which he has himself had occa- 
 sion to consult : — 
 
ON THE HISTOLOGY OF THE NORMAL KIDNEY. 9 
 
 1. " Quain's Anatomy," 8th edit. 
 
 2. Bowman, PMl. Trans., 1842. 
 
 3. Beer, Die Bindesubstanz der menschliclien Mere. 
 
 4. Eindfleisch, Path. Hist., Syd. Soc's. Trans., Tol. ii. 
 
 5. Strieker's Histology, Syd. Soc's. Trans., Art, Kidney. 
 
 6. Klehs, Handbuch der Path. Anat., Lief. iii. 
 
 7. Chrzonszczewsky, Virch. Archiv., 1864. 
 
 8. Southey, Barth. Hosp. Eeports, 1865. 
 
 9. Henle, Zur Anat. der Meren, Gott., 1862. 
 
 10. Henle, Handbuch , 
 
 11. Heidenhain, Arch, fur Mikrosk, Anat., 1874. 
 
 12. Ludwig and Zawarykin, Weiner Acad. Sitzungs- 
 
 bericht, vol. 48. 
 
 13. Schweigger-Seidel, Die Meren desMenschen und der 
 
 , Saugethiere. 
 
 There are, however, one or two points of special interest 
 to the morbid anatomist which seem to demand some little 
 notice at this' stage of our inquiry, as ignorance or disregard of 
 them has proved a fruitful source of all kinds of errors in the 
 study of pathological conditions, in that some writers have 
 been thereby betrayed into the mistake of attributing strictly 
 normal appearances to the results of disease. And here it 
 may not be thought out of place to bestow a word of condem- 
 nation on the practice which is, we fear, but too prevalent, of 
 attempting to study the pathology of an organ without any 
 precise acquaintance with its healthy structure. A prac- 
 titioner who is the fortunate owner of a large and expensive 
 microscope, fitted up with costly lenses, and apparatus pro- 
 cured regardless of expense, is but too apt to think that the 
 mere possession of such an instrument is of itself sufficient to, 
 render him an accomplished histologist. One might as well 
 suppose that the difiference between an artist and a dauber 
 lay in the completeness and excellence of their respective 
 pictorial armamentaria. A long apprenticeship of careful 
 observation is imperatively required of the histologist who 
 would do work worth the performance. With heart and mind, 
 with strength and purpose, he must address himself to his 
 task; the normal anatomy of an organ must be mastered 
 before proceeding to the pathological; — the eye as well as 
 the miad must be trained to observe and discriminate. No 
 amount of simple reading and listening to lectures will make 
 a pathologist who, when made, will repay the cost of manu- 
 
10 INTERSTITIAL NEPHRITIS. 
 
 f acture. Actual contact with facts is the one and only means 
 of appreciating their significance. For well says the trite 
 old adage : — 
 
 " Segnins irritant animos demissa per aures 
 Quam quse sunt oculis sutjecta fidelihus." 
 There is no royal road to histological proficiency ] we must 
 he normal anatomists first, and pathological anatomists after- 
 wards ; the scientific fledgeling cannot, chicken-lilce, run almost 
 ere his heak has chipped the shell ; he must crawl first, and 
 crawl very slowly sometimes. Nov does it at all foUow that 
 because a man is an excellent physician, he is also a compe- 
 tent pathologist. He may. be so, and indeed ought to be so ; 
 but proficiency in the one branch cannot be taken as evidence 
 of corresponding attainments in the other. But to resume. 
 "We shall glance very briefly at a few facts connected 
 with— (1.) The Eenal Tubules ; (2.) The Eenal Connective 
 Tissue ; (3.) The Renal Vessels. 
 
 1. The Tubules. 
 
 In almost every drawing the author has seen, the calibre 
 of the tubules, especially the convoluted ones, has been 
 represented as far too wide. Normally, it is but narrow, and 
 is often apparent only as a kind of three-cornered star on the 
 end of a seemingly solid cylinder. (See Turner's Anatomy, 
 engraving, page 789.) By far the greater portion of the 
 interior of the tubules is , occupied by epithelium ; and if 
 their lumen appears wide, it is owing to the partial falling 
 out of the epithelium during the preparation of the section. 
 Almost any good preparation of normal kidney will serve to 
 deinonstrate this fact ; and it is indeed generally admitted, 
 but almost as generally, we fear, ignored. Some little time 
 ago this narrowness of the calibre of the uriniferous tubes 
 formed the topic of a conversation between the author and a 
 clever pathologist who cultivates a somewhat rude and dog- 
 matic style of assertion. " Pooh," said this gentleman, " it's 
 a well-known fact." " True," replied the author, " but why 
 then is it not a well-remembered fact i" If we consider for 
 a moment the issues which depend upon it, we shall not be 
 disposed to underrate its importance. It vitally affects Dr 
 Johnson's theory, which we shall frequently have occasion to 
 aUude to in the ensuing pages, and it has continually led to 
 mistaken ideas as to the Blocking up of healthy tubules. We 
 
ON THE HISTOLOGY OF THE NOKMAL KIDNEY. 11 
 
 would also call attention to another normal appearance of no 
 less moment, namely, the natural granularity of healthy renal 
 epithelium. 
 
 2. The Ebnal Connective Tissue. 
 
 The existence of connective tissue in the kidney, which 
 was first described by Bowman and Goodsir, has been denied 
 by some writers, but is now universally recognised by all the 
 best authorities. (See Beer, Eindfleisch, Klebs, and Art. 
 Kidney in Strieker's Histology.) The renal connective 
 tissue is distributed along with the vessels in the same 
 manner as in the Uver. It contains cell-elements, fibres, and, 
 according to Ludwig, lacunar spaces in connection with the 
 lymphatic system. Eindowski also mentions lymphatics 
 with complete endothelial walls (Centralblatt 69, sec. 145). 
 Delicate connective tissue processes pass inwards from the 
 capsule into the substance of the cortex, which become much 
 enlarged on the supervention of interstitial changes. Connec- 
 tive tissue is likewise present in the glomerulus, binding together 
 the capillary loops, as first noticed by Axel Key. In proof 
 of the existence of this connective tissue, may be cited the 
 fact mentioned, the author believes, by Hyrtl, that the glome- 
 rulus, on being picked out from the surrounding tissues, does 
 not collapse, but retains its pristine form. Among the con- 
 nective tissue of the glomerulus are a number of rounded 
 cell-elements, situated between the vascular loops, which cel- 
 lular bodies become greatly increased in number in that post- 
 scarlatinal affection of the kidney to which Klebs has given 
 the name of Glomerulo-]S"ephritis. These bodies are not 
 merely cells from the epithelial covering of the glomerulus, but 
 true connective tissue corpuscles, as proved by the fact that 
 they are found lying, not only on the circumference of the 
 glomerulus, but also in its substance, between the individual 
 capillary loops. A demonstration of their anatomical site 
 can be obtained by placing an injected glomerulus on a slide 
 with a drop of water, and then squeezing it out by pressure 
 under a rather thick cover-glass. Logwood stains them a 
 deep violet. 
 
 3. The Eenal Vessels. 
 
 As before stated, the arteries of the kidney are accom- 
 panied by processes of connective tissue, distributed in a 
 
12 . INTEKSTITIAL NEPHRITIS. 
 
 manner similar to that observed in the liver. A kind of 
 spurious adventitia is thus formed, immediately external to the 
 adventitia proper, which is very thin. (See paper by Dr 
 Kingrose Atkins, Brit. Med. Jour., April 3, 1875.) On 
 picking out a normal renal arteriole from its surroundings, 
 this spurious adventitia adheres to it as a shreddy, ragged 
 investment. It is this spurious adventitia, and not, as 
 supposed by some, the real outer coat of the arteries, which is 
 primarily enlarged on the occurrence of interstitial changes. 
 This point will be fuUy dealt with hereafter, and need not 
 therefore be further discussed at this stage of our inquiry. 
 In the normal kidney, the glomerulus never entirely fills the 
 space inside Bowman's capsule. 
 
 Preparations of injected cat's kidney are useful, as afford- 
 ing a general idea of the normal structure of the renal 
 vessels, especially if mounted in dammar, which renders the 
 tubules transparent, and thus brings the injected vessels into 
 greater prominence. The author has made many attempts 
 to use the far more delicate silver injection, but never 
 hitherto with much success. Thinking the failure might be 
 due to the action of the urine salts, especially the chlorides, 
 upon the silver fluid, he, in several instances, carefully 
 washed out the vessels with distilled water, and with 
 distilled water acidulated with nitric acid, previously to the 
 introduction of the silver injection. This, however, did not 
 answer the desired purpose, and although he has not aban- 
 doned the idea, he has not, up to this time, been able to 
 accomplish it successfully. Perhaps this failure may have 
 been partly owing to the animals (chiefly cats) having been 
 killed before injecting the silver salt; for although the 
 injection was always performed with the utmost expedition, 
 and with every precaution, such as the immersion of the 
 body in warm water, there may have been time for the loss 
 of some of that textural vitality, in the absence of which 
 experience has shown that attempts at injection with silver 
 are invariably futile. Were he free to follow his own ideas, 
 the author would be inclined to try again on the living 
 animal; but considering the present state of the law in 
 this country, it is not likely that the opportunity will be 
 afforded him for some time to come. It is true that by 
 flight into Germany and France, distressed seekers after for- 
 bidden knowledge may find countenance and refuge at the 
 price of temporary expatriation; but, nnfortunatSy, now. 
 
HISTOEICAL E^SUM^, 13 
 
 as of old, it is equally true that, " Non cuivis homini con- 
 tingit adire CorintMuia." A little rest, a little slumber, a 
 little folding of the hands to sleep, this is the destiny to 
 which English Science is now consigned. So, to alter Long- 
 fellow's Hues, her votaries must learn to wait, since they are 
 not allowed to labour. Probably they may have ample leisure 
 to cultivate the virtue of patience. Charles Lamb has shown, in 
 his delightful Essay on Eoast Pig, how many hundreds of years 
 elapsed before the pig-taUed celestials became convinced that 
 a general domiciliary conflagration was not absolutely 
 essential to the proper culinary preparation of that savoury 
 animal, the form and fashion of whose caudal extremity they 
 have so industriously copied in their own persons since the 
 days of Confucius ; how much longer, then, will it take, 
 before the elimination of the perennial porcine and asinine 
 elements from our British Houses of Parliament is at last 
 successfully accomplished ? "We wiU. leave the reader to 
 muse on this distant contingency. 
 
 CHAPTEE IV, 
 
 HISTORICAL RisUM^. 
 
 The compilation of a complete bibliographical record of 
 aU the descriptions and theories, good, bad, and indifierent, 
 which, since the days of Bright, have been given to the 
 much-enduring medical world on the subject of Interstitial 
 iNephritis, would be a task alike beyond the range of the 
 author's reading, and the limits within which he would fain 
 confine the proportions of the present treatise. 
 
 It has, however, occurred to him that a short exposition 
 of the views of a few of the leading British and Continental 
 authorities might not only prove interesting from a historical 
 point of view, but instructive also, as evidencing the very 
 dififerent conclusions drawn by various observers from the 
 same facts. These theories are all, of course, more or less 
 coloured by the different pathological systems predominant 
 
14 INTERSTITIAL NEPHRITIS. 
 
 at tte time of their first promulgation; but many of the 
 older ideas have displayed a curious vitality, and, at the 
 present day, still continue to he firmly held, notwithstanding 
 the manifold changes which later discoveries have wrought 
 in the complexion of pathological science. The new light 
 thrown of late years upon the process of inflammation has, 
 however, induced many to adopt explanations of the morhid 
 appearances, very different from those which would have 
 been considered tenable before the researches of Virchow, 
 Lister, Cohnheim, Strieker, Eecklinghausen, Ludwig, EJ.ein, 
 and many other modern investigators. We shall omit all 
 mention of those authors who, without committing themselves 
 to any particular theory, confine themselves to a mere 
 enumeration of microscopical appearances, as the differences 
 between their several descriptions are so slight and unim- 
 portant, as not in any way to affect the question of the true 
 nature of the morbid process. For instance, some authorities 
 describe the colour as red, others as pale, whereas, in point of 
 fact, like the disputants who quarrelled over the colour of the 
 chameleon, both are right, and both wrong, the colour being 
 a matter simply dependent on the presence or absence of 
 mechanical hyperasmia. The essential pathological conditions 
 become visible only by the aid of the microscope, which alone 
 reveals those minute structural alterations of the kidney sub- 
 stance wherein they consist. Upon these alterations two 
 distinct interpretations have been put, and it is possible, 
 therefore, to make a primary sub-division of the theorists into 
 two classes — firstly, those who hold that the primary and 
 essential lesion has its seat inside the urinif erous tubules ; and 
 secondly, those who consider that the primary alterations are 
 to be referred rather to the interstitial tissues, all intra- 
 tubular changes being secondary to, and consequent on, 
 certain primary interstitial changes. Among those who hold 
 the former opinion, may be mentioned Johnson, Simon, 
 Freriohs, Niemeyer, Todd, and Lebert ; whilst of those who 
 advocate the latter, Eindfleisch, Beer, Klebs, Dickinson, 
 G-rainger Stewart, Green, and Jones and Sieveking (ia the 
 latest edition of their work, edited by Payne), are the most 
 conspicuous. 
 
 Besides these two very distinctly opposed schools, there 
 is another and smaller one, the members of which are dis- 
 posed to consider the diseased state as originating in the renal 
 vessels. Sir William Gull and Dr Sutton on the one hand. 
 
HISTOEICAL E^SUM^. 15 
 
 and MM. Cornil and Eanvier on the other, may, though 
 differing much among themselves, be grouped together under 
 this last head. 
 
 DR GEORGE JOHNSON S VIEWS. 
 
 De Johnson maintains that the primary changes, which 
 lead to the formation of the "smaU red granular kidney" 
 (which, by the way, is of tener pale than red, and in the early 
 stages is enlarged, instead of diminished in size), consist ia 
 destructive alterations of the epithelium of the uriniferous 
 tubules, due to the circulation in the blood of various morbid 
 products.' See Med. Chir. Trans., Vols. XXX., XXXIIL, 
 LVL; Trans. Path. Soc, 1877 : On Diseases of the Kidneys, 
 1852 ; Lectures on Bright's Disease, etc. 
 
 "We quote his own words as taken from the Pathological 
 Society's Trans., 1877, p. 390 : — "The primary and essential 
 structural change in the granular kidney consists in disinte- 
 gration and destruction of the glandular epithelium of the 
 convoluted tubes ; the products of this disintegrating process 
 appearing in the urine during Ufe in the form of granular 
 casts of the tubes, and the result is that when sections of the 
 kidney are examined microscopically, whUe some tubes 
 retain the normal lining of epithelium, others are filled and 
 rendered opaque by epithelium in various stages of disinte- 
 gration, and others are more or less completely denuded of 
 epithelium, a few granular particles only adhering to the inner 
 surface of the basement membrane. Then, as a result of this 
 destruction of their gland cells, many tubes are seen in 
 different stages of ateophy aiid contraction, and between 
 these contracting tubes are seen wide spaces, more or less 
 hyaline or fibrous, which are mainly occupied by the 
 atrophied remains of other wasted tubes and capillaries. In 
 some tubes the normal epithpHum is replaced by a lining of 
 delicate transparent rounded cells, each with a single nucleus ; 
 again, other tubes may be seen in various stages of dilatation 
 into cysts. This process of dilatation goes on until cysts more 
 or less numerous may be seen by the naked eye. The 
 explanation of this cyst formation is probably to be found in 
 the fact that some tubes continue to secrete an aqueous fluid, 
 while their lower portions are plugged by an epithelial debris, 
 and thus they become distended by their own secretion." 
 
16 INTERSTITIAL NEPHRITIS. 
 
 He further says that though there may be a little increase of 
 the fibrous stroma, he agrees with Drs Wilks and Moxon in 
 saying that it is "not much." This, though culled from one 
 of his latest utterances, is substantially the opinion first held 
 by Dr Johnson ia 1847, in a paper read before the Eoyal 
 Med. Chir. Society. On the same evening, his then colleague, 
 Mr Simon, read an independent paper on the same subject, 
 the result of his investigations leading him to adopt sub- 
 stantially the same opinions, though Mr Simon "believes 
 the transparent portions of the kidney to be microscopic 
 cysts," while Dr Johnson " interpreted them to be denuded 
 tubes, as they are now generally admitted to be." 
 
 As we propose presently to consider Dr Johnson's views 
 at more length, we shall pass them by for the present with- 
 out further comment. 
 
 VIEWS OF FREEICHS, NIEMETBR, ETC. 
 
 Frebichs (Die Brightsche Merenkrankheit, 1851) considers 
 the small red granular kidney to be merely the last stage of 
 parenchymatous nephritis, which, he says, passes through the 
 three stages of (1.) Hyperjemia and incipient exudation ; (2.) 
 Changes in the exudation; and (3.) Atrophy. Memeyer 
 (Text-Book of Practical Medicine, Humphreys and Hackley's 
 Trans.) agrees practically with Frerichs, though he allows 
 that there is a secondary or concomitant proliferation of the 
 interstitial tissue. He also mentions a primary interstitial 
 nephritis, leading to increase in the fibrous stroma, but this 
 he dismisses in few words as apparently of rare occurrence, 
 and comparatively unimportant. Lebert (Traits d'Anatomie 
 Pathologique, vol. ii, page 336), though a general follower of 
 Frerichs, seems to be in doubt whether the atrophied and 
 contracted kidney is not rather a separate form of Bright's 
 disease than a subsequent stage of the parenchymatous 
 variety. He says — " Nous avons surtout confirme les doc- 
 trines que professe Frerichs sur ce sujet." His description of 
 the atrophic form is as follows : — ' Dans la troisifeme forme 
 les canaux et les capsules s'affaisent, le tissu ceUulaire de 
 nouveHe formation autour des canaux se contracte et devient 
 cicatriciel, tout I'organe diminue notablement de volume et 
 de poids, la capsule est adherente, la surface est irregulifere, 
 lobul^e, creusde de siUons, les granulations sont nombreuses. 
 
HISTOEICAL EfiSUM^. ] 7 
 
 La consistance devient coiiace, la substance corticale est 
 surtout notablement rMuite de Tolume, les granulations 
 S6 montrent aussi dans les pyramides. . . . Les canaux 
 uriniferes renferment des Epitheliums granulo-graisseux, des 
 grumeaux de graisse, et des granules ; les cylindres sont 
 Egalement infiltr^s de graisse. Les contours des canaux sont 
 irr^guliers, plissEs, fibreux ; les capsules de malphigi sont 
 remplies de goutelettes de graisse ; beaucoup de capiUaires 
 dans les glom^rules ont disparu. La substance est pale, 
 an^mique ; on trouve quelquef ois beaucoup d'616ments fibro- 
 plastiques autour des capsules, meles de fibres, qui leur 
 donnent un aspect ooncentrique ; le tissu fibreux est parsemE 
 de goutelettes de graisse." Even in the second form, he 
 aUows some increase in the connective tissue stroma ; — 
 " Dans la seconde (forme) I'exsudation se trouve dans les 
 capsules, dans le parenchyme, dans les epitheliums, sous 
 forme de granules mSlEs de graisse. Une partie des matiferes 
 exsud^es s'organise en tissu cellulaire." See also Lebert's 
 Plates, 140, 141, and 142. 
 
 Todd (CHnieal Lectures on Diseases of the Urinary Organs, 
 1857) is more or less a disciple of Johnson, "though the evi- 
 dence of an inflammatory process having any share in the pro- 
 duction of this state of kidney," appears to him " to be very 
 xmsatisfactory." He considers that certain abnormal materials 
 contained in the blood are conveyed to the kidney for elimi- 
 nation, and that " in their passage through these glands, the 
 poisonous elements create a highly disturbed state of their 
 nutrition, a state possibly in some degree inflammatory, but 
 chiefly atrophic, the tendency of which is to cause the organs 
 to -waste and shiink." 
 
 VIEWS OF DICKINSON", EINDFLBISCH, KLBBS, ETC. 
 
 Dickinson (On Albuminuria, 2d edition) ; Bebe (Die 
 Bindesubstanz der menschlichen Mere) ; Eindpleisch (Path. 
 Histology, Syd. Soc. Trans.) ; Klebs (Handbuch der Patho- 
 logischen Anatomic, Dritte Lief.) ; Geeen (An Introduction 
 to Pathology and Morbid Anatomy) ; Jones and Sieveking 
 (Pathology, 2d edit., by Payne) ; and Aitken (Pract. Med., 
 vol. 2), though differing on some minor points, are aU at one 
 as to the essential nature of the morbid process, which they 
 refer to an Interstitial Nephritis, or inflammation of the con- 
 
18 INTERSTITIAL NEPHRITIS. 
 
 nective tissue stroma, leading to increase of the intertubular 
 tissue, owing to the presence of a small-cell growth, analogous 
 to granulation tissue, which growth presently undergoes a 
 more or less complete transformation into fibrous tissue. 
 This newly-formed fibrous tissue next proceeds to shrink, and 
 by its contraction compresses the secreting structures, thereby 
 leading to secondary changes in them. Dr Geainger 
 Stewart (A Practical Treatise on Bright's Disease of the 
 Kidneys, 2d edition, 1871) while maintaining that the 
 changes are due to increase in the amount of the fibrous 
 stroma, is of opinion that there is no proof of the inflam- 
 matory origin of this fibrous increase, and considers it rather 
 in the light of a connective tissue hyperplasia, unconnected 
 with inflammation both as regards origin and course. Dr 
 Stewart distinguishes between this primary interstitial over- 
 growth, and that secondary hypertrophy of the stroma, con- 
 sequent on Parenchymatous Nephritis. This last he considers 
 to have its origin, as stated by Johnson, Prerichs, and Niemeyer ; 
 while in the case of the true primary interstitial kidney, 
 which he denominates " Cirrhotic," he believes, in accord- 
 ance with others of his school, that the intratubular changes 
 are secondary to the intertubular overgrowth. The theory 
 of Drs Gull and Sutton we shall presently discuss in a 
 separate chapter : it is, however, shortly this ; — namely, that 
 the kidney changes are but part and parcel of a general 
 morbid state, consisting in the deposit of a " hyalra," or 
 " hyalin-fibroid " material in the adventitia of the arterioles, 
 and of a " hyalin-granular " change in the waUs of the 
 capillaries. 
 
 MM. CoBNiL and Eanvier attribute the change to a 
 chronic arteritis. 
 
 There is thus, as we have seen, no lack either of theories 
 or of investigators. On the question of the small red granular 
 kidney it is almost a case of " tot hominum quot sententise ;" 
 and, besides these prominent leaders of opinion, there is a 
 host of folloT^ers on either side. Some of these we shall now 
 very briefly indicate. 
 
 Dr Tanner (Practice of Medicine, 6th edit.) appears to 
 endorse the opinion of Dr Johnson; as does also Sir T. 
 Watson in the latest edition of his elegant and classical work. 
 
 Dr Bristowe (Practice of Medicine) does not commit 
 himself to any distinct opinion as to the essential pathology, 
 though he allows the reality of the connective tissue hyper- 
 
HISTOEICAL EISSUM^. 19 
 
 trophy, and further remarks that the origin is distinctly 
 inflammatory in certain cases. 
 
 Drs "WUks and Moxon also give forth an uncertain sound. 
 They say (Pathology, page 510) — "The term chronic desqua- 
 mative nephritis rests on a supposition as to the origin of the 
 disease, of which there is no sufficient proof. The pathological 
 nature of the change is prohably analogous to cirrhosis of the 
 liver, or sclerosis of the nervous centres. Some regard the epi- 
 thelium as the special seat of the disease ; others, the inter- 
 stitial tissue, virhich is supposed to increase and compress the 
 tuhes ; but no sufficient evidence of this is given. From 
 having been often able to trace the shrivelled tubes up to 
 wasted malpighian corpuscles, we are inclined to believe that 
 closure of these corpuscles may be the starting-point of the 
 disease. But all that can be certainly said is that the tubes 
 waste in the manner above described." Eespecting the 
 occurrence of a third or atrophic stage of the parenchymatous 
 variety, they say that though there is no proof of its exist- 
 ence, they do not absolutely deny its possibility. These 
 gentlemen also inform us that the consistence of the inter- 
 stitial kidney is not tough ! Had they the misfortune to be 
 fed on meat of the same consistence for a fortnight or so, 
 they might find cause to alter their opinion ; unless, indeed, 
 some beneficent fairy, compassionating their sad plight, were 
 to endow them with a strength of jaw equal to that of Old 
 Father WUliam in Lewis Carroll's racy piece of nonsense, 
 " Alice in "Wonderland." 
 
 Dr F. T. Eoberts (Practice of Medicine, page 855) .says ; — 
 " Most English writers are of opinion that the true cirrhotic 
 kidney is the result of chronic interstitial nephritis, attended 
 with proliferation of the intertubular connective tissue, which 
 becomes much increased, and compresses surrounding struc- 
 tures." He does not, however, express any positive leaning 
 towards one side or the other, and ends by remarking that 
 " the whole question is at present in a state of great uncer- 
 tainty." 
 
 Dr Eingrose Atkins (see British Med. Jour., AprU 3, 
 1875) and Dr T. J. Maclagan of Dundee, in a paper read 
 before the Medico-Chirurgical Society of Edinburgh (see 
 British Med. Jour., June 26, 1875), uphold Dr Johnson's 
 conclusions; while in Virchow's Archiv. for 1877 are two 
 excellent papers, the one by Thoma and the other by Ewald, 
 in which the opposite theory is advocated. 
 
20 INTEKSTITIAL NEPHRITIS. 
 
 In the midst of such, a cloud of conflicting witnesses, it 
 is perhaps no easy matter for the Independent observer to 
 keep his head cool, to preserve a judicial frame of mind, and 
 to form and maintain an unbiassed opinion ; for the eye is 
 very prone to see what it is led to expect, and the mind is 
 often apt to be unduly influenced by the spirit of partisan- 
 ship, or by one or another fashionable pathological idea. As 
 some sort of safeguard against this possible untoward influence 
 of precept, the author consulted his specimens first, and the 
 voluminous literature of the subject afterwards. Not tUl he 
 had carefully examined many dozens of sections, and had 
 begun, as he thought, to see in his own mind the dawn of a 
 well-grounded conviction, did he seek in the works of others 
 either strictures upon, or facts and arguments in support of 
 the conclusions at which he had thus, in a manner inde- 
 pendently, arrived. From that time forward, however, he 
 has made constant reference to a great mass of writings ; and 
 he trusts that while, on the one hand, he has endeavoured to 
 see and think for himself, yet that, on the other, he has not 
 been heedless or unmindful of those rich stores of informa- 
 tion so lavishly garnered up at the expense of the labours of 
 others. 
 
 CHAPTEE V. 
 
 ON GRANULATION TISSUE, WITH EEFBEENCE TO THE NtfCLEAE 
 TISSUE OF INTERSTITIAL NEPHRITIS. 
 
 As has been stated in the preceding chapter, Dr George 
 Johnson, and those who agree with him, attribute the appear- 
 ances seen in the small red granular kidney to the breaking 
 down and disintegration of the uiiniferous tubules and their 
 epithelium, which are, in his opinion, alone and entirely 
 responsible for the appearances met with in what is com- 
 monly known in this country as Interstitial, Cirrhotic, or Con- 
 tracted Kidney. Drs Wilks and Moxon also lend a partial 
 sanction to this view (Path. Anat.,' page 509), stating that 
 there is very little fibrous increase, except in the neighbour- 
 hood of the vessels. As Dr Johnson's theory is considered 
 
ON GKANULATION TISSUE. 21 
 
 at some length in Chapter VII. infra, we shall content 
 ourselves meanwhile with endeavouring to show the ahsolute 
 identity of the so-called "nuclear tissue" of interstitial 
 kidney, with that known as " emhryonic," " indifferent," or 
 "granulation" tissue, aiid seen, for example, in the first 
 stage of new formations, in healing ulcers, and in the repara- 
 tive process in wounds. If Plate i., which represents a 
 portion of granulation tissue taken "from a healing ulcer in 
 the human subject, he compared with Plate ii., which repre- 
 sents the "nuclear tissue" from a well-marked example of 
 early interstitial change, the resemblance between the smaU- 
 cell growths in both instances will at once arrest attention. 
 "We shall now proceed to consider whether we can adduce 
 sufficient evidence to warrant the conclusion that both are 
 substantially of the same nature. 
 
 On page 11 we made passing mention of the lymphatic 
 spaces and vessels discovered by Ludwig and Eindowski in 
 the connective tissue of the kidney. In this, as in all con- 
 nective tissue, there are two kinds of cells, stable, and mobile ; 
 the mobile being, in all likelihood, leucocytes which have 
 migrated through the vascular waU, passing through the 
 stigmata, and entering the lacunar system of lymphatics. 
 As these lymphatic spaces and vessels play a conspicuous 
 part in interstitial inflammations, it may be well, before pro- 
 ceeding further, to recapitulate shortly a few facts relative 
 to the anatomy of the lymphatic system which bear upon the 
 point at issue. 
 
 Note on the Lymphatic System. 
 
 Lymph- canals are of two kinds — lymph vessels proper, 
 with a regular endothelial wall, and irregular-shaped lacunar 
 spaces in connection with them, called plasma-canals, or 
 lymph-canalicular systems. They are easily demonstrable 
 by means of nitrate of silver, in the cornea, and in the pen- 
 cilled diaphragms of young rabbits, cats, and guinea-pigs. 
 In the plasma-canals lie the permanent branched connective- 
 tissue corpuscles of the part, which may be rendered visible 
 by means of Chloride of Gold ; but, besides these, the plasma- 
 canals contain a number of mobile or wandering corpuscles, 
 hke leucocytes, which are, in fact, white blood-corpuscles 
 which have found their way into the lymph-canaHcular system 
 by means of openings in the walls of the blood-vessels and 
 
22 INTEESTITIAL NEPHRITIS. 
 
 lymphatics, presently to be described. On the occurrence of 
 inflammation, their number becomes greatly increased. The 
 lymphatic spaces, demonstrated in the kidney by the injec- 
 tions of Ludwig, are simply the plasma-canals of its connective 
 tissue, which here, as elsewhere, contain the stable and mobile 
 corpuscles just mentioned. 
 
 On the surface of serous sacs, and in the walls of the 
 lymphatic vessels, are certain openings called stomata. Cor- 
 responding openings also exist in the walls of the blood- 
 vessels. They are called stigmata, and are in connection 
 with the lymph-canaUcular or plasmarcanal system, as are 
 also the stomata of the lymphatics. Thus an indirect com- 
 munication exists between the blood and lymph-vascular 
 systems proper, by the medium of the plasma-canals, into 
 which open the stomata of the lymphatics and the stigmata 
 of the vessels. Whether lymphatics and blood-vessels ever 
 directly communicate in the tissues without the intervention 
 of a system of plasmarcanals, is a point not as yet settled. 
 
 The plasma-canals follow the course of the blood-vessels ; 
 and when leucocytes pass through the vascular wall, they 
 enter the lacunar system, and become, as before stated, the 
 so-called mobUe cells of connective tissue. When the num- 
 ber of these migratory cells is increased by inflammation, 
 they occupy first those lacunar spaces in the immediate neigh- 
 bourhood of the vessels; and this fact, together with the 
 normally greater amount of connective tissue aroimd the renal 
 vessels, and consequent preponderance of plasma-canals in its 
 substance, serve to elucidate the occurrence of fibrous increase 
 around the vascular walls in Interstitial Nephritis, to a greater 
 extent than in the general stroma. 
 
 When interstitial inflammation supervenes in the kidney, 
 an abundant emigration of leucocytes takes place from the 
 vessels into the lacunar system of Ludwig. The inflamma- 
 tion being of a formative character, these leucocytes give 
 rise (either alone, or more probably in conjunction with the 
 fixed corpuscles, which by their division may take some part 
 in the process) to embryonic, indiiferent, or granulation cells, 
 which after a time assume the type of more or less fibrillated 
 connective tissue. The nucleus becomes oval, the cell elon- 
 gates, takes on a lanceolate or fusiform shape, and presently 
 fibrillation occurs, leading to the development of a greater or 
 less amount of wavy fibrous tissue. This fibrillation can be 
 
ON GKANULATION TISSUE. 23 
 
 traced from stage to stage, and is identical with the transfor- 
 mation of the round cells of cicatricial tissue, — so identical, 
 indeed, that the nature of the round-cell tissue Lq the kidney 
 is matter, not of conjecture, but of almost absolute inferential 
 certaiaty. 
 
 Dr George Johnson has never given any satisfactory 
 explanation of the above facts. A simple negation can hardly 
 be accepted as argument, nor will it, we think, in many cases, 
 suf&ce to make those of the adverse party distrust the results 
 of their own observation. In typical specimens of the latest 
 stages of the interstitial process, coarse, wavy, fibrous tissue 
 may be found in abundance, — ia far greater quantity than 
 can be accounted for by the shrinking together and approxi- 
 mation of that normally present, which is altogether so little 
 as to have led some writers into the error of affirming its 
 entire absence. It should be further remembered, that the 
 normal connective tissue is in great part ceUular; though, 
 without doubt, there is ,an admixture of fibres. Perhaps Dr 
 Johnson may be inclined to admit the fibrillar transformation 
 of the cellular connective tissue present in the normal organ 
 (see Path. Soc's Trans., 1877, page 391); but even this 
 concession would be very far from sufficient : for were the 
 appearance of fibrous increase in reality due to contraction 
 consequent on the destruction of the tubular and other 
 secreting structures, the diminution in size of the interstitial 
 kidney, — great though it be in extreme cases, — would, never- 
 theless, be inadequate to account for the large tracts of fibrous 
 tissue, so evident in many portions of the atrophied organ. 
 
 If, then, the fibrous increase be real and not merely 
 apparent, how, according to Dr Johnson's theory, can this 
 increase be accounted for ? Dr Johnson avers that there is 
 no fibrous increase, but the testimony of the author's prepara- 
 tions is entirely against him. 
 
 Again, it may be argued that the round cells of inter- 
 stitial kidney are smaller than those of granulation tissue. 
 This objection, however, is not worth much. Granulation 
 cells exhibit great differences in relative size, the largest 
 (excluding giant cells) measuring from about the Trinrth to 
 the xTOiyth of an inch in diameter, while the smallest are not 
 more than the ^wtr*^ °^ ^^ inch, or even less. Their size wUl 
 differ greatly, according to the amount of fluid present in the 
 tissue containing them ; and in the kidney, owing, firstly, to 
 the chronic or subacute nature of the insterstitial process; 
 
24 INTERSTITIAL NEPHEITIS. 
 
 secondly, to the density of the kidney substance ; and thirdly, 
 to the drain afforded hy the uriniferous tubules, .fluid in any 
 appreciable quantity is never met with. Ifothing but the 
 nuclei of disintegrated epithelium could in any other way 
 account for the round-cells in question ; and if we take into 
 consideration the fact, presently to be mentioned, that in the 
 first stage of the interstitial process there are positively no 
 intratubular changes observable (see Dickinson On Albumin- 
 uria), there is, in the author's opinion, no way of escape 
 from the inevitable conclusion, in favour of which so many 
 valid arguments are forthcoming, while those against it are, 
 for the most part, found on rigid examination to possess no 
 solid basis of proijability. 
 
 The following is a list of the principal arguments in 
 favour of the interstitial theory. Those which we have not 
 already discussed will be hereafter somewhat fully con- 
 sidered : — 
 
 i. In the first stage of Interstitial Ifephritis the kidney is 
 enlarged. Had the process been simply one of 
 wasting and disintegration of the secreting struc- 
 tures, we should expect diminution rather than 
 increase in size, 
 ii. In the earlier stages, . the intertubular septa are greatly 
 increased in width by the presence of a small-cell 
 infiltration, precisely resembling granulation tissue, 
 which in many parts forms large tracts, very con- 
 spicuous even under low powers, 
 iii. In the early stages, the tubules, if not actually per- 
 fectly normal, in that they are sometimes com- 
 pressed, are, at all events, easily recognisable; so 
 that there is little fear of confounding the products 
 of intra-tubular disintegration with those of inter- 
 tubular cell-infiltration, 
 iv. The round cells of the new tissue may be seen elong- 
 ating iato spindles, and differentiating into fibres. 
 They are, therefore, in a condition of growth, not 
 of decay, 
 v. Owing to this differentiation, an abundant fibrous in- 
 crease may be seen in the later stages of marked 
 specimens, — this increase being far greater than 
 could be accounted for by the approximation of 
 the small amount of fibrous tissue normally present 
 in the healthy kidney. 
 
author's own views. 25 
 
 CHAPTEK VI. 
 authoe's own views. 
 
 Feom what has been said in the previous chapter, it will hy 
 this time be pretty evident to the reader, that the views of 
 the author are in accordance with those of that school of 
 pathologists which ascribes the appearances constituting the 
 " smaU. red granular," or " interstitial " kidney, to the results 
 of a subacute or chronic inflammatory process, chiefly affect- 
 ing the cortical substance, and attended with increase of the 
 interstitial tissue. This is the opinion of Klebs, Eindfleisch, 
 Dickinson, and many others ; and the results of the author's 
 investigations agree substantially with the conclusions ex- 
 pressed in the works of these authorities. 
 
 Briefly, then, he believes that the origin of the morbid 
 process is to be referred to an inflammation, causing an 
 emigration of leucocytes through the walls of the vessels; 
 which leucocytes, either alone, or more probably aided in 
 some degree by the proliferation of the connective tissue 
 corpuscles, give rise to a smaU-cell formation of the nature 
 of granulation tissue, the cells of which, being at first round, 
 become subsequently spindle-shaped, and are finally converted 
 into fibrous tissue. This process is strictly an Interstitial 
 Nephritis, and by this name he prefers to designate it. For 
 descriptive purposes it will be convenient to divide the inter- 
 stitial changes into two stages ; though it must be understood 
 that all sorts of intermediate appearances are, as a rule, met 
 with in the same specimen, thereby, indeed, affording a neces- 
 sary proof of the connection existing between those constitu- 
 ting the two ends of the chain. These two stages are — 
 
 (1.) Stage of Oell-InflUration : 
 
 or Formation of Cfranulation Tissue. 
 
 (2.) Stage of Cell-Transformation : 
 
 or Fibrous Metamorphosis of the Granulation 
 Tissue. 
 
 We shaU first describe these two stages somewhat shortly, 
 and afterwards consider in detail those points which possess 
 special features of instruction and interest. . 
 
26 INTERSTITIAL NEPHRITIS. 
 
 I. Stage op Cell-Infiltration. 
 
 (See Plate ii.) 
 
 (a.) Naked Eye Examination. — Kidney generally heavier 
 than normal j enlarged, sometimes very appreciahly; colour 
 pale-whitish; surface smooth; capsule easUy detached, con- 
 gested veins heing often noticeable on the surface; consistence 
 soft and doughy, nearly resembling that of the parenchymatous 
 kidney. On section, the cortex is seen to be enlarged, its 
 consistence is doughy, and its colour yellowish-white, and 
 bloodless. (Some observers affirm, on the contrary, that there 
 is no yellowish tinge ; — but see Eiadfleisch. The colour is, 
 of course, not due to fat.) It has sometimes been described 
 as resembling a section of raw turnip. The Malpighian bodies 
 are red and promiuent. The medulla is congested, otherwise 
 ■^naltered. 
 
 Modifications. — According as the process has been more 
 or less chronic, the new tissue is more or less fibrous, and the 
 kidney may be either enlarged or lessened in bulk. The 
 capsule also may be to some extent adherent, and the surface 
 slightly granular. Some specimens are red, owing to passive 
 congestion. 
 
 This stage closely resembles the first stage of cirrhosis of 
 the Hver, in which the organ is frequently enlarged ; — Smooth 
 Interstitial Hepatitis. 
 
 (&.) Microscopic Appearances. — The capsule of the kidney 
 is seen to be thickened, and is often more firmly adherent than 
 in the normal organ, though sometimes separable with great 
 ease. Stretching inwards from the capsule into the substance 
 of the cortex, are bands of new material consisting of small- 
 celled or granulation tissue. These bands are due to an 
 enormous thickening of the delicate connective tissue pro- 
 cesses which normally pass from the capsule into the sub- 
 stance of the kidney. 
 
 Tubules and vessels are included in the new tissue, which 
 embraces and constricts them. On examining this nuclear 
 tissue with a high power, it is seen to contain multitudes of 
 round cellular bodies of the nature of leucocytes, in which, 
 under a very powerful lens, a nucleus is sometimes dis- 
 cernable. These cells may also be seen in process of con- 
 version into spindles, and the spindles again undergoing 
 transformation into fibrous tissue. The round cells are 
 
author's own views. 27 
 
 sometimes rather ill-defined ; but in most specimens they are 
 extremely conspicuous. The connective tissue along the 
 path of the renal vessels is increased by a similar formation. 
 These changes are not uniform, some parts of the kidney 
 being much more affected than others. The adventitia of 
 the renal arterioles is in the first instance perfectly normal 
 and unthickened, although the connective tissue following the 
 path of the vessels is, as has been said, increased in amount. 
 The middle or muscular coat of the arteries already presents 
 an appearance of thickening ; ■while the tunica intima is also 
 affected with that condition described by Heubner under the 
 name of Arteriitis Obliterans, which consists in a proliferation 
 of the inner coat, leading to ultimate occlusion of the vessels 
 affected. Wilks, Bristowe, Hughlings-Jackson, and some 
 others, have made passing mention of this lesion; but to 
 Heubner is due the credit of first investigating it, and bring- 
 ing it prominently under the notice of the profession. 
 
 The tubules are normal, with the exception of those con- 
 stricted by the new material, which forms a ring around them, 
 lessening their calibre, and leading to subsequent oblitera- 
 tion. CoUoid matter is often present in the tubules ; and 
 the glomeruli also are not unfrequently similarly degenerated. 
 Some authorities speak of the colloid material as being of a 
 waxy nature. This, however, is not the case, for it is stained 
 neither by iodine nor by methyl-aniline ; while, on the con- 
 trary, it stains with carmine in precisely the same manner as 
 colloid found elsewhere. It is derived from the renal epithe- 
 lium which after a time degenerates, owing to the pressure 
 exercised on the tubules by the new material. Globules of 
 colloid form inside the epithehal cells, which presently burst, 
 setting free the colloid in the interior of the tubes. The 
 epithelial nuclei appear, as a rule, to resist the colloid change, 
 for they are often seen arranged round the inside waU of a 
 tubule filled with coUoid, adhering more or less closely to 
 the basement membrane, and contrasting markedly with the 
 coUoid, which takes the dye much more faintly. In the 
 same manner, and from the same cause, the glomeruli become 
 converted into colloid masses. Bowman's capsule is much 
 thickened, and new material is generally especially abun- 
 dant in the neighbourhood of the Malpighian bodies. (See 
 Klebs, Virchow, and Traube.) The glomeruli consequently 
 become compressed, and their vessels are presently rendered 
 impervious ; degeneration then ensues, and, after a time, 
 
28 INTERSTITIAL NEPHEITIS. 
 
 nothing but a mass of colloid is left in the place of the 
 capillary loops. (See Plate viiL) The medullary portion of 
 the kidney is little affected. 
 
 This stage is identical with that described by Beer as 
 " corpuscular over-growth." The new material, which is 
 at first composed of lymphoid cells resembHng those of 
 granulation tissue, presently undergoes that fibrous transfor- 
 mation which constitutes the second stage of the interstitial 
 process ; but even at this early period, especially if the 
 progress of the change has been slow and chronic, fibrillation 
 more or less advanced may be here and there apparent, a 
 fact which conclusively establishes the connection between 
 the enlarged kidney of this stage and the shrunken, atrophied, 
 and granular one of the second. Eindfleisch, to be sure, makes 
 the remarkable statement (see Byd. Soc. Trans., vol. II., page 
 151) that, " even in extreme cases of contracted kidney, no 
 appearance of delicate striee, or of fibrillation can ever be 
 detected in the encroaching connective tissue." This assertion 
 is the more inexplicable, as even in the earliest stages observed 
 by the author, some amount of fibrillation has, as a rule, been 
 recognisable. 
 
 II. Stage op Cell-Teansfoemation. 
 (See Plate iii) 
 
 This stage corresponds to the "small red granular," 
 "cirrhotic," "contracted," or "gouty" kidney of other 
 authors. 
 
 The granulation tissue, the formation of which constitutes 
 the first stage, becomes in this stage dififerentiated into more 
 or less completely formed fibrous tissue, which shrinks, and 
 by its compression causes atrophy of the other renal struc- 
 tures, with great diminution in the size of the organ. 
 
 (a.) Naked Eye Examination. — ^Weight diminished, often 
 excessively; size visibly smaller, sometimes very much 
 atrophied and shrunken ; contour altered, irregular ; surface 
 rough, uneven, granular, or hobnailed; capsule thickened, 
 opaque, and very adherent, — so much so that, on forcible 
 tearing off, portions of the kidney substance come along with 
 it; colour pale, unless red from passive congestion, the 
 granular projections being light-coloured, "like parched 
 peas" (Dickinson), while the depressions between them are red 
 
author's own views. 29 
 
 from tlie presence of the superficial vessels, which run in. these 
 valleculsB. (See Coloured Plate, DicJdnson on Albuminuria ; 
 see also Bright's Reports of Medical Cases, 1827, vol. i., Plates 
 i.-iii.) Cysts are often seen on the surface. The consistence is 
 tough and leathery, somewhat like caoutchouc. On section, the 
 cortex is observed to be tough and diminished in size, being in 
 extreme cases reduced to not more than two or three lines in 
 thickness ; its colour is pale yellowish, uniform or mottled 
 with red. The convoluted tubules and Malpighian capsules 
 are frequently dilated into cysts. (See Plate vii.) These 
 are sometimes very numerous, some being visible to the naked 
 eye, while others are microscopic. The Malpighian bodies 
 are small and atrophied, and so approximated by the general 
 shrinldng as to appear abnormally numerous. The medullary 
 substance is generally but little altered, though occasionally 
 cystic; the pjrramids are sometimes hypertemic, sometimes 
 pale yellowish like the cortex. 
 
 (6.) Microscopic Appearances. — The ceU-infiltration of the 
 preceding stage is now in process of differentiation into 
 fibrous tissue. Many of the cells are seen elongating and 
 assuming a spindle shape; and the spindles, in their turn, are 
 here and there undergoing metamorphosis into fully-formed 
 fibrous tissue. True wavy fibrous tissue is most abundant in 
 the spurious adventitia of the vessels, 'and around the Mal- 
 pighian capsules and convoluted tubules ; that is to say, the 
 increase is most marked in those situations where fibrous 
 tissue normally exists. The Malpighian capsules are greatly 
 thickened, leading to compression of the vessels of the 
 glomerulus. In this stage, the smaU-ceU formation is very 
 distinct. Its elongation into spindles is perhaps best seen in 
 logwood preparations, as this reagent stains the cells more 
 deeply than carmine ; and while inferior for general purposes, 
 affords a somewhat readier demonstration of this particular 
 fact. The importance of the fusiform change in the shape of 
 , the infiltrated round-cells is very great, as it affords one of 
 the strongest arguments against Dr Johnson's theory of their 
 origin from epithelial debris. The dispute as to the nature 
 of the new tissue is to aU intents and purposes settled by the 
 fact of the cells assuming this fusiform shape ; for it is thus 
 seen that they are in a stage, not of regression, but of 
 growth ; not of disintegration and decay, but of progression 
 and differentiation. 
 
 The arterioles of the kidney also present many noteworthy 
 
30 INTERSTITIAL NEPHEITIS. 
 
 pathological appearances. Many of them are obliterated by 
 the pressure of the new material. The increase of the con- 
 nective tissue which accompanies them in their distribution 
 is now very evident. (See Plate ix.) 
 
 The adventitia proper does not at first share in the thick- 
 ening, but in many cases the process involves it secondarily, 
 and it becomes blended with the surroundiag new formation, 
 making, as it were, common cause with the general fibrous 
 increase. It is, however, often distinguishable as, a separate 
 structure, even in very advanced specimens of interstitial 
 change. Nov is there ever, according to the author's now 
 not small experience, any material of a " hyalin-fibroid " 
 nature to be found in connection with it. When thickened, 
 its thickening is secondary, and consequent on an extension 
 of the general interstitial change. 
 
 The tunica media is unquestionably hypertrophied. (See 
 Plates iv. and v.) Of this there can be no doubt; for in 
 well-stained specimens, there is little fear of even a compara- 
 tive tyro mistaking one coat for another. On this point the 
 author cordially agrees with Dr Johnson, whose claims to be 
 the first to call attention to this hypertrophy have been 
 hitherto too generally ignored. The hypertrophy appears to 
 be a true one, the multiplied nuclei of the contractile cells 
 being rendered very visible by the addition of acetic acid. 
 
 The tunica intima is frequently affected with Endoarteritis 
 Obliterans. (See Plates v. and vi.) The presence of this 
 condition, which passed unnoticed and almost unknown 
 until the publication of Heubner's monograph On Syphilitic 
 Diseases of the Arteries of the Brain, may formerly have 
 given rise to mistakes as to which of the three arterial coats 
 was hypertrophied. Now, however, it need no longer prove 
 a source of fallacy. It is well marked in kidneys taken from 
 syphilitic subjects, but is by no means confiiaed to these, 
 since almost all interstitial kidneys exhibit it more or less. 
 
 Endoarteritis Obliterans may, therefore, be considered as 
 a common, though, perhaps, not invariable factor in the inter- 
 stitial process. 
 
 Extensive changes consequent on the pressure of the new 
 material are now evident in the inriniferous tubules. The 
 epithelial cells become detached, and the tubes denuded of 
 their lining. In some cases the pressure leads to distortion 
 of the epithelial cells, as figured by Dr Dickinson; more 
 rarely, to fatty change; and again, very frequently to the 
 
author's own views. 31 
 
 formation of colloid. It must not, however, be supposed that 
 all the empty tuhules in. a mounted section are stripped of 
 their epithelium solely as the result of the niorbid changes. 
 Especially in thin sections, much epithelium will faU out 
 during preparation, in spite of every precaution. In deter- 
 mining, therefore, how much has been destroyed as the result 
 of disease alone, it is advisable to examine some of the thicker 
 sections, in which it is more readily retained. 
 
 Many tubules are entirely obliterated by pressure. Their 
 basement membrane appears, like the adventitia of the vessels, 
 to take a secondary share in the interstitial process. It be- 
 comes thickened and fibrous, and is ultimately blended with 
 the new formation. 
 
 Owing to the unequal pressure exercised on the tubules 
 at different points of their course, cysts and dilatations are 
 very common. (See Plate vii.) Colloid degeneration of the 
 epithelium may also lead to the formation of cysts. Thus 
 a tubule may be constricted at two places ; the epithelium 
 between these two constricted points next undergoes colloid 
 degeneration ■ the colloid is then carried away through the 
 very narrow yet still pervious opening, and escapes in the 
 urine as hyaline material, a cyst remaining behind. Again, 
 cysts may be formed by the vis a tergo of the uxine acting 
 upon a constricted point in the lumen of a tubule; and as 
 many points in the same tubule are sometimes simultaneously 
 narrowed, a tubule so compressed is often found to present a 
 series of moniUform dilatations. Perhaps also the contraction 
 of the new material may to some small extent further the 
 cystic change, by drawing asunder the walls of the tubes, as 
 is supposed to be the case in Bronchiectasis. 
 
 The thickening of Bowman's capsule leads to obliteration 
 and colloid degeneration of the contained glomerulus (see 
 Plate viii.) ; and on the disappearance of the capillary loops, 
 the interior of the capsule may be dilated into a cyst. Those 
 glonieridi which have not yet undergone the colloid change are 
 diminished in size, and much compressed ; while the general 
 shrinking greatly diminishes the distance between them. The 
 pressure often leads to rupture of the capiUary loops, and 
 small hsemorrhages are consequently not unfrequent. The 
 processes of new material, which have been before alluded to 
 as passing inwards from the capsule into the substance of the 
 cortex, may now be seen to arise opposite the depressions 
 between the hobnail projections visible to the naked eye on 
 
32 INTERSTITIAL NEPHRITIS. 
 
 tte kidney surface, — these depressions being caused by the 
 shrinking of the new tissue, while the hobnail protuberances 
 are due to the bulging of portions of kidney substance, sur- 
 rounded and strangled by its tightening grip. 
 
 The interstitial ' changes and shriaking above described, 
 are for the most part confined to the cortex. As a rule, the 
 medullary portions of the kidney are but slightly altered, 
 even in advanced stages. In certain exceptional cases, how- 
 ever, the cortical changes may involve the medulla also. 
 The iutertubular tissue is increased, coUoid matter is seen 
 in the straight tubules, extending almost as far down as the 
 papilla, and the epithelium ia many tubules is changed and 
 granular. 
 
 It should be noticed that those cases are very few and far 
 between in. which the whole, or nearly the whole, of the small- 
 cell formation takes on a truly fibrous type. In most 
 granular kidneys, even in the very last stages of shrinking 
 and atrophy, round ceUs and spindles are stiU visible over 
 large areas of the new formation. (See Plate iii.) 
 
 Having thus given an account, as succinct as possible, of 
 the various morbid appearances met with ia the two stages 
 of Interstitial ITephritis, we shall now proceed to carry out 
 our plan of considering in a little more detail some of the 
 results at vrhich we have arrived. Firstly, then, there 
 occurs the question. Is the interstitial ceU-infiltration to be 
 referred to a nephritis, or is it simply the consequence of a 
 hypertrophy of the -normal connective tissue, altogether apart 
 from inflammation 1 Dr Grainger Stewart, in his work on 
 Bright's Diseases of the Kidney, argues in favour of the latter 
 mode of origin, and quotes Dr Handfield Jones in support of 
 his position. On page 184 of the latest edition of his work 
 he states that the evidence in favour of the inflammatory 
 nature of the interstitial changes appears to him to be defec- 
 tive. (See also article by Dr Stewart, Brit. Med. Jour., Nov. 
 15th, 1873 ; and Eeport of Discussion before British Medical 
 Association, Sept. 6, 1873, Brit. Med. Jour.) He further 
 says : — " I know of no observation which warrants the asser- 
 tion that in the earliest stage free exudation is to be found 
 among the elements of the stroma ; and, as we shall presently 
 see, there is much reason to think that there is no such 
 exudation. In the absence of direct evidence, this view (as 
 to the inflammatory origin) appears to rest upon two con- 
 
authok's own views, 33 
 
 siderations : 1st, That the formation of connective tissue is a 
 common result of inflammation ; and, 2d, That the analogous 
 disease of the liver is supposed to result from inflammatory 
 action." Prom this statement it is warrantable to conclude 
 that the presence or absence of " exudation " conclusively 
 settles, according to Dr Stewart's opinion, the question as to 
 the presence or absence of inflammation, or at least throws 
 such a weight into the wavering balance that the unfor- 
 tunate nephritic theory is obliged then and there to kick 
 the beam. 
 
 But is " exudation '' necessary to inflammation 1 This 
 wiLL depend largely upon what the word is taken to signify. 
 If understood to mean merely the liquor sanguinis, the phe- 
 nomena observed in non-vascular structures at once negative 
 the conclusion that its presence is a sine qua non of the 
 inflammatory process. If, on the contrary, the emigration of 
 white 'blood corpuscles be included in the term, there is 
 abundant evidence of the outpouring of a vast number of 
 these in the first stage of nephritic cell-infiltration. "We 
 shall assume, however, that it is the liquid exudation, the 
 absence of which inclines Dr Stewart to reject the inflamma- 
 tory theory. And here, before going further, the author is 
 anxious to call attention to the fact that the liquid exudation 
 in a formative inflammation like the interstitial, is always 
 at a minimum ; while even in exudative inflammation proper, 
 the liquid exudation is at times very insignificant in quan- 
 tity, as, for instance, in the dry varieties of Pericarditis. But, 
 taking into consideration the structure of the kidney, we 
 should, far from wondering at its absence, be rather at a loss 
 to account for its outpouring in quantity, or long-continued 
 presence. In the first place, the interstitial inflammation is 
 chronic or subacute, and in an inflammation of this character 
 fluid exudation is always inconspicuous or absent. Further, 
 for aught we know, some slight fluid exudation may be pre- 
 sent in the earliest stages ; but these are rarely seen in the 
 post-mortem room, for the simple reason that they are seldom 
 attended with any fatal result. Moreover, the density of 
 the kidney substance, and the drain afforded by the urimfer- 
 ous tubules, militate strongly against the effusion or long 
 persistence of any fluid exudation. Green {Pathology, 2d 
 edit., page 191) well remarks : " In dense organs, as the liver 
 and kidney, owing to the compactness of the structure, a 
 large amount of effusion is impossible, and what there is, is 
 
 
 
34 INTEESTITIAL NEPHRITIS. 
 
 so intermingled with, the structural elements of the organ that 
 it does not appear as an independent material." Again, in 
 those rare cases in which a kidney comes imder the ohserva- 
 tion of the pathologist in the very earliest stages of the inter- 
 stitial process, it is actually enlarged, soft, and doughy ; the 
 capsule is thickened and juicy, and the general appearances 
 present a remarkable resemblance to those induced by paren- 
 chymatous inflammation. Surely this is a strange state of 
 matters if due to other causes than inflammation. Further, 
 be it remembered that the abundant small-cell infiltration is 
 not, in the first instance fibrous, or even of the nature of 
 differentiated connective tissue, but consists of cells precisely 
 identical with leucocytes, the emigration of which in such 
 numbers seems to point conclusively to inflammation as a 
 cause. Dr Handfield Jones, whose authority Dr Grainger 
 Stewart quotes, describes the occurrence of fibrous patches 
 in serous membranes, such as the arachnoid, pericardium, 
 pleurre, peritoneum, cardiac valves, etc., in the mucous and 
 submucous tissues of the stomach, and in the substance of 
 organs, such as the liver, lungs, testicles, and uterus. These, 
 he rightly argues, are not all due to inflammation. But, 
 further, he says, as quoted by Dr Stewart, " that the hyper- 
 trophy causing the increase and thickening of fibrous tissues 
 goes on and on, as a substantially independent process totally 
 unassociated with any trace of inflammation, even though it 
 may by possibility have originated in it." Now, this last is a 
 rather naive admission, and seems, in fact, equivalent to a 
 total abandonment of the position previously gained at the 
 cost of so much argument. If a fibrous increase is originated 
 by an inflammatory process, and due to the migration of 
 lymphoid elements consequent on inflammation, then the 
 overgrowth is unquestionably inflammatory, even though it 
 proceed after the subsidence of the inflammation. The cica- 
 tricial tissue of wounds is generally acknowledged to be 
 inflammatory, though we do not expect to meet with the 
 phenomena of inflammation in a scar a year old. The inflam- 
 mation simply supplies the material, which is afterwards 
 utOised at leisure. It is the waggoner who conveys the 
 blocks of stone to the site of the future building, — not the 
 mason who, with maUet and chisel, hews them into shape. 
 If, then, inflammation is, in the first instance, the provoca- 
 tive agent of a fibrous hyperplasia, providing the round-cells 
 which are presently to be differentiated into fibres, the fibrous 
 
author's own views. 35 
 
 overgrowth, when complete, is assuredly inflammatory, even 
 though the inflammation has long ago disappeared. 
 
 We must not be understood as wishing to refer all fibrous 
 increase to the result of antecedent inflammation. The 
 " simple overgrowth," described by Beer, in the kidney, 
 milk spots on the pericardium, and many other fibrotic 
 changes, are, it may be, not only carried on, but initiated 
 totally apart from any inflammatory action. But so-called 
 " Irritative Hypertrophies" trench so often upon the province 
 of inflammation, that in many cases, such as those where the 
 tissue elements are numerically increased, the author believes 
 the distinction to be one without a difference, and dependent 
 rather upon the degree than upon the nature of the changes 
 included under the term. The " corpuscular overgrowth " of 
 Beer corresponds to Interstitial Nephritis ; and thus he is in 
 accord with the present writer in attributing it to the results 
 of inflammation. It is a common fallacy to say that where 
 there is no lymph and exudation, there is, or has been, no 
 inflammation. The lymph and exudation may have vanished, 
 whereas the consequences of the inflammation may remain. 
 
 One can understand that a fibrous increase, such as that 
 constituting a "nulk-spot," may take place somewhat after 
 this manner : — Owing to some cause or another— from friction, 
 in the present instance — the normal subserous connective 
 tissue is excited to increased activity of growth. It enlarges, 
 and after a time, like the cuckoo in the hedge-sparrow's nest, 
 not finding its quarters sufficiently spacious for its increased 
 requirements, provides itself with elbow-room at the expense 
 of its next-door neighbours. But it is the same connective 
 tissue after all ; it has grown larger, and become a bully ; but 
 its textural elements have received no numerical additions. 
 In sljort, its elements are enlarged, but their number remains 
 unaltered. Such a fibrous increase need not, perhaps, be 
 accounted inflammatory; but if the connective tissue elements 
 are increased numerically, this increase is traceable, in the vast 
 majority of instances, to the results of an antecedent inflam- • 
 mation. It may be thought, that according to this view, too 
 great a prominence is assigned to inflammation as a cause' of 
 connective tissue hyperplasia; but yet how imiversal a pro- 
 cess inflammation is ! The labourer would, perhaps, be not a 
 little surprised, if told that his horny hands had been pro- 
 vided with their pachydermatous covering by the aid of this 
 so-much-dreaded condition ! Yet such is the case. A little 
 
36 INTERSTITIAL NEPHKITIS. 
 
 more of the exciting cause, and not an epidermal increase, iDut 
 a blister would be the consequence. It is perfect nonsense 
 to ascribe such an epidermal thickening to "Irritative Hyper- 
 trophy." Inflammation, and inflammation alone, is respon- 
 sible for it, as amply evidenced by the redness and heat of a 
 delicate hand, when subjected to some unaccustomed attri- 
 tion. To be sure, the inflammation goes no further than 
 congestion ; but though slight in degree, its nature admits of 
 no question. If the connective-tissue elements of a part are 
 increased, the new elements must have originated from some 
 pre-existing ones; and whether they arise from migrated 
 leucocytes, or from division of the permanent connective 
 tissue corpuscles, both these processes are, according to the 
 present state of our knowledge, alike characteristic of inflam- 
 mation. Of course, the transformation of already existing 
 cellular into fibrous tissue does not of necessity involve the 
 presence of inflammation ; and thus some appearance of 
 numerical hypertrophy may sometimes be caused ; but if the 
 increase be greater than can be accounted for in this way, it 
 appears to the author that the inflammatory theory can alone 
 sufficiently account for the presence of the new elements. 
 The advocates of "Irritative Hypertrophy" ma^ say that this 
 view is merely theoretical, and incapable of proof. True, it 
 is theoretical; but so is their own, and the onus prohandi 
 lies with them, not with us; for before proceeding to 
 separate " Irritative Hypertrophies " from inflammation 
 proper, it is but reasonable that something more than mere 
 supposition should be alleged in favour of such a divorce. 
 
 " Irritative " numerical hypertrophy, then, unless used as 
 the equivalent of " nascent inflammation " (to borrow a term 
 from Chemistry), is a name likely to mislead, and expressive 
 of a purely hypothetical condition. 
 
 The case, therefore, as to the inflammatory or non-inflam- 
 matory nature of the interstitial ceU-infiltration may be 
 shortly tabulated as follows : — 
 
AUTHOR S OWN VIEWS. 
 
 37 
 
 De Stewart, con. 
 I. There is no free exudation. 
 
 II. There is no direct eTidenoe 
 of its inflammatory nature. 
 
 The Author, ^o. 
 
 I. Free exudation is not to be 
 looked for, because — 
 
 (1. ) The inflammation is chronic 
 and formative. 
 
 (2. ) The density of the kidney 
 substance prevents its effu- 
 sion. 
 
 (3. ) Theuriniferous tubules drain 
 it off as fast as it is poured 
 out. Against this it may 
 be argued that the urine 
 contains little or no albu- 
 men in the earlier stages. 
 But, as shown by 1 and 
 2, there is little or no albu- 
 minous exudation poured 
 out, so that its absence in 
 the urine is not to be won- 
 dered at. 
 
 (4.) In the very earliest stages, 
 a small amount of free exu- 
 dation may, for aught we 
 know, be present (Klebs). 
 
 II. There is direct evidence, as 
 follows : — 
 
 (1.) The enlarged, soft, doughy, 
 and juicy condition of the 
 kidney in the earliest 
 stages. 
 
 III. Fibrous increase is often met 
 with totally apart from inflamma- 
 tion. 
 
 (2.) 
 
 The abundant infiltration 
 with lymphoid cells. 
 
 III. Increase in the size of the 
 original elements is often so met 
 with ; but increase in their num- 
 ber is very seldom, perhaps never, 
 so met with. 
 
 In conclusion, it occurs to the author that Dr Stewart's 
 reasons for rejecting the inflammatory theory, may perhaps 
 have heen due to his still holding, at the time of the pubHca- 
 tion of the last edition of his work, some of the older ideas 
 as to the nature of the inflammatory process. In this case 
 we may look for some alteration of his views in subsequent 
 editions. 
 
 Dr Stewart's conclusions are generally marked hy such 
 care and accuracy, and are in the main so consonant with the 
 results of the author's observations, that he has thought fit to 
 
38 INTEKSTITIAL NEPHRITIS. 
 
 discuss at some length this, their almost only point of material 
 difference. 
 
 So far as one may judge from the last edition of Jones 
 and SieveJcing's Pathology hy Payne, Dr Handfield Jones 
 seems to have modified his opinions as to the pathology of 
 contracted kidney; for in this reprint of the conjoint work, 
 the origin of the disease is clearly ascribed to a nephritis. 
 
 TEE NEW TISSUE, AND TEE CEANGES CONSEQUENT 
 ON ITS PRESENCE. 
 
 One of the most noticeable changes in the interstitial 
 kidney is the thickening and adhesion of the capsule. This 
 thickening is of a densely fibrous character, with here and 
 there a few flbrillating spindles, and' occasional round-cells j 
 smaU vessels and lymphatic spaces also, are to be seen in its 
 substance. The normal delicate bands of connective tissue 
 passing between it and the cortex are enormously in- 
 creased, and penetrate far into the cortical substance. So 
 firm is the adhesion caused by the thickening of these pro- 
 cesses, that in advanced stages large portions of the cortical 
 substance are torn off on forcible evulsion of the capsiile. 
 The author has never seen a specimen sufficiently early to 
 exhibit typically the stage of smaU-cell infiltration, which 
 doubtless occurs here as in the substance of the kidney 
 proper ; though in Glomerulo-Nephritis it appears to be com- 
 paratively but little affected. Interstitial kidneys are seldom 
 long allowed to retain their capsular investment. The 
 difficulty experienced in separating the capsule, seems to be 
 provocative of attempts to do so ; and these are generally so 
 unfortunately successful that by the time the specimen 
 reaches the hands of the histologist, there is seldom any 
 capsule left to separate. Of course if we make our own 
 post-mortems, it is within our power to exercise some restraint 
 over our evulsory propensities ; but post-mortems in private 
 practice are rare. 
 
 In order to determine whether or not the apparent new 
 tissue is in reality a something superadded to the normal 
 elements of the kidney substance, or simply an appearance 
 produced by the destruction of the tubules and epithelium, 
 we should examine rather those specimens which exemplify 
 
author's own views. 39 
 
 the early stages, than those later ones in which there has 
 been great destruction of the secreting structures. Although 
 the tuhular epithelium is often hiit little changed even at 
 later periods, yet by thus directing our attention to specimens 
 in which, save for the results of compression, it is to aU 
 intents and purposes normal, we do much to eliminate 
 sources of confusion and fallacy. At the outset, however; 
 we have to confront the difficulty caused by the extreme 
 rarity of such early specimens. In this dilemma we derive 
 valuable aid from the examination of the interstitial tissue 
 in cases of Glomerulo-Nephritis, such as that represented 
 in Plate, ii. In these the round-cell infiltration is abundant, 
 while, owing to the comparative integrity of the tubules, its 
 nature is unmistakeable. Glomerulo-Nephritis is, in fact, 
 simply an Interstitial Nephritis, differing only from the 
 common variety in its anatomical site of greatest intensity, 
 — i.e., attacking not merely the general interstitial tissue, 
 but also that which binds together the vascular loops of the 
 glomeruli. In consequence of this peculiar anatomical situa- 
 tion, it is a dangerous and fatal disorder; and such cases 
 afford perhaps the most typical examples of early interstitial 
 change which evgr find their way into the hands of the 
 pathologist. 
 
 The normal connective-tissue septa are much increased in 
 width, and as the tubules are generally pretty normal, and 
 even when compressed are stiU recognisable, there is the less 
 danger of mistaking connective-tissue increase for disintegrated 
 tubules and epithelium. Indeed, there is but slight fear of 
 a practised observer falling into this error. It may be argued 
 that the epithelial nuclei stain with reagents in precisely the 
 same manner as the lymphoid cells of the new tissue. Granted ; 
 but for all this there are ways and means of appreciating a 
 difference considerably greater than that between tweedledum 
 and tweedledee. The epithelial nuclei are sharply defined, 
 round in shape, never fusiform or clavate, though they may 
 be oval, and larger and more opaque than the lymphoid cells. 
 Then, again, they lie in relation to portions of compressed 
 tubules, -which afford a ready means of identifying them. As 
 to the tubules themselves, it is the author's belief that their 
 basement membrane never becomes disintegrated. It enters 
 into the process going on around it, and undergoes fibrillation 
 with even greater readiness than the new material itself. If 
 warrant for this assertion be demanded, the author would 
 
40 INTEKSTITIAL NEPHRITIS. 
 
 direct attention to the constricting ring generally seen around 
 an atrophied tuhule, wliich ring is formed of the thickened 
 basement membrane, which (as in the case of Bowman's 
 capsules) is distinctly more fibrUlated than the surrounding 
 small-cell tissue. (See Niemeyer ; Humphreys and Hockley's 
 Trans., 1876, vol. II., page 23; also FiiZfo and Moxon's 
 Pathology, page 509). In these constricting rings, and 
 in the thickened Bowman's capsules, spindles are often very 
 apparent; and in these two situations, as also in the in- 
 creased connective tissue around the vessels, the process of 
 transformation of the round-ceUs first into spindles, and 
 subsequently into fibres, may be very satisfactorily observed. 
 ISTot that it is at all difficult to recognise it elsewhere ; but in 
 these places it is often very plainly and beautifully exem- 
 plified. Later on, the same thing occurs in the adventitia 
 proper of the renal arterioles, which becomes thickened, and 
 is presently blended with the surrounding new material 
 (See Plate ix.) It should, however, be distinctly understood 
 that this is a secondary change. The fibrotic process, far 
 from beginning in the adventitia of the arterioles, involves it 
 only when the changes elsewhere have become very evident. 
 Picro-carmine in one per cent, solution (Eanvier's receipt) 
 gives a very good demonstration of the coats of the arterioles. 
 The adventitia and intima are stained yellow, while the 
 muscular coat is coloured red. The newly formed tissue 
 around the adventitia is coloured red, if not advanced in 
 fibrillation ; if fibrous, it is yellow also ; but the adventitia, 
 being denser, is easUy distinguishable by its deeper coloura- 
 tion. Double staining with carmine and osmic acid answers 
 the same purpose extremely well, and the importance of the 
 aid afforded by these reagents in enabling us to recognise 
 and distinguish the several coats, can scarcely be over- 
 estimated. All dubiety, aU uncertainty vanish with their use. 
 Dr Galabin {On the Connection of Brighfs Disease with 
 Changes in the Vascular System, page 14,) says: — "It is 
 somewhat difiicult in a transverse section to distinguish 
 between the circular muscular fibres and the fibrous tissue out- 
 side them." This difficidt matter becomes an easy one with 
 the assistance of picro-carmine. Of course, a whole regiment 
 of bottles fuU of staining fluids will not make a competent 
 histologist out of a neophyte ; for microscopic reagents require 
 to be used as Opie mixed his colours^with brains ; but in 
 the hands of a practised observer and dainty manipulator, 
 
, author's own views. 41 
 
 they are capable of affording the most absolute eridence as to 
 which is which in the matter of the arterial coats. 
 
 The middle or muscular coat is, as has been already- 
 stated, hypertrophied. (See Plates iv. and v.) This hyper- 
 trophy is noticeable at a comparatively early period in the 
 history of the interstitial changes ; indeed, the author has 
 scarcely ever seen an undoubted example of the ordinary 
 variety of interstitial kidney, the arteries of which did not 
 show it in a greater or less degree. He is therefore led to 
 consider it as a practically constant appearance ; though all 
 parts of an artery are not equally affected by it, as is easily 
 seen in longitudinal sections embracing any appreciable length 
 of the vascular coats. The hypertrophy appears to be a true 
 one ; that is to say, the enlargement is probably due to increase 
 in the number of the non-striped muscular elements. In these 
 the author has seldom observed any notable structural altera- 
 tions ; according to his experience they colour normally with 
 carmine and other reagents ; (GuU. and Sutton say that the 
 nuclei do not absorb carmine so readily as in healthy vessels) ; 
 the nuclei are normal in shape, nor has he ever seen them 
 fattily degenerated. Dr Dickinson (On Albuminuria, 2d Edit.), 
 while admitting the existence of the muscular hypertrophy, 
 says that degenerative changes also occur in the middle coat 
 of the vessels. His illustrations are taken from the arteries of 
 the pia mater. Traube and Ludwig also hold similar views. 
 The author has pretty frequently met with this apparent 
 atrophy. At times it appears to him to be not so much 
 atrophy as an absence of hypertrophy, those parts of the 
 muscular coat which still retain their normal thickness 
 appearing ■ wasted, by contrast with the adjoining greatly 
 hypertrophied portions. At other times, he must confess, it 
 looks very like atrophy proper. The muscular coat appears 
 more homogeneous than natural, and is in some places un- 
 questionably reduced in thickness. This condition of the 
 tunica media is almost invariably accompanied by consider- 
 able obliterative thickening of the intima. The occasional 
 muscular atrophy is, however, no argument against the co- 
 existence of the abundantly evident hypertrophy. (See 
 Johnson, Trans. Path. Soc, 1877, page 385.) 
 
 The occurrence of thickening of the middle coat in the 
 early stages of interstitial kidney, may be taken as an argu- 
 ment against the true muscular character of the increase, 
 since muscular hypertrophy is a slow and gradual process. 
 
42 INTEKSTITIAL NEPHIIITIS. 
 
 But, as has been often before mentioned in the present treatise, 
 the very early stages of Interstitial Nephritis rarely come 
 under clinical, far less under pathological, observation. What, 
 therefore, the morbid anatomist recognises as an early stage 
 of iaterstitial change, may in reality be the product of a 
 morbid process -which has lasted for months. Interstitial 
 JS^ephritis is essentially chronic, or at most subacute ; the 
 fatality of its initial stages is almost nil; and a sufficient 
 time, consequently, elapses between its supervention and its 
 recognition at the autopsy, to allow of even the tardy develop- 
 ment of muscle cells. The absence of hypertrophy of the 
 muscular coat in the author's speedUy fatal cases of Glomerulo- 
 nephritis, fiu-ther tends to strengthen these conclusions. 
 
 In a monograph like the present, which deals solely with 
 the Morbid Anatomy of interstitial kidney, it would be out 
 of place to propound or endorse any theory as to the cause of 
 this muscular hyperplasia j suffice it to say, that the author is 
 convinced of its existence. (See Plate iv.) The hypertrophy 
 is far too great to admit of its being explained away on the 
 ground of post-mortem contraction, analogous to the so-caUed 
 " concentric hypertrophy" of the heart. The muscular coat 
 is frequently two or three times as thick as in normal arteries, 
 and no possible amount of mere contraction could give rise 
 to such an appearance of increase. Confirmatory evidence in 
 favour of its true muscular character is given by Dr Grainger 
 Stewart (Brit. Med. Jour., Sept. 6, and JSTov. 15, 1873); 
 by Dr Atkins (Brit. Med. Jour., April 3, 1875) ; by Dr 
 T. J. Maelagan (see Report of Trans, of Med. Ohir. Soc, 
 Edin., Brit. Med. Jour., June 5, 1875); rather hesitatingly 
 by Dr Galabiu {On the Connection of BrigMs Disease with 
 Changes in the Vascular System) ; and in the 2d edition of 
 Jones and Sieveking's Pathology, by Payne. Again, on 
 examining the arterial coats in longitudinal section, the mus- 
 cular nuclei are seen in greater numbers than in unaffected 
 vessels ; which not only proves the true nature of the hyper- 
 trophy, but at the same time negatives the theory of post- 
 mortem contraction. Sir W. GuU and Dr Sutton say the 
 muscular layer varies in thickness, and that it is difficult to 
 say what are or are not its normal dimensions. Well, so do 
 men vary in stature ; yet if we meet with a man eight feet 
 high, we caU him a giant. How much more Brobdignagian, 
 then, should we consider him if he towered above our 
 diminished heads to the height of twelve or eighteen ? Yet 
 
AUTHOK S OWN VIEWS. 
 
 43 
 
 tHs disproportion is no more than actually exists between 
 the muscular coat of healthy arteries, and that of the hyper- 
 trophied vessels of Interstitial Nephritis. 
 
 We subjoin a few measurements, showing the relative 
 thickness of the muscular coat as compared with that of the 
 whole arterial wall. It will be seen from this table, that 
 interstitial arteries, as compared with normal ones, show 
 thickening of the media and intima, whereas the adventitia 
 is but little increased. 
 
 NOEMAL. 
 
 Abvestitia. Media. 
 
 Intima. 
 
 li 
 
 2 
 1 
 2 
 
 2 
 2 
 3 
 About 3 
 Disorganised 
 2 
 
 1 
 2 
 1 
 
 2J 
 
 Nearly 3 
 
 4 
 
 2i 
 2 
 2 
 About 3 
 3J 
 2 
 
 24 
 
 2 
 
 About 2 
 
 5 
 
 2 
 2 
 
 3^ 
 
 2 
 2 
 
 14 
 
 28 
 
 2 
 
 3 
 
 44 
 
 5 
 
 3 
 
 2 
 
 2 
 
 2 
 
 1 
 
 14 
 
 3i 
 4 
 
 54 
 34 
 
 2 
 
 24 
 44 
 44 
 3 
 About 2 
 2f 
 2 
 2 
 
 About J 
 
 1 
 
 Nearly 1 
 
 Much wrinkled 
 
 4 
 
 4 
 
 Nearly 4 
 
 Nearly 4 
 
 4 
 
 INTERSTITIAL. 
 
 Adventitia, 
 
 14 
 
 2 
 
 2: 
 
 2 
 About 3 
 
 3 
 
 2 
 About J 
 
 3 
 About 2 
 
 2 
 About 2 
 
 2 
 
44 ' INTERSTITIAL NEPHBITIS. 
 
 From these measurements it is evident that the intima, as 
 well as the media, is very generally thickened by the "Arteriitis 
 Obliterans" of Heubner. For the awkward and cacophonous 
 word " Arteriitis," we prefer to substitute the term " Endo- 
 arteritis," which is sufficiently euphonious to merit exemption 
 from the category of 
 
 " "Words which should only he said on holidays, 
 ■When one has nothing else to do." 
 
 Atheroma is already known by the term Endo-arteritis 
 Deformans, and there appears to be no valid reason, save the 
 German nationality of its discoverer, for the introduction of an 
 extra " i " into the name of the unfortunate Heubnerian lesion, 
 whereby its back is broken for aU purposes of utterance. 
 
 The inner coat may be anatomically divided into three 
 layers, exhibiting distinct structural differences. The inner 
 surface of the tube is lined by a layer of irregularly lanceolate 
 epithelioid cells. Preparations of frog's rectum and bladder 
 injected with nitrate of silver afford a very beautiful demon- 
 stration of this epithelium. 
 
 Immediately underneath this epitheloid layer is one of 
 greater pathological importance, consisting of connective 
 tissue, with branched corpuscles lying in lacunar spaces, 
 similar to those in the cornea, etc. The corpuscles are 
 demonstrable by chloride of gold, which, though a somewhat 
 uncertain reagent, gives occasionally very beautiful results ; 
 while the lacunse in which these cells He, are rendered visible 
 by the action of nitrate of silver, which stains the ground 
 substance of a dark colour, leaving the lacimse visible as 
 irregular patches of a lighter hue. The ground substance is 
 for the most part homogeneous, though it may sometimes 
 present an appearance of striation, or even of fibrillation. A 
 longitudinal elastic network is sometimes said to be present 
 in this layer. The last and thickest portion of the inner coat 
 consists of elastic layers which are superimposed on one 
 another as a varying number of longitudinal fibrous networks, 
 which not unfrequently assume a membranous form with 
 perforations, constituting the "fenestrated membrane of 
 Henle." 
 
 Having thus glanced briefly at the normal structure of the 
 inner coat, we shall be in a position to appreciate the morbid 
 alterations induced by the obliterative changes above referred 
 to. These are probably initiated, and have their chief seat 
 
author's own views. 45 
 
 in the middle or connective-tissue layer of the inner coat. 
 The microscopic appearances are, shortly, as follows : — The 
 inner coat becomes thickened, and assumes a sort of fibrous 
 character, the sides of the lumen of the vessel being, in the 
 advanced stages, rough, ragged, and splintery, like coarse 
 cocoa-nut matting. (See Plate vi.) ' The fibrous filaments 
 have a concentric arrangement around the axis of the vessel, 
 and obscure spindles are often noticeable among them, together 
 with large roimdish, oval, or irregularly spheroidal bodies of 
 the nature of connective-tissue corpuscles. Eo trace of 
 epithelial lining is in most instances discoverable. In the 
 earliest stages, the sides of the narrowed lumen are stiU 
 smooth, but present no appearance of epithelium, unless 
 some irregular cells close to the inner edge may be considered 
 as such. (See Plate v.) The elastic coat of the intima 
 appears to be separated more or less completely into its 
 component layers. Small vessels are sometimes seen in the 
 proliferated intima. These require high powers for their 
 satisfactory demonstration (such as Hart. oc. 3, x obj. 9, 
 wide angle, tube out). The thickening of the intima goes 
 on until at last the affected arterioles are completely occluded 
 by a fluffy, ragged material, which, when the artery is alto- 
 gether obliterated, becomes denser and more fibrous, and 
 assumes the appearance of more or less perfect concentric 
 fibrDlated rings. Sir W. Gull and Dr Sutton have noticed 
 this occlusion {Med. GMr. Trans., vol. Iv., page 275). 
 Dr Grainger Stewart also makes mention of a thickening 
 of the intima in the arterioles of the pia mater, but says 
 he has never seen evidence of diminution of the lumen {Brit. 
 Med. Jour., Nov. 15, 1873). 
 
 The author has never seen the proliferated elements 
 arranged in distinct layers of different morphological type, as 
 represented in syphilitic arteries by Dr Greenfield {Path. 
 Soe. Trans., 1877, plate xiii.); the appearances as seen by 
 him being more comparable to Dr Barlow's drawing (plate 
 XV., fig. 1, ibid) ; though in the author's specimens, spheroidal 
 cells were more abundant than spindles; fibres more abundant 
 than either; and epithehum rarely and doubtfully present. 
 Something, however, may be due to the size of the arteries 
 examined; for those in the author's specimens were much 
 smaller, and necessitated the use of far higher powers. 
 
 The process seems to consists essentially in a proliferation 
 of the connective-tissue corpuscles of the middle layer of the 
 
46 INTERSTITIAL NEPHRITIS. 
 
 inner coat, with subsequent fibrillation of the connectire 
 tissue. Such a theory is ia accordance with the behaviour 
 of connective tissue elsewhere, under like inflammatory con- 
 ditions, and is in the author's opinion a satisfactory explana- 
 tion of the nature of this iateresting lesion. (See also Thoma, 
 Vir chow's Archiv., Band 71, Heft ii.) 
 
 It is evident that this narrowing and obliteration of arteries 
 must materially contribute towards the causation of secondary 
 intratubular changes ; for owing to the direct obstacle thus 
 offered to the blood supply, the nutrition of the tubules and 
 their epithelial contents must be interfered with almost as 
 seriously as by the presence and pressure of the increased 
 interstitial tissue. The intratubular cell-infiltration might 
 even, if very abundant, give rise in the first place to the form- 
 ation of new vessels for its nutrition ; but the obstacle occa- 
 sioned by the blocking up of the normal ones, admits of no such 
 extenuating circumstances. Intratubular nutrition is, there- 
 fore, impaired by two causes ; firstly, by the presence and 
 pressure of the new material, which presently shrinks, and 
 obliterates not only any vessels which may have been formed 
 for its nutrition, but many of the normal ones as well ; and 
 secondly, by the blocking up of the normal arteries by obli- 
 terative changes in their intima. Eemembering, then, these 
 two factors of interference with blood supply, it is no wonder 
 if, after a time, intratubular changes f oUow in the wake of the 
 intertubular increase.* The tubules themselves are com- 
 pressed, and their nutriment is cut off; and, accordingly, 
 we find the secreting structures undergoing various forms of 
 secondary alteration. The epithelium is loosened from the 
 basement membrane of the constricted tubules ; sometimes it 
 breaks up into a finely granular mass ; sometimes it undergoes 
 coUoid degeneration; less frequently it becomes fatty; in 
 other cases a few epithelial cells appear to have vanished en 
 masse, their remaining neighbours being nearly normal, 
 though this may be partially due to the falling out of the 
 absentees during the preparation of the specimen. The 
 author has noticed that the protoplasm of the epithelial cells 
 occasionally stains with carmine and other reagents in an 
 apparently capricious manner. This is probably due to com- 
 
 * Klebs thinks that the interference with blood-supply has even 
 more to do with the atrophy of the kidney than the shrinking of the 
 new tissue. 
 
author's own views. 47 
 
 mencing degenerative change. He has also in a few instances 
 remarked a similar deep colouration of the connective-tissue 
 corpuscles in the substance of the glomeruli, which he regards 
 as the herald of impending coUoid degeneration. Sometimes, 
 also, fromsome unknown cause, thelymphoid cells of the nuclear 
 tissue are stained with a clearness perfectly diagrammatic. The 
 nuclei of the epithelial cells often vary in the extent to which 
 they absorb the colouring matter- but this inconsistency 
 cannot be looked upon as an indication of actual abnormality, 
 as the same thing occurs in normal specimens, and is very 
 likely due to unimportant chemical changes. The epithelial 
 nuclei are the most persistent of aU the intratubular elements; 
 and a tubule is often seen in transverse section, with the nuclei 
 still clinging to its inner wall, from which aU. trace of the 
 cells themselves has disappeared. 
 
 Altogether, considering the immense interference with 
 function which the presence and shrinking of the new material 
 cannot fail to induce, the intratubular changes, though great, 
 are not more than might be expected from a like cause. In 
 the later stages some epithelium is fatty ; much is entirely 
 destroyed, and much also converted into coUoid; many 
 tubules are dilated and cystic (see Plate vii.) ; the denuded 
 basement membrane is thickened, fibrous, and blended with 
 the new material; the glomeruli become impervious, and 
 finally degenerate into coUoid masses (see Plate viii.) ; 
 Bowman's capsules are thickened and fibrous like the 
 basement membrane of the tubules ; many tubules are com- 
 pressed and atrophied, and others are entirely obliterated. 
 But while fully recognising the importance of these intra- 
 tubular alterations, we cannot agree with Dr Johnson in 
 regarding them as the primary or essential part of the 
 morbid process. They occur as a consequence and not as a 
 cause; and are subsequent, not antecedent, to the primary 
 smaU-cell increase of the kidney stroma. 
 
 Before closing this chapter, it will be necessary to say a 
 few words on a form of renal disease closely resembling true 
 primary Interstitial Nephritis, namely, that increase in the 
 fibrous stroma sometimes seen in the later stages of chronic 
 parenchymatous inflammation, and consequent on a secondary 
 irritation of the connective tissue occasioned by the primary 
 intratubular affection. The clinical history of such cases, 
 and more especially the marked appearances of intratubular 
 change, together with the much less evident granularity of 
 
48 INTEESTITIAL NEPHRITIS. 
 
 the kidney surface, the less firm adhesion of the capsule, and 
 the much smaller amount of fibrous increase, alike concur to 
 separate this condition from that consequent on true primary 
 interstitial inflammation. This secondary fibrosis has been 
 well described by Dr Grainger Stewart in. his treatise on 
 Bright's Disease (Op: cit : 2nd Ed., p. 16), and great credit 
 is due to him for clearly establishing the distinction between 
 it and the true primary one; for while, on the one hand, 
 Johnson and his school have fallen into the manifest error of 
 regarding aU intertubular alterations as subordinate and 
 secondary to intratubular changes, we must be careful to guard 
 against rushing into the opposite extreme, by ascribing aU 
 intratubular changes to primary intertubular increase. In the 
 present treatise we shall not enter into a detailed account of 
 this secondary form, which belongs rather to the domain of 
 the parenchymatous inflammation upon which it is conse- 
 quent ; but shall refer our readers meantime to Dr Stewart's 
 description in the second edition of his work; also to a 
 discussion on Bright's Disease, held during the forty-first annual 
 meeting of the Brit. Med. Assoc, (see Brit. Med. Jour. 
 Sept. 6, 1873), in which Dr Grainger Stewart again affirms 
 and expounds his views on this subject. 
 
 We may shortly summarise the contents of the preceding 
 chapter as follows : — 
 
 1. The "small red granular," "cirrhotic," "interstitial," 
 
 or " gouty " kidney, is the result of a true interstitial 
 inflammation, attended with increase of the normal 
 stroma, owing to the formation of a tissue composed 
 of indifferent or embryonic cells, which new tissue is 
 presently transformed into more or less completely 
 developed fibrous tissue. 
 
 2. For descriptive purposes, two stages may be distinguished 
 
 in the history of the morbid process — i.e. (1.) a 
 stage of Cell-Infiltration ; and (2.) a stage of Cell- 
 Transformation. 
 
 .3. The original lesion is essentially intertubular, and all 
 subsequent intratubular changes are secondary to, and 
 consequent on, the primary intertubular change. 
 
 4. The adventitia of the renal arterioles is not at first 
 hypertrophied, but may subsequently become so 
 by an extension to it of the hyperplastic process 
 afiecting the connective tissue, which normally 
 
DR GEOEGE JOHNSON'S VIEWS. 49 
 
 accompanies, and is distributed with, the vessels. 
 (See Plate ix.) 
 
 5. The tunica media of the renal arteries is hypertrophied, 
 
 sometimes greatly ; the hypertrophy being probably 
 due to true muscular increase. Sometimes, however, 
 this coat is atrophied. 
 
 6. The tunica intima of the arterioles is frequently 
 
 thickened and proliferated, the increase being of 
 the same nature as that described by Heubner under 
 the name of " Aiteriitis Obliterans," and by Thoma as 
 Fibrous Endarteriitis. 
 
 7. The already familiar designation, "Interstitial Nephritis," 
 
 is pathologically correct, and fulfils all the require- 
 ments of an accurate and scientific terminology. 
 
 CHAPTEE VII. 
 
 DR GEOEGE JOHNSOn's VIEWS. 
 
 " I FIND myself once more called upon," remarks Dr John- 
 son iu a paper published iu the Pathological Society's Trans- 
 actions, 1877, page 389, "to maiutaia'that the small red granular 
 kidney is not the result primarily and essentially of an iuter- 
 stitial nephritis, or of an arterio-capiUaiy, or any other form 
 
 of fibrosis, as Sir W. Gull and others believe I 
 
 still maintain the view that the primary and essential changes 
 in this form of renal degeneration are intratubulai, and con- 
 sist of degeneration and disiategration of the granular 
 epithelium.". . . . He quotes Drs "Wilks and Moxon, who 
 say (see Op : cit : page 509) : " Some authors, especially Dr 
 Dickinson, describe an iucrease of fibrous tissue. We think 
 there is a little increase round the vessels, but not much. 
 The patches, apparently of fibrous tissue, figured in Dr Dickin- 
 son's excellent drawings we have always seen, but high powers 
 resolve these patches into the remains of tubes, as indeed 
 would probably follow from consideration of the drawings 
 themselves We have found that a fibrillated condi- 
 tion prevails in the tube walls, which become coarse looking ; 
 but all large patches of apparent fibre we have always 
 found to be chiefly made up of apparently wasted tubes." 
 
 £) 
 
50 INTERSTITIAL NEPHRITIS. 
 
 Dr Johnson goes on to state that this is the opinion which 
 he maiatained in 1847 (see Med. Ghir. Trans., vol. xxx., On 
 the Inflamrtiatory Diseases of the Kidney ; see also paper by 
 Mr Simon, in the same volume), and which he has subsequently 
 seen no reason to alter, .save that in his paper in the 33rd vol. 
 Med Ghir. Trans., he made mention for the first time of the 
 fact of the muscular hypertrophy of the arterioles. We have 
 quoted Dr Johnson's own words as given in the report of the 
 Pathological Society's Transactions, in order to avoid aU chance 
 of misrepresenting or overcolouriug his ideas. 
 
 In our former Chapter on Granulation Tissue we noticed 
 the identity of the interstitial process with that which pro- 
 vides for the repair and healing of wounds. This we shall not 
 again discuss. When Drs Wilks and Moxon admit that there 
 is a little increase of fibrous tissue around the vessels, they admit 
 a fact glaring and patent ; for the increase is oftentimes not a 
 little, but goes as far as the formation of patches or oases of 
 coarse unmistakeable fibres. (See Plate ix.) But let us 
 not be misunderstood ; — ^by this admission we afford no sup- 
 port to Sir W. GuU. and Dr Sutton's theory of Arterio- 
 Capillary Fibrosis ; for it is not the adventitia of the arterioles, 
 but the connective tissue distributed with them, which is thus 
 hypertrophied. (See Thoma, Virch. Arch., Band 71, Heft i.)* 
 In three situations, as before mentioned, fibrillation is most 
 conspicuous; namely, around the vessels, external to their 
 adventitia, — in Bowman's capsules, and around wasted tubules 
 (Klebs, Traube, Virchow, Thoma, and Dr Eingrose Atkins, 
 Brit. Med. Jour., April 3, 1875) ; but it is not absent else- 
 where — far from it. Neither is the fibrous appearance due 
 merely to the shrinking of the connective tissue normally 
 present, for reasons which we have already discussed. 
 
 On page 390 of the Pathological Society's Transactions, 
 1877, Dr Johnson gives a detailed account of his interpretation 
 of the appearances met with in the small red granular kidney. 
 To that account, as the latest exposition of his views, the 
 author wiU now refer. In it he affirms that " the primary 
 and essential change consists in disintegration and destruc- 
 tion of the glandular epithelium of the convoluted tubules." 
 Here again we arrive at a direct conflict of evidence, and who 
 
 * Thoma says — "Es liegt somit offenbar eiue pathologisohe Bind- 
 gewebsneubildung vor, welche zuerst weich und zellreich, spater derb 
 und narbig wird, und sich im Ganzen der Gefassverzweigung anscLIiesst. 
 
DR GEORGE JOHNSON'S VIEWS. 51 
 
 shall decide 1 "We shall not convince Dr Johnson, neither 
 will Dr Johnson, with the evidence on which he at present 
 relies, succeed in convincing us. As to the state of the 
 epithelium in the early stages, the present writer is entirely 
 at one with Dr Dickinson. (Thoma also, Virchow Arch., 
 Band 71, Heft ii., page 47, says, — "Nirgends zeigen die 
 Epithelbekleidungen in uncomplicirten Fallen selbstandige 
 Erkrankung, weder im Bereiche der bindgewebigen Wucher- 
 ungen, noch auch in den relativ intact gebliebenen Abschnit- 
 ten der Einde.") Dr Johnson says the tubes are filled and 
 rendered opaque. (See also page 219, Johnson on Kidney 
 Diseases, 1st ed.) This is precisely what they are normally. 
 If they present much appearance of lumen, it is owing to 
 falling out of the epithelium. Cut a small section of fresh 
 normal kidney, not too thin ; place it directly on a slide 
 without washing it, and examine with Hartnack oc. 3 x 
 obj. 7 ; or, in spite of its having been washed, take any 
 characteristic normal specimen (not too thin a one, as these 
 part with their epithelium^ more readUy,) and examine it 
 with the same power. This will show what is, or is not, 
 the typical appearance of healthy convoluted tubules. The 
 kidney which furnished one of the author's Iformal Series 
 was in all respects typically healthy, being that of a strong 
 male adult kOed by accident, and in this kidney the opacity 
 of the tubules was constant. The tubules of the kidneys of 
 healthy cats, are also uniformly opaque. "Other tubes," 
 says Dr Johnson, " are more or less completely denuded of 
 epithelium, a few granular particles only adhering to the 
 inner surface of the basement membrane." Perfectly cor- 
 rect ; but this is a secondary change, consequent. - on the 
 presence and pressure of the increased interstitial tissue. 
 " In some tubes," pursues Dr Johnson, " the normal epithe- 
 lium is replaced by a lining of delicate transparent rounded 
 cells, each with a single nucleus." (See also Brit. Med. Jour., 
 Feb. 15,, 1873.) The author has observed these " ceUs," 
 but he has seldom observed the fact of their nuoleation. If 
 nucleated, as they are sometimes, though rarely, they are 
 lymphoid cells which have escaped into the tubules via, the 
 capillary loops of the glomeruli. Such are more frequently 
 seen inside the tubtdes, in that variety of Interstitial 
 Nephritis which more especially affects the glomeruli. (See 
 Chapter on Glomerulo-Nephritis. See also Art. by Dr Klein, 
 Pathological Society's Transactions, 1877, page 436.) The 
 
52 INTEESTITIAL NEPHRITIS. 
 
 presence in quantity of these lymphoid cells in the tuhules 
 ■would he very likely to give rise to secondary intratuhular 
 changes, such as compression, loosening, and shedding of 
 epithelium. Dr Johnson may, of course, state in return that 
 their presence is due to a primary intratuhular epithelial 
 change ; hut in that case we should expect to find the epithe- 
 lium in much the same condition as in parenchymatous - 
 nephritis. Dr Johnson may, perhaps, maintain that it is so ; 
 hut we cannot give in our adhesion to such a doctrine. Mor^ 
 frequently these " cells " are, in reality, not cells al aU, heing 
 nothing more nor less than the nuclei of the cells of the 
 tubular epithelium, which, heing more persistent than the 
 other cell-constituents, remain after the secondary intra- 
 tuhular changes have caused the disappearance of the 
 epithelial ceU-wall and protoplasm. 
 
 Again; Why is it that cysts are so frequent in the 
 small red granular kidney, and so infrequent as a conse- 
 quence of Parenchymatous Nephritis, either acute or chronic, 
 where the intratuhular changes are undoubted ? Why should 
 one form more than another of intratuhular change lead to 
 cystic formation and dilatation of the tuhules? On the 
 hypothesis of intertuhular increase the presence of these 
 cysts is easily accounted for ; but how does Dr Johnson 
 account for it 1 Let us see what his paper says : — " The 
 explanation of the cyst formation is probably to he found in 
 the fact that some tubes continue to secrete an aqueous fluid 
 while their lower portions are plugged by accumulated 
 epithelial dSbris, and thus they become distended by their 
 own secretion" (Pathological Society's Transactions, 1877, 
 p. 399). According to this explanation, cystic formation 
 should be at least as common in the parenchymatous, as 
 in the interstitial form of inflammation. But is it so ? The 
 answer is not far to seek. Except in cases where chronic 
 intratuhular changes have induced a secondary interstitial 
 nephritis, examples of cystic change in the tubules are merely 
 accidental. 
 
 Dr Johnson says that the phenomena, as described by him, 
 are caused by the irritation of the renal structures, owing to 
 the circulation through them of some blood poison, such as 
 those of gout, rheumatism, alcoholism, lead-poisoning, and 
 chronic dyspepsia (to which the present author, in accord- 
 ance with Dr Bristowe, would add syphilis). This irrita- 
 tion, he says, soon destroys the delicate epithelium, while 
 
DE GEORGE JOHNSON'S VIEWS. 53 
 
 the basement membrane of the tubules, the capillaries, etc., 
 remain much, longer, in accordance with the law of "the 
 survival of the toughest." The author agrees with Dr 
 Johnson as to the blood poison (that is, in cases of bi-lateral 
 Interstitial E"ephritis), but differs from him altogether as to 
 its effects on the kidney structures. The irritation being 
 chronic, and not very intense, is just as likely to give rise 
 to interstitial as to intratubular change. The nature, of the 
 irritation, then, affords no argument for Dr Johnson's theory, 
 though it ' may, perhaps, by its chronic character, furnish a 
 slight presumption against it. " In some parts,',' pursues 
 Dr Johnson, " the basement membrane and the Malpighian 
 capsules appear to be thickened, and assume a fibrous texture, 
 so that an examination of the granular kidney without 
 reference to the normal structure, and especially to the 
 appearance of the fibrous network which is seen on examina- 
 tion of a normal kidney after washing away the gland cells, 
 might lead to the belief that the tubes are surrounded by an 
 abnormal fibrous tissue." Of course, after the gland cells 
 are washed away, there remains a " fibrous network " in the 
 normal organ ; but a large proportion of this network con- 
 sists in the natural condition of vessels only, as is seen 
 on examination of carefully injected specimens. It is well 
 known that Dr Johnson's "fibrous network" — that is 
 to say, speaking roughly, one-tenth part fibre and nine- 
 tenths vessels, exists between the tubules of the normal 
 kidney ; but now comes the question. If this fibro-vascular 
 stroma be found in the smaU red granular kidney, as it 
 very commonly is, increased to four or five times its natural 
 dimensions, where is the argument in favour of Dr Johnson's 
 conclusion afforded by its existence in normal quantity in 
 the normal organ? Dr Johnson ought not to be content 
 with washing the gland cells from a section of healthy 
 kidney ; let him take also an advanced shrunken and 
 granular kidney in the second stage of Interstitial Ne- 
 phritis, and wash them out of this also, and then put the 
 specimens side by side under two microscopes; when, in spite 
 of the superior vascularity of the former, he will find the 
 " fibrous network " far more abundant, in the nephritic. As 
 to the basement membrane and Malpighian capsules " appear- 
 ing " to be thickened, they "appear" to be so much in the 
 same manner as the sim appears to shine, or as day and night 
 appear to an unprejudiced and minute observer to succeed 
 
54 INTERSTITIAL NEPHRITIS. 
 
 each other. Dr Johnson proceeds — " The remarkable 
 changes -within the uriniferous tubes receive no explanation 
 from the theory in question {i.e., the theory of an Intersti- 
 tial Nephritis). They are, therefore, left unheeded, and, of 
 course unaccounted for." The author trusts that, should the 
 present essay ever come under the eyes of Dr Johnson, that 
 renowned pathologist will have no cause to complain of the 
 question of iutratubular changes being shirked or slurred 
 over ; for, according to the best of his ability, he has not left 
 these changes either unheeded or unaccounted for, but has 
 striven to show that they are explicable in a more easy and 
 consistent manner, on the theory of increase of the fibrous 
 stroma, than on that of primary intratubular inflammation. 
 
 Dr Johnson now proceeds to point out a " few amongst 
 the insuperable objections to the theory of interstitial 
 fibrosis, which is so confidently maintained by some 
 pathologists." The first of these is the red colour of the 
 granular kidney. This is held to be "quite inconsistent 
 with the doctrine of intertubular deposit, which must 
 inevitably obliterate the capDlaries, and render the cortex 
 more or less pale and anaemic." To teU the truth, this does 
 not sound very insuperable ; for the contracted kidney of 
 Interstitial Nephritis is oftener pale and red. Thoma, VircJi. 
 Arch., Band 71, Heft 1, says: — "Die Farbe des Organes 
 schwankt je nach dem verschiedenen Blutgehalte von einen 
 schmutzigen "Weissgrau, bis zu blassrothen und matt dun- 
 kebothen Schattirungen." If red, the colour is due to passive 
 congestion; but so frequently is it pale and anaemic, that in 
 the description in Chapter VI., paleness has been stated as the 
 rule, and redness as the exception. But Dr Johnson assumes 
 that an intertubular deposit must have an obliterating 
 influence on the iatertubular capillaries, vastly in excess 
 of that which the author is disposed to allow or ascribe to 
 it. He compares the anEemia which would result from such 
 a deposit, to that "visible over a circumscribed spot, when 
 arteries and capiUaiies are obstructed by embolic patches of 
 fibrin." But surely it is one thing to plug up an artery 
 completely, and another to exercise pressure upon its outside, 
 — ^pressure which it is quite unwarrantable to assume to be 
 severe enough to cause immediate and total occlusion. 
 Such anaemia, he says, is visible in the large white kidney. 
 Surely not. Otherwise, if at aU comparable to that induced 
 over a limited tract by an embolism, it would, by affecting 
 
DR GEORGE JOHNSON'S VIEWS. 55 
 
 the whole kidney, produce not anaemia, hut gangrene. 
 Again, he_ says that we should expect fatty transformation 
 of the epithelium, consequent on the pressure of the inter- 
 tuhular deposit. "Why fatty and not colloid 1 Degeneration 
 of some kind we should both expect, and do actually meet 
 with; hut the author quite fails to see why it must of 
 necessity be fatty. He agrees with Dr Johnson in saying 
 that fatty intratubulai change, consequent on Interstitial 
 Nephritis, is comparatively rare, but he accepts in its stead 
 the extensive colloid transformation, which Dr Johnson has 
 "left unheeded, and, of course, unaccounted for." There 
 are also changes of a disintegrative nature, which point 
 to a loosening of the attachment of the epithelium to the 
 basement membrane, and compression of the cells one 
 against another in the narrowed tubules; and presently we 
 find a stage in which the tubules are in parts altogether 
 denuded of theic lining. There is no need to go over again 
 in this place the history of changes which we have before 
 minutely particularised; suffice it to say, that these changes 
 are quite consistent with the hypothesis of interstitial 
 increase. 
 
 The next "insuperable objection" is the following : — " On 
 examining a section of the kidney, the characteristic tntra- 
 tubular changes may often be seen in various stages of pro- 
 gress, whUe the intertubular capillaries surrounding these 
 morbidly changed tubes are injected with blood, and evi- 
 dently quite normal." Here again Dr Johnson is assuming 
 complete circulatory arrest as a consequence of intertubular 
 deposit. The consequence, we repeat, of such complete 
 arrest would be gangrene. Indeed, the author does not be- 
 lieve in the complete stoppage of the circulation, even in the 
 very small capOaries, during the first stage of cell-infiltration. 
 ■He could even conceive, as he has before hinted, the forma- 
 tion at first of new vessels for the nourishment of the exuded 
 mass of lymphoid cells. T^e process of vascular obliteration 
 takes place in the stage of ceU-transformation and shrinking 
 of the kidney, not in that of cell-infiltration and enlargement. 
 But we have yet to account for the fact of the intratubular 
 changes being seen " in various stages of progress, while the 
 intertubular capillaries surrounding these morbidly changed 
 tubes, are injected with blood, and evidently quite normal." 
 Pirst of all, then, the author diflfers from Dr Johnson on the 
 question of facts. "Where the intertubular changes are most 
 
56 INTERSTITIAL NEPHRITIS. 
 
 marked, there he has likewise remarked the consequent 
 intratuhular alterations : hut where the intertuhular changes 
 have been iasignificant or ahsent, there^ he has, he may say 
 invariably, found the intratuhular structures normal also. 
 But even granting Dr Johnson's statement, is there no 
 way of accounting for inttatubular change as consequent 
 upon interstitial iifiammation, even though the parts in the 
 immediate neighbourhood of. the tubule maybe comparatively 
 normal? Already in this chapter we have mentioned the 
 occasional presence of leucocytes in the tubules. May not 
 their presence be sufficient to account for the occasional 
 occurrence of this phenomenon 1 The escape of blood into 
 a tubule from actual rupture of the capillaries of a glomeru- 
 lus connected with.it, might also produce the appearance, or 
 even the reality, of intratuhular change. 
 
 The fact that interstitial changes may be induced in 
 a kidney by obstruction of its ureter, appears to thb 
 author to be a fact of no significance either way, though 
 mentioned by Dr Johnson in the above-quoted article in 
 support of his own theory. Subacute or chronic irritation 
 from any cause may induce interstitial inflammation; and 
 to the author it seems a matter of little moment whether 
 this irritation arise from a blood poison or from a local 
 cause. 
 
 While entirely agreeing with Dr Johnson, as to the 
 hypertrophy of the muscular coat of the arterioles, the author 
 differs from him on an anatomical point respecting the 
 structure of this coat. On page 114 Med. Chir. Trans., vol. 
 xxxiii. ; on pp. 149,. 150, Med. Qhir. Trans.,Mo\. Ivi. ; and on 
 page 384 Path. Soc's Trans., 1877, in criticising a drawing 
 of Sir "WUliam Gull and Dr Sutton's {Med. Chir. Trans., vol. 
 Iv., plate vi., fig. 7), he avers that the muscular coat consists 
 of two layers, an inner longitudinal, and an outer circular. 
 This statement is at variance with , aU modem anatomical 
 teaching, and contrary to the results of the present author's 
 investigations. Of the curious drawing criticised by Dr 
 Johnson we shall have occasion to speak in the ensuing 
 chapter, so that we shall pass it by for the present. But the 
 author believes, in common with all accepted anatomical 
 authorities, that the muscular coat of the arterioles is arranged 
 in hut one direction, and that a circular one (See Klein, Path. 
 Soc's. Trans., 1877, pages 433-4) ; and of the hypertrophy 
 of this circular layer there is, in his opinion, ample and 
 
DR GEOKGE JOHNSON'S VIEWS. 57 
 
 conTinciag evidence. What Dr Johnson terms the inner 
 longitudinal muscular layer, is probably nothing more than 
 the intima thickened by Endoarteritis Obliterans. Such, at 
 any rate, must have been the case in the arteriole figured on 
 page 114 Med. Ghir. Trans., vol. xxxiii. 
 
 The author has seen the appearance of hypertrophy of the 
 muscular coat in arterioles taken from the tongue of a cat ; 
 but he is quite ignorant of the state of this animal's 
 kidneys. 
 
 With regard to the view that the muscular hypertrophy is 
 simply the result of fost mortem contraction of the muscle 
 cells, ■while perfectly convinced in his own mind that no 
 amount of contraction coidd produce so marked an appear- 
 ance of thickening, it was the author's intention to perform a 
 series of experiments which he was in hopes Would con- 
 clusively settle the/ question. It was his purpose to ascertain 
 the amount of apparent thickening, if any, of the tunica 
 media in the arteries of animals poisoned both by a single 
 large dose, and by a succession of small doses of some drug 
 causing contraction of the arterioles, such, for instance, as 
 ergot. Unfortimately, however, for the completeness of his 
 researches, they had not reached this stage before the passing 
 of the recent prohibitory enactments, so that he was presently 
 compelled to apply to the Home Secretary for a licence 
 authorising him to proceed. This was curtly and peremptorily 
 refused, without the ' assignment of the smallest reason. If, 
 however, it be a consolation to have companions in rnisfortune, 
 the author was soon able to avail himself of this sorry crumb 
 of comfort ; for he speedily learnt that he was but one out of 
 many sufferers from a piece of legislation, which if it continue 
 to be enforced, will have the effect of so retarding the flood 
 of scientific progress in this country, that in the course of a 
 decade or so, our legislators may proudly reflect upon the 
 fact that during that period the world has been preserved 
 from some hundreds of useful discoveries, and the march of. 
 intellect in these islands retarded not a little by the ingenious 
 disposition of a very formidable and effectual stumbling- 
 block, planted in the way of the pioneers of knowledge and 
 humanity by a Government which, despite its pretended 
 oligarchical tendencies, has proved itself but too ready to hand 
 over the control of the educated few to the ignorant many, 
 and to purchase evanescent popularity at the price of lasting 
 f oUy. Truly, if the intellect of the nation is to be thus hedged 
 
58 INTERSTITIAL NEPHKITIS. 
 
 about ■with, contumelious restrictions, we shall come at last 
 to echo the dreary dictum of Sophocles — 
 
 Iv T(j) <j)poveiv yhp fji,rj8ev ijSio-tos /8ios 
 
 Ajax. 654. 
 'Tis a happy thing to be a numskull. 
 
 Metaphorically speaking, a dose of Curara has heen given to 
 British Science, and its limhs, formerly so active, now hang 
 paralysed and useless. Better paralyse the legs of a frog than 
 the brains of a nation. But we digress somewhat. 
 
 On page 107, Med. Chir. Trans., vol. xxxiii., Dr Johnson 
 makes the curious statement that, as a consequence of the 
 destruction of the gland cells, and arrest of the process of 
 secretion, oil globules collect in the interior of those blood- 
 vessels in which the circulation has ceased. Such a collection 
 of oil globules the author has never seen, nor is he without 
 grave doubts as to its even occasional existence ; for, in spite 
 of the constant use of osmic acid, he has in no single instance 
 detected any sign of intravascular fatty change. The 
 condition has, however, been mentioned by other authors. Dr 
 Galabin (On the Connection of Bright' s Disease with Changes 
 in the Vascular System) says (page 14), "As to the state of 
 the capillaries or minutest arterioles, I have found a granular 
 or apparently fatty condition common in cases of granular 
 kidney." He does not say in what situation, whether 
 inside the lumen, or in the coats ; and the present writer 
 thinks it not improbable that the numerically increased 
 muscular nuclei of the tunica media may have been mistaken 
 by Dr Galabin for fatty granules, — an error not quite so 
 impossible as might at &st sight appear. Sir W. GuU and Dr 
 Sutton (Med. Chir. Trans., vol. Iv., page 281) describe groups 
 of fat granules aggregated together in the walls of the smaller 
 arterioles of the pia mater. Todd also {Clin. Lect. on 
 Diseases of the Urinary Organs, 1857, Lect. 4, page 109,) 
 says that the canals of the minute afferent arteries of the 
 Malpighian bodies are sometimes blocked with oil. Never- 
 theless, we suspect that with the improved methods of 
 microscopical observation now becoming general, the discovery 
 of oil in the vessels of interstitial kidneys will become less 
 frequent day by day. 
 
VIEWS OF SIE "WILLIAM GULL AND DE SUTTON. 59 
 CHAPTEE VIII. 
 
 VIEWS OF SIE WILLIAM GULL AND DR SUTTON. 
 
 In the fifty-fifth volume of the Medico-GMrurgical Trans- 
 actions, Sir "W. GruU and Dr Sutton first published their 
 now well-known paper, on " Aiterio-CapiUary Fibrosis," a 
 supposed general morbid state of the vascular system, of 
 which, as they maintain, the lesions, occurring in Interstitial 
 Nephritis are but part and parcel. "We quote verbatim from 
 this paper the following summary of the results of their 
 investigations. {Med. Ghir. Trans., vol. Iv., page 283.) 
 " (1) That the arterioles throughout the body, in that con- 
 dition usually called Chronic Bright's Disease with 
 contracted kidney, are more or less altered. 
 "(2) That this alteration is due to a 'hyalin- fibroid' 
 formation in the walls of the minute arteries, and ' a 
 hyalin-granular ' change in the corresponding capil- 
 laries. 
 " (3) That this change occurs chiefly outside the muscular 
 layer, but also in the tunica intima of some arterioles. 
 " (4) That the degree in which the affected vessels are 
 altered, and the extent to which the morbid change 
 is diffused over the vascular system in different 
 organs, varies much in different cases. 
 " (5) That the muscular layer of the affected vessels is 
 often atrophied in a variable degree. 
 " These facts show that there is a morbid state in which 
 the kidneys are contracted, the heart hypertrophied, and the 
 minute arteries and capillaries altered by a hyahn-fibroid 
 formation. Further, that the kidney changes are often, but 
 not always, a part and parcel of this morbid state. The 
 absence of such lesions of the kidneys proves that they do 
 not constitute an essential and indispensable part of the 
 general process." (Page 286.) 
 
 "We wiU further allow Drs GuU and Sutton to describe 
 the "hyalin-fibroid" substance in their own words. "A 
 fine hyalin or hyalin-fibroid substance was seen between the 
 convoluted tubules, which made the tubules appear wider 
 a^art than normal. In some parts this substance had a 
 homogeneous appearance ; in others it had a striated or fibroid 
 
60 INTEESTITIAL NEPHKITIS. 
 
 appearance, like a network, and contained minute indis- 
 tinct nuclei (1) ; and in others it had a coarser and more 
 defined fibre-like character. This substance was seen in con- 
 siderable quantity round the Malpighian bodies, and in stiU 
 greater amount in and around the walls of the minute arteries.' 
 (Page 274.) 
 
 In the first place we would ask attention to the fact that 
 the foregoing description of hyalin-fibroid substance answers 
 alniost equally weU. for granulation tissue : and, in point of fact 
 it is simply and solely the granulation-tissue deposit between 
 the convoluted tubules, to which Drs GuU and Sutton apply 
 the term of "hyalin-fibroid" substance. It is but an alteration 
 in name, and that.for the worse ; since such terms as "nuclear 
 tissue," "granulation" or "embryonic tissue," "smaU-cell 
 infiltration," " infiltration with lymphoid cells," and the like, 
 convey a correct notion of the pathology of the new formar 
 tion, whereas the appellation, " hyahn- fibroid substance," 
 points to an etiology which, as we shall presently see, is but 
 slightly corroborated by facts. Further, this " hyalin-fibroid " 
 alteration is said to be seen in the walls of the minute arteries, 
 outside the muscular layer, and also in the tunica intima of some 
 arterioles. In the earlier stages of granular contraction, Sir W. 
 Gull and Dr Sutton say (page 275), " In the walls of some of 
 the minute arteries, and also outside and around them, there 
 appears to be an excess of fibroid tissue, and the arteries, in 
 consequence, seem thicker than normal. In making this 
 observation, we are well aware that there is normally more or 
 less of areolar tissue around the minute renal arteries, there- 
 fore it is difficult with any degree of certai;nty to appreciate 
 any slight increase in such tissue, but after careful observa- 
 tion, it seemed to us that the outer coats of the arterioles, 
 even at this early stage, were thickened by increase of fibroid 
 tissue. The muscular tissue did not appear increased," 
 According to the present author's experience, the "areolar 
 tissue around the minute renal arteries " is the seat of smaU- 
 ceU infiltration at an early period in the history of Interstitial 
 IN'ephritis, as might be expected from the presence of the 
 lymphatic spaces before alluded to as demonstrated by 
 the injections of Ludwig. But as to the adventitia proper, 
 it is far otherwise. In a great number of instances it 
 remains normal and unthickened, even in very advanced 
 stages of granular contraction ; and if thickened at all, this 
 thickening is due to a secondary extension of the process of 
 
VIEWS OF SIR WILLIAM GULL AND DE SUTTON. 61 
 
 hypertrophy going on in the connective tissue surroTinding 
 it. This connective tissue is both early increased and early 
 fibrillated, and on casual observation might, perhaps, convey 
 the idea of thickening of the adventitia, though that coat 
 is distinctly visible as a narrow, dense, finely-fibriUated ring, 
 quite normal, and but loosely connected with its hypertro- 
 phied surroundings, as may be proved by picking it out 
 ■with needles. In the author's specimens, thickening of the 
 adventitia proper is only seen in a very few of the most 
 advanced ; and in these it is simply due, as just stated, to 
 an extension of the processes going on around. Primary 
 or early thickening of the adventitia, whether hyalin or 
 fibroid, the author has absolutely Tiemr seen ; hyalin changes 
 in the adventitia he has also never seen, if we except that 
 thickened and translucent appearance sometimes observed 
 in the loops of the glomerulus, which is probably the 
 harbinger of impending coUoid change. Fibroid thickening 
 of the adventitia he has only seen late in the disease, and 
 as a secondary consequence. He does not, however, in the 
 least impugn the absolute correctness of the description 
 given by Sir "W. GuU and Dr Sutton of the appearances 
 seen by them in their own specimens; though he is per- 
 suaded that if such a state of matters as that described by 
 them is visible in their preparations, it is simply owing, as 
 stated by Dr Johnson {Med. Chir. Trans., vol. Ivi.), to the 
 methods of manipulation and mounting to which they were 
 subjected. Sir W. GuU and Dr Sutton admit that their 
 specimens were not mounted by themselves, but by an 
 assistant ; and they coidd therefore have had no opportunities 
 of observing any changes which might ensue in consequence 
 of the use of reagents and mounting fluids. ItTow, certain 
 mounting media, especially glycerine, are very prone to alter 
 specimens preserved in them. Dr Galabin {Ou the Connection 
 (^ Bright' s Disease with Changes in the Vascular System, -pa.ge,s 
 13 and 14), and also, to some extent, Dr Grainger Stewart {Brit. 
 Med. Jour., Kov. 15, 1873) confirm Dr Johnson's statements 
 as to its untrustworthy character, especially if acidulated. 
 These allegations the author has verified, and he thoroughly 
 concurs in the condemnation of pure glycerine as a mounting 
 medium. "WeU-made Farrant's solution, and Eimmingt6n!s 
 glycerine jelly, though both containing glycerine in some 
 form or other, are free from these objections. Arteries of the 
 pid mater, moimted in glycerine alone, or in glycerine and 
 
62 INTERSTITIAL NEPHRITIS. 
 
 camphor water (the fluids used for the preparation of Drs 
 Gull and Sutton's specimens), rapidly present appearances of 
 hyalin change, and still more so if acetic acid be added. 
 With care and pains also, " hyalin-fibroid substance " may be 
 largely manufactured in the kidney ; that is to say, if the 
 specimen has not been hardened in chromic acid, ■which seems 
 inimical to its development. Fresh kidney, mounted in 
 acetic acid and glycerine, readily assumes this guise ; kidney 
 hardened in bichromate solution or Muller's fluid less readily, 
 though the author has had' some success, even with specimens 
 so treated. 
 
 Plate X. represents an instance of these factitious changes. 
 The vessel there 'figured was taken from a normal kidney 
 hardened in Miiller's fluid, and was itself normal before 
 undergoing the following treatment. First of all it was 
 stained late in the afternoon in ^ per cent, solution of 
 osmic acid, and then allowed to remain all night in a bowl 
 of clean water. On examination in the morning it appeared 
 quite natural, under both low and high powers. It was 
 then spread out upon a shde, and covered with glycerine 
 acidulated with a drop or two of 1 to 8 solution of acetic 
 acid. After remaining thus for about two hours, a cover 
 glass was placed on it, when, upon, renewed examination, it 
 presented the remarkable appearances given in the woodcut. 
 From this it wUl be seen that no distinct muscular coat and 
 and no intima are distinguishable. The wall, whose thick- 
 ness is very irregular, is apparently composed of "hyalin- 
 fibroid" material, surrounded by a somewhat denser ring 
 representing the adventitia proper. Around this is some 
 connective-tissue, pretty normal in general appearance, though 
 rather "hyaline," and swollen to nearly twice its original 
 proportions. Curiously enough, close to this strangely 
 metamorphosed artery was another and' smaller one much 
 less altered ; for though its wall appeared nearly homogeneous 
 from blending together of its coats, it was not swelled out 
 like that of its neighbour, thus aflfording a striking example 
 of the capriciousness of these spurious appearances. On 
 comparing Plate x. with two of Sir W. Gull and Dr Sutton's 
 drawings (Figs. 6 and 4, plate vi. Med. Chir. Trans., 
 vol. Iv.) a close resemblance vdll be observed, more 
 especially in the case of Fig. 6, which represents an arteriole 
 from the muscular tissue of the heart greatly thickened by 
 fibroid material. In Fig. 4, the globular bodies inside the 
 
VIEWS OF SIE WILLIAM GULL AND DK SUTTON. 63 
 
 arterioles are puzzling, though they may possibly merely 
 represent swellings of the intima caused hy the glycerine. 
 
 The author has never seen anything exactly like the 
 arteriole in Fig. 7 of the same Plate, though three more 
 or less feasible conjectures might be hazarded as to its 
 nature. Thus, it might either represent an artery with 
 thickened media and intima, the adventitia from some cause 
 being left unfigured ; or, an artery with thickened intima, 
 the outer and middle coats being confused by the glycerine ; 
 or, lastly, the glycerine may have confused the middle and 
 inner coats, while greatly swelling out and distending the 
 external one. However this may be, it is at least certain 
 that glycerine tends to render the three arterial tunics 
 separately indistinguishable. 
 
 Were it permitted us, we should recommend future 
 observers to harden their specimens of kidney in chromic 
 acid of the strength of 1 part to 400, letting them remain 
 in this fl-uid at least four weeks ; a preliminary sojourn in 
 Muller's fluid of about three weeks' duration being advisable, 
 especially if the pieces of tissue are large. Let them then 
 be cut in the freezing microtome, a strong solution of gum 
 being used for imbedding. Before cutting, they should 
 remain for a night in plenty of clean water, to allow the 
 chromic acid to soak out. After cutting, let them be mounted, 
 not in glyceriae, but in thick Parrant, prepared with strong 
 gum solution, or in good glycerine jelly, such as Eimming- 
 ton's. They wUl then pass through the ordeal unchanged, 
 and give their testimony in a trustworthy manner. Should 
 Drs Gull and Sutton thus treat their next series, we venture 
 to predict that it will not prove rich in " hyalin-fibroid " 
 material. 
 
 Mr D. J. Hamilton, Pathologist to the Eoyal Infijcmary, 
 Edinburgh, who had an opportunity of inspecting Drs Gull 
 and Sutton's specimens, once told the present author that 
 there appeared to be nearly as much " hyalin-fibroid " 
 material in the healthy as in the abnormal ones. Of this we 
 have no doubt ; for normal arteries mounted in glycerine often 
 present very much the same appearances as diseased ones. 
 
 Plate V,, fig. 1, vol. Iv., Med. Chir. Trans., represents some 
 Malpighian bodies, as seen by Sic "W. Gull and Dr Sutton. 
 Bowman's capsule is with perfect correctness represented as 
 thickened and fibrous; but in place of the glomerulus, a 
 number of " fat and other granules " are figured in the 
 
64 INTERSTITIAL NEPHEITIS. 
 
 drawing. The author has never seen such an appearance in 
 any specimen examined by him. Some of the " fat 
 granules" remind him somewhat of the nuclei visible in 
 the same situation in Glomerulo-Nephritis ; but altogether 
 this drawing is nearly as puzzling as that of the arteriole. 
 
 Lebert {TraiU d'Anat. Path.) says, referring to the 
 atrophic form of Bright's Disease, " les capsules de malpihgi 
 sont remplies de gouttelettes de graisse " (vol. ii., p. 336), but 
 it is probable that his description refers to the atrophic or 
 third stage of parenchymatous inflammation. (See Dr Grainger 
 Stewart's work already cited, 2d. ed., page 16.) The author 
 would not say that a glomerulus never becomes fatty in 
 ordinary uncomplicated Interstitial Ifephritis; but he can 
 affirm unhesitatingly that among hundreds of specimens he 
 has never seen one so changed. Was there any parenchy- 
 matous nephritis in the kidney which furnished the 
 drawing? We conclude not, as Drs Gull and Sutton 
 make no mention of it. The kidney was from the body of a 
 girl nine years old, an unusual, though not unprecedentedly 
 early age for interstitial changes ; for Dr Barlow {Lancet, Aug. 
 1st and 8th, 1874) records a case of granular kidneys, with 
 hypertrophied heart, in a child five years and eleven months 
 old. On the contrary, out of 79 cases collected by Dr 
 Galabin from the post mortem records of Guy's Hospital 
 during the four years 1869-72, there was none younger than 
 ten years. Perhaps the case may be one of those secondary 
 fibrotic ones described by Dr Stewart. Or, again, the 
 irrepressible glycerine may be responsible for the "fat 
 granules ; " for the appearance of the glomeruli, in sections 
 mounted in glycerine, especially if the vascular loops contaia 
 blood cells, is often not a little curious. 
 
 On page 177 {op. jam. cit.) Sir W. Gull and Dr Sutton 
 attribute the granularity of normal renal epithelium to 
 mechanical congestion, and consider it as a sort of post-mortem 
 phenomenon. It is, however, equally evident in the kidneys 
 of cats rapidly bled to death by cutting the throat, or by 
 complete decapitation; though in such specimens post- 
 mortem or directly ante-movtem congestion is, from the 
 manner of death, impossible. The conclusion, therefore, 
 appears inevitable, that granularity is the natural and typical 
 condition, though it may, 'of course, be indefinitely exagge- 
 rated as the result of disease. Still the noribal granular 
 appearance shotdd always be remembered in estimating the 
 
V1J4WS ui>' am william gull and dk button do 
 
 normal or abnormal nature of the granularity of epithelium 
 in any given kidney. 
 
 In the present monograph, the author is not prepared to 
 follow Drs GuE and Sutton into their elaborate paper on 
 " Aiterio-CapiUary Fibrosis " in the spinal cord. (Path. Soc's. 
 Trans., 1877.) Should he have the opportunity, he wiR 
 gladly do so at some future period; nor is he altogether 
 unprepared to begin the prosecution of such investigations ; 
 though, up to tMs time, material to work upon has been 
 entirely wanting. Yet, though diseased spinal cords have 
 found their way but very sparingly into the author's 
 hands ; though those winch he has hitherto possessed 
 have been as few and far between as angels' visits, 
 or as the currants in a confectioner's bun, there are a few 
 observations which, from his acquaiutance with the 
 normal structure of the cord, he may perhaps not 
 unwarrantably venture to make. Firstly, then, he begs 
 to congratulate Drs GuU and Sutton upon their enforced 
 abstiaence during this investigation from the use of the 
 staff of that broken reed -^ glycerine. Canada balsam, 
 is an excellent mounting medium for nervous tissues, and 
 only second, perhaps, to well-prepared Dammar fluid. In 
 either of these fluids, specimens may be mounted, with ordi- 
 nary care, without the least fear of adventitious change. 
 Secondly, he would aUude to the fact that in the cord, as 
 in the kidney, more or less connective tissue is distributed 
 with the vessels, which connective tissue cannot in any sense 
 be said to constitute then? adventitia. In interstitial inflam- 
 mations, it may be taken as a rule that the greatest increase 
 of connective tissue wiU be met with in those parts which 
 contain the most normally ; and, as a consequence, it is not 
 surprising, if as mentioned by Eindfleisch (Path. Hist, 8yd. 
 Soc's. Trans., vol. ii.), the foci of fibrous thickening in Inflam- 
 matory Induration of the cord present a red spot or line in 
 their centre, which is, in fact, a distended blood vessel. 
 But a connective -tissue inflammation cannot be said to be 
 an " Arterio-CapiUary Fibrosis," simply because the dis- 
 tribution of connective tissue in any given organ follows the 
 path of the blood vessels. 
 
 Rindfleisch, however, in speaking of Inflammatory Indurar 
 tion of the cord, says that the adventitia' of the vessels is made 
 up of concentric layers of round cells (op. cit., p. 350) ; and 
 he further states that the vessels are in a state which he 
 
m INTERSTITIAL NEPHKITIS 
 
 woTild not scruple elsewhere to call one of chronic inflamma- 
 tion. Drs Gull and Sutton (PatJi. Tram., 1877, p. 377) quote 
 this passage in support of their conclusions, for Eindfleisch's 
 Inflammatory Induration is, in their opinion, simply " Arterio- 
 Capillary Fibrosis," as seen in the cord. The statements of so 
 accurate an authority as Eiadfleisch must always have great 
 weight, especially when corroborated by the results embodied 
 by Drs Gull and Sutton in their careful and beautifully 
 illustrated paper. "We will not, therefore, attempt to deny 
 that the arteries, as also the capillaries of the cord, which 
 last have, as Strieker believes, a continuous layer of pro- 
 toplasm on their outer surface, are really involved in the 
 process of Inflammatory Induration. "What, however, we 
 entirely fail to see is, that this state of matters in the cord 
 has anything more than an incidental connection with the 
 very dissimilar kidney lesions. There is no condition of the 
 renal vessels analogous to this in Interstitial Nephritis. The 
 two pathological states appear to us to be quite different. 
 Assuming, with Eindfleisch, that the first anatomical element 
 of Inflammatory Induration, or, as Drs Gull and Sutton would 
 doubtless prefer to call it, " Arterio-Capillary Fibrosis " of the 
 cord, is to be recognised in alterations of " individual vascular 
 tufts," the present author can testify with a clear conscience to 
 the fact of no such alterations being visible in any of his speci- 
 mens of interstitial kidney. IsTever, under any circumstances, 
 has he seen the adventitia of the renal arterioles " made up 
 of concentric layers of round cells, often five deep." Thicken- 
 ing of the adventitia he has seen, but it was not the first 
 anatomical element of the disease, — no, nor the second, nor the 
 third, but a very late and entirely secondary one. As to the 
 influence of reagents in inducing an appearance of thickening 
 of the outer coat in the case of vessels from the pia mater, 
 Dr Grainger Stewart says (Brit. Med. Jour., Nov. 15, 1873), 
 " The conditions which I have observed are ... . first, a 
 more or less marked thickening of the coats of the small arteries. 
 This is in some cases so distinct as to attract attention by its 
 wavy fibrous appearance and the sinuous outline of the vessel 
 where no reagent has been applied. But these appearances be- 
 come much more distinct when the specimens are placed for a 
 short time in water or in glycerine, or when a little dilute 
 acetic acid is added. In many cases the application of these 
 reagents produced an appearance of thickening, certainly of 
 increased prominence of the external coat, even when the 
 
VIEWS OF SIR WILLIAM GULL AND DR SUTTON 67 
 
 vessel without reagent appeared natural. Eut the appearance 
 thus artificially produced differed from that of the true 
 thickening in that it -was never wavy or fibrous looking. I 
 found no evidence of free exudation or of the presence of any 
 solid material in connection with the outer coat. The condi- 
 tion thus described corresponds exactly to the appearances 
 of the specimens of so-called hyalin fibroid disease which I 
 examined." He also found evidence of thickening of the 
 tunica media, and in some cases of the intima. The tunica 
 media was never atrophied, nor was the lumen of the vessels 
 diminished. No thickening or exudation was seen in the 
 walls of the capillaries. These facts were gathered from the 
 examination of a series of twenty-three cases, in twelve of 
 which the vessels were normal. But here ends all that is 
 favourable in Dr Stewart's evidence to the theory of Arterio- 
 Capillary Fibrosis ; for -out of ten cases in which the outer 
 coat was thickened, there was no Bright's Disease whatever 
 in six. Dr Stewart is, nevertheless, clearly of opinion that 
 some of his cases presented a thickening of the outer 
 coat of the arterioles, not traceable to the use of 
 reagents. But Sir W. Gull and Dr Sutton are not much advan- 
 taged by this admission; for Dr Stewart's statistics go to 
 prove that the thickening was altogether unconnected with 
 Bright's Disease, either as effect, or as necessary concomitant. 
 In the walls of some of the vessels were small aneurisms, due 
 probably, as we may conjecture, to that diseased state known 
 as Chronic Peri-arteritis, which might quite satisfactorily 
 account for the thickening; unless, indeed, Drs GuU and 
 Sutton would include this also in their "Arterio-CapiUary 
 Fibrosis," in spite of the entire absence of connection between 
 it and Nephritis of any kind. Now, the author has seen 
 plenty of Chronic Peri-arteritis ; but he has never seen any 
 thing of the nature of "Arterio-CapiUary Fibrosis" in the 
 vessels of the pia mater, or elsewhere, except as a consequence 
 of the use of reagents. Not that he would aver that the 
 adventitia is never thickened; — it may be so from many 
 causes ; but what he states is simply this, that so far as he 
 knows, there is not a grain, or the ghost of a grain, of evidence 
 to connect this thickening with Interstitial Nephritis ; whUe, 
 on the contrary, there is strong proof in favour of a relation 
 subsisting between thickening of the tunica media and this 
 variety of renal lesion. Such evidence is afforded in the 
 course of Dr Stewart's paper above-mentioned, as well as by 
 many other authorities already quoted. 
 
68 INTEESTITIAL NEPHKITIS 
 
 The thanks of pathologists are due to Sir W. Gull and 
 Dr Sutton, not only for the careful manner in which they 
 have sought to collate facts in support of an ingenious theory, 
 but also for having, by their example, afforded a powerful 
 incentive to others to prosecute researches in the same 
 direction, thereby condueiag greatly to the wider and more 
 thorough ventilation of the whole question. But whUe 
 sensible of the benefit they have thus rendered to the 
 profession, the author is unable to accept their principal 
 conclusions, his own investigations having led him to believe 
 that they have fallen into certain errors already stated, which 
 may be epitomised under the following heads : — 
 
 (1.) In the interstitial kidney, Sir "W. GuU and Dr Suttqn 
 
 have probably, in many instances, mistaken the middle 
 
 for the outer coat of the arterioles, and have thus been 
 
 misled by a factitious appearance of thickening of the 
 
 latter. Their use of glycerine as a mounting fluid 
 
 has probably done much to further this confusion. 
 
 (2.) In other instances, though " well aware that there is 
 
 normally more or less of areolar tissue around the 
 
 minute renal arteries," they have fallen into the 
 
 error of confounding this with the adventitia proper, 
 
 a mistake also, perhaps, traceable to the use of 
 
 glycerine. 
 
 (3.) In the pia mater, brain, spinal cord, and other organs, 
 
 they have observed a state of matters partly real, 
 
 partly factitious, which, in consequence of their 
 
 ideas as to the nature of the kidney lesions, they 
 
 have been led to consider anatomically identical- 
 
 with those lesions, whereas material differences exist 
 
 between them. 
 
 In conclusion, then, there appears at present to be no 
 
 conclusive evidence of the existence of a general morbid state 
 
 characterised by " Arterio-CapUlary Fibrosis " and "hyalin- 
 
 fibroid " changes ; for such a state of matters does not exist 
 
 in the kidney, and there are grave reasons for doubting its 
 
 existence elsewhere. 
 
NOTE ON GLOMEKULO-NEPHEITIS 69 
 
 jStote on GLOMEEULO-NEPHEITIS. 
 
 The materials of the following note have heen gathered 
 from an examination of the kidneys in three cases of post- 
 scarlatinal nephritis. 
 
 Klehs (Handbuch der Path. Anat, Lief: iii., pp., 644-647) 
 was the first to direct special attention to a post-scarlatinal 
 change in the glomeruli, to which he gave the name of Glome- 
 rulo-JSTephritis. A. Beer, Dr Bristowe {Path. Soc's. Trans., vol. 
 viii. , p. 2 3 5, ) and Dr Wilks {ibid. , vol. vi. , p. 2 6 4) had previously- 
 remarked conditions more or less similar • but to Klebs 
 belongs the credit of first accurately describing the micro- 
 scopic anatomy, and of clearly distinguishing this variety 
 from others previously recognised. Until recently, post-scar- 
 latinal nephntis was generally considered to be of the Paren- 
 chymatous variety, though Biermer, Coats, Wagner, and 
 Cayley have described cases in which the changes were inter- 
 stitial. "We shall first give a translation of Klebs' descrip- 
 tion, and then proceed to a consideration of the appearances 
 as seen by ourselves : — 
 
 " On post-mortem examination, the kidneys are seen to be 
 slightly or not at all enlarged, firm to the touch, the capsule 
 easily separable, the surface smooth, and the parenchyma 
 hyperaamic. On careful inspection, the glomeruli appear pale, 
 like small whitish spots. The urinif erous tubes are often unaf- 
 fected, though occasionally the convoluted tubules are some- 
 what cloudy. On microscopic examination, we find neither 
 interstitial changes, nor that proliferation of epithelium known 
 as Eenal Catarrh, a state of matters often supposed to exist in 
 default of other perceptible derangements ; so that with the 
 exception of the condition of the glomeruli, there seems to be 
 nothing beyond the congested state of the kidney to account 
 for the symptoms (anuria, uraemia, and acute dropsy). This, 
 however, is palpably insufficient, since complete retention of 
 urine and acute uraemia have never been observed either in 
 active or passive hyperaemias of equal intensity, such, 
 for example, as those consequent on poisoning by carbonic 
 oxide, or on mechanical congestion. If a thin section of the 
 fresh, kidney be made with a Yalentin's knife, the anaemic 
 condition of the glomeruli becomes still more evident ; and if 
 the sections be washed in water, the glomeruli stand out in 
 
70 INTERSTITIAL NEPHRITIS 
 
 their substance as objects daiker and denser (triiber) than the 
 uriniferous tubules, while in direct light they are visible to 
 the naked eye as white spots. On microscopic examination, 
 the whole interior of the capsule is seen to be filled with some- 
 what smaU angular nuclei lying embedded in a finely granular 
 mass ; while on the inner surface of the capsule the epithe- 
 lial lining is seen in profile as a row of flat, knobby projec- 
 tions. The vessels of the glomerulus are almost entirely 
 obscured by the nuclear mass. It is somewhat difficult to 
 ascertain accurately the real anatomical situation of the 
 manifest nuclear increase ; and this can only be done by 
 careful isolation of the glomerulus " — and picking it to pieces 
 with fine needles — " whereby one learns that the epithelial 
 lining of the glomerulus is stUl visible, and is, indeed, as a 
 general rule, even more closely adherent than normally. The 
 epithelial cells are for the most part polygonal or clavate, 
 with large, oval, bladder-shaped (blaschenformigen) nuclei, 
 and very often adherent by one corner to the surface of the 
 glomerulus ; in certain cases I have seen them fattily dege- 
 nerated, but as a general rule, their substance has a clearer 
 and denser (heller und fester) appearance than under normal 
 conditions. By carefully separating these epithelial cells, we 
 recognise in the fragment of glomerulus, around and between 
 the unchanged and empty capillary loops, the same small 
 angular nuclei, abeady so conspicuous on a general view of 
 the glomerulus. The difierence of these elements from those 
 of the epithelium, both in respect of form and situation, shows 
 quite clearly that their origin is due to a multiplication of 
 the connective tissue corpuscles of the glomerulus, owing to 
 the presence of which the vascular loops are subjected to 
 compression." (Klebs, op : cit : Lief, iii., pp. 645-6.) 
 
 On the question of naked eye appearances, the author is 
 entirely at one with Klebs, so that there is no occasion for a 
 reiterated description. "We shall therefore proceed at once 
 to an enumeration of the microscopical appearances observed 
 in the three specimens already alluded to. These respectively 
 afforded examples of the early, intermediate, and later stages 
 of the lesion. 
 
 On examination with a low power (Hart. oc. 3, x obj. 7), 
 the attention is principally arrested by the dense appearance 
 of the glomeruli, which occupy almost the whole of the 
 interior of Bowman's capsules. Even with this power 
 especially if the tube of the microscope be drawn out, small 
 
NOTE ON GLOMEIIULO-NEPHRITIS 7l 
 
 bodies like grains of sand can he seen covering the loops of 
 the glomeruli. These small bodies can also be seen in 
 scattered foci among the general intertubular stroma, and 
 especially around the vessels. {See Plate xii.) Most of 
 the uriniferous tubes are unchanged, save here and there in 
 the immediate neighbourhood of the Malpighian bodies, 
 where some few may be seen whose epithelium' is granular, 
 cloudy, or more frequently fatty. The capsule of the kidney 
 is slightly thickened, and the interstitial tissue appears more 
 abundant and distinct than in the normal organ. 
 
 On examination with a high power (Hart. oc. 3, x obj. 7), 
 a most interesting series of lesions becomes visible. The 
 Malpighian bodies are the parts principally affected. Bow- 
 man's capsules are thickened and infiltrated with round cells. 
 These round cells are also aggregated outside the capsules, 
 their numbers varying with the intensity of the process, and 
 the stage at which it comes under observation. The unaltered 
 epithelial lining on the inside of Bowman's capsules can be 
 recognised without difficulty. Inside the capsules, on and 
 between the capillary loops of the glomeruli, are great 
 numbers of smaU. roundish, oval or angular bodies like 
 leucocytes, which correspond to Klebs' ' nuclei.' (See Plate 
 xi.). As mentioned on page 11, a certain number of 
 corpuscular bodies are normally found in this situation ; but 
 in Glomerulo-Nephritis their number is very largely increased. 
 Speaking roughly, there may be perhaps six or eight times 
 the normal number in the earlier examples, while in extreme 
 cases Bowman's capsules are often completely filled with 
 them. They are probably derived both from migratory 
 leucocytes, and from proliferative increase of the normal 
 corpuscles. A number of the Malpighian bodies may be 
 entirely obscured by dense corpuscular aggregations, situated 
 anatomically both within and around Bowman's capsules. 
 
 These abundant ceU-accumulations must evidently exer- 
 cise great compression on the vascular tufts, and thus present 
 a serious obstacle to renal circulation and excretion. The 
 compressed and empty capillaries of the glomeruli are not 
 infrequently converted into more or less dense fibrous masses, 
 wholly impervious, and continuous here and there, if not 
 entirely, with the inner circumference of their thickened 
 capsules. (See Klein, Trans. Path. Soe. 1877, pi. 33, fig. 7.) 
 The number of corpuscular bodies on the surface and in the 
 substance of these fibrous glomeruli is invariably greatly 
 
72 INTERSTITIAL NEPHRITIS 
 
 diminislied'. The fibrous glomenili stain but faintly with, 
 carmine and logwood, thus contrasting markedly with their 
 capsules, which continue to absorb the colouring matter 
 readily. 
 
 These processes of cell-aggregation, in and around the 
 Malpighian bodies, constitute the characteristic features of 
 the disease, and those upon which the clinical symptoms of 
 anuria, uraemia and dropsy appear to be mainly, if not entirely, 
 dependent. But the present writer cannot corroborate Klebs 
 in asserting the complete absence of other anatomical lesions ; 
 for in his specimens, as in Dr Klein's, there were abundant 
 evidences of ordinary Interstitial Ifephritis, as well as of 
 minor intratubular changes. Dr Klein, in the paper above 
 referred to, endeavours to account for the interstitial changes 
 on embolic grounds. Having encountered emboli in the 
 arteries of a kidney from a case of thirteen days' duration, 
 accompanied by very intense interstitial inflammation, he 
 thinks it not impossible that embolism may always stand 
 " in a causal relation to the interstitial inflammation." He 
 states no grounds for this conjecture, which appears rather 
 hasty, considering that emboli were only seen in one case out 
 of his series of twenty-three. As the author has observed 
 but one doubtful embolus in a single artery, he is unable to 
 concur with Dr Klein in ascribing the interstitial changes 
 to this curious and apparently very unusual cause. The 
 interstitial affection is eminently characteristic. The inter- 
 tubular cell-infiltration is so abundant and evident, that, 
 in our humble opinion, such specimens might serve to con- 
 vince even Dr Johnson as to the reality of an interstitial 
 ceU-infiltration. In these cases the round cells cannot 
 possibly be confounded with epithelial debris ; and their 
 intertubular situation is thus placed entirely beyond doubt. 
 Glomerulo-Nephritis is, in fact, nothing but an interstitial 
 nephritis, specially affecting the glomeruli, and in consequence 
 of this special anatomical site, proving fatal in the early 
 stages with a rapidity and constancy fully equal to the 
 rarity of a like result in the initial stages of the ordinary 
 variety. 
 
 Around the arterioles there are large accumulations of 
 migrated leucocytes. {See Plate xii. : also Klein, Path. Trans., 
 1877, pi. 32, fig. 4.) The intertubular capillaries are much 
 dUated, and contain great numbers of white blood-corpuscles. 
 Sometimes the leucocytes accumulated outside a vessel have 
 
NOTE ON GLOMERULO-NEPHRITIS 73 
 
 the appearance of lying in a sort of adenoid reticulum, as 
 noticed by Klein ; but this appearance the author is disposed 
 to attribute to underlying capillaries, the walls of which are 
 more or less visible through the superincumbent mass of 
 lymphoid cells. The author has not seen any germination of 
 the nuclei of the middle coat of the arteries such as that 
 mentioned by Klein, neither has he observed any hyaline 
 degeneration of the intima, as stated by the same authority. 
 In his specimens all the arterial coats were perfectly normal. 
 Small interstitial hsemorrhages, evidenced by the presence 
 of red blood corpuscles, and hsemorrhages into Bowman's 
 capsules from rupture of the glomerular loops, are by no means 
 iiifreqiient phenomena. 
 
 Intratubular changes are present to a greater or less degree. 
 These changes are not uniform, but sporadic, a few tubules 
 here and there being affected, while others in their neigh- 
 bourhood remain perfectly normal. On the whole, the tubules 
 thus altered are few in number, compared with those which 
 remain unchanged. The convoluted tubules are more fre- 
 quently affected than the straight. Those tubules in the 
 immediate neighbourhood of the Malpighian bodies seem 
 especially liable to undergo alteration of their contents. 
 The alteration^ consist of cloudy swelling and granular 
 degeneration of the epithelium, the cells breaking up into 
 a mass of small, dark granules, which occasion more or 
 less blocking up of the lumen of the tubules. Fatty degenera- 
 tion also is a change of still more frequent occurrence. 
 It often appears to begin in the nucleus of the epithelial 
 cells, and is rendered very evident by staining with osmic 
 acid. Eed blood-corpuscles and leucocytes are frequently 
 seen inside the tubules. Their presence may have something 
 •to do with the intratubular alterations, which are secondary 
 to the interstitial changes, and may be accounted for both by 
 the entry of blood cells into the tubules, and also on the score 
 of deficient blood supply, due to the pressure exercised by the 
 small-ceU tissue, both on the glomeruli, and also on the inter- 
 tubular arterioles and capillaries. Dr Klein also regards the 
 intratubular alterations as secondary, for he says — " This {i.e., 
 the parenchymatous change), becomes distinct after the intersti- 
 tial changes have reached a certain degree, and they (dc) are 
 quite insignificant before this degree of interstitial nephritis 
 is attained." And again: — The "more intensive {do) the 
 degree of interstitial change, the more marked is the enlarge- 
 
74 INTERSTITIAL NEPHRITIS 
 
 ment of the kidney, and the more distinct is also the paren- 
 chymatous nephritis, the number of urinary tubes, which 
 either contain casts, or are in process of destruction by being 
 ilooded with the inflammatory products (especially cells), 
 increasing gradually. ... It follows from this that the 
 intensity of the parenchymatous change, is dependent upon 
 the degree of the interstitial nephritis." In the author's 
 cases, he has never seen any deposit of lime in the epithelium 
 or lumen of the urinary tubules (Klein). 
 
 The changes just enumerated are most conspicuous and 
 widespread in the cortical portion of the kidney, though the 
 meduUa is by no means exempt. 
 
 Dr Klein ascribes the corpuscular increase on the surface 
 of the glomeruli to a proliferation of epithelial nuclei ; 
 but as mentioned by Klebs, the nuclear bodies differ from 
 epithelial cells or nuclei, alike in form and in anatomical 
 site. They are situated between the vascular loops as well 
 as on their surface, a fact which is alone sufficient to negative 
 the supposition of their epithelial nature. Dr Klein also 
 states that in the course of his investigations, he has never 
 seen any accumulation of these nuclear bodies within the 
 Malpighian capsules, in numbers sufficient to be likely to cause 
 compression of the vessels of the glomeruli, and consequent 
 interference with the circulation. He admits, however, that 
 his cases were probably diiferent from those described by 
 Klebs. Of this there can be no doubt, for a very cursory 
 inspection of the author's specimens would suffice to confirm the 
 accuracy of Klebs' description, and to demonstrate beyond 
 doubt the immense obstacle which the excessive nuclear 
 proliferation must of necessity occasion to the free passage of 
 blood through the capillary loops. Indeed, a more favour- 
 able condition for the development of anuria, ursemiaj and 
 acute dropsy could scarcely be imagined. 
 
 The principal changes just described, may be thus briefly 
 recapitulated : — 
 
 SUMMAEY. 
 
 A. Special Changes. / 
 
 (1) Increase of nuclear bodies, probably leucocytes and 
 proliferated connective-tissue corpuscles, inside Bow- 
 man's capsules, on the surface and between the loops 
 
SUMMARY 73 
 
 of the glomeruli, in such quantity as to occasion 
 serious circulatory obstruction from pressure on the 
 vascular loops. 
 
 (2) Thickening and nuclear infiltration of the substance 
 
 of Bowman's capsules, with great accumulation of 
 nuclear bodies in the immediate neighbourhood of 
 their outer surfaces. 
 
 (3) Fibrous degeneration of the glomeruli, consequent on 
 
 pressure and obstructed circulation. 
 
 B. GeNEEAL IHTEESTITIAL CHANGES, ETC. 
 
 (1) Appearances consequent on general Interstitial Nephritis, 
 
 namely, dilatation of capillaries, with accumulation of 
 leucocytes in their interior, migration of leucocytes 
 through the walls of the vessels, and connective-tissue 
 increase from small-cell infiltration. 
 
 (2) Small haemorrhages, interstitial, and into the interior 
 
 of Bowman's capsules. 
 
 (3) Embolism (?) of an artery, in a single instance. 
 
 G. Sboondaet Inteatubulae Changes. 
 
 (1) Sporadic parenchymatous nephritis affecting principally 
 
 those tubules immediately adjacent to the Malpighian 
 bodies, and characterised by (a) cloudy swelUng ; (&) 
 granular degeneration; and (c) fatty degeneration of 
 the tubular epithelium. 
 
 (2) Presence of leucocytes and red blood corpuscles in the 
 
 interior of the uriniferous tubules. 
 
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 RiNDOWSKi, Centralb., 69 S. 145. 
 EoBBETS, F. A., Practice of Medicine. 
 
 Schwbiggbe-Sbidbl, Die Nieren des Menschen und der SaHgethiere. 
 Simon, Med. Chir. Trans., vol. 30. 
 SoTTTHEY, Barth. Hosp. Bep., 1865. 
 
 ,, Beport of Med. Chir. Trans., Lancet, April 13, 1878. 
 Stewaet, T. Geaingee, A Practical Treatise on Bright's Disease of 
 the Kidneys, Second Edition. 
 ,, Brit. Med. Joum., Sept. 6, 1873. Beport of 
 
 „ Brit. Med. Journ., Sept. 6 and Nov. 15, 1873. 
 
 Steickee's Histology, Syd. Soc's. Transl. 
 Eecklinghausen, On the I/ymphatics in Belation to Connective Tissue, 
 
 Berlin, 1862. 
 Tannee, T. H., Practice of Medicine. 
 Thoma, Virch. Arch., 1877. 
 
 Todd, E. B., Clin. Lect. on Dis. of the Urinary Organs, 1857. 
 TuENBE, W., Anatomy. 
 ViEOHOW, Cellular Pathology, by Chance. 
 "WatsoNj Sir T., Practice of Medicine. 
 WiLKS and MoxoN, Pathology. 
 WiLKS, Trans. Path. Soc, vol. 6. 
 
 MS. Graduation Thesis by Dr Eobert Saundby, for Degree of M.D. in 
 the University of Edinburgh, "The Participation by the Walls of 
 the Blood-vessels in the Morbid Changes of the Connective Tissue, " 
 1877. In the Library of the University of Edinburgh. 
 
DESCRIPTION OF PLATES 
 
 Plate I. — ^Hart. oc. 3, obj. 7. Typical granulation tissue, from a 
 healing ulcer in tlie human subject. 
 
 Plate II. — Hart. oo. 3, obj. 7. Patch of interstitial cell-infiltration 
 (ordinary interstitial nephritis in the first stage), 
 from a case of glomerulo- nephritis. Most of the 
 tubules are normal, though a few are somewhat 
 compressed : others are empty, from falling out of 
 their epithelium during the preparation of the 
 section. The new tissue bears a close resemblance 
 to that of the healing ulcer (Plate I). 
 
 Plate III. — Hart. oc. 3, obj. 7, tube out. Second stage of inter- 
 stitial change, or that of cell-transformation. The 
 round cells of the interstitial tissue are seen in 
 process of conversion into spindles and fibres. The 
 basement membrane of the tubules is thickened and 
 fibrous : but the tubules themselves, though some- 
 what compressed are but little altered. Two of 
 them however contain colloid cylinders. The 
 nuclei of the cells of the tubular epithelium are very 
 apparent, owing to the specimen having been treated 
 with Acetic Acid. 
 
 Plate IV. — Hart. oc. 3, obj. 7, tube out. "Wall of an artery in 
 longitudinal section, a, intima somewhat thickened 
 and fibrous : J, muscular coat, hypertrophied, with 
 numerical increase of muscle nuclei : c, adventitia, 
 normal and unthickened : e, e, e, compressed 
 tubules; the lowest one is empty save for the 
 epithelial nuclei which remain adherent to the 
 thickened and fibrous wall : d, interstitial tissue in 
 a stage of advanced fibrillation : /, tubule containing 
 colloid. 
 
DESCRIPTION OF PLATES Ttf 
 
 Plate V. — Hart. oc. 3, otj. 9. Portion of the coat of an artery in 
 transverse section, a, adventitia, normal and 
 untUckened : 6, muscular coat, moderately hyper- 
 trophied : c, tunica intima exhibiting an early and 
 interesting stage of endo-arteritis obliterans, d, d, 
 d, cells of the epithelial lining of the lumen (?), or 
 perhaps identical with g : f,f, f, elastic layer of the 
 tunica intima split up into its component layers : 
 g, g, g, rounded cellular bodies, probably proliferated 
 connective tissue corpuscles from the middle layer 
 of the intima. 
 
 Plate VI. — Hart. oo. 3, obj. 9, tube out. Transverse section of an 
 artery in an advanced stage of endo-arteritis oblit- 
 erans, a, intima thickened by a fluffy, ragged, 
 fibrous material, like cocoa-nut matting: b, b, 
 roundish corpuscular bodies, probably identical with 
 those marked g, in Plate V : c, fenestrated 
 membrane or elastic layer of intima split up : d, 
 muscular coat, fairly normal : /, lumen, much 
 narrowed by the obliterative thickening ; its walls 
 are ragged and destitute of epithelium. 
 
 Plate VII. — Baker oc. A, obj. 1 inch. Cystic Kidney, Shrivelled 
 and denuded tubules, and arterioles with hyper- 
 trophied media are seen among the increased 
 interstitial tissue. Four large cysts formed from 
 dilated tubules, and several tubules in various 
 stages of cystic dilatation are represented in the 
 engraving. The large cysts were plainly visible 
 with the naked eye. 
 
 Plate VIII. — Hart. oe. 3, obj. 7, tube out. A glomerulus transformed 
 into a colloid mass. Bowman's capsule is thick- 
 ened and fibrous, and appears continuous with tha 
 surrounding interstitial increase. A few com- 
 pressed tubules are imbedded in the increased 
 interstitial tissue. 
 
 Plate IX.— Hart. oc. 3, obj. 3, tube out. A moderate sized arteriole 
 from the kidney. The tunica media is somewhat 
 hypertrophied, and the intima appears thrown into 
 
80 INTERSTITIAL NEPHEITIS 
 
 folds, but the coats are otherwise pretty normal. 
 The connective tissue distributed with the vessel 
 is much increased : immediately around the tunica 
 adventitia this increase is of a densely fibrous 
 character ; but at the circumference of the field of 
 view it is less completely fibrillated, and contains 
 round cells. Denuded and dilated tubules are seen 
 near the vessel lying in the midst of the fibrous 
 increase, and altogether outside the adventitia of 
 the vessel, which is plainly visible as a dense dark 
 ring. 
 
 Plate X.— Baker oc. A, obj. J inch. Artificial " hyalin-fibroid " 
 substance, in the coats of an arteriole. This curious 
 factitious specimen is described on Page 62 of the 
 Tezt. 
 
 Plate XI. — Hart. oc. 3, obj. 7. A glomerulus with its adjacent 
 tubules, from an advanced case of ' glomerulo- 
 nephritis. The capillary loops of the glomerulus 
 are entirely concealed by a dense congeries of 
 "nuclear bodies.'' Bowman's capsule is much 
 thickened, and around it are seen numbers of 
 nuclear bodies similar to those obscuring the capil- 
 lary loops. The uriniferous tubules contain 
 leucocytes and granular matter, and some of them 
 appear empty, and denuded of a portion of their 
 epithelial lining. The contents of one tubule 
 (represented by the darker shading), have become 
 fatty, and were stained black with Osmic Acid, 
 
 Plate XII. — Hart. oc. 3, obj. 7, tube out. An arteriole in transverse 
 section, with its surrounding meshwork of capil- 
 laries, from a lightly pencilled preparation of 
 glomerulo-nephritis. The coats of the arteriole are 
 normal, but numbers of leucocytes are seen col- 
 lected immediately outside the adventitia. The 
 capillaries communicating with the arteriole are 
 crammed with leucocytes. At the bottom of the 
 drawing a dense congeries of cells marks the site of 
 a Malpighian body, 
 
PLATE I. 
 
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 E. P. B., scnip. 
 
 PLATE IL 
 
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 B. C. W., delf. 
 
 B. P. B., smtljo. 
 
PLATE in. 
 
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 B. C. W., delt. 
 
 E. P. B., scMii). 
 
 PLATE lY. 
 
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 1" ^ 
 
 B. C. W.,(fe!(. 
 
^^■vii 
 
 
 'b ■i ~» ^ 
 
 
 B. C. W., Mt. 
 
 n 'f 
 
 E. P. B., sciiip. 
 
 PLATE VI. 
 
 B. C, W., dOl. 
 
 E. P. B., scitjp. 
 
PLATE VII. 
 
 J. p. E. R., delt. 
 
 E. P. B., sculp. 
 
 PLATE Till. 
 
 B C. W., delt. 
 
 E. P. B., sculp. 
 
PLATE IX. 
 
 "^ "^--",'vl- 
 
 
 B C. W., delt. 
 
 E. P. B., sailp. 
 
 PLATE X. 
 
 
 
 
 ii. 
 
 5«V ^5-~. ""'•1.1-.- 
 
 1 . ^*>* 
 
 J. p. E. H., 6M. 
 
 . P. B,, s(Ml/p. 
 
PLATE XI. 
 
 / 
 
 ■A 
 
 -'\ 
 
 
 \ „ Inl . '' ' ' 
 
 
 
 B. C. W., d«. 
 
 ( M 
 
 1 - / 
 
 
 PLATE XIL 
 
 ^■^ ,i;>-^ 
 
 
 "n!*"-. 
 
 
 B. C. W., delt. 
 
 E P. B., 
 
NOGRAPHS OF 
 IHE ROCKEFELLER INSTITUTE 
 FOR MEDICAL RESEARCH 
 
 ^^- ^^ October 15, 1919 
 
 TOTAL DIETARY REGULATION IN THE TREATMENT 
 OF DIABETES 
 
 Bv 
 
 FREDERICK M. ALLEN, M.D., EDGAR STILLMAN, M.D., and 
 REGINALD FITZ, M.D. 
 
 NEW YORK 
 
 The Rockefeller Institute for Medical Research 
 
 1919